 Well, good evening everyone and welcome to what I think is going to be one of the more interesting meetings That all of us have been to if it goes well And I know it will because of the amazing collection of intellects that are collected here in this room As we began planning for this particular workshop. We thought we ought to try to achieve a Diversity of perspectives that would be unlike most of the other meetings that any of us go to and I think we've done that Given who all of you are and the remarkable array of expertise that you represent But I think the other aspect of this meeting that's going to make it different is it's blue sky in nature And that we really are asking all of you to think well outside the usual boundaries of a scientific workshop Or it are a theme specific meeting Into the future of where genomics ought to be going in the course of the next decade or more and that is a real Opportunity I think to take off the usual constraints and over the course of the next a couple of days To really collectively see what we could come up with in a way of truly bold and exciting notions About what genomics should become and I mean genomics in the broadest sense genomics including all aspects of the biology and the medical Implications the ethical legal and social issues the technologies that need to be developed the computational aspects and a whole lot Of other things too, so this is a very large and challenging Agenda we have in front of us, but I think we have the right people to do it And I think as I will explain a little bit the way in which this fits into a larger plan To evolve a specific set of proposals Means that we don't have to walk out of here on Friday with a document all signed and sealed about what genomics will be For the next few years, but I hope we'll be substantially closer to that than we are here this evening What I thought I would do in this opening, and I hope it won't be a terribly long presentation Is to give a clear sense or at least try to about what we have done so far in the genome project? Because I think there's a lot of people here who would not consider themselves genome scientists And maybe not entirely clear about what the current efforts have achieved and obviously we're going to be building upon that foundation So it's probably good if we all make it clear what the foundation currently looks like I am going to explain a bit about the context of all this in terms of how this meeting fits in with other things that are happening And then I'm going to give you a charge about what it is that we hope to see happen at this meeting And a bit about the logistics of how that's all going to come about which includes a few mysteries that won't yet be revealed So that's that's the intention for this evening First of all, I'd like to express some sincere thanks to people that have helped very significantly in pulling this ambitious workshop together In particular the four people you see here who have been sort of the planning quartet from NHGRI Eric Green, Mark Geyer, Kathy Hudson, and Elka Jordan Who have been working as a very effective group to try to plan out many of the details that got us here I want to thank all the people who have agreed to give talks in the plenary sessions tomorrow and those who have agreed to chair breakout sessions And special thanks because they've really worked tirelessly to the two people standing in the back there near the back door Karen Hages and most especially to Susan Mix who have done incredible things to make this happen I saw them late last night putting stickers on the back of your identification tags so they were hard at work at the very last minute Well this is a cartoon which came out right about the turn of the new millennium and it's perhaps an apt metaphor One that many people have used the notion that the genome project is an adventure, a biological adventure into new uncharted territory The human genome project here being compared to Lewis and Clark out there exploring new territory And we are called here the Lewis and Clark expedition of the 21st century Well the 21st century is just getting going and most of that expedition lies ahead of us And I think the context here is for us to try to figure out collectively what that looks like Perhaps one could say that already the genome project has surveyed the territory called the human DNA sequence And got a pretty good idea of what its basic landmarks are But if you want to see this come to benefit humankind we still have most of the expedition ahead of us So the genome project of course did not arise all of a sudden de novo one day It came about because of a series of deliberative discussions Not unlike I suppose this one but happening some years back And some of you in the room were part of those including the person who will give our summary tomorrow Or rather the next day, Maynard Olsen So let me bring you back if I could to 1988 to the publication of this document Mapping and sequencing the human genome which was the result of the Albert's panel And it should be pointed out though that that set of recommendations Which basically then became the blueprint for the human genome project Didn't arise immediately just out of that group's discussion But was fed into by many other sources as well I'll come back to I think in many ways we should think of ourselves now In a somewhat equivalent stage where we have been operating on a series of five year plans Which have been pretty much built around those original recommendations But as you'll see most of those specific goals have now been met And so we're in a circumstance of really needing to think much more boldly and broadly About what genomic research should become in the future So in that regard this is unlike some of our preceding five year planning meetings As important as those were, this is probably even more so A few of the milestones that were accomplished in the first ten years of the genome project Are illuminated here on this timeline and I'm not going to go through those Because it would take too long and you're familiar with most of them But just to point out that those also did not come about randomly But as a result of having set a series of specific goals And aiming for certain timelines to be achieved And then challenging the scientific community to come forward and accomplish them Which in every instance they did and this is really quite a notable record of achievement That many of you were major parts of and which of course we hope to see continuing Oh, Nick I guess that's sort of in the wrong place, thank you for moving in Now those particular goals came about again because of a planning process That identified them as desirable products And just to run through what that looked like The original five year plan published in 1991 In this document which looks very much like a government printing office product And in fact was, went through the first five years of what we hoped to achieve That actually was supplanted only a couple of years later By a five year plan which covered the years 93 to 98 And you were all sent a copy of this one which was published in Science Magazine And then indeed in 1998 the current five year plan Published in Science went through a series of very specific goals That we have been looking at rather carefully ever since As our guideline for what the scientific community felt would be the most important And achievable goals over this five year period And I want to spend a little bit here talking about how we've done in that I hope you had a chance to look at that article Because I think it is instructive to see what it was That the best and brightest minds of the genome and non-genome community Were able to come up with the last time we went through this process About what we thought we could accomplish So there's a series of quite a number of goals there, seven to be exact And under each one of those there are specific sub-goals And I thought it would be useful to look and see how we've done So under human DNA sequencing When this was published in October 1998 We said that we would have finished to the standards End by the genome project which are pretty rigid and strict 33% of the genome by the end of 2001 In fact as of today we have finished 61% We said we would have a working draft of the genome by about now And of course as you know that was generated a year and a half ago In June of 2000 Although the publication describing that and the analysis of it came out last February And we said we would complete the human genome Again to the definition of essential completeness Which is a rather specific one By December of 2003 We currently aim to do that by April of 2003 Although of course that isn't here yet So that's a prediction, not a current status in the strict sense of the word And one of the specific goals of the effort was to make sure that Access was free and unrestricted And we have adhered to that in every sense of the word Which I think has been a good thing for the scientific community Just a couple of words about how did we do all of this Since it was a pretty significant effort Sort of like this proverb Which is to say that it is important to understand the alphabet And for DNA that means getting the sequence And if you were paying attention in March of 1999 And going to the internet to see how far along things were You would have seen about 15% of the sequence completed And then over the course of the following months Thanks to the efforts of 16 genome centers around the world And more than 2,000 people that those areas got filled in very nicely And by May of 2000 90% of the sequence was in fact complete And here is a photograph of the folks who assembled at Hinkston Hall In Cambridge a couple of years ago as part of that coordinated effort Which you can immediately see as an international effort As well as it should be And I think this is something that has served the genome project Extremely well from the beginning as its international character And I would certainly argue whatever we decide to do next Should have that same character The genome after all belongs to all of us This of course was the copy of nature back in February That described the sequencing and the initial analysis And represented I think from the scientific perspective The major milestone being as it was a peer reviewed publication With a great deal of input from some very bright people Who helped us analyze the sequence Many of whom are here with us at this meeting And in case you have heard that there's a picture of Watson Crick Buried somewhere in this mosaic But you haven't found it yet I'm going to spare you a little trouble It's right down there Speaking of Watson and Crick I think there is a reason perhaps why we have chosen This April 2003 time point As the projection of finishing all of the chromosomes To the same standards that have already been achieved For 22 and 21 and a few others That are also now getting wound up and written up And in fact there is sort of a poetic appeal of that Because that will be the 50th anniversary Of this very significant one page paper In nature April 25th 1953 When Watson and Crick described the structure of DNA And as part of the 50th anniversary of that In April of 2003 we expect to also be able to say That the human genome sequence is now finished And we are on track to do that I would like to assure anybody who is concerned That after all of the hullabaloo of announcing Working drafts and publications That the sequencing centers might have sort of lost interest In this they certainly have not And many of them are here and can assure you That they're working their butts off To get this job finished Closing up those gaps And dealing with the messy areas That didn't go so easily the first time through And as we track the closing of the gaps Of the sequence the whole effort is very much on track To achieve that completion by spring of 2003 So that's the sequence goal What about sequencing technology? That was the second goal that is enumerated In the 1998 plan In fact it's very interesting to go back and read that And we said and we thought this was extremely bold That by 2003 we should be able to finish 500 megabases a year of sequence We're currently by my estimates Mark Gaier is going through all of the efforts All of the data that's been accumulated from the genome centers Finishing about 1400 megabases a year The cost for a finished base pair in 98 was 50 cents And it seemed as though it might get stuck there For a little while and so projecting That we could get it down to a quarter by 2003 Was not a projection that everybody bought into But it was put down anyway Well look how we did The current cost of a finished base pair Is about 9 cents Which is obviously responsible for the fact That we've been able to do so much sequencing In that interval And novel technologies that is Instead of continuing the very effective But perhaps ultimately not cheap enough Methods of capillary electrophoresis Sequencing instruments You're going to see in a couple of these slides That I've just put down support Because the way we worded the 98 plan Was a bit vague It says we should work on this And of course we have worked on it So in my report on the status I would say it's progressing But you could obviously pin me down a bit here As to whether we've actually achieved What we aim to And in some instances I would say It's gone faster in other cases slower And maybe that's one of the lessons for this group As we begin to talk about planning for the future As specific as we can be And then we'll know if we succeeded or not I'll just show you one example Of a novel technology for sequencing That I thought was pretty cool That David Burke showed to me a couple of weeks ago When I was visiting Ann Arbor Sequencing instrument, a model, a pilot model David will tell you it doesn't quite Have the resolution that he would hope for Here's the actual thing in my hand So you can get a sense of the size of it So that's obviously a little smaller Than a 3700 And it obviously can therefore Operate with very small volumes And all the various components Including running the reactions And doing the separations are built into this chip Most of what you see here are just the connections In order to allow you to hook it up That kind of micro-electromechanical systems approach Has clearly been an exciting one But it's been a challenge to reduce that To anything approaching practice And that challenge is still remaining To be fully met But one that one would hope would continue To yield up a promise Of increasing throughput and reducing cost Which if we want to see sequencing Happen in a truly prodigious way We have to continue to see that curve Move in a beneficial way The goals for human variation By the way there were no goals For human variation in 1993 And that was not part of the original Specific plan for the genome project As I read it Although it was sort of expected It would come along somewhat after that So the goals in 98 Which were at the time rather ambitious Were to support technology For SNP discovery And I think what we've learned Is that the most efficient way for the human To discover SNPs right now Is to use the fact that you have the sequence And simply do shotgun sequencing From other individuals And you find lots and lots of SNPs that way And of course they're mapped Because the sequence is there To lay them against Technology for SNP scoring Was to be supported And I think it's fair to say There's been a proliferation Of ways to approach that But I would not say at the moment That there's been a clear winner In terms of the competitive nature Of these And they're all still way too expensive So it's not clear that we've Fully succeeded at that Although there's been A lot of technology development There is one goal here That I would say we have not achieved And by 2003 We may or depending on what The scientific plans are For the next year or so We may decide that we can get The same information without Specifically going after this This was the goal of trying to Identify the common variance In coding regions of most genes And we have a modest fraction Of the genes for that has been done But for the most part The focus on developing variance Has been done in a random fashion Without focusing specifically on the gene And then maybe something That people at this meeting Will end up talking about For all I know The SNP map We thought this was really ambitious That we'd go for 100,000 SNPs By 2003 We now have about 3 million And again that came about Because of technological improvements And particularly because Of having the sequence to lay Those random reads against And then we argued that We needed public resources of cell lines And those have been supported In particular the PDR The Polymorphism Discovery Resource This collection of cell lines That's been used by many groups Including the SNPs consortium That has been responsible For a very large fraction Of the SNPs that are out there Now in DBSNP That is a cell line resource That I think has turned out To be quite useful And there are others as well That have been collected Or in the process of being collected So human variation has come along I think more quickly Than most people expected One can go for instance To the web And pull out a couple thousand Base pairs of sequence As you see here on chromosome 7 And if you look in that same region If it happens to be in one That's been well mined Well goodness you're likely to find SNPs In the same area nicely placed On the sequence Waiting there for you To assess their significance But assessing their significance Is not so straightforward And we have had intense discussions Over the last year or so About whether there would be ways To facilitate the process Of doing whole genome associations Where you scan the entire genome Looking to see Can you identify SNPs That are associated With a particular phenotype And of course to do that Looking at every SNP in the genome Is going to be prohibitively Expensive with current technology But if you could identify a subset That basically give you All of the information Because they are after all Correlated with their neighbors Because of this thing Called linkage disequilibrium You could save a lot of time And money And that is the reason For a project that's now very intensely Under discussion To build a haplotype map For the human genome And basically define once and for all All of the common haplotypes That is all of the blocks of DNA Where the SNPs are in disequilibrium With each other And to do so in a fashion That then allows you to pick A subset of the total number of SNPs Hopefully only a modest subset A subset that you could score Perhaps a couple hundred thousand And then use those to carry out Your whole genome association studies This effort has been intensely discussed Since last summer When we held a major workshop on the topic And it's beginning to take shape As an exciting new opportunity Goal number four Technology development for functional genomics If you looked at the 98 plan You would notice it's a bit on the vague side here Because we wanted to support things here But we weren't very specific about in what way And here is an area I suspect Where people at this meeting Will focus more heavily than we did Or three or four years ago Because at that point It wasn't quite clear What functional genomics Was going to turn out to be You'll notice that technology Was used in this particular instance Because we weren't sure That we wanted to advocate For a collection of large data sets At that point But now I suspect Some of you may very well Want to advocate for such large data sets The only specific thing I want to draw your attention to That you might not be aware of Which actually fills I think rather nicely This need for CDNA resources Along with a number of other Such resources that have been generated By groups like Rieken The mammalian gene collection Which is an NIH effort Which has been contributed to By a number of NIH institutes And has been led until recently By Rick Klausner and myself And now that he has gone off To another position It's still a joint effort Of NHGRI and NCI and Bob Strasberg Is serving as the czar of this enterprise And if you look at the output of this It's actually getting pretty exciting That there are more than 8000 Human full-length CDNAs That have been produced And an expectation that that will grow rapidly And there are a number of people in the room That are part of this challenging And ambitious multi-center effort To try to generate a full-length CDNA For all human and mouse genes Over the course of the next few months To a year or two And it will be interesting to see How that develops And obviously that is a resource That many people had hoped to find In their hands Which is increasingly so These clones are available Not only as sequence But as actual clones That you can order and use in experiments I could tell you by the way If you're looking for a CDNA For a gene that's known to be involved in disease There's about 900 genes by my count That appear in OMIM As being responsible for a disease That Victor McCusick considers to be genetic While of those 900 genes 91% of them now have a full-length CDNA In this collection So if you're out there Busting your butt Trying to get that 5 prime end Of that gene that's making you crazy You can probably spare yourself the trouble And simply order up a clone Goal number five Comparative genomics The goals that were placed in the 98 plan Were we thought ambitious But actually a lot more has been done Than what we initially imagined At that point in part Because sequencing has come along so nicely The C. elegans sequence Was supposed to get finished in 1998 And it certainly was And now we have underway As a joint effort of WashU In the Sanger Center A sequencing of C. brixie A companion roundworm With expectation That the comparison between the two Is going to be tremendously valuable In terms of understanding Which parts of the genome are functional And getting the gene models right Drosophila melanogaster aimed for 2002 Got done as you all know As a wonderful collaboration Between Jerry Rubin and Solera With the data being published In March of 2000 And we now see about to start A companion drosophila Namely pseudo-obscura Which has potentially the same value As I just mentioned for the roundworm In terms of providing annotation information That will really help a lot And understanding which parts Of the genome are doing what The mouse, what we said in 98 Was that we were going to aim for a draft But it doesn't say exactly when we'd have that And that we try to have a complete sequence By 2005 In fact, and I'm not sure everybody Is fully aware of this as you might Because much of this data has appeared In the last couple of months Right now, if you go to the databases Both as traces and as sequence You can find about five and a half X coverage Of the black six strain of mouse The goal of finishing still says 2005 It may be that that can be beaten But we haven't officially said so By the way, there is this new publication Which you can find in several places But it's on the NIH site On the mouse page This mouse genome monthly is an effort To try to keep people up to date On what's happening with the mouse genome Sequencing consortium effort Which is jointly carried out by The Sanger Center, Washington University Whitehead and the EBI folks Who are handling most of the informatics And this particular issue, number one Which just came out contains within This diagram here Which is a description of what You can expect to see as far as The mouse sequencing effort Over the course of the next little bit And as you know, we're sort of here In late 2001, so we are essentially At the point of having this Five to six X shotgun Assemblies have already been undertaken And some of them are now available If you want to go to the EBI site And annotation of that Is also getting underway And then in 2002, there will be Heavy effort devoted to back by back Sequencing in order to Achieve a finished mouse genome There's also an effort, as you can see here To carry out some sequencing Of additional strains in order to generate A nice collection of SNPs That should be very useful for people Who are trying to map various phenotypes On back crosses. So I think it's fair To say the mouse effort is considerably Further along than we would have contemplated In 1998. There are other large scale animal Sequencing projects that are also Underway and going quite well. And I think, again, as one goes Through this, you realize what A prodigious expansion there has been In sequencing capacity in these Last three years. Because in 1998, we thought we were stretching pretty Hard to make the projections that were made And yet not only have things been Exceeded as far as human and mouse But these other things are heavily Underway. Rat has now reached About 2X coverage. As I Look at the traces appearing In the trace repository to NCBI This being a joint effort between Dr. Gibbs, who oversees the project Along with collaborators at Celera and at genome therapeutics. Zebrafish being done at Sanger And I'm sorry if I don't quite have the coverage Right because I did this in a hurry a little bit Ago and I didn't have a chance to go and look But I gather it's about 1X. Tetra Oden, an effort that Jean Weissenbach has been working on For some time, which has been a very useful Set of data for annotating the human genome Now at about 6X coverage, I believe With some of that data more recently Being supplied also by Whitehead The joint effort Led by the JGI to sequence The Pufferfish Fugu Was announced recently as Having reached about 5-6X coverage As well. And Siona Savigni Which is a C-squirt Being sequenced at the Whitehead Is now, the sequence Is present at about 10X coverage And is the process of being assembled So there's a lot of stuff here And if you're interested in doing comparative sequence analysis You have large databases to work with But obviously we want them to be even larger If you're going to learn the most that you can From Evolution's lab notebook I have not made separate slides For goals 6, 7, and 8 From the 98 plan Because when you look at those particular goals They're extremely important And I hope nobody will take it Because I've put them here together on one slide That I'm saying they're less important Let's get that straight The LC part of our goals In 98 I would venture to say Probably the most important part And I think it may very well be true This time as well But they don't perhaps lend themselves To tabulation in quite the same way As how many bases you're going to finish Or what your cost for base pair is going to be So I'll refer you back to the document To read through those particular recommendations In these three areas And I will expect that this meeting Will also tackle those in significant ways In particular And I've arranged it that way By having some breakout groups To talk about several of these topics Well, okay, that's where we are now Now let's talk about where we need to get to I like this cartoon because It feels this way on certain days If you're in the lab trying to understand What the genome is telling you Three billion pieces And what exactly does it all mean And I think that really is the challenge That now lies ahead of us Which I hope this meeting will address Which is a remarkable moment in history With this incredible array Of fantastically interesting data That we don't understand very well And really move it forward Into the applications to biology and medicine That were the reason for doing the project In the first place Now obviously many of those applications Are already happening and hooray for that But let's talk about over the next couple of days How we can speed that process up Of course a very major aspect Of that is the application to medicine How are we going to take those discoveries About the genome, identify the genes That are playing a role in disease susceptibility Use that information for diagnostics Preventive medicine, pharmacogenomics And develop better therapies This diagram that I'm fond of showing Is one that isn't going to happen Without a lot more creative ideas An effort going into the process Of moving from top to bottom And how in fact are we collectively Going to ensure that that happens At the maximum speed because that's And in the midst of all that How do we do that in a fashion that is sensitive To all of the other issues That surround the study of the genome And its applications This quote from Albert Schweitzer Might very well be the motto of the ELSI program We must not allow our technology to exceed our humanity How are we going to achieve that In a responsible fashion Well Your job is to be predictors then I have to tell you You're taking on a risky task Somebody insist That this was really said by Yogi Berra But I have it on good authority That if he said it he wasn't the only one So yeah, we are asking you To do something pretty unusual here And scientists aren't necessarily known For sticking their necks too far out When it comes to trying to think 10 or 15 or 20 years ahead But that is very much the intent Of this meeting And I will tell you that it hasn't always gone well When other people have made an effort to do that And some of them have been fairly distinguished For instance, this quotation I found By a fairly well known person Thomas Watson, by the way Who happened to be chairman of IBM I think there's a world market for maybe five computers We wouldn't have said anything like that Would we? Another quotation The concept is interesting and well formed But in order to earn better than a C The idea must be feasible So who said that? No professor evaluating Fred Smith's paper Which proposed FedEx Which Fred Smith went on to found And obviously did pretty well So yeah, right, academic criticism At this meeting may be taken With a grain of salt as well We need to be bold here And not put down great ideas Just because they don't fit our models Another quote We don't like their sound And guitar music is on the way out A timely quote for the past week Or so, Decker records Rejecting the Beatles in 1962 Final one Who do you suppose said this? 640k Outta be enough for anybody Bill Gates So as you're thinking about Sequencing capacity, don't make this mistake Okay, so our charge is To do better than that, but it's going to be hard Of course The best way to be sure you're right Is to create the future It'll happen the way you intended it to And you'll appear to be incredibly bright Let me put this now In the last few minutes here Into context of what the planning process is Because I think you deserve to have some notion Of how this meeting fits into An overall scheme that actually has already begun Began back last spring And will play out Over the course of about the next year At the end of which we hope to have Something that looks like a plan For what NHGRI should be doing For the next 5 or 10 years So the purpose Is develop this plan It says 5 years here, but I'm not wedded to that at all There may be a reason why 5 years Made sense in previous iterations Of this and that reason may no longer apply So that's something that could be Factored into our discussions But we do need to have this plan in place I would say by the spring of 2003 when the human genome Sequence is essentially completed Then many of the goals that were Already on our table Will have been dealt with and we'd look sort of Silly if we don't have something else To offer up as a substitute So I wouldn't want this to go on much longer than that We need a vision of course The process has already begun In a fashion that includes The entire institute And most of you who are here May not be entirely familiar With the fact that there's a difference Philosophically between the extra mural And the intramural aspect of NHGRI So let me quickly say a word about that The extramural program has been around Since the beginning when we were still a center It is the place where we spend most of our resources The intramural program Was founded in 1994 And was specifically aimed To try to study Applications of genomics to disease Taking advantage of the Aspects of a bench To bedside that are particularly Possible to achieve on the NIH campus With the clinical center Which is this remarkable place That has more than half of the clinical Research beds in the country So the intramural effort has been More applied. You have amongst you this evening A number of folks from the intramural program Who are branch chiefs You have a number of other folks Who are on our board of scientific counselors Who advise that program And we think it's particularly appropriate This iteration that we do this Planning process jointly because as time goes on I think the difference between The program which was focused on the goals Of the genome project and the intramural program Focused on the applications are beginning To get closer together. Furthermore The LC effort, the research program Has been part of our planning Process each time, but we have A policy operation in the genome Institute which is in my office In the director's office which is directed By Kathy Hudson which is our office Of policy and public affairs Which has been very much involved In the rough and tumble business To take research conclusions And seeing if they can actually be Implemented at the policy level And we felt very much this year That that process ought to also be Connected with the planning And so in fact they are. So we have these three components Each one of which has an ad hoc Working group of our advisory council To oversee them but these are all Interlocked by the fact that They have some shared members and they All report to the advisory council NHDRI. Just to quickly Tell you who those people are Most of them are at this meeting so You will see them in your breakout Groups and in the hallway and at lunch Here are the folks on the council Who are assigned to our extramural Planning group. They are all members Of our council. Here are the folks Who have agreed to serve on our Intramural planning group. As you Can see a number of them are Members of our board of scientific Counselors which is the body Roger and Janet are members Of the advisory council and Then we have some other folks as well Like Carl Barrett and Jim Batty Who are scientific directors or Institute directors for NIH And the policy LC group You can see the folks who are Listed there. This is a vigorous Group of folks who actually met This afternoon. I had a very Useful and important Gathering from what I have learned And this also includes as you can see Four members of our council and One of the board of scientific Counselors. Those are who those People are and they are charged With assisting us and pulling this Altogether so that by the spring Of 2003 we have a blueprint that Everybody feels has made the Most of all of these creative Folks. Now what have we Already done? I said the Process had begun. Here is a Listing of workshops that have Already happened and the Last of which is the one you are Right now starting here this Evening. These have focused on a Variety of topics. Minority Training workshop back in April. A workshop on protein sequence Databases in May that we held Jointly with the NLM. A joint Sequence assembly workshop which Was looking at whole genome Shotgun versus back based sequencing Which we held jointly with Celera. Comparative genome Sequencing workshop in July out Now we are trying to prioritize Additional genomes for large Scale sequencing. I didn't mention That when I was going through the Comparative genomics. I might say One word about it right now. There Is now a process which involves A white paper that needs to be Put together by an investigator or A scientific community or a Sequencing center or some Combination of those who are Interested in seeing a particular Genome get into the queue for And look at those documents and Assess the relative values based Upon the size of the community and The value of the information. And Then as sequencing capacity becomes Available in the centers that have It, we'll try to slot these new Genome sequences into that A particular pipeline. And if You want to know more about that Process, you might want to talk to Bill Gelbart who's standing in the Back because he's going to have A very important role in overseeing The human variation Haplotype map project. I mentioned This sim map idea and this very Much got a thorough airing in A public meeting in July out of Which have come several working Groups that have been working out The details and that discussion Continues and I'm sure will come Up in various forms during these Couple of days but it actually Has acquired a lot of momentum. There is of course interest in Haplotypes in both the public Sector and we have representatives Here at the meeting who are Interested in that from the private Sector perspective as well. In fact I should say we're fortunate that we Have a broad diversity of Perspectives at this whole meeting. Not everybody here wears an academic Hat or a private sector hat. Some People wear both and that's as it Should be. We had a meeting in October to talk about behavioral And social factors and their Interaction with genetics that Are an additional sort of a follow-up To the April meeting just a week Ago where all of our grantees came For a further discussion about How we could improve our outreach To minorities in training in Genomics and then here you are In this public meeting on the Future of Genomics which is Obviously a large and much broader Kind of meeting than the workshops That have preceded. Now out of This meeting we hope to get a Broad sense of what some of the Plans are that we haven't necessarily Attended to yet and so we would Expect them to hold additional Topic specific workshops in 2002. There are some of these that Are already under consideration but You shouldn't be constrained in your Thinking by that. We expect that We'll probably hold a large scale Protein analysis or a proteomics Meeting together with the general Medical Sciences Institute and the NCI sometime in the next few months The plans for that are already There is an intention to consider A large scale gene expression or Expression array meeting to talk About opportunities in that area Many people have been excited with The sequence coming along as well as it is And other aspects of chromosome biology Desperately seeking explanation That this might be a great opportunity To talk about that topic. We clearly need to do more about databases And particularly the idea of having Databases for model organisms where You don't reinvent it each time And there is an effort underway to Organize a meeting of that sort. We'd have some rough plans For a meeting of the LC group On race and ethnicity and genetics Research. And then next fall We would aim probably Again back here at Ehrlich House To convene a similarly large And broad group. Excuse me, I have a bit of a bug. With the intention at that point Of having a much more mature Expectation Of what our plan might look like And at that point The meeting would be much more devoted To reviewing what that draft Seems to be looking like And trying to tell us whether we've got it right Or whether we've missed some important things. So that's the basic Outline, but again I would hope That we will fill in some other ideas here Thank you For other workshops As a consequence of your deliberations I'm sure there are other topics that need to be fleshed out A lot more than we'll be able to do In just these two days. There are a couple of meta issues That might be also talked about Either specifically in the breakouts Or lunches or breakfast or whatever I guess one is It doesn't make sense to have these five year plans anymore Well, is it Appropriate to have a Systematic, regularly Occurring planning process I think it would be hard to argue that that's a bad idea Because it's the right time interval And is it appropriate to do it in this global way As opposed to topic by topic And a semantic question That actually is pretty important I think for us all to decide on What was the human genome project And is it over If you look at the original definition And I think it is the definition That most people have kind of attached themselves to By 2003 it's essentially going to be over Because the goals that were laid out By that national academy panel Will essentially have been achieved And it may be a little embarrassing I mean the other alternative is to say Well, yeah, but it evolved and we came up with some other topics But are we really going to say 40 years from now When we still don't entirely understand the genome That we're still doing the human genome project And if we're not going to say it 40 years from now Well, what is the natural point To sort of make the juncture and say Okay, the genome project is completed Let's have a victory celebration And now what we're doing is genome research That's a labeling issue But it's an important one That's probably one that would be useful To have some broad discussion And even an international kind of sense Of consensus before we make a conclusion One of my pet peeves is That we ought to get rid of the word post genome era Because that won't serve us very well If we're spending all this time Talking about how to understand the genome Maybe we've been in the pre genome era But we certainly are not in the post genome era We're finally in the genome era And we're going to be here for quite a while Okay, well winding down Let me give you some specific charges and information What is it that we're asking you to do? I hope you had a chance to read the email That came around about a week ago That enumerates what we had in mind In bringing you to this meeting And I'll just hit a couple of the bullets We really want you to reach Beyond the usual horizon Of a grant cycle Which is the way often people are forced to think So that means Thinking to five or ten or fifteen years Not three And of course in the grant cycle When you think about three years You're really writing about the stuff you already did And writing it as if You hadn't done it already And that thinking is not what we're after here either I think we all kind of know what we've done And where we are now And the intention of this meeting is really To get out there beyond that usual limit And imagine where we want to be And how to get there And that's what we've asked our speakers Tomorrow morning to do Each one of them is to imagine themselves In 2020 In their area And what they hope genomics will look like And then to think backward from that About what we should have done In order to get there And I think if we adopt that same attitude In our discussions throughout the meeting It will be useful And I think the constraints Thinking boldly, expansively Out of the boxes become such a cliche I was tempted not to put it on the slide at all But you know what I mean, out of the box We need to identify new areas That maybe haven't been discussed by anybody So far But that are ripe for exploration Even in a high risk way But that shouldn't exclude familiar areas That have been sort of moving along okay But could really take a leap forward With an ambitious new approach Do not worry at this meeting At all About how the ideas that we come up with Are going to be supported or by whom That's not the intention of this part Of the process, we'll get there We'll have to get there because by spring of 2003 We have to have a blueprint For what the National Human Genome Research Institute is supposed to be doing Over the course of the next few years But I don't want that to bother you In the slightest in these discussions Clearly there are many players In the future of genomics research There is the NIH and there are many other institutes At NIH represented here at this meeting Who have major stakes in genomics There's the Department of Energy And our colleagues from DOE are here as well There is private industry, both biotech And pharmaceuticals and of course There's the international community A very critical part of the whole endeavor And ultimately we'll have to sort of sort out About who is best positioned To take on which part of the plan But I don't think that that should be A part of the conversation In the next couple of days Don't worry about that so much And I would encourage you as you're having These discussions, although the breakout groups Tomorrow afternoon are going to be topic specific In the same way that the opening plenaries are Try not to be too narrow though If you're debating a particular Goal in the medical arena It would be good to think about its LC consequences And its technology consequences And its training consequences If you can manage to do so To compartmentalize We will make sure not to be compartmentalized Tomorrow evening by mixing this up a bit And I'll explain that in a minute So that's the basic idea Of the way in which we hope the meeting Will progress Now some practical matters You may notice there are some cameras In the room and lights That are making it rather warm up here The plenary sessions are being videotaped And will be webcast And that was our intent because many people Have not come to the meeting who wanted to Because this particular venue is limited To about 180 people And particularly our colleagues at NIH Many of them were interested in being able To see the proceedings by webcast And that's what the videos are about This is a public meeting This is not a closed meeting There are some members of the press present So you should consider this as fully An open meeting which is just the way We like to do things You want to right now take off And look on the back of it Because there's some useful information There that's going to tell you something About how you spend tomorrow afternoon and evening There should be two tags on there One says afternoon breakout group And one says evening The afternoon breakout group Should specifically identify A place and a topic That you're supposed to Repair to at about 3.30 Tomorrow afternoon People have already asked me do they have to go They were assigned to Well, it would really be nice if you did Because we made some effort here To try to mix people up in a fashion That put strength in the area Of the topic in the room But also had other perspectives So it just wasn't all the geeks In one particular theme that got together And if you decide To reselect yourselves It might increase the tighter of experts And decrease the tighter of generalists And that would be too bad If you can, please stick to the assignment Now, the evening breakout group You may be wondering about Because there is a room there For everybody, but it probably says Mystery group something, 1, 2, 3, etc So what's that all about? Well, we thought it would be A good thing To have the evening groups be cross-cutting Topics that were not specific To one of the theme areas That are going to be presented during the morning to morning And yet at the same time We weren't exactly sure What those optimum cross-cutting topics Might be because we haven't had Tomorrow afternoon yet So there are going to be folks In each of those breakout groups In the afternoon from NHGRI Listening to the discussion Particularly paying attention to whether there are Examples of topics that seem Like they're ripe for that kind of Cross-cutting further investigation And we will ask The breakout group leaders To get together For what's been called the dinner from Hale Tomorrow Where in the course of a rather short period of time We will try to figure out what those topics are And also who would be an appropriate leader And so don't be surprised If sometime during dinner tomorrow Somebody comes and taps you on the shoulder And says, guess what The topic that we've decided would make A great breakout group is the following And we'd like to ask you to lead the discussion And I hope you'll be willing to do that If you're running for the room Or avoid dinner altogether Because that would be unfortunate I'd like to reassure you That you will be given access To staff people Who will help you through this So it shouldn't be too painful I'd also like to reassure you That we do have in our back pocket Some topics in case nobody thinks of any So that we're certain that we do have Evening breakout groups But we're not going to tell you what those topics are Some people will be a little punchy After a rather intense date And this should be an opportunity To really try something a bit different I would like to ask That at the conclusion of this presentation And yes, we're almost done All the plenary speakers for tomorrow And the afternoon breakout group leaders Meet up here at the front With me and a few of the other staff To be sure we've all got our signal straight And I would also, as far as a practical matter I'd like to tell you the whistling swan pub Where we're in the silo house Will be open this evening and tomorrow evening As well until 1130 And it's a nice place to unwind And meet with your colleagues And I hope you will take advantage Of the other aspect of this meeting Which is the diversity of attendees To find out something about what people are doing Who are not necessarily the folks That you talk to every day And when you go to the pub Or when you sit at breakfast or lunch Mix with some folks that are not And see people at another Sound like I'm talking to a bunch of campers But you know what I mean So again, coming back to the charge here I want to think, have you think about What's happening here as far as this process That I've outlined that is going to emerge In the spring of 2003 With a new blueprint for genomics Is perhaps has more in common With what the national academy panel did 13 years ago Than with what happened five years ago When we were working out the details Of the project, goals that had been For the most part already established But had to be put into Specific terms of timetables Costs, deliverables and so on We really have the opportunity now To rewrite this book And I think that's a fantastic Intellectual experience And one that I'm looking forward to very much In that regard, I guess I should Leave you with a quotation Since I've already left you with several This is my favorite quote for people As far as looking into the future From somebody who's not Dan Cuell But somebody who's a rather accomplished athlete And this is a quote that Arnie Levine used once Actually in one of our planning meetings a few years ago It's from Wayne Gretzky This is what we all want to do Skate where the puck is going to be And not where it is right now That won't help very much, although it's a good thing to know that The goal of this meeting is Skate where it's going to be a few years from now And then we will have succeeded Thank you very much