Harvard Book Store; WGBH Forum Network; Drawing the Map of Life: Inside the Human Genome Project

And now I'm very excited to welcome Victor McElheny to Harvard bookstore to discuss his new book drawing a map of life inside the human genome project. Mr. McLean a science writing has appeared in Science magazine the Boston Globe The New York Times and elsewhere. He helped found the Knight Science Journalism fellowships at MIT and he's the author of two previous books insisting on the impossible. And Watson and DNA drawing a map of life tells the story of the human genome project from its early beginnings as an unlikely proposal put forth by a few pioneering geneticists to its completion in 2003. Along the way Mr. McInerney introduces us to the scientists who helped make this incredible accomplishment possible. And he explores the genome project implications for the future. Salon said of the book the widespread impact of genome sequencing is only now beginning to be felt and a new era of genetically informed medicine is just around the corner and Publisher's Weekly called the book clear and illuminating. So please join me in welcoming Victor McElheny. Thank you Mike and thank you all for being here it's wonderful to be here with new

friends and also with other people who've been with me every step of the way. A lot of literary enterprises over the last 20 years although this talk is about genomics and how it may change our perceptions and our lives I suppose we ought to know that this evening is the forty first anniversary of two American space pilots taking the first walk by human beings on the surface of another planetary body the moon. It was tremendous fun to be at Mission Control in Houston that evening as a reporter for The Boston Globe watching a big screen in the auditorium of what is now the Johnson Space Center while Neil Armstrong and Edwin Aldrin explored a silent surface in black and white television. The dusty ground that they walked on resembled the snowy surface of the South Pole where I had been nine years earlier. Covering researchers at work on a continent dedicated by treaty to

science. July 20th 1969 was a fine day in the history of technology and science where our view of the universe we inhabit was enlarged. What an example of the positive side of our civilization. Both before and after the moon walk. I was a science writer covering among many other things the revolution in biology that intensified after the 1953 discovery of the double helix model of DNA. It was hard to imagine any more important aspect of the science that dominates our present. Then the basic research on how a living cell. The fundamental unit of life operates according to the laws of physics and chemistry. Some of the most exciting biology stories that I covered were the discovery in the 1960s of simple systems for turning genes on or off. And in the 1970s the discovery of an enzyme that allowed the copying of DNA is a chemical cousin

RNA into DNA. And the first reports of transferring genes from animals into bacteria. The technique that became known as were common DNA. And gave birth to the biotechnology industry. For the next few minutes I'd like to talk about some of the latest developments concerning that unbelievably elaborate sub microscopic library known as DNA. It appears that DNA arose built billions of years ago perhaps because it was a more stable form for storing genetic information than RNA. The complete Endowment of the DNA in each of our cells constitutes the genome. To cybering the genomes of largely anonymous reference individuals was the subject of the biggest undertaking in the history of biology the Human Genome Project. Its origins achievements and effects are the topics of drawing the map of life. As we've been told endlessly in recent decades DNA has a dual

function. The tactical one of supplying information millisecond by millisecond to operate living cells and the strategic one of transmitting information to the next generation. By the way all these don't often get to talk about a topic that involves every single one of the 10 trillion cells in the bodies of each of his listeners. And of the hundred trillion bacteria that live on and in each of us. I wrote drawing the map of life with the idea that a narrative history of this amazing and exploding project would be more interesting and comprehensible to the general reader than a textbook explanation. I thought the personalities and development of the leaders who carried it out in a single scientific generation let say 15 years would help make the story come alive. Two of the best known genomic leaders James Watson and Craig Venter.

Who gave a book talk in this place some time ago became in 2007 the first named individuals to have their complete genomes posted on the web. Many people know the name of Francis Collins who led the biggest part of the American Human Genome Project from 1993 to 2000 and Aidan now heads the U.S. National Institute of Health. He's had his genome analyzed by rival companies but he hasn't posted his secrets. Also well known as Eric Lander who now directs the brode Institute at MIT and Harvard right here in Cambridge. He spearheaded the move back in 1998 and 1999 match inventors private industry challenge using an advanced sequencer called the prism. Thirty seven hundred Ventre aim to produce the first human genome by going faster than Collins and his nonprofit partners all around the world. But Lander argued successfully that the nonprofit collaborators had to take back the lead. But many others are less

well known. An example is the modest Hamilton Smith who in 1968 discovered that an enzyme that chopped up DNA in a specific way. And opened the door to reading DNA in manageable pieces. He shared the Nobel Prize for this achievement. A lot on the faculty at Johns Hopkins He now works with Craig Venter on making artificial life. There's been some news about that quite quite recently. Another key figure is the quiet Oklahoma not Mike Huckabee or from Leroy hoods lab at Cal Tech. Now a venture capitalist in Palo Alto. After playing a central role in inventing and building the first generation of DNA sequencing robots in the 1980s a hunter killer galvanized the relentless incremental tweaking of those early machines that made them indispensable. For the first round of genome sequencing.

Biologists learned a lot about the tweaking that is crucial to innovation during the Human Genome Project and they're still learning. A third less well-known genome leader was the witty skeptical chemist. And consensus philosopher Maynard Olson now at the University of Washington who led development of a way to store big pieces of DNA in chromosomes. Yeast or yaks in 1987. Olson told the committee of heavy hitters including Jim Watson that cut the deal for the genome project that the job would be much harder to do than they expected. Anything simpler wouldn't be worth doing. Also it also was the one who wrote in 1995 that the time had come to start sequencing in a big way with existing technology. And in 1998 he told Congress they couldn't gamble on just leaving the human genome to better. He said all I had to go on was a press conference.

But it took seven years of research and interviews and many hours listening to presentations by the genome researchers to learn enough to tell this big and complicated story. The first part of the book embraces the much covered big race to get the initial draft human sequences back in 2000. They were one of them was put on the Web almost immediately and then a more finished version was produced three years later. Although the two projects assembled their drafts within a few days of each other. In a kind of tie. That was celebrated at the White House. The nonprofit project won a great victory. Now everyone takes for granted. At Bermuda in 1960 in 1906 the leaders vowed to post the data for free on the web each night. As a result the strings of GS and season tees and days that make up the code of DNA cannot be patented

are open to science for ever. But the meaning of an achievement only becomes clear as its results are used. That's why the second part of this book summarizes the technological and intellectual explosion that has been going on in the last 10 years with a lot less coverage than before 2000. As scientists exploited and refined the battery of tools that they built they ran into a blizzard of surprises which for a scientist is joy. Settled ideas of the nature of the gene are changing profoundly. Researchers keep discovering more and more micro our own eyes that exert fine control over the expression of those genes. Ambitious and expensive studies involving tens of thousands of volunteers. All around the world citizens of a genomic age have uncovered a host of genetic factors linked if modest way to common human diseases. There is intense pressure to demonstrate the practical utility of

genomics and some of its techniques and insights are beginning to enter medical diagnosis to help guide treatments especially cancer. Drawing a map of life makes a simple case. But a new scientific and technological force has been loosed in the world that we have to understand if we want to be more than passive bystanders. This new force is called genomics. This inquiry into the complete endowment of DNA carried by every cell in our bodies is enabled by an astonishing array of new tools produced by fast growing swarm of small and big companies that have emerged alongside the Human Genome Project. The tools include machines to amplify DNA. The pc our invention that made quirky Kerry most famous and the sequencers that spell out the billions of units of DNA in order in the past five

years a second far faster generation of sequencers has taken over the market a market on a third even faster generation is emerging. Also very widely used. Are the so-called DNA chips or micro arrays invented in academia and industry around 1995. It's not terribly long ago that can sample your DNA at many points at first thousands them hundreds of thousands now millions. The chips provide a tremendous shortcut in revealing the millions of slight differences in DNA that make one person more or less at risk for the disease. Crucial to storing analyzing and displaying the cataract information from these machines are faster and faster computers an ever evolving software. The hardware and the programs have been revolutionizing business and daily life over the last few decades

have also revolutionized biology. One result of the partnership between genomic machines and computers has been a reduction in the last 10 years of more than ten thousand fold in the price of decipher in the whole human DNA sequence. This firestorm of innovation is expected to cut the price tenfold again in the next few years. The combined capability of these devices is moving so fast that we seem to be only a few years away from complete human DNA sequences complete genomes for the cost of a CAT scan. All of us can expect to know a lot more about our genetic makeup in the years ahead. The process will be a new and taxing form of adulthood. The story is as big an event in the in the history of technology as it is in the history of science. As in fields like astronomy or physics there's a constant

tension between discoveries and hypotheses. The new capabilities the telescopes or the particle accelerators or computers or enzymes for cutting up DNA often appear first making it possible to probe new systems of greater complexity than before. And biology is complex. And recent years despite a good deal of hype and a lot of worry about whether people can deal with information about their genomes. It's become clear that the new techniques and ideas are revolutionizing how biological questions are framed. It's also clear that this tidal wave in biology reaches far beyond our future health to our agriculture our energy and our environment. Gentlemen it is not only likely to affect our ability to control costs of medical care by preventing disease focusing treatments more accurately and developing more drugs it is also central central to the continued tailoring of plants to

grow more food on fewer acres for more people with less environmental damage. In addition increased you know acknowledge is crucial to harnessing plants microbes. Not only to produce renewable energy but also to help clean up polluted environments. No wonder that this genomic enterprise both private and public involves thousands of scientists across the world and billions of dollars every year. There's little question that applications of genomics will reinforce some controversial social changes in medicine agriculture energy and environmental protection. Patients who know much more about the genetic and other factors that affect their health will demand that their medical care system make fewer mistakes. Indeed the need for effective use of genetic genomic information by both patients and medical professionals could very well put pressure on the American medical system to be more like those of other

wealthy nations that cost only two thirds of much. In agriculture prejudices against genetically modified crops will have to be of banned and. And new methods of harnessing renewable sources of energy will challenge the environment and the existing array of massive energy companies. The force of genomics is a new element in our lives but it is not alien or unfamiliar. It is a fresh aspect of the industrial civilization that we depend upon for our survival. It rises out of some hundred and fifty years of astonishing advances in biology medicine sanitation and agriculture which picked up momentum in the 1840s 50s and 60s. Just when the railroad and the telegraph from the steam ship were spreading across the planet. People learned how to anesthetize surgery patients. Learning that infection rises from the world of microbes. They tightened the sanitary discipline

of operating rooms on hospital wards. Well big cities began to draw fresh water from a distance and agricultural experiment stations were created to breed plants and animals in an organized way the central role of microbes in the fermentation of bread beer wine and cheese of wonderful Cortef were discovered DNA itself was discovered in 1869 the year that you imagined a journey to the moon from a launch facility in Florida. This was only a decade after Darwin published The Origin of Species in just four years after Mendel reported the rules of inheritance he had worked out in his garden. And but no. As we see all the time today the unfolding of new nineteenth century technology went maddeningly fast and slow. In the early 1880s for example just as mechanical refrigeration and Central Station electric power were taking hold. The microbes responsible for

tuberculosis was identified. But a widely usable vaccine for TB did not appear until the 1920s. And I saw nigh as it. Which attacks the micro directly. Did not clear TB sanatoriums until the 1940s and 50s. Meanwhile however massive drives for greater cleanliness and daily life took hold screens on Windows indoor toilets running hot water central heating food processed in sterile conditions vitamins to supplement diets many of these walled people off from infection even before the source of the infection was fully understood. Along the way our standards for educated doctors and nurses were raised and new medicines and surgical techniques went into wide use ethical dilemmas presented themselves again and again. Who would be told the magical facts and when. Who would receive treatment when resources were limited. The same classical issues beset the

applications today and in the future of genomics. But as in the previous revolutions in Applied Biology The pace has not slowed down the enterprise has not ceased to grow. This makes it hard for me to share in the comments that so many have made in the last month. As people observed it if not celebrated the 10th anniversary of the first human genomes. I think a great deal of change is happening. And the prospect for a lot more soon is strong. As we move toward the question period I'd like to mention a recent illustration of our increasingly genomic Europe. It involves the birth of genetic diagnosis based on sequencing with a new steadily cheaper machines. All of a person's genes or even an entire genome. The story became public last fall. In 2008 a Turkish family underwent tragedy and anxiety. The parents were first cousins. And one set of grandparents was first cousins also.

Such consequently is often associated with so-called recess of diseases caused by a mutation that is inherited from both parents. After two spontaneous abortions the couple had twins born prematurely after only 30 weeks of pregnancy. Only four days after being born the little girl died. Her brother lived but did not thrive. At 5 months of age he was seriously dehydrated. His doctors were divided about the diagnosis. Was it a disease of the kidney. Such as the rare Barger syndrome or of the gastrointestinal tract. The boy urgently needed treatment but what treatment. The doctors in Turkey set off by air a sample of the boy's blood. To Professor Richard Lifton at Yale whose famous work on the genetics of cardiovascular disease gave him much experience of the salt handling machinery that affects blood pressure and related heart

disease. Lipton also is an enthusiast for using the latest tools of genetics to track down the genetic sources of disease. Deciding to sequence the boy's DNA Lifton and his colleagues streamlined the process by capturing only 1 percent of DNA that carries the blueprints for the body's proteins. What we used to call genes and which we're now worried about this DNA about 34 million of those A's and T's and G's and C's make up what is called the X ohm. The x home capturing was done with a DNA chip made by a company called Roche nimble Jan.. Then with the DNA was sequenced on a machine from a company called Illumina in 10 days the cause of the boy's illness was found a single change at a single spot in a single gene. It was congenital chloride diarrhoea not barters syndrome. The diagnosis was confirmed back in Turkey. The boy's treatment changed and

he began recovering. It appears to be the first time a DNA sequencing diagnosed a hitherto unsuspected disease. But it was not the last. Soon became apparent. A researcher in Texas whose complete genome was sequenced on another of these second generation machines found the exact cause of the form of peripheral neuropathy that he had suffered from all his life. It's a disease called Shark o Mari tooth. A family in Utah two parents and their children learn the exact causes of two genetic diseases afflicting the children. Medical centers of begun sending DNA samples of people with genetic diseases to a California company called Complete Genomics which sequence the Utah family a scientist at Stanford inventor of one of the new sequencing machines in the third generation bootleg time on one at Stanford it bought to sequence himself. And

then he turned his genome over to a medical team who published a detailed medical work up in the British journal Lancet. Imagine doing that with your information because a relative who died early from sudden heart failure the doctors advised him to start on an aspirin and a staten. He's hesitating. And Jim Watson who's benefiting from the comparison of his complete sequence with Craig Venter's after starting on a beta blocker for high blood pressure. Watson began falling asleep at the theater. The genomic comparison show that Watson didn't have Venters more normal Caucasian one a one day variant of a drug metabolizing gene called c y p to p 6. Instead with the 10 variant Watson metabolizes the beta blocker much more slowly. So now he takes his pill once a week. Not every day there's a zillion of these but I think we should go to questions.

Your question had to do with tensions between the academia and industry over access to genetic information and those those tensions certainly are real and they will always be there. I think my research has shown at least to me that the amount of cooperation along with the competition and the tension amount of cooperation is simply enormous and the academic people would not be able to do their work without the machines that are coming out of industry as a separate issue from patents but as the machines are in constant development there is a constant conversation between very very exited and hard nosed laboratories and the commercial companies that are providing them with the equipment. So the researchers can't operate without the equipment. On the other hand the companies can't sell it unless it passes muster in

some very tough interactions with scientists. So it goes it goes both ways. It's exactly like the Russians and the Americans cooperating by competing in space. As far as patents are concerned there there's been a huge issue all the way along about what's patentable in this field there are thousands of genetic patents that have been issued ever since the United States Supreme Court ruled that a microorganism that had been genetically altered was a patentable object in 1980. So there's the U.S. Patent and Trademark Office has a lot of work to do on these. There is a central issue which came up strongly in the early 90s which is whether the whether the DNA sequence is itself an invention on the whole that's been ruled. No. The the NIH actually decided to try to apply

for some patents on one form of DNA sequence. They were told by the patent office that this was not patentable and they eventually withdrew that request. More recently as some of you may have heard a judge sitting in New York a federal judge has ruled that the patents on which the genetic tests for breast cancer are sold by Myriad Genetics in Salt Lake City are not valid. That is certainly going to be argued pretty pretty strongly. So I think these sorts of issues about intellectual property and so on are very salient somewhat confusing. But they haven't stopped. The enterprise. Well clearly the whole subject of Alyssa ancestry where did we come. Are we actually members of a particular Native American tribe by inheritance or or not. These are actually quite concrete and difficult issues for for people this type of information is becoming

available. So you have some personal problems of that kind. On the other hand we are also in the middle and I don't want to take a Pollyanna view of this but we are in the middle of a period of learning about the human past that is totally extraordinary we are getting a much more concrete picture from the study of human genetic material of where people came from and where genetic variability is greatest which is in Africa where we came from and try to follow our migrations across the surface of the earth it is a magnificent story and many of the details that we never knew before which are also of course details that show the linkages between us how close we are to each other. That's a kind of contrary. Cultural trend that I think is going on so there is a rather strong benign aspect of

understanding human variation as well as some concerns that people will be able to peg you or identify you or direct your schooling or things like that. We have very little evidence so far that that kind of selection. Is is going on but it certainly is an issue that is on the table and that that's part of that adulthood that I was talking about. Now the question had to do with the dark side that I may have encountered during my researches and it's clear that there is always a dark side with any kind of knowledge about the human body or about human illness the the difficulties that are faced by someone who now receives some information about a propensity for a disease or whatever. That's a shock. That's something that some people don't want to deal with or won't be able to deal with. This type of disclosure to people has been there from the very beginning of an organized way of trying

to deal with human illness so that although I think the dark side is there it is a dark side that we are living before we ever get to genomics. And I think people have to understand that that there's a whole. Set of problems having to do with respect for people and respect for how they feel about things and we need to learn as much as we can about how to tell people about information whether we should tell them. There's a lot of disputes about this. A good deal of the research that presently goes on about which is trying to find genes by studying thousands and thousands of people those people don't get their own personal results back. And the reason that they don't is to preserve their anonymity on their privacy. So there's a genuine concern about that. On the other hand you have the ethical issue of something may come up in a study like that an incidental finding of something really serious that the person could really do something

about and needs to be warned about. So there's a very lively debate about issues like that of when is it ethical to communicate the information and when is it ethical to withhold it. But it is not an issue unfamiliar to the medical profession or to us patients. The question has to do with whether there is a genetic aspect to behavior on a moment by moment basis. I I really I don't know the answer to that this moment by moment basis that I'm talking about is really a sort of textbook kind of thing. The cell has a lot of genes in it that are turned off. But it has thousands of them that are on and what that means is that they can be copied to make a protein to do a job like to digest the sugar or to make another protein or to chop up another protein whatever. You have thousands of these jobs in any living

cell. All the 10 trillion that you you have so that the DNA is this stacks of a library and you have really fast runners that are going in there and grabbing a piece of information that is needed the signal that is needed. Very typically is something which touches the outside of the cell and sends through a cascade of minor alterations a signal to the center of the cell the stacks the library. Turn that gene on we need a few of those. So that's what I meant by the tactical thing the strategic thing is to make an accurate copy of the whole thing. So that then the cell can divide into two daughters. And so that a large creature on a lawn aeration like us can reproduce can transmit accurately to offspring. So that's why I use the terms tactical and strategic. Well actually if you look

in my book this is not necessarily a totally honest answer but if you look in my book you're going to see the pictures of several women who are indeed in leadership positions. We can think of the Genome Sequencing Center in St. Louis where. We have. Elaine Martis as one of the central figures there and we can look at the center a similar very big sort of semi industrial place in Houston at the Baylor College of Medicine. There you have a figure like Don I must name who's now and both of these people's names appear on the papers because they the work that they do is crucial to the outcome. I think my own experience in going to meetings of the genomic crowd who get together for conclave a lot of the time is one at a Cold Spring Harbor in May. Women are extremely strongly represented in there. One of the leaders of the human micro

biome project that is. Building up right now is clear Fraser Liggett who runs a special center for Genomics at the University of Maryland Medical School in Baltimore. So there I think there are a large number of examples I think that the number the role of women in the genomic enterprise is increasing probably pretty rapidly. Yes there's been a great many projects. It was an impulsive but very important decision by James Watson who was the first director of the biggest part of America's genome effort when he became director. He announced sort of out of the blue that a percentage of the money they came from Congress to do the project would go for ethical legal social implications of the work I think he understood totally that unless that was part of a program that the program would

not thrive. That Congress which is the patron. Would require that these issues be looked at. These issues continue to be looked at. Just late last month I think it was the full House Energy and Commerce Committee which supervises health matters among other things held a really full dress hearing about the potential risks and problems of creating an artificial microbe. So essentially the issue that you raise is like a Greek chorus all the way along with genomic work that you have to keep thinking about the ethical issues of whether people are going to be able to deal with the information whether we are going to harm people with information that they get. Are we as another question here was talking about. Are we going to destroy people's sense of identity or to categorize them or whatever those issues remain there. They have been part of

the program from that day to this. And they are constantly part of the discussion. You have other issues that are a little different from the same moral ones or ethical ones. You have a lot of practical issues that also have to be considered and one of them is simply the level of information that we have and that our doctors and our nurses have. About these matters. Supposing we learned something from a test and we went and spoke to the doctor about that. How much education does the doctor actually have to discuss that with you. How much education does the nurse who is a crucial figure have about genetic matters. So you do have some practical questions that go right along side the flip side the philosophical ones. But it's clear that the work cannot be conducted without thinking about these things and that people are constantly brought to think about them again and again as the capabilities

grow larger. This meeting that I spoke of that happens at Cold Spring Harbor every year in May always has a session on the ethical legal social implications of genomic work and I've attended several of the sessions and they're extremely interesting and I think they have an influence on the way people do their work and the way people funded. We had a question about tools first hypotheses or ideas. Second I have a quote in the beginning of the book from Sidney Brenner about how progress in sciences is measured by techniques and discoveries and ideas probably in that order which was a clever remark by Dr. Reiner. I think that the way people in the field are looking at it now is that they want to stretch and they see very good prospects of stretching the capabilities of the machines that they have. You used to at the beginning of the Human Genome

Project have a lot of discussion among the scientists that we can't do this sequence thing until you know the until the second coming of Christ because it's so hard and we're going to need a whole new generation of machines and the very machines they were talking about of course now exist and dominate the market. These machines are appearing in new incarnations on the order of about once a year and the chemicals that are used in them are also evolving and the methods of analysis of the data are evolving. I think everybody is kind of holding their head at the Cataract of information. They think that the biggest challenges are going to be in software to analyze these floods of information because if you think there's a flood of information now there is going to be a much bigger flood of information. When a medical center makes

sequencing part of its normal process of handling difficult cases that which is essentially only a few years off so we're going to be looking at multiplication and multiplication and multiplication of the data at the same time you want the machines to be cheaper. That is they're there they're workings to be cheaper. And so people are pushing. And you have this incredible competitive already of second generation machines and third generation machines all being developed at the same time. It's for Roche This is the fiery furnace of creative destruction or whatever you want to call it is it's going on at an enormous pace or rather faster than it has ever been seen in the history of technology many people think. So you people are driving like crazy for machines that can do it faster and cheaper and better and more accurately analyze the data better. So I don't think that they are now thinking in terms of some.

Fairy Land machine that you have to have in order to make this good for people. I think it's the let's stretch the capabilities that we have which is an itself an enormous task. So the question has to do with whether there is a link between the genome and intelligence. And I think that people are convinced that there is. I think that the present focus is if we were talking about in some sense about neurophysiology or the structure operations development disordering collapse or whatever of the brain we have a lot of we have a lot of things that to worry about that have a genetic component. But you think yeah I think a lot of the thinking is rather specific that is can we understand the genetic background of let's say Alzheimer's disease or what is a good genetic description of autism.

There's a lot of the scientists are actually thinking in a less I guess universal way that then your question would have them do their focus on specific problems of neural physiology neurodegenerative disease. And they are finding links. That's not quite the same thing as intelligence which is I think a lot of us would agree is somewhat plastic culture driven concept. So I think it has to be the latter that is I think it has to be available to the poor we obviously are. There has been the ideal in medical care always that it is supposed to be available regardless of your ability to pay. And we all know that all medical systems rationed by price. Even the most efficient ones which are on the other side of the Atlantic. But we

we certainly have a system in which there is a good deal of rationing by price. On the other hand you also have a system that is fighting that all the time where they're trying to be income blind in the provision of care. There's a lot of medical sociology that that goes along with that. One part of your question touches on the nature of the support for a field like biology or agricultural research. This is a commons. This is something where a lot of this research is not of the sort that private industry could sponsor. Because it's so far away from profitability. So that you you in the field of agriculture and the field of biology and medicine you look to the state to provide the crucial support. On the other hand a lot of this is of supply the support from the state and that means

individual members of Congress who ask very tough questions and who question hearings about their disease. OK. I mean you you can look at the transcript it's unbelievable you'll have members of the committee who say now what about this disease. What about that disease. So you have a lot of interest and those people are the patrons they're the people who've signed to write the check much more than evanescent people like like presidents. So they care about this they are supplying the support for it because private industry isn't going to supply it. However there is another aspect which is that a lot of times the money that is needed for what you might call transformative studies something a little risky something that isn't quite such a sure thing. Quite a lot of the money for that comes from very rich people. It comes from philanthropists that comes from Ely and it is brode or people like that are Bill Gates and Melinda Gates. A lot of this money for the

really risky stuff is given by private individuals who have been enriched by our economic system. In a way that you might not totally be comfortable with. But there they are and the Real Estate of Los Angeles has turned into one of the world's most important biomedical research institutions. So there's a there are a lot of subtleties here but there are a lot of forces that say this is supposed to be used for the benefit of all. And a perfect example is that the work of the Gates Foundation which is pushing to make all kinds of sort of workaday preventive preventive medicine steps of Able to people who can't pay for them. Well we've been living with the way this is has to do with whether we're moving toward a new generation of eugenics of the sort that sprang up in the early part of the 20th century at about the same time as the science of genetics was taking form. And I think people

are very concerned about the risk of that in all of my contacts with biologists over the last 45 to 50 years. They don't want to live the scenario of a brave new world they don't want to have a factory that makes Alpha babies and Delta babies and lots and lots of Delta babies to run the factories and so on. Those motivations I don't find in the people who lead this leave this field. So I think that brings us to the end of our question and answer period. And thank you very much.