BIOLOGISTS have broken the genetic code. They've read some of the instructions that determine the composition of simple organisms. They've altered a few plants and bacteria. Now some of them are after a far bigger prize - the human genome. The genome is the entire 3 billion-letter ``text'' that contains the genetic instructions for the formation of human beings. That's roughly the number of letters in three year's run of a major seven-day-a-week metropolitan newspaper. So far, the longest such ``text'' the biologists have read is the 172,000-letter sequence of the Epstein-Barr virus - less than 10 percent of a single newspaper issue, using the analogy above. An intensive, dedicated project to go from that to getting the complete sequence of the human genome's 3 billion letters would be the most ambitious single effort biologists have ever undertaken.
Cost estimates run between several hundred million and $1 billion. It probably would take 10 to 20 years to complete. This would catapult biologists - who are used to working in small groups on small programs - into the realm of ``big science.'' It would be for them what building a particle accelerator is for physicists or orbiting the Hubble space telescope is for astronomers - a prospect some biologists view with trepidation.
As momentum builds toward organizing such a project, there is sharp debate among biologists about the wisdom for rushing ahead.
For Walter Gilbert of Harvard University, a dedicated effort to sequence the human genome would be ``like pursuing the Holy Grail.'' The Nobel Prize winning microbiologist says it would create the biological equivalent of the Rosetta stone - ``a complete library of information that biologists could search'' to find the genetic instructions for making a human being. It would be a major aid in understanding gene-linked diseases and developing medical treatments for them. It also should aid in developing many new drugs based directly on chemicals the body uses naturally.
For Nobel laureate David Baltimore - director of the Whitehead Institute for Biomedical Research and a professor at the Massachusetts Institute of Technology - this would be ``a huge, low-priority project'' that would divert scarce funds from more urgent biological research. He warns that such ``a megaproject invites [undesirable] bureaucratic control of science.'' He says that, though researchers might find it helpful to have the full genome sequence available, ``it is not crucial'' to good research. He urges letting the genome sequence emerge in its own good time as various scientists decode parts of it in the normal course of biological research.
For Douglas Brutlag of Stanford University, creating such a powerful biological tool would indeed have ``tremendous'' medical pay backs. But it would also raise moral, legal, and ethical issues ``about what purposes we want to put this information to.''
For the United States Department of Energy (DOE), which supports a modest start on this work, and the National Institutes of Health (NIH), which funds most US biological research, it could be a turf fight.
The DOE's interest in the genome stems at least partly from its need to know more about the kind of genetic damage atomic radiation causes. The department's Office of Health and Environmental Research is asking for $12 million in fiscal 1988 for a program to develop engineering, mathematical, and other aids for genome sequencing - more than twice the $5 million for fiscal 1987.
Last April, a subcommittee of the department's Health and Environmental Research Advisory Committee urged DOE to mount a more ambitious program to actually sequence the human genome. It would have DOE increase the budget for its work to $40 million for 1989 with further increases over the next five years to a final level of $200 million annually.
At this writing, it is uncertain how DOE will respond to such advice. But were the department to move into this field aggressively, it could begin to dance on turf the NIH considers its own. For its part, NIH already spends some $300 million a year to support US biological research, including $100 million on human genome work. NIH director James Wyngaarden, who sees no need for a dedicated genome sequencing program, considers his agency already to be a strong supporter of genome investigators.
Meanwhile, Walter Gilbert, eager to get on with the work, has been raising money for his own new Genome Corporation. He claims that the company can move aggressively enough to do the sequencing job in a decade at a cost of only a few hundred million dollars at most.
This has raised the question of whether or not a private company can copyright such basic information. Dr. Gilbert, who explains he would be selling ``ease of access,'' says his company would make information available to all who want to pay a reasonable fee. Participants in a genome workshop organized in July by the congressional Office of Technology Assessment could not arrive at a consensus on the issue.
But if Gilbert's company does succeed and tries to copyright part or all of the human genome sequence, his right to do so is likely to become an issue in Congress, if not in the courts.
Whether the federal government (or a private company) mounts an intensive decoding effort or the information is produced more slowly through normal research, there is one point on which biologists agree. The human genome will eventually be read. Some of the more interesting parts will be available within a decade. Noting this, Dr. Brutlag told a symposium held in July by Stanford University and IntelliGenetics, Inc.:
``... This is going to give us more information probably about each of us than we ever want to know, or at least the capability of finding out more about our own genetic traits than we want to know. ... I think people better start thinking about the way that this information should be handled, because it's going to be there.''