Clinton, Blair Stoke Debate on Gene Data

President Bill Clinton and British Prime Minister Tony Blair's brief statement of March 14 supporting free access to human genome information unleashed a slew of clichés, including "too little too late" and "water under the bridge." But initial misinterpretation of the statement led to a temporary slide in biotech stocks. By the end of the day, Celera Genomics Corp. of Rockville, Md., had dropped 19 percent, while Incyte Pharmaceuticals of Palo Alto, Calif., plummeted 27 percent. Even thoug

Apr 3, 2000
Ricki Lewis

President Bill Clinton and British Prime Minister Tony Blair's brief statement of March 14 supporting free access to human genome information unleashed a slew of clichés, including "too little too late" and "water under the bridge." But initial misinterpretation of the statement led to a temporary slide in biotech stocks. By the end of the day, Celera Genomics Corp. of Rockville, Md., had dropped 19 percent, while Incyte Pharmaceuticals of Palo Alto, Calif., plummeted 27 percent. Even though the stock market soon rallied, ill will lingers between the public and private genome sequencers that the statement addressed.

As in much in life, timing influenced the impact of the Clinton-Blair remarks. Reportedly in the works for months, the announcement was set to coincide with the awarding of the Medals of Science and Technology. But it came on the heels of Britain's Wellcome Trust's March 5 public release of correspondence detailing the acrimony between the public and private genome efforts.1 "The communication between the public and the private sector fell apart, so lo and behold, Clinton and Blair issued a statement. To use old labor-negotiating terms, they wanted to bring it back to the bargaining table," says Art Caplan, director of the Center for Bioethics at the University of Pennsylvania.

The statement is a mere three paragraphs. The first acknowledges the importance of the project. The final paragraph, without resorting to actual name-calling, shakes a subtle finger at the private sector: "We applaud the decisions by scientists working on the Human Genome Project to release raw fundamental information about the human DNA sequence and its variants rapidly into the public domain, and we commend other scientists around the world to adopt this policy."

The middle paragraph gets down to business. It begins, "To realize the full promise of this research, raw fundamental data on the human genome, including the human DNA sequence and its variations, should be made freely available to scientists everywhere." The paragraph ends with what should have comforted biotech company stockholders: "Intellectual property protection for gene-based inventions will also play an important role in stimulating the development of important new health care products."

Unfortunately, word got out ahead of the statement, and the White House news staff goofed. Early on March 14, White House press spokesperson Joe Lockhart told a group of reporters that the president would restrict gene patents. A 9 a.m. radio report began, "CBS has learned that President Clinton later today will unveil an agreement with Britain to ban patents on individual genes." By 10 a.m. CBS hedged, reporting that the event would be a "statement of principles urging a ban on patents on individual genes." Finally, at 12:45, White House science adviser Neal Lane told reporters that "... the statement is not about patents or what should or should not be patentable."

Backdrop to the Statement

The White House statement makes more sense when placed into the perspective of recent history2--which could be subtitled "Public Consortium vs. Celera Genomics." Although Celera is not the only company sequencing the human genome, it is the most visible.

J. Craig Venter and PE Corp. of Norwalk, Conn., formed Celera in May 1998, vowing to sequence the human genome sooner than the public consortium, and at a tenth of the cost. From anyone the claim might have seemed ludicrous, but Venter had the invention of expressed sequence tag (EST) technology behind him, and an impressive collection of sequenced genomes from The Institute for Genomic Research, which he also founded. Celera has always maintained that it would make genome information public but license the rights to mine it for discoveries, while patenting 100 to 300 "valuable" gene sequences. "We provide the data, and they can make the discoveries," says Venter, "they" referring to early clients from Big Pharma. But it is access for other researchers that concerns many. "Very few people are ... awake at night worrying whether Merck can afford Celera's information or not. As long as the information is out there for students and researchers, and scientists in developing nations, that will get us where we need to be in a short time," says Caplan.

But that time isn't here yet. In March 1999, Francis Collins, director of the U.S. National Human Genome Research Institute, and Michael Morgan, executive for genome sequencing of the Wellcome Trust, which funds part of the global public effort, announced a compromise in accuracy to accelerate the sequencing timetable--a move widely interpreted as "Let the race begin." At the same time, researchers deep into the soon-to-be-obsolete meticulous work of positional cloning began to recognize how valuable that working draft would be. "The effect of Celera on the genome project has been positive. It forced a rethinking of strategy. Prior to Celera, the goal was a high-quality finish, put one segment out, do the next. But for anyone who wants to use genome data, the draft is the important thing. Even to just roughly know the sequence in the region you are working in will be so enormously valuable that it makes no sense not to do that first," says David Galas, chief academic officer at the Keck Graduate Institute in Claremont, Calif. Galas headed the Human Genome Project at the Department of Energy from 1990 through 1993.

Fast forward to March 2000. Four representatives of the public consortium met with Celera executives on December 29, 1999, seeking cooperation. When weeks passed and Celera had not responded, the group sent a long letter, dated February 28, to the company, outlining their "fundamental differences." It was this correspondence that the Wellcome Trust made public on March 5. Yet despite the communication breakdown, Celera has demonstrated, with the unveiling of the Drosophila melanogaster genome sequence,3 that it can cooperate with the academic sector. But for the human genome, the stakes are much higher, and neither side could agree on a time frame of exclusivity of sequence data.

At issue seems to be when genome data is released--the public consortium does so daily. "Celera announced that they will wait until the sequence is final before they release it. This implies that until then, it will not be available," says Joseph Brown, president and CEO of LifeSpan BioSciences in Seattle. "The letter revealed March 5 essentially stated that an adversarial relationship had developed. There was growing concern that the human genome sequence would not be made public in a timely manner, and Clinton and Blair were setting policy in stating that that could happen," he adds.

Response

All involved swiftly tried to put a positive spin on the Clinton-Blair statement. Later in the day at the White House, Collins said of the sequence, "To ensure that this information is available for researchers to develop a new generation of diagnostics, treatments, and preventive strategies, this fundamental information must be placed in the public domain for all to use freely."

Celera's official response began with a welcoming of the statement, reiterating that the company's mission "is completely consistent with the goals of assuring that the world's researchers have access to this important information to enable advances and discoveries that will improve the human condition." But the Celera response, perhaps understandably, also had a defensive tone: "Celera is in the business of discovering and disseminating valuable scientific information, not withholding, delaying, or politicizing such."

The Washington, D.C.-based Biotechnology Industry Organization (BIO) focused on the key sentence addressing intellectual property. "The joint Clinton-Blair statement acknowledges the vital role that patents play in providing an incentive for this research. It is quite clear that no patent would ever be issued for raw fundamental genome sequences, the type of data covered in the Clinton-Blair statement. Generating this raw data--something that a machine can do--is not an invention for which a patent is appropriate," said Chuck Ludlam, BIO vice president for government relations.

William A. Haseltine, chief executive officer of Human Genome Sciences Inc. in Rockville, Md., explained at a press conference a week after and in response to release of the White House statement that gene patents are part and parcel of doing science. "If research is supported by the federal government, and has an application, it must be patented. [National Institutes of Health] has been filing patents on genes and proteins as drug targets and diagnostic markers for years." The effect of gene patents on research may in fact be positive, rather than a deterrent, adds Donald Pochopien, a patent attorney at McAndrews, Held and Malloy Ltd. in Chicago. "The announcement is not going to affect the biotech industry very much. In fact, it may help. People will be able to improve uses of genes, then patent that as a new invention."

The misinformation from the White House was especially confusing because hundreds of human DNA sequences have already been patented.4 "Patent law is derived from the Constitution, and the same statutes are required of all inventions--they must be novel, useful, and nonobvious. Gene sequences must have a useful application," explains Judy Jarecki-Black, a patent attorney with Womble, Carlyle, Sandridge & Rice in Atlanta. And outside of an act of Congress or Parliament, there is little that Clinton or Blair can do in this regard. "The president cannot force a company to makes its data freely available. That could be construed as a taking by the government without due process and appropriate compensation--not too different than the government stopping by your house and taking your furniture away just because the president decided he did not want you to own any furniture," says John Kilyk, a patent attorney for Leydig, Voit and Mayer Inc. in Chicago.

Life after the End

It might not be a coincidence that an anagram of "genome" is "ego men," for at times the personalities loom large over the scientific issues in what Caplan calls "a massive ego dispute." But all that should be put aside, maintains Galas. "The main question is how to get a more rational discussion about a partnership between the private and public communities. Who gets control, and when we get to see the completed genome, all that can be worked out." The White House statement, he adds, did nothing to solve the dilemma.

A battle of the egos today, over credit for a project with an endpoint, means that the matter will ultimately be moot. While a draft will enable researchers to fill in their blanks and overlap their gene segments, applications are already in full swing. Gene therapy trials have been ongoing for a decade, and DNA microarray technology is on the verge of yielding its first commercial products. And genomics companies are deciphering patterns of gene expression in different tissues.

LifeSpan, for example, has developed a database of expression patterns of G protein-coupled receptor genes that can help its pharmaceutical company clients predict drug responses at the cellular level. "We have made extensive use of the public domain data. The results and efforts of the Human Genome Project have been of immense value for academic researchers and small companies by providing access to raw human sequence. They are laying the foundation for the next stage in biology, understanding where genes are expressed and how they work," says Brown.

In short, on the day that the human genome sequence is revealed, the sun will still rise and set. But the repercussions of the accomplishment will mold medical science in ways that we might not yet even imagine. Concludes Ludlam, "We have a hundred years of genome research to do, and we need the full participation of the public and private sectors to understand what this genetic information means." It is perhaps the ultimate irony that the human foibles of some of the major players threaten to strangle the completion of this long-awaited endeavor.

Ricki Lewis (rickilewis@nasw.org) is a contributing editor for The Scientist.

References

1. E. Marshall, "Talks of public-private deal end in acrimony," Science, 287:1723-4, March 10, 2000.

2. R. Lewis and B. Palevitz, "Sequencing stakes: Celera Genomics carves its niche," The Scientist, 13[15]1, July 19, 1999.

3. Science, in press.

4. D. Steinberg, "Biotech faces evolving patent system," The Scientist, 14[5]:8, March 6, 2000.