The ferocious debate over gene splicing is ended.
Images of Frankenstein's monster have receded into the pages of literature. The predictions of new, dangerous forms of life slithering down some laboratory drain have dried up for all but a few. The environmental lobby groups that pushed the issue have all dropped it.
With lttle fanfare and few reporters present, the committee responsible for regulating gene-splicing work in America has voted preliminary approval of an end to federal regulations of the experiments. The committee declared, in effect, that gene splicing is no more or less dangerous than any other experiments in biology.
As the long debate developed, it became clear that the argument was almost religious. The question raised, again and again, was not whether gene splicing can be done safely but whether it should be done at all
Any new scientific discovery offers the possibility of both beneficial and destructive effects. With gene engineering, there also was and is a feeling among many that it is sacrilegious.
The plantetary revolutions of Copernicus and galileo challenged man's central place among the stars. Darwin's theory of evolution challenged man's superior place on earth. The gene revolution takes the next step. Life, at least in its mechanics, is shown to be mere chemistry -- awesome to the scientists, but still chemistry.
Worse, the formerly "sacred," secret mechanisms of life are now being manipulated. God's own tabernacle of life, some feel, has been violated.
One of the chief opponents of research on the deoxyribonucleic acid (DNA), and the one most often given credit for leading the opposition, was Jonathan King, an MIT biologist and a leader of the activist organization, "Science for the People." He was asked at a hearing in Cambridge, Mass., whether he was afraid even of experiments that were classified safe enough to need no special containment.
"Yes, he said, he was. "I am personally, privately, organically afraid . . . It's tampering, as far as I'm concerned, at the most profound biological level.I hate to say it here publicly because my scientific colleagues, you know, are going to give me a lot of abuse. I think it's sacrilegious."
It was the scientists themselves who started the whole debate, quite accidentally, around 1973.
Standing at the beginning of this technology, looking ahead, scientists got frightened, says Norton Zinder of Rockefeller University, who has followed the debate from the beginning. They decided to do the responsible thing, to openly voice their concern though they were not exactly sure what their fears were about.
Within about five years the scientists began frantically working to halt the debate they started, lest they create not a monster in the lab but a monster on Capitol Hill -- a law that would direct the practice of science in university labs, actually banning some research and limiting many other experiments.
What they created, in eight years of debate and five years of federal regulations, was unique in the history of science. It was the first time scientists ever voluntarily banned a whole class of their own experiments.
This is a stark contrast to the events during World War II, when scientists outside Germany not only refused to stop work but refused to stop publishing their results, even though it was fairly certain that scientists in Nazi Germany might utilize the work. The military finally had to intervene and force a ban.
So the voluntary ban by biologists, the only such public and widespread ban in science history, came to be called by some "the noble experiment."
Others thought it not only ignoble but very expensive.
There are now scattered at universities around the nation elaborate, expensive laboratories built to contain the supposed biohazard. The labs ave double sealed doors, elaborate negative air pressure vents, social scrubbing facilities, and glove boxes for experiments -- hundreds of thousands, possibly millions, of dollars worth of equipment that is now useless.
The high-containment lab at Harvard alone cost more than $150,000 and has never been used for anything that couldn't be done in the same room without the expensive equipment.
Many university departments have built these facilities . . . MIT has one, Harvard has one of these white elephants, and they are piled all over the United States. That is a very expensive result of the debate and the regulations," said Philip Sharp, molecular biologist at MIT.
Besides the cash costs in laboratories, and the money spent complying with regulations, Sharp says, there has been a cost in the delay of research.
Some experiments were simply banned for two or three years until the federal guidelines began to be relaxed. This included a complete halt to all work directly related to human disase, such as cancer and the fatal anemias. Other experiments were halted for up to six months or a year while being cleared by federal and local agencies.
"We couldn't work with human DNA for years. We couldn't work with cancer [genes] -- and now that is some of the most exciting work in years; we're learning things now that we could not learn in any way other than with recombinant DNA," says Zinder, the Rockefeller University biologist.
Through the years of debate a whole field of relatively unwordly scientists -- the molecular biologists -- were introduced to politics and the ways of the world. They didn't like it.
The meeting that can be termed the opening shot in the Great Gene Wars was not a public meeting or a protest meeting. Held in New Hampton, N.H., in 1973, it was one of those regular meetings scientists hold just to trade information. But biologist Maxine Singer and others got another item put on the agenda.
The very first experiments done with the new gene splicing technology seemed very dangerous to some. Nobel laureate Paul Berg at Stanford had been taking the genes of a cancer-causing virus and inserting them in a little intestinal bug called E. coli. The virus, called SV40, had never been known to cause cancer in humans, but it had caused cancer in human cells grown on a laboratory plate.
Since Berg inserted these SV40 genesinto a bacterium that could live in the human intestine, some of the younger lab workers raised an alarm: could the E. coli escape their test tubes and infect a lab worker? If that was possible, could E. coli with its brand new SV40 cancer genes now be capable of causing cancer?
Or, still worse, could it cause an epidemic of cancer? E. coli in the intestine multiplies very rapidly and is periodically flushed out of the system into the city sewers and thence into waterways. It would be a case of a bug common in nature suddenly, artifically becoming a cancer agent.
Because of this concern, two questions came up for a vote at the very last minute; whether the scientists should send a letter asking the respected National Academy of Sciences to look into the possible risks, and whether the letter should be made public.
Both proposals passed. Scientists now say they did not realize what they had done. They didn't think about the press, or groups in search of an issue taking this one up and working it hard. They expected that the discussion would be limited to their own closed circles.
Soon, however, there were press conferences and headlines using the word "Frankenstein." One historical event, whose name became a code word for the controversy, was an international meeting of Asilomar center in California in 1975.
This produced stories saying biologists feared their own work so much that they were willing to ban it or build special containment labs for some experiments. SCIENCE THAT FRIGNTENS SCIENTSTS! screamed one magazine cover. Strict federal rules governing gene splicing work were established.
Then came another landmark event, Cambridge and Mayor Alfred Velucci. The Cambridge City Council hearings were to make things even more difficult than Asilomar had, according to Zinder.
"Then the bottom blew out," he said. "If there was one critical event in this whole thing it was probably the Cambridge hearings. It was because of the entire structure of the event." Elements in the volatile mixture:
* Cambridge, an industrial, blue-collar city with a few eminent universities,
* Harvard, known for its leading working molecular biology.
* Mayor Velucci, known for his threats to turn Harvard yard into a parking lot.
* George Wald for the opposition, a Nobel prize winner who had given up science to take up social protest.
* Mark Ptashne, a hard-nosed young biologists, to defend science and Harvard.
* Science for the People, the Boston activist group which was good at organizaing grass root protest.
The chemistry was explosive. The hearing in the summer of 1976, covered by national television and newspapers, saw Velucci listen to a presentation by Ptashne of Harvard, then go on the attack with a series of questions: "Is there a zero risk of danger? . . . Do scientists ever exercise poor judgment? Do they ever have accidents?
Velucci's voice was rising and the audience began cheering. "I have made references to Frankenstein over the past week, and some people think this is all a big joke . . . this is not a laughing matter . . . we could have a major disaster on our hands."
Cambridge banned outright some varieties of gene splicing research at Harvard and MIT for some months. Then, after a citizens' commission reviewed the issue, Cambridge adopted an ordinance that was more restrictive on gene-splicing research than the federal regulations.
Cities and states around the country passed similar laws. Cambridge, Amherst, Waltham and Boston in Massachusetts. Berkeley and Emoryville in California. Princeton, N.J., and Seattle.The states of New york and Maryland.
Following the Cambridge hearings there was a burst of activity on Capitol Hill. More than a dozen bills were introduced to control a whole class of work in biology, the first laws that would have directly prohibited work in science. Only a strenuous effort by scientists prevented the bills from being passed.
The issue had taken off on its own, far beyond what the scientists imagined in the beginning. By 1976, most scientists were convinced the experiments were safe, although the debate rolled on for several more years.
Nobel laureate David Baltimore of MIT says he was upset that several groups took what was originally a responsible action by scientists and distorted it to the point where "we would hve ended up with strict laws and would have hamstrung science."
Two things, chiefly, changed the minds of the scientists who has worried about the research.
There was a series of experiments to determine the likelihood of an accident. The strains of E. coli used in experiments were tested to see how long they could survive in human intestines alongside the wild and well-adapted E. coli that normally lives there.
The answer, roughly, was that they reproduce poorly and cannot last more than a day under most circumstances. Also, it was found that the experimental varieties of E. coli do not pass bits of their genes back and forth with other E. coli, as some bugs do.
So, E. coli with artifically implanted genes are unlikely to pose any risk.
Baltimore adds that molecular biologists learned a lot from neighboring fields about how bacteria live and become infectious. He learned that it actually is a very complex and difficult process for a bacterium to cause disease. Very few bacteria are capable of it.
"No random combination of traits [added to bacteria by biologists] is likely to make any orgamism more pathogenic. In fact it is likely to make it less pathogenic," he said. "To be a pathogen requires not just that the bacteria produce a toxin."
A toxin also must have the ability to act powerfully on some chosen human cells, and the bacterium must be able to bind itself to the cell wall and be able to defeat the human immune response.
Scientists also learned that mixing genes of different creatures, which was thought to be an invention of man, actually is quite common in nature. Therefore, says Baltimore, it is likely that most of the gene combinations that biologists would be mixing artifically have already been tried and discarded by nature.
Some scientists still believe that more experiments to assess risk are necessary. Sheldon Krimsky, a professor of social science at Tufts University and a former member of the NIH recombinant DNA advisory committee, argues that "only a small piece of the large risk assessment that was planned has been completed."
He says that most of the work done has concentrated on risks in the laboratory, which most now feel are less important than the possible risks in commercial gene engineering.
Geoffrey Karny, a congressional staffer who has worked on the DNA issues, believes that the end of federal regulation only closes phase one of the gene wars. Phase two is now beginning as the more than 100 commercial gene engineering companies begin to make products -- bacteria and plants with new properties -- and send then out into the environment.
Like pesticides or other products one thought safe, these new products should be governed carefully, Karny says, lest we have a whole new series of unpleasant discoveries about the sensitivity of the environment.
Experience has taught us that any new technology, when sent out into the world, has unforseen consequences. Often the benefits overwhelm the bad effects and make them acceptable. Sometimes not.
But among the most interesting effects of the gene revolution is philosophical. Whatever the final effect on man's thinking about himself and his world, the secret -- the secret of life itself -- is out.
It is impossible now to do what was suggested by Bertolt Brecht in his play "Galileo." A character in the play objected to spreading the news of Galileo's discovery that man is not at the center of the great universal theater.The discovery should be hidden, he said, out of "the highest of motives" -- protecting those unfortunate souls who believe in the old way. They would be crushed to discover the earth is no theater, but merely a stone ceaselessly spinning about the sun in a cold corner of the cosmos, he argued.
Galielo ignored the plea and continued on with his brave new science.