Originally published in Synapse on Sept. 29, 1983.
Editor’s note: Last week, in part one of this two part series on commercial genetic engineering laboratories. Synapse looked inside two of the major companies — Berkeley-based Cetus Corporation, and Genentech of South San Francisco. In part one. it was revealed that in the early years of the industry, the National Institutes of Health (NIH) maintained extremely stringent safety and containment guidelines. These have been relaxed in recent years.
This week, Synapse attempts to assess the safety in this young, but burgeoning industry. In question is whether transforming living organisms or creating new ones could be an order of magnitude more dangerous than other kinds of scientific inquiry.
In general, the labs approve of the relaxed NIH guidelines, but more for reasons of psychology than safety. “It’s conceivable that there are dangers which are unknown,” Frank McCormick, a senior scientist at Cetus and former UC Berkeley post-doc, admits. “So to be on the safe side, things are contained. Although I would imagine that the safety limits are excessive in reality, which is the way it should be.” Art Levinson, a scientist at Genentech, goes one step further, arguing that “to the extent that (the NIH guidelines) reassure the public that research is being done safely, they’re important. I think that’s their main value.”
Frank has a story about a genetic lab in Birmingham, England. “Smallpox got out of one lab through the ventilation system — what they thought was a closed hood — and it was actually vented through another lab. One or two people died. Then the professor committed suicide.” But such an accident could take place in any lab using pathogens, not just a genetic lab, he adds. The most dangerous materials are still stringently regulated, while only those shown to be “harmless” fall under the new, relaxed guidelines. And most of the private labs do very little, if any work with live pathogens. Art says that in a sense, the whole debate on DNA dangers is overblown. “What we’re learning now is that genetic transpositions are actually part of the evolutionary process — viruses pick up genes and move them around from species to species.” How could humans do worse? This is where disagreements between experts in the field begin. Robert L. Sinsheimer, formerly a leading genetic scientist, is now Chancellor of the University of California at Santa Cruz. He was among the sponsors of the moratorium and is one of the most respected voices in the field. Chancellor Sinsheimer advocates a slow and careful approach — even at the cost of delaying potentially important developments.
Speaking to him leaves one with a feeling of caution. Sinsheimer agrees that genetic transfers occur in nature. But how commonly, and over what evolutionary range? “No one really knows,” he maintains. “I don’t think this takes place on the sort of scale accessible to genetic engineering.”
When asked about the relaxed NIH guidelines, Sinsheimer explained that worries about possible dangers decreased when alterations were made on the chief bacteria used in recombinant DNA research, Escherichia coli (E. coli). It’s an amazingly prolific bug, commonly found in humans and a mainstay of molecular research for decades. Scientists developed weakened strains of E. coli which stand little chance of survival outside the lab.
But according to Sinsheimer, E. coli is only one case. “I think (the NIH guidelines) have been diluted to a point where they’re almost meaningless. Because there has been no problem (with E. coli),” he notes, “people are leaping to the conclusion that there couldn’t he any problem and they’re extending these techniques to other organisms, such as yeast and fruit flys. We know a lot less about the likelihood of their survival outside the lab.” Accidents may happen Although scientists dispute the likelihood of dangerous organisms escaping from the lab, they agree it is certainly not impossible. But dangerous compared
with what? “There are already a lot of very virulent organisms around in nature, and that virulence has evolved over eons,” Henry Erlich, another Cetus scientist notes. “I’m not sure you could improve, if that’s the right word, on natural virulence.” But Sinsheimer takes it back a step with a reminder that this is uncharted territory. The chances for catastrophe? Sinsheimer paused before replying. “Let me put it this way: One can deliberately make some very dangerous organisms. The question really is, ‘how likely is that to happen inadvertently?’ I think less likely than we originally feared, but I must confess I don’t know how one could quantify that.”
It’s the possibility of deliberate misuse that scares Frank. “Germ warfare,” he said letting the words sink in before continuing. “That’s where the technologies being prepared at this place and universities could really be applied horrendously. That’s an area I have thought about and worried about. You could immunize a whole population against a certain toxin — then give it to the opposition. That kind of possibility has been around for a long time, but it can really be developed now.” (Synapse will explore the germ warfare question in a future issue.) Altering animal forms Frank told another story about a man who built the better mouse. He took a rat
gene clone for a growth hormone and implanted it into fertilized mouse eggs. What resulted was a mouse twice its normal size — a sort of mouse offshoot. It was a major step in a long search for the genetic basis of animal development. “He was in a state of shock for months afterward, thinking about the implications,” said Frank. “He was afraid the public would say,, ‘just what we need — thanks to the scientists we have giant mice!’” Frank laughed, but the obvious visions of giant beef cattle dance before the eyes of Central Valley farmers. And giant people?
Genetic control of size — although a major development in itself — is “relatively trivial to change,” according to Frank. “We don’t know enough about animal development to fiddle with much else,” meaning different animal forms. He continues, “one could imagine implanting genes to overcome certain traits into fertilized human eggs; for example, to produce a growth hormone to overcome dwarfism.” Hemophelia might also be cured in this manner.
The long term implications of this research are uncertain. But it is clear that mass scale techniques for large animals or humans are decades away, if they are developed at all. The cloning of entire humans, perhaps the wildest and most popular science fiction ruse, it not even in the picture, and may never be.
Yet, if “trivial” alterations of mice (and soon, humans) can be managed, it’s more than likely that profound alterations will be accomplished in years to come. How can we feel secure that such methods won’t be abused? For example, might a future despot design populations for particular tasks, perhaps those requiring great brawn, or a prediliction for repetitive motions? Highly unlikely. Frank explains, tor convincingly pragmatic reasons. Such alterations are vastly complex and difficult. But even if possible, “by adapting the phenotype (the detectable expression of a person’s genetic make-up) rather than the genotype — by administering drugs or exerting social control — you could achieve the same effects without genetic engineering, arid much more effectively.” Some would say it’s happening right now.
Henry Erlich believes these aren’t the kinds of issues only scientists should decide. “As the technology evolves,” he asserts, “the use to which it’s put is a political or social issue, not a scientific one.” But he does believe scientists have a special responsibility by virtue of their knowledge and involvement.
There’s an uneasy parallel that Sinsheimer may have overstated in a 1976 speech at UCLA in response to the newly released NIH guidelines, but the words give pause. “The atomic age began with Hiroshima. After that, no one needed to be convinced that we had a problem. Now we are entering the Genetic Age; I hope we do not need a similar demonstration.” Trade secrecy Many people in a democratic society find trade secrecy a rather unappealing characteristic of the business world. But the way our economy works, corporations and in some cases, universities have clear proprietary interests. At issue is whether these interests conflict with the public’s right to information on potential dangers of the products in question. The recombinant DNA industry is new and volatile. Fortunes can be made or lost overnight on the basis of information — which may be a process, technique or even theory — long before it results in a product. Some people, including those scared by all this “playing with nature” (Art calls them “fundementalists”), are also concerned that the high level of secrecy in the industry could be a problem. But like potential dangers, secrecy may be relative. There is evidence that genetic labs are surprisingly open. Scientists wither in the absence of collegial discourse. Many would leave the private companies for the universities from whence they came if not permitted to publish their findings extensively.
Sharing information is the way all scientific disciplines are advanced, including those directed to profit. Besides, even the largest of the private companies are miniscule compared with the plethora of university labs, and would probably not survive without intellectual cross-fertilization.
Nevertheless, the industry rivals E. coli in its proliferation of commercial secrets. “I’d put it in the same area as the chemical and other pharmaceutical industries.” Frank argues. “There’s nothing particularly novel about what we’re doing that would make it any different.”
According to Henry, “typically, the things that are kept secret are not the cosmic, global things, but relatively minor ones — like a way of purifying a protein.” Oversight In the late 1950s and early 19605, a supposedly safe tranquilizer for use during pregnancy was hailed as a wonder drug. The widely used drug was thalidomide, and its legacy represents one of the worst oversights in medical history. Of the newborns who survived, at least 6,000 suffered gross birth malformations. Drug companies accused of criminal negligence, as well as governments in several countries, were forced to pay tens of millions of dollars in damages to the victims and their families.
According to Art, it can take up to seven years to obtain Food and Drug Administration approval for a new pharmaceutical. He says the FDA is increasingly scrupulous about its work, as a response to this kind of tragedy. Some critics of the Reagan administration beg to differ, but notwithstanding, accidents are still known to happen.
It’s a matter of historical record that as long as there has been a profit to make, a certain percentage of insensitive, careless or even malicious manufacturers have littered the marketplace with defective or dangerous products. The pressures of a young, competitive and capital-intensive field can be compelling. Human behavior being what it is, few possibilities can be completely ruled out. The consequences are unknown.
But it is true that this industry has a special incentive against such behavior. It’s still creating a secure nitch for itself. “Sure, these companies want to make money,” another Cetus researcher explains. “But they also want to establish themselves as viable, safe sort of entities... Who’s going to invest in (unscrupulous) companies, or buy their products?”
Anyone who has scrutinized the actions of American business and science cannot but maintain a healthy skepticism despite such reassurances. But there’s an almost irresistible sense of wonder and fascination for this work that comes through in all the scientists and technicians. This is a field that’s not going to go away, and one beginning to make important contributions that will increasingly touch our lives. On balance, it’s hard not to feel immensely impressed, awe inspired that human beings have managed to figure it all out.
