 This is the 29th annual seminar series, and as you know, this year we're working on the topic of disparities. The series this year is co-sponsored by the Urban Health Initiative, the Global Health Program, and also by Dr. Chin's Robert Wood Johnson's Disparities Program along with the McLean Center. This is the first actually of 27 seminars on the topic of disparities, divided into roughly nine each quarter for the fall, the winter, and the spring. Many of the speakers are from the University of Chicago or from the city of Chicago, but there will be 10 or 12 visitors from other groups nationally. We're delighted that the opening session today will be presented by Professor Rick Kittles. Professor Kittles is at UIC in the section of hematology oncology, and his research utilizes novel methods to uncover genetic changes leading to the onset of prostate cancer and its progression in treatment. He studied health disparities and how genetic ancestry can be used to map genes, looking at common traits in diseases. We all know Professor Kittles and worked with him when he was here at the University of Chicago in the Department of Genetic Medicine. Also, he serves as the scientific director of the Washington, D.C.-based African ancestry incorporated group. I've reviewed a number of Professor Kittles recent publications, and they're really quite remarkable. Published in 2010, a paper in gastroenterology on genetic heterogeneity and colorectal cancer in Americans of African versus European descent. A paper that Professor Kittles published in cancer in 2010 looked at gene sequence variants in relation to prostate cancer risk among men of African descent doing a case control study. The papers are really many and very deep and fascinating. Rick, it's a delight to welcome you back to the University of Chicago, and thank you for being our first speaker in the seminar. I must say, it's always good to be back at the U of C. I treat the U of C as my Chicago home. Just so you know, I'm not going anywhere. You'll see me every now and then. Good, thanks. I had no idea that the date that I proposed would be the start of this seminar series. Yeah, well, hopefully I won't do any harm to the rest of the series. But today I'm going to talk about some topics that are near and dear to me, race, biomedical research, and the politics of trust. And I use the term politics of trust because very often we don't think about what we do and how it impacts the average person, people on the street. When you deal with genetic information and health information of individuals, it's about trust. It's about respect, and some of us think of, if you're a clinician, you think of yourself as providing a service, but it goes beyond that. You really are entrusted with this information, and I don't think we think about that often enough. And so I want to talk some about that because there's a history of trust across the varying communities that we deal with. And some there is greater trust, others there's a lack of trust. And I think it's about how not only we interact with these communities now, but also how we understand the history and try to reconcile issues that may have arose previously. So we talk about genetics. I get really excited because things are rapidly advancing in genetics. And all of you, I'm sure, remember the project, the International Human Genome Project, where scientists all over the world were involved in sequencing the human genome. And we found that there were about 20,000 genes in the human genome and 3 billion of these nucleotides, those chemical bases. And there's about 14 million SNPs, which is a class of polymorphisms. These are variants in the sequence. And so if we compare the genome of any two people in this room, it will be different. And we've cataloged close to about 14, about 12 to 14 million. I have to get the actual number because most of them are rare, seen only once, okay? And so after the human genome, we then went on to the mouse because this was big science, right? Think about it. I mean, it cost tens of millions of dollars, if not hundreds of billions of dollars, actually to sequence the human genome. And so the machinery, the personnel then went on to the next question, which was the mouse and then the rat and then the dog genome in 2004 was completed. The dog genome, I tell people all the time, is very important because the dog is a good animal model for cancers, human cancers. Like prostate. And I tell folks all the time, the only other mammal that naturally gets prostate cancer besides the human male is the dog. Yeah, naturally. And the women always smile and laugh when I say that. The guys look at me funny. But seriously, naturally, human male, the dog. But it also was important in understanding, you know, our best friend, right, the dog, the canine genome, right? And we found that there's about 19,000 genes in the canine genome, which is why some of us resemble our pet dogs. After sequencing those five individuals across the genome, we found out that it was important to understand variation, genetic variation, because genetic variation impacts not only what we see physically, but also things we don't see, like risk for disease. And so then came trying to study as much of the human population diversity as we can. And so we have a lot of technology that allows us to do that. And so, for instance, we can look at a sequence and a gene and look at it in three different people. And they may have a different allele. What we call this is a SNP. This individual may have a CC, a TT, or the third individual may have a CT, a heterozygote. Now, for the most part, many of these polymorphisms have no major implications in terms of health. But for some of them they do. Think of a disease called sickle cell, where it's just really one polymorphism, one substitution of one of these bases in the beta-globin gene that creates so much havoc in those individuals that have sickle cell trait or disease. So instead of having a circular red blood cell, they have a sickle-shaped red blood cell, right? It doesn't flow through the vascular system as well. It can get caught up in capillaries and have a crisis, all because of one polymorphism. That is quite common in West Africa, some parts of West Africa. Not all of West Africa, but some parts, parts that historically experienced malaria. And so here's a situation where polymorphisms may provide advantage for survival in a population, but then in another environment, a vastly different environment, it could create problems. So this is something that we see a lot when we think about the evolutionary history of these polymorphisms. And so as I said, the technology is rapidly advancing. So I get excited when I see these. These are my toys, but they're costly. They're costly. We can answer a lot of questions. In fact, we can answer a lot of questions faster than we ever could imagine. The sad part is we're asking the same questions using the new technology. You see what I'm saying? But this is expensive. Each one of these machines here costs about the same amount as a condo in Chicago. So just think about that. When that happens, you have a situation where you have the haves and the have-nots, right? So some universities, institutions, medical centers, research labs have a lot of these sequencers and genotypers, platforms. Many of them. And then others have none. And so the rift is widening even more and more because the technology is very expensive. And so, you know, I tell the students when I'm here, when I was here, I used to tell the students, you should be excited and grateful that you're in Chicago because this is a have institution. All right? You go down the street, Chicago State, it's a have-not, right? So I think we need to understand that this technology, while it's important, and can answer some very interesting, exciting, and important questions, it does deal with the economy, you know? So in terms of the benefits of this technology, it's not really equitable. That's what I'm trying to say across all communities. And so we have this era of genetic and genomic ancestry and challenges related to health. I use genomic ancestry because we're moving away from race. I'm going to talk something about that. Why race is not really that important anymore. Race captures some information, but not what we want to do in terms of getting to the next level as it relates to disease. And so what are these challenges after we sequence the genome? We know that one of the biggest challenges is how do we define ourselves? Group definition and membership. Identity has been shifting ever so much as the technology has been increasing. Think about what I'm saying. Science and society are intersecting in ways that are quite exciting, but also uncomfortable. Folks are redefining themselves. What does it mean to be an African American? What does it mean to be a Hispanic American? Why are we using these terms defining people by language? What does that mean biologically? So this tension is exciting right now because it has to be reconciled. And people reconcile that differently depending on how they were raised, how they were socialized. What's important? What's the value? What's the utility of the technology? So I'll get into some of those stories. Can we accurately assess genetic ancestry? How does ancestry relate to issues of skin color and SES? For a long time we thought that we could just type these markers for ancestry and go away, put away with race. Don't even ask people what they are, just type these markers and put them on some scale of genetic ancestry. But we find that ancestry is related to issues of skin color. And skin color modifies the social interactions. So while you may have high levels of let's say West African ancestry, like I would say myself but I thought I had high levels. Why don't we use Wesley Snipes as an example. High levels of West African ancestry. Pretty dark skin, right? So we say okay well we don't have to ask him what he is, we can just type these markers. But skin color modifies his interactions with society. So that has to be taken into account too. How useful is ancestry for informing us about disease risk? The issues of health disparities? Are they due to biological differences? That's the big million dollar question, right? And we're finding out that for the most part the bulk of health disparities have very little to do with biological differences. They have more to do with social determinants. But there are some like prostate cancer that have a strong genetic underpinning. And then how do we prevent repeating the negative past abuses of race? So with the challenges come the promises, right? The technology is advancing. We have increased research in diverse populations. So I meant to tell you guys Ghana today is a studying white man. You know, we're now looking at women. We're looking at Africans, Asians, Indians. So it's important to understand not only the biology of these and the genetics of these populations but also the social-cultural variation that's within those groups and between those groups. And so then becomes the integration of epidemiological, cultural, and population history. So that's what we're seeing more and more. We're not just saying, well, these are some West Africans and these are some Chinese samples. But people are trying to investigate much more about the history of these populations and how they define themselves. And so with the technology, I think it's very exciting because, as I said, we have these ever-emerging new sort of disciplines. Like, for instance, pharmacogenomics, right? Which really wasn't, you know, it's been pretty recent that that's been advancing. And it's advancing pretty rapidly. And so I put this picture up. Anybody know what this picture is? It's a cell dividing. It's a very important cell that's dividing. It's the HeLa cell. HeLa, H-E-L-A, stands for Henrietta Lacks, African-American woman from Baltimore, Maryland, who died of cervical cancer back in, I think, 51 or something like that. And when she died, her cells were, before she died, her cells were taken in several biopsies and her cervical cancer cells. And they were growing up in the laboratory at Hopkins. And she had no idea. Her family had no idea. And those cells were quite important. In fact, they were one of the first cells that were immortalized and that were continually growing for decades at that time. So folks were trying to keep these cells growing continuously, but they would die. And then when they got ahold of her cells, they kept growing. And so that presents these ethical issues, right? The ethical dilemma, right? The advances of HeLa that the HeLa cell has provided has been enormous. I don't even think most people in this room could fathom the amount of information that we've gained just from that one cell line and the amount of money that companies have earned based on this one cell line. However, her family, many of them still, illiterate, poor, lack health insurance or underinsured, have gotten absolutely nothing. So that's the ethical dilemma, right? And so from a historical perspective, we know that this isn't new. This wasn't new. This was going on before 1950 with the war tribunal, the Nuremberg war tribunal, where the German scientists were accused of experimenting or doing research on individuals. The syphilis study in Tuskegee, Alabama, everybody knows that one. In fact, most folks in the black community who know very little about research know about the Tuskegee study. It's as if it was like imprinted in our genes. There's no sort of Sunday morning breakfast discussion about this, but we know about it. We know something bad happened. We know that we were exploited. And so there's some serious implications still today. And so this is back in, it started in 32 in Tuskegee, Alabama, and the public health service actually wanted to find out what was so different about African-Americans and the natural history of syphilis in the African-American population. This was an interesting study. They actually had an African-American nurse who was engaging the community, the men. She made them feel very comfortable. They provided medical service to these men, medical exams. But then when penicillin came about, they didn't give them penicillin because they wanted to see the natural history of this pathogen in the body, the natural history from start to finish. And so they were denied penicillin. And then the study was stopped in 73. This is Nurse Rivers, the African-American nurse I was telling you about. And what's very interesting about this study is it was actually CBPR before we knew about CBPR. And what do you mean by that? It was community-based participatory research. There's an institute, a college in Tuskegee called Tuskegee Institute, it was called Tuskegee College at the time. And there was a lot of important federal officials who were on the board of Tuskegee at that time. And they were having a discussion about what are some of the issues in Tuskegee County. And the folks at Tuskegee said, well, if it wasn't for this bad blood, this syphilis, we would probably do better. We'd be better off. And so that's how this whole study emerged. It was actually a discussion among the community members. And then they determined the best way to get those individuals to participate in engaging the community. So CBPR at its worst though, in a sense, because the outcome really wasn't beneficial for those individuals. At the same time, there was a woman named Henrietta Lacks who was having some woman's issues, went to the doctor, and was diagnosed with, I think it was stage three or four cervical cancer. She was born in 20, she died in 51. Her and her husband were Southern tobacco farmers. First cousins, they were related. It wasn't uncommon. They lived in Baltimore. They had five children. Now, they were poor. They litter it for the most part. And he was, what do you call those guys? He liked to go step out. What word can I use here? Philander. Philander? Okay, let's use that word. Philander. So he gave her several STDs multiple times. And ultimately, I believe, and many believe that he gave her HPV, which led to the development of the cervical cancer, which is why those cells continued to grow. They were immortalized at that point by the virus. And so the story is quite interesting. And it was written up by a woman named Rebecca Skloot recently, Skloat, who spent a lot of time with the family and wrote a very interesting story. However, she didn't really deal with the racial issues at the time, race, which was very, very important because Henrietta, when she was sick and went to Hopkins, which was a major hospital on the East Coast, it still is, they had two, at the time, two wards, the black ward and the white ward. Had she have been white, she would have went to the white ward and probably got a little bit better treatment. And more than likely would not have been a research subject. But pretty much all of the black patients, since they couldn't pay, ended up being involved in research. So think about that. Since you were illiterate, you really didn't, you lacked the education in terms of research literacy and health literacy. And you wanted a service provided medical care. You go there because it's free, but yet you end up being a research subject. I don't know if that's coercion or not. I would leave that up to the ethicist. The fact that she didn't know. So in 51, as I said, diagnosed with cervical cancer, oh, I'm sorry, it was stage one. Within a year, she was gone. The chief gynecologist, Tallinn, when he did the biopsy, he took the cells to Dr. Gay, who was a major researcher doing tissue culture work and was trying to have these cells grow, trying to immortalize cell lines. He got ahold of those cells and they just took over the lab. He became very well known for those cells. Now, probably one of the most important results with the HeLa cell line was the polio vaccine development. You know, you have to grow up these, the polio, it has to grow in cells in order to develop the vaccine. And for many of the cells they were trying to use, they couldn't, it wasn't stable. They were unable to grow. But then they used the HeLa cell and it was quite successful in growing up the polio virus. That's when the vaccine was, it became very important in the development of that vaccine. Now, where did this happen? At Tuskegee. At Tuskegee. So, and a lot of people don't realize that the first mass production of the polio, of HeLa cells for the polio vaccine was done at Tuskegee Institute. They were growing up tons and tons of HeLa cells. And there were scientists involved, students involved, all of them of color. Not having any sort of clear connection in terms of where these cells came from. And they were shipping those cells all over the world so that countries all over the world could develop the vaccine. And in fact, if it wasn't for that, polio wouldn't have been eradicated at the time. It was also useful in studies on the effects of the atomic bomb, advances in vitro fertilization, cloning, gene mapping. In fact, I used it when I was in graduate school and we're using it now currently in the laboratory. Cancer research, viruses research, all surrounding HPV. Not all, but many of them surrounding HPV. Cells brought and sold for billions of dollars. So this is the book I was talking about. Very fascinating book. Spent a lot of time with the family, but really didn't deal with the politics of race much. Now, one of the reasons why HeLa cells have been so important in terms of biomedical research was because she was African-American and part of her gene pool was from West Africa. In fact, she has a common maternal lineage. Her mitochondrial DNA actually goes back to Sierra Leone. We were able to look at the mitochondrial DNA of HeLa cells and look at where an African may have arisen from. What's fascinating about this is that the variation, genetic variation is much more extensive in people of African descent. This is a study that was done recently where they resequenced 250 genes in Hispanic-Americans, European-Americans, Asian-Americans and African-Americans. And you'll notice here, the African-American bar, a larger number of these polymorphisms, these snips that were found in those genes, the number of them were much more higher among African descent than the others. And it's not until you get to the common polymorphisms, those that are greater than 30%, that you see sort of an equal distribution. But the low-frequent variants and the rare alleles are much more common in African people. That's big. That's very, very important to understand because many of these genes that were sequenced were either drug transporters, metabolizing enzymes, or known genes that impact risk for disease. And so here's a situation where we know a lot about the variation in European-Americans with very little about African-Americans. So we're not really capturing much of the variation that's contributing, that could contribute to disease and drug efficacy. So now the race is on, right? To study people of African descent. So this is a recent dump from HapMap. The HapMap project is a project that the federal government put together to collect samples from different parts of the world and sequence, discover polymorphisms, and find the frequency of these polymorphisms in these populations. The populations are Yoruba from West Africa, Han Chinese, Sef, French, Sef. They're French Europeans. I guess that's the prototype of Europe. It's French, France. And then there's another Asian population, the Japanese. So we actually have two Asian populations in HapMap, Chinese and Japanese. And I find that interesting. That was really about political power. It's interesting because you can say, oh, well, maybe the Chinese could represent us. They said, no, they can't. We're unique. Genome is unique. And they still believe there. Okay? And so we have two Asian populations at HapMap. And so from the, and then after HapMap, build one, there were several other iterations of HapMap. And so we now have African-Americans. We have some mixed groups, Hispanics, a lot of other groups. But anyway, the recent dump of data showed a very large number of SNPs that were found. But when they looked at where they came from, of course they came from the African populations. So still, when you hear, oh, we know all about genetic variation, we still know very little. There's a lot more that we're still, there's a lot that we're learning daily. And so this is important because there is a study design called genome-wide association studies that allow us to interrogate the genome to look for risk alleles or genes for disease. And in fact, there have been a large number of these GWAS studies over the last five, 10 years. And we've been quite successful in finding genes for Celiac and atrial fibrillation and colorectal cancer, breast, prostate. We just submitted a paper on prostate cancer, the first GWAS in African-Americans meant for prostate cancer. It took 10 groups across the country to get together to do it, but it was just submitted this week. Very interesting findings. Crohn's disease and others have been quite successful in terms of mapping genes using GWAS approaches. However, one of the things we do know is that the genetic architecture across populations varies. So risk alleles discovered in one group may not necessarily confer the same level of risk in others. This is important because genetics and clinical practice are becoming more and more situated together. This is that new field of personalized medicine, individualized medicine, genetic medicine, right? Better diagnostics, pharmacogenetics, new drugs, new biology, and better risk assessment so that we can then ultimately come up with good ways of modifying that risk. This is what's going on. Over the next five or 10 years, you're going to see a lot more of this happening, especially now that we're finding these variants, these risk variants across populations. Now, why should you care? Well, many people will say, well, you can take an active role. You can take an active role in clinical decision-making. Genetic tests are currently available. Many of them deal with cardiovascular disease, heart disease. And so how do you make informed decisions based on these risk alleles? Genetic medicine, however, may actually increase health disparities. And that goes back to what I said earlier about you have the haves and the have nots because this is not cheap. This is not cheap. So you'll have a clinic. You'll have two clinics. You'll have one on the Gold Coast and you'll have one near Washington Park. And where's the one where you will see folks getting the genetic tests? However, the genetics alone will not help us. I like this. It must be in the genes somewhere. This is why the new thing are genes and environment. Looking at populations and trying to understand risk, not only biological risk, but environmental risk, too. This is important because they work together to produce almost all phenotypes. You may have alleles for height, height, height alleles, height genes. But if you don't eat, something's going to happen. The environment, particularly important for geneticists because of issues of selection, if you know the history of these populations. They may be informative gene environment interactions, may be informative for treatment or modifying effects of genes. We can mass detection of genetic effects if not controlled for. And environmental effects may vary across populations. Now, let me give you an example. This is a study from the NHANES group where they looked at vitamin D levels, by sex and age and all of that. The three groups, non-Hispanic whites, non-Hispanic black, I don't know what that means. And Mexican Americans, right? And they looked at 25-hydroxy vitamin D in the serum in nanomoles per liter. You'll notice that whites have, the average is about 80 nanomoles per liter. African Americans almost have, about 50, 49. Mexican Americans in between, right? This is important because vitamin D actually is made in the skin due to exposure from the sunlight. However, if you have dark skin, it blocks the sun from getting into the lower dermis where the conversion of 7D hydrocholesterol occurs. So, biology and the environment are interacting there, okay? Good, perfect example. You can also take dietary supplements for vitamin D. Do like I do because I live in Chicago and I have dark skin. You know, the sun is only out about three days a year here, right? So, I take, I go to CVS and I take D3. I take over 3,000 units a day because that's about what you would get. No, you get a little more if you went outside with your shirt off for a half an hour. Midday. Not in the winter, right? In the summertime here in Chicago. But nobody can do that. I would love to see more women do it, but I'm just saying nobody would do it. Nobody would do that. Now, vitamin D is important. In the blood, it goes to many different organs. Breast, it's implicated in breast, colon, and prostate cancer because it's involved in apoptosis. It inhibits angiogenesis. It goes into the kidneys where it could actually regulate blood pressure. There are some really interesting clinical trials going on now where they're looking at blood pressure regulation by vitamin D supplementation into the pancreas where it's involved in blood sugar control. So, not only does it implicate cancer, but also hypertension and diabetes. And then also is involved in parathyroid hormone regulation. Now, as I said, you can get it from natural sources. If you were to eat salmon, fresh, wild salmon, you get about 1,000 units in the serving. Most folks in here are saying, well, what about milk? Because you're always taught milk. Milk has very small amounts of vitamin D. Fortified milk is about 100 units. We actually need several thousand a day. You can get it from shiitake mushrooms. You can get about 1,600 units from that very expensive shiitake mushroom. Good serving of that. It's always good. However, exposure to sunlight for half an hour, which is sure it off, about 3,000 units. Or you can take, like I do, vitamin D3 over the counter. Now, this didn't come out, but what I wanted to show you was the environment is very important. Had my figure come out on this slide, it would show that along this axis is BMI, and along this axis is percent hypertension. So from low to high hypertension, and BMI goes from low to high. And there's a line here that goes across these three regions. There's two populations in West Africa. There's two populations in the Caribbean. And then there's one population in Maywood, Illinois. And these are African descent populations. Nigeria, and Cameroon, Jamaica, and I think Barbados, and Maywood, Illinois. These are blacks. And you'll notice... Oh, you won't notice it, but... Imagine. You can imagine. The line goes from low BMI to high, and also increasing hypertension. In fact, hypertension is pretty low. It's about less than 10% in West Africa. Less than 10%. But if you go to Maywood, Illinois, it's closely approaching 40% prevalence. Now, what's so different? I mean, these are all African descent populations. What's so different? Very little. The environment's a big difference. You know, because they don't drive cattle-like escalades in Nigeria. Well, not everybody. They don't drive, you know, as much. And they don't stop at windy drive-throughs. Eat five meals a day, some six. Or... And they exercise a lot more. So, that's very important to understand. Because one of the biggest ways of modifying risk for hypertension is to just walk a mile a day. Take the elevator. I mean, take the elevator. Take the stairs. Take the stairs instead of the elevators. Contributing factors for health disparities, as I mentioned before, many of them are socially determined. So, while there's gene-gene and gene-environment interactions that could impact, like, for instance, vitamin D levels, which could impact risk for disease, but also stress, because stress is real. Life course selection, cultural factors, behavioral differences, and there are some. Even within groups, there are serious behavioral differences. Right? Think about how one copes with stress. Some people are very cool with coping with stress. It's like water on the back of a duck just flows right off. Others get stressed out. Start smoking. Start drinking. Erratic sexual behaviors, all kinds of things emerge because of stress. And so, I think we have to understand that in order to fully understand these health disparities, we have to look at the environmental, these social determinants in ways that we may not have in the past. Racism is also real. And then, of course, SES, an institutional arrangement. Now, why did I say all of this? Because, you know, you can teach people to eat healthy, but if there's no place to eat, like on the Chicago South Side, to get, not no place to eat, but no place or very few options to get healthy foods or food, then you're going to have issues like this where the South Side area and the West Side, which are areas where these food deserts are in the city, are also areas where there's high BMI and the food balance score is worse. Now, this is real. This has absolutely nothing to do with genes. So, like for instance, I couldn't do much with this, right? I couldn't solve this myself. This is economics. This is politics, you know. This is legislation. And so, one of the things we did do, though, was we set up two farmers markets right around here. We helped these community organizations develop these farmers markets. Now, that was real. Folks went out there on Saturdays or Sundays and got all kinds of fresh produce from farmers from the southern Illinois. You know, I forget that Illinois is big. You know, I've just been here for years. I've only been here for years. There's a lot of farmers down south. Many of them are black in southern Illinois, Missouri, all the way down to Oklahoma. And so, many of them come up and set up at these farmers markets. Those are real. Discrimination. If you want to know anything about, if you want to know some good studies about discrimination in health and outcomes, check out the journal Black Psychology, this issue in 2009, which was February 2009, it came out. The whole issue dealt with studies looking at racism, trying to quantify the effects and outcomes on health. And one of the things that I found very interesting in that journal was this study where they looked at correlations of perceived discrimination. Not even, you didn't have to say it was real or not, just the perception of discrimination on health in these clinics. And what you notice here is that, and these are quite significant, if the patient perceived discrimination in terms of with the physician or his office or her office, there were negative correlations with health. General health pretests after four weeks, after 16 weeks, the only thing that was positive was a number of chronic diseases. But this is what I find interesting, the fact that the idea that you and the doctor are working together as a team to better your health, all of those negatively correlate. So this is real. The problem is trying to quantify this and then also trying to reconcile it so that we can overcome that issue. I mean, we talk about cultural competency, I don't hear that much anymore, we used to talk about it a lot, but it's about perceptions. Now, why community participatory research? Because you can build and maintain trust. When I came here in 2006, I spent two and a half years out there in the community talking to folks, finding out what the issues were, what was important to them. One of the biggest issues was nutrition. We started working with some of the medical students, some of the undergrads and grad students to develop programming around nutrition with the communities. It was very important that they saw that we can. And I think that's part of the framework in which we can operate successfully. And this is important because as this technology and the information is emerging, the new technologies I was saying, the new treatments and interventions that could helpfully eliminate disparities, if they're not involved in that, they're not going to accept it. You have to bring them into the mix. And there are many different levels. I'm not going to get into this, I'm sure you guys know, to CBPR. But know that the Tuskegee study of untreated syphilis was a classic example of CBPR. And of course the barriers deal with respect, willingness to share power, that's major. I talk to researchers all the time and I say, well, you know, if you really want to get access to this group or if you want to increase your numbers or whatever, you should go talk to these individuals, this community. And many times they'll say, I don't, you know, I'm not sharing any information. And so that's something that I think is major. Accepting another's perspective also is big. But what's also big too is the fact that there are very few blacks and Hispanics doing this research. Now, this is a representation of grants from NIH by race and ethnicity. Now you'll notice that since for the last, and this is up until 2010 actually, the numbers haven't changed much. Last 10 years have been pretty much the same for African Americans. About 1.7% are funded researchers. Hispanics, about 3.5%, and then others, about almost 20%. This is real. And so we talk about these pipelines, we talk about increasing the numbers, but we're doing, it's not really having an impact. At least I don't see it. So back to race real quick and then I'll end. This historically has been the problem in biomedical research. We've used race as a proxy. So you go through the literature and you'll see there'll be a study looking at stroke or heart disease or prostate cancer. And it'll say race is the biggest risk factor. Ancestry is the biggest risk factor. What does that mean? African Americans highest risk for stroke. What does that mean? Does it mean that there's some genes that blacks have that's contributing? Or does it mean that the environment, some diet, chicken and watermelon or something? What is it? It doesn't allow you to tease apart the risk factors, the biological and the environmental risk factors. What we're doing now, more and more, is that we're actually, instead of using race, we're actually looking at genetic background, we call that genetic ancestry. And we're measuring the environment better because geneticists are now talking to other people. Geneticists are very fickle. I don't know if I wanted that recorded, but very fickle people. And they say, well, they don't know, they don't understand what I'm doing and I don't understand what they're doing. But the social scientists actually have some good ideas. And so when you think about complex disease, you have the risk coming from the biological and the risk coming from the environment. Then you have an interaction. And the only way you can accurately measure that is by studying them individually and not confounded by race. So how do we do ancestry stuff? Well, this was a good study that came out of Ohio where they had two groups, two cohorts. One that self-reported as black, the other one that self-reported as white. And they typed genetic markers and estimated African ancestry from zero to 100%. And you'll notice that these individuals here had less than 10% African ancestry. Those who said that they were white. But then you look at those African-Americans, look at that distribution, look at that spread. There's a significant number, even though it's not a lot, but it's still real, of African-Americans. These are folks who self-report as African-American. They go to black barbershops, at least most of them do. Who genetically have more European ancestry than other African-Americans. On average, it's about 80% West African ancestry. So it's a very heterogeneous, macro-ethnic group. High genetic heterogeneity due to the antiquity of being African, the African ancestry, but then gene flow or admixture with non-Africans. And mainly it's white men. Mainly white men. I got to tell you guys this story. You'll hear about it more after today. So all African-Americans have some level of European ancestry. So even me, okay? Even me. But recently I actually looked at some prominent African-Americans, you know, like Martin Luther King's lineages. And we find that one of the biggest civil rights leaders in our time has a European Y chromosome. Which a lot of people would be shocked to hear. They'd be like, wow. So he had on his paternal line somebody who was of European ancestry. And that's about 40% of black men that we test. We look at these Y chromosomes. 40% of them have European Y chromosomes. That is major. Because when we look at the other side in terms of the female contribution it's only about 5%. So that's called sex bias gene flow. And that's because of the behavior of slaveholders during the beginning of slavery and then through slavery. And then after, for the most part. And so when we look at across the United States the pattern of genetic variation in African-Americans differs depending on the history, the local experiences in those communities. So anyway, I'm going to go through this real quick. But I'll leave it here. So this was a study where we looked at colorectal cancer here at UFC. And we did this, I did this with Nathan Ellis and Sonya and Anthony Skoll. I mean Anthony, Andrew Skoll. And what we wanted to do was look at some genetic risk factors for colorectal cancer. But before we could even look at genes we had to really estimate how much variation was it within those so-called racial groups, African-Americans and European-Americans with colorectal cancer. And then control for that variation. So look at the spread here for those African-Americans and then those that are white, European-Americans. And these are the French seph samples in green and these are Nigerian-Europe. But there is no clear dividing line. I mean there's back and forth here. I think that's very important for us to understand because as we start talking about individualized, personalized medicine, we're going to go beyond the whole by-deal of the race-specific drug. Because there's a lot of variation even within these groups. So it's important for us to estimate that. And I think that's probably been one of the biggest contributions of these ancestry markers in biomedical research is allowing us to just move away from race and rather interrogate genetic variation. This is another way of showing some of that data. So a triangular plot of West African, Native American, European ancestry. And so in this red square, could be somebody like Holly Berry who has her mother's European and her father may not be 100% Mandingo. But there are some blacks who have more European ancestry than some European. So there is no dividing line. Hispanics also vary heterogeneous, grouped together because the federal government says they speak Spanish. So we have Mexican-Americans from Colorado, a high level of Native American ancestry and Spanish-European. But then we have another group of Hispanics who if we're doing a study on asthma would be grouped together with them, Mexican-Americans. These are Puerto Ricans and look at the distribution. Much less Native ancestry, much more West African ancestry. So I think that this has been a lesson for a lot of folks looking at risk for disease and then also, like I said, treatment outcomes. When we look across the United States at different African-American communities, we see a lot of variation. A lot of variation. And it's not all sort of this homogeneous group. The lowest level of European ancestry we saw was in the Gullah Sea Islands of South Carolina. We published this, we looked at the Gullah folk, Charleston and Columbia, South Carolina all in one state, vastly different numbers there in terms of European ancestry. The lowest is in the Gullah, the highest in Seattle, Washington. Almost four out of every ten folks that we recruited in that study had one white parent. So just socially, it's a different group. And these African-Americans are socialized much differently out West than they are in the rural South where the history of race has been quite strong. Which is why when I was younger and I used to go to San Francisco, I used to be like, something's wrong with these folks out here. It's different. They're just different. It's different because they don't necessarily see themselves like, I saw myself as a black male in New York. Okay? If you think about multiculturalism and diversity, all of that emerged from where? Out West, the Pacific Northwest. Washington State, Sacramento, Sacramento, all of that stuff. Tiger Woods is a perfect example. What did he say years ago? He said he was Cable Asian. He's not black, he's Cable Asian. He wanted to say, he was saying he was mixed. And he appreciated all of his mixtures. Caucasian, Asian and black. However, he was quickly reminded that he's black. Now some of y'all are wondering what's going on in South Carolina, right? From low to high levels of European ancestry. So Columbia had the highest. It's a major highway. It's a capital of South Carolina. The University of South Carolina is in Columbia. But most importantly, Strom Thurman was in Columbia, South Carolina. So remember what I said about the local experiences? Those are very important. Local histories, really important. We can't just group these all together. But one of the things that has been a problem for a long time is when we do these genetic studies we set up these consortiums where people recruit and put all of these samples into one analysis. But they're different environments and also biology. And so because of these markers we can now control for that heterogeneity in these big consortium studies. I'm going to end with this here. And I apologize for having so many slides but I always do. This is why I have sort of... I'm kind of ambiguous about pharmacogenomics because these big drug companies don't necessarily... While they say they want to go more personalized and individualized, that's not how their economic plan is, their business plan. Their business model is set up around marketing to populations, to everybody, and not just to individuals. But anyway, this was the by-deal publication of the combination drug, the clinical trial, where they looked at isorbidinitrate and hydrolysine in blacks with heart failure. This is a very, very important study. I was excited because I said, wow, they're studying heart failure in blacks. This is very important. But then I read the paper. And okay, it says here, studies suggest that people identify themselves as black may have on average a less active renin angiotensin system and a lower bioavailability of nitric oxide. So you look at the literature, that's pretty consistent. I mean, there is some differences there. They haven't really been able to identify what's going on, but there are some differences there. But then they say their trial represents a departure from the recent approach to the design of cardiovascular trials. A large heterogeneous population, we examined a specific population because they said, you know, those blacks. A heterogeneous population may have substantial variations in genetic and environmental factors that influence disease regression and response. Now based on everything I've said, does this make any sense? No, it doesn't. And so we have to really go away from that. This actually is that whole racial sort of model. And while it was important to see if in fact this drug did have some level of efficacy in the African-American population, we also have to understand that not all blacks are going to respond to it. And in fact, not all did. There was only a 43% improvement in survival. So what were some of the issues? Who was black, race was this crude proxy, just self-report, skin color, whatever. The trial didn't test other groups, so we don't know if actually by-deal works better. And then, of course, while great, there are important functional variants there. What did those individuals have in terms of genotype that made them respond while others didn't? That's where this should be going. And that's where I hope this is going. Because if not, then we're going to continue to stall on our route to personalized medicine. So with that, I will end and I will say this. This is the future paradigm. We're going to be, hopefully, more opinions, predictive, personalized, to preempt, but none of this will happen unless everybody participates, because those communities that are not part of the discussion are not going to benefit. Thank you very much. So, Rick, I have a question. When you do research, like on the south side of Chicago, how do most south side residents self-identify when you talk of ancestry versus race? First thing I say is, how do you define yourself? Because that's important. I'm not saying we throw away race, because when somebody says that they're an African American or a Hispanic American or whatever, that means something. And so there's some that could, those variables could be important in the study. I then also have them go deeper though. So I ask them, what is your mother's ancestry and what is your father's ancestry? And then I say, what is your mother's mother's and your mother's father's? So they go back to their grandparents, and they'll do just like they did for themselves, African American or whatever, and then you can really see sort of the complexity in that family. I mean, in that individual, based on the family history. Okay, and so the last point that about a week ago, or two weeks ago, and I don't know if you saw it, the Chicago Defender ran an eight-part series. It was called the Legacy of Tuskegee Clinical Trials in 2010. Right. And so you're right, because there have been several studies actually two studies done one in 1990 and then one in 2000 that said most African Americans and Latinos don't know about Tuskegee and that's not their reason for non-participation in clinical trials. But even if they cannot articulate that most that are involved in research will tell you we don't want to be guinea pigs and be experimented on. So the interesting thing I thought about the Defender's eight-part series is they're trying to put out in the community this whole push towards personalized medicine. The person who did the series is someone who has participated in clinical trials herself, but her caveat is the community does not know the questions to ask and also she herself being a freelance writer doesn't always have insurance so she signs up for studies so that she can get the free healthcare particularly in depression and when she brought up the issue of race to her white therapist the whole structure of the trial and the therapy changed because the person back to what you said had a different perception of what is racism as opposed to the person and she then felt there wasn't this trust between the two of them. That has big implications as it relates to that trust. But engaging the participant and learning as much we want to learn as much as we can about the community and the individuals in the community I just always found it much easier and you gain much more information when you ask them sort of these questions about their parents and their grandparents and it also because sometimes people say I didn't show this data but sometimes African-Americans say that they're Native American they will say that and look just like me they say I'm Native American and then you got to walk them through because being a Native American is important to some people actually it's important more and more for some people because of what's been happening in terms of reparations and all that for moving them on these reservations. Yes. Stand up off the floor to ask the questions. The first is a little maybe scientific and that's the question of whether or not it's more complicated just genes and environment I thought I heard you say at one point that the same gene in a particular racial group might behave differently and so aren't we even talking about gene-gene interactions at that level too it gets very complicated. You can have not only gene environment but also gene-gene or you can have more working together gene-gene environment it can be quite complicated but with more and more disparities work is going towards looking at that looking at how where the direction of risk is coming from and all of that and the complexity of that. And then the second question is I think a very significant one for anybody who wants to work in community-based participatory research is your judgments or advice about who stands for the community right right well I mean historically I mean early on people you know folks thought that you could just go to the head honcho and he'll give permission or she'll give permission but I mean it goes beyond that it really depends on the on the on the structure of that community and the history of those communities so it's complicated it's not just a you know who's gonna who can consent you know it's much more than just going to that one person I think we really have to study these populations a lot more deeper in order to understand that. I really appreciate your insight about Tuskegee being a community-based research program I think that's a I didn't know that and I think it's an interesting way of looking at it. There were a lot of discussions back and forth before it even started Right right but I don't think it's been positioned like that until I mean I haven't heard it before but I think it's interesting now to think because we see this as such a positive you know a positive thing now that we're doing and so I would and I'm sure the people who are doing it especially the black woman who's involved with see themselves as doing a very positive thing for the community at the time. So my question is 30 years from now 40 years from now how do you think we'll look back at the community-based research we're doing now in terms of you know was it a good thing was it you know what were the possible I think the jury is still out on that I think that there's sporadic success but it's not everybody's not enjoying this right now you know there are some institutions that do it quite well and they have been for a long time and so while there's others that are just trying to catch up now so it'll be interesting to see after 10 years sort of how but the successes that I do see are very important and exciting so I'm not saying we should stop I just you know I think we have to be very very careful you also have to understand too now it's an education that goes both ways and so the community may not understand a lot about research and they definitely don't understand the pipeline the research pipeline because I'm sure folks at Tuskegee knew that papers are going to be published that they were not going to be given the drug penicillin once it was found to be efficacious for syphilis they wouldn't have said do this you see what I'm saying so we have to understand the whole pipeline too or we have to describe that in a way that the community understands it because a lot of times the community thinks that they're going to get data back right away you know I have people I've recruited for several years ago here in Chicago who try saying you know where's my data you know I'm like this is a research study you don't get that back we don't give that back so that pipeline is important the whole research pipeline because I think Heela is a perfect example of when things get out once you give it up and then most people will tell you that it is highly unlikely that the Lax family her descendants are going to get anything from this even though we know it was wrong because of there was no protection there so I think that's an important new sort of dimension that we should really look at in terms of CBPR is making sure the community understands the full gamut of the research because they have a research they have issues and sometimes their issues correlate in terms of their research questions and we get all excited but we have something else we're going to do with it than what they want so I would like you to speak to a little bit to using race more as a social standing and the interaction with social environment I used to think that race was this it could be looked at in terms of social standing but I don't know when you have an example and I'm just talking now like Barack Obama these examples where it doesn't necessarily hold and there's these sort of issues with it race is real and they'll get me wrong and politically social politically in the United States historically it's been used a lot in terms of across many different institutions but using it as a measure for social standing I'm not sure Rick I apologize for not telling you that you were going to be the keynoter in this series it was by oversight but you did a fabulous job and I want to thank you so much