Exploring Heart Disease: A Journey Through History and Anatomy
School
McGill University**We aren't endorsed by this school
Course
CHEM 183
Subject
Biology
Date
Dec 12, 2024
Pages
146
Uploaded by KidRabbitMaster980
Final notes all lecturesWorld of Chem: Drugs (McGill University)Scan to open on StudocuStudocu is not sponsored or endorsed by any college or universityFinal notes all lecturesWorld of Chem: Drugs (McGill University)Scan to open on StudocuStudocu is not sponsored or endorsed by any college or universityDownloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
HEART DISEASECaitlin Malcolm-Pottle
- The heart has 2 functions. • It will circulate deoxygenated (used) blood through the lungs to pick up oxygen and it will then take oxygenated blood and circulate it through the rest of the body. - Traditionally, bluedescribes blood that is deprived of oxygen and redis used to described oxygenated blood. - Oxygen is carried by red blood cells, more specifically by hemoglobin molecules. These have an iron atom embedded in their centre and is it that iron atom which oxygen attaches to. - The heart has 4 chambers. The top chambers are known as atria/atrium. The bottom chambers are the ventricles. - Used blood returns to the top right hand portion of the heart. The used blood is gathered up from the body through the vena cavaand it flows directly into the top right hand portion of the heart which is the right atrium.From there, through the tricuspid valveit is directed down into the lower part of the heart, the right ventricle.Muscles there contract and push the used blood through the pulmonary valve and out from the heart towards the lungs. This is the pulmonary artery, it is the only artery that carries deoxygenated blood. - As the blood circulates through the lungs it picks up oxygen from the air that we inhale and it comes back into the heart. It comes back into the heart through the pulmonary veins. Veins are blood vessels that flow towards the heart. The pulmonary veins will transport the blood into the top atrium on the left side, and then through the mitral valveit flows down into the left ventricle. From the left ventricle it goes out through the aortic valveinto the aorta. The aorta is the largest blood vessel in the body. The aorta subdivides and will send blood everywhere in the body through the arteries which then subdivide further into tiny blood vessels called the arterials. HEART
- The heart pumps 5-6 litres of blood every minute through 100,000km of blood vessels. It beats up to 2.6 billions times during an average life.• 100,000km is a great distance, to compare, the circumference of the Earth is only 40,000km. How is it that we have so many blood vessels in our body? They divide and divide and subdivide until they reach every part of the body. If we were to put these end to end, this is how you get the 100,000km. - The arteries contain oxygenated blood. The veins are the ones that return the used blood to the heart. - When we get down to the smallest subdivision, we get to the arterials. These are the ones that connect the arteries to the veins. Here, only single red blood cell can flow through, this just goes to show us how small they really are. HEART DISEASE - The heart may fail to pump enough blood.- There may be some impairment of the electrical activity of the heart. This is the electrical stimulation that is needed to force contractions of the heart to push out the blood.- There can be a reduced flow of blood through the coronary arteries. Coronary arteriesare the arteries that feed the heart itself. The heart is a muscle, so it needs a supply of blood just like any other muscle. The coronary arteries are called this because they sit on top of the heart like a crown. They supply the oxygenated blood to the heart, if they are blocked, then the heart itself is devoid of oxygen and this can result in a heart attack. - The valves play an important role in how the blood flows through the chambers of the heart. If there’s a malfunction with the heart valves, then the blood will not be pumped efficiently to the lungs or rest of the body. RISK FACTORS- There are various risk factors that predispose people to heart disease. - Family history is very important. If someone has a history of heart attacks, strokes in the family, then they are more prone to these conditions. - There are also some interesting signs that may indicate a greater risk. For example, a particular crease in the earlobe is seen in people who are more likely to have heart disease. Obviously the crease in the earlobe does not cause the heart disease, you will not reduce the problem by cutting off the ear. Why? It’s not really clear, but whatever genetic factors are involved in creating this heart disease are involved in the functioning of the heart.
- Men who go bald early are more prone to heart disease. This may be due to the imbalance in hormones, the same ones that cause baldness may play a role in heart disease.- Being male is also a risk factor. Men are more likely to develop heart disease than women.However, heart disease is still very important in women, its still the number 1 killer of women. It is just less prevalent in women than it is in men. • There’s been a lot of research into this trying to find out why women are less prone to heart disease. The idea that comes up is estrogen. Women have more estrogen than men and in menopause the production of estrogen decreases. After menopause the production of estrogen decreases and we know that after menopause women are just as likely to suffer from heart disease as men. Can you protect women after menopause with estrogen supplements? Many women take estrogen supplements to reduce the symptoms of menopause. Does this also reduce the risk of heart disease. A very logical question, but unfortunately it turns out that this is not the cause. • Estrogen supplementation after menopause does not reduce the risk of heart disease. It was a viable option and during the 1960’s, women were taking estrogen hoping for this benefit, but from a large number of studies, estrogen supplements do not protect them from heart disease. • However, estrogen supplements can still play a significant role in reducing fractures because once you start to lose estrogen, bone density is reduced. Estrogen can prevent osteoporosis. - Smokingis a big risk factor for heart disease. Probably more of an important risk factor than it is for lung cancer. Several reasons why it is a risk factor. • Carbon monoxide is part of the smoke and that will reduce the ability of the blood to carry oxygen.• Smoking also introduces all kinds of particulate matter and combustion byproducts into the body which the body senses as a foreign substance. Whenever the body senses a foreign substance, it mounts an inflammatory attack against it.- Obesityis also a risk factor. Those who are overweight are more prone to heart disease. People who are overweight are more prone to diabetes which predisposes to heart disease. The more weight you have, the harder the heart needs to work to supply the oxygen to all of those cells all over the body.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
DIABETES- Overweightis a risk factor for diabetes and diabetes is an independent risk factor for heart disease. - Diabetes is an increased concentration of glucose in the bloodstream. Glucose is essential, its the main source of energy in the body and the main nutrient that the brain uses for its energy source. If there’s too high a level of glucose, then it will react with proteins and fats and produce what’s called “advanced glycation end products.” These can damage tissues and can damage the coronary arteries which initiates inflammation which can result in a heart attack. - How do you know if you have high blood glucose? You have to measure it, you cannot know what your glucose level is without measuring it. There’s 2 systems that are used. • The milligrams per decilitre (mg/dL), this is mostly used in the United States.• Here we use milimols per litre (molecule/L) - The conversion is very easy. Mg/dL = mmol/L x 18 or mg/dL divided by 18 = mmol/L. For example if you have milimols per litre of seven, this would correspond to 126 milligrams per decilitre. - The simplest test to see if there’s a chance of diabetes is by taking a fasting blood glucose test.You don’t eat anything over night and you will take a blood sample in the morning where they will measure the glucose level. • If its above 7 mmol/Lthis is diabetes. • Prediabetes is 5.5-7 mmol/L.• Generally the test will be recreated if its under questioning, if its consistently above 7 then its declared as diabetes. - If there was a question about seeing how serious the condition is, they will normally do a oral glucose tolerance test.This is a better indication. You’re given a solution of sugar to drink (75g) and your blood glucose is measured 2 hours later. This gives the doctor an idea of how well you metabolize glucose. • If its over 11 mmol/L then it would be diabetes. • Prediabetes would be about 7.8-11 mmol/L.- Another measurement that’s commonly used to measure blood sugar level over a protracted period of time is the Hemoglobin A1c test.This is a blood test, this test will tell you what your average blood sugar has been over the past few months. • If the value is less than 7% then that corresponds to an average blood glucose of 8.3 mmol/L which is okay. You want it to be under 7%.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- If you are going to take a blood test in the morning after you have been fasting, ideally you would be below 6, if its above 7, you need to evaluate it further. If you measure it after a meal, you want it to be no greater than 14, however 10-14 is suboptimal, you should want it to be below 10. • The way to know over a period of time is to measure your A1c level. - Blood glucose can be measured these days relatively easily. For diabetics there are many ways to do this.• There can be a patch that attaches to the body. There’s a little needle that sticks into the body which draws blood and the information is transmitted to a device that will give you an immediate read out. This is the thing that NHL player Max Domi uses. He has to monitor his blood glucose levels carefully throughout the game so he uses this device. - There’s another device where you have to prick your finger and you put the blood on a test paper which you then put into the machine. There’s other devices that you can just carry around with you and it will give you a constant monitoring. These days the monitoring has become much easier. - Unfortunately, about 50% of all people who have a prediabetic condition will go on and develop diabetes so they have to make sure to monitor there condition.• This includes avoiding a lot of sugary foods, a lot of high carbohydrate foods, and a lot of high starchy foods because starch in the body converts into glucose. • A diet that contains a lot of vegetables, like beans and also fish. This is good to have.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Another risk factor is blood cholesterol. When people hear this word they know that its associated with heart disease. - The only way to know if you have high cholesterol is by a blood test.- Cholesterol is not a poison. It’s an essential biochemical. The body needs cholesterol because it is used for the synthesis of the sex hormones and the synthesis of the adrenal gland hormones.We cannot live without cholesterol. However, the body can manufacture cholesterol, we do not need it from an outside source. If we synthesize or ingest too much cholesterol it can build up in the coronary arteries and cause a heart attack. - Cholesterol is also measured in mmol/L. It is a blood test and you want your total cholesterol to be less than 5 mmol/L. It is much more instructive to know what your LDL and your HDL levels are. These are referred to as either bad cholesterol or good cholesterol. Cholesterol itself is not soluble in water, and blood it essentially water. So how does cholesterol get transported around the system? It has to be attached to the lipo protein and the LDL cholesterol gets carried around the body to get deposited into the cells that need cholesterol. However, if there’s too much of LDL, then some of it starts to build up in the coronary arteries which can trigger inflammation which in turn triggers heart disease. HDL is good cholesterol, it is cholesterol that is attached to rescue vessels, they pick up any excess cholesterol and transport it out of the system. So we want LDL levels to be low, and HDL level to be high. • You want your total cholesterol to be less than 5. LDL should be less than 3, and HDL should be greater than 1. - There are genetic components to heart disease. The APOE4 gene, people who have this gene are more prone to have high cholesterol as well as Alzheimer’s disease. These people should have to pay greater attention to their diet to reduce their risks. This needs evaluation through genetic profiling but this is not commonly done unless there’s a reason to suspect that someone has this gene. APOE4 is more common (20-30%) in Africans and Caucasians than in other ethnic groups. • There is a way to lower your blood cholesterol level through diet. A low fat diet will lower cholesterol, a low sugar diet will also help reduce cholesterol levels. - Eggs are a source of cholesterol so some people shy away from them, but they are very nutritious. When we look at studies, people who eat eggs do not have a greater risk of heart disease. It is not the cholesterol that we ingest in the diet that is the problem, it is the cholesterol that the body forms through biochemical reactions in excessive amounts and those reactions are triggered by the ingestion of saturated fats, like butter and the hydrogenated fats like margarine which are more responsible for high blood levels of cholesterol. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- We know now through a number of studies that eating 6-12 eggs a week in the context of a healthy diet does not raise LDL cholesterol. Theres no reason to shy away from eggs.- Bacon and butter is a bigger problem. Danishes are also a problem. One strip of bacon will not be a big problem, but there are many people who eat more than 1 strip of bacon on a daily basis. - It’s the saturated, hydrogenated, and trans fats in our diet which are the problem. We need to emphasize the poly and mono unsaturated fats. Olive oil is a great mono unsaturated fat and canola oil is a great source of poly unsaturated.- You want to limit your saturated fat intakes which are heavy creams, butters, and cheeses. These are the one that increase blood cholesterol. - In pastries like donuts you have both high sugar and high fat. Coconut oil is high is saturated fat.- When the chemical process of hydrogenation is used to convert an unsaturated fat to a saturated fat because saturated fats work better in commercial kitchens in baking and cooking, this comes with the formation of trans fats. Trans fats are unsaturated fats, but they have a different configuration. Trans fat should be in the same category as saturated fats, they are more prone to building up cholesterol in our arteries. - Around a third of all heart attacks and strokes could be avoided if people paid attention to their diet and took appropriate medication if they had been diagnosed with high cholesterol. • The statin drugswill prevent excessive cholesterol formation in the body by interfering with an enzyme that is involved in the synthesis of cholesterol. The statin drugs also play another role, they act as an anti-inflammatory substance. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Lipitoris a classic statin drug. It’s one of the most widely prescribed drugs in the world. Obviously like any other medications, there are side effects, but they don’t affect many people who are taking the drug. Most complaints are about muscle aches. - Homocysteine. This is another chemical that is produced in the body which has been linked with heat disease. It tends to build up in the body when there’s an insufficient intake of B vitamins. The theory has been that homocysteine can also result in the buildup of deposits in the coronary arteries and has been implicated in heart disease. • It turns out that this was overblown. It is true that without adequate B vitamin intake, homocysteine can reach levels that are potentially toxic to the cells that line the blood vessels. However, when the proper experiments were done and people with high homocysteine were supplemented with multiple vitamins to try and reduce the levels it did not make any difference. Homocysteine may be some sort of a marker for the disease, but it is not involved in triggering heart disease. • The B vitamins which are generally recommended for lower homocysteine levels. The foods that contain the B vitamins are the fruits and vegetables but these are the fruits that are recommended anyway for anyone who is trying to control the risk of heart disease. The same kind of diet that we recommend for lowering cholesterol is the same kind of diet we recommend for lowering inflammation and is the same for lowering homocysteine. It’s all the same diet that is mostly plant based, does not necessarily need to be totally plant based. - The most active area of research in heart disease is inflammation. It has been labeled the secret killer. Inflammation is responsible for playing a role for many conditions. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Inflammationis the body trying to protect itself against foreign invaders which can be bacteria, viruses, physical splinter in your body, it can be components of your diet, components of cigarette smoke. It’s stuff that the body perceives as foreign and it tries to eliminate it. There are various mechanisms by which the body tries to eliminate it, most of them involve white blood cells. - The classical signs of inflammation include heat, pain, redness, and swelling. These are the hallmarks of inflammation. When it happens on the outside of the body, its quite easy to recognize. However, when it happens inside of the body like in a coronary artery, its hard to know that its there. - There are many types of blood cells involved. There are white blood cells which have several different functions. Some of them will play a role like the. Mast cells, they will allow the opening up of the arteries so that more white blood cells can come to the cite of infection. • Neutrophilsare classic white blood cells, they basically digest bacteria and viruses. • Macrophageswill release chemicals called cytokines and those cytokines are signalling molecules which will bring other white blood cells to try and attack any kind of invader or plug up any holes in the skin with blood clots. - All of this is part of the immune reaction. - When you have a buildup of cholesterol inside of a coronary artery, then this can trigger an inflammatory response. The body receives that buildup as being some sort of a foreign substance. Sustained low levels of inflammation can then increase the size of the deposits, and the deposits can even break open and that’s when you get a blood clot which can cause a heart attack or stroke. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- If you have high levels of cholesterol (LDL cholesterol), then those particles of LDL cholesterol will settle on the inside of the walls of arteries. This is sensed as a foreign invader and the immune system kicks into action. The white blood cells them come to help like the macrophages which will try to consume the LDL particles. Then they themselves are converted into plaques, deposit in the walls of arteries and this can buildup over the years. Over time, as many inflammatory chemicals circulate in the blood stream around the deposit, they can weaken what is called the fibrous caparound the plaque. The plaque can burst open and then a blood clot can form and that can be catastrophic, it can cause a stroke or heart attack. - With Covid-19, there’s increasing talk of inflammation. In many cases it turns out that the problem isn’t caused by the virus as much as by the body’s reaction to the virus. The virus can directly affect the heart, their are receptors all over the body called the ACE inhibitors. The receptors for those are activated by the virus, and that’s how the virus enters cells. The virus can infect the heart, but it can also cause systemic inflammation. This inflammation can lead to plaques in coronary arteries.- Covid-19 can be associated with embolism, cardiac arrhythmia, small blood clots forming, so inflammation is very important in many ways. It can be directly triggered by the virus affecting the heart or there can be systemic inflammation. The most important way that the SARS-COV-2 virus gets into cells is through angiotensin-converting enzyme receptorwhich are located everywhere in the body. It is also possible that the pro-inflammatory substances that are secreted all over the body as the body engages its immune system and release the cytokine molecules. The cytokines are the chemical messengers that bring other white blood cells to the location of the inflammation and it is the activity of all of the white blood cells and the chemicals they release that can cause all of the problems. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- How do we know if there’s inflammation? This can be determined by a blood test. There’s a protein called C-reactive proteinand one can do a blood test for that. It turns out that healthy men who have the highest level of C-reactive protein have a much greater (3x) risk of heart disease. This is because the C-reactive protein is an indicator of inflammatory action.• Depending on how high it is, its usually measured in mG/L. A very high level generally means a bacterial infection, viral infections don’t raise the CRP levels quite as high.• This is not something that is done as a routine blood test, it is something that needs to be requested. It is an indicator of whether or not someone is at risk. HYPERTENSION- Hypertension is elevated blood pressure. The term hypertension is somewhat misleading because it sort of implies that you need to be tense and anxious to have high blood pressure but this is not the case at all. Anxiety can bring on hypertension, but you can have high blood pressure without ever having any kind of anxiety what so ever. - The first ever measurement of high blood pressure was carried out by Stephen Hales (1677-1761).He carried out an interesting experiment in England. He took a horse and attached a glass tube to the femoral artery and wanted to see how high the blood would spurt out into the glass tube. They had noticed before when ever their was an opening in the body through an artery the blood would pump out in tune with the heart beat. He wanted to see just how high this would be pumped. - It was much later in 1881, that Samuel Siegfried Karl Ritter von Baschinvented the first sphygmomanometer. This is the device that is now used to measure blood pressure. It is a cuff that goes around your arm and the pressure is measured in millimetres of mercury. They’re looking at a column of mercury to see how high it can be pushed by the pressure applied by the blood. This is still done today, but the devices today don’t literally have mercury in them anymore, they’re electronic devices. - The blood pressure is measured in terms of 2 numbers:• Systolic• Diastolic (D= denominator)- Systolic pressure is the one that’s exerted. This is the maximum pressure when the heart is beating. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Diastolic is in between heart beats- The number that we should strive for is 120/80. Anything lower than this is better. Hypertension is anything over 130/90 (80-89 borderline.)• Measurements have to be repeated because hypertension measurements can be very variable. - It can be measured in the doctors office but this often leads to “white coat hypertension.” People are nervous in the doctors office and their blood pressure tends to be high. The best way is to measure it at home with a device and to keep track of it by measuring it relatively often to get an idea of what it is.- Anxiety is not the same as hypertension, but being unhappy, anxious, and troubled can lead to high blood pressure. They did a study where they found that people who were not involved in happy marriages had higher levels of blood pressure. Those who were in loving and supporting relationships had reduced blood pressure. - What can one do to control high blood pressure?• Exercise is great, people who exercise tend to have lower blood pressure. How much exercise? Normally 3-4 30 minute slots per week, this is what is roughly recommended. • Diet is also important. The dietary approach to stop hypertension (DASH diet), this is a diet that has been studied for years to see how effective it is in lowering blood pressure. It turns out to be very effective, it is a diet that contains a lot of whole grains, fruits and vegetables, low fat dairy products, and its restricted in fats, not much meat, not too much fat, butter, or high fat cheese. The does not mean you can never eat it again, the amounts matter though, so those items should be limited in quantity. • Bananas are a very good part of the DASH diet because they are high in potassium. Potassium plays an important role in controlling blood pressure. ‣We should be taking in about 4500 mg of potassium. This is a lot compared to the amounts available in the serving sizes. So theres a lot of people who don’t get enough potassium a day. If someone has blood pressure problems its a good idea to increase your potassium by eating some bananas. - Too much salt can lead to an increase in blood pressure. Salt is sodium chloride and the North American consumption on a daily basis is roughly 3400 mg per day. This is a lot, the usual recommendation is no more than 2300 mg, this translates to about 6 grams of salt because salt is sodium chloride and not all of the salt is sodium. Those 6 grams of salt are very readily ingested in a day because salt is found in all kinds of foods (breads, cookies, cakes, cold cuts, etc.)Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Only about 15% of our salt consumption is the salt that is added at home to the food. Most of it is in processed food. To be optimal, we should be under 1500mg of sodium which is about 2/3 teaspoons of salt a day. • This is not so easy to achieve in the North American diet. Always remember to look at the serving size. - Is one salt better than the other? No. Salt is salt, essentially all salt is sea salt. Ordinary table salt is highly purified so its 99+% of sodium chloride, where sea salt and Himalayan pink salt which is a mine in Pakistan has some impurities in it, it has some other salts including magnesium and calcium salts other than just sodium salt, but those are found in very small amounts, they may give a slight tinge of colour to the Himalayan salt, but they have no role to play in nutrition. - Kosher salt is called this because according to Jewish dietary laws, blood has to be drained from meat before it is eaten. By covering them outside of meat with salt, moisture.blood is drawn out from inside the meat. The larger the grains of salt, the better it works because small salt grains dissolve into the meat. The difference between kosher salt and ordinary salt is just the size of the crystals/grains, kosher salt, Himalayan, and sea salt are much coarser. Table salt has the smallest grains. - A teaspoon of kosher salt and a teaspoon of table salt will not have the same amount of salt. This is because the large grains don’t pack together as well as the small grains, so their will be less salt in a spoonful of kosher salt compared to a spoonful of table salt. - On dry foods, when you sprinkle it with salt you can use less kosher or sea salt because they are bigger crystals and will make more contact with tastebuds giving off a saltier taste. In terms of health, the differences are minor. Theres no reason to chose one over the other if you’re thinking of any kind of health effects. Taste wise, if you’re sprinkling it on dry foods, then sea salt or kosher salt might you can use a little less to get the same flavour. - In science theres always different opinions. Dr. James DiNocolantoniohad a theory that all of the talk about salt has been overblown and he suggest that cutting back on salt will cause brittle bones and memory loss, etc. He recommends eating 7.5 to 15 grams a day. This is not based on any scientific evidence, many studies have shown that when you reduce salt, theres a significant decrease in heart attacks and strokes. Theres many studies that show reduce salt intake reduces the risks. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- If exercise and diet cannot control blood pressure properly, one has to resort to medications. - The first medication that is tried is usually a diuretic. This causes you to urinate more which means that your blood volume is reduced and therefore your blood pressure is reduced. • After that, theres also ACE inhibitors, Beta blockers, Calcium channel blockers, and Angiotensin receptor antagonists. DIURETICS- Hydrochlorothiazideis the one most commonly used. - Diuretics make it difficult for the kidneys to retain water and salt, and this causes a greater excretion of urine. Basically reducing the volume of the blood, and if theres less blood, the pressure against the side of the blood vessels is reduced. - Vasotec, an angiotensin converting enzyme inhibitor that blocks the production of a substance: Angiotensin 2, this is a chemical the body produces to increase blood pressure. This is done when for some reason blood pressure has dropped, for example if someone fainted and their blood pressure dropped, then you would want to increase their blood pressure. BETA BLOCKERS - They block the action of adrenaline. Adrenaline increases blood pressure, adrenaline is the fight or flight hormone, you want more circulating blood when you are in such a situation. Beta blockers interfere with the action of adrenaline and they reduce blood pressure by throttling back the force and speed of the heart beat because adrenaline would increase that force. CALCIUM CHANNEL BLOCKERS- They are widely used today, Nifedipinewould be a generic version of it. These calcium channel blockers act by diluting the arteries and when the arteries are diluted, the pressure is reduced. They are beneficial not only in reducing blood pressure but also for angina and other problems of a weakened heart. ANGIOTENSIN 2 RECEPTOR ANTAGONISTS - Most recent type of medication. They block the action of angiotensin by binding to its receptor sites. (Lock and key mechanism). This blocking action stops the angiotensin from tightening the arteries and raising the blood pressure.ANGIOTENSIN CONVERTING ENZYME INHIBITORS Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- The most talked about problem with the heart is heart attack. HEART ATTACK - Angina: A sensation of feeling of pressure on the chest, as if someone was sitting on your chest. This is one of the signs of a heart attack but not the only one, you can also have pain in your arm or in your jaw. In order to really understand what is happening, you have to examine the coronary arteries. - The heart is a muscle that pushes blood around the system, it pushes blood into the lungs to pick up oxygen and takes the oxygenated blood and propels it around the body. Because it is a muscle, it requires a source of oxygenated blood itself, this is delivered through the coronary arteries. The coronary arteries sit on top of the heart. The blue are blood vessels that are returning the deoxygenated blood to pick up oxygen through the lungs. The coronary arteries stem out from the aorta which is the largest blood vessel in the body. The aorta emerges from the left ventricle of the heart and it subdivides into the arterials and supplies oxygenated blood around the system. - If we were to dissolve the heart away leaving behind only the coronary arteries, we would be left with the arterial tree.The major coronary arteries subdivide into smaller and smaller ones. There’s the left descending coronary artery, there’s the right descending artery, and there’s one going around the back of the heart called the circumflex artery. • A blockage anywhere there will impair the flow of blood to all the tissues that are below the point of blockage. If we get a blockage way up somewhere on the coronary artery tree, everything below will be devoid of oxygen. It depends on where a blockage occurs.• We can have a first glance of what is going on by using an analogy of the arteries as if they were part of some plumbing system/water pipe. A water pipe can build up deposits inside, this will impair the flow of water. This is a problem in plumbing and this is a big problem if it happens in the arteries as well.• When looking at a water pipe the deposits are attached to the interior of the pipe itself, whereas when it comes to the coronary artery the deposits build up in the lining of the blood vessel, they’re not attached to the outside of the vessel as in the case of the water pipe.
- When the blood vessel is normal then the red blood cells cruise through easily. When there’s a build up of deposits the blood vessel lining starts to ballon out and impairs the flow of blood. The real problem comes if the deposit burst open and a blood clot forms there in which it will completely choke off the flow of blood. - You can have angina without having a heart attack. Angina is due to the impaired flow of blood. As long as some part of the heart is not getting oxygenated blood, there’s an issue. The issue becomes greater with exercise because the demand for oxygen is greater. • Angina pectoris can be exercised induced or can also happen at rest when for some reason the artery goes into a spasm and if there is already somewhat of a blockage there, then the spasm will completely close down the artery.TREATMENT- The classic treatment for recurring angina is nitroglycerin. The same nitroglycerin which is used as an explosive, however, in this case it dilates arteries which is exactly what you want. When you have arteries that are narrowed and cannot deliver enough oxygenated blood, you want to open them up and that’s what nitroglycerin does. • Nitroglycerin breaks down into nitric oxide in the body which is the active ingredient that opens up the arteries.- There’s many version of nitroglycerin that are available. Sublingual tablets because the skin underneath the tongue is thin allowing for rapid absorption. Theres nitroglycerin spray where you spray it underneath the tongue as well. There’s also nitroglycerin ointment which you put on the skin, this is people who have recurring problems of angina. They want a steady infusion of nitroglycerin, however there are some issues with this. Someone had a heart attack and the ambulance had to be called. They had to try and use a defibrillator, but the person had some nitroglycerin ointment on their skin and it didn’t react very well with electric current which caused popping sounds, but its not a lethal situation.
- There’s also nitroglycerin patches that can be put on the skin which will slowly release nitroglycerin over a period do time so that someone who has exercised induced angina can put it on before engaging in exercise. - Some people are rather inventive. There’s one gentleman that figured since nitroglycerin was so good at opening up blood vessels that it might help open up blood vessels somewhere else in his body. He rubbed one of these patches on his organ and then had relations with his wife. His wife ended up having a terrible headache, not surprising because it is well known now that nitroglycerin has a side effect of headaches. - There are also nitroglycerin capsules that can be taken and these are time released. Someone who has recurring problems of angina could take this to reduce the chance of an angina attack. - Some websites sell Arginine as a treatment for angina. Arginineis a common amino acid that we get in our diet. In this case the claim is that a purified form of arginine would release nitric oxide in the body. This is true, nitric oxide is the active ingredient. The idea is that arginine would deliver the same kind of effect but theres no large clinical studies that have shown this to be true, its not science based enough to rely on arginine as a treatment. • However, its very often pushed in natural health stores because it can be sold without a prescription. There needs to be further researched on this. It’s not that it can be dismissed out of hand because it is true that arginine can be a source of nitric oxide but there needs to be clinical trials to see if its effective or not. BETA BLOCKERS- Beta blockers block adrenaline. Adrenaline is a hormone that is produced by the adrenal glands, it is the fight or flight hormone. When it is released by the adrenal glands it will result in a dilation of blood vessels, in a fight or flight situation you need to inhale more air to deliver more oxygen to the tissues. Beta blockers reduce the effect of adrenaline.- Beta blocker fits into the adrenaline receptors but do not activate it. They do prevent the adrenaline from fitting it and therefore can reduce the workload of the heart because if its not being stimulated by adrenaline, it doesn’t have to work as hard. - There’s many versions of beta blockers, propranololis probably the most famous one and has a long history of safe use. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
CALCIUM ANTAGONISTS - Calcium antagonists do the same kind of thing as the beta blockers, they reduce the amount of work that the heart has to do by preventing stimulation of the heart muscle through the infusion of calcium from the bloodstream. Calcium antagonist like cardizem (diltiazem)are used in the treatment of angina. - Angina can eventually lead to congestive heart failure. This happens when the heart is unable to fill or empty properly because of the impaired flow of blood through the coronary arteries so the heart is not working up to its maximum efficiency. • The big problem is with the left ventricle (bottom left chamber). This is the one that contracts to push the oxygenated blood out into the body. It’s very important that this muscle functions properly. Whether its a slight or large impairment of that muscle that will determine the extent of heart disease.• If there’s a problem with the left ventricle, this can be catastrophic. For example, if instead of the blood flowing out into the aorta through the aortic valve, if there’s some kind of anatomical malfunction in the heart, the blood from the left ventricle instead flows out into the right ventricle. It’s important for the left ventricle, the muscle around the left ventricle to be working properly, if it isn’t, that can result in congestive heart disease. Heart disease is due to coronary artery disease, or constant high blood pressure, heart valve problem, abnormal heart rhythms, or even thyroid problems. - Congestive heart disease is not necessarily a death sentence, it can be treated. In a cartoon that dates back to the 1800’s, the two of the main diseases that they had to confront was consumption/tuberculosis and dropsy (congestive heart failure) which is the retention of fluids in the body because the heart isn’t working properly. The first treatment used in the treatment of congestive heart failure was discovered by William Witheringwho was a physician in the 18th century (1741-1799) in England. • He followed up on some folklore stories about an old wives tale. Supposedly there was someone in his neighbourhood who was treating people who were complaining about various kinds of heart problems with an extract of the foxglove plant. He followed up on this and did some experiments and discovered that it works. One of the first clinical trials. He gave some of his patients the extract of the foxglove and some others did not receive it. He found that the ones that got the medication got better. This was a natural treatment for congestive heart disease. The foxglove plant, also sometimes called witches bells, was a very effective source for the extract called digitalis which was used to treat congestive heart failure. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Digitalis is a mixture of compounds. These compounds have been separated. Today someone who is suffering from congestive heart disease are not told to go and make a tea of digitalis leaves. They are given a prescription of digoxinwhich is one of the compounds extracted from the foxglove plant. It is still isolated the same way, now it is purified.- Congestive heart disease requires very often the use of other medications as well. There are the angiotensin converting enzyme (ACE) inhibitors which will relax constricted blood vessels which allows an enhanced flow of blood. There are the beta blockers which improve pumping function, and the diuretics that will eliminate water from the body so the heart can do less work.- There’s also the question of CO enzyme Q10. It is a natural occurring substance, it occurs in the heart muscle and it is involved in energy production. It can also be made synthetically, and the question is if it can improve cardiovascular health. It is true that when measurements are done, levels of CO enzyme Q10 are reduced in hearts of congestive heart failure patients. It is also true that it is necessary for energy production. However, we do not have any clinical trials that would be convincing enough to suggest that it should be used as a mainline therapy, but theres no big risk in using CO enzyme Q10. One does have to put a question mark beside this because although it does make some theoretical sense, we don’t have the kind of evidence that you have for the angiotensin converting enzyme, beta blockers or the diuretics. - Sometimes it can result in cardiac arrhythmia. This is an irregular heartbeat. When this happens the flow of blood will be impaired and it can also lead to heart attacks. There are medications used for the treatment of heart disease. • Sotalol hydrochlorideis one of them. It will regulate an irregular beating heart. There are a number of other medications used as well, the one that’s most commonly used today is Amiodarone. Whenever irregular heartbeats are detected which can occur as a consequence of congestive heart disease, this is the drug that can regulate the heartbeat. - If medications are not enough to regulate the heartbeat, there are implantable devices that can be used called a pacemaker. It can be surgically implanted, it is not a difficult operation. The electrodes are placed into the chambers of the heart and the pacemaker will deliver the electrical activity that is needed to make the heart contact as it should in a proper rhythm and prevent any kind of arrhythmia. These days, the batteries used are very long lasting.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
HEART ATTACK (MYOCARDIAL INFARCTION)- Whether were asking about cardiac arrhythmia or the buildup of deposits in coronary arteries can eventually result in a heart attack. This occurs when the flow of blood is totally blocked off from one part of the heart. This can result in excruciating chest pain, but it doesn’t necessarily produce chest pain.• The deposits, the low density of cholesterol build up in the walls of the coronary artery. The macrophagestry to eliminate the cholesterol. Eventually the artery balloons out and if it burst then you get a blood clot forming, and with the formation of a blood clot, it can basically choke off the flow of blood completely. - Plateletsrelease chemicals that cause the blood to clot. The platelets gather at the site where the clot will form. They release chemicals that form these fibres that then snare the red blood cells and form a kind of net. The blood cells that are ensnared in this web of fibrin is what causes them blood clot. Once you have a blood clot, you have impaired flow of blood. - There are roughly 1.5 million heart attacks a year in North America. 25% die immediately, but another 25% are unaware.This happens when the the artery that is choked off is not one of the major coronary arteries. This is usually picked up in a subsequent examination like the electrocardiogram. This will show if the patient had any previous heart attacks. - What triggers a heart attack? It can be many factors, sometimes anxiety, exercise, or even a sudden change in temperature. However, it usually happens when theres a pre-existing heart condition. - When someone has a heart attack they have to get to the hospital as fast as possible, this is what can save people. In the hospital there are many tings that can be done. Morphine, Oxygen, Nitro, and Aspirin are the main ones used in the immediate care for a heart attack victimbecause it can be accompanied by excruciating pain which the morphine takes care of. Oxygen inhalation will boost the amount of oxygen in the blood stream so if theres impaired flow you’re at least increasing the oxygen concentration. Nitroglycerin will dilate the blood vessels. Aspirin will try to break down blood clots, aspirin is an anticoagulant, it can dissolve a blood clot. The doctor will take a blood sample to test it for Troponin. Troponin creatine kinase is an enzyme which is secreted by cells that are starved of oxygen. When a muscle becomes starved of oxygen, it releases enzymes, this is usually an indication that a heart attack is in progress.
- The most dangerous feature of a heart attack is that it can cause ventricular fibrillation. This is when the bottom left side of the heart, instead of beating in rhythmic fashion, it goes into fibrillation. This means that it is not effectively pushing out blood into the aorta. This is picked up on an electrocardiogram. An electrocardiogram is a tracing of the electrical ability of the heart. A physician can look at this and immediately see if a heart attack is in process or not. - If there’s indication of ventricular fibrillation or any other kind of fibrillation, they will use a defibrillator. This is the classic scene you see in movies and TV shows. The electrical current can regulate the irregular beating heart. - The aspirinthat they use is just a regular aspirin which is available as acetylsalicylic acid. It’s one of the most effective things tht can be done to counter the effects of a heart attack. It is not a bad idea to carry around aspirin tablets. Theres no harm that can be done by taking a small dose of aspirin, and if anyone thinks that they are having a heart attack, this is a smart thing to do. Theres even a wallet that has a “Smart Wallet Pill Card”. - It is also possible to dissolve a blood clot very quickly in the emergency room. When a heart attack has been diagnosed and they think their is a blood clot, they can administer thrombolytics. This is a chemical that will dissolve the blood clot. Tissue plasminogen activator (TPA) is the classic one that is used. It is used intravenously. It is used in acute heart attacks. It will dissolve the fibres that make the net. The tissue plasminogen activator has to be used quickly if theres suspicion of a blood clot. Plasminogenis a complex protein in the body that when activated by the plasminogen activator will release plasma which is the active ingredient that will dissolve the blood clot. If the blood clot has been succefully dissolved and someone is on the way to recovery from a heart attack, they will often be given a medication to prevent another blood clot from forming. Plavixis one of these, Heparinis sometimes used, its one of the oldest drugs that is known to prevent the formation of blood clots, it depends on the hospital protocol.- Other drugs that are used after a heart attack is angiotensin converting enzyme inhibitors.This will reduce the work of the heart. It brings down blood pressure. Beta blockersare also used, they reduce the oxygen requirement of the heart, so it makes you less likely to suffer another heart attack. - If they diagnosed a blood clot and the hospital has a cath lab, then this will be called into action. It is a surgical procedure, not too complex, it involves physically getting rid of a blood clot through a catheter.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• The physician will snake a very thin catheter up into the heart as they are looking through a monitor. The catheter is usually introduced through the upper thigh into an artery and they can see exactly where the catheter is going. The idea is to get the catheter which has a ballon attached to the end of it to the site where the blood clot has formed. • Carefully the doctor will insert the catheter into that position and engage in a process known as angioplasty. This is essentially using a ballon to push the blood clot aside. • It comes from the femoral artery in the thigh, it gets pushed up, and then they locate the place of stenosiswhich is the place where the narrowing or blockage is occurring. The catheter is introduced there, and the balloon is inflated. When the balloon is inflated, it will push the deposit aside and open up the artery. • Often they will insert using the ballon, and the balloon will be surrounded by this stent which is a spring like device that gets left behind when the balloon is deflated. - On the left the artery is occluded. They insert the catheter surrounded by the stent. They then blow up the ballon which pushes the ballon and the stent so that the deposits are pushed out of the way. The catheter is then withdrawn and the stent is left in place. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- It is not a permanent solution to the problem. Even though you have placed the stent which opens up the artery the underlying problem of why these deposits occur has not been solved. Placing a stent doesn’t solve the problem totally because their will be sequential narrowing either at the position or a position around where the stent is. (Arteries narrow again in 15-25% of people, this re-narrowing is called in-stent restenosis.) Scar tissue can also form where the stent has been planted and that scar tissue can also block the flow of blood. - There are also stents that will release drugs in a slow fashion. Siri li us is an anti-inflammatory drug which prevent as inflammation taking place around the coronary deposits and hopefully preventing subsequent heart attacks. BYPASS SURGERY - Once the heart has been damaged or the artery is occluded in such a way that it cannot be opened up with angioplasty then bypass surgery may be necessary. The bypass surgery includes bypassing the blocked artery. To do this, you need to open up the chest and expose the heart. The surgery actually involves creating a by-flow, a flow that bypasses the point of occlusion. - They sew a tube that goes around the blockage, delivering blood below the blockage. This tube is usually an artery taken from the leg, but it can also be a synthetic blood vessel. When the chest is open, and the heart is exposed, the heart has to continue functioning, but the surgeon cannot operate on the beating heart. They need to stop the heart from beating and need to put a heart-lung machineon the patient that takes over the work of the heart and lungs. • These heart-lung machines were first introduced in the early 20th century. They were complicated back in those days, bot today they are sophisticated and computer controlled. The blood goes out of the patient and goes through this machine where it is oxygenated and then goes back into the patient. • When the machine is at work, the heart is stopped and the surgeon can manipulate around the heart and can do all the sewing that is necessary. One part of the team would work on the heart and the other is harvesting a vein from the leg. Then they test it to make sure there are no leakages in the vein. They will sew it around the area and bypass the blockage. Then they will try to restart the heart and this is a critical moment. Usually the heart starts beating again. People who have bypass surgery often go and live relatively normal lives after. They will need to be taking medications, these medications prevent the formation of blood clots because manipulating the heart and the surgery causes tissue damage and possible blood clot formation and possible inflammation.
• Medications like dipyridamoleand monoclonal antibodies such as Abciximab are used. It’s a combination of surgical treatment and drug treatment that allows people to lead relatively normal lives. - Of course their are consequences. It turns out that people sometimes will have mental issues after undergoing coronary artery bypass surgery. Depression is relatively common because someone has come face to face with death.- Another form of surgery involves replacement of heart valves. This is a surgery that has been done quite effectively since the middle 1900’s. It can involve using a pig heart valve to replace a human valve or sometimes a simple mechanical device. The first heart valves that were used as replacements were these ping pong balls as types of valves. When blood flows the ball goes up, in between beats the ball goes down. Today their are more sophisticated valves then this. - Now there’s the question of a mechanical heart. The heart is just a pump, and engineers know how to make pumps.Artificial hearts have been built, one of the first ones was called the Jarvik7. It was effective, the only problem with this is as the blood flows through it, it causes the blood flow to be irregular and the blood smashes against the sides of the plastic which can cause blood clots. This was a short-term replacement until a heart for transplant can be found. Today there are more sophisticated artificial hearts, some of them can be used for quite some time but the big problem aside from the blood clot formation, is the power supply. You need quite some energy to cause the blood to flow through and pump out. You need some sort of external drive. Once this artificial heart has been implanted, the person is attached to a pump. This is why it is looked at as a stopgap measure until it is possible to find a heart for a heart transplant. • Frédéric Thiollethad one of these artificial hearts implanted and carried around a power supply. He lived for 1,250 days with the artificial heart. HEART TRANSPLANT - The biggest problem with heart transplant is that theres not enough hearts available, people don’t sign their donor cards. - The first heart transplant was performed in 1967 by DR. Chris Bernard in South Africa. It made headlines around the world. Louis Washkanskywas the one to receive the heart, he was a dentist. Unfortunately, he didn’t survive very long. However, it wasn’t because of the heart, it was because the body perceived it as a foreign substance. The artificial heart pumped properly, but it was the rejection of the artificial system by the body that caused the problem.
- Today this is much less of a problem. Drugs have been developed, Cyclosporineis the classic one which will prevent the rejection. Today there are people who have lived for decades with implanted hearts. • There were all kinds of controversy at first with this kind of heart surgery. They thought that the person would take on the characteristics of the donor, none of this has ever happened. This has become relatively routine surgery. - Children have also had hearts implanted when they were very young and have grown up with them. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
HORMONESCaitlin Malcolm-Pottle
THOMAS ADDISON 1855- Another British physician noted upon autopsy that people who had shrunken or atrophied adrenal glands while they were still alive had complained of poor appetite, had low blood pressure, had weakness and anemia, and they had discoloured skin. He thought that the adrenal gland must be releasing something that prevents these symptoms from occurring. - By 1895, an extract of the adrenal gland was being used to raise blood pressure in people who suffered from low blood pressure. CHARLES BROWN-SEQUARD 1889- He was a highly respected physiologist both in America and France. He carried out what turned out to be a seminal experiment in the history of hormones. - He started with dogs, he was interested in the testes of them. He had noted that when the testes were removed, the health of the animals would start failing. He thought that there was something being released by the glands that kept people in a healthy state. - He experimented on himself. This was long before you required permission from ethic committees so that you can carry out experiments. It was not so unusual in those days for scientist to experiment on themselves. • He injected himself with the macerated dog testicles and guinea pigs as well. He claimed to be rejuvenated, had feelings of rejuvenation. This gave rise to all kinds of commercial enterprises and people started selling Brown-Sequard’s extracts of animal organs. They were claimed to be testicle extracts and were suppose to be rejuvenating concoctions. SERGE VORONOFF (1866-1951)- He was one of Brown-Sequard’s followers. He was a physician, originally of Russian descent but was working in France. - Instead of just injecting extracts, he thought why not just transplant the whole gland. - He made a deal with the French government to allow him to remove the testicles of executed criminals. He transplanted these into millionaires. The idea was that they would feel younger. - Soon after he ran out of testes, he ran out of executed criminals. He thought the next best thing would be a chimpanzee.
• He started a farm located in Italy to raise chimpanzees. He harvested there testicles and inserted them into the scrota of aging men. He developed a huge following and many other doctors did this as well. • There was anecdotal evidence of benefit, but it could’ve been mostly due to the placebo effect. It’s not likely that there was enough testosterone leeching out from these transplanted glands to cause any kind of significant effect.- He became very popular and wrote a book about the benefits of grafting, but not everyone liked this. - Sir Arthur Conan Doylewho was a physician and the creator of Sherlock Holmes was disenchanted with these stories of the gland transplants. He thought that this was stretching the boundaries of science too much, that scientists were trying to play God. • He wrote a Sherlock Holmes story about this, called “The adventure of the creeping man”. It was about an aging professor of physiology and he starts exhibiting strange behaviour. Sherlock Holmes is called into the case by his children who saw him swinging in the backyard on a tree limb to limb. He had made a monkey of himself by using glandular extracts. This was his way of showing that he did not approve of this phenomena. JOHN ROMULUS BRINKLEY (1885-1942)- In North America John Romulus Brinkleyhad bought himself a mail order diploma in medicine which was possible in those days. He apprenticed with a doctor for a short period of time and then he had an idea. • He had grown up on a farm and had seen the activity of goats. He had noticed that they were horny and enjoyed many sexual escapades. So he thought why not insert goat glands(testicles) into humans. • He made a lot of money with this. He carried out numerous operations of transplanting goat testicles into humans. There were very little side effects because he had never connected the testicle to anything. He claimed rejuvenation and he got a lot of anecdotal responses from people saying they felt better. ‣One of the most interesting ones was from a farmer. He had said that his wife had been complaining about him being a “flat tire”, so he sought help from Brinkley who suggested the glandular transplant. A year later, Brinkley received a letter from him, thanking him for the transplant because he had felt so much better and was able to father a son. He had named his son Billy after the goat.
DOLANKSI 1894- Another physiologist who was working with dogs. He was trying to find out how it was that when an animal or human ate something, and the stomach secreted some acid, how did the message get sent to the pancreas to force it to release digestive juices. • It was known that the digestive system involved acid release which was stimulated by food in the stomach, and this then triggered the release of various kinds of fluids from the pancreas that aided in the digestive process, but how was this signal sent.- Dolanskithought that perhaps the acid went into the blood stream and it circulated in the blood stream and that’s what triggered the pancreatic to secrete its juices. He thought that if this was the case, he could inject some acid into the rectum of the dog because that would also go into the blood stream and should also trigger some release of hormones from the pancreas. • He tried it, but nothing happened.- He gave up on this idea. ERNEST STARLING 1902 - A few years later he pushed this a little further. He thought that maybe the acid was stimulating something in the lining of the intestine which was then released into the blood stream and that was how the message got sent to the pancreas. - He experimented with dogs. He injected the ground up duodenumwhich is the top of the small intestine where it meets the stomach into the jugular of the dog. Within a few seconds, the pancreatic fluids began to flow. This means that their was something in the duodenum that was going into the bloodstream upon food entering the stomach and that message caused the pancreas to release its juices. • This was the first hormone to be described, it was secretin. Secretinis a chemical that is stored in the intestine and when stimulated by acid secretion in the stomach in response to food entering the stomach, the secretin goes into the blood stream and receptors in the pancreas pick it up and start releasing their juices to aid digestion.
HORMONE (WHAT IS IT?)- The definition is a substance that’s “stirred into action” this comes from the Greek. We just saw an example of that, when the hormone secretin was released into the blood stream, it stirred the pancreas into action.
• This is why there’s so much concern these days about substances that we refer to as endocrine disrupters which are chemicals which can interfere with the hormonal system. - The pituitary is often describes as the conductor of the orchestra. It influences so many other systems in the body. For example, it releases adrenal cortical tropic hormone (ACTH) which stimulates the release of cortical steroidsfrom the adrenal gland. There’s the growth hormonethat stimulates muscle and bone growth. There is the melanin stimulating hormonefor the skin, thyroid stimulating hormonewhich causes the release of hormones from the thyroid gland, the follicle stimulating hormone which releases eggs from the ovaries, there’s the breast which can be stimulated with prolactinand oxytocin. Prolactin causes milk production, oxytocin is said to be the hugging hormone, it allows mothers to feel great affection towards their babies. So there’s all kinds of signals that come from the pituitary gland that transmits the messages to other organs in the body which can carry out various functions. - Prolactin, a protein hormone that stimulates milk production. It is triggered by the pituitary. - Somatotropinis a growth hormone. It’s found in highest concentrations when the body is actively growing, as we get older levels of this in the blood stream drop. This is why there’s a theory that using human growth hormone can have rejuvenating effects. A deficiency in this will result in very short stature, and if theres an excess in this, usually when there’s a tumour on the pituitary gland, this causes excessive growth. • Classic picture including General Tom Thumbwho was made famous by PT Barnum. Was a great entertainer, the Barnum and Bailey circus was started by him. He also had museums where he exhibited all kinds of unusual people/objects. One of his stars was General Tom Thumb. He was very small because he did not have enough growth hormone. • Sandy Allen (1955-2008),the largest women ever. She had excessive amounts of human growth hormone because of a pituitary malfunction. She drove a car where the front seat had to be removed, she sat in the back seat, the steering wheel had an extension but she was able to reach the pedals with her feet. • Robert Wadlow (1918-1940)he was the tallest man ever. Unfortunately these people don’t live very long because their giant size comes with some medical problems. The heart has to work harder to circulate the blood over that great height, and people who have this problem which is referred to as acromegaly. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Follicle stimulating hormone (FSH)causes an egg to be released from the ovaries. This is needed for fertility- Thyroid stimulating hormone (TSH)causes the thyroid gland to release its two hormones into the bloodstream which controls metabolism. - Adrenocorticotropic hormone (ACTH)is released by the pituitary, causes the adrenal glands which are located on top of the kidneys to release their hormone, cortisone, which fights infections. • Andre the giant, the wrestler also had this problem and only lived to the age of 42. • You get this extreme sizebecause of the pituitary problem, but you also get these facial and bone deformations. It is treatable in many cases with surgery of the pituitary gland if it is caught early if its because of a tumour on the pituitary. - Today, human growth hormone is used therapeutically. People who are of short stature, this is the term expected to be used, we don’t use “dwarf” or “midget”.• Children who are born today with a deficiency of a growth hormone can be treated with growth hormone. This is because it can be made by genetic engineering techniques. It used to be extracted by the glands of cadavers, but it was associated with problems because sometimes the solutions we used were contaminated from the original cadaver of various viruses. Today this is no longer the case. • This is a medical or genetic condition, generally for adult height of under 4 foot 10. HUMAN GROWTH HORMONE- As we get older, the concentration of human growth hormone in our body decreases. What happens if we don’t let it decrease, is it possible that it could have a rejuvenating effect? - There was a study back in 1990. A paper was published in the New England Journal of Medicine which is a highly prestigious publication.Daniel Rudmanwas the leading author. They had enlisted 21 men which is not a large number, it was a pilot study. They injected them with human growth hormone which was very expensive, it costs 17,000 $ per subject.
• Some of the men claimed that they felt better, that they looked better and that they felt stronger. Their was an increase in muscle mass and lean tissue. (Objectively measured). There was a decrease in fatty tissue (objectively measured), increase in skin thickness and increase in the average density of lower back vertebrae. This would be associated with benefit of rejuvenation.• However, the study was stopped after 6 months. There was an increase in blood pressure, the glucose levels in the blood increased, there was carpal tunnel syndrome found in some of the subjects and their was breast enlargement. They stopped the study, but the quacks had jumped onto the bandwagon. They were selling what was said to be human growth hormone all over the place based on this study.• Rudman had to write a letter to the editor saying that the human growth hormone they were using was associated with side effects that were unacceptibnle and that was they were reason for stopping the study. However, this did not stop the quacks. • In turns of performance their was no significant improvement. The people kept selling what they said was human growth hormone which could not have been because it was very expensive at that time. Today it is much less expensive because it can be made by recombinant DNA technology. There’s no need to extract cadavers, you can just implant the gene that codes for the hormone into bacteria, and the bacteria will churn out the hormone. - The government eventually cracked down on the promoters of human growth hormone even though that’s not what they were selling. Today it’s used in medicine, its a standardized version only available to physicians. • So, in the quack industry they knew their were so called human growth hormone stimulators. Sylvester Stallone uses this, but the story is that he may have actually paid to have real human growth hormone injected. Growth hormone activators are the things being promoted. They say that human growth hormone is a protein, which it is, and that the exact amino acid composition has been determined which is also true, this product contains a mixture of amino acids that are found in human growth hormone. Taking this is like putting bricks, windows, doors on an empty lot and waiting for it to assemble themselves.. its not going to happen. Just because you have the raw materials to make human growth hormone does not mean that the body will use them to do that. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• The reason why human growth hormone synthesis winds down in the body as we age is not because of lack of raw material, its the wind down in all the enzymes needed to make the human growth hormone. So these products do not increase human growth hormone in the body. These products make all kinds of claims of lowering body fat, increases muscle tone, reduces wrinkles, can increase endurance and stamina, this may be true if actual human growth hormone was injected, but it’s not true for these products. ‣It is on the market because of there very careful with the wording they use.- It’s not only humans who produce growth hormone, animals do this as well. You can extract hormones from animals and use it in humans, or you can try to use human growth hormones in other scientific studies. There have been a few studies that suggest that there’s faster recovery in fractures with growth hormone, but these studies are early and still need evidence. - The cow produces there own version of the growth hormone. In this case it is responsible for triggering the production of milk. Bovine Somatotropinor also known as Bovine growth hormone (BGH)is secreted by the pituitary just like in humans. It can increase milk yield by 20%. This is something that farmers would like to see. • The treatment can be sold, the injection of Bovine growth hormone into cows to produce more milk. However, this comes with some controversy. There’s also a massive movement against this to eliminate Bovine growth hormone, activist claim all side effects. There have actually been no side effects noted. There was first concern that the cows may develop mastitis which is cracking in the utter due to the fact that it was being enlarged by the increase production of milk. This was only a theory that never materialized.• Because of the public concern promoted by the activists, the use of Bovine growth hormone in animals has declined. In Canada it was never approved in the first place, but in the US it was. - Pigs also produce porcine somatotropin. It is possible to increase their size by injecting some of this hormone which can be made by genetic engineering techniques. The expression “fat as a pig” may actually have some meaning here. Right now its not being used, even though it would be perfectly safe and could make the meat cheaper, it’s because of the fear of any genetic modification backlash. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- It would indeed allow the pigs to grow more rapidly and change the distribution of muscle to fat, requiring less feed. So one could argue that this would allow more people to be fed, but the public is too suspicious of this technology. THYROID GLAND- The thyroid gland sits right around the trachea and it is in the form of a shield like they use to use in the Ancient Greek days and the name comes from Ancient Greek. - It’s a small gland but it does big things. - In Ancient Rome, Pliny, the natural philosopher noted that people who suffered from goiter, which is an excessive growth on the neck, can be treated by eating burned seaweed. It was not clear how they came to this conclusion, it might even be possible that the Ancient Chinese noted this before, its very hard to know people of the lack of historical records. • Before scientific medicine would be to try and eat something. This meant they would try all kinds of things, but most would not work. Sometimes they would chance on something that did, and if it did work, that would become the essential form of treatment. - The thyroid gland was first described in detail byLeonardo DaVinci(1500). He drew all kinds of fascinating anatomical diagrams which were highly detailed. His diagrams of the heart were so good and detailed that a surgeon based a new type of operation on his diagrams. He did not know the function of the thyroid gland, he was just interested in the anatomy. - In the early 17th century (1602), Felix Plattergave the first description of a condition known as cretinism. It is characterized by physical deformities and learning disabilities. Today we know this is due to iodine deficiency in the diet because iodine is required for proper synthesis of the hormones by the thyroid gland. - In 1789, Francois Emmanuel Foderein France made the connection between cretinism and goiter. He stated that people who suffer from cretinism were likely to go on and develop goiter and vice versa. People who had a large goiter were likely to eventually show some kind of loss of mental faculties. - In 1811, Bernard Courtoisin France discovered iodine in burning seaweed. He was not looking for anything to do with thyroid chemistry, he was trying to make potassium nitrate which was needed for gun powder. He was trying to extract this from seaweed because seaweed contains nitrates. • He found when he heated up his seaweed it released this pink gas and this eventually came to be called iodine, the Latin word for purple.
- Bernard Courtois was a chemist, he was not into the thyroid, but it was a very important discovery. Soon after, in 1820, Jean-Francois Coindetin France began to realize why seaweed had functioned as a treatment for goiter. It must be the iodine because he had seen Courtois discover iodine in seaweed. He wrote a paper about this, and it went into practice. People started to use iodine to treat goiter. - In 1835, Robert Gravesdescribed a condition in which the goiter went together with these bulging eyes and palpitations, a very fast heart rate. This came to be called grave’s disease, it is due to over activity of the thyroid glands, too much production of thyroid hormones. - In the middle of the 19th century (1860-1890), Dr. William Gullin England described another version of cretinism. This was adult onset, it mostly affected women after menopause pause. He wrote a paper describing these cretinoid conditions that affected some women (not a large number).- In 1822 William Ordcoined the term “myxedema” which described women who had stopped menstruating and who had these cretinoid features. He recognized that this was a hypothyroid condition, that the thyroid was not working properly. - In 1891 Victor Horsleyused monkeys to show that this condition, cretinism and body wasting are due to deficiency of thyroid function. By the late 1800’s it became clear that this gland was very important, that it could either be under active or over active. Treatments began to be used. - In 1891, a paper describes treating this myxedema, which was hypothyroid condition (too low), by injecting with a hypodermic needle extracts of the thyroid glands of sheep. This was the first treatment of a hypothyroid condition. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- In 1895, Adolf Magnus-Levydiscovered that the basal metabolic rate is influenced by thyroid function. So the thyroid did many things in the body including affecting our metabolic rate.- In 1914, Hakaru Hashimotowho was a Japanese researcher reported that a poorly functioning thyroid, that is a hypoactive thyroid, could be caused by a build up of white blood cells. Eventually an under active thyroid would be named “Hashimoto’s thyroiditis” or Hashimoto’s disease and that term is still used today for this under active thyroid gland. - The big break through in thyroid research came in 1914 when Edward Calvin Kendallisolated thyroxin from a huge number of pig thyroid glands. He wasn’t able to get the structure of the molecule right at that time, but he was successful in isolating thyroxinwhich is the active ingredient that is released by the thyroid gland. This made treatment of hypothyroid condition possible because anyone affected by it could just be given thyroxin, the thyroid extract. - It was soon noted that there were dietary factors that could influence how the thyroid gland worked. In rabbits that were fed large amounts of cabbage, they developed an enlarged thyroid. This eventually turned out to be because there were compounds in cabbage that would interfere with the absorption of iodine by the thyroid and it needed iodine to generate the thyroid hormones. - Dorothy L. Sayerswho was one of the great mystery writers in English literature, in 1933 capitalized on the thyroid stories. Lord Peter Wimsey was her detective, but in this case it was all bout thyroid problems. A lady had hypothyroidism for which she was being treated with thyroxin and because of a complicated situation, her husband wanted to do away with her and took away her medication and she started to spiral down hill until lord Peter discovered the problem and saved her. It’s always interesting for how mystery writers will take real life stories and put them into their stories. - In 1956, Deborah Doniachand Ivan Roittshowed that this condition, Hashimoto’s thyroiditis was an autoimmune disease. This means that the body stats to attack itself, like arthritis. This is when the body generates antibodies that then attacks the thyroid gland and prevents it from properly synthesizing the thyroid hormones. • This is a problem because the thyroid controls metabolism. There can be all kinds of problems that occur with an improperly functioning thyroid gland. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
HYPOTHYROIDISM- It results in fatigue and sluggishness, slowing of the heart rate, tendency to obesity, the skin feels clod and clammy, you get brain fog; trouble thinking, and hair also starts to fall out. There are a lot of consequences of a hypothyroid condition GOITER- As the thyroid gland attempts to extract the small amounts of iodine from the blood stream it grows in size. Sometimes it can be quite catastrophic. It’s not necessarily symptomatic, these people live normally with it, but it can be corrected these days with surgery. - There are foods that can interfere with the iodine uptake. - Sometimes people with thyroid problems will religiously stay away from these foods because they are worried. It is true that they contain goitrogens, it is mostly a laboratory finding, so you would need to eat a truck load of cabbage in order to have any kind of effect on impaired iodine absorption. This is not an issue. - In North America and the Western world, hypothyroidism is very rarely seen now because of the widespread availability of iodized salt and when potassium iodide is added to salt, you don’t need much iodine, it’s enough to allow the thyroid gland to function properly. This was one of the first and most important food additives (iodine to salt). People try to decry additives as being poisonous substances but here’s a case where the addition of iodine to salt has saved many people from having thyroid malfunction. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
TREATMENT- The treatment is very straightforward, introduce thyroxin. Today it can be synthesized. Levothyroxinis the way that it is used, when you synthesize thyroxin in the laboratory it comes in 2 versions, right handed and left handed version, they are mirror images of each other and it turns out that one of these are more active than the other and that’s the one that it used in this medication. Synthroidis a common name for levothyroxin. - What happens if the thyroid gland over produces it’s hormones? It results in jitteriness, anxiety, nervousness, a very rapid pulse, fatigue, hair loss, and weight loss. HYPERTHYROIDISM- The condition whereby there’s too much of thyroid hormone produced is what we know as grave’s disease. This is also an autoimmune disease. When the body produces certain antibodies that attach to the thyroid, they stimulate it to make more thyroid hormones.• That results in the bulging eyes, it can result in goiter. • George and Barbara Bush were both amazingly stuck with Graves’ disease. This is not a disease that can be caught from anyone, so it was a statistical quick that both husband and wife happened to suffer from Grave’s disease. They investigated the plumbing of the White House to see if there was any kind of iodine that was present in the water, nothing was found, it just so happened that they both suffered from the disease. TREATMENTS- There are drugs that can block the formation of the hormone. Methimazoleis one of them. An interesting possibility is to use radioactive iodine because the iodine will concentrate in the thyroid gland and the radioactivity will destroy part of the gland, it’s also possible to surgically remove part of the gland.• This idea of using radioactive iodine is the reason why in case theres a nuclear accident, people would be urged to take non-radioactive iodine, potassium iodide supplements.This is so that there thyroid gland would load up on the regular iodine, so if there’s any radioactive iodine release from the nuclear accident, it would not be absorbed into the thyroid gland. We have seen that in nuclear accidents such as the Chernobyl accident which released a lot of radioactive iodine which led to the increase in thyroid cancer.
• Now around nuclear power plants, people are given iodine to take just in case of an accident happening as it would reduce the chance of having thyroid cancer. - Surgery is also possible, you can remove part of the thyroid gland which means it produces left of the thyroid hormone. This is not an invasive surgery, it is generally just a 1-2 day procedure. • Generally after this surgery the patient will have to take synthroid because the thyroid gland after the surgery will not produce enough of the thyroid hormone, so there’s a balancing that always comes about. - The hypothalamus sends a signal to the pituitary gland, the pituitary gland in turn responds to the signal (TRH) and it will then send a signal to the thyroid gland and that signal says to start producing the hormones. There are 2 thyroid hormones, T3and T4. Each can be individually tested in a blood test, so can THS be tested as well. The exact medial problem can be determined by the relative ratio of the THS, the T3, and the T4. • Separate glands are involved, including the hypothalamus, pituitary, and the thyroid. The pituitary is important because it causes the release of the thyroid hormones. - Sitting on top of the thyroid gland are the parathyroids. They are very small. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
PARATHYROID- Together with the thyroid they regulate the metabolism of calcium and phosphorus. These are important in bone formation, calcium phosphate is the basic material of bone. Calcium is needed for the heartbeat. The exact amount of calcium and phosphorus in our blood stream is very important. - Our bones are essentially calcium phosphate. Where does the calcium and phosphorus come from? Both found in many foods. You don’t need to consume dairy to get calcium. Dairy is a good source of calcium, but there are other good sources like orange juice, soy beans, sardines, beans, collard greens, broccoli, etc. • There’s no deficiency in calcium if someone doesn’t consume dairy. - Once you inject the calcium, how does it get into the blood stream? It has to go from the intestine into the bloodstream. How does it get into the intestine? It gets into the intestine when we eat the food, from the intestine it has to get into the plasma, the circulation of the blood. This is where vitamin D is important. This is the so called “sunshine” vitamin. It is needed for calcium to be absorbed into the plasma. If there is too much calcium it will be secreted by the kidneys. If there’s not enough calcium then the kidneys will release less and less of the urine (equilibrium). - Calcium is also used in the formation of bones. In this case it needs a hormone, that is calcitonin. It is produced by the thyroid and whenever there is a need for more bone formation, the thyroid will release calcitonin and that will deliver the calcium from the plasma into the bone. • If it turns out that for some reason calcium levels in the blood drop and calcium is needed for the functioning of the nervous system, then the bone will serve as a supply of calcium. It will start dissolving and release calcium back into the circulation, this is guided by parathormone which is secreted by the parathyroid glands. It is this back and fourth activity that keeps calcium at a normal level in the blood stream. • If there’s an excess of calcium and the kidneys are incapable of eliminating it all in the urine, then there’s a chance of kidney stone formation. - Ingestion of calcium is important for bone formation because in order for it to get into the plasma and into the bone it first has to be eaten. It is also important so that calcitonin can be formed and this can be used therapeutically. If calcitonin is the hormone that delivers the calcium from blood stream to the bone, which it is, is it possible to increase calcitonin levels to combat osteoporosis.
• Yes this is possible. Calcitonin can be isolated from salmon and it can be used as a nasal spray. ADRENAL GLANDS - These glands are located on top of the kidneys, there are 2 of them. There are 2 parts to the adrenal gland, there’s the cortexwhich is the outer layer and the inside which is the medulla. They both have different functions, they produce different hormones. - The most famous hormone of the adrenal gland is adrenaline. This is the fight or flight hormone, it is produced by the medulla. It is also called epinephrine. We call it the fight or flight hormone because it readies the body for situations where extra energy is needed. • It increases blood flow to the muscles, it increases the output of blood from the heart, and it increases blood sugar which is used by all cells as a source of energy. • This is why when people are confronted by a dangerous situation they can run faster than they’ve ever run before. The adrenal glands kick in and release adrenaline which makes you have more energy.- The cortex of the adrenal gland produces a different set of hormones called the corticosteroids. Corticosteroids have a different function from adrenaline, they protect the body from infection, exertion, and allergic reaction. - The adrenal glands produce their hormone upon a hormonal signal that comes from the pituitary gland. This is ACTHand when that message comes, the adrenals will crank out aldosteroneand cortisol, these are the corticosteroids. - In 1855, Thomas Addisonwas the first scientist to have any kind of insight of what the adrenal glands do and what their function is. He noticed upon autopsy that adrenal glands were shrivelled in people who had complained during life of feeling un-energetic and he described this as an adrenal deficiency. Addison’s diseasewas named after him and is characterized by weakness, loss of appetite, feelings of nausea, tendency to vomit, and hyperpigmentation which means the skin becomes coloured. • He was the first one to make a connection between the symptoms in a patient and atrophy adrenal glands that he observed upon autopsy.
- In 1912, Harvey Cushingwho was perhaps the father of neurosurgery. He was a leader in introducing new techniques in neurosurgery and he also studied the endocrine system. He described a malfunctioning of the pituitary gland and some of the symptoms that were associated with that. He was the first one to note that the pituitary gland had an effect on the adrenals and that there was an imbalance of hormones because the pituitary overstimulated the adrenal glands. This was called Cushing’s disease. Later on it was discovered that it was due to a tumour on the pituitary gland which allowed the gland to crank out more ACTH. • Cushing was also the first person to introduce the blood pressure measuring device in North America. This used the mercury thermometer. • He was also a Pulitzer prize winning writing. He recorded the life of William Osler in 3 volumes. William Osler is very famous to McGill because he was a McGill medical graduate and was a professor of medicine at McGill university. He came to be known as one of the most famous physicians in the history of medicine. - Olser introduced the idea that medical students should be allowed to go to hospitals and see patients instead of just sitting in lecture rooms which was the way that medicine was historically taught. He also establish the practice of medical residency. • It was called residency because back in Osler’s days these doctors would stay in a residence near the hospital so that they would always be near the patient. A brutal business, they were always on call. Not the case today.• He wanted nothing on his grave stone other than the fact that he was instrumental in teaching medical students and he regarded this as the most important work that he did. He changed the way that medicine was taught. - In 1936, Edward Calvin Kendall, a chemist, isolated a compound from the adrenal glands of cows. He was picking up on the work of Addison. Addison had shown that their was some sort of connection between illness and malfunctioning adrenal glands. Kendall thought that the adrenal glands must be producing some sort of compound that keeps people healthy. Further corroborated by some of his experiments whereby he removed the adrenal glands from animals and they then perished quickly. However, when he injected those animals with an extract of adrenals of healthy animals then they were able to live. • This made it obvious that the adrenals were producing something that was critical to life and he wanted to isolate this.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- In 1936 he isolated “compound E” from bovine adrenals and later on this was renamed as “cortisone”. - In 1937, Taddeus Reichsteinisolated a very similar compound from adrenal glands. It had very small difference in molecular structure and it turned out to be hydrocortisone. This is a drug that’s available over the counter to use on all kinds of rashes, it works very well as an inflammatory substance. - Philip Henchwas working at the same place that Kendall was working at. He was a medical doctor. He made a very interesting observation, he noted that when a patient suffered from jaundice which is yellowing of the skin and of the eyes because of a problem with the liver where it does not metabolize used hemoglobin well and bilirubin was building up in the body. He noticed that when people suffer from jaundice or when women became pregnant and they had suffered from arthritis before, their arthritis symptoms improved. A very unusual observation, he chatted about this with his colleague Kendall, and he suggested that when someone is afflicted with jaundice or during pregnancy, the body produces a number of chemicals. These in their molecular structure to him seemed very similar to the “compound E” that he had isolated from adrenal glands. This opened up a door to the possibility of using this “compound E” to try and treat arthritis. • In 1948, both Hench and Kendall put this into practice. Their was a lady was suffering from arthritis and nothing that the doctors tried worked. She refused to leave the clinic until they did something to help her. This gave a situation to Hench and Kendall to try this “compound E”. The results were amazing, when the lady was injected with this extract of the adrenal gland, within days she showed remarkable improvement. By the fourth day she was so well she went shopping, something that she had not done in a while. Within a few weeks a number of other patients showed similar results. This was the beginning as what we refer to today as corticosteroid therapy or steroid therapy. - By 1949 a patient had the same kind of result upon treatment with ACTH. This is the hormone that is released by the pituitary gland that stimulates production of the cortical steroids in the adrenal gland. This was another possible treatment for people with arthritis. - In 1950, Arthur Nobilecame along. He found that by converting cortisone to a chemical similar to it called Prednisone the results were much better. The early results with cortisone were very good in terms of improving arthritis, but as the patient started taking it for a longer time, side effects began to show up. They started to develop a characteristic moon face, fatty deposits on the body, hair growth, and Cushing syndrome. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Prednisonewas preferable to cortisone because it had fewer side effects and the same positive effects. Their was a lot of publicity about prednisone when it turned out that president Kennedy who was elected to the presidency in 1960 suffered with Addison’s disease. He was treated with prednisone, this only came to light later, when he was no longer president, he was assassinated in 1963. In those days they did not divulge presidential illnesses. - Corticosteroids like prednisone are used in all sorts of conditions that are inflammatory conditions. What is an inflammatory condition? The 4 hallmarks of inflammation are: • Redness • Swelling • Warmth • Pain - For example, when you cut your hand it gets red because blood is flowing there to bring the white blood cells there to battle any kind of invader that may have gotten into the bloodstream which is also why the tissue swells because of the enhanced blood flow. It becomes warm and there is pain associated with this process. - Inflammation can also happen inside of the body when there’s a coronary deposit, when you get a plaque in a coronary artery which can cause inflammation. You can also get inflammation in the lungs, asthma is an inflammatory disease. - Asthma, and various other kinds of lung disease, allergies, arthritis, lupus, and Crohn’s disease can all be treated with corticosteroids. While they are very effective drugs, they treat the symptoms, they do not cure the underlying disease. There are very few drugs that actually cure disease, antibiotics are one, but other than that there are not many that cure disease. Drugs generally treat symptoms of a disease and often to an extent that the disease becomes essentially invisible but is still there. - Inhaled corticosteroids are different from the inhalers that you use for an acute attack. The steroids are used to suppress chronic inflammation. When someone has bad asthma, they would still use Ventolinas a rescue inhaler when theres an asthma attack, and they would regularly use a corticosteroid such as fluticasone, budesonide, or beclomethasoneon a regular basis to prevent further attacks. - One of the newer corticosteroids is dexamethasone. This was developed in order to try and increase the efficacy and decrease the side effects of prednisone. This is a common process in development of pharmacological substances. When you have something that works, but is encumbered by side effects, you try and change the molecular structure hoping for a better side effect profile. Dexamethasone is one of those drugs, it had found use inn a variety of treatments especially in serious lung inflammationsDownloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• We heard a lot about this drug when President Trump came down with Covid 19. He was given dexamethasone, it was interesting that he was given that because the guidelines that it should only be given to patients with Covid 19 who are already in the hospital and on a ventilator or supplemental oxygen. - All drugs have side effects, one of the side effects of dexamethasone is that it gives you extra energy. He did have extra energy after the hospital. The course of treatment is several days and it is also connected to insomnia. - The problem with these corticosteroids are the side effects which are called Cushing syndrome.Cushing was the first one to note the various effects on the body from improperly functioning adrenals which is over production of their hormones. Cushing syndrome is a collection of various signs and symptoms that are due to prolonged exposure to these corticosteroids. A sign is something that can be seen from the outside, anyone can seen it, a symptom is something that the patient feels.• This can be due to long term use of medications that are based on corticosteroids but Cushing’s disease is also part of Cushing’s syndrome. Cushing’s disease is caused by a tumour in the pituitary gland. The classic signs of Cushing’s syndrome are:‣Moon face (fatty build up on the bottom of the cheeks)‣Fat build up on the back (buffalo hump)‣Bones become weaker ‣Skin becomes thin and easily bruisedAlso predisposes to ulcers, diabetes, and high blood pressure- People need to be careful with the use of these steroidal drugs. They can be very effective for a large number of conditions. However, long term use is associated with Cushing syndrome, and some of these symptoms are very serious. - There’s also thinning of the hair, there’s a propensity for acne with the overuse of steroids, red cheeks, and discolouration of the skin, also abdominal weight gain. These are not pleasant symptoms so you always try to get away with using the lowest dose of prednisone or dexamethasone or whatever that is being used which is sufficient in controlling the symptoms. Wound healing is also slowed down when someone is on high dose of these corticosteroids. - In 1950, Calvin, Reichstein, and Henchreceived a novel prize. They were credited for finding out the mysteries of the hormones of the adrenal cortex, their structure and biological effects. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
PANCREAS- The pancreasis found next to the liver, next to the colon. It has very important functions, it is the producer of the hormone insulin. Insulin is said to be the cells gate keeper for glucose. Glucoseis needed by every cell as a source of energy. In order for the cell to absorb glucose it requires insulin. - The names that are immediately linked with the development of insulin are Frederick Banting and Charles Best, two Canadian researchers working at the university of Toronto. - In the 1920’s, they studied dogs and their pancreas. They discovered the role of the pancreas in terms of energy production. They discovered that the pancreas produces the hormone insulin which is a complex protein. Without the production of insulin, the body cannot function. - Type-1 diabetesis when the body is incapable of producing insulin and has to be supplemented. In type-2 diabetes, the body is still able to produce insulin, just not enough.• Glucose has to enter a cell where it undergoes metabolism. In order to do that, insulin has to prime that cell, without the insulin, the glucose cannot enter, that presents a serious situation.- Insulin could be used to treat diabetes, you can get it from animal glands. The Eli Lily company processed animal pancreas’, mostly pigs in those days, to generate insulin. It was one of the biggest developments in the history of medicine. - The early insulin products were based on pig insulin. Later it was also possible to use beef insulin. Both worked very well, before this, type-1 diabetics would die at an early age. • Insulin needs to be injected because insulin is a protein. It would be digested immediately if you took it orally. It does not cure the underlying condition, it just treats the underlying disease by supplementing the insulin that the body is unable to produce. - Today through recombinant DNA technology which is genetic engineering, it is possible to produce insulin that is identical to human insulin. While the pork and beef insulin works very well in people, its not 100% identical. Insulin is a protein, a chain of amino acids. Pork insulin and human insulin differ from a few amino acids, this apparently does not make a difference in the efficiency, but their may be a difference in the side effects. Human insulin should work better.
• The way they have done this is to isolate the gene in humans that code for the production of insulin, insert that gene into a bacterium, let the bacterium multiple, and then it will churn out human insulin. This is now being used today, and it does have a better side effect profile. - Another drug that’s commonly used, but its for type-2 diabetes. In type-2 diabetes the pancreas is still capable of producing insulin, just not enough to handle all of the glucose in the bloodstream. Metforminlowers the amount of glucose that is present in the bloodstream. The liver produces glucose, most people know that the source of glucose in the diet is either from sugary or starchy substances. These are immediately broken down to glucose. The liver also forms glucose from non-carbohydrates sources like proteins and fats. Metformin reduces this process, therefore reducing the total amount of glucose in the bloodstream allowing the small amounts of insulin present to deal with the glucose. • Insulin is a Canadian discovery. It has changed the lives of many people. GONADS- Gonadsare the sex organs. The hormones that they generate are what make men into men and women into women. • The main male hormone is testosterone. • The main female hormone is estrogen. ‣They are both steroids (4 ring system). ‣The difference between the two hormones is not a lot, they are very similar, but that small difference makes a very big difference when it comes to their affect on the body. - Both men and women produce both testosterone and estrogen, but in different amounts. Men produce more testosterone and women produce more estrogen. • Normally these are in proper balance, but not always. When they are not in proper balance, that’s when there’s a possibility that people who were born into one sex but do not feel that they should be part of that sex. They think that while their body is of one gender, their mind is of another gender. This is the transgender situation, where people will undergo hormonal treatment or surgery to satisfy their needs to be in the proper body. This has nothing to do with sexual preferences/homosexuality. This is a condition whereby a person has a mental state that conforms to the opposite gender then what their body is. • One situation where a man thought that he should really be a women. This requires a change in hormones, it requires taking estrogen, and it is possible to have a sex conversion. A total sex conversion involves surgery.
• The classic example is Bruce Jenner. The American Olympian who won the decathlon in 1976. The decathlon is a 10 event system and you get points in each event. Bruce Jenner had been transformed into a women (Caitlyn Jenner). He had been taking estrogen for a long time. It is unknown if he has had the critical surgery or not. • Caitlyn Jenner is now very happy with her life and feels contented. - It is also possible to go in the other direction. • Surgery can be involved to remove the breasts. The hormonal treatment is with testosterone, this changes the body structure and makes hair grow. There are also experiments these days to form a penis or to transplant a penis to make the operation complete. This is not a perfected procedure yet. - The testosterone is injected with a syringe because it has to go directly into the blood stream. It engages in a large variety of reactions. One of the reactions is the conversion of testosterone into a very similar molecule called dihydrotestosterone. This is a problem because it causes the prostate gland to be enlarged. This is what surrounds the urethra, so if it gets enlarged it makes urinating difficult. This is a situation that you want to avoid. When men have an enlarge prostate, to prevent to formation of dihydrotestosterone which is done with a medication that blocks the conversion of testosterone into dihydrotestosterone, this is finasteride which goes by the name of proscar. This will be helpful in people who have benign prostate hypertrophy, which is a benign increase in the size of the prostate, the idea here is to reduce the size by blocking this conversion. • Dihydrotestosteroneis also the reason as to why men lose their hair, if there’s excessive conversion to this. This is why finasteride, but this time under a different name; propeciais used as a treatment for hair lose. It works well. You block the conversion, and that allows more hair to grow. This is useful for men, not for women. • Both finasteride and propecia are only available by prescription. • Not everyone who uses propecia will have the great effects that they show, it works differently on people - The libido/sex driveis also linked to testosterone. Low levels of testosterone lead to a low sex drive. The only way that you have a low levels of testosterone is by testing it with a blood test, there’s no other way. It’s possible to get testosterone supplements to help increase their levels.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- There’s another kind of drug known as the anti-androgens. The androgens are the male sex hormones. The anti-androgens are the ones in the body that block the effects of the androgen hormones by fitting into the receptor cites that the hormone would fit into. (Lock&Key Effect). Zoladexis one of these drugs, it is used in the treatment of prostate cancer because that is a disease that is linked with high levels of testosterone, so you want to block the levels of testosterone, these anti-androgens will do that. - Another interesting connection of using these anti-androgens like Cyproterone Acetateis probably the best example, they can be used in the treatment of people who have various kinds of sexual defiance’s. If they are treated with this, they no longer have the urges that they usually had. This is referred to as medical castrationbecause it essentially blocks the effect of testosterone and the theory is that the sexual offenders do what they do because they are out of control with too high of testosterone levels. There are situations where people who have been arrested and found guilty of such activity are given the choice of either going to jail or taking the drug to undergo the chemical castration but they need to continue taking the drug. Many of them do choose the chemical castration method because it is preferable to sitting in jail. • The best example of the medication is the story of Alan Turing. He was the father of the modern computer industry. His work during the Second World War was critical to the war effort. This is because people he had designed the Turing machine which was an early form of a computer which was able to decode the German messages that were sent in code. The machine is used to send codes where every letter is turned into a different letter and you need to have a decoding system to understand the message. Turing designed this decoding system which was able to decode the secret messages during the war which was tremendously helpful to the allies. There’s a station of him in England. Unfortunately his story does not have a happy ending, he is said to have committed suicide but this is not clear if he did or not. He was found dead in his bed and there was an apple beside his bed. That apple was supposedly laced with cyanide. To be a homosexual at that time was not accepted in British life, he was accused of lewd acts, he was sentenced to go to jail unless he accepted to undergo Cyproterone acetate therapy. He did agree to this, but this caused him such frustrations that maybe this led to his suicide. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
ANABOLIC STEROIDS- Testosteroneis one of them. The term anabolic means muscle building and the reason that men are more muscular than women is because testosterone is an anabolic steroid, it leads to the formation of the proteins which muscles are made of. - Comic books and magazines had advertisements of bodybuilding. Charles Atlaswas one of the first bodybuilders who achieved fame. He was telling people how to exercise, however, this was also the time people started experimenting with various kinds of hormones. - Body builders are very muscular, and they have a large amount of testosterone like compounds floating around their blood stream. The question is can you do this without taking hormones, yes you can with a lot of exercise, but it becomes easier when you’re helping it along by taking hormones. This also goes for women as well. When they start taking testosterone they will also notice other bodily changes that may not be desired. - The use of steroids in athletic competitions is where it gets interesting. These steroids allow you to build muscle so they enhance athletic abilities. • In the 1972 Olympics, it is thought that the Russians and the East Germans were already using steroids in order to help there athletes. Some of the women athletes started to look like men, they had unusual hair growth, had wider shoulders, and had more of a “man” physique. • In those days there were no regulations about using drugs during the olympics. Today we have all kinds of regulations, but athletes still do it and know how to cheat the system. - By the 1980’s, the use of these anabolic steroids, testosterone like compounds was quite widespread in the athletic community, especially among weight lifters. • All of a sudden they had been lifting weights that had not been done before. It’s been said that today the weights that the weight lifters are lifting would not be possible to do without the use of anabolic steroids. - Of course there is testing of the blood, but these people know how to circumvent this. They don’t take this just before competition, they mostly take it during training and because the half life of these drugs are quite short, they can just give up the drugs before the competition and they won’t be found in the blood. - A tragic example here in Canada was during the 1988 Olympics when Ben Johnson won the 100m run and got the gold medal for it. The 100m run is probably the elite event of the olympics, but the winner is crowned the world’s fastest runner.
• So, Ben Johnsonwas crowned the world’s fastest human until a blood test showed that there was Stanozololin his blood. At first he tried to say he didn’t know how it got there, but there was no doubt that he had abused the drug and later on he admitted to it and he was stripped of the gold medal. - Athletes do cheat, there’s many ways to circumvent the system that detects cheaters. It is based on taking urine samples and looking for drugs in the urine. In order to conceal steroid use, they can insert a catheter into the bladder, drain out the urine, and through the same catheter, they can introduce urine they have taken from a friend who does not do drugs. When they have to give a urine test, they will be giving someone else’s urine. Now, during urine tests, there has to be a witness to the process. They have to see where the urine is coming from, but this does not detect this kind of cheating. This detects someone hiding a vile in their shorts or something and using that. This could still be happening today, but it was happening a lot in the 1980’s and 1990’s.- The use of anabolic steroids in order to increase energy and muscle growth does not go without penalty. There are side effects, similar to effects of increased amounts of adrenal hormones circulating in the blood stream. The side effects include: • Acne • Excessive hair growth • Aggression • Propensity for liver disease • Depression • Reduction of good cholesterol (HDL)• Testicular atrophy: When steroids are being introduced from the outside, the body does not sense the need to produce them. • Breast development: This is because the body tries to counter the overuse of steroids by synthesizing more estrogen. - Lance Armstrongis another famous person who used not only anabolic steroids but various other chemicals as well. He used Erythropoietin (EPO), this increase the amount of blood into the body and it’s ability to transmit oxygen to all of the cells. He used cortisone and human growth hormone. He also did illegal blood transfusions. He denied using all of this and that he was innocent, but it was all proven. • He was a great cyclist, he would’ve probably won a lot of the competitions without the use of these substances. He was so determined to win that he took to cheating. So, instead of going down as the greatest bicyclists in history, he goes down as one of the cheaters in that field. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- The racing industry is one of the ones that is plagued with the use of various kinds of drugs, some of them legal, but many of them illegal. - In the recent Olympics the Russian team was accused of doping, and tests did show this. They were using a variety of anabolic steroids to improve their performance, but this is just cheating. The cheaters seem to be one step ahead of the scientists who develop the tests to find these drugs. If you change the molecular structure just a little bit, it requires a different test to detect it. Doping is unfortunately still going on. ESTROGEN AND PROGESTERONE - Estrogenis the hormone that is responsible for the secondary sex characteristics which is the lack of hair on the body, fat distribution, breast growth, etc. - Progesteroneis the pregnancy hormone. - The menstrual cycle in women lasts on average in women 28 days. From day 1, estrogen levels start to increase, and it reaches it’s maximum effects roughly in the middle of the cycle, around day 14. This is also the time that progesterone starts to be produced. If there is no pregnancy, then progesterone levels will decline, and so will the estrogen levels by day 28, then the lining of the uterus is shed, this is known as menstruation. - There’s a condition known as premenstrual syndromewhich strikes some women in the second half of the menstrual cycle. They become irritable and don’t feel like themselves. They claim depression, mood swings, hostility and anger, nervous tension, craving for sweets, water retention, weight gain, headaches, and joint pain. Not every women experiences this, but there are some who find that the second half of the menstrual cycle is very difficult because of there symptoms. They seek treatment for this. - There are some cases where women have tried to get away from committing crime and blaming it on hormonal imbalances. Some of this has gone to court, but it doesn’t seem like anyone has gotten away from it. - There’s some evidence that by taking magnesium supplementsand vitamin B6 reduces the symptoms of premenstrual syndrome. However, this is kind of a grey area, there isn’t even universal agreement that this syndrome exists. There’s a lot of anecdotal evidence that women claim to not feel right during the second half of the menstrual cycle, but this requires more research. There’s no big risk in taking both these supplements.
- Progesterone is referred to as the pregnancy hormone. This is what allows the fertilized egg to be implanted in the wall of the uterus. - The ovaries store all of the eggs that a women will ever have. Every month, once they reach puberty, the ovaries release an egg which will travel down the Fallopian tubes, and if it happens to encounter sperm and is fertilized, then a pregnancy is on the way. • Only 1 sperm is needed to get in there and fertilize the egg. - Why is it that a pregnant women can not get pregnant again? This is because the body knows that pregnancy is a difficult situation and that 1 at a time is enough. How is it that an egg is no longer released? The release of an egg comes from a signal from the pituitary gland, the so-called follicle stimulating hormone (FSH).This stimulates the ovaries to release an egg allowing it to travel down the Fallopian tube. When a pregnancy is on the way, progesterone levels increase, and it is this increase that is picked up by the pituitary gland and prevents the release of the egg. • Levels of progesterone do not decrease during the second half of the cycle is a pregnancy has ensued. Levels do in fact rise, and those levels prevent the release of an egg and it also allows the fertilize egg to be implanted into the wall of the uterus. - How was the theory of the birth control pill formulated. The basic idea was that if progesterone prevents pregnancy, then why not administer progesterone to a women to prevent pregnancy. The first problem was where do you get progesterone? Progesterone is formed in the body in very small amounts. The first way that they were able to isolate enough to work with and determine its molecular structure was from pregnant sows because their biochemistry is similar in this sense to humans. They produce progesterone when they are pregnant, but they need an awful lot of pregnant sows to produce a few milligrams of progesterone. This was okay for research, just trying to determine the chemical structure, but in order to do clinical work, to see if this could prevent pregnancy or not, they needed much more. A company struck a deal with a milk delivery company. They thought that the best source of getting progesterone was from the urine of pregnant women. The deal was that if any pregnant women who was willing to leave. A bottle of her urine in front of the door in the morning, they wold be given a free bottle of milk. This is how the company was able to collect the pregnant urine, this is where the expression “the milk man did it” came from because it was in the interest of the milkman to have as many women pregnant as possible because they would make more money because they would be paid for every bottle of urine they brought back. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Eventually the molecular structure of progesterone was worked out, but this business of collecting urine of pregnant women was not a way to get large amounts of it to do the clinical trials. - Russell Marker(1992-1995), a brilliant chemist came along. He investigated various plants because he knew plants produced a variety of steroids, and since he knew that progesterone was a steroid and he wondered whether or not he could find a plant that had some chemical that could be converted into progesterone. He found a plant in Mexico, it was a kind of yam like a sweet potato and it contained a compound called diosgenin. This could be converted into progesterone in the laboratory. For the fist time, there was an ample source of progesterone that could be used in the trials. - Progesterone had to be injected, it could not be taken orally. The question was to change the molecular structure in such a way to make this drug still effective and to be taken orally. After a number of experiments, a chemist by the name of Carl Jurassy, developed a compound named Norlutin. It has a chemical similarity to progesterone, but it can be taken orally. The idea was that if you take this orally, it tricks the body into thinking that this is progesterone and that will prevent the release of eggs from the ovaries. • The first thing was to try this on animals, especially on rabbits because they have a proclivity for reproduction. It worked, when they were treated with this substance, they were unable to impregnate the female. • The first clinical trials were carried out in Puerto Rico. There’s a bit of a cloud hanging over that because it isn’t quite clear if the subjects were informed of what was going on and that it was an experimental treatment. However, it did work, in the early 1960’s they had found a way to formulate the pill so that there was no egg to be fertilized. The early birth control pills were put on the market and their were many versions of these. The early ones caused some side effects which was called breakthrough bleeding. They then added some estrogen to the pill and that solved that particular side effect. • The modern birth control pill has much less of a progestin than the early ones, it has some estrogen and the side effects are very few. The idea here is to take a pill everyday, but you actually only need the active ingredient 21 days. You don’t want to take a chance on missing anything or miscalculating so the pill box is designed in such a way that you take a pill everyday although some of those pills, 7 or 8 of them are just sugar pills. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- The pill works well, there are some side effects. In some cases it can cause high blood pressure. The only time that any significant problems were noted were in people who also smoked. The birth control pill is safe, but you must remember that pregnancy also comes with complications.- There are other ways that progesterone and estrogen can be used to prevent pregnancy. There are inserts that can be implanted underneath the skin and they slowly release the chemicals. This hasn’t turned out to be very popular, even though its very minor to make an incision in your skin, its hasn’t turned out to be used a lot. - The understanding of how pregnancy works and the chemistry of progesterone has also led to the formulation of the so-called abortion pill or the morning after pill. Theres a lot of controversy hear. The abortion pill and the morning after pill are not the same thing. - The morning after pill is taken the morning after or as soon as you can after having unprotected sex. This is known as Plan B. The active ingredient here is a compound that is very similar to progesterone. The morning after pill essentially allows the body to think that there’s a pregnancy already underway and therefore, a novel egg, even if its fertilized will not get implanted in the wall of the uterus. It is a form of progesterone, a molecule very similar to it, and when its in the bloodstream then a fertilized egg will not be implanted and it also has the ability of reducing the chance of an egg being released by the uterus. It has to be taken very soon after unprotected sex. - The abortion pill, or the RU486is a different drug. It can be taken weeks or even months after a pregnancy. This basically is a drug that once again has a similar molecular structure of progesterone, but it blocks the action of progesterone. A constant level of progesterone in the bloodstream is important in order to keep a fertilized egg implanted in the wall of the uterus. If the action of progesterone is not there, the lining of the uterus will start to shed and the fertilized egg will be lost. • This drug will start the breakdown of the uterus lining and that will initiate menstruation and bleeding which is sometimes quite intense. It can come with pain, so this has to be followed medically. This is something that can be used in the case of rape. This is not something that should be used in as a birth control method, this is only used in an emergency type of method. This drug is an antiprogesterone. Mifitonis the generic name and it is legal, but is available only by prescription as they have to be medically followed. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Besides progesterone therapy there’s also estrogen therapy. This is a treatment used after menopause when women are no longer making there own estrogen. Estrogen is the main female sex hormone, and seeing as after menopause the body no longer produces it, this causes side effects. The skin becomes dry, the main issue is generally wearing of the bones, this condition is known as osteoporosis. This leads to veterbral fractures and easy hip fractures. Estrogen supplementation that is used in people who are prone to osteoporosis. - In the early 1960’s and on, it was quite routinely provided to women after they reached menopause in order to prevent the post-menopausal symptoms. It prevents hot flashes and the nasty symptoms that some women have. However, there was a stumbling block when some studies showed that estrogen supplementation increased the risk of breast cancer. Prescriptions in the 1960’s were very popular, Premarinwas the main one. The name is interesting becomes it comes from the fact that it is isolated from pregnant horses. It was a very commonly prescribed medications. However, there were contraindications: • Migraines • Stroke • Kidney Disease • Diabetes • Hypertension • Liver disease • Breast or uterine cancer ‣Whoever has these things are not candidates for the use of estrogen therapy. - There were also concerns that in healthy people estrogen treatment can result in symptoms like cyclic bleeding, and most women are happy to be rid of the cyclic bleeding. High blood pressure is another possibility, but the most worrisome is is breast cancer. This is because breast cancer increased quite significantly in the 1960’s and all of the indications were because of the prescription of estrogen. • There was a lot of publicity about this. In magazine articles, the number that was often quoted was a 30% increase in breast cancer risk. So, women reading these magazines and sees this headline and are taking these supplements, the next thing they do is throw away the pill. - In the 10 year period following menopause, the chance of any women developing breast cancer is about 3-4%. So out of every 100 women, 3-4 women will develop breast cancer. If they are taking an estrogen supplement, this increases to about 5%, so 5 out of every 100 women. So where does the 30% increase come from, it’s the difference between 3.5 and 5 that’s a 30% increase. That is called the relative risk, the absolute risk is much less, you’re just talking about an increase of about 1 breast cancer case in 100 women. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• One could also say this in a different fashion, “A post menopausal women who takes estrogen reduces her chance of remaining cancer free from 96% to 95%.” It’s very important to understand the difference between relative risk and absolute risk. - There are many women who take estrogen supplements and who are happy with it. Because of this concern of estrogen therapy, Premarin, there are a number of so-called natural estrogens which are on the market. These are compounds that similar in molecular structure to estrogen that are isolated from various kinds of plants. They can be isolated from soy for example. However, the evidence is very weak that these can have the same kind of effects as Premarin. So if someone really does have symptoms, Premarin is the way to go. ENDOCRINE DISRUPTORS- A any chemical that disrupts hormones, that is either a hormonal agonists, that it behaves like a hormone, or an antagonists, so that it blocks the action of a hormone. This can have very significant effects on physiology. - There are substances in our environment that have properties similar to hormones. Bisphenal A is the chemical used to make poly carbonate plastics and trace residues may be left behind. We also have phthalates, these are substances used to soften plastics, they are called plasticizers. In the laboratory they have hormone disrupting functions.
ALTERNATIVE MEDICINE Caitlin Malcolm-Pottle
• Chlorine dioxide is a simple molecule; ClO2. It has bleaching potential and does have anti-microbial possibilities in Petri dish. This does not mean that consuming this will have any benefit. Robert Young has written what he claims to be a scientific article, this is total pseudo science. This immediately becomes apparent, even to the uneducated because the formula he proposed for chlorine dioxide, he used a capital ‘L’, which is not conventional. Also, ClO2 is an inorganic compound, composed of oxygen chloride, and he says potassium gold, which is nonsense. As soon as you see some fundamental errors like this, you can dismiss any kind of value the book might have. He has been successful in pulling in some pigeons, and charging a lot of money for his treatments, he’s been in jail once, and it’s possible that he goes again. PIGEON THERAPY- This is not therapy for mentally ill pigeons, this actually uses pigeons in order to treat human ailments. - For example, a patient complaining of a stomach ache. The therapist will take a pigeon and hold it onto the belly of the patient, suggesting that the disease will be transferred to the bird. The bird does not like this one bit, and then all of a sudden, it dies. The pigeon is discarded in a a garbage bag and a second pigeon is used, the same thing happens and a third pigeon may be used. By this triple therapy, the patient may finally say that they are feeling better. This is nonsense, it is animal cruelty. The reason that the pigeon dies is because the therapist snaps it’s neck with his thumbs. The person undergoing this therapy believes in it, and believes that he or she will actually feel better. Mind over body, however the SPCA should be going after these people as its animal abuse. Luckily, this is a rare situation. This is just to show the wide spectrum of treatments being proposed. URINE THERAPY - Urine therapy is based on drinking urine, mostly your own but can be sometimes the urine of others. The urine supposedly has all kinds of magical powers. You can enrich it apparently with some vitamins and then it can cure all ailments including aids. - These people actually hold conferences, it’s an annual thing. The population has grown. They talk about all the benefits of urine, you can even buy urine if you don’t like the human urine they have cow urine for sale as well.• There are also urine dispensers where you can apply it to your skin or drink it. You will obviously get people telling you that felt better after urine therapy. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
EAR CANDLES - You put these candles in your ear and light one end. The vacuum that it creates sucks out disease from the body. There’s all kinds of claims about what this can do. The rational explanation is that the vapours will suck out disease, there are natural oils involved, etc. • The physics of it is nonsense. Although the candle will produce some hot air, and the hot air rises, it does not produce any suction down the tubular inside the candle. This can be proven very easily because you can take a candle and light it and hold a piece of Kleenex under it, and you’ll see that it won’t be sucked up. CUPPING- This is where they put a glass cup that has been heated very quickly on the skin. As it cools down it produces a vacuum. This is quite easily done by taking a piece of cotton soaked in alcohol and they heat up the inside and quickly clamp it on the body. The idea here is that this will suck toxins out of the body. • The result leaves the cupping marks on the body, or if you’re unlucky and hasn’t been properly done, you could be left with terrible burns. This is not alternative medicine. This makes no sense whatsoever. WHAT IS ALTERNATIVE MEDICINE?
• The placebo effect has been dramatic throughout history. Why is it that bloodletting went on for thousands of years when we know it doesn’t work. This is because when you think it works, you start to feel better.- Doctors use to purge patients. This was suppose to eliminate poisonous toxins from the body. The placebo effect was operative, often the patients felt better after. - Historically, the best example of the placebo effect, was a scheme hatched by Anton Mesmer (1734-1815). Mesmer qualified as a physician. He also developed an interests in magnets. He wondered if magnets which really seem to have magical properties. He wondered whether or not if magnets formulated of loadstones could somehow affect health, could they draw disease out of the body. He organized a clinic for patients to hold onto magnetized rocks so that they could suck the disease out of their bodies. The patients claimed to feel better, at least 30-40% of the time. This is the statistic usually quoted for the placebo effect.• The patients were happy, but physicians in Vienna were not happy because Mesmer was stealing there patients. It was a lot more attractive to them to sit an hold onto a metal rod instead of being bled or purged. They forced him out of Vienna. • He ended up in Paris where he opened up another healing salon. By this time he had discovered that maybe holding onto the magnets was not all that important. Originally, he had devised this scheme of magnetic rods attached to magnetized water that you would hold onto, but he also found that healthy people exuded a certain magnetism and that all you had to do was to be close to someone who was healthy and then you would receive their animal magnetism. ‣In his healing salon in Vienna, he found that if he hired good looking young men to magnetize the hypochondriac women who were the main clients at his clinic then they would feel better. According to his diary, some of these women had to be taken to the back room for further treatment. The whole idea of ‘Mesmerizem” which is the term we use today, it is a classic example of the placebo effect. - King Louis the 16thwho was king at that time, he thought that this was an effect that should be further explored. He organized a committee which had as it members Benjamin Franklinwho at that time was US ambassador to France, Joseph-Ignace Guillotin, a physician who had urged that the guillotin be used in order to prevent pain. The guillotin was already being used to behead people, but they were also using terrible methods such as tearing people apart using horses. Guillotin said that if they were going to do this, then at least kill them mercifully. The third member was Antoine Lavoisier. The king had asked them to look into mesmerism, to see if it was real or not.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- The three of them came back with a report. They concluded that many of the patients felt better after being mesmerized. However, they concluded correctly that the healing was all in the imagination. They also concluded incorrectly that it was useless. But, it was not useless because it did have people feeling better. - Today the use of the placebo effect is made use of by all kinds of therapies and commercial products. For example, a jar that supposedly magnetizes water which is a challenge because water is not a magnetic material. If you don’t want to buy that, you can buy a magnetic cup where you pour the water into and you drink it. Supposedly it has all kinds of healing effects and some of the people who make use of these will tell you that they feel better. The placebo effect, there’s no real physiological here because there’s no change with the water when you pour it into the cup or the device. In this case, it’s referred to as absurd. - When it comes to alternative medicine there are modalities that are reasonable even though there is no hard evidence for this yet. Many herbal treatments, for example, St-John’s Wort, which is a mild anti-depressant. When you take a look at the controlled studies that have been done, there’s many unanswered questions, there’s no consensus that it really does work. It may work in some people older some conditions, but further trials are needed, you cannot dismiss it as totally ineffective. - Another example of a current therapy that would be in the alternative category is one that came out recently for Covid. It is Fluvoxamine, this is a serotonin reuptake inhibitor which is used for depression. It has been found to have some efficacy in keeping people out of the hospital if its used at the earliest symptoms of Covid. Results of some trials have actually been published, but in science, we never place great emphasis on 1 single study, we always want to duplicate it and we want consensus. There were contrary opinions, there was an editorial suggesting that maybe the results weren’t all that impressive, but we cannot dismiss this. So far, it’s in the category of an alternative treatment because there’s not enough evidence for it. - Acupuncturewould be in the category of an alternative treatment. There are studies that have been done on acupuncture, and some of them do show effect, but it doesn’t seem to matter where you put the needles, but studies show that it can work. However, there are more studies that show there’s nothing more than just the placebo effect. It is not totally unreasonable that somehow putting needles into the body distracts you from feeling pain. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Also in the category of alternative treatments would be chiropractic. For some conditions, mostly low back pain and other muscular conditions, it can be of benefit. However, the benefit are over calculated. - Chiropractic was introduced/invented by Daniel David Palmerwho was a Canadian. He had no scientific background, he started out as a fish salesman. He developed an interest in spiritualism. He was a dedicated spiritualist, spiritualist are people who think spirits exist, that after we die we become spirits, and that it is possible to communicate with spirits. He said that the idea of chiropractic, the manipulation of bones, came to him during a seance where he communicated with a spirit of a departed doctor who had died 50 years earlier. Somehow this doctor communities to Palmer the information, that 95% of all disease is due to these so-called “subluxations” which only chiropractors can identify. These are irregularities in the spine when the bones move out of position. If they can be realigned then you can head off disease. • Palmer also considered that chiropractic was a kind of religion, that needed a religious head. He compared it to Christianity and Islam and basically looked on himself as the fountain head. Even back then when he first started to make claims of healing, he was regarded as a quack because he claimed that he was able to cure disease with his magnetic hands. He used his hands and placed them along the spine and that he had the power to realign the bones. • Palmer started to get customers that were happy with the treatment. This really invigorated him, and in fact he developed a school for chiropractic which was in Iowa. The school had students, he developed a whole education system for chiropractors. However, he ran afoul of the medical community who claimed he was practicing medicine without a license and they said that there was no evidence of this hands-on healing. He was actually arrested for practicing medicine without a license. He was given the option of either paying a fine or go to jail. He chose to go to jail, and he spent 105 days in jail before getting out. He went right back to practicing chiropractic. The gentleman who really put chiropractic through the headlines was his son, Bartlett Joshua Palmer(1822-1961) with his classic phrase “Early to bed, early to rise, work like hell and advertise!” This is something that chiropractors have taken to heart ever since that time because they claim that this realignment of the bones in the spine works miracles. It seems to be good for everything. As a general rule in science, the more claims made on behalf of any substance or some form of treatment, the less likely that any of them are true because life doesn’t work like that. Treatments are generally very specific. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Covid-19 came in very handy for the chiropractors because they started to make the claim that these adjustments improve immunity. However, there’s no evidence for this. They also suggest that chiropractic adjustments improves immunity by 200%. They also suggest that pregnant women should have chiropractic adjustments to make sure that they give birth to healthy babies. Anytime is chiropractic time, you should visit your chiropractor for optimal health. They even suggest that babies should be adjusted. • Chiropractors don’t limit their practice to just using their hands, they will also sell out of their offices a variety of dietary supple to, most of which don’t have any evidence. They will sell “chiropractors blend”, but these are just products made by some company and you can any label that you want on it. - Is there any risk in going to a chiropractor? Unfortunately there is, there are people who have suffered strokes from a very rapid movement of the head which can cause a tear in an artery in the neck and that can lead to a stroke. It does not happen often, and chiropractors are very quick to point that out. They say that they have debunked all of this, that there is no greater incidence of stroke with chiropractic treatment then with any other kind of treatment. This is actually not so, there are studies that have been done on this and the potential dangers of neck manipulation. They launched the study by looking at a 32 year old women who had died from a stroke from being manipulated, but they also discuss a range of other cases. Yes there’s not many cases of this, but you need to take into account the risk-benefit ratio. Is there any benefit to that rapid manipulation of the neck. There seems to be no benefit of it, no evidence, so why take that chance. - There are some conditions such as low back pain and various kind of muscle aches that do respond to chiropractic the same way that they respond to massage therapy and osteopathic manipulation. It’s not totally useless for muscular pains, but when they start making claims that they can treat other diseases that’s when you should start questioning the risk-benefit ratio. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
WHAT IS COMMON TO ALL ALTERNATIVE TREATMENTS? - They all lack evidence of efficacy and that’s why we call them alternative. If ever there is evidence, then alternative becomes conventional.- Modern scientific medicine does not want to exclude treatments that work. However, we like to see evidence before putting something into practice. - Dr. Barry Marshallin 1983 came out with the suggestion that ulcers could be caused by a type of bacteria called heliobacter pylori. The scientific community said ‘what are you talking about, we know what causes ulcers, ulcers are caused by too much acid in the stomach, they’re caused by too much stress’. Marshall proved his case, he infected himself with heliobacter pylori and showed that he could cure the condition using antibiotics. Eventually their were proper randomized control double blind trials performed, and it was clear that heliobacter pylori could be cured using antibiotics and that Dr. Barry Marshall together with Robin Wrren received a Noble prize for this discovery. • This is now conventional treatment. We know that ulcers can be treated with antibiotics. This also resulted in related investigations about ulcers. For example, how do you know that you’re infected with heliobacter pylori. ‣There’s a rather simple test that you can do. This test includes swallowing some urea which is a central carbon atom. It’s not a carbon 12, its either a carbon 13 or 14 isotope so that its route through the body can be followed. It turns out that if you do have heliobacter pylori in your stomach then an enzyme that this bacterium produces splits apart urea into ammonium ions and into bicarbonate and that bicarbonate is eventually released into the air as carbon dioxide. One can test whether or not the carbon dioxide in the breath contains the labeled carbon. If there’s no heliobacter pylori in the stomach then the urea does not get broken down and just gets expelled in the urine. So, if you swallow the urea an you find carbon dioxide that came from that urea in the breath it means there must’ve been heliobacter pylori in the stomach. These tests are quite routinely performed and if it turns out to be positive the therapy is launched, there’s 3 types of drugs used. You want to reduce the acid content in the stomach, use an antibiotic, and this 80% of the time will solve the problem. The test itself is easy, you breath into a bag and the contents of the bag are analyzed instrumentally.
- The whole idea of heliobacter pylori started out as an alternative treatment because there was no evidence, but as soon as there was evidence it crossed the bridge into conventional treatment and is now used universally. It’s now called science based medicine. SCIENCE BASED MEDICINE
• Naturopathy is a practice, not a medical practice. It claims that without drugs, without surgery, they use natural substances and natural modalities such as fasting, nutrition adjustments, homeopathy, acupuncture, and herbal medicine, etc and they can heal in a very effective fashion. This is quite the antithesis of modern medicine which uses drugs and surgery in order to treat patients. • There’s a basic fallacy in naturopathy. This is that nature is equipped to cure all diseases. No, there’s nothing magical about nature, it is true that there are some medications that are derived from nature like morphine, digitalis, and vincristine from the Madagascar periwinkle which are all drugs used in modern medicine. There’s no magic in nature. There are many toxics substances in nature including ricin and castor bean. Poison ivy is also not a pleasant thing to role around in. - Something that naturopaths have that most physicians do not have is time. They spend a lot of time with patients questioning them about all kinds of things and very often that just what people need. However, they also use therapies which are highly questionable. For example, detox kits. This naturopath in BC promotes detox kits, the whole concept of detox doesn’t make any sense unless you’re talking about a specific substance that has to be removed from the body, there’s no such thing as a general detox. • “Dr.” Anke Zimmermanhas been in the news for the treatment of a kid who had very aggressive behaviour. She claims that she had success with treating him with the saliva of a rabid dog because his behaviour was like a rabid dog. She was using the tenants of homeopathy to cure this kid. This was even frowned upon by her own homeopathic association. Nevertheless, she did not give up, and she claims to continue to use her treatments. - Alternative therapies are very popular. There are more visits to alternative practitioners than to conventional physicians annually. Why? Because thee alternative practitioners are charismatic, they have a lot of time, they have the trust of the patient. • For example, Andrew Weilwho has been called America’s doctor. He’s been on the cover of numerous magazines, he has a website.. he’s a Harvard educated physician. He has written a number of books, “Mind over Meds” where he talks about situations where you can use so called natural therapies instead of prescription drugs. In this case, he knows when to tell someone to use the herb of some kind or to go see the oncologist. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• His popularity is because of his persona. He speaks very well, he’s had specials on TV on where he tells people what to eat, how to have a healthy diet. However, he also blends it with recommending certain herbs. For example, cure for liver disease, milk thistle. There isn’t any evidence for that. In fact, there is evidence against it. ‣There’s a study which shows that milk thistle is not the magical substance to cure liver problems. - He is a very interesting guy, speaks very well and seems to be very trustworthy. He’s also on TV, and once you’ve been on TV, you get this reputation of being reliable. • He’s been on TV with Dr. Oz. Dr. Oz has a very large following. Some of the stuff he does is very good, and is certainly not alternative. When he walks you through a large mock up of the intestines or the lungs, he knows what he’s talking about. However, he often goes of the path and talks about pills to stop aging or the miracle of red palm oil for longevity, or how you can use a miracle pill to burn fat without exercise, diet, or any effort, how a coffee bean extract can result in weight loss. This is all alternative stuff because there is no evidence that any of these actually work. ‣There’s not a ingle study in the literature to show that weghtloos is tied to raspberry ketone. - Although some of the stuff he says is very legitimate, most of the stuff is highly questionable and once he gets into the really far out stuff, how can you trust him? For example, talking to the dead. He had a guest, Theresa Caputowho calls herself the Long Island medium. She claims to talk to the dead. Or he will have John Edwardwho is also one of these people who talk to the dead. They will put on a whole show, with a silly kind of collage of words you can pretend to communicate with the dead. - The scientific community is not happy with Dr. Oz. Doctors are unhappy because for people who watch the show, they come into the doctors office asking a whole bunch of questions about things they have seen about far out therapies. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
ALTERNATIVE MEDICINE CONCERNS - There’s a misrepresentation of conventional medicine. They kind of set up a battle between themselves and conventional medicine and claim that conventional medicine is killing people by cutting them, burning them, and poisoning them. These are the key words for surgery, radiation therapy, and chemotherapy.- They claim that organized medicine is hiding effective treatments from people. They are privy to those secrets. - They have the usual antiestablishment rhetoric about how they have been able to determine that there are drugless, nonsurgical options so stay away from conventional medicine. - For example, there is another book by Kevin Trudeauwho is your typical snake oil salesman. He has no scientific background but looks charming, dresses well, and looks trustworthy. He is the only person in the US history who has ever been banned from doing infomercials on TV. • The book that he promoted and that he sold millions of copies called “Natural Cures “They” Don’t Want You To Know About”. Here are some of the highlights; “Animals in the wild do not get sick”. This is nonsense, of course animals in the wild get sick. The thesis here is that they don’t get sick because they don’t go to doctors and know how to cure themselves just by eating the right foods. “Cancer is caused by an acidic pH”, nonsense. “Pasteurization kills living enzymes”, this is another absurd statement because enzymes are just molecule,s they are not living so you cannot kill them. “Irradiation changes the energetic frequency of a food”, what does this eve mean? “You should get 15 colonics in 30 day”; that is you should infuse water through the rear end to wash out you colon. “You can change your DNA by thinking correct thoughts”; would be amazing if this could happen. “Rebalance your body with frequency generators”; some sort of contraption that he or his cronies sell without any kind of evidence.- He started making claims about using certain supplements for weight loss. These claims could be proved to be ineffective. He ended up in jail for 10 years. He was called the ‘uncontrollable huckster’ for selling fake weight loss tips. • This is a problem, because people who read this book will believe it.- Another concern about alternative medicine is the introduction to pseudoscientific ideas. This may seem scientific to the uninitiated. Things like applied kinesiology. • This is when just being next to some supposedly therapeutic substance will have an affect on the body.
• You don’t have to swallow it, you don’t even need to rub it on your body, you just need to be near it. • For example, someone had taken with a hidden camera for the 2020 documentary program on American television on ABC. Someone went into a health food store complaining of aches and pains. The salesperson was pretending to be knowledgeable in therapies. He said to put the little finger and thumb together and then he tries to pull it apart, of course he can easily do this because there’s not much strength there. Then he gives the person a vial of something to hold in the other hand and once again tries to pull the fingers apart and this time has greater difficulty because that vial somehow has infused the person with extra strength because you need this product. This is nonsense, but you will see people performing this in shopping centres. It’s a classic scam, but people are taken in by it. - There are also devices that claim to zap away disease. One of the books by Hulda Clark. She had her original degree from McGill. She became naturopath and came to the conclusion that all cancer are caused by a parasite that lives in our liver. We can detect if its present, we can detect what foods will allow it to escape from the liver and cause havoc in the body. She tells you to go to the RadioShack, she tells you what parts to buy to put together this instrument called the zapper. If you don’t want to build it yourself you can buy it from the company that she founded, it’s called the ‘MedaZap’. It resembles a device that was sold in the late 1800’s which was also suppose to be a cure-all device. • Her theory was that you can determine the toxicity of your household products that is the products that will allow that parasite to escape from the liver and cause disease. How do you do this? You use the zapper and it makes noises and by listening to the right kind of noise as you hold it next to some food, you can test this food and determine whether or not if theres any toxic chemicals in it. She even tells you that aluminium causes Alzheimer’s disease and you can test your propensity for Alzheimer’s disease. To do this, you want to take a piece of brain and put it on one side of the instrument. You don’t use your own brain, you can buy it in the store. You put aluminium on the other side and then attach the zapper which will tell you whether or not if you have aluminium in your brain. ‣If there’s a positive result then you can use cloves, wormwood oil, black walnut tincture to get rid of the parasite. - After she came out with the ‘cure’ for cancer she came out with another book “the cure for all diseases’. Apparently it didn’t cure all diseases because she then came out with a book for the ‘cure’ of HIV and AIDS. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Hulda passed away. She passed away from multiple myeloma which is cancer which is one of the conditions she claimed to cure with her zapper. - There’s something called therapeutic touch. This is a technique introduced by a nurse practitioner of the name Dolores Kriegerwho maintains that the body is surrounded by an aura and if there are imperfections in this aura, then that causes disease. She has written a book about this and there’s belief even in the medical community that their may be something to this. There are surgeons like Dr. Oz who operate when the therapeutic touch practitioner are waving their hands over the patient trying to reconfigure their aura. Interestingly enough, this is something that can be tested. • There was a paper published in The journal of the American Medical Association which is one of the prime journals in the world. To test this, all you need to do is enlist some people who say they are therapeutic touch practitioners and who can detect the auras of people. You put them behind the screen, and you ask whether or not if they can detect an aura by putting your hand above their hand. If they can detect an aura they should be able to do this blindfolded. • This experiment was done and was highly critiqued even though it was published in the reputable journal. One of the participants was Emily Rosa, a young girl, the daughter of one of the physicians who had organized this study. This is what they critiqued, it doesn’t matter what he age was, this was a perfectly good test.‣None of the therapeutic touch practitioners who said they would be able to do this, were able to detect the presence of an aura. - A closely related technique is Reiki. This is similar to therapeutic touch except that they do touch the patient. There is some benefit here because it could lead to relaxation. This again is a question of mind over body, but it is not going to heal the underlying disease.- Another form of alternative treatment that is now being promoted is called tapping. This is not exactly tap dancing, but it is not all that far removed from it either. These tappers start tapping the body with their fingers in various places of the body. They claimed that it somehow has a healing energy for the body. You have the usual proponents, people who themselves suffering from some sort of condition and they discovered that this method helped them so therefore they are so keen in promoting this because they want everyone to learn about this business. This is the kind of thing that gets you on Dr. Oz because it’s interesting and unusual. You can go to Times Square in New York and people would be tapping away.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• However, the only thing that they may be tapping away are some of the symptoms that they feel through the power of the body, and the mind body connection. If you think you’re going to be better, you will feel better, but there is no change in the underlying physiology of the body. - This whole business of alternative medicine is a very complex one. The important thing to understand is what we refer to as alternative medicine is the stuff that is not taught in medical school for several reasons. • Some of it is just quackery • Some of it may turn out to be legitimate, but there’s not enough evidence for it. • In the world of science we’re always looking for evidence. HOMEOPATHY- What homeopathy is not: it is not herbal medicine, it is not accunoucnture, it is not aromatherapy. It is not a zinc treatment that it called ‘homeopathic’, in this case it does contain a substance, whether it’s active or not is hard to say. - Homeopathy is a therapeutic system based on the hypothesis that like cures like. This means if a substance causes some symptoms in a healthy person, then that substance will treat or cure those symptoms in a diseased person but this substance has to be diluted to the extent that it does not contain a single molecule of the original. • These homeopathic medicines can be derived from a variety of plants, animals, mineral matter, etc. HISTORY- Homeopathy has been with us for a very long time. It has been with us since Samuel Hahnemannwho is a physician came up with this idea way back in the late 18th century (1755-1843).• He was a legitimate physician, trained as any physician was in those days. What did they learned? They learned how to use the lancet which is a device used to bleed people by making a cut in the artery. They learned how to use leeches to bleed people. They learned how to make people eliminate substances from their stomach: purgatives. • Their was one drug back in those days that actually seemed to have some efficacy. This was the extract of the bark of a tree that grew in South America. It had been imported into Europe by the Jesuits who learned about it from Natives in South America who had discovered that by making a concoction from the bark of the tree, which came to be called Peruvian bark as it came form Peru would alleviate fevers.
- Samuel Hahnemann knew about this and used this in his patients who suffered from malaria. Malaria is a terrible disease which is transmitted by mosquitos which is associated with fever. He used this, but of course their were problems with what exact dose should be used as these are not standardized extracts. He became his own guinea pig to try and find out what kind of doses would be appropriate. He started to give himself larger and larger doses to see what that would do, eventually he got a fever. He had been healthy when he had been taking this and then he had developed a fever, so he concluded that a substance of an unhealthy caused symptoms that would cure those in a diseased person. • He began to do a bunch of what he called ‘provings’. He tested other substances to see what exactly kind of symptoms they would produce. For example, he would start giving to volunteers a small amount of arsenic until they developed some sort of symptoms which of course they eventually did including gastric pain, vomiting, and diarrhea. He then would stop and conclude that arsenic treatment in a very dilute solution would be the remedy for food poisoning as it gives rise to those symptoms. • He continued with cantharide beetleextract which was better known as Spanish fly. If you give this to healthy people it eventually causes a burning sensation in the URL-genital tract. He concluded that this would be beneficial for urinary problems. He came up with what was called the material medica which is a compendium of all of the numerous substances that he tried and the symptoms that they were supposed to be curative for all based on the similar similabus curantur which is Latin for “like cures like.”- So he came up with these extreme dilute solutions. He didn’t understand in those days just how dilute they were because they didn’t know anything about molecules. He made up these dilute solutions and infused them into little sugar pellets and came with a whole bunch of homeopathic remedies. These were all based on what he called the law of infinitesimals.This is that the original solution was diluted to the extent that there was nothing there. • One day he made a house call and found that the remedy that he gave the patient worked even better then expected. He had gone to the patients house in a carriage over the cobblestone streets. So he wondered that if the shaking had anything to do with changing the remedy. He came up with another principle of homeopathy which is the principle of succession so that in between dilutions, you have to bang the solution into a leather pillow usually a set number of times (usually 100 times.) Today, homeopathic companies actually have machines that do this. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- The original substance which in a healthy person would cause some symptoms would then be diluted. Each dilution would be 100 fold, you would take 1 drop of the original extract and add 99 drops of water and then take 1 drop of that and add 99 drops of water, etc. Each of these are called 1C dilution, C is the Roman numeral for 100. Today we can make a rough calculation and determine that by the time that you have done a 12C dilution, their isn’t a single molecule of the original left. Then this solution which is essentially just water or alcohol depending on which solvent is used to do this is infused into a sugar pellet and that’s how you get these homeopathic remedies. • For example, aceticum acidwhich is a diluted vinegar solution is said to be especially indicated in pale, lean persons, with lax, flabby muscles. Also, it can counteract sausage poisoning. • There’s all kinds of homeopathic remedies, there’s one made of gun powder. It is said to be good for abscesses, acne, bites, blood poisoning, boils, carbuncles, etc all of those are suppose to respond to his dilute solution of gun powder. • Another example is homeopathic rabbit anus. There’s extract of the Berlin Wall, it is suppose to reduce anxiety because the Berlin Wall caused anxiety. There is homeopathic oxygen, they claimed that this is ozonewhich is diluted in water and then of course is diluted and diluted and diluted, etc so in this case the ozone would evaporate out of the water. How is this made? They say that dilutions of the preparation called Oxydolwhich seems to be hydrogen peroxide. This is all nonsense, but it is said to be effective for anemia and effective for cancer. • There’s also homeopathic X-ray, 200C dilution. It is supposed to give relief of itching, skin rashes aggravated at night and in bed. This is obviously going to be ineffective because it cannot possible contain anything.- The 12C dilution mentioned earlier is already diluted to the extent that thee is nothing left from the original solution. In homeopathy, the potential ion increases with dilution, so a 30C dilution is thought to be a really effective homeopathic remedy, of course this dilution does not even contain a molecule that came into contact with the original substance. - The question we ask is if homeopathy dilution or delusion? Homeopath maintain that their preparations work the same way as vaccinations work, that homeopathic drugs act like vaccines by stimulating the immune system. This is false, vaccines obviously contain measurable amounts of an active ingredients.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Vaccines also give rise to measurable amounts of antibodies. We’re hearing a lot about this these days with covid. Vaccines contain substances that are similar to the disease causing agent. For example, with the Covid vaccine, what is injected is the messenger RNA that gives rise to the spike protein in the cytoplasm of the cell. So there’s a similarity between this and the causative agent. In homeopathy, there’s no similarity between the substance that is diluted and the disease. - After dilution there’s not a single molecule left of the original substance. Homeopaths have to admit this because they have chemists breathing down their neck demonstrating that after such a dilution there can’t be anything left. So they came up with a solution, this solution being that the dilution and the shaking leaves an imprint in the solution. You cannot leave an imprint in a solution.. they resort to talking about how water molecules conform organized patterns. As the hydrogen is attracted to the oxygen of another molecule and they say that this somehow indicates that there could be some pattern induced by homeopathic dilution. There are these attractions but they last a picosecond, which is a trillionth of a second. (A picosecond is to 1 second as 1 second is to 31,700 years.) This is absolutely inconsequential.• One also asked the question that how come that solution remembers only what the homeopath wants it to remember? Remember that the water that is being used has at one time been in contact with everything. So why does it not remember our output? Urine? Why does it remember only what the homeopath wants it to remember? - The fact that the theory of homeopathy is scientifically implausible is not enough to rule it out because who knows, maybe their is some mechanism that modern science cannot explain. So. We don’t rule it out because it’s implausible, the question we ask is if there’s any evidence. If there’s no evidence, that’s the reason to rule it out. EVIDENCE- 1988: Jacques Benvenistewho was a legitimate researcher in France. He did not start out as a quack, he was investigating diluted substances and discovered that there actually was a response to a diluted solution that had none of the original substance left. • He submitted a paper to Nature, this was a very reputable publication. They agreed to publish the paper, but the referees who had looked at the paper were extremely sceptical. However, Benveniste had submitted the data and of course the referees do not try to reproduce a study, but there was such concern among the referees that the publication in the journal came along with an editorial reservation.
• This was that there were serious concerns raised, however, professor Benveniste was going to collaborate and allow other independent researchers to go into his lab and take a look at his work. So, Nature put together a crew of experts in immunology. They also invited James Randi, he passed away last year, he was one of the worlds top experts in detecting pseudoscience. He had made a name for himself as an escape artist and musician. Magicians are very good at detecting fraud. • He was one of the members of the community, and they were welcomed by Benveniste in his lab. They investigated, they asked his researchers to try and duplicate the work, and no matter what, in the presence of the committee, it could not be reproduced. To this day we do not know where the original data came from whether if it was fraudulent or erroneous, whatever the answer is, it could not be reproduced. ‣There’s a Netflix documentary on Randi called “An Honest Liar.”- Benveniste was very disturbed. He kept maintaining that his data was correct. He went on to found a company called “Digibio.” There he seems to have really gone off the tracks because he was promoting homeopathic E-mail, that the memory of molecules could actually be transmitted on the internet. This is a classic example of pathological medicine where someone believes in his work so much that they refused to give up their belief in spite of a lack of evidence, almost like wishful thinking. - Is there any evidence for benefits of homeopathy? We take a look at this journal which is the journal of homeopathy and they conclude that in this case, a randomized double-blind placebo controlled trial using an extract of a particular plant was useful. They found some evidence, well perhaps they did..• If you do enough experiments you will sometimes find some spurious results. For example, if you take 100 coins and toss them in the air what are you likely to find when they fall? Maybe 52 heads and 48 tails, next time you do it you might get 45-55. If you do this enough times, you might get one time where you get 30 heads and 70 tails and if that is the only one you report then it seems to be biased. There have been many experiments done on homeopathy, most of which show no result at all, but a few by random chance alone will show results and therefore it can bring up the false belief that homeopathy works especially when the homeopaths cherry pick the data that they want. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Of course what we want to do is to not look at one single experiment, you want to look at compendium and see what the consensus is.• This is what The Lancetdid, this is one of the worlds prime medical publications. In August 2005 they looked at everything that was published and came to the conclusion that there was no evidence. - The Cochrane Collaborationwhich is a compendium of experts around the world who volunteer their time to look at data in controversial situations came to the same conclusion. - Of course the homeopaths fight back. They stated that “the problem is if you try to prove homeopathy using a scientific paradigm, as by using double blind studies, you’re trying to standardize the therapy, but homeopathy is individualized to each patient, so if a remedy works in Andy, who says it will work in Bill?” They claim that you cannot test it, but if someone makes a claim, there is a way to test it. Because none of these claims have been corroborated, many regulatory organizations around the globe have come to the conclusion that homeopathy is just a placebo effect. The national Health Service in the United Kingdom came to this conclusion, Australia declared homeopathy useless. • In Canada, homeopathic remedies can be sold, but according to the government they have to have a number, a DIN(drug identification number)-HM(homeopathic)• This gives the impression to the consumer that this is a product that has been approved by Health Canada. However, the only thing that this number means is that it’s a homeopathic remedy which is allowed to be sold because it has been deemed to essentially contain nothing and therefore there’s no concern about it. But, the average consumer would assume that if you have a health Canada number on a product means that not only is it safe, but effective. This is not the case. RISK- Given the fact that the dilutions are so extreme they are below the Avogadro number which means that they contain nothing, so how could there be any risk.• Every October 23rd, the date chosen because it stands for Avogadro’s number, skeptics of homeopathy around the world gather and guzzle down all kinds of homeopathic remedies. This can be rabbit anus, or Berlin Wall, or plaster from Berlin Wall, or cavity from Berlin Wall, or it came be one of the prime homeopathic remedies which is oscillococcinum, a remedy claimed to work against colds and the flu. It is made from the extract of the heart and liver of a duck, it is an extract like all homeopathic remedies essentially contains nothing.
• It is made from the heart and liver of the duck, it is a 200C dilution. Even animal rights activist do not need to worry about this. The liver of one duck would be enough to supply the world for many years. - In the tenants of homeopathy, the smaller the amount to which you are exposed, the more effective it is. So when you’re eating a lot of homeopathic remedies it’s not suppose to do anything because it only works in great dilution. There’s no risk of toxicity. • The risk is steering people down the wrong path. For example, there are homeopathic remedies for malaria. Malaria is a serious disease so if someone trusts this remedy, they are putting themselves at risk instead of taking proper care to not get bit from mosquitos. If someone is using Mozi-Q which is suppose to be a homeopathic insect repellant. No it does not work, but it may give people confidence about what it “could” do. • They are more serious ones, HPV (Human Papilloma Virus) is a very disturbing virus because infections which it can eventually lead to cancer. So to suggest that there is some kind of homeopathic remedy to treat this is extremely disturbing. • Equally disturbing are homeopathic nosodes. These are said to be alternatives to vaccinations. Health Canada has cracked down on this and they made them put a warning on the product “this product is not intended to be a substitute for vaccination”. These warning don’t mean much, these nosodes are usually given by homeopaths in there office, and when you have products there the law doesn’t apply, it only applies to substances sold in a store. Homeopaths will of course downgrade the warning and promote the efficacy of it. This is a dangerous business because they maintain that it is an alternative to the MMR vaccine and is a very irresponsible thing because you’re not protecting children by given them a substance that contains nothing. - Just a couple of days ago we found out that the homeopaths are into supposed preventatives or immunization against covid. We learnt that one of the top quarterbacks in the national football league, Aaron Rodgers of the Greenbay Packers said that he had been immunized. He came down with Covid, and it turns out that he was not immunized at all, he had taken some homeopathic remedy that he believed protected him. There’s a lot of nonsense now about Covid-19 and all types of remedies, but there are these terrible cases where homeopaths are telling victims that they can protect themselves against Covid with homeopath remedies.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• A homeopath was even arrested for selling vaccine cards claiming that people had been properly immunized but what they were using was not the vaccine but these homeopath pellets.- Even more serious is the claim that you can treat cancer homoeopathically. This is not just theory, this is real, there are desperate people who have tried homeopathy to treat there cancer. The real risk here is being steered away from conventional treatments. There was a tragic case of this lady who died of colon cancer was treated by a homeopath who gave an excuse that the reason that the treatment did not work was because the patient became too late and had already had some conventional treatment. Classical homeopathy will cure you unless your immune system has already been ravished by drugs or chemotherapy. • What can we do about this? Our office in Quebec has been successful in getting some pharmacies to put a warming on the shelf’s where they were selling homeopathic products that they were not shown to be effective. However, whether or not if this has an impact or not is hard to say. WHY DOES HOMEOPATHY PERSIST AFTER 200 YEARS? - Scientifically it makes no sense and there is no significant evidence that it works. Part of it is the placebo effect. If you believe something is working, it will.• For example, if you have a common cold and you take a homeopathic remedy and you really believe in it, you wont be as aware of your symptoms as you would be.- There’s something called the regression to the mean. This refers to the fact that symptoms of many conditions just have random fluctuations. For example, things like arthritis some days you feel better and some days not so well. If you take a homeopathic remedy and it happens to coincide with one of your good days, you think it was because of the remedy. However if there’s no such coincidence, you never think about it again. - There’s also the possibility that along with homeopathic remedies there are standard treatments being used but the patients forget about that and gives credit to the homeopathic remedy. - In some situations a homeopath will recommend some lifestyle changes like better nutrition or more exercise which can help. - Another reason why people gravitate towards homeopathy is the fear of conventional treatments. Radiation and chemotherapy are not very attractive, if someone tells you that you can solve your problems by swallowing some pills, it looks better.
- Hahnemann was not what we would call today a charlatan. He thought that he was performing good science. In his view his remedy worked because he got symptoms when he took the Peruvian bark, he saw that it cured his patients, but when he was using it as a treatment he was using a much more dilute solution than he used on himself to trigger symptoms. In his mind, using a dilute solution and the more dilute it is, the better it worked. - In 1991 a study was carried out by a professor in Germany, W. H. Hopff. He found that cinchona barkdid not even trigger malaria symptoms. So, all of homeopathy is based on a fallacious concept. - Samuel Hahnemann is still revered by homeopaths. He is buried in Switzerland. The bottom line here is that hundreds and hundreds of trials have failed to deliver significant evidence supporting homeopathy in any particular treatment but it is still with us, and does not seem like it will disappear. MISREPRESENTATION OF EFFICACY AND SAFETY OF VARIOUS TREATMENTS - In Texas there’s a clinic run by Burzynskiwho is a Polish trained physician who came to the conclusion that a particular kind of molecule that can be extracted from the urine; neoplastons or antineoplastons. These are substances found in the urine and he somehow cocnluded that they have therapeutic effects against cancer. He has been very successful with his client and charges a great deal of money with his patients.• When you look at the statistics here, you find that the patients that go to this clinic are not helped. They will die. What he is doing is giving hope to people. Very early on in their treatment they will say that they are feeling better but this is because of the placebo effect.There’s no evidence that these antineoplastons do anything in preventing cancer. • There’s a lot of this false information going around. There in newsletters, publications of all kinds which claim to have secret formulas to treat all kinds of diseases. ‣For example, in a brochure a statement may say “A miraculous plant preparation that cures arthritis in 14 days and makes drugs unnecessary; A topical cream that reverses osteoporosis; a treatment that erases asthma in 4 days.” All of these have in common a lack of evidence.
• Sometimes the outcome can be catastrophic. There was a young later passed away at a young age. She did not like the shape of her body, she wanted to have a large rear like the Kardashian’s. She went to a ‘clinic’, but it was actually someone’s home. It was a practitioner without any kind of training. They injected her with silicone. Medical silicone is a legitimate treatment in the hands of a plastic surgeon, but not in the hands of a untrained person. Allison Spence injected her with silicone and unfortunately the young lady died. She was charged with manslaughter. The pathology had showed that she had died of embolism because of the silicone injections. Her boss who pretended to be some sort of medical professional also pleaded guilty and they were sentenced to prison. STEERING PATIENTS AWAY FROM POSSIBLY EFFECTIVE TREATMENTS - There was a young boy of the name Ezekiel Stephan (2010-2012)died at a very young age. This occurred in Alberta. His parents took him when he became sick to a naturopath. The naturopath recommended smoothies with apple cider and olive leaf extract, horse radish, and an echinacea tincture. Unfortunately the boy had meningitis, and by the time he was taken to the hospital it was too late. The parents had bought into the idea that naturopathy was a legitimate alternative to conventional medicine. They were put on trial because of the death of their child. They were arrested and they were found guilty but then the verdict was overturned probably because they did not intend to kill the child. The parents were mislead and the real crime was just believing in naturopathy. • You would have thought they had learned there lesson, but they are still into all kinds of marketing of all kinds of therapies. For example, EMPowerplus nutria all support for mental and physical wellbeing. This is basically a vitamin mineral supplement. They claim that it has all kinds of therapeutic benefits but there’s no evidence. They say scientifically proven, but there’s zero evidence for this. - Extracts of apricot pits contains a compound called amygdalin. When consumed it can release cyanide in the body. The argument is that the cyanide will destroy cancer cells. It can destroy cancer cells but it will also destroy other cells. • This story hit the press when Steve McQueenwho was a great actor, he came down with mesothelioma with his a lung disease due to asbestos exposure, it’s a type of cancer. Instead of going the conventional route, he resorted to amygdalin which is also referred to asLaetrile (Vitamin B17).
- Amygdalin has been put to the test and numerous studies show that it is not an effective treatment for cancer. However, cancer victims are desperate and they’ll try anything including going to ‘John of God’ in Brazil who is a totally uneducated peasant who rose to fame when he was interviewed by Oprah. He had a so-called ‘clinic’ in Brazil where desperate people from around the world would come to be treated. He would put surgical scissors up there nose and extract what he said were tumours. It looked very impressive because the surgical scissors went right up the nose. People are unaware of the human anatomy. It’s a carny trick of putting a nail up someone’s nose which you actually can do because there is a passage there. Obviously no one should try this, but this is what ‘John of God’ was doing and people were flocking to his place from around the world to be treated of cancer. Eventually the law caught up to him after he had become a rich man and he was jailed. He was jailed not for the unconventional treatments, but it turned out that he had made a career out of raping some of his patients. • He was in prison and he was released from prison to house arrest during covid-19 because he was in poor health. • His daughter Dalvais one of his accusers. She said that he was a monster and she alleged that she was beaten and raped from her father until she ran away at the age of 14.• This man had quote ‘treated hundreds and hundreds of people for cancer’ who knows how many he had killed from distracting them form legitimate therapy. WHY THE BELIEF IN ALTERNATIVE MEDICINE?- Frustration with conventional medicine, the lack of understanding the nature of the disease and the lack of understanding cause and effect. • For example, we know that the rooster crows every morning, and the sun comes up every morning. One could say that the roosters crowing makes the sun come up. In primitive societies this has been a belief. - The lack of understanding the placebo effect. People believed that because snakes were lubricated internally that extract of snake oil would be beneficial to arthritis. Today of course we have many modern versions of snake oil. • For example, we have a machine that is said the be capable of detecting and curing disease. This machine is called the EPFX-SCIO machine. It scans the body for 9000 frequencies each associated with a different compound, much as anti-virus software would do on a computer. It operates as biological speeds (up to 1/1000 of a second) charting the resonance or response of the body to these frequencies, comparing them to a norm and ranking them in degree of reactivity, identifying both acute and chronic imbalances.
‣This is absolute scientific nonsense. These are random words put together by a gentleman who calls himself Dr. Nelson. If you listen to him he calls himself an inventor. William Nelson first vocational experience were in quantum physics and electrical engineering when he worked on the navigation system for NASA. During the Apollo project in 1970, 3 men had technical difficulty on their way to the moon. Most said it was impossible to get them back to earth, but Dr. Nelson said nothing is impossible. He had the vision skills to calculate the mathematics for the navigation system. Dr. Nelson successfully reprogrammed the gyros and the 3 men landed safely. He never had anything to do with NASA and this is total fabrication. ‣He is one of the prolific lecturers and writers on the subjects of quantum, biology, energetic medicine, homeopathy, alternative medicine, and the entire field of naturopathy. He has taught mathematics, meditation, mystic philosophy, etc.‣He became a medical doctor and a licensed clinical counsel or in Ohio. ‘He has also been Nobel prize’. He is an interesting person, believe it or not, at night he ‘transforms’ into a nightclub crossdressing singer. ‣He sells his machine for thousands of dollars. He lost his American passport so he cannot come back to the US because of the fraud. He now is located in Hungary from where he runs his empire. People around the world has spent thousands of dollars buying this machine which does absolutely nothing but they hope that it would detect cancer and cure it. - A much simple device is the‘Zero Point Energy Wand’ which looks like a pen. It is referred to as a phenomenal energy tool. It is supposed to discharge energy blockages, it energizes the body, it facilitates heating, it can even energize foods, liquids, pets. It balances and imbalances. Not only do they make health claims, they make medic claims as well. They claim that it will give you a face-lift. It sells for about 300$. • When putting it in an X-ray, the only thing found was pure metal. So its nothing but a piece of metal, but you’ll have people swearing by it saying that they had been helped by it. • Joe Schwarcz was approached by two ladies who said they had been on a trip to Poland where they discovered a wonderful substance that could cure almost everything. It was a product called Pimat. It came with a thick book that explained how it worked, that it had a particular pattern on it, some sort of geometrical configuration that exuded radiesthetic colours.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• The two ladies asked if their could be any kind of legitimacy here. Pimat is a small piece of cotton that has a pattern of red dots on it which are suppose to be the healing dots, they focus the energy of the universe into the body. How do you use it? You lie on it, you put it under the small of your back. He describe that you should always do a controlled experiment where you would have the substance that reports to be beneficial and look at it relative to a placebo. In this case it was easy to come up with the placebo because the claim was that it was the specific pattern of red dots that were curative. So the placebo would be a piece of cotton the exact same as the Pimat but without the red dots. In order to do this in double-blind fashion the subjects could not know what they were using, it would have to be in an envelope. They asked a company that markets Pimat to do this study for them and they agreed. They produced both the Pimat and the control, they put them in cotton envelopes so nobody knew what was inside except the statistician who would look at the numbers and compare the results. • So, Joe enlisted a number of volunteers. For 2 weeks they had asked them to fill forms about how they had slept, if their wee any kinds of aches or pains. This was before giving them the controlled or Pimat, so they didn’t know what the experiment was about. For the next 4 weeks, they gave them either the Pimat or the controlled to sleep on and then 4 weeks later they exchanged. This gave 10 weeks of data. Obviously, water they slept on the Pimat or the controlled made no difference. However, there was a difference in the firs 2 weeks and the next 8 weeks. So just sleeping on something that they thought would have some kind of benefit made the different. Again, a classic example of the placebo effect. The dots had nothing to do with it. - Lack of realization that sometimes therapists, even ones with legitimate degrees will say things that are simply not true. For example, in a book by Christiane Northrup who is a legitimate MD, but she seems to have gone off the rails. In the book she states that “Karen completely cured herself of Lou Gehrig’s disease by loving herself unconditionally just 15 minutes a day.” Nobody in history has ever been cured of this disease. This is totally misleading. • You can’t always trust people even though they reliable degrees. - There’s also the lack of understanding of the unreliability of anecdotal evidence. Just because your neighbour tells you that they took some homeopathic remedy, it does not mean that it worked. You have to do proper testing and trials to make sure that it does. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- These days people tend to listen to celebrities. They think because of their fame they are knowledgeable. For example, Suzanne Somers rose to fame on a sitcom called three’s company. She was an actress and she was diagnosed with breast cancer. She claims to have cured herself with natural therapies. She goes around giving lectures, she looks healthy and speaks very well. But, the real story is that she was diagnosed with breast cancer and she had a lumpectomy which is that the tumour was removed. She refused chemotherapy and she refused hormones (tamoxifen) and she took some so-called natural therapies like Iscador which is extracted from a tree. In her speeches she claims that this is what cured her, but it was in reality the lumpectomy. She also refused to take hormonal therapy, but she claims to take bio-identical hormones for rejuvenation. These bio-identical hormones are just estrogen. The same estrogen that can be found in a pill except that it is extracted from a natural source. CELEBRITY SCIENCE • Listening to these people can be problematic, sometimes life threatening. - Michaela Jakubczyk-Eckert, an East German model who was very young was diagnosed with breast cancer. Unfortunately she waited to long to go to the doctor. When she finally did go, they did a lumpectomy. They removed a lot of the cancerous tissue, but then she went to a naturopath who told her it was her internal conflicts that was causing the illness. They told her that the cancer could be eliminated but that she must stop the chemotherapy and resort to psychological treatments. Unfortunately this did not work and the disease spread, and she passed away. - The bottom line here is that alternative medicine is not a good alternative to medicine even though its proponents make very seductive cases for it. For example, natural news which is one of the most disturbing cites on the internet. They state that everything natural is superior to any kind of synthetic drug. They have a story there about Micheal Douglaswho was diagnosed with esophageal cancer, for which he underwent proper chemotherapy and then they compare him to Suzanne Somers who used natural treatments. When comparing the two pictures, the message is that Micheal Douglas looks horrible because of the chemo and that Suzanne Somers is radiant because she took a natural treatment. • This is how you can steer people down the wrong path. - It is also true that scientific medicine does not always have the answers and have made plenty of mistakes in the past.
- For example, in the 1800’s who were anxious and who were judged to be suffering of hysteria, hysteria paroxysm. This was treated by doctors with what they called internal massage. - There was Dr. Walter Freemanin the 1950’s who carried out brain surgery. He was a properly trained surgeon. He did this on people who had mental disease by basically putting a spike up their nose and cutting off a piece of the brain. One of President Kennedy’s sisters underwent this procedure. - Also, in the 1960’s it was quite common to keep patients who had a heart attack on bed rest for 6 weeks. Today we know that this is not the right thing to do. - Arthritis sufferers were told to wear gloves with radioactive material in there which was not a good thing. - Doctors also promoted cigarette smoking. - When it comes to alternative medicine it’s important to be a critical thinker. - Sometimes you find surprising results which at first don’t seem to make sense. - Suppository’s are designed to have one end that has a tip like a gullet and a blunt end at the other. The suppository is to be inserted into the rear with the tip first (bullet end). However, it turns out that this is not the right way to do it. If you insert the suppository the other way, it works better, why? Because as the anal sphincter closes down on the beveled end, it will propel it inwards like a rocket. Interesting study done in Egypt. - Nobody has a monopoly on the truth, we need to investigate. “Science based” medicine may not always work, and that there isn’t always an answer, but this is the way to go. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
SCIENTIFIC PUBLISHING Caitlin Malcolm-Pottle INFORMATION- Facts change, they evolve. - There were ~8 million active science researchers who put together ~3 million publications. The math works out to 5-6 papers of every single minute of every single day. EFFICIENCY OF DIFFERENT COUNTRIES- Switzerland leads the world. - China is not on the list because they produce an enormous amount of enormous papers but because there population is so high the ratio obtained isn’t that well. - A few years ago, Samuel Arbesmancame out with a book called “the Half-Life of Facts.” Many facts have an expiration date because new information comes in and reestablishes those facts. - The language of science has gone from Latin (hundreds of years ago) to German (hundred years ago) to English. This does not mean that other countries don’t produce good science in their own language, but publications are now generally in English irrespective of their country which is originating those papers.
- Popeye is one of the cartoon characters widely recognized around the world. He use to say, “ I’m strong to the finish, ‘cause I eats me spinach.” In any event he’s widely known, he was celebrated in a movie with the late Robin Williams. • Most people think that Popeye is considered to be extremely strong because of the iron content of the spinach that he is so widely known to consume. In 1870, a German chemist calculated the iron content in spinach as 35mg in a 100g serving which isn’t that much of a serving, but that’s a lot of iron. So, it grew that Popeye was strong because of the iron. However, it turns out that the 35mg was simply an incorrect number and it was actually 3.5mg and only 10% of that iron was actually present. Yet people started to talk about Popeye and his strength and that it was due to the iron. If you ask most people what his strength was caused by, most people would still say the iron. ‣About 7 years ago, this was worked up to being a popular item in the press. “Sorry Popeye, spinach doesn’t make your muscles big.” They revealed that the love of the food was due to a misplaced decimal point. - It also turns out that even the book that came out got it wrong initially. It was due to Mike Suttonwho published a paper on spinach iron and Popeye. “Ironic lessons from biochemistry and history of the importance of healthy eating, healthy skepticism, and adequate citation.” • He read and punished this in the internet journal of criminology. - Popeye was only once ever shown to be eating spinach. He said that spinach is full of vitamin A and that’s what makes humans strong/healthy. This was in 1932, the original source of these cartoons was 3 years early in 1929. He examined every single panel for like 80 years and never found any other reference to spinach other than this single panel, and no reference to iron whatsoever. • Even this was not correct because beta keratin is what is in spinach and it’s a precursor to vitamin A. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Ben Goldacreis an important writer in England. He comments, “Communal reinforcement is the process by which a claim becomes a strong belief, through repeated assertion by members of a community. The process is independent of whether the claim has been properly researched, or is supported by empirical data significant enough to warrant belief by reasonable people.” Goldacre is basically saying that if lies are repeated long enough and strong enough, they become a belief of a large community. - “Several studies have found that repeated phrases and ideas create a sense of familiarity in the mind, and can create the illusion of truth.” D. Thompson. This is what propelled Hitler to prominence in the 1930’s because he repeated and repeated lies until the public believed in the German public and that was the origin of much of his “success”. - The major message here is that public so widely believed that iron was the source of his strength and that’s what the public still believes even though it isn’t true. THEORIES- If you have enough facts, you can develop a theory. - For example, the theory to how the pyramids were constructed. They are enormous structures. One way to look at it is to think of what other way could you think of other then people building these by hand to build them. - If you were interested in doing research on this topic and you approach the Egyptian government and claim that you have a theory and if they can fund this theory then they can show that their theory is true. They would need some simple equipment to show that pyramids are just the tops of old gigantic buildings if you dig down far enough.• The answer is not entirely clear how they got there, a bunch of theories could be said about how they did get there.HOW DO WE GET OUR INFORMATION?
WHERE DO THE “FACTS” IN OUR TEXTS COME FROM? - What year did the Wright Brothersfly? It was in 1903 on December 17th that the Wright brothers flew a plane heavier than air, propelled with a motor with a person on board. • The headline in NewYork Times “Wright Brothers Give Account of Airship Test in North America.” “SOARED AGAINST A GALE.” They were deliberately trying to raise the airplane against the wind because it would lift the plane, but they needed to have enough speed so that the plane could take off. ‣120 ft in 12 secs which is equivalent to a slow jog or fast walk.- The Wright Brothers were bicycle repair guys from Ohio. They went to North Carolina. Eastern coast of North Carolina was known to have a substantial breeze. In Kitty Hawk North Carolina which is where they took their equipment and built the airplane. • There was a hill where they could work with where they practiced with a glider just to see what was possible to do to control the drift of the airplane as it moved into the wind. ‣It was not being propelled by any motor yet, just practice and experiment after another. - The end of the first flight was 12 seconds, distance 120ft, Pilot Orville. - An idea of the real impact. It would have flown about the length of one wingspan of one side of the airplane of the modern jet airplane. - Pretty soon the information went around the world and people started to do their own experimentation. - They flew around Manhattan later of the following year. - In the park “field for flight”, the monument is at the top of that hill from where they did their experimentation. - They were celebrated in 2003 with a stamp in the US. THE NATURE OF SCIENTIFIC RESEARCH - 1. Simultaneous/near simultaneous discovery happens. People are working on projects all the time. If you are doing some scientific research or even any other kind of research, be very clear that someone else is probably doing something rather similar to you. This is why simultaneous research is almost always taking place. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- In other countries people were working on this in other counties. In Italy, 1908-1910. They were giving their own efforts to aviation research. CREDIT/PATENT ISSUES- Who was the first and who gets credit? - It turns out that there was another individual, Samuel Langley. Those who look at movies dealing with the CIA know that Langley Field is in Virginia and that’s essentially where the CIA is located. Langley was a pioneer in air research and was doing about as much as the Wright Brothers but he was not successful in giving birth to an airplane that was capable of flying with a motor and someone on it. What he did, 7 years (1896) before the Wright Brothers, he was experimenting with a steam powered craft that clearly would not be able to take off on it’s own. • Steam as they said, went 100ft in the air for about 1/2 a mile. - They were launching these from a type of device in the water for reasons that it would not damage the aircraft that much if they hit the water as opposed to do it on land. They had to have a launching arrangement just to test the efficiency of this craft they were putting together. - He was doing very good research even up to 2 months before the Wright Brothers. He was eventually celebrated with a stamp, “Aviation Pioneer.”- Their are also people who came before them that deserve credit. Otto Lilienthal (1848-1896). In 1893, he had a sophisticated gliders that he used. There was a person on the glider but it was not being propelled and it wouldn’t go too far without any wind. - “If I have seen farther, it is because I have stood on the shoulders of giants.” - Sir Isaac Newton. This shows that it is very rare that anybody puts together a theory or an invention solely without reference to anyone else or any other time. - 7 years ago, there were some documents that were uncovered in Connecticut that seem to illustrate that the individual Gustavo Whiteheadwho was also experimenting with aircraft had actually put one into the air on his own in the same way that the Wright Brothers did. However, there were no photographs or any other person who could verify this, it was just discovered as a writing. Whether it happened or not is not very clear, Connecticut wants to claim this but there’s always something new coming in. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
EGO ISSUES- If you’re working on something and putting your heart and soul into it, your ego will be flattered by the success that you may achieve and the protection that you may want to make to your own success. - Wilbur and Orville Wright were not lobbying to have their aircraft put into the Smithsonia institute which is the major museum in the United States. Eventually it made it there, but it was only 45 years after the fact. It is now currently in the Smithsonian. They had to put 605 pounds into the air, it did take a little effort to do so. • Why did it take 45 years for this discovery to be recognized by the major museum in the United States? Samuel Langleyand his supporters were associated with the Smithsonian institute and they just wanted Langley to get credit for his work. They were a little bit too aggressive and kept the Wright Brother’s from being recognized until 1948. - Another modern discovery, namely of DNA. It turns out that Watson and Crick did not discover DNA. Frederich Miescherin 1869 discovered DNA by examining that comes from the puss of wounds. His research was put to the side by the fact that this person he worked under did not think his work was very good. It turns out that it was not a protein, carbohydrate or fat. It was some other combination of chemical entities that meant that it was different. • Eventually Miescher was able to publish his work. The arrangement in Europe, in the late 1800’s was that there was one professor at an institution/university who’s work took over all of the other people who worked under that individual. • In North America, and in most other parts of Europe and South America, etc. The professor is an individual who has the rights to work on their own projects and to get funding on their own and to be an independent observer of the scientific method. This was not the case in Europe at that time. Miescher was relegated to a secondary position and his paper was not published, however it eventually it was. - Oswald Averycomes in before Watson and Crick. He was born in Halifax (1855-1955). He was working at the Rockefeller Institute for medical research in the 1930’s and 1940’s. He was a very calm and collected man, was also very shy. • In 1944, he published a paper that really put everything in motion for Watson and Crick and others to work on DNA.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• He published a paper that showed the DNA of a particular fractions of deoxyribonucleic acid had the capacity to reproduce which was the real key in all of this. People thought for some time that Oswald Avery should have won a Nobel Prize for this, but he did not. - So, in the nature of scientific research, simultaneous discovery happens or near simultaneous discovery. One of the individuals engaged in this near simultaneous discovery was Linus Pauling. He received a Nobel prize in the late 1930’s (1937 or 1939?) for his work on the chemical bond and how it was put together. He was a pacifist and obtained another Nobel prize for peace later on in his life. He was probably the premier scientist of this era, of the 1930’s, 1940’s, 1950’s and 1960’s. • He was after the secret of what DNA was all about. He published a propesed structure for nuclei acid which turned out to not be correct, this was in 1952. He was doing this with molecular models.- Watson and Crick were working at Cambridge in the UK were fearful that Pauling would work this out first because he was better known and better equipped to solve this problem. • Watson and Crick were essentially ‘scientific nobodies’. Crick in his 30’s was working on his PhD in physics. Watson was only 22 and received a PhD in what would be called now molecular biology at the university of Chicago. He came with a broad brush desire to solve this problem of DNA. He and Crick got together to work on this. - They published a paper “Molecular Structure of Nucleic Acids: A structure for deoxyribose nucleic acid.” They had a phrase that was important: “It has not escaped our notice that specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” • They set the stage for an enormous interest in their work. - Who gets the credit for all this? - It turns out that a person at that time who did not get nearly enough credit was Rosalind Franklin (1920-1958).She died before the Nobel Prize was awarded, there were books written about if this was deliberate or not because she was a women. At that time in the 1950’s, women were not prominent people in science. She was working for Maurice Wilkins at Cambridge and she was the one who put together the X-ray photographs that Watson and Crick really needed. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- She died of cancer prematurely. - The key feature is if it’s a helix, it would have this particular array of key features in this ‘x’ arrangement. - Watson and Crick published the paper without reference to her or Maurice Wilkins who was also working on this. He was working at King’s college and Rosalind was working with him in a loosely held arrangement. - Collaboration often works, but Watson and Crick didn’t really steal this, they were given the X-ray photographs which triggered there knowledge of what was really happening what that particular structure. • Watson wrote a book on this topic which is worth reading. He describes it, and he was a bit of an extrovert so he gobbled up the credit. - The collaboration that works is really illustrated in a simple carton. Somebody working on circular stones, and someone working on a box. They talk it over and they get together to come up with a completely knew invention. - Collaboration does work, but Watson and Crick did not provide enough credit as we would normally do in this era. - As for Ego issues. Pauling was the scientific giant of the 50’s and 60’s. Pauling had given the famous Baker lectures at Cornell in the chemistry department in 1937 for which he won the Nobel Prize for his work on the science of the chemical bond. - In 1987 he was there at Cornell giving the 50th anniversary of the Baker lectures. • Pauling also wanted to get ahold of these X-ray photographs. He stated in a recording that he ‘wasn’t working very hard on it’, however this is doubtful. Ego plays a role wherever you are, you have to watch out this with individuals you are working with. Make sure that their egos are under good management. - Who coined the phrase “Theory of Relativity?” • Max Planckcoined this phrase. JOURNALS- In the middle 1800’s, the Journal of the Chemical Societybecame the first journal that was peer-reviewed. This means that the articles were sent to individuals who would have a opportunity to understand the article and give a good review.
- Up until that point journals were more like the writings of the scientific elite which were not reviewed by anyone except for the editor or the editor staff. - The Journal of the Chemical Society in the middle 1800’s is where the peer reviewed literature started to become created, this is an important milestone. - For example, what were people looking at, at that time. “Distillation of Meconic Acid.” Meconic Acid comes from the exudate of the poppy, its a product that they were looking at, they would scrap it up and put it on to see what it was involved with.- Or, “On the Occurence of deposits of Crystallized Phosphate of Lime in Human Urine.” This was a peer reviewed operation that was taking place. - There are several types of publications:• Journals • Books • Reviews - The essential primary literature are composed of three types of publications. Full paperswhich are the details of all the scientific work, the ‘recipes’. Notesare short full papers. Communicationsare the short urgent type of a publication in the primary literature, this is what Watson and Crick published, they published it rapidly. • Sometimes it might take a year to get a full paper published. ACADEMIC RESEARCH- You have to have an idea of some kind and then the next step is to write to granting agencies to obtain funds as it costs a lot of money to propagate research. • Let’s say a grant is secured, some time passes, you get a result, and it’s time to publish. You send the paper to some journal, hopefully based on the fact that the journal will be suitable for the reception of that article. That’s where the peer review process kicks in. • You have the researcher doing a complicated situation, then you have the editor. Most papers that get sent to a journal eventually get published somewhere, not always in the journal of choice but most of them will get published. The editor then has to chose 1 or more (normally more than 1) referee to judge whether the paper seems reasonable. They simply read the article, judge whether it’s been reasonably put together, if it has been sourced properly, and then that information will get sent back to the editor. It is not so common that a paper will have nothing wrong with it, usually there are some criticisms. Sometimes the criticisms are sufficient that indicate the paper should not be published.
• The editor may ask for the referee to illuminate other features, but normally it is then sent to the researcher (like getting your homework back). The researcher will most likely have to make some corrections to their paper. Then it get sent back to the editor where they might send it to the referee for further illustrations of the corrections that the researcher made, most likely not, but could happen. The editor, sometimes with the editorial staff, will make the decision as to whether the paper is published or not. They will send that recommendation to the researcher. • In the case that the paper was accepted for publication, all of this back and fourth business is an important part for the referee peer review situation. At no time does the researcher know the identity of the referee. One could argue about if this is the right thing to do or not. Some people may harbour grudges, so it is usually better that the researcher does not know who the referee is, and the referee can feel more free to give their honest opinion. - When you receive a critique of your paper, it may hurt your feelings a little bit. Some editors are more harsh while others are more kind. - Sir Hans Adolf Krebs (1900-1981)is famous for the Krebs cycle illustrating how science is put together at the molecular level. - He wrote originally in 1937 to the editor of nature. The editor presents it’s compliments to H. A. Krebs. He basically rejects it. - Krebs won a Nobel prize for this very work that had been refused originally. This is not the first time that work was refused initially in a journal and then won a Nobel prize. A COMMUNICATION - A personal example, the first communication sent out by David Harpp. It was typewritten, before computers. The graduate student was John G. Gleason, his first graduated student and probably the best one he ever had. • It gets correlated into a more coherent looking document. It gets sent to the journal of American Chemical Societywhich is one of the best science chemistry journals in the world. Then you wait for the referees report. - First paper as a professor at McGill.- The referees offered some suggestions for which they would not get any credit other than if the suggestion were taken up in the paper as a change in the paper to say that a referee has suggested these particular features. This is the right thing to have done since they have spent time addressing the mechanism of this particular reaction.
NAMES ON PUBLICATIONS - Normally, for chemistry, the first author is often the person who did the most work, and the last author is often the person who is the senior person in the documentation who illustrates the permanency of that position at the university/company publishing the paper. This is not always the case, in geology, if you are not the first author you are relegated to a subservient role. The first author is the one that counts mainly for everybody, they are usually the senior author. So it varies considerably. - In chemistry there is an asterisk appointed to the person who is the person to whom communications should be directed. Each division of science is a bit different in it’s way of giving credit for people. - What do you do in a collection, mapping, and annotation of over 28,000 cDNA clones from japonica rice? 75 authors, each has a spot. They’re not in alphabetical order, there just done in a convenience for where they were with the 8 different locations of the individuals. • This is not that common. More normally it would be 2-4 authors and sometimes disagreeable considerations take place as to who will be second or third. This is usually up to the senior author who is funding the research.- C. J. Pedersonwho was from Du Pont company. He wrote a paper “Cyclic Polyethers and their Complexes with Metal Salts.” It was a single author paper, and it was the reason for his Nobel prize in 1987. He was fundamentally involved with how molecules capture ions. This paper has bred thousands and thousands of other papers. • So these papers can be as few as 1 which is very rare, or it can be as many as 90 or more which is relatively rare. More normally it would be 2-4, it could be 5. The order in which they are presented can be alphabetical, it can be whatever that particular subdivision of science dictates as the way their culture operates. There’s no absolute way of presenting credit in the authorships. THE EXTENDED LIFE OF RESEARCH- Once a paper is published, it needs to have an extended life such as “Chemical Abstracts.” However now it’s all automatic and is all online. Those original articles, which are the original abstracts. This means there’s a lot of work to review because their so small and the document is pretty big. - The paper that David Harpp wrote with his 2 colleagues the abstract was about 5 sentences. It describes what is going on.
- Those 5 sentences which can from a communication wound up in a organic chemistry test as 1 simple sentence. How do the facts get to be in a textbook? They get to be by way of all of the research that is done, the referee system that takes place, the publishing of the article, the abstract, and essentially the summary of the abstract. - A more fundamental paper that they eventually published wound it’s way into an organic chemistry text.• This particular paper ended up in an advanced chemistry text with 2 sentences. SCIENCE PUBLICATIONS - There are many, science can’t keep up with the flood of new journals. This is just science, geology, mathematics, chemistry, physics, and biology, its leaving out another number of entities. - If we spread out chemistry, analytical, physical, organic, inorganic, theoretical, those are not even the modern versions of what names are associated with the different categories in chemistry. ARCHIVES- The original archives were all done by hand in Columbus, Ohio. They were put together in volumes, painful to pick off the shelf. Now they are relegated to the different buildings around McGill. They are all electronic now. - The vast majority of scientific papers that are published are honest efforts to report facts. • There is no sin in science more previous than falsifying data. There is no accusation that can be made that is more serious than to be guilty of a sin. ‣So there is fraud. Flawed cancer studies lead to shake-up at University of Oklahoma. - Retractions of papers does not happen very often, the percentage is very low. However, when it foes happen, it often makes headlines. - It turns out that the national institutes of health who sponsor a lot of research in the United States have scientific misconduct conferences because there is so much money involved. - Reviewers déjà-vu, French Science Sleuthing Uncover Plagiarized Papers. Stealing one experiment is stealing an entire paper. All that was done was to exchange from the original article the name of another plant. This was discovered, and it happened not to long after, ~10 years later the paper was brought forward.
• So although this happens, even though it is not that common. What are the consequence? For academics it is not good. It could be loss of grants in the future, loss of job, and in the USA it could be a felony. RECENT SITUATIONS - Predatory journals are journals that try to get people who are insecure in there research to publish in them. - David Harpp got a few weird emails requesting his presence at some meetings. OPEN ACCESS - There are subject to dubious refereeing and it is not clear whether the editor is someone who simple excepts the papers. He - You must be careful with what you are looking for.
MEDIACaitlin Malcolm-Pottle- We are flooded with information, but the question is how much of it is relevant and reliable? We have to know how to filter information. INTERNET- When you go on the internet, there are millions and millions of websites and blogs, etc. Some of this is very seductive and looks very scientific. • For example, stomach acid. An experiment that is replicated on many websites, stomach acid is said to be in a glass, and it’s suppose to show how terrible Coca Cola is when you drink it and what it will do when you drink it. When they pour the Coca Cola into the glass, there’s an immediate chemical reaction, there’s an emergence of this weird black material. ‣What they actually did was put some concentrate sulphuric acid in the glass and added some sugar. Sugar is found in Coca Cola and the chemical reaction between concentrated sulphuric acid and sugar, the sulphuric acid dehydrates the carbohydrate and forms elemental carbon. It rises out of the beaker as a ‘giant snake’. It also has a pretty revolting smell when you do this because all kinds of sulphur compounds are given off. However, what they are using here is concentrated sulphuric acid plus sugar in the demo. If you do this with dilute sulphuric acid and sugar, then nothing much happens, you need concentrated sulphuric acid. ‣Coca Cola is not pure sugar. The acid in our stomach is hydrochloric acid, it is not concentrated sulphuric acid. So, while this is an impressive demo, it has nothing to do with what happens when you drink Coca Cola. There are many reasons to abstain from drinking significant amounts of any soft drink because they are high in sugar and also contain small amounts of caffeine, but they won’t do anything in your stomach like what the demo was trying to show. TV- A very popular program in Canada is Dragon’s Den. There’s a bunch of millionaires looking to invest in innovated schemes, sometimes they do and sometimes they don’t. There’s one episode where there was a chiropractor who claimed to have developed a new device that sounds absolutely miraculous. • It was called “Neuro Connect.” It optimizes your balance and controls your body strength.
• To advertise they started out by saying how the little clips that you put on your body will energize you, improve your balance, and do all kinds of wonderful things. • They proceed with a demo, they take one of the dragon’s who is a golfer and ask him to show his swing. They then see that if the swing can be improved if the device is used. They put on the device, and they claim that the swing is improved. Of course this demo was meaningless. They give the explanation, the clips get put on, you even put one of your golf club, and it then sets some kind of quantum entanglement which means nothing in this context. The summary states that it will circulate a sudden energy patter that causes the central nervous system to be more responsive to nerve receptors in joints and muscles. ‣This is an absolute meaningless statement, and they have no evidence for it. They then ask another Dragon to come up and hold out her arm. This is the applied kinesiology. The guy tries to push down her arm on the first try, and he easily does so. However, then he puts this clip on her and then tries to push down her arm but has a lot of difficulty because she has been ‘energized’.”‣It’s not only the clips that they’re promoting, they also have a spray. This is an energizing spray, so after he sprays her, he once again have trouble pushing down her arm. ‣They also say that it protects against radiation from cell phones. If you read through the label, it’s just a mixture of all kinds of substances. They tell you the “if you have someone test a previously strong muscle, it will weaken when you place a cell phone over the front midline of your body.” This is not a fact, its total nonsense. ‣However, they are obliged to give a disclaimer. “There’s no scientific proof that Neuro Connect EMF protection eliminates the harmful effects of radio frequency.” So if there’s no proof, what are they talking about? ‣This stuff is sold online and its pretty expensive. - This has actually been tested at university of Toronto. They tried it, in science we don’t dismiss anything, things need to be tested. Of course nothing was found. Marketplace also did an analysis on this and eventually health Canada ordered the people to stop advertising selling this, but it hasn’t been effective. They still have a website and are still selling the products. Unfortunately Health Canada just doesn’t have the manpower to go after all of these poeple who are making unsubstantiated claims. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Remember claims that seem to defy everything that we know about science require a lot of evidence. Of course they have not provided any evidence whatsoever. - The US version of Dragon’s Den is Shark Tank. A very similar program, some of the Sharks have appeared on both shows. - Sarah Lee and Christine Chang were two ladies who approached the Sharks with a line of cosmetics, nothing very special about it. However, after they appeared on the show, you started to see advertisements about the products that they supposedly were promoting on the show. The product that they actually promoted was ‘Tundra Chaga.’ This is some sort of cream with a mushroom component, nothing really special about this, there was no big investment. • After the show, you started to see ads online. Ads of the same ladies but their names are different. Now they are Angela and Yoojin Kim. The product that they are supposedly promoting is Lucienne skin product. The promoters of this product have hijacked the picture that appeared on the TV show, they altered it so that it looks like they are promoting Lucienne skin and they also claimed that the Sharks invested huge amounts of money. They did not invest even in the original. So here they hijacked the picture and are saying that it is on behalf of the product that they are now promoting called select skin. ‣This product never appeared on the show, its completely different. They were just trying to ride on the coattails of the two ladies who really appeared on the show with a different product. - Even the ad for select skin had been stolen. It was taking from another product that had nothing to do with the Shark show. - The two ladies are now promoting a completely different product, ‘miracle testosterone pill.’ These two ladies have never been on the show, the ladies who originally appeared were promoting a cosmetic, but now their picture has been stolen and their names have been replaced with a product that never even appeared on the show. There’s a lot of dirty business in advertising and trying to steal others promotional material. - Whenever we look at the media, we have to have a critical eye. There’s just so much nonsense out there we have to look for facts and what is fact based. - Joe was at a birthday party in grade six which there was a magician. This is what got him interested in advertising, media, and portraying science properly. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Joe started reading chemistry and seeing all the interesting things about it and he started to see that there were all kinds of ways that you could fool people. - He was given a chemistry set as a gift. One of the chemicals included was silver nitrate and their was some copper wire. The experiment was to put the copper wire into the solution of silver nitrate. What happens is that the silver ions are reduced to metallic silver, the copper is oxidized and the silver plates out on the copper wire. He made an observation, that when you got silver nitrate on your hand, it changed colour, almost indelible black. This is because when silver compounds are exposed to light, they will turn into metallic silver. This is the basis of the photographic process when film was being used. - Joe and some of his friends went up to Saint-Joseph’s Oratory. They put some silver nitrate into the holy water. The pilgrims would come and dip their finger into the holy water and then touch their forehead in the form of a cross. When they came out and the sunlight would hit them, they would see this black cross on their forehead. They thought that they had seen a miracle. You have a colourless substance and expose it to light and then it turns into a black material.- Joe was exposed to the TV program “I dream of Jeannie.” This was a sitcom where an astronaut marries a real life Jeannie. The show started with him finding a bottle, he accidentally rubs it, and the Jeannie merges out of the bottle. Joe wonders how this could happen. He did eventually figure out how the smoke came out of the bottle, inside of the bottle, their were 2 compartments. When the bottle was tilted, the two chemicals mixed together, and when they mixed, it generated steam. In one compartment there was hydrogen peroxide, and in the other was manganese dioxide. Manganese dioxide acted as a catalyst, breaking down hydrogen peroxide into water and oxygen. This is a highly exothermic reaction, meaning that it produces a great deal of heat, so much heat that the water turns into steam and it comes out of the bottle. • This is an interesting reaction. This is one that Joe has used in one of his books, “The Genie in the Bottle.” He described this reaction in his book. He thought it was appropriate because chemistry is really like a genie in a bottle. You can do wonderful things with it, but it can also be a double edged sword. The same chemical can be used for good or bad. For example, morphine can be used to take away pain, or it can make people addicted. Chemistry is two-faced. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
CONNECTIONS
- The Komet could rise above any allied airplane very quickly and then come diving down and pick out the planes like flies. The flight time of the Komet was only about 8-9 minutes, so it never became of practical importance during the war. Had the war lasted longer, the Germans would have probably developed a much more viable weapon using hydrogen peroxide technology. - After the war the whole concept of rocketry was slimmed down to make the rocket belt. This has the same chemistry, hydrogen peroxide generates hot gases. The rocket belt was originally introduced to the North American public by James Bond in the 4th James Bond film which was “Thunderball.” In one of the opening scenes of the movie, James Bond takes off in this rocket belt. This is a real device. • Like any rocket, you need some hot gases emerging in one direction which will propel the vehicle in the opposite direction. Hydrogen peroxide breaks down to form steam under the influence of a catalyst. Nitrogen, compressed gas pushed the hydrogen peroxide through a valve into the gas generating chamber where it was mixed with a catalyst, this formed the steam, the steam comes out f the vehicle and creates the thrust. - The rocket belt still exists, they do exhibitions with it. The problem is that the time that it can fly is only about 30-40 seconds because that’s the amount of hydrogen peroxide that can be stored. - Hydrogen peroxide can also be used in the natural world. Thebombardier beetlehas a device on his underbelly where he can spray a hot toxic mix of chemicals to ward off his predators. Hydrogen peroxide is once again needed. In one of its gland in its abdomen it stores hydrogen peroxide and a compound called hydroquinone.Both of these are produced from the food that the beetle eats. When the beetle gets scared, it squeezes it’s belly and that brings the hydroquinone and the hydrogen peroxide together with various enzymes in an adjacent chamber. When this happens there’s a chemical reaction. The hydrogen peroxide reacts with the hydroquinone to form a compound called quinone together with steam. This is what comes out of the turret underneath the beetle and the predator learns to leave this guy alone. • Hydroquinone which derives from the diet of the beetle is stored together with hydrogen peroxide and when these combine with the enzyme it forms quinone and steam. What you have here is chemistry similar to the genie bottle and all of the rockets. - There are also all kinds of uses for hydrogen peroxide. The skunk for example, it releases a terrifying compound. It falls into the chemical category known as the mercaptans. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• They are compounds that have sulphur and hydrogen in them. - What do you do if your dog gets sprayed by a skunk. Tomato juice is not the right remedy, this is a myth. You want to use hydrogen peroxide and oxidize and react with those mercaptans and it will change them into a compound that doesn’t have a smell. • 1L of 3% hydrogen peroxide. 1/4 of baking sofa. 1 TBSP of dishwashing detergent. - There’s all kinds of claims that hydrogen peroxide can produce miraculous effects when it comes to disease. One of the claims being that it can be used in the treatment of cancer. • They call it a medical miracle. This is total nonsense, hydrogen peroxide has no role to play in the treatment of cancer. - Chemistry has all kinds of connections.- An ad by a naturopath: “Any part of the body that might for any reason have been oxygen deprived will benefit from this increased oxygen.” Hydrogen peroxide will not increase the amount of oxygen in your blood stream, this is total nonsense. I doesn’t stimulate anything, there’s no treatment of cancer using hydrogen peroxide. • These people are just purveying magic. There’s no magic in hydrogen peroxide except for the chemistry magic when hydrogen peroxide is mixed with a a catalyst. - In 1980 at the ‘Man and his World” which was an ongoing exhibit that was in Montreal. This grew out of expo 67. In 1980, with professor Harpp and Fenster they were asked to mount the chemistry display at the UNESCO pavilion. UNESCO is the scientific arm of the United Nations and they wanted some sort of mini science museum, little chemistry shows. They hired some students and they did different demonstrations, they had a pretty large audience over 2 summers. • They had several hundreds of thousands of people saw these shows and there was a little theatre where they would watch these 20 minute long shows about chemistry. All kinds of people attended the shows including Pierre Trudeau who was the prime minister, mayor drapery who was the Montreal mayor at the time, and sitting at the front was a very young Justin Trudeau. - One of the experiments that they performed was the making of polyurethane. You pour together these 2 solutions and almost like magic this mushroom like cloud rises out of the glass. This foaming material is used in all kinds of ways.Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• This was at the time when Miss Piggy was at the height of her fame. She was in fact made of the same material that they were demonstrating, polyurethane. - This was at a time when a lot of people were using Urea-formaldehyde to insulate their homes because there had been the energy crisis in the 1970’s and people were looking for ways to save money on energy. • Urea-formaldehyde was a foaming material that could be sprayed and it was a very good insulating agent. However, if it was improperly applied, it would leave behind residue of formaldehyde which is a dangerous substance. • Already there were lawsuits at the time, they were suing for the use of this poisonous foam. However, what they were using was polyurethane. - One morning Joe found an article in the Montreal Gazette which was about them, that they were “trying to put a positive spin on a dangerous material.” He saw this at about 7 o’clock in the morning and then by 9 o’clock he had a letter on the reporters death explaining that they had been demonstrating polyurethane and not urea-formaldehyde. Just because two substances look similar does not mean that they are the same. For example, you can have 2 glasses of clear liquid, 1 could be water and 1 could be vodka. They look the same and you can only tell the difference once you taste it. • The journalist then printed a nice ‘mea culpa’ article. This is essentially an apology, a retraction the day after. • It turned out that the story was not quite finished. The next morning he got a phone call by radio station CJAD asking if he would like to go on the air and comment on the controversy. He agreed, but stated that there was no controversy. He told the story, and they seemed to like what he did because the next week there was some other question that came up about science and asked him to go on the air again. Pretty soon they asked him if he would like to do this on a regular basis. • The second question that he was asked was, ‘is it safe to lick your balls’, the person speaking left out the word ‘golf’. Golfers have a habit of of picking up the golf ball and kissing it before putting it back down and hitting it, this is for superstitious reasons. The question came up because the person had read that pesticides were used often on golf courses and he wondered whether or not that picking up the golf ball and transferring it to his mouth if this would cause him potential harm. ‣They talked about how only the dose makes the poison. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
‣Joe also explained that the chances were the amount of pesticides transferred would be too little to make any kind of difference. He also suggested that their were better things in life to do then to do around kissing golf balls. - CJAD is the longest running radio show on chemistry in the history of the world. It is the only radio show on chemistry in the world. - The word chemical has essentially become synonymous with toxin or poison. People have this impression that chemicals are bad things and that we should stop using chemicals, we need to fear chemicals. For example, acetic acid is something to be avoided as a chemical, but vinegar which is the exact same thing, is a “natural cleaning agent.”• People want chemicals to be locked away. Chemicals are not good or bad, its always a question of how you use it. - Joe keeps repeating this statement, “chemicals are not to be feared or worshipped, they are to be understood.” - Chemistry isn’t the work of the devil, chemistry should be in the lime light because everything around us is based on chemistry. We are just large bags of chemicals, everything that goes on in our body is a consequence of chemical reactions.- In 1939 at the New York World’s fair, there were a lot of exhibits that tried to paint chemistry in the proper light. For example, the DuPont pavilion introduced the slogan, “better things for better living through chemistry.” At that time, nobody had any negative comment about this because chemistry was doing wonderful things. There were new fibres being introduced, new plastics that were being introduced and this kept going for decades. In 1964, the New York World’s Fair, chemistry was still in the spotlight. The DuPont pavilion had a shown inside. They had actors playing the roles of molecule and they played out a number of chemical stories. This was at a time when chemistry and science were flying high and people were jumping on the chemistry bandwagon. There was no negative about this. • Compared to today, we now have a chemistry set with no chemicals required. You’re suppose to go and get your own vinegar and baking soda which seemed to be the only safe chemicals that they wanted you to use. Any chemical can be used safely. It’s important to understand that so people don’t fear chemistry or chemicals. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• Not all chemicals should be targeted as being poisons to be eliminated for our life. They should not be regarded as being wolves in sheep’s clothing. Chemicals have to be judged on their own terms and we have to think about what kind of critical thinking can be applied to how we can use substances in a safe fashion. • Sometimes critical thinking is even missing among highly educated people. Dr. Joan Gussowwas a professor of nutrition at Columbia university. In an article in Times Magazine, they were urging people to eat local which is a good thing. In this article she was talking about our food supply and talking about buying locally. She came out with this statement. “As for butter versus margarine, I trust cows more then chemists.” • Why did she prefer cows over chemist? This was all about margarine. Margarine is not a natural product, it is a man made product. Margarine is made by taking unsaturated oils like corn oil, canola oil, any oil that has double bonds in it. There’s a process where you hydrogenate it to make it into a solid fat. Liquid fats are generally the ones that have multiple double bonds in their structure, when you get rid of those double bonds by hydrogenation you convert them into a saturated fat. Saturated fats are problematic because these are the ones linked to heart disease. • So anyway, margarine is made by taking unsaturated fats and hardening them. At the same time that you are doing this, you get a reaction known as a isomerization reaction. This is where the structure of the double bond changes, it goes from a cis configuration to a trance configuration. This is what is referred to as a trance double bond. Trans double bonds are equally as bad as saturated fats when it comes to our cholesterol profile. ‣This is interesting because originally the reason that margarine was concocted in the first place was because people were afraid of butter, so they were resorting to things that were made from unsaturated fat. It turned out that the trans fat that were part of the production of margarine, were as bad as the saturated fats. Studies started to emerge about how trans fats are just as bad as saturated fats and that they were associated with mortality, coronary heat disease, and that these should be avoided. - It was up to chemist to try and figure out how to get the so called toxic trans fat out of our food supply. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• Now you have margarine without trains fat in it. Chemist very cleverly found a way to produce margarine without having trans fats in there. By avoiding the hydrogenation process going through something called transesterification. • So, was professor Gussow smart to say that she trusted cows more than chemist because cows don’t produce margarine? No. Chemist have a way of solving such problems, it was quite a silly statement to begin with. IMAGE PROBLEMS
• It’s suppose to do everything; help prevent kidney disease, supports immune function, but this is all total nonsense. All that baking soda and lemon water will do is produce carbon dioxide gas, there’s no healing effect. - The monster lab soon disappeared and kind of reappeared the next year as “Doctor Dreadful.” This toy had the same chemistry as the first time. Bicarbonate and citric acid, instead of sizzling the flesh off a monster it made foam in a glass, a carbonated beverage. MAD SCIENTIST - Some of the blame can be put on Mary Shelley. She is the creator of Frankenstein. There are many myths about Frankenstein. Frankenstein was the creator, he was not the monster. In the book he was never referred to as a monster, only as a creation. Frankenstein wasn’t even a doctor, he was a medical student who was very disturbed when his mother died and he sought to create life. He took body pieces and put them together in hopes of bringing them back to life. Once the body has been put together there’s some sort of electric gizmo that brings it back to life. • Victor Frankenstein was the medical student trying to do this. - Spark is the word of interest here, was she using it metaphorically or was she talking about a real spark? We don’t know. Mary Shelley was the wife of Percy Shelley, they went on a trip to Europe together with Lord Byron and the weather was bad. They had to spend a lot of time indoors and to past the time they decided they would all write a story and see who could come up with the scariest story and this is how Mary Shelley came up with Frankenstein.
• Where did the idea come from? Usually fiction is born out of something. In this case it was probably born out of the work of Luigi Galvani, an Italian physician who experimented on frogs with batteries. He basically laid the foundations of the science of electrical chemistry. Galvani was the first one to realize that if you took different metals and put them together with some sort of electrolyte in between you would generate a current out of it. He built a battery and he showed that when you applied the current from this battery onto the limbs of a dead animal such as a frog it would quiver. In those days, it kind of looked like the animal was being brought back to life. Not only were there demonstrations of frogs being “reactivated,” there were even demonstrations with dead people. • One of Galvani’s nephews, Aldini went around the country with a large battery hooking it up to recently dead people and showed that when the battery was hooked up he could create all kinds of motion in the body because he could activate the nervous system. We know that Mary Shelley was at one of these demonstrations and this could be where she got the idea for Frankenstein. She thought that this was a situation where science was being pushed further then it should be. - In a poster for the original version of the Frankenstein film the ad said “monster science created, but could not destroy.” This really wasn’t a horror story, it was a philosophical story showing what happens when science doesn’t have a boundary, when scientist do things when maybe it should have been alone. • This has persisted today. When people want to vilify genetic modified foods, they say ‘fear of frankenfoods.’ Frankenstein has been ingrained in our life. - Mary Shelley may have had the idea that the creation was a problem because science cannot always predict was will happen. In the book, the creation acts in a very civil fashion. It was only when people started to pick on him did he turn into a monster. It really is a story about what people do when they are confronted by something they don’t understand. - Today we have this problem. People constantly being confronted by things they don’t understand like genetic modified foods. If you take a look at what legitimate scientist think and what the public thinks, theres a huge divergence. • For example, when you look at genetic modified foods and look at the scientist versus the adults in the US, 88% of scientist think that there’s no issue, only 37% of the public. You take a look at another question, childhood vaccines, 86% of scientist are pro, only 68% of the public. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- The question is who do we trust? Shouldn’t we be trusting people who are trained and know how science works, who know how to read literature and who have some ability for critical thinking, isn’t this what we should be looking for? Unfortunately this is not what’s happening, these days people are getting their information from the internet. • This is like trying to drink from a fire hydrant. There’s so much information and its very difficult to separate the facts from fiction. There’s a lot of misinformation and there’s a lot of disinformation which is misinformation that is being disseminated on purpose. Misinformation can simply be some mistakes. - The food babehas a huge following on the internet, she has no scientific background, but she plays a very good game. • She got famous for this classic statement, “you wouldn’t eat a yoga mat, would you?” Where does this come from? One day she was looking at the label of some rolls and notices azodicarbonamide. This is a chemical that is used as a leavening agent. It releases a gas when heated, that gas is nitrogen and that causes bubbles to form in the dough very must like yeast. As a food additive it has been tested, theres no problem with nitrogen gas being produced. She also discovered that the same chemical azodicarbonamide is used in the making of yoga mats. Yoga mats are made of a plastic and in the plastic those bubbles are created by azodicarbonamide. Therefor she comes to the conclusion that when you are eating at subway you might as well be eating a yoga mat. She had a lot of success with this, and subway actually took out this additive in their product because of all the publicity. - Just because something is commonly used in food, but also used in something that is not edible doesn’t mean that its dangerous to consume. - She also made a splash with her question on the internet, “ do you eat beaver butt?” She was implying that whenever you eat vanilla ice cream you’re eating beaver butt. Where does this come from? She read that beavers produce a secretion from glands near their rear end. This is a mixture of a number of different compounds and one of these through a system of chemical reactions can be converted into vanillin. This is of academic interest, nobody produces vanillin in this way, it would not be economical. There are very simple ways to make vanillin from wood, and from lignin which is found in wood.• So although someone showed that this is possible to do this, it does not mean that its being done. It was an interesting academic exercise. She comes to the conclusion that when you eat ice cream, you’re eating beaver butt. This is nonsense. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• The synthetic vanillin used in ice cream has nothing to do with beavers. - She also has this saying, “if you can’t spell or pronounce it, you probably shouldn’t eat it.” Whether we should or should not eat something, it should not be determined by the number of syllables in the chemical name or whether we can spell it or not. It has to be determined about what we know of the substance. - She has been very successful having written a book about this. It’s not that everything she says is wrong, but the basic concepts that we should be fearing every chemical that we come across is just not scientifically justified. We always need to ask what the evidence is, who studied this, and what was actually found. - On television they had a discussion about trans fats. Who do they ask? Do they ask a leading scientist who actually know something about nutrition? No. They ask someone with zero background on this subject acting as an expert. - It doesn’t mean that legitimate documentary programs on television should not be looked at with a critical eye, this is because they make mistakes too. • 48 hours was a program on CBS. It was a highly respected program and usually they did really good things. However there was this one time when they were discussing the building of a landfill. There was opposition from people who live near this landfill which is understandable. On the tv show, they described where this landfill would be built, and rocks would be the lining of this giant pit that would be built. They interviewed a couple of people form a town nearby who were opposed to this. They came with a little demonstration. They took a piece of rock that was from one of the ones surrounding the landfill. They wanted to show what happens if discarded acid gets into this landfill. They poured some acid into the jar with the rock they took from the landfill, and pretty soon it starts to foam up. Somehow they even managed for a dog to approach this bottle and be horrified and run away. • This stone that surrounded the landfill was essentially marble, or limestone(calcium carbonate). This reacts with an acid to release carbon dioxide gas. So the foaming was this carbon gas bubbling out. • In truth, the reason that this site was selected in the first place was because calcium carbonate is a base. It’s a neutralizing material in case any acid should get into the landfill. When it does, it breaks down into harmless carbon dioxide. However, this part never got translated into the document. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
ADS ON TV- Liquid lustre is a car wax. Ammonia has a terrible smell and it’s not something you want around. The guy sprays some ammonia on the hood of the car. He says that they will attack the shine on the car with ammonia, and that they will add hydrochloric acid too, which is highly corrosive. As soon as he adds the hydrochloric acid, you start to see these white fumes coming off. It looks like the metal is dissolving. What really is happening is that the ammonia reacts with the hydrochloric acid to form a salt, ammonium chloride. The ammonia is actually being neutralized by the hydrochloric acid preventing any damage to the car. INVESTIGATIONS- Joe had received a call a couple of years ago from a lady who said that a friend of hers had heard about this healer who was coming to Montreal and could do miraculous things by just hovering his hands over the people. She wanted to know if this was real or not. This interesting Joe, and he looked into the gentleman.• His story was an interesting one. He said he was in the Israeli army and one day he woke up really early in the morning and had seen a shining light on top of a mountain so he climbed up and saw this giant thing hovering over the mountain and the next thing he knew was that he woke up. After that he had this talent of being able to hover his hands over people and heal them. - He had all kinds of testimonials saying that they had been healed. Joe had sent one of his helpers to see what this was all about. She comes back and says that she had to lie down on this table and tell him what her problems were, he hovered his hands over her body and she said she felt the electricity. She said she felt her hair rising, that she had felt something. - So, Joe consulted the amazing Randi. Joe told him exactly what his assistant told him. He said that you should go and buy yourself the electric touch. This is a device that you get in magic stores and you were it around your leg. It generates static electricity. This will enable you to pick up little bits of paper with your hand. - Joe called him and made an appointment. It was 75$ that they were charging for the appointment. Joe lies down and at first doesn’t feel anything, but then he walks around behind him and comes around the other side, and he starts to feel his hair rising. He just didn’t know how he was doing this. Joe wanted to do a few experiments to see what is happening here but made a mistake when mentioning that they should try it with his shoes off. That’s when he declined the offer. So Joe can’t be 100% positive, but he says that he’s 99% positive because it’s the exact same effect that you can produce with this device.
- This just shows how careful you must be before you believe anything. If you believe in something, chances are it will happen. If you think something will take away your pain, it very often will, this is the classic placebo effect. • There’s nothing wrong with the placebo effect, but there’s something wrong with trickery. When someone is telling you that they have a power but they don’t actually have any power.• This is why you need to engage in critical thinking. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
DRUG MARKETING
CLINICAL TRIAL - In a clinical trial you have a hypothesis, in this case the hypothesis was that the bezoar stone could counteract the poison. Then design an experiment to test it, and then the results are recorded. The results in this case did not turn out very good for the cook because he died. This was a very primitive trial. - A more sophisticated clinical trial was carried out by James Lindin the 18th century (1716-1794). He was a Scottish physician, he was interested in scurvy. This was a terrible disease which mostly afflicted people who had been spending a lot of times on ships. There diet on the long ocean voyages was essentially dried biscuits and the water they would take along in kegs and salted meat. • He was not the first one to restore cases of scurvy. Jacques Cartierdid this, he explored Quebec in the 16th century (1491-1557). His men suffered extensively from scurvy. • Many of his men died, but Jacques Cartier learned something from the Natives. They were familiar with this disease and they showed him how to make a tea from spruce branches. Many of them recovered, then he had no idea why, but today we know. Scurvy is disease due to vitamin C shortage in the body. Plants such as the fur do have vitamin C which was able to reverse the disease. - It was James Lind who really carried out a clinical study to show that this was really the case. He eventually published in a classic work called the “Treatise of the Scurvy.” He carried out a legitimate clinical experiment on board a ship.
• He had the idea that since scurvy was seen in long ocean voyages it was somehow related to a lack of something in the very rudimentary diet that the sailors had. - The important this here is that he had a control group which is the men who kept eating the regular ship rations. - Once he learned about the effect of citrus, he started to give citrus fruit to the sailors and they began to recover. This was accepted soon after by the navy as a protective against scurvy. (It took several years before sailors were given daily rations of citrus juice). This tradition still goes on in the British Navy. Brits are called limeys because of the story of James Lind who gave citrus fruit. Rarely did they give limes, it was mostly lemons and oranges but the name limey stuck. - So we do credit James Lind with carrying out the first proper clinical trial.- William Withering (1766-1799)who was another British physician who also carried out a relatively primitive but very demonstrative clinical trial. He had many patients who suffered from heart disease, and he had heard about a lady supposedly called “Mother Hutton” who supposedly had a remedy for heart disease. He learnt about this from stories that circulated. She told him that she made this brew from the foxglove plant. • Withering decided to try this on his patients. He used an extract of the foxglove, gave it to his heart patients, mostly the ones who suffered from congestive heart disease and they improved. Today Withering is remembered in many ways including the William Withering pub in England. • He, like James Lind, wrote up his research, “An Account of the Foxglove.” Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Today, the extract of the foxglove is still used to treat congestive heart failure. Patients are told to not go and just randomly graze in a field of foxglove. The plant is extracted, the extracts are purified and the compound responsible for the activities is isolated and its called digoxin. - There’s an interesting history in how drugs come to be. Obviously in these days we want to have solid information for how a drug works before putting it on the market. There’s all kinds of studies done to see just how effective a medication may be. - There’s a classic hierarchy of evidence.• We rely modestly on meta-analyses and systematic reviews. Essentially, these are studies of studies where you take a look of all the high quality studies that have been done on a particular subject and pool them all together to see what the cumulative data shows. Hopefully then, mistakes can get cancelled out. The best meta-analyses are the ones that gather randomized controlled trials, these are the trials where you have a group that you’re testing, and you are going to compare then to a control group. Neither the experimenters nor the subjects know who is getting what until the end of the study. • Next we have cohort studies where you take a look at a large group of people and follow them to see what happens to them as they go through life. You try to relate aspects of their lifestyle to any disease that may pop up. • Then we have case-control studies where you take a look at patients who already have a disease and you look back at their history and look at what they may have done different from other people who don’t have their disease.• Cross sectional studies is where you take a large group of people and you ask them questions about their lifestyle at a given point in time and see what you can make out of that. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• Then we have animal trials and laboratory studies and case reports which are the weakest form of evidence. CASE REPORT - A physician submits a letter in a form of a case report to a journal to advise other doctors of something interesting that has been found. This is not a study, but is something that is deemed worthwhile reporting. - In this case, a lady who has asthma used her inhaler, but after using it she started having terrible breathing difficulties. It turned out upon x-raying her that there was some unusual looking item in her lungs. It turned out to be an earring. What had happened was that she had stored her asthma inhaler in her purse and she failed to put the cap on the inhaler. Somehow the earring that she also had in her purse got into the breathing tube of the inhaler. When she inhaled it, she inhaled the earring, not noticing that this happened. - This is an interesting case report because it alerts other physicians to tell their patients that they should be putting the cap on the inhaler because unexpected items can get into it. ANIMAL STUDIES - While many studies of drugs and toxins are done on rodents, mice or rats. The human is not a giant rodent and we don’t have the exact same physiology. With rats and mice, we can do experiments with very large numbers which you can’t do with people. Furthermore, you can expose the animals to substances that can be toxic but you can’t do this to people.- For example, here is a study about a particular component of diet, palmitic acid. The study shows that the consumption of palmitic acid in implanted tumours causes the tumours to metastasize more quickly. This was a study done in rodents which are not perfect models for humans. However, if it turns out as it did in this case, that dietary palmitic acid does have an effect on the rate that an implanted tumour will metastasize that will then serve as a springboard to investigate what may happen in humans. But, you cannot directly extrapolate from this and say that you should stay away from palm oil because it contains palmitic acid which causes more rapid metastasis in a tumour that is implanted in a mouse or in a rat. - This is a preliminary study that may eventually lead somewhere. IN VITRO STUDIES - This is where you usually expose cells in a Petri dish to some substance to see what the effect is.
- Phthalates which are chemicals that are added to many plastics, mostly polyvinyl chloride, in order to make the plastic soft and pliable. Unfortunately, these have the possibility of acting as endocrine disruptors which are hormone like chemicals and we want to be very careful about exposure to those. - In this case, they took some cells in a Petri dish and exposed them to different phthalate to see what the effect was. You can see whether or not the phthalate bind to estrogen receptors, if they cause a more rapid multiplication of cells, if they kill cell, etc. There were no dramatic findings in this case but this is a typical in vitro study. Once again, you cannot directly extrapolate this to people, it serves as a starting point for further investigation. - We are most interested in studies that are done on people. There are various types of studies done on humans. OBSERVATIONAL STUDY - All you do is observe a population, a group of people. You do not interfere and you don’t test anything, you just make an observation to see whether or not you can come to any conclusions. - Stories have circulated that women during pregnancy who experience a lot of heartburn, they give birth to babies with more hair. At first this seems like a total unrelated thing, but nevertheless, the scientist in this case decided to investigate this. This is a typical observational study because all they did was observe a group of women. Ones who reported heartburn and others who did not. Then they just looked at the babies who were born to see if they had more or less hair. Contrary to expectations, it appears that an association between heartburn and severity during pregnancy and newborn does exist. There’s probably some sort of hormonal connection here, that a hormonal disruption results in heartburn which also has an effect on the way the babies hair develops. This has to be looked into further, but this is a typical observational study. CROSS SECTIONAL STUDY- This is where the researchers make an observation at a single point in time. For example, do people who exercise have lower cholesterol? They would look at a number of people, measure their blood cholesterol and then ask them about their exercise habits and see whether or not there’s a relationship, but this is at only 1 given point in time. - For example, they investigated whether or not it is true or not if people who drink a lot of beer develop a beer belly. This is a common belief.
- At a single point in time, they asked the people about their beer consumption and they measured their waist circumference. They came to the conclusion that their was no relationship between the beer and waist circumference. CASE CONTROL STUDY - This can give you a lot of very good information because here you are looking at patients who have a disease. You look back in their history to see what they may have done differently from other people who don’t have the disease. The classic example of a case control study which turned out to be very useful was the link between smoking and lung cancer. • This goes back to a paper in the 1950’s in the British medical journal where Richard Doll and Bradford Hill interviewed a large number of lung cancer patients and they quickly released that what they had in common was that they were smokers. This type of study can give you very strong evidence. PROSPECTIVE COHORT STUDY - This is where you have a theory and in order to try and confirm it, you are going to follow a group of people to see whether or not you can gather information that either rejects or enhances the basis of the theory. - For example, the frequency of consuming organic good and cancer. The question is do people who consume a diet of mostly organic food, do they have a lower cancer risk? So you select a group of people and you follow their diet usually through questionnaires that they fill out, of course you’re replying on the fact that they are filling out the questionnaires honestly. Then you follow their disease patterns. It turns out that in this case, people who consume a diet of organic food had a lower risk factor. This does not have a cause and effect relationship, you can’t prove that the organic diet had anything to do with the cancer risk because it could be that people who eat an organic diet exercise more or that they are less likely to smoke and less likely to engage in any activity that would impair their health (third variable problem). This is the kind of thing you can find out form a prospective cohort study. RANDOMIZED CONTROLLED DOUBLE-BLIND TRIAL- This is the gold standard when you are doing a study on drugs. This is where a group of subjects are given a drug and they are compared to a group who is not given a drug but is given a placebo instead. Nobody knows who is getting what until the end of the study and a statistician will decode the study.
- For example, a randomized control trial of vitamin D in children to see whether or not there was any possible link to autism. A group of children were given vitamin D, these were children who were diagnosed to be on the autism spectrum and the other group were given a placebo. The groups were followed and it turned out that the children who were given the vitamin D had improved behaviour. META-ANALYSES - This takes a look at the best possible studies and puts all the results together to see what the conclusion is when you’re looking at all the studies deemed to be good studies. This is how we the most useful information because you’re looking at a whole collage of studies. - For example, they looked at the link between people who suffer from depression and whether or not they are consumers of alcohol or cocaine. They looked at all of the studies that examined this connection and when you put all the data together, the conclusion was that there was a link between depression and alcohol or cocaine consumption. • More recently there was a meta-analyses on the aspirin given for the prevention of cardiovascular events. Small doses of aspirin has been prescribed to people to try and protect them from heart attack and stroke, however there is always a risk with giving people aspirin because it is an anticoagulant and it can cause bleeding. When they put together all of the studies on the low does aspirin use, the risks out weigh the benefits. Based on this meta-analyses, advice has gone out that using low does aspirin to prevent the first heart attack is not indicated. It is still the right thing to do once someone has had a heart attack because the chance of a second heart attack is then increased and your risk benefit ratio changes. HOW DOES A DRUG ACTUALLY GET TO THE MARKET?
• So examination of the bark of the tree based upon all the stories revealed that it contained salicin. - From South America we learned from the Natives about Curare. The use Curare as a poison on their poison darts and arrows which would easily bring down an animal. The question is why? Research about the active ingredient which is Curare became extremely important in medicine because it can be used to relax muscles in surgery. - Sometimes we get idea from folklore. China has a long history of so called traditional Chinese medicines, its basically folklore where they use all kinds of herbs and spices, plant materials, some of which eventually turned out to have medicinal effects. For example a substance that is used now to treat malaria called artemisininis extracted from a plant that was used traditionally in Chinese medicine to treat fevers. - These days most pharmaceutical companies will look around and consult traditional healers, even witch doctors and shamans just to see whether or not their may be anything in the regimens that they used. - Sometimes you can information from animals. There are some animals, mostly chimpanzees, when they get sick, they search out certain trees so its interesting to investigate these to see if there’s any medication possibility there. - The biggest source of possibility for drugs are plants. Plants produce a very large number of different compounds, hundreds of different compounds, many of which can have biological activity. • For example, the Yew treeproduces a compound in its bark called Taxolwhich turns out to be a very effective anti-cancer agent. This was just determined by randomly studying compounds from the yew tree and seeing what effect it had in a laboratory culture. It turned out that it impaired the division of cancer cells and then went to animal studies, and later human studies. Now its widely used. The Autumn Crocos contains colchicine. This has long been used as a treatment for gout. Extractions and separation of the components eventually yielded colchicine as a drug.Vincristineis isolated from the Madagascar periwinkle. It is used in the treatment of cancer. - Just by studying compounds found in plants, you sometimes get lucky and get ones that work. You usually need to examine a lot of compounds before you find that one works. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• Reserpinecomes from Rauwolfia or the snake root plant. It was one of the first effective blood pressure lowering medications. THEORY- Some drugs are developed based upon theory. This is becoming more and more so as we learn more and more about how substances work. For example, Parkinson’s disease is due to a shortage of the neurotransmitter dopamine. Therefore it stands to reason that if you can somehow increase the levels of dopamine in the synapse, which is the little space between the nerve cells, where these neurotransmitters function, that you would have a way of treating Parkinson’s disease. It turns out that this works. • The classic treatment for Parkinson’s disease is Carbidopa. This allows a higher concentration of dopamine to get into the nervous system and enhances the binding of more and more dopamine to receptors and it treats the symptoms of Parkinson’s disease. It does not cure the disease, but it treats the symptoms. This evolved directly from knowing how Parkinson’s disease is manifested. - Vaccines are designed to prevent the infection in the first place by preventing the virus from entering a cell as the virus can only multiply inside of a cell. It cannot multiply by itself, it has to hijack the cells genetic machinery in order to reproduce. - Now we have antiviral drugs. The first one used against covid-19 was Remdesivir, but it had to be injected intravenously. This is a problem because it meant people have to be in the hospital. The idea was that at the first sign of infection, you try and circumvent the multiplication of the virus by introducing this medication. This is a pretty complex molecule, but it was theoretically designed. It was designed to mimic adenosine. • Adenosine is one of the building blocks of RNA which is the genetic code of the virus. The thinking was that it you could infuse this drug into the system then the RNA that was being formed would somehow be altered because instead of adenosine being embedded into the RNA chain, it would be the drug. It turns out that this was good thinking because what happens in this case is that when the virus releases its RNA to get incorporated into the genetic machinery of the host cell in order to grind out more RNA molecules which then will produce proteins that are needed to make more viruses, it turns out that when you replace adenosine in RNA with the drug (remdesivir) this leads to the impaired synthesis of an enzyme. That enzyme is needed by the virus to make more RNA, so basically the virus cannot multiply.
- Merckhas come up with a drug, Molnupiravir. This can be taken orally. The idea here is that the first sign of a symptoms you would take the medication to keep you out of the hospital. The molecule is a simpler one, but again it was theoretically designed to mimic uridinewhich one of the building blocks of RNA. What happens in this case by replacing uridine with the medication, the RNA becomes a mutant. The molecule folds in a different way, and this means that it cannot send out the proper signals for multiplication. The whole idea is to use the drug that replaces uridine in the molecule structure of the RNA. - Pfizerhas also come up with an oral drug called Paxlovid. This one works by a different mechanism. Paxlovid is what we call a protease inhibitor. This complex molecule embeds itself in an enzyme. That enzyme is a protease. Proteases are used by the virus to break down very large proteins into smaller useful ones that it needs. In this case, a virus produces a very large protein called the polyprotein. Proteases breaks down this polyprotein into smaller fragments and those smaller fragments are the spike protein that the virus needs in order to infect a cell. By using a protease inhibitor you will impair the production of the spike protein and therefore the virus cannot enter a cell. All of these drugs have undergone proper randomized controlled double-blind placebo trials and they work well. They don’t replace a vaccine because a vaccine protects against an infection in the first place. These are designed to work once there is an infection, hopefully to keep people out of the hospital. ANALOGUES OF OTHER/EXISTING DRUGS - Once you find the drug that works, very often you play a little of molecular roulette. You alter the structure a little bit to see if it will work even better. • For example, Libriumwas developed as an anti-anxiety agent and based upon its molecular structure, Valium was designed. Valiumalso turned out to be a little better than Librium. - This is a very common procedure in pharmaceutical chemistry. Once a drug works, you try to make for small changes in molecular structure to see if you could come up with something that works better. ACCIDENT- There are drugs that can be discovered by accident. • For example, Alexander Fleming’sdiscovery of penicillin. The story is that he was looking for substances that had an antibacterial effect. He was looking for such substances in saliva and looking for substances in tears without very much success. What he did was that he grew bacteria in a Petri dish.
• He studied the added different substances to it to see if the multiplication of bacteria could somehow be inhibited. As the story goes, he left for the weekend and when he came back, one of his culture dishes had a mold growing in it that had flown in from the window. • He saw that around the periphery of the mold, the bacteria had died. He got the idea that there must be something that is produced by this mold that kills bacteria and turned out to be penicillin. • He was never able to isolate it, it took a long time; 10 years until it was finally isolated by Ernst Chainand Howard Florey. They shared the Nobel prized with Alexander Fleming. Although he could never isolate penicillin itself, but without his observation, there would have been no penicillin. HOW DO DRUGS GET TO THE MARKET- It always starts with research, but the research has to be generated by some kind of an idea. Once you have an idea, you begin with some preliminary preclinical studies. These can be in vitro (in the laboratory) or with animals. • The idea is to see whether or not there’s any reason to go further, to see whether or not there’s any merit, does the drug do anything?- You probably first start in the laboratory with cell cultures to see whether or not there’s any effect on the cells, even before going further, it is very important to test for safety because if you are going to start trials in humans, you have to make sure there’s at least a degree of safety. • Animal trials can be used both to test whether a drug works against a disease, but also importantly to test whether or not it is toxic. This is normally done by determining the LD50. It is not a pleasant thing to think about, it is a way of determining just how toxic a substance is by seeing what dose it takes to kill 50% of an animal population. Obviously the smaller the dose that does that, the more dangerous the substance is.- Once you have done your preliminary laboratory and animal investigations, it is time to see what can be done in humans. - In these animal experiments, every year there is a large number of animals used in the world.
- Mostly it is mice, guinea pigs and rats being used, but other animals are used as well. • This obviously raises some kind of objections. The most vocal group is PETA, the people for the ethical treatment of animals. They will attack any research which they deem that uses animals in an inappropriate way. For them, any use of animals is inappropriate. They say that a life of a fly is the same as a life of a rabbit which is also the same as the human life.• Most scientist don’t agree with this, human life is placed above all others. Unfortunately sometimes animals may need to be sacrificed to save human lives and most scientist believe that this is an acceptable situation. - It does depend on what you are testing and what the potential benefit is. There is a case where PETA is attacking POM which is a manufacturer of a pomegranate beverage. They claim that the experiments that are being done to prove that pomegranate juice actually has some health benefits are unacceptable. - Some of these experiments are not necessary. You don’t need to determine if pomegranate juice has any kind of health benefit by essentially using animals in an inappropriate way. This is different from seeing whether or not a drug that you’re going to use will treat cancer or not. There the animal trials are legitimate. - We would not have the medications that we have today if it were not for animal research. For example, Frederick Bantingand Charles Best were the discoverers of insulin which was all done using dogs. They would take the pancreas of the dog and from that insulin was isolated and they would treat diabetic dogs with insulin. • Diabetes is a very serious situation, it’s not like saying that maybe drinking pomegranate juice might have some trivial benefit. - It’s not a question of using animals or not using animals, it’s a question of making sure that the animals are used appropriately and that animals are not tortured in anyway. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
STEPS TO GET A DRUG TO MARKET- You start with these preclinical trials of laboratory Petri dishes etc, and animals. Believe it or not, most drugs do not make it past this stage because they are either not shown to be effective in cell culture or in animals, or because they are too toxic to use. IN VITRO AND ANIMLA STUDIES - The one’s that past this stage, the company that is doing the research will apply for investigation on new drug application. INVESTIGATIONAL NEW DRUG APPLICATION - This allows them to go on and investigate the drug further. The government now knows that this investigation is underway. It all begins with the phase 1 studies. PHASE 1 STUDIES - These are all human studies now. They have 1 single goal, and that is to determine whether or not a drug is safe. In a phase 1 study, you are not looking to see whether its affected against any condition. You are just looking to see if its safe, and what dose would be reasonable to give to a patient. • In a phase 1 study they will enlist 20-80 healthy volunteers, usually they are paid although not a huge amount of money. They will be given different doses of the drug and they will check to see safety, side effects, etc. This is usually conducted for about a year. If the drug passes, then they will go on to phase 2 studies. Only about 20% eventually get approved. PHASE 2 STUDIES- Phase 2 will take a lot at whether the drug works or not against a certain condition. This time there are hundreds of subjects who are enlisted and these phase 2 studies can take several years. Sometimes, but not always, they will have a control group, meaning that the subjects are divided into two groups, one group gets the placebo and the other gets the drug. However, this is not a requirement for phase 2 studies. • In a phase 2 study you want to see over a significant period of time with a significant number of subjects whether or not the dosage of the drug which has been determined to be safe in the phase 1 studies will work against the disease. If the phase 2 studies come out positive, especially if they have been placebo controlled. A placebo is of course any kind of inactive substance. For injections it is usually saline, a salt solution. For tablets it can be a sugar pill. You want to use this to take away the body mind connection. Often times when someone thinks that they are taking something that has pain relieving ability, they will have subjective pain relief even if there’s no real physiological activity.
PHASE 3 STUDIES - This is what will determine if a drug gets to market. Here you will always have a placebo group, and this time you can have thousands of subjects. These studies can take up to five years. By the time that a drug gets to phase 3, it has a pretty good chance of being approved because it has gone through the phase 1 studies showing that its safe and it has gone through the phase 2 studies which show that its safe and effective, and now you have it scaled up to thousands of subjects. Even thousands of subjects are not a guarantee that you will learn everything about a drug. If some drug has a side effect that affects 1 in a million people, you won’t see that in a phase 3 trial. If you have a drug that is eventually that is goi got be taken from millions of people, then of course the side effects will show up. • Once the phase 3 studies have shown that you have a drug that works, its effective and safe, the company will apply to have it marketed.NEW DRUG APPLICATION- This is a submission of data to Health Canada or in the US to FDA. The decision is made to whether or not to review this. This decision is made pretty quickly (60 days). This really is just a question whether or not the studies have been properly carried out. Usually once you get to this stage of a new drug application the regular agencies will decide to review it. REVIEW OF DATE, LABELING, FACILITATES- It will take anywhere from 6-12 months for the authorities for the authorities to review the data, to come up with labeling instructions, they will investigate the facilities for where it will be manufactured to make sure that a good manufacturing practice will be followed. APPROVAL OR REJECTION- If the drug is approved then the drug goes on sale, but the story does not end here. It goes on to phase 4. PHASE 4 - This is where data is collected for up to 10 years from people who are using the drug to see whether or not anything has popped up that did not pop up in the phase 3 trials. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
THALIDOMIDE- This was a drug that got approved but had catastrophic consequences. This was a sedative taken by women who were pregnant in order to ease morning sickness and to help them sleep better. It turned out to have a severe side effect where some babies (about 10,000) were born with malformed limbs. - This drug had gone through all of the required testing but it was never tested in pregnant women because you do not in general test drugs in pregnant women. Thalidomide is held up as the example of the failure of the testing system, but it really isn’t that, all the requirements were met, it was tested in people although not in women in their first trimester of pregnancy, it was tested in healthy adults, it caused sleep, it looked like it was going to be a good drug. It was tested in chimpanzees without any kind of problem, so this was one of those rare drugs where an effect was seen that had not been predicted by any of the testing. Unfortunately this can happen because testing of drugs in pregnant women is not something routinely done.- Dr. Frances Kelseywas a McGill graduate, she eventually got a medal for her work from President Kennedy because she was the one in the US who was in charge of decided whether or not thalidomide should be allowed. She got nervous from some of the data the she saw because some of the reports indicated neurological problems, some people got tingling in their fingers for example. She was unhappy about that and thalidomide never got approved in the US. It got approved in Europe, most of the thalidomide babies were born in Germany and it was the work of Frances Kelsey who saved many North American babies because she was suspicious of the drug even though it had gone through the proper testing. - Some medications were found in phase 4 trials to have some problems and were removed from the market. Hismanal, the antihistamine was one of these. This one had a risk of fatal heart rhythm abnormalities when it was used together with certain other drugs. We saw the same thing with Seldaneand with Baycolwhich was a cholesterol lowering drug. HISMANAL- All of these had been approved, they were on the market, but they were eventually taken off the market. - Baycol was quite extensively used. It was only after years of use did the side effects begin to show up. This is because when you have a rare side effect, you don’t see it until large numbers of people are taking the drug.
- Fenfluraminewas an appetite suppressant drug that was introduced into the market as Redux. It was approved in 1996, and just a year later it was taken off the market because various kind of problems showed up, mostly heart valve abnormalities. It is no longer with us. Interestingly enough, fenfluramine is still manufactured in china and sometimes its illegally imported into North American and sometimes its illegally incorporated into herbal supplements. - Vioxxwas an anti arthritis drug that worked extremely well. Most patients who took it were very happy with it. It was taken off the market, it was recalled by Merck(the manufacturer). There were heart irregularities that showed up after it had been on the market for years. The problem with this drug, was that the company supposedly was aware of the problems before they were ever made to take it off the market. There’s a backstory here, it seemed that the company already knew about these complications, but nevertheless they kept marketing the drug. If you ask people who were taking vioxx, they would tell you that they would happily sign a disclaimer form if they could have the drug back again because it was so effective. It was even more effective than the anti arthritis drugs that followed it. • Vioxx could legally still be sold because it was voluntarily taken off the market by Merck, there’s also talk about this drug coming back. - More recently we had a story about a drug that was quite commonly used and still is quite commonly used for heartburn and gastrointestinal problems. This was known as Ranitidine, but it is often sold as Zantac. The reason that there was controversy about this drug was because it was found to be contaminated by N-nitrosodimethylamine which is a potential carcinogen. There’s still some question about just where this comes from and how it is introduced in the manufacturing process. - Ranitidine was taken off the market but now it is back on because both Canada and the US are allowing it as long as the company does testing to make sure that it does not contain any N-nitrosodimethylamine. - Just where it comes from is a mystery. It seems to be the break down of the active ingredient when the drug is subjected to certain conditions such as warm conditions. The company has somehow seemed to have solved this problem and are now testing every batch so you are quite safe to take ranitidine because every batch has to be tested to make sure that there’s no N-nitrosodimethylamine in there. It still isn’t quite clear how it forms. - How do you find such contaminants which are present in trace amounts? The equipment used is gas chromatography mass spectrometry. This together with liquid chromatography mass spectrometry can’t detect very small amounts of contaminants. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
• These are classic analytical techniques found in labs these days and this is what the company now uses to determine whether or if there’s any N-nitrosodimethylamine in there samples. - Another drug that was caught up in the same business is Valsartan. This is an antihypertensive, a blood pressure lowering drug. This was also found to be contaminated with dimethylnitrosamine. It probably comes from the dimethylformamidewhich is a solvent used in the manufacture of this drug. This may be a contaminant that comes about in a different way than Ranitidine. - Valsartan is on the market because every batch is now being tested to make sure there’s no toxic residue in there. The only reason that we’re able to determine these things is because of the sophisticated chemical technology that is available to find substances down to parts per billion and sometimes parts per trillion level. ACCELERATED APPROVAL - Sometimes you can have a drug that seems to be so effective for a serious disease that you want accelerated approval. Companies can petition for this. • For example, gleevec is a cancer drug which is used for the treatment of leukaemia. The early face of trials showed that it was extremely effective against the disease for which there was no other treatment. The company petitioned the government and they got approval in record time. This can happen when you have a situation where your have a disease for which there is no effective treatment and the drug looks very good. In rare cases such as this, because there is no other treatment, they will approve it without having it go through all of the phase 3 trials. • This was a case where gleevec was effective agaisnt chronic myeloid leukaemia where other drugs were not nearly as effective. Phase 2 studies showed that there was a significant reduction in cancer cells in bone marrow and blood. Gleevec has since been used extensively and is a very effective drug. PROBLEMS WITH CLINICAL TRIALS
• They injected it into the subjects, and it had terrible consequences even with very small amounts. Within an hour of receiving the drug, 6 of the 8 volunteers were rushed to intensive care. It was a horrific situation. • What happened here is that the drug triggered a Cytokine storm which is an overreaction of the immune system. The immune system was attacking the body itself in all kinds of strange ways. For example, their circulation was cut off, their fingers became necrotic. • This is a very rare situation where you have gone through the laboratory trials especially with monkeys and it turns out that you have this horrific consequences in humans even in very small doses. UNNECESSARY TRIALS - These are trials for drugs that are referred to as ‘me too’ drugs. You may have a drug that is very effective for a certain condition, but its off patent, meaning that the company is no longer making money off of it because generic versions are available. So they may come up with a slightly modified version of the drug. This doesn’t seem to have any greater effectiveness, but it will have greater market potential because you can once again get a patent for it and you can get a license to sell it without any competition for years. Some of these trials that go on which really don’t have much of a prospect with coming up with a drug that is going to make a huge impact. MONITORING OF STUDIES- Monitoring of studies is very difficult. There are a lot of trials in North America so there are a lot of people that are involved. You have to make sure that the subjects understand what exactly the trial is about and what exactly they need to do.SUBJECTS COMPREHENSION OF THE TRIAL - If they have to take a drug every morning or every night, if they have to take it with or without food, report any side effects, they have to be totally away of what exactly it is that they are to do and what it is they are to report. - When you have so many people being placed in so many trials, reporting and monitoring is a problem. Some of these people are just lost to follow up. Some people will initially volunteer for a trial and then disappear halfway through.FINANCIAL CONFLICTS OF INTEREST- An example of this, Jesse Gelsinger (1981-1999) has become famous because of his death. He was suffering from a rare disease, transcarbamylase deficiency. It comes with a build up of ammonia in the blood. There was no treatment for the disease at that time.
- They tried in a clinical trial a novel modality by injecting a modified virus into his body which was suppose to improve the immune system. He had a severe inflammatory reaction to this, a Cytokine storm. • It turned out that the researcher had a financial stake in the company that was studying the drug that was used and was pushing to use this drug because of his financial state even though there was some preliminary evidence that it hadn’t been properly tested. He had failed to report those adverse effects that had been seen in other patients. - Another clinical trial, Emily Whiteheadwas a young girl who was diagnosed with a type of leukemia. She underwent an experimental treatment which involved T-cells. T-cellsare a type of immune cell, the T is because these cells are normally synthesized in the thymus gland in the neck. They were able to reprogram these T-cells to attack these cancer cells. • It was very successful, she still did have a Cytokine storm that was triggered by this intervention, but by this time there was a drug that was available, a monoclonal antibody,and this is what saved here. The orignal drug got rid of the cancer, this drug was not available for Jesse Gelsinger. - These are phase 1 trials, and it was an unusual phase 1 trial because this was tried only on 1 subject. CONFLICTS OF INTEREST - For example, University of Toronto did a study where they looked at 70 studies of a heart medication. 96% of the studies that were supportive had ties to drug companies. 37% of the critical researchers had drug company ties. - Whenever there is an invested interest when researchers have a grant from a company, there are more likely to find positive results. This is because they know that their grant would probably not be renewed if the results are contrary to what the company expects. This doesn’t mean that all researchers can be bought off, but unfortunately sometimes, perhaps even subconsciously there is favouritism to companies giving grants. It’s always important when looking at a research paper to take a look to see where the funding has come from. - Once you have gone through all these hoops and hurdles, you want to find a name for the drug.
NAMING OF DRUGS- This is very important, pharmaceutical companies spend a lot of effort trying to find the right names. You want names that doctors will remember, a name that has some sort of meaning, and a name that conjures up some type of imagery. • For example, Viagra. This is one of the most commonly prescribed drugs today. This is a drug developed by Pfizer, and it has been a very successful drug financially.- Where did the name come from? There was a lot of discussion before this was arrived at. It’s a combination of “vigor” because you want to project the image that a man becomes more vigorous and “Niagara falls” because it is a very powerful waterfall with a lot of energy. They combined these two and this is how you got viagra. - Cialiswhich is a competitive for Viagra. This name was coined from “ciel” which is sky in French, “the sky is the limit”. Those names have worked quite well, both drugs have sold well. - Lipitoris a drug that is sued to lower blood cholesterol. The name comes from the word “lipids” these are the fats in the blood, and “organic” a very marketable term. - Xenicalis a drug that is sued to curb the appetite. You want to “x” something out, the thing that you want to “x” out is calories, this is how they came up with Xenical.PROBLEMS WITH NAMES - Sometimes they can be similar to other drugs. Celexa, Cerebyx, and Celebrex are all quite similar. In the old days when doctors use to write prescriptions by hand, there could have been some confusion because they are notoriously poor at handwriting and the pharmacist would mix up these medications. This is less likely now because all prescriptions are basically written on a computer. - Drugs of course are very heavily advertised.• US: ~12 billion dollars a year in the US. • Canada: ~1 billion - There’s more money spent on advertising (23%) then on research and development (16%.) - The pharmaceutical industry is not a philanthropic industry as some people would like to see. It’s a business. On the other hand, the way you come up with good drugs is when you have a chance to make profits on it.
- This is why prior to the collapse of the Soviet Union, and you looked at the top hundred drugs in the world, none of them came from the Soviet Union because there was no money to be made there. It’s when you have money to make, when the profits are there when research gears up. - Just because companies spend a lot of money on promotion, this doesn’t mean that it undermines the whole pharmaceutical industry, its really the potential for profits which lubricates new drug development. - Pharmaceuticals spend more money on advertising then other industries. • Pharmaceuticals: 23%• Beer and Cosmetics: 10% • Consumer Products: 4%- If you are accustomed to watching the news on the American major networks (ABC, CBS, NBC) at night, you’ll notice that in the news, virtually all of the ads are for pharmaceuticals and these are not cheap. - Once you have a drug you want to reap profits from it, you can do this because of the patent laws that are there which are somewhat different in different counties. Here in Canada, we have bill C91(1993), which gives a company 20 years patent protection. This means that if a company comes out with a new medication, they can sell it for 20 years without any other country selling the same drug. This sounds better than what it truly is. Your patent protections starts from the very moment that you file a patent. That is at the very beginning of the research, it takes many years to find a drug that works, but all of that research is within this patent period. It usually takes 10-15 years from beginning to until a drug hits the market. So in actual fact, it may only be like 5-6 years because most of that patent protection period was taken up by research to put the drug on the market. GENERICS- Generics come into play once a patent has worn off. After the 20 years, any company can start selling that drug. However, it has to be equivalent to the trade name drug. In order to get a market to get a generic drug on the market, you have to show that it is essentially the same as the trade name drug. It has to be the same in quality, purity, efficacy, etc. It doesn’t mean that there are no possible differences because the fillers that are used in the drug, when you make a medication, the active ingredient in a pill is only a small part of that pill because usually its only a few milligrams. In order to have a pill of significant size that you can take, it has fillers in it. Sometimes the drugs are coloured as well, so these are not necessary the same as you have in the original medication.
- The generic companies have to show that their drug is equivalent in terms of efficacy. Tetracyclineis an antibiotic, it can now be sold by many companies because the patent for this has long worn off.• Some of the companies that cell tetracycline: - All of these cell the same drug, it might be slightly different in terms of excipients in the pill, the colours and shapes of the pill. The prices can also be very different. - Amoxilwhich is an antibiotic, its in the penicillin family also has different prices. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Diazepam, an anti-anxiety drug. It is sold by Roche as Valium for 14.45, but you can get it from Apotex for 0.61$.- A doctor can in fact write a prescription, deliver as written. That is, the pharmacist must fill it the way that a prescription is written. - The law here in Quebec is that any prescription that is written has to be filled by the pharmacist using the cheapest available version of that drug, except if the doctor writes deliver as written. Why would they do this? There’s actually no reason to do this. - Prices differ a lot between Canada and the US. • This is why there’s so much controversy in the US about the pricing of drugs. The insurance companies will very often refuse to pay for some drugs because they are so expensive.- The argument of course that the companies use is that they have to recoup the money spent on research. When you’re taking a medication with only a couple of milligrams of the active ingredient, you’re not really paying for that active ingredient which is usually not very expensive to produce. What you’re paying for is the research that has gone into that which could have taken 15-20 years. In the US it seems to be excessive recouping of that money. - The companies have to show that there generic version of the drug has the same bioavailability. This is that it’ll rise to a maximum concentration in roughly the same time as the trade name drug and it will have the same kind of decline in the bloodstream, this is the requirement. There is really no reason as to why the generic drug should not be as effective as the trade name drug. There has been a couple of cases because of the way that the pill is formulated, the excipients, it might not disintegrate in the stomach in the same way, there may be some slight variation. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
ORPHAN DRUGS - These are drugs designed to treat disease that are very rare. These diseases are so rare, so few people have them, that the company doesn’t really have a chance of making money off of these drugs, you can’t possibly sell enough of them. It usually takes a great deal of research to come up with these. - One example is Gaucher’s diseasewhich is very rare. You have to inherit a defective gene from each one of your parents in order to have this. It is somewhat more prevalent in Ashkenazi Jews of European origin. This disease can affect many parts of the body, this is because of the build up of a certain kind of fatty material, the glucocerebrosides. These build up in the bones, lungs, liver and the spleen. Those organs can be enlarged, you can also have low red blood cells (anemia), easy brushing caused by a decrease in blood platelets (thrombocytopenia), lung disease, and bone problems, etc. It is a very nasty disease. The chemistry of this has actually been worked out. The build up is in certain white blood cells called macrophagesand the chemical in question is glucocerebroside. In Gaucher’s disease, the enzyme to break down the glococerebrosides is missing and therefore the drug does not get broken down into glucoseand ceramidewhich are innocuous substances. It’s the glococerebroside that is the problem, its what builds up and causing symptoms. • The answer is to replace the missing enzyme. This can be done. Imigluceraseis the enzyme that will break down the problematic compound. The only issue here is that its 25,000$ a month. Pharmaceutical companies cannot make money of this stuff because there’s so few patients. Very often they will have all kinds of arrangements to be philanthropic. COVID-19 VACCINE- We have had some very encouraging news from two major companies, Pfizerand Moderna. These encouraging results come from the phase 3 trials, the drug looked good in the phase 1 and phase 2 trials, but the phase 3 trial is the one where you actually test it in a placebo controlled way. - The basic idea behind both of these vaccines is to trick the body into thinking that it has been invaded by the virus, this will generate antibodies to the virus. The virus has on its surface these spike proteins, those are the proteins that it uses to invade cells. By tricking the body into thinking that it has been invaded by the virus, the body will generate antibodies to these spike proteins so that whenever it encounters the real virus, it will neutralize it. - The whole idea of antibodies is that they will bind to the virus and prevent the virus from binding to cells.
- How do you generate antibodies without exposing the body to a live virus. The two vaccines that we are talking about here, both use a platform technology that has never been used before. This is the technology of messenger RNA. RNA is a molecule that serves as a template for a cell to synthesize protein. The genetics of this virus are known, this was released by the Japanese in January of this past year. Researchers now exactly what genes are involved in making this spike protein. Those genes can be inserted into a molecule of messenger RNA which is then injected into the body and ends up in cells. Their code for the production of parts of that spike protein. The body itself generates parts of the spike protein and triggers the formation of antibodies to that protein so that the next time the real virus is encountered, the antibodies are there and attempt to neutralize it. It seems to work. - In the Pfizer study, they enlisted 22,000 people in the vaccine group, and 22,000 in the placebo group. A very large number to monitor. After 3 months, 162 developed symptoms of Covid-19 in the placebo group. Only 8 developed symptoms in the vaccine group. This difference cannot happen by chance alone. 162 out of 170 were in the placebo group, that equals 95% efficacy. This is an outstanding efficacy, the only vaccine like this is the measles vaccine. For the flu vaccine, you’re happy if you get 70% of efficacy. • The one stumbling block here is that this vaccine has to be transported at very low temperatures (-70 degrees Celsius). This requires dry ice, but this isn’t a big problem. - The Moderna vaccine uses a very similar technology. They had a trial, 15,000 vaccine group and 15,000 in the placebo group. 90 developed the symptoms in the placebo group and only 5 developed symptoms in the vaccine group. Once again, this is statistically impossible to happen by chance alone. 90 out of 95 equals 95% efficacy.• This looks very good, but this is still a relatively small trial, we only have in each one less than 100 people came down with covid-19. What we don’t know is whether or not the vaccine was effective in preventing a symptomatic transmission. They have not released this data yet, but it will be released, so we’ll be able to see whether or not it also cut down the chance of people transmitting the disease even when they are not symptomatic.- The number of people here in these studies who came down with symptoms is very low compared to what you see in the average population. This may be because the people who would enlist as subjects in these studies are people who are health conscious anyway. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504
- Their are many questions to be asked here. We still don’t know how long this immunity lasts. Long term side effects, not likely, but not impossible. - This is a very encouraging finding and it is better than anyone had predicted. - For Moderna, -20 degrees Celsius is enough to keep it stable. The distribution would be somewhat simpler. - Potentially vaccinating billions of people around the world, this will take a lot of vaccines. Right now the companies are gearing up, and the chances are that Pfizer will have 50 million doses ready by December or January, but 50 million doses is just 25 million people because they are a double dose vaccine.• So, it will be a long time until a large enough number of the global population can be vaccinated to try and achieve heard immunity. • We still have to keep wearing the masks and physical distancing. Even with 95% success rate, you still have 5% of the population that’s not protected. When you have a global population of 8 billion people, 5% of that is still a very large number. It’s not going to be an instant fix. - This is a situation where the vaccine looks good. Unfortunately there’s a large number of people who say they will not take it no matter what, some of these are just the anti-Vaxer’s who think that vaccines don’t work. Some people are just skeptical that the virus has been ruled out too quickly. - Within a year in North America, we should have a number of people vaccinated to at least take the edge off of this problem. Downloaded by Mila Ablasou (mila.ablasou@gmail.com)lOMoARcPSD|19161504