[MUSIC] Welcome back. Let's have a little chat about epidemiologists. Now, epidemiologists are scientists who study the environmental causes of disease, as opposed to geneticists, they study its genetic causes. The epidemiologists have generally resisted the genetic revolution, but like geneticists, they've made bold claims. They say, for example, that 80% of common disease and 30% of cancer is preventable by changing diet or taking exercise, and controlling alcohol and not smoking. What was first described by Tim Spector in his 2012 book, Identically Different. Apart from successfully reducing smoking, which accounts for about 30% of cancer deaths, most public heal, health interventions for common diseases have failed. There have been some recent changes in the incidences of asthma, and allergies, and shortsightedness, and heart disease, and diabetes, schizophrenia, autism, and many cancers. But these remain largely unexplained by known environmental factors. As we discussed last time, social isolation an other stresses contribute to some of these by conditions by weakening the immune system. But the usual suspects, alcohol and coffee and tea and sunshine and exercise and diet, they usually have tiny individual effects in disease, in spite of getting huge media coverage. And we now know that whether you drink alcohol or take regular exercise or smoke cigarettes is influenced by your genes regardless of your environment. Now a few examples of environmental factors without a genetic component and conversely genes don't work alone. They usually depend on other genes and on environment. Many genes only turn on in response to some environment. There haven't actually been many new ideas in epidemiology in the last 30 years. And little thought has been given to explaining exactly how different environments exert their effect and how they can interact with genes. But that is changing. And in the last few years this has actually become one of the hottest areas in biology. It's got hot because of new techniques. And one of these is called Mendelian Randomization, or MR for short. And MR uses our knowledge of human genes to pinpoint how the environment and our lifestyle choices affect health. And last week I mentioned that, some genes are protectors. They protect your health. Well, MR simply involves finding out whether it matters to people if they have good or bad versions of genes for a trait. And it can clear up all sorts of conflicted epidemiology. So for years people thought that raising high-density lipoproteins, so-called good cholesterol, would protect them from heart attack. But a large trial of a drug that raises good cholesterol published in 2012 saw no such benefit. Now an MR could have saved them the expense. There's a 2012 computer study using records of 170,000 people that participated in other studies from the people with gene variants causing high or low levels of good cholesterol had the same heart attack risk. Another example, previous epidemiological studies that charted mother's drinking and children's IQ have given conflicting results. And that's probably because women who don't drink during pregnancy are brighter than most that do drink. And their brains, their genes for brains are passed to the child. Ask it to obscure any effects of drinking. We also found that heavy drinkers are more likely to be obese than heavy smokers. So how do you know that it's, that IQ is due to drinking and not to smoking? How do you separate out these confounding effects? Well, Mendelian Randomization can solve this issue. Women who have a versions of enzymes, alleles of enzymes called alcohol dehydrogenase, that rapidly break down alcohol, have children who average 3.5 IQ points higher than mothers with badly functioning alcohol dehydrogenases. But that's only if their mothers drank during the pregnancy. So faster rather than slower breakdown of alcohol prevented 3.5 IQ points worth of damage. But note, that this study is not showing how much higher IQs would be if no alcohol was consumed. However, now we know that alcohol does affect IQ, why risk it? [UNKNOWN] and I both mentioned epistasis. No gene is an island. Genes are team players. They have to integrate their activities to produce tissues and organs and the enormous confederation of ten trillion cells that is you. And, and then those ten trillion cells have to interact with the environment. This means that you need genes that integrate the various functions of your body, including your brain, and that integrate your body with the environment. So, most of what those [UNKNOWN] genes involves said regulation. Which in many cases, is controlled by the environment. So the question is, then, how can the environment switch a gene on or off? As an example, we're going to look at the hormone, cortisol, that Dr. [INAUDIBLE] has already mentioned. When you have a lot of cortisol flowing, flooding through your veins, you are by definition under stress. You may remember from last week that there's a system in your brain that responds to fearful things, two bean-shaped structures in the temporal lobes of the brain called the amygdalla, one on either side. They just sit back in front of your ears. They are shown in green in this figure up here. They're part of what gets called a limbic system, involved in memory and emotion. The limbic system is an old part of the brain. We share it with other animals. The hypothallamus and the hippocampus are also shown in this figure. And they're also components of the lympic system. The hypothalamus there, sitting in red just above the green amebdola, helps links together the nervous system in and the hormonal system. It's got a lot of neural connections to the cerebral cortex and amebdola. And if your cortex thinks stressful thoughts, or you experience stressful events, the cortex and or the amebdola are going to send signals to the hypothalamus and it will get the adrenal gland to release cortosol into the blood stream. So I mentioned stressful thoughts can cause cortisol to be released [INAUDIBLE]. But most animals don't have cerebral cortexes. For the run of the mill animal, stress is just caused by the outside world. It gets stressed when something, chases it. It doesn't brood over past horrors. And for last, with our big cerebral cortex, connected by loads of axons in the limbic system. Stress can also be caused by things we think about. When you confront something that frightens you, you suffer a bereavement, you smell something that reminds you of a frightening event. You hear the person, or thing, in all the world you hate or fear the most. Or you just think about the worst thing that can happen to you and that's going to trigger the limbic system of your brain. Cause the adrenal gland to release cortisone. [SOUND] [SOUND]
