On Capitol Hill: One Day In The Hard Life Of The Genome Project

A routine hearing turns explosive when a critic of the program finds himself under attack by a prominent senator WASHINGTON - On the morning of July 11, in the rear of Room 366 of the Dirksen Senate Office Building, health policy analyst Robert Cook-Degan was pacing anxiously. It was supposed to be a routine hearing, a chance for officials from the government's Human Genome Project to explain to a very sympathetic audience how well two federal agencies - the National Institutes of Health and the Department of Energy - were working together on this first "big science" project in biology and what technological benefits might flow from mapping and sequencing the 3 billion base pairs that constitute the human genetic code. But Cook-Degan, a former senior analyst at the congressional Office of Technology Assessment and a consultant to NIH's genome center, sensed trouble. Two of the witnesses - Harvard University biochemist Bernard Davis and University of Utah biochemist Martin Rechsteiner - were scheduled to testify that they opposed the size and scope of the multibillion-dollar project at a time when individual investigators were having a hard time obtaining federal grants. And he was worried that the legislator who had requested the hearing, Sen. Pete Domenici (R-N.M.), would not take kindly to criticism of a project that the senator had helped create and one that promised to be a boon for his state's largest employer, Los Alamos National Laboratory. Two hours into the hearing, conducted by the energy research and development subcommittee of the Committee on Energy and Natural Resources, Cook-Degan's fears were borne out. Even after listening to Nobel laureate James Watson, head of NIH's Center for Human Genome Research, Caltech biologist Leroy Hood, Genentech president and CEO G. Kirk Raab, and others talk about how the project would revolutionize biology and lead to cures for thousands of genetic diseases, Harvard's Davis didn't pull his punches. He said simply that he didn't think it was such a hot idea scientifically, and that it certainly wasn't worth the sizable budget increase that the Bush administration was requesting. "The fundamental goal is to understand the human genome and its products, and not to sequence the genome because it is there," Davis told the subcommittee. "A shift of funds from the HGP [Human Genome Project] to the general support of investigator-initiated research could advance this goal." Domenici, as they say around this town, went ballistic. He launched a verbal attack normally reserved for the most contentious political debates, those between a powerful committee chairman and a Cabinet secretary, for example. Indeed, one NIH administrator later confessed to never having seen such an outburst directed at a private citizen. "I am thoroughly amazed, doctor, at how the biomedical community could oppose this project," Domenici bellowed. "I am absolutely amazed at how you could do that I cannot conceive that this small amount of money for this project, $200 million a year over the next five years, could conceivably be opposed by the biomedical community of this country I cannot believe that you are going to insist on business as usual in this field. It is beyond my comprehension, I repeat, beyond my comprehension." Davis, formerly Watson's colleague and no stranger to controversy in his long and illustrious career, was clearly taken aback by the attack. He had already testified that he believed his views, "although a minority view here represent a majority view of biomedical scientists around the country." But he felt compelled to repeat his point - that the statement had been endorsed by his entire department at Harvard and by his professional society's public affairs committee. "If I were only presenting my own idiosyncratic point of view, senator, then I would feel properly chastened," he replied. "But I would urge you not to underestimate the extent of unhappiness in the biomedical community over the issue. . . . There is great uneasiness over certain aspects of this program, including the notion that it somehow deserves to be a crash program, very generously funded, at a time when there is famine in other areas of science." Welcome to the congressional hearing. It's a ritual conducted thousands of times a year in the nation's capital, part entertainment and part substance. Hearings are a chance for legislators to showcase programs of particular interest to them, to question the people running those programs, and to make sure that federal dollars are being spent wisely. Hearings are also a chance for politicians to get across their own views on a subject, and to push their own agendas. While the issues before a congressional panel range from foreign aid to the savings and loan fiasco, science and technology are a frequent topic of conversation as well. There are some two dozen committees and subcommittees with jurisdiction over that portion of the federal government that conducts or pays for research, and scientists are called on regularly to explain aspects of these programs before audiences both sympathetic and skeptical. The events at a hearing are carefully scripted to achieve a certain effect. Participants are likely to make statements that occasionally exaggerate, if not misstate, the facts in order to make their points. A free-flowing debate on an issue is rare - the legislators who attend do so normally because of a strong attachment to the subject, and a lack of interest keeps away those who are least informed about an issue. As a result, scientists accustomed to having hard numbers and cold logic carry the day will be disappointed at what does, and does not, happen at a congressional hearing. Still, as Davis can attest, there is always the chance that the unexpected will occur. More positively, as Cook-Degan noted after the hearing, "word about what goes on gets back to other senators," and it's not uncommon for words spoken during a hearing to influence later debate on an issue. Imagine - all this, and more, in a three-hour hearing. And the admission is free. Following are highlights of a long morning's journey into science policy in our nation's capital. What took place July 11 is known, in political terms, as an oversight hearing. Domenici wanted to hear how the Energy Department was handling its portion of the Human Genome Project, an effort it launched in 1987 but has since been forced to share with a growing NIH presence. (DOE wants to spend $46 million on the project in 1991, while NIH has requested $108 million. Last month, however, the House trimmed that request to $66 million. If agreed to by the Senate, that total would nevertheless be a $10 million increase over current levels.) Domenici's enthusiasm for the project is due in large part to the presence in his state of two DOE-funded national labs, Los Alamos and Sandia, although Sandia is not involved in the HGP. He and other supporters also see the genome project as a way to develop some of the advanced technical tools that are needed to bolster the U.S. economy in its struggle to remain competitive internationally. Those two issues - where the project was headed and how it could help the U.S. stay ahead of the Japanese and Europeans - were on the top of his agenda for the hearing. Martin Rechsteiner has worked hard to make known his concerns about the Human Genome Project. In fact, doing so has become practically a second career for the University of Utah biochemist. In January Rechsteiner penned a letter expressing his view that much of the information to be generated by the project would be worthless, as well as his fear that it is receiving money that would be better spent on investigators seeking individual grants from NIH. Then he sent it off to hundreds of his colleagues, asking them, in turn, to convey their feelings about the project to federal science administrators. The title of that now infamous letter - presidential science adviser Allan Bromley has mentioned it repeatedly in speeches before scientific audiences as an example of how not to lobby the government - summed up Rechsteiner's opinion of the project: "Mediocre Science, Terrible Science Policy." The letter was originally submitted to the FASEB (Federation of American Societies of Experimental Biology) Journal. But it's only this month, in the current issue of the journal, that the letter is finally appearing in print. And it is flanked by a letter in favor of the project, coincidentally co-written by Rechsteiner's colleague at Utah, geneticist Ray White. Rechsteiner says that he had to lobby hard to be heard - sending a total of 47 letters to the top officers of all seven of FASEB's constituent societies - before editor William Whelan agreed to run his piece. Whelan, a professor of biochemistry at the University of Miami, says that he intended all along to run the letter, but that he felt a countervailing view was essential. The delay, he says, was simply a matter of "miscommunication" between the journal and the authors of that counterpoint. In the meantime, Rechsteiner has been busy promoting his cause. In addition to his recent testimony before the Senate, he's fired off a letter to Science in response to an article (248: 1600-1, June 29, 1990) on the issue. But the letter was rejected, he says. And he is scheduled to appear in an upcoming issue of Trends in Biological Sciences (TIBS) in a debate with Caltech biologist Leroy Hood. Hood and other supporters of the project believe strongly that their views, embodied in a 1988 National Academy of Sciences report on how the effort should proceed, will ultimately prevail. "I'm convinced that we need to do this, and I think that the criticism is basing its arguments on faulty premises," says Daniel Nathans, a Nobel laureate and a microbiologist at Johns Hopkins University, in a typical comment about Rechsteiner's opposition. Nathans believes that scientists should lobby for more money for all areas of biomedical research rather than attacking the genome project's share, and he says that opponents fail to understand that the project will benefit all researchers. But Rechsteiner has no plans to give up his fight. Several university biochemistry departments have reportedly generated petitions opposing the current scope and nature of the genome project. And Rechsteiner thinks he's making progress. "The campaign has been much more effective than I ever expected," he says, pointing as evidence to the recent cuts in the program voted by the House of Representatives. "But I have to be careful about what I say. I don't want to sound petty, vindictive, or personal in my criticism." --J.M. But Domenici's staff hadn't taken into account what appears to be growing opposition among biochemists and microbiologists to this expensive big science project. So last spring, when his staff asked the subcommittee on which Domenici sits as ranking minority member to put together a hearing on the subject, subcommittee staffer Ben Cooper felt obliged - even if it went against the wishes of some members - to include witnesses on both sides of the issue. Cooper, a physicist who has worked on the energy committee for 16 years but has only recently gotten involved in the genome project, did his best. He lined up Watson and his DOE counterpart, David Galas, to present the administration's side, followed by Davis and Rechsteiner to present opposing views. He hoped the quartet, once they had completed their testimony, would generate a lively panel discussion that would explore all the relevant issues and, most importantly, educate the senators. But the battle was never really joined at the hearing. Domenici's staff says the senator was more interested in listening to the proponents, including officials from the three DOE-funded labs working on the project, Hood, and Raab. If time permitted, they made clear, he would entertain the views of Davis and Rechsteiner. As a result, Davis was not called upon until the end of the hearing, when all but one of a dozen members of the press who showed up at the start of the hearing had left the room. Thus, with all of the proponents having aired their views and with the senators growing weary, Davis was left to wonder whether his side would have any time to present its arguments. The discussion was further skewed because Rechsteiner didn't make it to the hearing in time. The day before the session, Domenici realized that he had a scheduling conflict, and asked if the hearing could be changed from the afternoon to the morning. Cooper was able to reach all of the witnesses, but Rechsteiner. As a result, when the Utah biochemist walked into the hearing room shortly after noon, he discovered he was three hours late rather than two hours early. "I was disappointed that I couldn't testify," Rechsteiner says, adding quickly that he is convinced the exclusion was not deliberate. "But I think that there has been a systematic attempt to stifle debate on this subject, and the hearing is one more example of that fact." His absence left Davis as the only naysayer in the room. In addition to his criticism of the scope and pace of the project, Davis told the committee that he thought proponents of the project were exaggerating the benefits that would flow from it. But committee members didn't want to hear that message. On the contrary, subcommittee chairman Sen. Wendell Ford (D-Ky.) had earlier in the day urged witnesses to explain how the project would strengthen the U.S. economy. Even though national lab officials conceded that royalties from licenses generated by patents granted in connection with the genome project were tiny - one administrator estimated they have yet to reach $100,000 - Ford persisted. "But there could be some big money in this particular program, couldn't there?" he wondered. "Yes, sir," replied Anthony Carrano, director of the genome center at DOE's Lawrence Livermore National Laboratory. And then the Kentucky legislator, thinking about the tobacco farmers back home, took the plunge. "Because when you grab the breakthrough and you start saving lives, and we do not have to worry about smoking cigarettes anymore, well, then you have got my money," he declared. His comment drew a laugh from the audience. But Carrano remained silent, apparently not willing to contradict the chairman of the Senate committee with legislative control over his laboratory and its programs. A similar exchange occurred when Domenici pressed Watson on the importance of moving ahead quickly to retain a competitive edge over the rest of the world. "What if the U.S. doesn't go ahead?" the senator asked. "Aren't the Japanese interested in mapping the genome, too?" Despite his belief that the project is vital, Watson felt obliged to stick to the truth. "They're doing a little," he acknowledged, "but not much." Galas added that the Japanese this year are spending a paltry $7 million, spread across four ministries, compared to the $150 million sought by the Bush administration. But keeping the U.S. on top was never far from Domenici's mind. Thanking Hood for his testimony, Domenici made a point of praising the Caltech scientist and entrepreneur for recognizing how the project will "prime the American economic pump" by developing new technologies. And he sent a message to the rest of academe about the type of basic research he thinks is most worthy of federal support. "It is indeed an honor, and very refreshing, to hear from a distinguished professor such talk about the applications of health research to America's economic future," Domenici said. "I think that more academic leaders will need to talk this way or we won't be able to continue supporting all their wonderful work." Unfortunately, Hood had supplied faulty data to support one of Domenici's favorite themes, namely, that the genome project will help keep the U.S. ahead in biotechnology. Hood described how a company based on genome technology developed in his lab, Applied Biosystems Inc., has become an important contributor to the nation's trade balance, with more than one-half of its profits derived from sales of sequencing and other biotech equipment to Japan and Western Europe. Ironically, that company is now going through hard times (The Scientist, June 25, 1990, page 1) and some industry analysts question whether it can hang onto its niche in the market. And the number Hood used - $180 million in profits last year - is about 10 times what the company says it made in the year ending June 30, 1989. In fact, Hood's figure was some $22 million higher even than the company's total annual sales for the year. Hood says that he got the information from the company, but vice president Michael Hunkapiller confirmed that the number submitted in testimony was inaccurate. Finally, after sparring with Davis, Domenici was ready to pronounce himself satisfied with the current state of the U.S. Human Genome Project. "I think that it has been an excellent hearing," declared the ranking minority member of the subcommittee and a key figure in the current budget negotiations with the White House. "As someone who is supposed to know all about the federal budget, I am rarely in a position where I can look at a program and say that it is exciting enough to keep somebody like myself energized while we are busy trying to reduce the deficit. But I have found one here. And I am absolutely convinced in saying that we would be foolhardy if we did not proceed." It remains to be seen whether his colleagues will agree with him, reversing the cuts that the House had made in the program's proposed 1991 budget and insisting on the administration's original request. And, the question of whether it's best to proceed in such a fashion will continue to generate debate within the scientific community. But for now there's a record of the Senate's having explored the subject. And it leaves no doubt where Domenici stands on the issue.

On Capitol Hill: One Day In The Hard Life Of The Genome Project

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