Focus 580; Sequencing the Human Genome

Good morning. Welcome to focus 580. This is our telephone talk program My name's David Inge. Glad to have you with us this morning. In this part of focus 580 we will try to explore some territory that actually we've been over before but I think it's worth re exploring because for people who aren't scientists I think it's difficult and it's worth trying to talk about and think about because if you look at the history of medical discoveries what we're talking about here may well be the biggest maybe the most important medical research project that's ever been undertaken and we're talking about here is mapping and really understanding the human genetic material that thing that so often referred to as the blueprint for all of us DNA. Our guest this morning is Dr. Eric Greene. He works at the National Institutes of Health in Washington. He's chief of the senior investigator in chief of the genome technology branch. He's also director of the NIH intramural Sequencing Center and he's a bit involved in this research doing it and watching it and thinking about it for quite a long time. He's been at NIH since

1994 and before that did medical research at Washington University in St. Louis where he got his Ph.D. He is both an M.D. and Ph.D. doctor and he's here visiting the campus to give a talk yesterday will be doing some other things. This is all part of an initiative looking at the new biology that's being sponsored by the Center for Advanced Study on the campus there. Among other things is the organization that's responsible for the Miller comm series and we've had a lot of those folks on the program in fact we have a couple this week. This is something a little bit different. A program that involves some talks and some visitors this semester and next semester and we will have a number of them here on the program so for people outside of Champaign Urbana you'll have the opportunity to hear from them as we talk this morning with Eric Green. Your question certainly are welcome. All you need to do to be part of the conversation is pick up the telephone and dial the number here in Champaign Urbana 3 3 3 9

4 5 5. We also have toll free line that's good anywhere that you can hear us 800 to 2 2 9 4 5 5 so any point here if you have questions you're welcome to call. While we ask people if they just try to be brief just so we can keep things moving along while anybody can join the conversation. Three three three W I L L toll free 800 1:58 W while. Well thanks very much. My pleasure to be here. Appreciate it. If I may all ask a question like this to start if we go back to. Watson and Crick the guys who discovered DNA this was I that was 1940. Well they discovered the structure of DNA identified the structure of DNA at its height so I guess we had the. What I'm thinking about is at that point what it was we knew. So I guess we knew that there was this stuff and this was this determined what we what we are what we look like. And all of that and we knew we knew what it looked like it was this twisted helix structure. Yeah. People maybe you know they've seen pictures of it they were kind of had this idea what it looks like.

But it passed that point about it how much did we really know we didn't know a whole lot but the inside of the structure paved the way to understanding that it was the DNA that transmitted the genetic information from one generation to another or from one cell to another. This was the package this was the material that encoded all the necessary elements of life. And up until that point there was some confusion there was some debate. But once they understood the structure of DNA it became very clear how all of this fit together and how it was that the degenerate genetic material was fundamentally encoded in this chemical called DNA. And so here here let me ask a basic dumb person on the street question then. The the relationship between genes and DNA. So DNA is simply the material. That is consists basically consists of four different chemicals one starts with one starts with a one starts with the one starts with C that's why you always hear DNA represented in G's A's T's and C's and

it's basically information content coded in the order of those letters across a stretch of DNA and the human genome for example we all have our genetic blueprint that consists of about three billion of these letters in a very precise order in certain parts of that order are certain words and those words of the genes those are the things that actually make something so imbedded in this long long string of letters is information and some of that information or actual genes that actually encode for something that makes for example a protein. And the genes live on the chromosomes so chromosomes. I like to think of the chromosomes as sort of the suitcases that carry the DNA from one generation to the other they are the structures that how is our DNA protect the DNA take care of it and make sure that when cells divide all the DNA gets a properly sorted so that each new cell gets an appropriate set of blueprints and same applies when you go from one generation to the next and that's what

chromosomes are. Right and then in every every cell that has a nucleus has chromosomes. In it yes. Certainly that's OK and that's all there and that's why you can sample different kinds of things you can have skin you can have blood you can get different kinds of body tissue and extract from that the DNA. And that's why you get is you can take that and you can tell where who what person did this come from because that's in. That's right and in fact your skin cells carry the same DNA as your brain cells as as your hair so all of that is the same DNA and an absolute it's very specific to each individual. OK. So then then going back to to what we knew before we actually started to look at the need DNA to sort of take it apart to try to look at what the various The pieces were that we knew that this was the this was the code for a human being or for other sorts of creatures too. We knew that it was incredibly complex. The question

was then well how exactly does it how is it made up and how does it do than what it. What it goes on to do well and in fact the last thing you said is really the next phase I mean one thing we did know in the case of the human genome is that we had to order 3 billion bases. We are there and they're in order. We need to determine what the order was and we needed to understand then as a starting framework to go in and actually attempt to read that sequence once we determine exactly what the order of all these letters are starting at 1 and ending at 3 billion or so. OK so there the very first step is you mention the fact that there are these. It's this long line of these four letters as I actually look at that way so the very first thing that you had to do before anything else you went had to be able to say well this is the order in which the letters come. And just just add just that much. And here here's a metaphor that I really like to use because I think it is actually fairly accurate it's relatively easy to digest and it incorporates what you mention about chromosomes.

Basically what our chromosomes are encyclopedia volumes from one end to the other just as from page 1 to the last page of a given Encyclopedia volume are the series of letters and every one of our chromosomes has something on the order of one hundred fifty million of these letters and we have twenty four encyclopedia volumes we have twenty four chromosomes one through twenty two x and y. And what the genome project of sensually attempted to do was to take each volume one to time and determine the precise order of the bases the G's the A's the T's and the C S from the very beginning of that volume from the very beginning of the chromosome to the very end. And essentially we are well on our way towards having that finished there's still some more work to be done but we have a fundamentally organized each of the twenty four volumes. They're all set we know most of the letters we know most of the order of all those letters and we are entering a new exciting phase we want to start opening up those volumes and reading it and now interpret it having not organized this it seems that that in the way that lay people talk about this

we may be using terms that to us. It seemed to be the same thing but to scientists mean something different. And this is so we talk about mapping sequencing and interpret ing. Yes those not to you to me that that might seem sort of to be the same thing but to you and other people who do this work. We're talking about three very different things. So let me let me tell you what each of those things are mapping was getting these volumes organized one page after the other. This was done by laboratory work the details aren't important but you put your book together sequencing was actually opening up that book and reading the letters one at a time figuring out what the first letter was to the three billion flat or was that was sequencing interpreted as like a great novel a great Hemingway novel. You may read it you may have a lot of people read it but it takes many many years of careful scholarly work before you can fully interpret what it means. That is the phase we are just entering into now is the interpretive phase.

And that's if we because now again a lot of the reporting on the issue has been what it is we think when we have accomplished that work what it is we think that we can we can do with it we talk about genetic medicine. But to get to that point we have to have the interpreter the interpretation done so that then we can not only say this is this is how all this information is ordered. This is what it looks like. That is still a step from that to say now I can tell you what this what a prick with this. If we look at particular sections I could tell you what that section does. We're still not at that point. Well we are in a very limited way. Maybe we understand this sentence here we understand that paragraph there maybe we even understand this page in this volume but we do not understand a small fraction of what we have ahead of us. But it's as if we've walked into a room which we've been grappling around with for a long time in the dark and all of a sudden somebody threw a light on and all of a sudden it's very complicated room and a lot of exciting things to go explore. But at least the light is not at least you have the tool to fundamentally now

start to ask much more sophisticated questions than you could previously. Our guest this morning in this part of focus 580 is Dr. Erik Greene from the National Human Genome Research Institute. He is chief of the genome technology branch and director of the NIH intramural Sequencing Center and he's here visiting the campus to talk with people here about the kind of work that he's been involved in and where things stand in this very very large and complex research effort of coming to understand human genetic material what it is and how it works. And that's what we're trying to do here this morning talk about some of the basics and your questions of course are welcome 3 3 3 W I L or 9 5 5 and I think I goofed up at that 3 3 3 9 4 5 5. I hope that's right. I've only done it about a half a billion times 333 W. while toll free 800 to 2 2. My mind can only hold so many complicated things at one time. So when when there was a big win in June of last year

there was this big big announcement huge press conference. That was when President Clinton was still there. We had the guys who were the leaders of both the private sector and the public efforts there. A great big thing got lots of news coverage on the front page of all the the newspapers from that coverage I suppose a casual observer would have thought well that we're announcing the fact that we're done. Correct. You know but that's really not quite right when when that. That announcement was made that press conference was held. What was it that they were celebrating at that point. They were celebrating a spectacular milestone. But we really have to emphasize it was a milestone. Essentially what was being announced at that point was the fact that the genome project had successfully derived a crude but fairly fairly useful and comprehensive draft sequence of about 90 percent of the genome by that I mean that for all these encyclopedia volumes we had filled about

90 percent of the pages with fairly accurate sequence that wasn't perfect. Think of it like a rough draft of a paper you may be writing that maybe there was a typographical error here or there. And maybe there was some bad grammar and maybe there we even missing a sentence a couple of places but fundamentally we had a pretty good idea of What About 90 percent of our genetic blueprint look like. And that was a you know considering how quick this happened considering all of it was way ahead of schedule as it had been originally outlined for this program. It was exciting and importantly the other thing being announced was that all of this information all of this new insight into our genetic blueprint was all available on the Internet and that scientists already were taking advantage of it even before it was truly finished to perfection a level of type quality which is what we're working on now. But this was exciting and that's what heralded that big announcement in June of 2000. Now there was also then this year and February of this year there was another. Sort of big announcement and the big announcement then was to announce that scientists had

done what academic scientists typically do is that in June of 2000 the announcement was Hey all this has been accomplished and it's all out there on the Internet for anyone to look at. Then all these scientists went back to the laboratory and back to the computer labs and they spent the next six or so months starting to analyze this data trying to start to do the first pass interpretation of what is it that our genetic blueprint actually looks like and then they did what scientists do. They wrote some very significant papers that were published in very prominent journals Nature and Science and those journals then published these huge landmark papers in February of this year and so there was another big announcement saying not only we accomplish that we've now you know sort of published it and put it into the permanent literature archives which is very important very symbolic for science. One of the things that I know I'm sure that many scientists are pleased about and people who are interested in having access to this information is that the process that we've talked about is going more quickly than at one point we thought that it would. It

seems that various points along the way the the target date the date at which we thought important things would important milestones would be hit continue to get closer. You know all that is at one point we thought it would take until 2005 you know and now we're saying well maybe it will be done two thousand and three totally do you know. And I know that here too to fully answer this question one would have to get into the technology the technique that maybe would be more complicated than you can do on the radio but I guess I'm wondering if you can talk a little bit about what it is that happened that has allowed the process to speed up as we have gone along. I think this could best be summarized by just really emphasizing to you that the goal that was set out for the Genome Project captivated so many people's interest even beyond biomedical science. It got engineers interested it got computer scientists interested it got physicists and chemists people were very fundamentally exciting.

It's all how exciting all of this was going to be and really brought to bear people that otherwise weren't doing genetics were doing molecular biology. Their contributions in technology in computer science in physics than in physics in chemistry really resulted in some tremendous advances in instrumentation and the kind of tools that were necessary for doing DNA sequencing and doing the kind of manipulation we needed to do in order to accomplish this goal. And that just Year after year resulted in accelerations that proved to end up resulting in a product that came in much thinner than any of us really anticipated in our wildest dreams. And I guess as I understand it the what has happened is that the process has largely been automated so that it's something that can be done. You create equipment. You put it together with computers and that those the machines essentially do the work. It's very industrial process of large scale sequencing whether it be the sequencing the human genome or other genomes has now been reduced to practice so that the

laboratories doing this look much more like manufacturing plants than they do classic biology laboratories. There are two there have been two major sort of parts to this effort. There is a publicly funded effort that has involved you and other scientists like you and National Institute of Health and people like that and then there has been a private sector. Effort. And it's this company celeb genomics Greg Venter's company has been involved in that. How how exactly did that happen I mean how is it that we ended up with the public and the private efforts working kind of working side by side. It's actually fair to go back actually to the beginning of the genome project. Even in the planning phases in the late 1980s a lot of people thought the genome project was a bad idea because nobody would be interested in what it would produce. And ironically as soon as the Genome Project began there were lots of companies that started

creeping up even long before is still there that thought that they could do things to complement what the public Genome Project was doing and potentially be able to develop products to be able to sell subscription rights to look at new data and so forth and Solera was just sort of one of many such companies and Salerno was basically started by the company that had developed the latest and newest and greatest DNA sequencing instrument. And their idea was instead of just selling instruments maybe we should get into the business of also sequencing and maybe we should be trying to sequence the human genome and perhaps sell the ability to look at that data to companies and to academic labs and so forth and so they proceeded to do that. They use a slightly different approach than the public Genome Project did. And in the end I think this end up being that the press picked up on this as being somewhat of a rivalry and and but in fact they had very different agendas. The genome project in the long run is about completing the job they're not worrying about making money they're not worried about developing profits they're not they're

releasing all of their data every single night on the Internet and celerity nomics has a business plan that they want to extend what they're doing into arenas that may eventually be able to build a business around them. Well is are they now charging for access to what they have discovered much of their sequence they you can only access it based on paying them a subscription fee so that there is still there are certain kinds of data now that that's still used if you want it you got to absolutely for it. Absolutely. OK. We have a couple of callers here we get people involved in the conversation. 3 3 3 9 4 5 5 for champagne Urbana folks toll free 800 to 2 2 9 4 5 5. We first go to local color this is someone in Champaign and it's Line 1. They're very exciting speakers. Thank you for being on. We have had an evolution of the cell structure of life the pro-Kerry attic and the you carry attic selves and

one produce just clones of the parents and now we have the male female. The duality here going is are there any theories on how that change occurred from pro-Kerry attic and you carry out excels. You better do you better explain what for the rest of us who don't know you but explain what that means. So I mean the fundamental question the caller is asking is you know you have major classes of organisms pro-Kerry out of organisms are like bacteria. These don't have nuclei and they're much simpler organisms actually their genetic blueprint is much much much smaller. You carry out of organisms are more complex organisms certainly humans are among them but there's many even the common brewers yeast or bread yeast is that you carry out an organism and their genomes are typically bigger and some of them are substantially bigger like the human genome and I think the caller was generally getting at you know what inside are we starting to get.

At a cellular level of what does it take to be a bacteria a pro-Kerry out of was a take to be a you carry out with its more complex cellular machinery and nucleus and many of the things it can do. And it's by far too it's a very good question is by far too broad of a question to try to address in a forum like this I would stress that. One thing I didn't mention I think it is worth emphasizing this really gets to the heart of what the caller is asking is that the the human genome project was given the name human because it sounded good and it was. It captivated people's imagination. But the truth is the project was broader than that and from the beginning actually long before sequencing the human genome project attempted to sequence and did successfully sequenced the genomes of bacteria and of yeast and of the fruit fly and of worms that all this was to develop a framework for being able to compare genetic blueprints to to try to address the fundamental questions the caller is asked of. What is it about a minimal genetic blueprint that results in a bacteria being as simple as it is and then what does it take to enhance that a little to then become a you carry out Excel

and then of course the next question is What does it take to then become a multicellular organism. And then we're interested in then what does it take to become a mammal. Then what does it take to become a primate and then what does it take to become human. This is the heart of what we're getting at I can't give a simple answer I'm not sure we have a simple answer to his question but finally we're starting to get the tools that we need to start to ask and answer those questions by being able to lay out these different genetic blueprints not on the table we do it on the computer and look at them and compare and start to really get great insight into the fundamental basis of what it means to be these different classes of organism. Wonderful thank you. Thanks. I guess as I maybe I missed out of stay in the question but it seems an interesting one but but an awfully large one. And that is that if you if you think that there are if you talk about the fact that there are some organisms that reproduces essentially by making it simply by making copies of themselves and then you have others where you have two individuals and what happens who is whose genetic material is different. And then every time they reproduce it's like shuffling a pack of cards you're getting something that's a little bit.

Yes but you also have organisms that are somewhere in between those two. So this is you know reproduction is just one example of increasing complexity you see as you go to more and more complex organisms. And so I mean you could pick on that as a good example to look into but I could give you lots of other biochemical examples of where you carry out some more complicated than pro-Kerry odds were multicellular organisms that may have a nervous system are more complicated than the East for example which does not. So I guess I'm thinking though that some kind of basic level I guess if you believe in natural selection you would have to think that that shuffling the pack. Would you would potentially give you more advantage than if you were doing a simple more simple kind of thing where every each generation has pretty much the same as the general. Yes but they're picking up genetic variation as they go along. They're doing that as well. All right to Aurora. Why number four. Hello. Yes sorry to say I came in late in the program and maybe some of these questions were answered. Wow. 1. What prompted the beginning of this

project. And that is as it is. Have you had a very surprising find something that has really startled you in this and I'll hang up and listen. Oh well thank you for the question. Two very good question. What originally started this. People could point to a variety of things that really can be traced back you know a number of years especially in the 1900s in particular there was some advocates who thought that if we were ever going to understand cancer for example which fundamentally is a genetic disease that we were just completely in the dark of understanding cancer without having a better understanding of our genetic blueprint. Other people believe just at a fundamental level that if we really don't want to understand lots of aspects of biology that we just needed to once and for all decode genomes in the human genome being being one of them. Department of Energy actually deserves a lot of credit they really spearheaded a lot of these early discussions. They were very interested to understand Taisha And these are genetic changes

that result from energy sources or energy exposures. And so they thought this was very important to try to elucidate the complete sequence of humans and other organisms so that's really at the core of the. But also I think with time people recognize that if we were going to tackle the many diseases that have strong genetic predispositions and causes we really needed to have better tools and those tools had to come in a better understanding of our genetic blueprint. The second question any any big a surprising find there's so many surprising finds even from the friend. There's going to be so many more I can guarantee you. One of the humorous ones that sometimes people like to just sort of mention and this sort of came out from the papers that were published is that a paper published in February of this year is that it looks like humans you mentioned genes genes of the functional units that are the key sentences in our genetic blueprints that actually make something that make a protein. It seems on the surface that humans may only have maybe twice as many genes as the lowly fruit fly. And this was a real ego blow

to mankind and womankind because we clearly were so much more complicated than a fruit fly how can we only have twice as many genes there. Well that and again the issue is that over time people had made guesses here. And again it was based on the idea that the we think we're very complicated in advance so we must be we have tons and tons of genes lots more than than other simpler animals and one of the things we found out was that our estimate was away high was way higher probably although it turns out we probably have even more complicated interest software because even with a only twice as many genes we probably can do funnier and different things with them to get greater functionality out of our genetic blueprint and that's the kind of things we're going to be learning more and more about in the next decade. Well then though as we then do the sequencing and the analysis of simpler. But life forms than us. The laboratory mouse and the fruit fly and single celled organs and so forth. Do we then think that we're going to come to the understanding that in that

there is certain material that is common to all of these are absolutely and as you go along you're taking some basic building blocks and then when you get more complex you're keeping those but you're adding some more stuff and then you're adding some more stuff and you're adding some more that's actually the case and were actually more mixing and matching that's what we're learning that we clearly do is that we share many of the same genes with with yeast in flies and worms and it's we just have ways of using them in slightly more complicated fashion. So then doing the mapping of yeast in flies and worms will not only will it give us an understanding of yeast and flies and worms but that contributes to our understanding of absolutely humans. Absolutely. To Urbana here one number two. Hello. Yes. Hi yeah I was hoping that the speaker could answer a couple questions for me. I was wondering if you could talk about some of the ethical questions that scientists face in doing this research and also some of the potential dangers of the that the technology might produce. And I'm going to hang up and listen. Thank you.

All right. Thank you. Well I appreciate the caller's question is I think it's a good one it gives me a chance to talk about a very important and unique aspect of the genome project really unprecedented for a biomedical research program. Was that from the very beginning from day one the genome project earmarked a portion of its budget that would be solely used for the Study of ethical legal and social implications of the research and the program and this is called the LC program. And there have been all sorts of important studies that have been done and have been and policy programs that have been formulated as a result and the reason for that is exactly what the caller alluded to. This is very powerful technology very powerful tools very powerful infrastructure that has been created. But it is a two edged sword. It's like a lot of important technologies that can be used for such good. But we have to be so cautious as a society to not let it be used for anything bad. And on the one side

of the sword is a nice sharp edge that's going to provide us all new tools for attacking problems in medicine and in human health and human disease. But on the other side of that sort is another sharp edge that for example could be used to discriminate against individuals who have a predisposition to a disease to deny them health insurance to deny them life insurance or deny them a job. And we have to be very careful not to let that happen we need to make sure that good comes out of this and that we have good strong laws in place that will prevent this from being misused and used as a tool for discrimination. And there are the LC program has been very effective and continues to work very hard to try to get good strong laws passed some states have done at the federal government has done some of it. There's better laws that are still needed. And that is exactly something where we really have to make sure that that good comes out of this. People are protected so they learn to appreciate how useful this endeavor was rather than to feel threatened by it. Back in the beginning when this project was proposed. I think that there were

some medical researchers who were concerned that it would that there was only so much money available to do medical research of medical research. And the concern was that this project would be very expensive and would soak up a lot of that money and that as a result there would be less money for research and there were things that maybe were deserving of funding that wouldn't get funded. Has this ended up costing as much as we at one time thought that it would. Well actually it's remarkable it's coming out that the people who planned this who in the nineteen 80s who actually had no idea what major technology developments were going to come to pass. They actually laid out a pretty good plan even cost wise what this would end up requiring and they were pretty much on target and did not require a substantial amount more money. The critics that you mentioned which clearly were quite vocal. In the late 1980s early 1990s. You don't hear from them as much Actually you do hear from many of them many of them have come forth and said you know what we were

wrong that this didn't end up sucking money out. You have to put this in perspective. Our whole Institute the National Human Genome Research Institute in NIH has less than 5 percent of the total and I edged budget and we were supporting the bulk of the genome project work in the United States. Part of it remember is that genome project is not just about the United States it's not just about the NIH the DEA we also contributes to this is an international project and we had major international partners that came onboard and many countries contributed to this and that actually helped substantially and getting the job done in a highly efficient fashion. I don't think in the end this has been detrimental to the funding of research in the States I think it's just the opposite I can tell you that being at the NIH the number of times I've had opportunities to speak with very enthusiastic members of Congress who have really found the genome project to be an exciting thing they can point to as a success story. And it's I think it's really been part of the reason why NIH continues to do well in getting funding. Well as is it the case that as things have gone along that people particularly of laypeople

have. Have picked up an appreciation for what this knowledge will enable us to do once we get to the point that we really have indeed gotten through with the interpretating of the genome so we really understand exactly how it works and then we hear to the point of trying to you know when it's not working correctly trying to do something about it. I think it's the I think we're at a very hard period of time now I think for the general public in particular. There's a lot of new complicated information. You alluded to it at the beginning of the show I mean genetics is complicated and all this new stuff of deciphering the genome is pretty complicated. And yet we're at a phase where we can't point to lots of examples to say oh and this led to this new treatment or this new diagnostic test. I think we're going to have that in a small number of years. I don't think it's going to solve all of our health problems but I think you're going to have and there's even a few examples we can give already I think with time people are going to learn to

appreciate as good examples come forth how this is really going to end up impacting the way medicine is practiced at least for some diseases and I think that it will be much easier to sort of comprehend what has been accomplished. Well we we talked about the fact that again there may be sort of terms that in that lay people would use loosely. And I would talk about mapping and sequencing and interpreting and to the fact point of the fact that for people who do this work we're talking about things that are really different. We also talked about the fact that as time goes along it seems that the goals end up coming closer and closer that is it doesn't take as long as we thought and that so we're thinking that now to complete the sequencing work. Maybe by the spring of 2000 three you know thinking that that will be done. However there is still this other step of inter-breeding and to how how long do we think that will take. I don't think anybody should even feel confident to predict because it's that is not going to be a defined end point you could say

it was easy to sort of say or at least try to say when you were going to determine the order of three billion bits of information but interpret it as sort of I like to make an analogy by saying well when will we fully understand good Hemingway novel a good Shakespearean play. I mean when do we really understand that I think you lots of people could question that it will go on for decades still trying to reinterpret it. I think the human genetic blueprint is going to be probably just as comp I'm sure even more complicated. And so I think we can stay we can go through milestones we can say when we have a full inventory of all of our genes when will we have a full appreciation of what all of certain classes of sequences do. I mean those sorts of questions could be answered and probably by the even going back to one of the earlier callers really understanding what is it in the blueprint that would allow a seld to be a you carry out Excel. I would even want to venture to gas I mean this is really just the beginning of something it's by no means the end of anything and this could go on for decades this is what all scientists and clinicians are now empowered

with this new information and it's going to take a long time to fully interpret. But I think you'll start seeing benefits even at the very early interpretive steps. Well I'm sure the things that for again for your average person the things that they're going to be most interested in are genetic diseases diseases that have genetic component and I think now we're coming to appreciate that that a wide variety of diseases probably do have a genetic component virtually all diseases maybe almost everything so it could be every everything from diabetes to all timers to see if we might think that. Do we think that maybe if we get a better understanding of the role the genes play we can use that information that to develop. Treatment methods so I would expect that those are the kinds of things that we would we would be concentrating on or at least to your average person. That's what they wanted I was. When are you going to be able to really use that to do something dramatic about cancer or heart disease or all timers or you know some range of things. And that's exactly my point is I think that's when people will start to be confronted with the fruits of the

genome project when they start to see a change in how they are treated as a patient how to basically for certain diseases how it may change diagnostics how it may treat their change their appearance. But at the same time we should be cautious these are really hard problems all we have not completed anything we've just provided a foundation for all new approaches for studying diseases. Yes we could point to certain examples I can tell you that since the genome project began. Practically every week another gene is found that is associated with a specific disease and it correlates very nicely with each year the genome project marched on more and more of these genes have been identified and I'm sure people have heard about them. Genes associated with breast cancer and Alzheimer's and so forth. And again even that is a triumphant occasion. But at the same time it's just like flipping the lights on in a room again now you actually understand what the genetic defect is. It doesn't necessarily tell you automatically how to fix it. And that's the next phase and. But again

we're operating at a whole different level of sophistication by having a gene associated with a disease and being able to ask questions that previously you were completely in the dark about. You know I guess to that there people should appreciate did that it's it's maybe more complex than finding a gene that's responsible for some problem that we would go and we could say aha this gene right here this is the Alzheimer's chain. If we could just figure out how that works and why sometimes it works and doesn't and we could fix it. Well then we there would be no more Also I was disease. It may indeed not be as simple and straightforward as one problem. One gene and one fix well for some diseases it's that simple Cystic fibrosis is one that a lot of people are aware of that's one gene. Now there's a lot of different ways that gene can be changed or mutated typographical errors I like to think of it and but it is one gene causing one disease but diseases like Alzheimer's or diabetes hypertension and the like cancer certainly it's very clear that for many of those

it's going to end up being a series of maybe a handful or even more genetic changes in a series of different genes that are going to lead to a predisposition to a disease that maybe will get the disease or maybe with the problem with certain environmental exposures or certain foods or so forth would would would lead to that disease. That's really complicated stuff we would never be able to untangle that if we were constantly just trying to figure out what the letters were on the different pages of the book. It's at least becomes approachable by having all of that in front of you and then be able to do studies in much more sophisticated ways. Well I know that there's egg you said that ad and rightly so that making an estimate of how long things take is is very difficult but when we're thinking about getting to the point where we have substantially interpreted. The sequences and that we are getting to a pretty good understanding of what's what and starting to think about applying that for a goodly number of human diseases let's say. Are we talking about more than 50 years but less than

100 years. Or what kind of timeframe are we talking about. I think over the next I really believe that over the next five years you're going to start to see a number of new diagnostic tests. For example in fact you are there already are out there so if I can be confident that over the next five years where we will be able to diagnose certain diseases based on DNA testing of individuals and that may change certain they I mean point to for example we know so much more now about colon cancer than we knew even just a handful of years ago and we know there are certain genes that if mutated that individual is a much greater likelihood of developing colon cancer. And the reason that's very useful is that if we identify those individuals that is something they can be screened for and colon cancer is one of these examples and if you're screened and you're caught early enough and you're treated you know you the morbidity is significantly less than if this is gone unscreened and untreated and you catch it at a very late stage. These are the kind of examples I think that's

one for colon cancer I think there's going to be others for other disorders that will then result in abilities to have lifestyle changes preventive medicine that will yield benefits. What will be a little bit longer will be taking the genetic discovery and then going in and coming up with a treatment for it being a new drug being a gene therapy or being some other type of therapy. Now there are examples of some very exciting developments on one drug in particular for a certain form of leukemia that seems to be quite quite a significant advance and that drug was actually designed by understanding a genetic basis what was going wrong in that form a leukemia. And that's a nice example. But you know not all the other examples are going to come as quick as that. It's going to be many years. I think you'll see incrementally over the next five years certain things that over the next decade even more and I'm hoping 50 years from now where we're looking back on this and recognizing that boy we have come a long long way but I can't quite tell you exactly what the timetable is going to be now but 10 minutes left actually less than that maybe more like it or nine minutes in this part of focus

580 We're speaking with Dr. Eric Green Green chief of the genome technology branch director of the NIH intramural Sequencing Center at the National Human Genome Research Institute. And your questions are welcome. If you'd like to join here conversation do take the opportunity to call in now don't wait till the very end. 3 3 3 9 4 5 5 toll free 800 2 2 2 9 4 5. Here's color in your bene line number one. Hello. Hello. Yes. What do we have to the question. Interpret the data from the Human Genome Project. I want to ask the speaker to present to see you on some of the most promising approaches. The interpretation I'm from my background I'm mostly familiar with issues such as protein folding from the chemical side of things as well as some of the Association of genetic mutations with human diseases.

Other approach general approaches that the speaker may be familiar with that I'd appreciate of commenting on. Sure it's an excellent question. I think there's going to be many different types of approaches that will have to be brought to bear on this very challenging aspect of interpretation. I will tell you my own personal view is one of these really are two major things that are going to be done and have to be done one of which was actually very relevant to what the work that I do at the NIH is that one of the most powerful ways to interpret the human genetic blueprint is to basically sequence other organisms get the genetic blueprint of other organisms and then compare them. Basically when you find sequences that are in common between let's say humans and mice for example. When you see sequences in common that is most often due to the fact that evolution has held those sequences in check because they're important. When you see sequences that are very different

then that's probably because they're not as important. So one of the ways to eliminate the important regions of our blueprint is by sequencing other blueprints of other animals comparing it and then figuring out what's in common is likely very important and what's not uncommon is probably less important or else is unique to that particular animal. Now this goes hand-in-hand with the second tool which I think will increasingly be made more and more powerful and that is better in better computer tools. I think without question that most of this interpretation is going to be done by very sophisticated computational exercises that are going to have ways of synthesizing the sequence comparing the sequence developing tools for identifying the different functional units within our sequence. And then I guess the third component of course will be additional complimentary experimental work. But to think for a minute that it's going to be one mode ality that's going to result in interpretation is very naive. It's going to be several different approaches brought to bear. I think a lot of it's going to be sen around very good computational biology though.

Thank you very much. Thank you and next person here is in Chicago line for Hello. Good morning gentlemen. I'm a little late to the probe. And so if I ask a question and it's not what you're talking about I apologize and I just want the human genome. So I was wondering what your guests thought of a national DNA databank. I don't know if there's been talk about this especially when it comes to a convicted felon you know sort of like a crime scene here but there's been talk that maybe we can do it for more than just that and I wondered about his opinion on that. Yeah it's a complex good question it's a complicated question and it depends for what purposes you would want to be banking away DNA I mean one you alluded to one maybe for the purposes of sort of in the forensic arena for having DNA available for testing in a criminology type way. And that's sort of one set of issues or another set of issues relate to should we be collecting DNA from every new baby that's born for the purpose of being able to catalog whatever diseases that individual may get and these are complicated studies a lot of ethical issues associated with that there is.

Do people want to be giving away their DNA and what's going to happen to it and I'm not sure you want to make a move like that until you have stronger protections so that the guns the two sort issue we don't want to have something come back that we meant to do something very good and end up coming back to haunt people and so I think until there's better protections we don't want to go too far in that direction. Well I understand that the military has already started. Do it and so we can identify casualty Central and I believe that to some extent that is true but again that's been done a very focused way for very specific reasons and so that's absolutely right I think that would be within a different context for a specific reason. Well let me get this straight if you took someone's DNA and you went to a crime scene and you found evidence of DNA there what do you do you want to throw the computer is that the way it works in a brief answer there are there are ways of essentially gaining a fingerprint if you will of that DNA. There are tests that can be done to look at very specific parts of someone's genetic blueprint. And by that everybody is unique and so if you have that sample

and you have some individual that you think may be a match you can do tasks at the DNA sequence level and absolute determine if it is a match and that's exactly the way friends and he's going which is not a computer printout. Well I mean the computers are involved in interpret it but essentially it's generating data at a DNA sequence level. I said Well I think it is we need to be careful what you said because I understand in the future you'll be able to determine whether someone will be able to get a disease or something like that. And after the ship's company got ahold of that they could possibly deny you coverage. Exactly why we need better protections. I'm going to have to jump in here. My apologies for cutting in on the call I'm just going to have to do that because we have used our time and we're going to have to close out. We want to say it to our guest Eric Green from the National Human Genome Research Institute at NIH. Thanks very much. My pleasure in here.