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Eric Green: Well, good morning, everyone. I'm Eric Green,
director of the National Human Genome Research Institute, and I'm delighted to welcome all
of you to this day-long special symposium entitled Genomics Landscape a Decade after
the Human Genome Project. Thank you very much for coming, and I can guarantee you we have
a very special event in store for all of you as the day progresses.
Let me immediately point out to you that it is DNA Day. It's April 25th, which is DNA
Day, as celebrated every year. Now, it's a particularly special DNA Day, and, of course,
the origins of DNA Day relate to the fact that indeed it's held each year to commemorate
this remarkable discovery of Watson and Crick, the double-helical structure of DNA and this
famous publication in Nature. But it is, you know, worth pointing out that today, of all
days, is the 60th anniversary of this remarkable publication, which is the reason why we chose
to have this symposium today as we're having it.
But, in fact, a lot has happened in the past 60 years, and, in fact, one of the most monumental
things that's happened in the last 60 years that particularly relates to this remarkable
discovery about DNA was the Human Genome Project, which took place from 1990 to 2003. And the
thing we're really celebrating today and commemorating today was the completion of the Human Genome
Project, and that completion was announced in this press release -- actually, it was
announced from this podium and associated with this press release precisely 10 years
and 11 days ago, where the international consortium involved in sequencing the human genome and
carrying out the goals of the Human Genome Project declared the goals complete, and the
project is over.
So that's really why we are here. We are here today to celebrate, commemorate this remarkable
achievement that was wrapped up 10 years ago, and, in fact, shown here are some banners
that especially the NIHers in the audience might have seen on some of the light poles
around campus, have been up for a couple of months and will remain up for a number of
months.
So what I thought I would do to open this symposium is really to help reflect back on
what all of this really means, and to think about how much the world has changed, and
I, in describing to you some of this, I really want to frame it around essentially a 23-year
interval, if you will, with three major punctuation marks, if you will. Thinking back on the year
1990 when we began the Human Genome Project, I can vividly remember it; I was a participant
from day one on the front line, and it was a remarkable endeavor to be a part of. I can
also vividly remember the year 2003 where announced, here at this podium, the completion
of the Human Genome Project, and there was great celebration and great fanfare. And when
we find ourself now, in 2013, celebrating this completion of the first decade having
now in hand the sequence of the human genome for a full 10 years.
Well, these are three time intervals, if you will, to think about, and the world really
has changed if you think about, you know, we've changed U.S. presidents, we've gone
from Bush I to Bush II, and now we have Obama. We've changed the way we listen to music.
Back then, we tended to listen on cassette tapes, but then, by 2003, we were using Discman,
and we were using CDs. Of course, nowadays all of us use MP3 players to listen to music.
Our computers seemed to have changed quite a bit. Back in 1990, there was the desktop,
was sort of the main use for all us, but by 2003, of course, we had mostly found the convenience
of laptops, and nowadays all those things are pretty much done on our smartphones. And
even the way we communicate has changed in these 23 years. Back when the Genome Project
began, the main mode of communication was the fax.
I will point out, true story, when the Genome Project began, it really, for about the first
six or 12 months that I was involved in some of the earliest efforts to map and sequence
chromosome 7, I had collaborators elsewhere who were sequencing teeny bits of chromosome
7, and the way the sequence information was being conveyed to me so that I could design
polymerase chain reaction assays was by fax. They'd fax me the sequence, and I would look
up and actually try to figure out exactly how to design all of the nucleotide primers.
It's astonishing in thinking about it, and we quickly figured out more efficient ways
of electronically communicating, but that was -- that was the means of convenient communication
then. Of course, by 2003, the world had changed, and we were all emailing prodigiously, but
now we've decided that email is too lengthy, and so most people are communicating through
tweets.
Well, that's how we've communicated. What about science? How has science changed over
that, and how has genomics changed, and how has NHGRI changed, as the institute I now
have the great fortune of leading. And then this is really where it becomes now relevant
for this symposium, is different eras for genomics and for NHGRI. And I can't help but
remind everybody that the way the Genome Project was completed was by following a strategic
blueprint, if you will, articulated in several documents, including the National Research
Council report and also a report from the Office of Technology Assessment, and that
was the earliest of blueprint laying out how to pursue the goals of the Human Genome Project.
At the institute level, we had leadership of Jim Watson, who you'll be seeing more of
later in videotape, and Elca Jordan [spelled phonetically] shown here was directing our
extramural research program and serving as the institute's deputy director.
If you fast forward, then, 13 years to the completion of the Human Genome Project, it
all happened with great fanfare and great celebration, and I can vividly remember April
14, 2003. With the completion of the Human Genome Project, we distributed, to members
of the attendees of a symposium held right here in this auditorium, this DVD, and in
that -- and this is showing the cover, is shown, the image is shown here -- and in that
DVD included, burned onto to a disk, the complete sequence of the human genome as just completed
by the Human Genome Project. And this became, if you will, a commemorative piece of the
Genome Project. It was a great stocking stuffer for several Christmases to come --
[laughter]
-- and actually was put in multiple, and this is a true story, multiple time capsules, this
was put into to be unearthed at some future date.
As I mentioned, we had a symposium here as we tend to do, and this was actually a two-day
symposium, and this was sort of some of the graphical elements from that symposium. Importantly,
once again, we needed a blueprint for moving forward, a strategic plan, if you will, and
on the day the Genome Project ended came out this publication in Nature from our institute
that had wrapped up a strategic planning process and really served as a guiding set of goals
and strategic ideas for moving the field of genomics forward.
Shown here is Francis Collins, a little less gray as you'll see later today, back then
at this podium announcing all these things about -- I've just alluded to, and kicking
off the symposium. And then halfway through the day, on April 14 of 2003, came a press
conference just on the other side of the lobby out here that formally was announcing the
completion of the Human Genome Project. And you have individuals like Mark Walport who
was -- is and soon to no longer be head of the Wellcome Trust, Eric Atrinos [spelled
phonetically] from the Department of Energy, Elias Zerhouni, then director of the NIH.
There is Jim Watson, of course, Francis, and Bob Waterston, one of the directors of one
of the genome centers that had been responsible for sequencing the human genome.
And then we find ourself here now in 2013, once again guided by a strategic plan that
we actually published a couple years ago, and very much articulates what we are pursuing
in genomics, some of which you'll be hearing about in talks sprinkled throughout the day.
And once again, finding ourselves at a symposium commemorating, celebrating, but also looking
forward to what the field is going to bring us, and that's really why we have all gathered
here today.
What about the science? How have things changed over these three time intervals? And, of course,
the thing that has driven this more than anything have been technologies for sequencing DNA.
1990, when the Genome Project began, some of those early sequences that were generated
that were then put on pieces of paper and faxed around, such as to me, were generated
using Sanger sequencing methods, and radioactive sequencing, and the classic sequencing ladder
you'd see on an autoradiograph. Of course, shortly thereafter, and certainly what was
responsible for sequencing the genome as part of the Human Genome Project, were more automated
methods with imagery such as this reflecting Sanger-based sequencing results. Cut, wow,
as you'll hear about throughout the day, I'm sure, the world has completed changed with
respect to sequencing technologies, one of which is sort of shown in an icon form here,
but multiple different technologies are now available for sequencing DNA. And with that
has come remarkable advances with respect to the cost of sequencing and the speed of
sequencing, and you can think about it just in terms of sequencing the human genome, how
much time it would take to sequence a human genome or how much it costs.
Well, back in 1990 and throughout the Human Genome Project, we sequenced that first human
genome. It took about six to eight years of active sequencing to generate that sequence,
and it cost something out of the order of $1 billion, but when the Genome Project ended,
had we gone back and immediately sequenced a second human genome, our sequencing center
colleagues and researchers, you know, sort of on the back of the envelope to calculate
what that might cost, and estimated that if they went immediately to sequence a second
human genome, it take probably about three to four months, and it would cost much less,
only $10 million to $15 million.
But of course today, today, we can sequence a human genome with these next-generation
sequencing technologies for something like two to three days with promises that probably
by the end of the calendar year, that'll be down to a day, and, of course, the price is
well below $10,000. It's more like $4,000, or $5,000, or $6,000, depending on how you
calculated; very, very much en route to get it to a $1,000 genome, we believe, in the
next few years. With that, of course, has come the generation of many human genome sequences.
1990, there were none. By 2003, you had your first, but, of course, there's thousands,
and the number is growing and will continue to grow at an impressive pace.
Besides just about the human genome sequence, of course, have come opportunities to sequence
other genomes, other vertebrate genomes. Back then, there were none. By 2003, we had several,
and today, there's over 112 vertebrate genome sequences available in public databases. In
terms of non-vertebrate, you carry out of genome sequences. Back then, there were none,
when the Genome Project began. By the end of the Genome Project, there were 14, and
now there's 455. And if you go to smaller genomes, such as prokaryotic genomes, the
numbers of even more impressive, from zero to 167, and today, 8,700, and I'm sure rapidly
growing.
This is still the databases, of course. If you just look at GenBank, and you look at
the total DNA bases in GenBank, once upon a time, we only had about 49 million bases
in GenBank. By the time the Genome Project ended, it was up to 31 terabases, and today,
about 150 terabases. And a lot of that data was generated with whole genome shotgun sequencing
that came to the fore throughout the Genome Project. When the Genome Project began, there
was no such thing as whole genome shotgun sequence data available. By 2003, there was
about 9.6 terabases, and today, closing in on 400 terabases of whole genome shotgun data
available.
So, of course, that's a remarkable amount of data, both about the human genome sequence,
and vertebrate sequences, and other sequences, and total amounts of sequence data. We'd also
turned out attention to understanding how variation exists across the human population
in terms of our genome sequences, and those numbers have also grown remarkably just in
terms of knowledge about single-nucleotide polymorphisms, single base differences in
our genome that are publically available for researchers to use. Back in 1990, we had a
rather unimpressive knowledge of just a little over 4,000 such polymorphisms. By 2003, we
had several billion, but, of course, today, through efforts such SNP Consortium, and the
HapMap project, and the 1,000 Genomes Project, that number is well over 50 million known
human polymorphisms available for study.
Those polymorphisms, and other aided by technologies and aided by knowledge of how our genome work,
has led our abilities to be able to focus our attention to study the genomic bases of
disease. We've seen remarkable advances both in rare genetic diseases involving single
genes and more genetically-complex diseases. In the case of rare genetic diseases, of course,
you can look at it two ways. You can either look at diseases that we now know the molecular
basis for, or you could look at the gene level, how many genes are implicated in rare diseases,
and both ways you look at it, it's impressive. You look at the number of diseases with known
molecular phenotype, or molecular basis known. When the Genome Project began, there were
only 61 diseases for which we knew the molecular basis, but, of course, the Genome Project
greatly accelerated that even during the Human Genome Project, so by the end, that number
was up to over 2,200. Today, that number is rapidly approaching 5,000. If you look at
it from a gene-specific basis, how many genes have been implicated with rare genetic disease,
when the Genome Project began, the number was 53. It had grown considerably by the time
the Genome Project ended to about 1,474, and now that number is rapidly approaching 3,000.
In terms of complex genetic diseases, there's been similar advances. Of course, this is
a far more complicated endeavor to really get at the specific variants that are conferring
risks for common or genetically-complex genetic diseases. But what, of course, has come to
be a very valuable strategy are these genome-wide association studies developing statistical
associations between specific known variants and inheritance of risks for getting a particular
complex genetic disorder, and these GWAS studies were -- didn't exist back in 1990, and, in
fact, didn't really exist in 2003. There were other strategies, but they weren't particularly
efficient.
But now, fast forward. How many publications have been described successful genome-wide
associations studies? Over 1,500. And while we don't yet know the exact variants conferring
risks for these common diseases in all cases or even very many cases, we've learned a tremendous
amount of where to search now in the genome to try to find which variants are the ones
of biological importance. And indeed, much of this data has allowed us to then do replication
studies to actually demonstrate that, indeed, some of these variants truly are going to
be relevant for conferring risk for common diseases. Once upon a time, of course, it
was zero. When the Genome Project ended, there were actually a handful of cases. They weren't
-- they weren't found by genome-wide association studies but by other means. But now, we have
almost 3,000 variants that have now been replicated as being disease-associated.
Now, has that led to changes in the practice of medicine? Well, little bits here and there;
I think the forward-looking talks you'll hear today will point a picture -- paint a picture
about how things are going to be changing as we think about important ways of applying
genomics to improve medical care. But there has already been some progress, and there's
various metrics one could use. This is one, just in terms of understanding the genomic
basis for drug response and recognizing that people respond differently because of different
variants, and that may be relevant for selecting the proper medication for the individual patient.
If you just look at drugs for which the FDA has now recognized the importance of having
pharmacogenomic information on the labels for that drug, when the Genome Project began,
there were only four such medications. When the Genome Project ended, that number was
almost 50, and now that number is over 100, with, again, anticipation of that number growing
with time.
So I hope this is giving you a flavor of these three time points across a 23-year span, from
before the Genome Project and, really, when the Genome Project began, when it ended, and
then where we are today. And really what I want to do in really going through those numbers
was just to set the stage to start to paint this landscape, if you will, of the changing
genomics landscape that really you're going to hear now put into greater detail from the
speakers that will follow.
So that's what I wanted to emphasize, but I do want to also say a few additional things,
starting with a huge, huge thanks to a number of people who have made today's symposium
possible. I really want to give a strong shout out, "thanks," to a group, a committee, if
you will, of NHGRI staff listed here who have made today possible, in particular Rudy Pozzatti
and Brad Ozenberger who co-chaired this group, and Annette Sante, who sort of handles all
things logistic, who is running around out there making sure everything is going to happen
perfectly. A lot of the graphics associated with -- that you'll see and have seen in the
program and so forth, Darryl Leja. And then you're going to see several videos sprinkled
in, three of them throughout the day, and Larry Thompson and his team have been responsible
for these videos, and a big thanks to them for putting this together. I think you're
going to enjoy them tremendously. These other individuals also, thank you as well.
So the other thing I wanted to point out is sort of what the logistics are going to be
for today in terms of speaker introductions. We knew you wanted to hear from the speakers
much more than you wanted to hear from NHGRI staff introducing the speakers, and so we
deliberately put bios of each of the speakers in the program. And if you don't have a program,
please get one. And so what we're going to do is not have detailed introductions of each
speaker. I'm going to handle the morning session and just introduce the speakers, and at the
completion of each talk, we're going to -- if people have questions, please go to microphones
that are out there in -- on each aisle, and in part, we need to have people at microphones
because we're videotaping all of these, all of the talks, and we want to make sure we
can capture all of the questions. And then in the afternoon session, Mark Guyer, deputy
director of the National Human Genome Research Institute, will be moderating, and, again,
we're just going mostly be introducing speakers and keeping everything moving along and on
time.
So I now have the pleasure, though, of introducing a special speaker, who's the second one, and
I want to tell -- don't take my slides down. I want one more slide I want to show. And
I want to tell a little story before I turn this over to her. And the story is really,
it's a feel-good story, I think, from the point of view of demonstrating how wonderful
collaborations can happen within the government when good ideas are pursued. When I became
director of NHGRI three and a half years ago now, one of the things I was very interested
in was to continue to explore ways that we could increase genomic knowledge, especially
to the general public. We're thinking about this in many areas, but wondering how we could
pursue outreach, knowing that genomics is becoming increasingly relevant to people,
especially as it finds its way into medical care.
And one of the things I always wondered about, and I admit, having been at NIH for 18 and
a half years, and raising children in the area, was spending lots of time at the Smithsonian,
especially with my kids, wondering why was it that the National Institutes of Health,
which has so much interesting things going on in the biomedical research area, and the
Smithsonian, which is an incredibly impressive institution and its set of museums, they're
only 10 miles apart or so, and yet you walk around the Smithsonian, and you rarely see
much in the way of information coming out about the NIH, or collaborations and exhibitions
that represent partnerships between the Smithsonian and the NIH. And so I turned to Vence Bonham,
who runs our education program at NHGRI, and I said, "We should do something about this.
Let's find out if there's something we can do with the Smithsonian."
And we got a meeting with the Smithsonian's secretary, Secretary Clough, and some of his
high -- his senior staff, and we had a wonderful meeting exploring various ideas of what might
be -- in terms of ways to have our institute and genomics interact with the Smithsonian,
who actually have a lot of interest in genomics. And, true story, this happened in June of
2011, and the secretary turned to me and said, "Is there anything special happening in genomics
that we could sort of rally around and do something big?" And I said, "Funny you should
mention that." The light bulb went off in my head. I hadn't thought of it until that
moment. I said, "Well, there's this thing in April 2013 we'll be celebrating: the 10th
anniversary of completing the Human Genome Project. Let's do something. Let's do an exhibition
together," and boom, it happened, by a series of remarkable meetings and developing of collaborations
and partnerships, and the rest is history.
Although it's been very fast and furious, and on a timeline that usually doesn't happen
for the development of exhibitions at the Smithsonian, but it's going to happen, and
it's going to happen very soon. And Kirk Johnson, who is now the new director of the Smithsonian's
National Museum of Natural History, was fortune enough to be able to get here today to briefly
introduce you to this and tell you about this, and so he's the first speaker, and I'm delighted
that he was able to come join and really be the first of a series of speakers in today's
symposium.
So, Kirk.
[applause]