With millions of human genotypes now determined, our information about human genetic variation is increasing faster than many other areas of science. That pace stokes an appetite for expanded investment. But has this information led to measurably improved, actionable understanding of illness and disease? Genomic medicine is fundamentally a biological and public health topic. Is the genome the major repository of the information we need in health? If so, to what extent might genomic approaches reduce the burden of disease in the community? Will they meet the promise of preventing/eradicating disease and illness? If not, what alternative approaches carry greater promise? What data is most salient/compelling to sway funding sources?
Christopher Contag, PhD, Director, Institute for Quantitative Health Science & Engineering; Chair, Department of Biomedical Engineering, Hannah Distinguished Professor of Biomedical Engineering and Microbiology & Molecular Genetics, College of Natural Science
Nigel Paneth, MD, MPH, University Distinguished Professor, Departments of Epidemiology & Biostatistics and Pediatrics & Human Development, College of Human Medicine
Leonard Fleck, PhD, Center for Ethics and Humanities in the Life Sciences, College of Human Medicine
Audio transcription (may not be 100% accurate due to automated transcription):
Let me say a couple words of introduction by way of our session in a little bit more substantive. First of all, it seems to me that nobody can argue that precision medicine is something that is extraordinarily elegant from a scientific point of view. So we’re not gonna argue about that. Likewise, nobody can argue that our capacity to do genetic and genomic testing has yielded enormous amounts of data that we would never have imagined possible 20 years ago. Likewise, no one can argue that the cost of generating this wealth of data has decreased dramatically over the past 20 years. However, the whole purpose of acquiring all this data and doing all this testing is to yield comparable large gains and health for individuals or for the health of the population as a whole. As our two speakers are going to demonstrate this afternoon, that’s something that’s arguable. So we got something to argue about. And so those t questions that we’re going to be addressing would be something to this effect. Has precision medicine yielded value for our health, has precision medicine, yielded value for our money, and have we as a society, made a wise investment in this regard. Now, with that, we’re gonna turn to our survey items are gonna put up the first item and for the benefit of those of you who are not directly capable of seeing the screen. I’m going to read each item when he’s available. Now they broadcast. Oh, they’re broadcasting it so everybody can see it. Okay, go ahead and put up item number one. So since the 19 sixties, in the U. S. Age adjusted heart disease, death rates have Ah, I’ll say a increased by about 70%. Be increased by about 30%. The state about the same. The decreased by about 30%. Ah, e decreased by about 70%. So go ahead and respond. And that’s that. And I should be seeing responsive coming in. And I’m Yeah. Do you know how to get the results coming in? They aren’t showing up on the how was it working makes you that they show up on the phone, but not on the screen. There we go. Okay. So Okay, good. Okay. So you can see the results of the question right there. And I’m, uh and I’m not going to read those off right now, so we’ll goto Question number two 42% of you on the first question, 42% of you responded a second question. Which biomedical discovery or development in the 20th century? Do you think was most important? A. Antibiotics be vaccines, See imaging technology. Such a ct, m r i d The structure of DNA A e the risks of smoking that’s deliberately vague. Yes. Wait. Did not you choose what it’s important for you and you deliver for you. Did you two decide what is important? Does everybody responded? Yeah, there we go. So 47% of you say antibiotics. 40% vaccines, 11% DNA, 2% imaging nobody about risk of smoking. Item number three The benefits The benefits of genomic testing that is whole genome sequencing as well as a broad array of more specific genetic tests would be increased if these were accessible to all. Not only those who can pay for them responding. A. If you strongly agree with that statement, be if you agree, see if you’re uncertain. The if you disagree E If you strongly disagree, go ahead and respond. The benefits of genomic testing such asshole genome sequencing, as well as a broad array of more specific genetic tests, would be increased if these were accessible toe all and not only and not only to those who can pay for them and looks. 39% of you strongly agreed with that statement. 36% agreed, 11% uncertain, 9% disagree, and 5% strongly disagree. I don’t number four last item from a personal and public health perspective, we’re much better off as a society and as individuals having access to genomic testing such as whole genome sequencing, as well as a broad array of more specific genetic tests available in a clinical setting, a strongly agree, be agree, see uncertain de disagree e strongly disagree. From a personal and public health perspective, we’re much better off as a society and as individuals having access to genomic testing. Such a whole genome sequencing is, well, the broad array of more specific genetic tests. And that’s the word. I think you’re a for results. Yes, 34% of you strongly agreed with that statement, 33% agree 19% uncertain, 10% disagree. 3% strongly disagree, and now we’re going to find out how agreeable or disagreeable our two speakers are. We’re going to begin with Dr. Chris Contag.
Can everybody hear me? Okay, great. So the acoustics in this room are horrible. So if you’re back getting beer or filling up your plate, keep the conversation to zero because it’s very hard to hear across in the room. So also, if you want a better view of what’s going on, these conference rooms are available. Sit in any of the three conference room from the 1st 2nd or third floor and welcome to research date I. Q. We had a fantastic day with all the poster presentations and this event ending research day at I. Q is fantastic. It’s I couldn’t ask for a better turnout. I couldn’t ask for a better discussion partner in moderator. And what a way to celebrate research and I Q. So we have the title promises, promises, and the second promises has a strike through. I’m gonna focus on the promise that doesn’t have a strike through if you want my perspective from the get go. So if someone in your family today is diagnosed with lymphoma, you have a considerably increased risk of being diagnosed with lymphoma yourself. Does these risk is heritable? My father died of complications of lymphoma. His brother, my uncle died of lymphoma. My brother is a 10 year survivor of lymphoma. My sister survivor of lymphoma. Does this give me a tenfold increase in being diagnosed with lymphoma? A 34 3 immediate family members. What is that number? So my brother, my father and his brother lived on different continents. Totally different lifestyles. My brother, sister and I live as far away in the U. S. And still live in the U. S. Is humanly possible. And yet we have this. This pattern of disease risk disease risk is heritable. Despite the knowledge that the foam is heritable today I can’t determine my own risk. I can’t advise my children as to what their risk could be. And I have no prediction for all my nieces and nephews what their risk will be for lymphoma. So if we know disease, risk can be heritable. What should we a scientist do? What should be his condition’s d’oh. We could be prom at pragmatic and say Just wait till someone symptomatic the family histories enough and irradiate them to damage the other tissue surrounding the lymphoma. Or we could be proactive and intervene early and try to make a diagnosis early enough where the treatment is less, Uh, less, uh, toxic. So the genome sequence has been determined that predictions are being made there being made that the promise of determining disease risk for a wide variety of diseases. But why am I in the medical community still unable to answer this question? Who’s at risk in this group of about 100 people? We could test all 100 people every year for lymphoma, and that would be a proactive way to do this test. Or we could do a genomic analysis, figure out who’s at risk and just test the high risk people with a more expensive test. That, to me, would be a cost saving activity. So who in the room is an experimentalist and does experiments every day but your hand up, or even if not every day, you consider it once in a while. Are you experiment with your kids at home or you doing experiments? Sometimes I’m guessing most all of you do that. So when you do an experiment, how many of you make a gases to the anticipated results of that experiment. Is there anybody here that doesn’t say if I do this experiment that could be list this or that We all create expected results and how many of you would use those expected results? When you then analyze your data, put your hands up. If you like your expected results and you use them to benchmark what you’re doing, how many of you like getting unexpected results? Put your hands high if you like unexpected results. Absolutely, huh? So my advice to every young scientist is going to every experiment with your eyes wide open, because it’s the unexpected result that leads to the leaps in science. You need to have a maximum awareness of your data on what the date is telling you and expected results are good, but they tend to be incremental in what they what they predict. If I make that prediction than anybody else’s, similar knowledge in this room would make the same prediction. So it’s good it advances science, but it’s predictable. It’s incremental. It’s the unexpected results that are really key, Freeman Dyson said in his essay. The scientists, as a rebel every time we introduced a new tool. It leads to new and unexpected discoveries because nature’s imagination is greater than ours. Thanks, Samuelson said. It’s the nature of discovery that it cannot be planned or programs. So despite these words of wisdom, when your accent asking the taxpayers for dollars to support your research, where there’s a grant of program or small project where there’s 100,000 for multiple billions, you better have a plan. You better have a program, and you better have a notion of what you’re expected. Results could be so in 1999 Francis Collins said that in 15 to 20 years there would be a complete transformation of therapeutic medicine. That was his expected result, and he called this project the Human Genome Project in that cost $2.7 billion of taxpayer money. But now, 20 years later, that transformation a therapeutic medicine has not occurred. He did not get his risk expected result. So we entitled this bruise and views promising problem promises, promises with a strike through. In the second promise, we did that because we have not achieved a complete and total transformation of therapeutic medicine. However, if we specifically dwell on those respected. Those expected results will not only be disappointed because we haven’t transformed therapeutic medicine but will also miss the tremendous opportunity afforded by the unexpected results. Let’s talk. Take a few moments to focus on the promises without the strikes you. So the human genome cost the taxpayers of United States. $2.7 billion was estimated in 2011 that the Human Genome Project. In the sequencing, the June left lead to 800 billion in economic impact, which is a conservative estimate. A 300 full return on the taxpayer. Adopt taxpayers dollars. So it’s one of the objectives of the NIH. To drive innovation, economic growth. And, as Lance said, that is something that we seem to all except. But the incalculable impact of this project that has had a cross discipline has been really transformative, from agriculture to basic biology, we guide breeding of her animals, using the gym today so again, tremendous impact. We’re engineering genomes to make better models of human biology and disease so that we can better predict outcomes again a significant impact. And the U. S. Is a global leader in genomic sciences because of this push for the Human Genome Project. But as Len said, we’re not here today to talk about the things that we seem. Many of us seem to accept that we’ve made significant intellectual advances. And impact of the project has been dramatic on economic growth here to focus on the promises in clinical care delivered today very pragmatic. Practical question. What’s different today than 20 years ago, when the genome was proposed to be sequenced? So I’d like to argue that there’s there’s really significant optimism for genomic medicine and, you know, and using genomic medicine to predict human health. And, um, this sequence was released in 2003 which is only about 16 years ago but should be focused on the 20 year old predictions that were made by Francis Collins in 1999 ish. We focus on what’s new, so let’s put this into perspective by examining other scientific advances. The smallpox vaccine is described by gender and 17 96. It took 223 years to use that vaccine to eradicate smallpox from the human population. The polio vaccine was first used in 1995 64 years later, we still haven’t eradicated polio from the human population. The sequence of 1,000,000,000 base pairs of human single human genome was published No. Three, and since that time, about 500,000 genomes have been determined completely, which is about 30.6% of the human population. So not only is genomic medicine and Nations field, it was founded on a monumental task of completing 303 billion base pairs of sequence data. What are expectations? They’re integrating that knowledge in the health care in 16 years? Are they realistic now? Were they realistic back in 1999 when Collins proposed this? So those are the questions we’re here to answer today? I would argue that sequencing the human Joan Gino was likely the greatest technological achievement of our time. Delivering on a variety of promises, I would argue that it’s predicting risk of cancer, metabolic disease, cardiovascular disease. It’s given us a framework in which to predict and correct genetic diseases. Prepare patient parents for the birth of a sick child. And if you’re diagnosed with cancer today, their FDA approved test in a commitment of identify your driver mutations and the accessory mutations that oncologist can use to guide your therapy. One such approved Testes Foundation one. Testing Formica Genomic test. Tell your physician how you respond to available drugs again, a significant benefit. So I think we’ve been witness to the greatest technological advance to work in our time. And it’s not the genome sequence in itself. That’s that technological advance. It’s the advances of bringing the cost of sequencing down from two point $7,000,002,000. That is the key. That is the unexpected result for one of them and Gina typing to tens of dollars for Gina type. So the development in the deployment of technologies for ascertaining inter individual genetic differences, where the genome project has really over, delivered and really made an impact that is the cost that is reducing the cost of sequencing so called next gen sequencing. It’s the unexpected result of the genome project. Why is that important? Well, the low cost of genetic sequencing has led to commercial testing a maternal blood for trisomy 13 18 21 Down syndrome, as well as other fetal, uh, any employees and certain copy number variants that I the concept of being able to pound by sequencing has allowed us to count essentially, um, transplanted gnomes. So when a woman is pregnant, there’s a transplanted genome, and that genome can be detected in her blood. So in this scenario of counting genomes, deep sequencing can provide explicit information of transplanted genomes, and this lead to many other perinatal genetic tests. Another, another example of a genome transplant is heart transplant, lung transplant, kidney transplant. We take a genome from one person. Of course, it’s in the context of an organ or tissue and put it into another. When that organ is rejected, all of that Deena gets dumped in the circulation, and we can now predict who’s going to fix their immune suppressive therapy based on what DNA is in their blood. For rare genetic diseases, direct sequencing of a patient or the families excel can provide a definitive answer and circumvent died a diagnostic ground wild goose chase. This is being implemented across the country, however, not in a large scale. The rare genetic diseases studies from multiple groups have shown that whole genome sequencing can result in the diagnosis first, many as half of the acutely ill inpatient infants informing clinical management is always reducing inpatient costs. So next gen sequences next Gen sequencing is enabled. Tremendous number of tools, including transcript don’t mix, aren’t a single singer named Chip analysis Committeeman Yeon Participation sequencing that this so called chip seek and look right of different molecules. This is led, of course, to direct to consumer genealogy Cos. 23 me and others and again, is Land said. That’s what we’re here to talk about. But 23 me is collecting self reported medical data, Um, as metadata and two met, making tremendous predictions about certain characteristics. Course. One of the characteristics they predict is curly hair, cleft chin and the mirrors a lot cheaper than then getting your genome, your genotype determined. But nonetheless, some of the predictions are making a pretty outstanding but not yet available to all of us is 23 me users. So the ability to predict complex genetic traits was demonstrated a couple of years here at MSU. Gustavo and Steve Schuh and others showed that they could predict human height from the human genome using the UK Biobank data, and you’re gonna say, Well, wouldn’t they tape measure. Be easier to measure your height than predicted from the genotype. Yes, but what that demonstrate is that we can predict complex genetic traits in this case, 20,000 snips instead of a handful or a couple dozen same algorithm now applied to breast cancer, osteoporosis, kidney disease and a CZ. We refine their screening protocols will have a dramatic impact on guiding patients on whether they should get a mammography at age 30 50 70 years of age, again reducing the cost by giving some insight into what, Who’s at risk? So it was unexpected complexity of the genome that was also one of the unexpected results. When I was a graduate student, we would have debates like this, and we would argue how many genes in the Human Genome 450,000. That was the range we all thought was about the right number, we thought, to make a human must take a least 100,000 genes with 23,000. So understanding the complexity of regulation, understanding how the genome is organized was one of the unexpected outcomes of the Human Genome Project and one of the things that has really slowed us down because there’s not one gene one disease. It’s 20,000 genes to predict height and equal complexity for many other complex diseases. I would argue that that cancer is a complex genetic traits. We know what the uncle genes are. The tumor suppressors are, but what we don’t know What are the variance in extra sounder matrix? What are the variance in immune system? What are the variance in other parameters of metabolism that control, whether cancer have the chance to grow or not? I think we’re missing an opportunity if we don’t think of these diseases with the complexity that we know they have. So there was a recent debate in Top Gear journals about four years ago, so whether cancer was the genetic disease or an environmental disease and I don’t think was a complete waste of time or effort. But it should have been pointed out that this time that the genome exists in an environment adapts environmental changes, usually without making changes in its in its own DNA. But that’s one of its program. Girls is that at adaptability. But cancer is a genetic disease. There’s no cancer ever described that does not have genetic mutation, and cancer is attributed to those gene mutations. These could be journalist germline and and then, if it’s not, Regina, tumor suppressor can be a heritable cancer. But there’s also a variety of other genes that predispose people to getting cancer. But all of these things are influenced by risk exposure to smoking radiation. But the science of environmental factors and healthcare has given us a lot of insights and lead to reduced rates of smoking, but in some population less so in lower socioeconomic classes. It’s given us better awareness of connections to diet and exercise to health. But we’re still in the midst of an obesity epidemic. So even though we have all this environmental information, that’s science suffers the same problems as genomic medicine. You can’t change people’s behavior by telling them their risk. You have to integrate that risk assessment into health care directly, and we need to make those connections so epidemiologists and geneticists should be tackling the problem hand in hand, just like the genome adapts to the environmental insults we should. We should be working together to tackle these threats to human health. Of all the tools and all the knowledge that science can muster If we’re gonna ensure a century hell of health for all people. We need to understand environmental threats and how we as humans respond to those insults. One approach or one side of views or unit. Unitary authorities are not the answer. We should be arguing whether scientific we shouldn’t be arguing whether scientific Pepsi or scholarly Coke is better. Better We should be working to combat ignorance and deliver truths about health to the least among us and most powerful around us. It’s our obligation of scientists to deliver truth, the truth about environmental threats, the health, you know, genetically encoded ability to respond to those threats. It’s not about battle to be fought between epidemiologists and geneticists, but rather a mission to inform and deliver education, knowledge and health all people. So I think it’s important to try to balance healthcare among everyone and address the failings of our system. Whether it’s an environmental sciences and and, um, epidemiology or genetics. We need to push society to refine their investments in health care to benefit all people across all socioeconomic classes. We should be fighting this. We shouldn’t be fighting this battle in scientific journals. However, the battle should be in the Legislature, in the board rooms and where the decisions are made as to holly deliver care and how we manage health, just demonizing genomic medicine or one other discipline won’t accomplish the aims we accomplished because it’s the discourse among prominent scientists. That’s important. But if we publish these things that serves to empower the ignorant with ammunition against scientific discovery, we’ve seen it in climate change. Any time there’s a disagreement in science somebody points, look, they disagree that this is important. I think it’s important to look at all of science and look at all sides of the equation, and not just narrowly. We should be critical ball, scientific discoveries, all advances. But we shouldn’t be biased against one area of inquiry.
Nigel, Did you disagree with anything?
I won’t respond specifically because I have a prepared talk, and I couldn’t have known what Chris would say, although I hope in the discussion we will get into a back and forth. So I first like to express my appreciation to Chris Contag, and to Libby Bogdan-Lovis and Leonard Fleck for organizing this discussion and thanks to all of you in the audience for coming and I hope entering into a dialogue with us. The title of this session is will genomic approaches to health redefine illness and disease? And I will interpret the word ‘redefined’ to include the central question for all approaches to health and disease. Namely, will it make a difference to the health of the population? Let me be clear, by the way, that my topic is human genomics, the base of the precision medicine movement. Understanding the general microbial agency disease has clearly been productive in improving public health. The title of this session uses the future tense, but predictions of the future are largely a matter of public relations and fundraising. The extreme promises of the genomic movement, and I will provide examples in a moment, have been very successful in funneling unprecedented amounts of funding towards human genome sciences and at the same time, and this is very important, obscuring those components of biomedical research, and we will talk about these too, that have actually been successful in improving the health of the public. We’re always told to be patient because any moment now, just around the corner, lies a golden age of genomically driven health. But I know that it’s been 66 years, since the Discovery of DNA. 30 years since the founding of the Human Genome Institute. And 16 years since the decoding of human genome. And for many of the predictions of genomic enthusiasts, we are long past the due date. Recognizing this disconnect between promising performance, Michael Joiner, an anesthesiologist and physiologist at the Mayo Clinic and I have been working for some four years with a group of some 30 now now 30 biomedical scientists agree with us, by the way, Greg Fink is one of them, my good buddy, where the claims will agree with us that the current domination with a biomedical research agenda by human genomics and the claims being made for its clinical on precision or personalized medicine represent threats both to the continuation of the public health advances in recent decades and to the biomedical research process itself. Michael and I have both of commentaries and jam and the journal of clinical investigation, and we had a special issue of perspectives and biology and medicine published in 2018 entitled The Precision Medicine Bubble, with 10 articles written by 15 of our group of scientists setting on in detail our case that genomic medicine is not ready to finding health and disease on several different grounds. From the mathematical, the biochemical to the epidemiological to the sociological – I did provide some extra copies. I think they’ve all been gobbled up that’s wonderful. Please read them. They’re also available as download PDFs at the MSU Library, you can download every one of these papers. I’ll concentrate Today’s talk on the subject of just one of the papers of the issue, one that I wrote with Sten Vermont, dean of the Yale School of Public Health. The principal thesis of that paper is that there has been virtually no health benefit from human genomic research, and such small benefits as they have been have been purchased at enormous cost. So I’ll first define public health benefits. A public health benefit is any improvement in mortality or severe morbidity measurable in population data. All the wonderful things that Chris talked about did not include measured changes in the population health. 20 years ago, in 1999 Francis Collins, then director of the National Human Research Institute Genome Research Institute at NIH for the most recent decade, director of NIH predicted in a paper that has been sited nearly 500 times that as results of the human General Project by the year 2010. I think that’s past, isn’t it? A young man could be found to have a gene that quadrupled his risk of getting lung cancer. And knowing this, the young man will give up smoking. That rosy prediction has come up short on two grounds. The first is the genome-wide studies of the past 20 years have not found genes for the common cancers, providing anywhere close to fourfold elevations of risk. Few have found relative risk, even a size one and a half for individual genes. And second, genetic information we know from actual trial data does not generally motivate behavior change. When I first read this paper, I wondered why anyone might be motivated to give up smoking because of a genetic relative risk of four for lung cancer, when the relative risk of at least 20 for smoking itself hadn’t convinced them to ditch the habit. So let me ask the audience, time for its participation – Who knows? Raise your hand if you know of a gene that causes cancer. Yes, BRCA. And just how many people in this room have heard of BRCA as a cause of breast cancer? Anybody not heard of BRCA? No hands up. No, no. Everybody has heard of BRCA. A few facts about BRCA genes, one which you all know about. First, they were discovered well before the Human Genome Project and owed nothing to that effort. Two, 30 years after their discovery, no specific treatment has emerged. Discovery of The gene has not yet lead the understanding of a molecular mechanism that could be interrupted by a drug, maybe in the future, 20-30 years. And third: this gene accounts for 5% of breast cancer in US. 5%. Now, let me ask another question. Who knows of a virus that causes cancer? Human papilloma virus. Who has heard but human papilloma virus can cause cancer. What cancer could it cause? Has everybody heard of that? Does everybody know that human papillomavirus causes cervical cancer? It’s not news to you? Any others? Yes sir. Epstein Barr Virus, Right. Any others? Yes. Hepatitis B. Anybody knew that hepatitis B is a cancer causing virus? Not many. Raise your hand if you’ve not heard that hepatitis B is a cancer causing virus. Lots of you. Very interesting. The human papilloma virus causes cervical cancer, and hepatitis B virus causes primary liver cancer. Let’s contrast the value of these two virus discoveries in Kansas, which some of you know about, with the gene fighting and cancer that you all know of. First, unlike BRCA, the two viruses cause at least 80% of cancers that they’re linked to. And second, unlike BRCA, both discoveries, led to the development of vaccines against infections with these viruses. These vaccines are likely to virtually eradicate these two cancers in people receiving them worldwide, 300,000 women die of cervical cancer each year, and 800,000 people die of primary liver cancer. In Taiwan with hepatitis B vaccine has been offered at birth since the 1980s. The instance of liver cancer is 75% less unvaccinated children and young adults in the incidents and people of the same age before the immunization program. That’s what I mean by public health benefit. To further illustrate how a genomic agenda tends to crowd out everything else in biomedicine – In the same 1999 paper, from which I quoted Francis, Collins said. Since the 1970s, nearly all avenues of biomedical research have led to the gene. I want to repeat that. Since the 1970s, nearly all avenues of biomedical research have led to the gene. What has happened in the past nearly half century since 1970 while biomedical researchers have been so utterly preoccupied with the gene. It sounds like from Chris’s discussion, they are very preoccupied with the gene. In 1978 I will remind you smallpox was eradicated. Now, you said sequencing was the greatest technical achievement. A conservative estimate is that this momentous biomedical achievement, in which genomic science played no role, has saved some 10 million lives. Since 1970 age adjusted mortality has dropped so significantly in the US that life expectancy has increased by eight years, from 71 to 79 notwithstanding a disappointing worsening in the last 2 to 3 years, which is very small compared to the overall trend. Most of that improvement is due to the extraordinary decline in mortality from heart disease, which dropped 67% between 1970 and 2017. 7% of you, 7% of you knew this, 42% actually thought it had increased by that. That’s how the real public health is driven out of consciousness by the media and by the genomic enthusiasts. In the same interval stroke mortality dropped 75%. Cancer mortality dropped 23%. If the age adjusted death rate of 1970 had not gone down, we would have had 820,000 more deaths in the U. S. And 2017 than we had. Genetic discoveries did not account for this massive public health advance. Fortunately for the health of the people, not all biomedical scientists were paying heed to Collins when he announced that nearly all avenues of our medical research led to the gene. I’ll give you just a few illustrations, and I could give many more of discoveries that renegade biomedical investigator, because they’re not looking at the gene, have made since 1970, that had led to measurable public health advances, measurable. 1, virtually eradication of vaginal adenocarcinoma in young women after biomedical scientists not working on the human discovered that these cases were virtually old. You two explosions diable still best drawing you know. 2, virtually eradication of reye syndrome after by medical scientists not working on the human genome discovered that these cases were virtually all due to exposure to aspirin. 3, halving of the death rate from sudden infant death syndrome after biomedical scientists not working on the human genome discovered that prone sleeping was a major risk factor of sudden infant death syndrome. What’s wrong with these people? They’re not looking at the genome. substantial reduction in the presence of a major malformation group Neural tube defects After by medical scientists, you can stay with me, not working on the human genome, linked this disorder to lack of folic acid in the maternal diet of time of conception. I’ve been searching intensively in the biomedical interest, any events of measurable reduction in mortality or severe mobility from any human genomic research and the only discovery that I can locate that qualifies. I wonder if anybody would guess this. Anybody want to guess it? What is the real poster child for genetic but really actually effects health? Think of drugs. Think of diseases. No, no, no, that’s That’s not a good example. Gleevec. Who’s heard of Gleevec? The use of the drug Gleevec or imatinib in chronic myeloid leukemia. If anyone can find other examples, I want to know them. Imatinib is a wonder drug. Five year survival from this disease has gone from 50% to 95%. Prior to the invention of imatinib, the U. S. Had some 3000 deaths a year from chronic myeloid leukemia. Now the figures nearer to a 1000. It appears the drug saves some 2000 lives a year. It’s a protein inhibitor. But as some of you know, the history of Philadelphia chromosome, the translocation 9 19 So there was a genetic history to it, course it goes long before the Human Genome Project. That saves 2000 lives a year. That’s what I’m talking about, measurable. But let me to put this in perspective. I just told you that the improvements in health since 1970 are now saving 820,000 lives a year. Imatinib contributes to 2000 of that. That’s about 1/4 of a percent, and that is the most impressive success in human genomics I can find. And then consider the cost of Imatinib. this drug must be taken for the rest of the patient’s life, although it may be possible to stop treatment after 8 to 10 years if all was going well, we’ve nearly $100,000 a year. And even though Ciba-Geigy’s patent has expired, the cost of generic versions of Imatinib are only about 10% less. Thus Imatinib costs at least a $1,000,000 a person to get treatment. Contrast this t one of the examples they gave of a public health advancement. It also saves 2000 lives a year putting babies to sleep on their backs instead of their fronts. No cost in there, not a single penny. this advanced. But in fact, all four of the examples I gave saves lives with virtually no expenditure, trivial expansion funds. Folic acid costs less than a penny a day, retail, much less wholesale. When we look at the actual bent public health benefits of human genomic research that has failed to deliver and contrast them with what has been done by my biomedical science, without any reference to the human genome during what has often been called the genetic era, I conclude that we must be in the grips of a gigantic fantasy. Unprecedented sums of money are now being spent by every NIH agency, by big pharma, by universities, including this one – all in pursuit of the Holy Grail of a promise of health via the human genome. I have sent out that this has not happened so far. But the failure of genomics to improve health is not a result of the inherently slow pace of science. It’s based on first principles. The vast majority of health risk lays in harmful exposures from our environment, not inborn risk. We’ve known this for decades. You cannot solve a problem if the basic theory used to fashion the solution is wrong. As the great British epidemiologist Jeffrey Rose famously said, if causes of incidents can be removed, susceptibility ceases to matter. Biomedical research is a zero sum game, every dollar invested in genomic research that fails to deliver is a dollar not invested in research that really matters, that really changes lives, that really improves health. Universities like MSU should re-evaluate their investments in genomic medicine in light of public health realities. If they do so, they will find many, many opportunities to use biomedical science actually improve health. Thank you very much.
Chris, Chris, now, has the three minutes to respond, Nigel has a chance to respond, and then we move on to your questions.
So I would still argue that the technological advance of smallpox vaccine is about 300 years old. It wasn’t in our lifetime. The advance was back then. What was applied in 78 was actually delivering it. But the technological advance was 300 years ago, and we haven’t yet. Really. We took us 300 years to actually deliver it appropriately. So it’s the time thing. The technological advance happened before our lifetime. That was my point. But I’d like to really thank Nigel for pointing out all of the by medical advances that are really amazing in tremendous, because I agree with all of that smallpox vaccine, polio vaccine, all the things that he illuminated. But if you think that there were 10 million Perry Natal blood tests done last year rather than amnio synthesis using a technology that was came right out of the genome, the Human genome project those those human fetuses that were put at risk by am Yes, Auntie Sis, we’re no longer at risk Because the test was done on blood samples, the parents of children with Trisomy 13 21 were notified prior to giving birth to a child with Down syndrome. They could prepare for their child with downstream it all because we can now count genomes that air in the maternal circulation. Um, if you inherit a P 53 mutation from your parents, you are likely to die of cancer by before age 50. When you put when you asked about when Nigel asked about cancer genes and BRCA mutations came up. The 53 mutation, a horrible mutation in a tumor suppressor that leads to many types of cancer, skips P 53 is expressed across the tissues and organs. So this is one of the surprises again out of the Human Genome Project, that there are genes that are repurposed and used across the different whole variety of different organs, tissue cells and biological processes. And that understanding is going to lead to a wealth of information and a benefit for human health. So I like the title of the of the bruising views tonight. Will it affect health care? My argument is yes. Unfortunately, it’s taken so much longer than the 20 years predicted by Francis Collins. And we shouldn’t dwell on one man’s predictions on one man’s expected results. We should look at the opportunities that have been afforded by the genome sequencing and really take advantage of that. And if you think about a 300 fold investment, a fearful return on initial investment in sequencing the human genome, I would argue that we haven’t misspent or dollars taxpayer dollars on that project. Um, I think behavioral changes a shared problem, whether it’s identified as an environmental risk or a genomic risk. It’s gonna be hard to get people to change what they do. Smoking, obesity, all these things that we deal with, whether it’s genetic or environmental. I would argue that we need to know both conditions well. We need to understand the environmental impact that you know, make predisposition if we’re gonna have a benefit and in future, and I, like again will it benefit human medicine in the future, I would guess yes.
Okay, So Chris began with a story, a poignant story about his own family, the risk for lymphoma, Hodgkin’s disease on those families to exist. And maybe we should scream for them. But we still would have to show that that screening improve survival. We haven’t shown that it’s an assumption, but you can prove these things because something’s way we know that screening improves survival, we have very good evidence that that’s prostate cancer, breast cancer, colon cancer. Now let me try and give another cancer scenario. Let’s imagine two women of Japanese ancestry fully Japanese answers. One lives in Japan and the other lives in the United States because her grand parents immigrated to the U. S. Three generations ago. This girl who lives in his woman who lives in the U. S. Has two parents, both also Japanese American. All four for grandparents of Japanese mentions the same gene pool as her second cousin in Japan. The breast cancer rest cancer incidence rate is five times 4 to 5 times higher in the U. S. Than in Japan. So are Japanese American lady who just twist breast cancer risk that you have a cousin in Japan or her neighbor who’s wide black. Whatever. What do you think The answer is us us. So knowing that And this is true of all migration studies for diabetes or hypertension, Cardiovascular disease, eventually all of the current common cancers. They all show this migration effect. Why would you jump onto the gene first? I’m not the environment. Why would you not ask? What is it that this Japanese woman in the U. S is doing about her? Japanese second cousin is not doing or vice occurs, OK, As for smallpox, the evidence actually has anybody had been an undergraduate. Listen to my undergraduate talk, son. Maybe some of you haven’t. I talk every year about the smallpox eradication program to undergraduates, and I point out, and I give the data that by the early 18 thirties, there was evidence in vital data of a reduction in small box sets, especially in places that used them. The German states, smallpox vaccination routinely and actually mandated it. Austria didn’t. You can see the differences mortality from smallpox striking already by the mid 19th century, so eradication takes a little while, but you can see improvement pretty quickly. And the examples I just gave you occurred, and I could give you many more. Not to mention the decline in Heart disease were occurring very quickly. Framingham established the risk factors for heart disease in the fifties. You really start to see within 2025 years since the beginning of the decline, which is largely due to the identification of those risk factors, particularly the cessation of smoking only A few percen, no zero thought that smoking was a great dance, but I would argue that of those five items smoking, cessation of smoking man save the most lives, even over immunizations in the 20th century, even over immunizations. It’s really astonishing how much money. But I think that was the single largest impact on the heart disease decline, which was going from an era when 60-75% of men smoke 1950 to 20% now. That’s huge, particularly effects on early heart disease. So, um, let me know synthesis another very good example. But again, how many feel deaths have we preserved? Have every safe from this? It’s a nice it’s nice to improve technology, but there was always screening to make sure amniocentesis was only done in some women because of, you know, nickel fold and those measurements of many other compounds to selectively do amniocentesis. Doesn’t feel that many kids, you know? I mean, so yeah, it’s a nice advance, but it’s again. It’s not earth shaking and we don’t see- I would ask you to show me a mortality change as the result of it, you know, and this is kind of thing we have to deal with.
With that we have to wrap things up as far as a formal program is concerned. Join me in thanking our speakers for a very provocative presentation. Thank you.