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May 10, 1998

Scientist's Plan: Map All DNA Within 3 Years

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  • The Struggle to Decipher Human Genes (March 10)

    A pioneer in genetic sequencing and a private company are joining forces with the aim of deciphering the entire DNA, or genome, of humans within three years, far faster and cheaper than the federal government is planning.

    If successful, the venture would outstrip and to some extent make redundant the government's $3 billion program to sequence the human genome by 2005.

    Despite a host of new questions, the charting of the full human genome would offer enormous medical and scientific benefits.

    The principals have high credibility in the world of genome sequencing. They are Dr. J. Craig Venter, president of the nonprofit Institute for Genomic Sciences in Rockville, Md., and Michael Hunkapiller, president and technical maestro of the Applied Biosystems division of Perkin-Elmer Corp. of Norwalk, Conn.

    Hunkapiller's unit is a principal manufacturer of the machines used to sequence DNA, or determine the order of chemical units. The venture will be financed by Perkin-Elmer, a longtime scientific instrument maker that has recently branched into the genome field under the leadership of its new chief executive, Tony White.

    A plan to form a new company for the venture was approved by Perkin-Elmer's board on Friday afternoon. The project could have wide ramifications for industry, academia and the public because it would make possible almost overnight many developments that had been expected to unfold over the next decade.

    One such development is individualized medicine, the tailoring of drugs and other treatments to patients depending on specific variations in their DNA sequence. The wide availability of individual DNA sequences would raise more urgently the longstanding but unresolved issues of privacy and control of genetic information.

    The possible possession or control of the entire human genome by a single private company could also become an issue of public concern.

    The new venture was conceived only a few months ago. Hunkapiller believed that a new generation of sequencing machines coming on line would be so fast that the whole human genome could be completed far sooner and 10 times more cheaply than envisaged by the National Institutes of Health.

    He approached Venter, who had developed the idea for a new sequencing strategy but lacked the means to execute it. The two men concluded in January that it would be possible to sequence the 3 billion letters of human DNA within three years, at a cost of $150 million to $200 million.

    The $3 billion federal program, by contrast, is now at the halfway point of its 15-year course, and only 3 percent of the genome has been sequenced. The strategy has been to divide the task and assign parts to various universities. Although the program has had many successes in pioneering a daunting task, serious doubts have emerged as to whether the universities can meet the target date of 2005.

    The human genome contains all the instructions -- some 60,000 or so genes -- needed to design and operate the human organism.

    Deciphering the script in which the instructions are written -- the chemical units of DNA -- would yield a trove of knowledge about human physiology and disease, as well as the power, in principle, to correct the errors in DNA programming that cause genetic disease. The genome, once deciphered, is likely to be seen as the foundation of human biology, and hence is the object of intense scientific and commercial interest.

    The proposal to substantially complete the human genome in three years would seem extreme hubris coming from almost anyone but Venter. But other experts deemed his approach technically feasible.

    "It's not impossible at all that he could succeed," said Dr. William Haseltine, chief executive of Human Genome Sciences of Rockville, Md. "He has demonstrated a fine track record of innovation and organization."

    Haseltine's company was for several years in uneasy partnership with Venter's institute.

    If successful, the new venture seems likely to impose adjustments on all the others involved in genome research, and to offer new opportunities. Congress, for instance, might ask why it should continue to finance the human genome project through the National Institutes of Health and the Department of Energy if the new company is going to finish first.

    The sponsors of the new venture insist that there will be more work for the human genome project participants to do, not less, because obtaining the DNA sequence is only the first step toward understanding what the genetic instructions mean and how they operate.

    "There is a strong case for Congress to increase funding for this work," said White of Perkin-Elmer. "The post-genomic world will be much more exciting."

    With the new company, Perkin-Elmer would seem for the first time to be stepping into direct competition with the customers who buy its sequencing machines and other genome-analysis equipment. White, however, has no evident ambitions to become the Bill Gates of the genome world.

    "We are anxious to talk to anyone who might feel threatened by this to make very sure that we are doing something compatible," White said.

    Even Venter, who is known for his direct approach, said, "We are trying to do this not with an in-your-face kind of attitude." He added that he intended to work closely with the National Institutes of Health. On Friday he briefed Harold Varmus, the director of the institutes, and Francis Collins, director of the agency's part of the human genome project, about the new company's plans. Neither was immediately available to comment.

    Venter forecast that the possession of the human genome sequence would stimulate new directions in medicine and biology, just as his sequencing of the first bacterial genome has led to a wave of other microbes being spun through sequencing machines. He said he intended to build a network of collaborators around the world to work on human genetic diseases.

    Venter and his new colleagues plan not just to sequence the human genome but to construct a "definitive" database that will integrate medical and other information with the basic DNA sequence. An important component of the new data base will be human polymorphisms, the geneticists' term for commonly found variations in DNA.

    Though all people and ethnic groups are thought to have an overwhelmingly similar sequence of DNA letters in their genome, there are many minor variations at certain sites on the genome, and these variations make each individual unique.

    The new company's database seems likely to rival or supersede Genbank, the databank operated by the National Institutes of Health.

    Having so much information in the control of one company is also likely to be a matter of some public concern.

    "The question is, can the moral and legal questions be addressed if the largest scientific revolution of the next century is going to be done under private auspices?" said Arthur Caplan, an ethicist at the University of Pennsylvania with whom Venter has discussed the new company's goals.

    The issues of genetic counseling and insurance have been around for some time, Caplan noted, but the new company's plans "accentuate the need to improve statutes governing the control of genetic information."

    Perkin-Elmer intends to be sparing in laying claim to intellectual property rights over the genome, believing the company will create more demand for its machines if it allows its sequences to be widely accessible. White said his company had a track record of liberally licensing its inventions so as to improve the chances of their becoming the industry standard.

    Whether the new company could gain a significant lock on the human genome in terms of patents is not at all clear. Human Genome Sciences, for example, has already obtained the full-length sequence of 80 percent of human genes, Haseltine said, and has presumably filed patent applications. The new company may therefore find that others have beaten it to the treasure trove.

    Even though many have now been sequenced, genes constitute only 3 percent of the total genome. Haseltine suggested that the long regions of DNA in between the genes were like cosmology, fascinating to know about but of little commercial interest.

    The new company will be 80 percent owned by Perkin-Elmer, with Venter and others owning the balance. Venter said he would resign as president of the Institute for Genomic Sciences, his place being taken by Dr. Claire Fraser, his wife.

    Other Places of Interest on The Web
  • The Institute for Genomic Research.
  • Perkin-Elmer Corporation.
  • Perkin-Elmer Corporation, Applied Biosystems.

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