University Place

So now it's my pleasure to introduce to you Dr. Kevin Strang. Dr. Strang has been at UW-Madison for quite a bit of time. He and I have collaborated several times in having conversations with members of the community and with students in my class and other classes on the topic of the world's second most popular drug. So, Kevin, if you're ready, it's all yours. (audience applauds) Thank you, Dr. Shakhashiri. So caffeine is number one, and when I speak to those audiences, they often, when I say, "What's the most popular?" They say, "Cocaine, marijuana," you know, illegal drug after illegal drug. They don't stop and think about a perfectly ordinary everyday substance like caffeine, which people take for a reason. It alters their body function. It has side effects. That's what a drug is. Anything we take with the intent of altering body function but that also has side effects because of the redundant plan that the human body's built on. It's a drug, and so I unapologetically tell college students, "Yes, you are ingesting a drug when you're drinking alcohol." So this is my general scheme for the evening. I've got three sort of overall things I'm gonna do. I'm gonna talk about why we drink. How does it work at a chemical, physiological level? I'm gonna then talk about some of the neurological effects that people are after. Why do people medicate themselves with alcohol? What are they looking for? We'll talk about that for a while, for the main body of the talk. And then at the very end, I'm gonna maybe be slightly controversial, maybe intrigue you and suggest some really great reading having to do with a particular reason we drink and that has to do with the cultural, historical, the history of alcohol in human civilization. So that'll be at the very end. So that's my general plan. So why do people drink? And I've polled many college audiences and I ask, "Why do you reach?" And I make 'em really think, "Why do you reach for a drink?" And it comes down to the first five on this list, basically are reasons people self-medicate with alcohol. To get a mood boost, it is a euphorigen. We'll talk about that. It increases social confidence. People have this misconception that is is an anxiolytic drug, it is a relaxant. It is not, and I'll show you a study that proves it is not. Many people you've heard of taking a nightcap to help you sleep, a very common thing in our culture. It turns out it's a terrible sleep aid, and I'll tell you why. And then escape from problems. So people drink to forget things that they want to forget, and that may work to an extent, but very often, as I'll talk about, they forget things that they're not intending to forget. And then the last thing, it's not really, people aren't self-medicating because of their culture or history maybe, unless they've got one of those families, I have one of those families, but I think it is an underlying reason why. I mean, here we are in the great state of Wisconsin. Alcohol is a very important topic, one of the most important public health topics on a college campus in a state that I think there is, which is why I'm so passionate about talking about this topic to all the audiences that I talk to. Okay, so at fundamental level, I bet most people who drink don't really know exactly how this drug works. It's unique in the drug world. When a pharmacologist designs a drug aimed at a brain protein or aimed at your kidney or your liver, they're often massive molecules that are shaped very specficially to attach to certain targets chemically. As we'll see, alcohol, it's a skeleton key. It's a universal key. So quickly, all about you, you're made of about 75 trillion cells and those cells make up the different organ systems of your body, and each one of those cells has some features in common and some different from cells that are in other organs. So you've got cells in your eyeball that when a photon of light strikes it, a neural signal goes to your brain and tells you you're seeing something. You've got cells that are in your muscles, for example, that can, much like ethanol in a combustion engine, they can turn chemical energy in the food you eat into physical force, into movement. These are all the things that cells are specialized to do, but there is a similarity among all those cells. It comes down to they are basically a bag of lipid, a lipid that has a consistency very similar to chris-kal oil, but at a molecular scale, that's a fairly stiff cell membrane or cell wall, and so you see the double blue band, that's a phospholipid bilayer membrane, and then you've got proteins. Proteins are the machines that distinguish one body cell's ability to do one function from another body cell's ability to do another function. So those photons of light are striking specific proteins in your eyes and you don't have those proteins in your muscles, which is why you can't see with your muscles. So those protein machines take on all kinds of form. They're ion channels, they're enzymes, they're receptors, they're signals. Anything your body can do, it does because of this generic membrane hosting the cell and then proteins that are in the membrane, proteins that are inside and out that act throughout your body. Well, it turns out the chemistry of ethanol interacts very nicely with proteins. So the cartoon at the upper right there. If you don't know, a protein is a long string of amino acids, and, by the way, this fabulous, elegant molecule here, DNA, that's where your genetic heritage lies, and what it really does is when you go to make a muscle cell or a brain cell or liver cell, the DNA that's in all of your cells is exactly the same, but what happens is different parts of it get expressed, get translated into a protein that gets put into that cell for its function. So remember that, all proteins are made from DNA, all the same DNA is in all of your cells, but only certain ones are expressed. So that cartoon of a protein, the green blob sticking out to the side, amino acids have side chains, side chains with chemical natures, and you heard a little bit about polar and non-polar bonds here. So the blue ones are to identify polar side groups that are very friendly with water. They dissolve well in water. They have electrical charges, some of them. And the green blobs represent animo acids that have something like a hydrocarbon side chain, something like these carbon-carbon with hydrogen chains with no oxygens involved. So that's a very oily type of molecular structure. The blue ones represent hydrophilic, a water-loving chemical structure, and depending on the sequence of amino acids, if you take that long string, if I dunk it into water, what's gonna happen to it, it's gonna fold. It's gonna fold into a shape. You know if you put oil and water in a jar and you shake it, they separate, right? That fundamental force is one of the huge forces that drives the design of the human body, hydrophobic interactions or the fear of non-polar substances for water. So in a watery climate, that's what that protein would do. It would fold so that all those blue blobs, the amino acid side chains are facing the watery bloodstream, if that's where we are, and the hydrophobic ones, the polar side chains are gonna be like the oil gathering itself together inside of a jar, and it turns out ethanol, so you've seen the structure, there's a simple representation of ethanol. It's an amphipathic molecule. It has both the non-polar and the carbon chains with the hydrogens, so that's a very lipid friendly, fatty friendly substance, and then it's got the O-H group at the other end, and I'm glad we also got the introduction. When I say alcohol, I'm always talking about ethanol. There are many alcohols obviously. But if you take that little tiny generic molecule and introduce it to a big protein that is folded in a certain way because of non-polar and pole side chains interacting with each other, it'll wedge into a crack and it might twist it open and make it function less well. It might twist it in another way and increase its function. It's highly random. It's like a skeleton key that can open any door, and you have proteins in every cell of your body, and so ethanol is this universal key that can affect proteins throughout your body, and so we're gonna talk about the brain today, but I think, if you're well aware in the popular culture, someone who drinks too much, the cardiovascular system suffers. High blood pressure happens. Heart failure happens. Any emergency room doctor will tell you that in December every year there's a rash of people my age and slightly older coming into emergency rooms with heart arrhythmias, with even heart attacks because they overindulge in alcohol that time of year and then one of the side effects of doses of alcohol are the arrhythmias of the heart. Gastrointestinal system, I'm sure you know that long, heavy use of alcohol will cause cirrhosis of the liver, it'll destroy the liver. Alcohol in high doses contributes to gastric ulcers. And urinary system, you might or might not be aware that if you drink 12 ounces of an alcoholic beverage because you're thirsty, which means your body is crying for more liquid volume, what will happen is that 12 ounces will come out in your urine as well as about four ounces of your own body fluid. So that's why people wake up in the morning after a night of drinking very dehydrated. Even though they've taken in all that liquid the night before, they're very dehydrated because alcohol blocks the kidney's ability to concentrate your urine. Reproductive and endocrine disorders, so very often women who are of an age where they're trying to conceive might have difficulty if they're regular alcohol users because alcohol will alter the shape of proteins that are hormones that cause the female menstrual cycle to regulate normally, and so you can have menstrual cycle irregularities that prevent fertility. I try not to say that to my college age crowd because I don't what them using alochol as a form of birth control. Not suggested. The reason people self-medicate though, at the lower right, is the nervous system, and so I'm gonna talk in more depth at a cellular molecular level. How does alcohol affect the nervous system? So on the left, you see a pink neuron, a nerve cell, and they're actually much longer, more dramatic than that, that's a cartoon, but the key feature here is that that pink neuron, you see a few dozen neurons coming to it and making contacts with it and then it's branching four times and it's contacting four other neurons. Well, in your brain and spinal cord, a neuron might branch thousands to tens of thousands of times, and so in your brain, you have maybe a hundred billion neurons but that isn't what makes you talented or intelligent or that's not why you have all the wonderful memories that you have. Your brain really functions on the synapses. Where those neurons touch each other there's a small gap, at the right, you see a bigger cartoon of the gap, called a synapse, and that synapse is a place where a chemical signal is sent from one nerve cell to the next either telling it, "Hey, you should fire a signal," or telling it, "Don't fire a signal," and when you branch a hundred billion neurons and interconnect them and any neuron in that set, in that network, every second of every day of your life, there are thousands of neurons telling that neuron, "You should fire, you shouldn't fire," and it has to make a decision. It's basically a processor that based on the total number of inputs, if more say, "Fire," it fires, and then its message gets passed along the chain. In those connections, in those chains is where all your memories are. If you learn something new about chemistry tonight, the reason you will remember it tomorrow is that your brain is physically different. The synapses between neurons are stronger, there are more of them, they're different. So very profound, the interconnection between neurons, that everything you learn, everything you are, everything you can do, is in those synapses. Well, if you look at the synapse close, you see a bunch of little oval circles. That's cartoons of proteins, proteins that are ion channels, proteins involved in releasing that chemical called the neurotransmitter when a signal comes down. So those proteins are abundant, and it turns out they're very sensitive to alcohol's effects to alter their shape. In some people, they're up regulated. Sometimes they're down regulated. Within a person and between people, it varies a little bit. I should've mentioned when we talked about proteins, me and just about anyone in the room, if you compared a protein in the same cell type in the same part of our body that does the same thing, we don't have exactly the same protein sequence. In fact, if you have an identical twin and if you looked at all your proteins, they're not exactly the same. Life experience changes the sequence of our proteins. It changes the expression of our DNA, and that's important because we're gonna talk about the wildly variable ways that alcohol affects people and that's part of the basis because this generic skeleton key of alcohol doesn't affect all proteins exactly the same. So this is a short list of neurotransmitters, the chemical signal between neurons that have been shown to be profoundly affected by alcohol, and at different doses, they have differential sensitivities, in different people with slightly different sequences of proteins, they're gonna have different effects, and so alcohol is a terrible medication because, I mean, what makes a good medication is when you take it. When anyone on Earth takes it, you want it to have a consistent effect. One like that is Valium. So Valium is a drug that you give to anyone on Earth, everyone has the same reaction. It's a very specific, it's an anxiolytic, it calms people down. It slows your brain down. Alcohol can do that but it can also do a lot of other things and it has to do with it affects so many different things, it's sometimes been called a pharmacological hand grenade. Cocaine is a pharmacological scalpel. It really affects one thing. Alcohol affects a lot of things, and so the outcome can be very unpredictable. So, one outcome. Why do people medicate themselves with alcohol? Well, very often, I mean, various words are used, to get a buzz, to get high. The word I'll use is euphoria. You know, you poll a college audience and you'll hear probably 50 different word. This is real. This happens to most people who drink alcohol. So you have these pleasure centers in your brain that are there for a good reason. When you do something that increases the likelihood of your survival or your species' survival, there's a pleasure center in your brain that lights up. You get this great feeling that reinforces it. It says, "Do that again." So if you get a big bowl of fatty ice cream, this center lights up. Do that again. You know, you'll survive the next famine. Someone tells you they love you and they really mean it and you know they mean it, this pleasure center lights up. Interactions between people are really reinforced by this pleasure center and specifically dopamine. The neurotransmitter chemical dopamine is a very important one. It turns out the way alcohol influences the dopamine pathway explains why binge drinking happens and it also can explain why some people become dependent on alcohol for enjoyment, and so I'm gonna explain this with a graph that I've kind of invented, a very simple graph, but follow my logic, if you will. So what we've got here is time flowing along the bottom axis. Your blood alcohol is on the vertical axis. And so if you have one drink, this is what it would look like. Your blood alcohol would rise while you were drinking it. When you stop drinking, your liver and stomach have enzymes we'll talk about later that can remove alcohol. About one drink an hour in an average person gets removed. So as soon as you stop drinking, the blood alcohol declines. Well, if you just felt okay and you didn't have that drink for any particular reason, most people on Earth will experience a rush, a euphoria, a sudden mood that is better than their mood was before they started drinking. Dopamine, it turns out, is a double-edged sword. Dopamine is a great thing. It lights up your pleasure center, it makes you feel good, but there are many disease conditions like schizophrenia, excess of dopamine is one of the underlying factors in people who have the mental disorder of schizophrenia. So anything in the body in excess, that body has a, what I call, what physiologists call a negative feedback response. They say, "Hey, that's too much of that," and so there are mechanisms that will compensate, that will counter it. Turns out dopamine, this happens very fast. So you might think, you slide from a happy place back down to your okay place, but what happens is, as soon as your blood alcohol starts down, the dopamine receptors have been desensitized. They've been hidden. What happens is your mood dips to below baseline level. People whose blood alcohol has fallen, even while it's still elevated, they're not happy anymore. I call this the rising phase effect 'cause in the rising phase, we feel good, and then when we're in the falling phase, blood alcohol is still elevated, but we aren't as sensitive to it, and this, if you've ever observed the student body at a UW football game and, you know, thinking that they're like camels that can drink a bunch of water before they cross the desert, many of them will drink a lot of beer before going into the game, so it will last the whole game long. Those who have overindulged, what you'll see, is they're going crazy in the first half of the game, that's the rising phase, and then 3rd and 4th quarter regardless of what's happening in the game you start to see them sinking lower and you start to see the body posture of someone who's not having fun anymore, and if you've ever been in a setting where you've drank and then stopped drinking and stayed awake, you might've experienced that. This is why binge drinking is gonna happen. It's inevitable, especially in young people. So binge drinking looks like this. You go to a situation, social situation where there's alcohol and your blood alcohol rises after your first drink and you say, "That's it, I'm done, I just wanted one." Well, as soon as it starts down, if you've got several hours of social yet to go and your blood alcohol is on the way down, the social situation isn't fun. Your pleasure center is turned down, and so people will reach for another one. As long as the rising phrase is maintained, the euphoria, the mood boost is maintained, and so in our culture, people tend to start drinking in the evening and they drink as many as it takes to get them to the end, and I say people, I'm talking about the young people that I normally speak to. Apologies to those of you who don't necessarily fit the profile of my typical talk, but binge drinking does occur and that's why it occurs, and they do it in the evening and then they stop drinking and go home, and what do they do? They lie in bed for eight hours or 10 hours or 12 hours, and they are not aware but they're feeling horrible. Their mood is terrible, but they're unconscious, and so they're not aware of it. People don't drink from eight to noon and then go about their day because you would have the worst day of your life. Pharmacologically, if that's when we drank, in the morning, you could not feel good all day long and I think it would be a negative reinforcement of drinking. So we drink in the evening so that we're unconscious. I'm not an anti-alcohol crusader. My version of what responsible drinking is is the following. It's be aware that high doses of alcohol has side effects, negative side effects you don't want. So aim for a number of drinks that's okay to have, and find a way to slow the rate of the rising phase so that you get that buzz, that euphoria without ever reaching the range where vomiting occurs and crashing of cars occurs and that kind of thing. And then there's a short time frame where you don't feel well. The rate of removal is the same. In my book, that's responsible drinking and having food in your stomach slows the rate of rise by three fold versus drinking on an empty stomach. Also, the type of liquor makes a big difference. So somebody who does a shot, a one and a half ounce shot of whiskey, it starts up just like the red pattern there and it starts going down very quickly to people who drink low alcohol, beer, wine, that kind of thing. You know, alcoholism as we know it didn't exist until the 1600s when distillation was discovered. So basically the ability to make the percent alcohol in the beverage go up into the 40 and 50 and 60% range, that's when alcoholism really became a problem. Did I see a question back there? -

Audience Member

Particularly at this point dopamine, then are you prepared at all to tell us about binge drinking's effects on somebody's judgement? -

Kevin

Oh, absolutely. -

Bassam

Can you repeat the question slightly? Yeah, so the question was, am I going to talk about the effects of binge drinking, especially on judgement? And that's exactly the point I'm about to make. You lead me to the point that I really need to make with my young audiences when I talk about this, so thank you. Yes, that's where we're going. So dopamine tolerance, think of it in two different time frames. In one bout of drinking, you desensitize and so you want more. It explains why people drink too much in a bout. Over time, the dopamine system can become desensitized to the point where someone chronically, to feel normal, to feel happy, and this is the definition of an alcoholic or an alcohol dependent person, they need something boosting their dopamine to feel normal, to feel happy, and it has to do with the dopamine system and related systems. So young people are going to binge drink if you give them access to alcohol. It's not their fault. It will happen because the left frontal lobe of the brain, which is where our impulse control center is, it doesn't mature until someone's in their 20s. If you put a M&M in front of a three year old and you say, "All right, I'm gonna leave the room, "and if you leave that there, "when I come back, I'll give you three M&Ms." They'll eat it anyway the minute you're outta the room. As we get older, we can delay gratification better and better and in our 20s is really when that left frontal lobe is developed, and so younger drinkers are gonna be more susceptible to the inability to say no to a second drink than someone who's in their 20s. We can control those impulses better, and of the people who binge drink early, by age 14 that data suggests, they have a 50-50 shot at some point being identified as someone who's alcohol dependent. People who don't drink until their 20s, until early 20s, only an 8% chance, still a chance, but the odds go way, way down. So early exposure to alcohol desensitizes the dopamine system in some people permanently and it makes them susceptible to alcoholism. CDC statistic, 17% of US adults binge drink, and if you take it to the college age, the group that I talk to most often, 50% binge drink regularly, and it's nine drinks at a sitting. I mean, I can't walk after three drinks, not that I've ever tried that. Well, I mean, I've tried that. Nine drinks, it's amazing the tolerance, the tolerance of youth, and there is a physiological difference between young and old people. I don't know if you've noticed, if you're scanning the newspaper and you see drunk driving arrest reports, very frequently you'll see people in their 40s and 50s being arrested fro drunk driving, and if it's a first offense, very often that person has been drunk driving for years and years, but our motor tolerance goes down as we get older. An 18 year old who is drunk is a better drink than a 50 year old who is drunk. Neither are good drivers, but if I had to compare them, the 18 year old is the better driver. Question? -

Audience

As you know, the Lewis and Clark expedition was, as you know, the Lewis and Clark expedition was fueled by copious amounts of alcohol. It was the most important thing they had on their journey. -

Kevin

Yeah, yeah. -

Audience Member

Why has it become, why did we adopt a more Calvanistic attitude towards alcohol in our society now? That's an excellent question, and if you can just hold off gratification, your left frontal lobe, if you can just dampen it, that's exactly what the finish line of this talk is about. There is a great book I'm gonna refer you to. I mean, every military campaign in history has been fueled by alcohol. It is such a part of our culture, the politics, war, religion. You can't extricate alcohol from our culture, and you're not wrong about Lewis and Clark, and there's a trade off that I'll talk about at the end having to do with, do you wanna die in your 20s of cholera or do you wanna die of your 40s of cirrhosis of the liver? And that's often been the choice that's had to been made throughout history, so. -

Audience

Think of the achievements. Oh, but lots of great achievements. I agree with that completely. Some of the greatest artists and writers of our time, alcohol fueled, and this book I'm gonna refer you to tells the story eloquently and beautifully. So great question. People drink, especially young people, to overcome inhibitions, and this same left frontal lobe of your brain that I talked about being your impulse control center, it also makes you shy. It keeps you from, say, some of you in an audience like this might have a very insightful question, but you're just a little bit too inhibited to raise your hand and ask it. That's normal, acceptable, important social behavior. It stops us from doing inappropriate things socially. Alcohol, that's one of the first centers it hits, and it increases our social confidence. To think normally, you need a normal balance of two neurotransmitters in particular. 90% of the neurotransmitters in your brain are either glutamate or GABA. Glutamate is the main gas pedal. It's the main excitatory neurotransmitter system and GABA is the main inhibitory one. Valium, by the way, stimluates the GABA system. The GABA system slows your brain down. It calms your brain. The glutamate system excites your brain, and for you to be normal and make normal good decisions, you need to have a good balance. So things happen to you and you have thoughts and you do something. You have some behavior, some external behavior in response to thoughts and to experiences that you have, and a lot goes in, this amazing 100 billion neuron processor you have is capable of accessing a lot of things in milliseconds before it makes a decision. I mean, you have a basic personality. Is the glass half full to you or half empty? You have an empathy compassion. They found neutrons in the brain now, by the way, that are the empathy neurons, that stimulating that neuron makes you understand how another person feels, but we all have an empathy and compassion with the exception of a few sociopaths probably. We have a sense of what's just, what's fair. We all have an understanding of cause and effect. If I touch an electrode to a bottle full of ethanol, what's gonna happen? And then much more complicated situations in the real world. If I use this racial slur to this person standing in front of me, what's likely to happen? Biological drives, we have parts of our brains that are programmed in sexual ways, in appetitive ways. We had this hedonistic appetite for salt that's a biological drive, and that goes into the decisions that we make. Situational memories, you've not only experienced life, but you've seen other people exerience lives and cause and effect, and you can access memories like that before you make a decision about what to say, what to do, how to act, and then cultural learning, things that are acceptable in one culture are not in another, and it takes a lifetime sometimes to learn exactly what's appropriate in a context, in the cultural context. So somebody says something to me, all of these different centers of my brain, I can access them, I can come up with a net judgment, and this is all synapses talking to each other, and then a behavior, an outcome results. Question? -

Audience Member

So glut GABA circuits are feedback loops then? So glutamate and GABA circuits are related in a negative feedback. So if you get too much glutamate activity, and someone who's like that might have anxiety and shaky hands, might not be able to sleep, and so there are negative feedback built in on both of those, so too much glutamate will tell the glutamate neurons to stop releasing so much, and also when the glutamate neurons release too much, GABA neurons will ramp up and they'll tell the glutamate neurons, "Calm down." That's how you stay balanced and feel normal. So it's well known pharmacologically that alcohol is bad for glutamate synapses, it inhibits them, and it's good for GABA synapses like Valium is. And so someone who has alcohol in their system, as the dose goes up effectively, if their brain was a computer, the processing speed gets slower and slower and slower as the dose rises, and so think of a computer with a slow processor. You can only have one window open at a time or a few windows open at a time, and effectively the human brain becomes like that. There's a very eloquent model by a scientist named Claude Bernard who used this really simple basic thing that alcohol does, slow the processor, to explain a lot of the unpredictability in the behavioral effects of alcohol, and the model's called myopia, and if you don't know, myopia means near sighted, and so alcohol myopia means basically on high doses of alcohol, a person becomes cognitively near sighted. All they can think about is what's right in fron of them at that moment. They can't, you know, a myopia person can see right here but they can't see in the distance and so as your brain becomes simplified by high doses of alcohol, something may happen to you and you may only access one or another but not all of the complex decision making circuits you have in your brain. So it's been shown very convincingly that people can be more empathetic and compassionate when they're drunk. If you've ever been to a fundraiser, one of the first things they do is they hand you a glass of champagne. People tip more, people donate more when there's alcohol in their system. It's also very clear that sexual assault, alcohol is a major factor on college campuses and elsewhere in sexual assault, basic human drives. Any kind of domestic violence, very often alcohol and basic biological drives override thoughts of cause and effect, consequences, situational memories, and so very simple model to explain, why does alcohol have such dispart effects? So here's a study that I'm gonna use to demonstrate that and also to debunk a myth. Alcohol is not an anti-anxiety drug. This study proves it. So this is how the study goes. Volunteers invited to a party and they're told, "Free alcohol," and this is college aged crowd, so it's very easy to get volunteers for a study like this. Half are given drinks. The other half have drinks and they smell like there's alcohol but there's not really alcohol. Everybody has to think they're drinking to have a perfect control, scientific control. So they all drink for half an hour and then the researchers say, "Oh, we forget to tell you. "In about 15 minutes, you have to go on stage "and give an impromptu speech, "what I most dislike about my body and physical appearance." So snakes, spiders, and public speaking are the things people fear the most, and so this was a stimulus designed to make these people anxious and so then they're gonna have to sit for 15 minutes and their speech is gonna happen. They're gonna have a crowd of strangers looking at their body as they discuss their body. I mean, what could be more anxiety-inducing than that? But then to make this experiment a little more complicated, so they got these two groups, the drinkers and the think they're drinkers, they divide them into four groups and one group just sits and does nothing, they're just waiting for their speech, and then there's three groups that are kept busier and busier sorting slides, an intellectual task that takes more and more mental effort, and then they measure anxiety, and they use physiological and psychotropic measures to see how anxious they got over the next 15 minutes. The data are very simple. This is what they look like. On the left, you see the people who thought they were drinking but were not, the placebo group. Any bar that goes up from the midline, they got more stressed, and any bar that goes down, they got less stressed, and you'll see they didn't experience a lot of stress, increase in stress during the 15 minutes. I mean, the ones in the black bar that were really kept busy sorting slides, they actually become less nervous because they didn't have time to think or worry about this speech, this impending speech. Look at the group on the right. The only group that became more anxious are the ones that had alcohol in their system and had nothing to do. Alcohol doesn't make you relaxed. Alcohol exaggerates whatever mood you're in. Whatever's happening to you, you're myopically responding to whatever is in your world. If there's a death in your family and you get drunk, that will become the only thing you can think about. If you're out at a party with your friends and somebody says something funny, you'll laugh uproariously because that's the only thing you think about. You become myopic. And in this case, anxiety was the situation and anxiety is enhanced, is intensified by alcohol. It doesn't relax you unless you're in a relaxing situation, then it does. And it boosts self-confidence, so I told you young people drink for self-esteem reasons. So here's where I'm a little bit irreverent, I apologize, but The Onion is funny because it's so often true, and alcohol beverage consumer confidence does skyrocket as the evening goes on very often because of myopia. When someone who's drinking can only think about what a great dancer they are or how good looking they are and they don't stop and think about all the times that there's been someone much good looking or better dancer next to them, their confidence skyrockets, and often they have brilliant epiphanies like this young man coming up with this brilliant tactic for being attractive to women, and not to sort of bias things from a gender standpoint, I mean, ladies, they have their own version of bad things arising from excess of social confidence. Here's to the question that I was asked earlier. Not only does confidence go up but because of the simplification of the processor and all of the things that you're not able to access at high doses of alcohol, bad ideas galore begin to spawn. So let me just flash a few bad ideas that you might spawn at high doses of alcohol. That's a bad idea, if you know anything about electricity at all. This is a bad idea if you're a doctor who works in the burn unit, for example. Halloween parties should never end this way. (audience laughs) According to the CDC, 38% of emergency room visits, alcohol's involved. Now stop and think how much emergency room visits there must be across this country. 38%, bad judgment and also motor coordination. Car accidents are a large part of that number, but bad ideas often leading to injury are because of the poor judgment, because of people whose normally brilliant minds are not functioning with all of their RAM intact. So another important thing is that in adults those proteins fold and then they unfold and you don't have necessarily irreversible cognitive effects until you get really, really high doses. So binge drinkers by the age of 14 have smaller brains and they're not as smart as people who didn't binge drink when they were young. So one interpretation of those data might be, oh, then maybe it's just the kids with small brains who are dumb to being with are the ones that are binge drinking so early. Animal studies have very convincingly shown that if you take identical groups of animals and one group drinks as adolescents and the other group doesn't drink until later, you see exactly the same thing. A big part of this is cause and effect. It shrinks. So I like to use this analogy to explain that. Think of your body's proteins as construction workers. So if a construction worker basically drinks in the evening, drinks on the weekend when they're not actually building, the building they're working on is gonna be fine. They're building when they're sober. But if they're drunk while they are building, a young person's nervous system is being built, those proteins are part of the building, the synapses are part of the building, twisting those proteins during the construction is gonna make for poor construction of the nervous system, and in the extreme, you get fetal alcohol syndrome, but you get more subtle measurable effects even in kids who just start binge drinking when they're 14. Okay. another self-medication mode, to forget, to escape from problems, and sleep and forgetting is gonna be part of the theme that runs here. So when people drink, if they're in a boring situation, dark quiet room, a nightcap will make you sleepy. It changes the brain chemistry in the direction that sleep becomes more likely, but alcohol induced sleep is not true sleep. It looks very relaxing. Somebody might seem difficult to rouse like they're in a deep, deep sleep. What it is is it's surgical anesthesia. Natural sleep, in natural neurological sleep, people's brains have time frames when they are much more active than even the waking brain. There are very important functions that happen, especially in a mode of sleep called rapid eye movement sleep. It's when you're dreaming. The brain has very important job to do and it has to do with going through the whole day's worth of data you've just lived, all the thoughts you had, everything you saw and heard, and it decides which of these things need to be encoded in a synapse that I want with me tomorrow and which was just superfluous detail that I might go crazy if I remembered. So that's happening when a person sleeps. When someone is in an alcohol induced slumber, or any level of alcohol, is gonna reduce the ability of the brain to do that. So very simplistically, short term memory, what's you're thinking about now becomes a memory through a process called LTP, long term potentiation, and that happens in REM sleep. Alcohol doesn't let you do REM sleep. You may be unconscious for eight or nine hours but you're not refreshed. REM sleep is what you need to feel refreshed, and people often feel very tired after a night in bed after a night of drinking because they didn't actually get REM sleep. The next night, you'll have to get catch up sleep. So this memory formation process does not happen as well or normally when someone lays down with alcohol in their system, so you can't drink to forget past memories. You can drink to forget what you did last night and people who drink to the point where they have blackouts, walk around, young people especially often walk around and function and do things and have conversations and pictures of them show up on Facebook and they have no memory. There was no recording. While alcohol is in your system, you can't form memory, but escaping past problems doesn't work, and people often become depressed because that alcohol myopia might focus their mind only on the depressing thing in their life. They can't escape from it. It consumes them. It becomes the only thing in their world. So relevant to my college student crowd, drinking goes on at colleges in great quantities. 50% of college students binge drink. Many college students fail out their freshman year. This is a big reason. They don't understand the relationship between learning, sleep, and alcohol. So they'll study for six hours on a Thursday night, they have a test on Friday, and they'll say, "Yeah, that's it. "I've studied it all, I'm done, I'm ready," and then rather than go to sleep, they go out with their friends. So they drink for three hours, they lay in bed for eight hours or 10 hours. They take the test and they find they have very little memory of what they studied during that six hour time frame. They don't understand that you need the sleep to concretize the memory. I tell my students, "If you study for six hours, "sleep that night." If you drink the next night, memories of the past are secure. You're not gonna ruin your college career if you can separate learning and sleeping from drinking. You can live the college experience to some extent. I urge moderation, don't get me wrong, but I'm not unrealistic enough to believe that I could ever get a college crowd to stop drinking because of anything I say no matter how scary, but if they can learn about the physiology of memory and alcohol and sleep, maybe I can save some college careers by spreading this message. Okay, and now to the question that we wanna get to, so sort of the little final phase I'm wanna talk about. So people drink because they're self-medicating for the reasons that we just talked about and with the mechanisms that we just talked about. Here we are in Wisconsin. We have a rich cultural history. We have an history of alcohol, drinking and alcohol, I mean, drinking in our culture in Wisconsin. I'm gonna quickly go through some animal studies that prove alcohol preference and alcohol behavior effects are, they're highly generic. They're highly producible. So for example, fruit fly studies. Many years ago, 40 years ago, fruit flies, you give 'em a little alcohol vapor and they do what humans do after they've been drinking, they tend to fall down, and it turns out if you take a bunch of flies and you expose them to a vapor and the first few who fall, you sweep 'em aside, and then later on, you introduce those and you introduce those and they have offspring, their offspring will be even more likely to fall down quickly. The fly line is called cheap date sort of humorously by the scientist who developed it because a low, low dose of alcohol, these flies become effectively inebriated or whatever passes for inebriated in a fly. So you can breed into them lightweightness, if that is a characteristic. There is a lab, it started in Stanford, now it's in Boulder, Colorado. 1960s, they took a bunch of mice and they, animals don't like to drink, so often they vaporize the alcohol, sometimes they inject it, but they get a bunch of mice drunk and they see how they behave, and then they'll say, "Well, these two both, "when they get drunk, they sleep a long time. "Let's breed them." And then breed their kids and then breed their kids, and you can selectively breed mice to have the entire range of behaviors that you might see in yourself or in your friends or in your families or in your culture. So some mice fall asleep after a little bit of drinking and they sleep for hours. Some mice fall immediately to sleep and they wake up with their heart pounding and sweaty, if you can interpret the mice behavior, and many people do this after heavy drinking. They'll only sleep a few hours. They have this rebound effect. They're wide awake. Some of these mice act like they're at a party, at a rave. They go crazy. They run around the cage when they're drunk. They don't fall asleep at all. Some them, the body temperature falls. Some of them, the body temperature skyrockets. Some are very degenerative tremor prone. When they sober up, they shake violently, which happens to many human alcoholics after a long binge when you deprive them of alcohol, and then there's also a super strain of college-aged mice that no matter how much alcohol you give them, they pass all the coordination tests. They'll have these rotating wooden bars and they'll have the mice walk across and how far they get says how coordinated they are, and so a sober mouse will make it all the way across. One that's a little drunker will fall off earlier and one that's drunker will fall off earlier. Well, this resistant strain of mice, they bred into their DNA, into their protein structure the ability to handle enormous amounts of alcohol, and they walk right across that bar and they don't fall down, and you see that maybe in people you know. There are some people you know who drink a little bit and they're silly and they're tipsy and they fall down and they slur their words, and others you might know who, after their ninth drink, might be hard to tell that they've been drinking, and I'm about to go into the cultural history why that might be. But more crossbreeding experiments have been done and these last two are kind of interesting. Animals don't like to drink alcohol usually, but if you can find a couple of animals that don't mind it and crossbreed them and then take their offspring and find ones that don't mind it or even like it and crossbreed them, you can breed in a love for drinking alcohol over water or fruit juice or anything else. So the love of the feeling of drinking alcohol is also genetic and can be bred into a population of monkeys. Another thing that can create alcohol preference, and this one is a little bit sad to me, it's an important experiment that was done and it's one you can't do in humans, but it is the natural experiment sadly is done. This group at NIH took a bunch of baby monkeys and they took 'em away from their mothers and they gave 'em all to foster mothers, half of which were known to be very good mothers. They cuddled the babies. They groomed them. They feed them well. And then half were known to be not very good mothers. They abused the children. They neglected them. They didn't feed them. They never groomed them. The equivalent of giving a monkey a bad childhood. And then later on, these big community cages they put 'em in and they had a choice, water, fruit juice, alcohol. Inevitably, the monkeys who were raised in stressful, abusive environments willingly, happily went after the alcohol and the ones that had good childhoods did not. So the DNA in your body, the proteins it expresses aren't automatic. What you're exposed to in your life has a lot to do with which proteins get expressed and in the alcohol abuse preference system, it turns out you can breed in effectively someone who's got a predisposition to be an alcoholic or to abuse alcohol. So this book is fantastic. If you like history, if you like culture, sociology, science, this book starts at the beginning of civilization and it studies the cultural, sociological effects of alcohol throughout history. It talks about alcohol and warfare. The Romans, how the Romans would invade territories. So the territory were drinking weak beer at the time. The Romans were sipping their high-alcohol wine for about a month and they turned them all into drunken sots, and then they had no problem overwhelming the populace because they were all a bunch of alcoholics had just been created and they weren't capable of fighting. But that being said, the Roman soldiers, they got regular doses of alcohol. When they went into battle, it made them courageous, it made them brave, and there's fabulous quotes from Ancient Greece and Roman and China, every civilization that has developed alcohol. So just quick snapshots of this book. The first evidence of humans producing intentionally alcohol, 10,000 years ago. 8,000 BC, they find residue of alcohol in pots, and it happens after humans start, they take up argiculture and they start living in cities, in groups. That's when alcohol production begins. By 1,000 BC, all over the world where people were living in cities, alcohol was being produced. It was an important commodity. It was being drank in large quantities. Now early on, it wasn't like the alchol we have today. I mean, it wasn't distilled spirits of high concentration. It was relatively weak beer and wine that doesn't even approach what today's wines are. So Iain Gately attests in this book most modern humans, people alive today are descendants of people who lived in cities who were exposed to alcohol as part of their religious systems, as part of their political systems. He goes into Prohibition. I mean, this book is a tour de force if you find alcohol and its effects or its use in our culture interesting. So he sets the stage. Then a beautiful book, one of the best books I've ever read and I highly recommend is The Ghost Map, and in this book, Steven Johnson really puts together the bottleneck that makes alcohol use an evolutionary selection pressure. So this is the story, and so just read the little subtitle, the story of London's most terrifying epidemic and how it changed science, cities, and the modern world. This is a profound book. It really tells us about how the modern world was shaped, everything from public healthy, sewer systems to what we understand about the germ theory, and science. This is a tour de force in science as well. This is a detective novel. It's the story of an anesthesiologist, brilliant man named John Snow and a clergyman named Henry Whitehead who independently are trying to figure out why is cholera killing people in London. Periodically, these outbreaks happen and hundreds of people die, and then the outbreak goes away and it comes back, and at the time, people thought it was bad humors, it was bad air. The germ theory, people didn't have any idea that there would be something in water that could make people sick. So this book is great. Read this book please. Well, here's the ghost map itself or one version of the ghost map, and so what you see on this map, so what Henry Whitehead and John Snow did is they basically, one of the pieces of evidence is they drew a map of the city. The orange circles are pumps and there's one called the Broad Street pump you'll see right in the middle. All the black dots are records of somebody died in that house, somebody died in that location. 700 people died in two weeks and if you drew this map, you'd see that it radiates. It's very dense around the Broad Street pump and around the other pumps, it's less and less, and some of the outlying cases, there were cases that people died in houses very never other pumps, but Henry Whitehead interviewed the family and they said, "Oh, he hated the taste "of the water from our pump. "He used to walk over to Broad Street "and drink from that pump," and so they traced, they figured out it was the well, it was the water where cholera lives and it was causing this outbreak. But there's a cool fact that is kind of a little subscript in the book but I jumped on because it's so cool. Literally feet from that pump, there's a brewery where there are 70 workers. Not a single one of them died, not a single one, and on interviewing, well, why is that? None of them walked to the pump because they get free beer with their lunch hour and they get free beer all day long, and so people who drink alcohol, alcohol was a safe thing to drink in the Middle Ages in these cities. In any city, alcohol was a safe thing to drink because the process of producing it was sterile. You didn't have cholera, you didn't have dysentery. So just really, really cool fact in there. So this is how Steven Johnson's scenario goes as far as human history, culture, and alcohol. Water in cities is inevitably gonna get tainted. Where large numbers of people come together in the era prior to us understanding sewage and public health and bacteria, epidemics of cholera, dysentery and other things are gonna break out. Those who preferred alchol to water and could handle its toxicity are gonna survive more often and have more children. Their genes are gonna be passed along. So you can imagine there are three groups of people, if there were an experiment, three groups of people. There's one group that likes alcohol but they get really drunk and unruly and they fall down and they can't function. There's another group that drinks alcohol and they're high functioning. They can drink it, tolerate it, detoxify it, and move on, and then there's a group that just don't like the taste of alcohol, they're gonna drink water. one of those groups is gonna be selected for, the one that can drink alcohol and can handle their alcohol. There are a couple of cultures on this Earth so I don't know if you're aware, in the scientific reports, it's very clear, sociological reports, there are a couple of populations of people on the planet who don't do well in the modern world with the alcohol we have access to, Native Americans and Australian Aborigines. Those are hunter-gatherer cultures that never gathered into cities. They never came up with a regular fermentation product that they got alcohol from, and so now in the modern world with the alcohol so present, the rates of alcoholism, the rates of all sorts of alcohol related issues in those groups are sky high, not because of, many racist theories have come out, you know, weak constitution and you just can't believe that there's the history where things like that, theories like that were actually given scientific credence. I think this is a very good explanation. They have been through a culture where they were not selected for their ability to handle alcohol. Not only do brain proteins and behavior get selected but very interesting phenomenon, not I won't go too much into alcohol detoxification but there is an enzyme we have in our body called alcohol dehydrogenase. Ethanol is turned into harmless acetic acid in two steps and that first enzyme, this is all it seems to do in the body. It starts the process of detoxifying alcohol. It's in your stomach. It's in your liver. There is no reason for that molecule to be there if it hadn't been bred into there by many, many generations of exposure to alcohol. It's the reason why people on average can get rid of one drink in an hour, and people who have lots of it can get rid of faster than that, getting rid of alcohol, so someone of Irish ancestry or northern European ancestry might be able to get rid of alcohol faster, much faster than someone who's, let's say, from Korea. In Japan, turns out 50% of the population or so has mutations in the enzyme, the second enzyme, the aldehyde dehydrogenase, so that it doesn't work, and when they drink, their skin turns bright red because the chemical acetaldehyde skyrockets. It's very toxic, and they vomit. A very low dose of alcohol, they become violently ill. So that's an example of a human population where those proteins are expressed differentially. Now let's come back to the state we love. When you say Wisconsin, you've said a lot about the alcohol culture. This ia compile from Google Maps. Everywhere you see an orange dot, that pixel has more grocery stores than bars and everywhere there's a red dot, there are more bars than there are grocery stores, and you don't have to be very good at geography to be able to pick out Wisconsin. The upper Midwest is a highly red place to be. And if you stop and think about what I just told you, these profound books about the cultural history of alcohol use, who settled the upper Midwest? It was settlers from large cities in Europe where if you didn't drink alcohol and if you weren't good at drinking alcohol, you would've died of cholera or dysentery, and so our culture is one that's been selected and now there's different, it's not just genetic. There are different kinds of culture. There's sociological cultures. There are ideas, the Wisconsin Idea, we hope to pass down good ideas to people. So there's also cultural learning that doesn't have to do with genetics, and that's part of this too. But Wisconsin has a drinking problem. I don't know if you're aware of that. We have clean water here. I mean, history has completely turned things. We understand the germ theory. We understand public sanitation. Not everyone has access to good drinking water, but for the most part in America, we do. But we also have access to alcohol and have bred into us I think this love of drinking it, and the public health problems are enormous. Six billion dollars a year in Wisconsin is what it costs to deal with alcohol issues. Alcoholism is a leading cause of domestic violence and other types of violence. One in 10 deaths are attributed to alcohol use in Wisconsin and an alcohol related car crash every two minutes and in every 30 minutes, somebody dies in the crash, and I think you it's frequently not the drunk driver. Frequently, it's the sober driver that they hit head on and I don't know if you know why that is, but a drunk driver, their reflexes are slow. They go into the other lane and they're so slow they're basically rubbery when they hit the steering wheel and dashboard, and any of you who knows about martial arts, if you relax into a fall, you don't break bones. A sober person will quick reflexes sees the crash, they stiffen their arms, they stiffen their legs, they stiffen their torso, and bones break and they penetrate organs, and it's just horrifically worse for somebody who reacts and braces for a crash than somebody who relaxes into a crash. So that's another sad fact about drunk driving accidents. Yes? (audience member speaking off microphone) Ah, no, thank you for point that out. No, the third statistic is a national statistic. First one is Wisconsin specific. The last two are national statistics. Thank you. So I have a habit when I talk to my young audiences, I mean, I'm sure if you've ever heard someone speak about public health and alcohol and Wisconsin and the deplorable record we have for how we drink, you'll hear something like, "We are number one. "Wisconsin is number one when it comes to binge drinking, "number one when it comes to "alcohol use per person." When I say that to a group of Wisconsin students, when I say, "We are number one," they didn't let me finish. They're like, "Yeah! Wisconsin is number one!" So I don't say that in my talks anymore. I say we are number 50. Wisconsin is the least responsible state when it comes to drinking and driving, when it comes to binge drinking, when it comes to the responsible use of alcohol. It's a sad fact, but I think there might be some explanations in the literature, in the evidence we have out there. Not that this makes it okay, understanding it. I think we are, I think it's really a goal to overcome our biology. It might be our biology, but I think society I think, the Wisconsin idea is about overcoming our biology with learning, and I'm hoping that we can learn better. -

Bassam

Please join me in thanking Dr. Strang for this presentation, thanks so much. Thank you very much. (audience applauds)