Leroy Hood describes eleven ways the Human Genome Project reshaped biology since its first publication a decade earlier. The project democratized genetics by making every gene public, proved there are no race-specific genes, and brought computer scientists and mathematicians into biology, creating a data-driven field. It also enabled medical diagnostics and pharmacogenomics, identifying hundreds of actionable genetic variants.
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I would say this is an excellent time to assess the impact of the Genome Project. It's been 10 years since the first reference genome sequence was published, and since that time an enormous amount has happened. But I think from a historical point of view, a question we can ask is, if in 50 years we look back and ask, what did the Genome Project do? I think there 10 or 11 points that we can make. So number 1, I think maybe in many ways the most important thing the Genome Project did was to democratize biology, and by that it made all genes available to all biologists. And this has given every field of biology uniquely powerful tools for discovery and for application to commercial kinds of opportunities. The second thing the Genome Project did, and from a selfish point of view I think it's a very important aspect, is for the first time it defined all of the human genes. That is, it gave us a complete parts list of the components in a human organism And from the point of view of systems biology, that parts list was essential to being able to do systems biology. So what the Genome Project did more than anything from my point of view was enable the emergence of this field called systems biology. We started the first institute in the year 2000, and there are now 60 or 70 institutes across the world that are at the leading edge of transforming how biology is actually finished. I would say a third thing that was done that was really essential was it revolutionized our understanding about protein. The ability to look at the digital organization of information in living organisms all the way from single cell to multi-celled creatures, the ability to see the continuity of life, the conserved kind of information, I think has absolutely transformed our understanding of evolution. And in some ways, it's had really fundamentally important implications I think, for society. Number one, there are no race-specific genes. It means all humans are a part of the same race. It means that if we differ one from another, it is almost certainly because of environmental conditions. And so if we, for example, want to deal with terrorism, the worst thing we can do is go to war. We have to bring to the terrorists education, healthcare, and the other opportunities that many throughout the world have. A second thing that it's done that I think has been transformational is it's shown the incredible continuity of life from the simplest to the most complex organisms. And I think for the first time it's given us a heightened sense of responsibility of mankind humankind, for preserving the environment, and preserving all of life. So I think this understanding of evolution and our relatedness has created a connectiveness that brings society together in a scientific as well as a societal way never before happened. The fourth thing that the Genome Project has done is it catalyzed in biology for the first time an enormous appreciation of technology. The creation on the one hand of machines for doing DNA sequencing, but on the other hand for looking at the activity of genes and ultimately for looking at the activity of proteins. And it's brought to biology high-throughput technologies that have transformed the kind of information that we can gather. A fifth thing that it's done is it totally has enabled a new field called proteomics, and it's done so because proteomics uses instrumentation called mass spectrometry, and the essence of that instrumentation is you have to know the molecular weight of all of the proteins or protein fragments that you're looking at in order to be able to measure them. And again, by giving us all genes, that gave us all proteins, and that absolutely enabled this new field, which is transforming fascinating aspects of biology right now. I think another area that it engendered in biology is it recruited to biology for the first time enormous numbers of computer scientists chemists and mathematicians. It created quantitative, real biology in a way we had never done before. For many years there had been a field more or less called theoretical biology, but my feeling about that field was it didn't ever really deal in general with the reality of biology, and it had very little influence on what biology came to be. When we brought in the computer scientists and the mathematicians to figure out how to deal with information that was exploding from the genome and other kinds of analytic measurements. This really was transformational. The Genome Project also transformed the sociology of science in two fascinating ways. Number one, it was the first project which absolutely mandated standards of quality control for the information it generated. This took an enormous battle, but in the end, funding agencies said it shall be so, and it was one of the best things that ever happened to the Genome Project because everything that was sequenced had a quality metric that was associated with this. And this is critical for the future, the new kinds of information we're generating We have to be able to do exactly the same thing. The Genome Project was an absolute model. A second aspect of the sociology of science that the Genome Project transformed was open data. That is, the idea was as soon as you generated this new information, you made it available for the entire community so everybody could get in and analyze it and use it to reformulate their own thinking about biology and about how you do genomics. And again, this open data, open source attitude has been a critical dimension in spreading the power of genome throughout the world of science and everything. I would say an 8th thing that the Genome Project did was to create, for the first time really, the field of medical diagnostics. So right now there are 200 to 300 variants in our genes that if we know a patient has them, we can suggest something that they can actually do about them. These are variants that are actionable, that will let physicians help the patient. And there are another set of conditions mutations, probably 70 or 80 in number, that involve the genes that metabolize drugs. And we also— this is called pharmacogenomics— and we also know that if patients have those variants, we have to be very careful about the kinds of drugs that they take and the amounts of those drugs that they take, so we can inform them. I think another area, a 10th area now that was really exciting is this whole idea that we opened up the genomes of single-celled organisms, of multi-celled organisms, of plants, of animals to instantaneous access. And not only has this transformed the biology practiced in many areas, and I would say microbiology is one of the prime examples. It has actually given us access to information that I think in time will let us transform and attack some of the most fundamental problems in human society. I'd say healthcare, global medicine, agriculture, nutrition, energy, and the environment. All of those are going to be solved and attacked in very powerful ways with biology, and at the core of those biology will be the information that came from the Genome Project. The 11th and final example that I'll give you is it has raised a fascinating and challenging question, issue for the field of biology itself. Itself. In the past, biology was largely populated by independent investigators, each of whom took on with their laboratories the solution of a particular problem of their own choice. So in many ways, biologists were like Brownian particles. They all moved totally independently of one another. But what the Genome Project was an example of is integrated cross-disciplinary science where we focused a whole series of scientists together with a particular objective and we coordinated and organized their activities. So in this case, they solved the sequence of the Human Genome Project. And what this has raised is the realization that there are really two major approaches approaches to biology. There is the small science approach epitomized by Cold Spring Harbor, still very, very important, but there is this big science, this cross-disciplinary integrated approach, and that is essential for taking on really big problems like the Genome Project and solving them in a coordinated and effective way. And I think this is an I mean, a lesson that's extremely important to the government politicians and so forth because, for example, back at NIH now, there's a big battle going on between big science and small science. NIH is dominated by small science advocates, and the real worry is the small science advocates are going to say, let's remove big science and only do small science. And I think what we get from the Genome Project is a compelling argument that our portfolio for science funding has to be balanced and mixed. We need big science to solve really big, integrated, organized, difficult problems. We need small science to really operate on the opportunities that come out of big science. The two together are enormously synergistic.
