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By Tim Stoddard

	Charles DeLisi Photo by Albert L’Étoile

Charles DeLisi, senior associate provost of biosciences and Arthur G. B. Metcalf Professor of Science and Engineering, will deliver this year’s University Lecture, entitled Crossing the Watershed: Biological and Other Worlds in the Post-Genomic Era, on Monday, October 20, at 7:30 p.m., in the Tsai Performance Center. Admission is free and open to the public.

An internationally recognized teacher and researcher, who is often hailed as the father of the Human Genome Project, DeLisi was dean of the College of Engineering from 1990 to 1999. He is the founding director of ENG’s Graduate Program in Bioinformatics, which provides an interdisciplinary perspective on the science, engineering, medicine, and ethics of 21st-century biology. As a preview to the topics he’ll address in the lecture, DeLisi recently spoke with the B.U. Bridge about the promises and pitfalls of genomics.

B.U. Bridge: When you were appointed director of the U.S. Department of Energy’s Health and Environmental Research Programs in 1985, you initiated what would become the Human Genome Project. What inspired you to do this?

DeLisi: I had thought briefly in the early 1980s, when I was at the National Institutes of Health, about whether I would see the complete human genome sequence in my lifetime. At the time I didn’t think it would happen. I knew that developing the technology for sequencing and analyzing the genome would require a major cultural shift in the way biomedical research was conducted and funded, and I didn’t see any reason to believe such a shift would occur. I was working mostly in immunology at the time, and although I had begun doing some work in DNA sequence analysis, I was largely an outsider to molecular biology.

A few months after I arrived at the Department of Energy [DOE], I reassessed the possibilities when I learned that some of the leading people in molecular biology — including Walter Gilbert and Lee Hood — were very interested in seeing the human genome sequenced. The major problem was turning that interest into national policy. I realized that a reference human genome sequence could be extremely important to the DOE’s long-range health and environmental mission. I was fortunate enough to be in a position to develop and present that tie to political leaders.

B.U. Bridge: Can you define what genomics was in 1985 and what it is today?

DeLisi: Genomics is essentially high throughput cell biology — the development and use of technologies to study the cell as the system of interacting proteins and genes that it is. There was no such science in 1985. Scientists generally studied one gene or protein at a time. The technology for studying the collective effects of large numbers of genes and proteins on changes in a cell’s environment was relatively primitive, and few people were thinking globally.

B.U. Bridge: A working draft of the human genome was announced with much fanfare at a White House ceremony in June 2000. Then last April the leaders of the Human Genome Project announced that they had finally completed the project. What aspects of the genome do we actually have in hand, and what remains to be done?

DeLisi: We have a fairly accurate sequence of more than 90 percent of the human genome, and the complete sequences of more than 100 other genomes, mostly microbial. The human sequence has not been fully parsed — that is, there are some 30,000 genes distributed over the genome, with intervening noncoding base sequences between the genes, but precisely where the protein coding sequences begin and end is not known for most genes. When we’ve identified the boundaries — in perhaps a few years — and when, perhaps a few years after that, we’ve identified the switches adjacent to genes that turn them on and off, we’ll have essentially a parts list. But this will not be like having the parts of a complex machine. The genome is not hard-wired — it’s adaptive. Depending on environmental and internal changes, certain parts are selected to function, such as when the genes for antibodies and other mediators of the immune response are activated in response to pathogenic microbes. Developing a predictive understanding of adaptive responses for even relatively simple eukaryotic cells such as yeast is a problem that is likely to occupy biologists for the next two or three decades.

B.U. Bridge: It’s often said that genomics has opened a new era in medicine. Will genomics ever be able to prevent or cure cystic fibrosis, autism, and other diseases that appear in early childhood?

DeLisi: I believe most scientists would feel comfortable saying that these diseases will all be cured, but no one can say when, nor can anyone be sure what form a cure will take. It is sobering to remember that Linus Pauling developed a relatively clear understanding of the molecular basis of sickle cell anemia more than 50 years ago, and there is still no cure. Nor is the etiology of sickle cell anemia quite so simple as was once thought, even though it is considered a single gene disease.

B.U. Bridge: How will genomics affect geriatrics? Can today’s BU students expect to have longer lives than earlier generations?

DeLisi: The life span of the average person has increased more or less linearly during the past 200 to 300 years, for different reasons at different times. During the last century the major factors were vastly improved sanitation systems, and then the emergence of antibiotics. Some 5,000 drugs are currently in commerce, directed at about 500 medical conditions. Genomics will no doubt profoundly increase our understanding of the cell, and most scientists expect those advances to dramatically increase the number of treatable diseases. Exactly how quickly that will happen is not clear. I do believe that the increase in life span will continue into the foreseeable future, and that the advances in genomics will contribute to that increase. But such beliefs are as much religion as science — they’re based partly on faith, and to some extent on history.

B.U. Bridge: Will genomics alter the course of human evolution? Will there be another hominid species living beside us in the near future?

DeLisi: The last half of the 20th century saw dramatic advances in computer science and genetics. As these fields continue to mature, and especially where they intersect, our ability to influence our own biological evolution will become possible. In addition, during the next 200 years or so, as colonization of the solar system progresses to the point where like-minded people can develop an eco niche, my intuitive feeling is that there is a real possibility of speciation. Such events, if they occur, will probably take place over hundreds of years, rather than over millions or tens of millions of years, as they did during much of evolution.

B.U. Bridge: Is the pace of discovery in genomics going too fast for policy to keep up?

DeLisi: I would ask the question with an inverted emphasis: Is the development of policy going too slow to keep pace with scientific and technological advances? The answer to the question in that form is, unfortunately, yes. Before leaving DOE in 1987, I proposed a policy that would require 3 percent to 5 percent of money appropriated for genomics to be spent on ethical studies, the results of which I hoped — and naively expected — would be converted into policy that would help assure access to, and wise use of, the technologies. A lot of thoughtful people have done a lot of serious thinking, discussing, and writing during the past decade, and it is also possible that the amount of public dialogue has increased over what it would have been if there had been no formal support. It’s difficult to know. But so far I don’t see an effect on policy, and I don’t think one can be too impatient about these matters, because technology is going to continue to raise problems at an accelerating rate.

B.U. Bridge: Do you think genomics has endangered our genetic privacy?

DeLisi: I think there are serious privacy issues with both major technologies: computer technologies and genetic technologies. No states have laws that classify DNA samples as the personal property of the donor, only four define genetic information as personal property, and fewer than half prohibit employers from requiring genetic information. Even if privacy laws can be passed assuring that samples obtained for medical purposes are used only for medical purposes, computer systems are generally not entirely secure against hackers. The obstacles to privacy in both cases are mainly economic and social, not technical. Progress toward solution, if there has been any, is much too slow when measured on the scale of technological change.

17 October 2003
Boston University
Office of University Relations