|Evolution of a
Genome Project Origins,
In an interview at a DNA sequencing conference in Hilton Head, South Carolina,* David Smith, a founder and former Director of the DOE Human Genome Program, recalled the establishment of this country's first human genome project. The impressive early achievements and spinoff benefits, he noted, offer more than mere vindication for project founders. They also provide a tantalizing glimpse into the future where, he observed, "scientists will be empowered to study biology and make connections in ways undreamt of before."
*The Seventh International Genome Sequencing and Analysis Conference, September 1995.
The genome project also is providing enabling technologies essential to the future of the emerging biotechnology industry, catalyzing its tremendous growth. According to Smith, the technologies are apable of more than elucidating the human genome. "We're developing an infrastructure for future research. These technologies will allow us to efficiently characterize any of the organisms out there that pertain to various DOE missions, with such applications as better fuels from biomass, bioremediation, and waste control. They also will lead to a greater understanding of global cycles, such as the carbon cycle, and the identification of potential biological interventions. Look at the ocean; an amazing number of microbes are in there, but we don't know how to use them to influence cycles to control some of the harmful things that might be happening. Up to now, biotechnology has been nearly all health oriented, but applications of genome research to modern biology really go beyond health. That's one of the things motivating our program to try to develop some of these other biotechnological applications."
Responding to criticism about not researching gene function early in the project, Smith reasserted that the purpose of the Human Genome Project is to build technologies and resources that will enable researchers to learn about biology in a much more efficient way. "The genome budget is devoted to very specific goals, and we make sure that projects contribute toward reaching them."
Progress in genome research requires the use of maturing technologies in other fields. "The combination of technologies that are coming together has been fortuitous; for example, advances in informatics and datahandling technologies have had a tremendous impact on the genome project. We would be in deep trouble if they were at a lessmature stage of development. They have been an important DOE focus."
According to Smith, more people and groups need to be involved in ELSI matters. "We have some ELSI products: the DOE-NIH Joint ELSI Working Group has an insurance task force report, and a DOE ELSI grantee has produced draft privacy legislation. Now it's time for others to come and translate ELSI efforts into policy. Perhaps the new National Bioethics Advisory Commission can do some of this."
New Model for Biological
"That's how I think about what we do at DOE," he said. "We're working a lot on technology and projects aimed at human and microbial genome sequencing. For understanding sequence implications, we are making major, increasing investments in synchrotrons, synchrotron user facilities, neutron user facilities, and big nuclear magnetic resonance machines. These are all aimed at rapid structure determination." Smith explained that now we are seeing the beginnings of the biotechnology revolution implied by the sequencetostructure tofunction paradigm. "If you really understand the relationship between sequence and function, you can begin to design sequences for particular purposes. We don't yet know that much about the world around us, but there are capabilities out there in the biological world, and if we can understand them, we can put those capabilities to use."
"Comparative genomics," he continued, "will teach us a tremendous amount about human evolution. The current phylogenetic tree is based on ribosomal RNA sequences, but when we have determined whole genomic sequences of different microbes, they will probably give us different ideas about relationships among archaebacteria, eukaryotes, and prokaryotes."
Feeling good about progress over the previous five years, Smith summed
it up succinctly: "Genomics has come of age, and it is opening the door
to entirely new approaches to biology."
David Smith retired at the end of January 1996. Taking responsibility for the DOE Human Genome Program is Aristides Patrinos, who is also Associate Director of the DOE Office of Biological and Environmental Research. Marvin Frazier is Director of the Health Effects and Life Sciences Research Division, which manages the Human Genome Program.