Things best left alone?

Genetic research could save mankind, or destroy it. Now that science can create new life, should it be allowed to do so?

Michael Enright December 27 1976

Things best left alone?

Genetic research could save mankind, or destroy it. Now that science can create new life, should it be allowed to do so?

Michael Enright December 27 1976

Things best left alone?

Genetic research could save mankind, or destroy it. Now that science can create new life, should it be allowed to do so?

Michael Enright

The office of the mayor of the city of Cambridge, Massachusetts, is only slightly less rococo than its current occupant, Alfred Vellucci. It is all dark mahogany, heavy-legged desks and chairs that moan with age, and a sombre, antique fireplace big enough to park a Volkswagen. The mayor, who likes to be called “Mr. Mayor” or “AÍ,” is short, rotund and excitable. A lifelong Democrat, he has been on city council for 22 years. The last time he ran for mayor, he cheerfully campaigned as “the Godfather.” He chain-smokes Lucky Strikes, speaks with a soft New England rasp, keeps the taxes down and. it is said by some, has a tendency to put his relatives on the city payroll. Until a few months ago, he was really nothing more than a good workhorse politician thinking about sidewalk repairs, new schools and the ever present traffic problem.

Now, because of “this DNA business,” he is something more. He is a statesman for the scientifically untutored, the ultimate layman trying to come to grips with an issue he knew nothing about six months ago. The most absurdly remote recesses of science have landed on his desk and now Mayor Vellucci can see the phrase “Mayor Vellucci of Cambridge” turning up on the front pages of the newspapers of the world. He tries to simplify what he does not understand and dress the issue in the rugged cloth of his own emotions.

“Look, you remember those fantastic red winesap apples? Gee, I used to love them, you know, the great big red juicy ones. Well, jeezus, one day you read in the morning paper that they’ve been dipping the things in red dye that can make you sick or give you cancer and whatnot.” The

“ We must never make experiments to confirm our ideas, but simply to control them.”—Claude Bernard, the founder of experimental medicine.

Doomsday scenario: ant crawls into specially designed recombinant DNA (DNA molecule is on facing page); a chain of events results, years later, in a sharp and sudden increase in cancer

Lucky Strike grinds into the ash tray and the Mayor shakes his head. “I mean what the hell kinda thing is that?”

Cambridge, with a population of 106,000, sits across the Charles River from Boston. It is a one industry town and that industry is education—specifically Harvard University and the Massachusetts Institute of Technology. The life of the city revolves around those two institutions, their faculties and their students. The Harvard-MiT axis gives Cambridge a muted, academic undertone that touches the town’s daily life, its movies, its restaurants, its bookstores, even the way people dress. There must be more corduroy jackets and desert boots in Cambridge than anywhere else in the country. The town-gown relationship has always been polite but cool. The academics who taught at the two schools lived in Cambridge, true enough, but they never really used the city.

It used to be that when Harvard or MIT wanted something of the city someone in the university called someone in City Hall and said this is going to happen. So last

June when Harvard applied to city council for permission tobuild a special kind of laboratory no one thought too much about it. But then no one had bothered to think of AÍ Vellucci, the mayor. Harvard scientists wanted to convert three rooms and a kitchen in the biology building into a containment lab for genetic research. In order to build the new unit, the university needed building and occupancy permits. And to get those permits, Harvard needed AÍ Vellucci. But the mayor had been tipped off by two well-known scientists that what the Harvard people were going to do in their new lab could be dangerous to the population of Cambridge, and instead of issuing the permits as a matter of course he ordered a special council meeting last summer where those in favor and those against could present their cases. In the history of American science, there had never been a meeting quite like it.

For the layman, biology seems to be the most scientific of all sciences. It involves men and women in white lab coats working with frogs and microscopes, Bunsen

burners, slides, petri dishes and bugs— most of all bugs. The scientists use the bugs—or their molecules—to see if their biology acts in the same way as human biology. In the last 30 years or so, some of the most exciting developments have had to do with genetics and molecular biology. In 1944. a group of scientists at Rockefeller Institute in New York showed for the first time that the basic hereditary substance of all cells was something called deoxyribonucleic acid or DNA, to save breath. Shaped like intertwining spiral staircases, DNA controls the growth and reproduction of all living cells and is found in the nucleus of every cell. Stretched along its length are genes, substances that dictate every characteristic in plant and animal life—the shape of a man’s nose, the color of a tomato, the reason we have hair on our heads and not on the soles of our feet. Genes control the manufacture in the human body of hormones and the acids that are needed to digest food and turn it into energy. The study of a single gene gives a scientist a key to the most profound secrets of the origin and continuation of life. It provides the scientist with the opportunity of rearranging the genetic material of living things and to make, in effect, new life. If the scientists were excited about studying a single gene, they were positively gaga over the idea of studying genes in tandem or genes that could be mixed with other genes. By recombining the genes of various organisms, biologists could study the behavior of genetic material and find out why some genes go crazy, as in diseases such as cancer. Science knows that some viruses are cancer-producing or carcinogenic. but these carcinogens don’t usually cause cancer unless they mix with other agents called promoters. Scientists don’t know' why this is but would love to find out.

The technique of gene transplantation is called recombinant DNA experimentation. This is what the Harvard biologists wanted to do with their new lab in Cambridge. But like all scientific discoveries, it was a Janusfaced development. For example, if you split an atom you can get two things: an atom bomb, as well as radiation waves to treat cancer tumors. It is the same with DNA. What was facing science at the moment that recombinant DNA techniques were refined, was not only the possibility of developing recombined genes that could explain the way certain cancer viruses work but also new, potentially dangerous, uncontrollable forms of life.

The technique is straightforward. A way was found to actually cut bits of DNA from a bacterium by using a chemical scalpel called a restriction enzyme. When the restriction enzyme does its cutting, it leaves what scientists call “a sticky end” on the DNA. When this sticky end is hooked up to another piece of similarly cut DNA, it immediately attaches itself to it. Now you have one DNA of a gene that has never existed before in nature, say the recombined gene of a fruit fly and an elephant. But one

The procedure: a bit of DNA is cut from a bacterium and hooked up with another piece of DNA; result is a gene that never existed before in nature, say that of a fruit fly and elephant

gene isn’t very much to study so science looked for a way to make hundreds or thousands of them to observe. They took the recombined gene and introduced it into a bacterium. They found that the new hybrid grew and reproduced as the host bacterium grew and reproduced. The trouble is the host bacterium they chose is something called E coli. They picked E coli because they know so much about it and its ways. But the natural home of E coli bacteria is the gut and bowel system of every human being, every bird and every mammal on earth. This raised the spectre of doomsday: what if one of these newly infected E coli ever got out of the lab? It could wind up in somebody’s stomach and from there to everybody’s stomach. According to scientists who believe it, a doomsday scenario could go like this: suppose an ant managed to get into a specially designed recombinant DNA and crawl around for awhile. It carries in its stomach ordinary E coli. Suppose this ant crawls in and out of a glass dish. Later, speciallyweakened E coli bacteria containing cancer genes are added to the dish. But the ant has left behind some normal, healthy coli which picks up the contaminated stuff during an experiment. Suppose there is a spill. The coli particles are splashed into the air and inhaled by the scientist. The spill is cleaned up and no one suspects anything because it was thought that the bacteria being used were weakened and safe. The scientist goes home and years later dies of cancer. There is perhaps a nasty increase in the incidence of cancer in his town. As one biologist put it: “You won’t get a mass epidemic of people falling over, but in 25 or 30 years, the population will be a little less healthy than they should be.”

The scientists in favor of research with recombinant DNA maintain that such a scenario is rubbish, that such biological accidents could be contained and that the benefits to mankind and to science far outweigh any hypothetical dangers. It was these two groups of scientists, each group brilliant and ambitious, who came into Mayor Vellucci’s council chamber to educate the politicians about the mysteries and verities of DNA.

The meeting began with a mixture of schmaltz and patriotism: the Pledge of Allegiance and the singing of This Land Is Your Land by students from Cambridge High. The room was jammed with some of the best scientific minds in the United States. Loudspeakers were set up in the foyer for the overflow. A staff member from Senator Edward Kennedy’s office was there taking notes. Vellucci asked the scientists to speak plain English as they explained why they were for or against recombinant DNA experimentation. Dr. Ruth Hubbard, a biology professor at Harvard and an opponent of the proposed laboratory, tried to explain the science of recombinant DNA. “The transfer of genes from higher to lower organisms occurs rarely if ever in nature. We therefore have

no way of evaluating the safety of this new technology that is in fact manufacturing new organisms, but we do know the genes sometimes act differently when they are in different environments. We cannot predict how the genes of E coli will act when foreign genes are put into it or how the foreign genes are going to act in E coli, but we do know that once these new organisms are made they will reproduce and spread and they cannot be recalled at will. The ordinary research that most of us do is unpredictable in the same way that I cannot predict what will happen every time I go into the kitchen to bake a cake. But I’m pretty dam sure it’s not dangerous and this is true of most research. The recombinant DNA research is different because we’re bringing together living elements that have not been together before and we have no way of predicting what will happen.” Hubbard’s central argument had an almost visual impact on the 10-member council: “we cannot call it back.'’’’

Those who wanted the lab built tried to

emphasize that recombinant DNA research could lead to immense benefits for man. For instance, it might be possible to produce bacteria whose sole task would be to manufacture insulin. Or it might open the way toward identifying and correcting genetic disorders by replacing sick genes with healthy ones. It’s entirely conceivable that the worldwide problem of starvation could be eradicated if plants that made their own fertilizer could be produced. But the politicians were worried about the ability of the scientists to contain in the lab what they produced in the lab. They had read the horror stories of fluorocarbons used in aerosol cans ravaging the earth’s ozone layer and DES poisoning their meat. They knew that the science that gave the world penicillin was the same science that had come up with DDT. Containment was the problem.

The Harvard biologists argued that guidelines recently set down by the National Institutes of Health in Washington are more than adequate in containing the

The conflict: what began as a problem in pure science evolved Into one of pure politics; if war is too important to be left to the generals, can genetic research be left to the scientists?

new forms of life. In addition to actual physical containment was an innovative safety feature called biological containment—the production of weakened bacteria that could only survive in the laboratory and would perish on the outside. Dr. Mark Ptashne, a molecular biologist at Harvard, tried to reassure the politicians that with all the precautions the experiments have little hazard. “I believe these experiments under these extraordinary conditions have less risk than many of the experiments that now go on in every university and every hospital and every research institution in the country. And that these risks are significantly less than the risks you live with every day, like crossing the street or owning a pet.”

It was clear from the tone of the meeting that more than science was involved. What began as an issue of pure science evolved into a problem of pure politics. Who was to have the say over what experiments should be allowed, the scientists doing them or the people living in the community where they would be carried out? It was the scientists themselves who exposed the dangers of this new genetic research. Two years ago at the mountain conference centre of Asilomar near Monterey, Calif., 139 of the world’s top genetic scientists met for four days to agonize over the moral burden of their experiments. What became apparent at the end of the conference was the fact that nobody could really say one way or another what the endpoint of the experiments would be. The risks of gene transplantation could not be measured. Now in Cambridge, the sociopolitical questions were raised all over again. The city council did the wisest thing. It called for a sixmonth moratorium on all recombinant DNA research in Cambridge. Then it appointed a special review board made up of ordinary citizens of the city, some with scientific backgrounds and some without, to study gene transplantation in all its confusing aspects. This review board, which meets weekly in the city hospital boardroom, was to report by the end of the year. The politicians will then have to decide the next step. As one harried councillor said: “My God, in my five years of being on this council, I never thought I would have to make a scientific, political decision, but I guess that it has come to that point, that the scientific world cannot make their own decision and is asking for help to protect the citizens of this city.”

One of the leading opponents of recombinant DNA experimentation is Dr. Jonathan King, a native of Brooklyn who went to Yale on a football scholarship, studied at Cal Tech, was active in the antiwar movement of the Sixties and has been at MIT for the past seven years. He belongs to a group called Science for the People. He wants all recombinant DNA experiments halted until it can be empirically shown that the danger is minimal. By opposing the research at MIT, which is the world leader in the science, King clashes

headlong not only with the scientific establishment but with the hallowed tradition of the free scientist working unencumbered by the political realities of the outside world. “Look, the merit of this type of experiment is scientific merit only. It doesn’t have any relationship to social needs. The idea of pure science is garbage. You see, scientists are brought up unaware that they are public servants paid for by public funds, not to entertain themselves but to contribute to society.” To King, the idea of a perfectly contained laboratory with no chance of the bacteria having contact with the outside world is ludicrous. “If you ever

get what we call a splash, that causes an aerosol, tiny droplets of the stuff in the air. You breathe in the bugs. It’s just absurd; you can’t keep the bacteria from getting out.” He is equally unimpressed with the theory that weakened bacteria with no chance of survival outside the lab could be developed for the experiments. “The weakened bacteria argument is stupid. The thing has to be strong enough to reproduce or it’s no good. It may be sick but it ain’t dead and even if it were the dead bacteria still give off DNA. These scientists say ‘We’ll create a bacterium that can’t exist without vitamins.’ Okay, so how many hu-

man beings take vitamins? Answer— everybody.”

It is King perhaps more than any other scientist who has injected political serum into what three years ago would be just another academic debate. And he knows the consequences. “You see there is a problem. If you stand up and say that this research is dangerous, we should stop it, then you’re interfering with somebody’s living. But it’s a question of accountability. If they pay for their research out of their own money and as long as it doesn’t do any damage, then okay let them go ahead. But the way it is now, they should be held responsible for their actions to the public.”

On the other side of the argument is Mark Ptashne. A slight man, he has a Woody Allen face and a way of slouching his way through a conversation with his feet up on the coffee table. He was born in Chicago and went to Harvard 15 years ago as a graduate student. His specialty is molecular biology and some of his colleagues say that at some point Ptashne’s work will

win him a Nobel Prize. The recombinant DNA controversy has wrenched Ptashne out of the cloister of his lab and thrown him into a political tempest. He doesn’t like it. He is urgently in favor of going ahead with DNA research as a way to improve man’s knowledge of life and disease and he dismisses as intellectually dishonest the argument that the experiments are dangerous. “Yes, this is important research, but 1 wouldn’t risk anybody’s life for it.” He is Jonathan King’s opposite number in the controversy and he charges King and the other opponents of the research with political manipulation of an issue that is essentially scientific. “The way the psychology works is this: we thought, naively, that by going the extra mile and making things that much safer people would be reassured. What has happened is that the guidelines and our attempts to make things safer have alarmed people, not reassured them. You tell them that Harvard is building a $500,000 facility to do research that isn’t any more dangerous

than keeping a pet cat, people don’t believe you. But it happens to be true. Our position at Harvard has always been the most conservative in the country. We don’t even allow tumor viruses to be used and they’re used in every other place in this country and in Canada.” He has letters from every American Nobel laureate in the field to substantiate his claim that recombinant DNA research is harmless. “There is not a single expert in infectious diseases in this country, not one—and God knows we’ve had enough of them at these meetings—who takes the view that these experiments cause a serious hazard. And these are people whose job it is to know what bacteria do or don’t do and who have no vested interest in the experiments. The overwhelming majority of informed opinion on this matter consider the idea of danger virtually a joke.”

The bigger question for Ptashne is the idea that maybe there are areas of nature where the scientist shouldn’t tread. “The honest anguish that exists is really moral, not scientific. Should man have knowledge? That is a profound moral, ethical argument. When a guy says no you shouldn’t have that knowledge, that’s a position I respect because we’re all conflicted about that.” What Ptashne does not “respect are those people who arouse the populace” on the grounds that these experiments will allegedly kill people; he believes that this is nonsense. “If you take seriously the argument that these experiments have to be stopped because they are dangerous, I guarantee you that you will then stop all experiments with animals, you’ll move all hospitals out of cities because hospitals are dirty places and you’ll even have to move all dogs and cats out of cities. The way the general developments are going, if they persist, we are probably going to see the end of science as a cultural activity as we now know it.”

Canadian research into recombinant DNA is not extensive. But Dr. Saran Narang, a scientist with the National Research Council, recently synthesized a new “linker” molecule that will allow genetic material to be easily inserted into a bacterium. That could bring nearer the day when new forms of bacteria might be created for the purpose of serving mankind. Nevertheless, other Canadian scientists are concerned over the implications of recombinant DNA research. One is Dr. Louis Siminovitch, chairman of the department of medical genetics at the University of Toronto. He is chairman of a nine-member panel set up last year to draw up guidelines for handling recombinant DNA in Canadian research. Siminovitch is a political moderate in the debate but he raises some interesting questions about danger versus benefit in bio-medical research. “Remember that what the public doesn’t appreciate is that there are labs all over the world, all over Canada, that are working with very pathogenic [diseasecausing] materials all the time. They have

The risk, by analogy: science was able to split the atom, making a number of things possible; on the positive side, the treatment of cancer by radiation, and on the negative side, The Bomb

to because they are labs that isolate infections. If you want to know if you’ve got Lassa fever virus, somebody has to do the work to see if you’ve got Lassa fever virus. If you want to know whether you have smallpox, somebody’s got to do the work and ÿou’ve got to have the labs in order to do the work.”

Dr. David Suzuki, a geneticist and perhaps the best-known scientist in Canada, comes down on the side of a moratorium. His argument is simple; delaying this research until we are sure it is safe won’t kill anyone; going ahead with it might. “In the past 20 years there has been a tremendous change in science and that is that the discovery-application time has been reduced significantly. Something discovered one day can be immediately implemented the next. And right now we don’t know the dangers of the implications of these experiments. The Cambridge meeting confronted a scientific elite with a new reality. Citizens, through politicians, are demanding a voice in defining the limits and direction of the research they’re subsidizing. No longer can scientists assume that because we know how to do something, we must do it.”

The Cambridge City Council meeting brought into fine focus the disturbing issue of morality in science. Even the biologists who want to continue their search for new genetic knowledge with recombinant DNA experiments have been forced to look beyond their laboratories to their public accountability. The ethics of untried science have now become a matter of public debate. The Cambridge experimentation review board may recommend that DNA experiments be allowed only under stringent supervision. Public pressure will be put on the international scientific community to observe safeguards in dealing with these bacteria. It’s conceivable that the Nobel Prize committee will be petitioned to withhold any honors to scientists working with recombinant DNA. The scientists who oppose the research will continue their fight in public by asking governments at all levels to impose moratoria on recombinant DNA experiments. Caught in the middle is the layman, who has to sort out the ethics from the science and decide which is greater, the risk or the reward. In a world where everything that man does, whether for nourishment, pleasure or enlightenment seems to cause cancer in rats, fears are compounded by confusion. Only prayer and fasting seem safe. Science has opened yet another bottle and both sides try to touch and describe the genie let loose. Al Vellucci and his apples are the dark side of it all. Polio vaccine, laser surgery and kidney transplants are the obverse. Even the scientists who are good at opening the bottles don’t know. Until more is known about recombinant DNA, how it works and what its long-term effects are, going ahead with it seems at best absurd and at worst potentially lethal. Man and his genes can afford to