Gene Implantation: Hazards of Genetic Engineering

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Gene Implantation: Hazards of Genetic Engineering

by Genetics and Social Policy Group

‘Science for the People’ Vol. 8, No. 2, March 1976, p. 10–12

Recent breakthroughs in the field of genetics have improved greatly our understanding of how genes carry information from one generation to the next, and how they specify the development and functions of all organisms. Associated with this new knowledge are powerful new technologies which allow the linking of genes from one organism to the next. In particular. molecular geneticists , have utilized newly characterized “restriction enzymes”  to couple genes from various living organisms to the ubiquitous intestinal bacterium, E. coli. Theoretically any organism could act as recipient for such gene implants. Bacteria are now being used because they permit easy, critical measurement of the technique’s success. However, the practitioners of gene implantations have recently been subjected to questions1 2 from both in and out of the scientific community about not only what they hope to achieve, but also if and how their experiments should be conducted. 

The ultimate justification offered for these experiments is the possibility of altering human genes. For example certain rare genetic defects such as hemophilia, thalassemia, sickle-cell anemia, and alkaptonuria might be correctable by genetic “surgery”. We will not discuss in this article the virtues or dangers of such eugenic theories.3 Rather we focus on the public health hazards of creating unnaturally altered organisms. Though few of us would be potential candidates for gene implants, all of us are subject to the risks involved. We certainly should assess the risks involved, and we should spend an adequate amount of time doing it. The social benefits of gene-implantation work which may arise will be of equal value whether they arrive in 20 versus 25 years, or 100 versus 105 years. For five or ten years now a slow, thoughtful research-based approach to limit the hazards makes sense. 

Before describing the dangers, it is worth reviewing the form that the controversy has taken. A small group of molecular-biology research directors addressed a letter to the scientific community and explicitly asked that all research on “recombinant-DNA” molecules (gene implantations) stop until the risks involved and safeguards necessary to conduct the research were evaluated for this. These scientists, who have proclaimed only the potential rewards of such experiments, have now been heralded by the media for what is deemed to have been an unprecedented event in the history of science.4 

A group consisting essentially entirely of research directors was expressly invited to attend a meeting at Asilomar in California where these questions were discussed. A resolution representing the consensus of the meeting was adopted, calling for the establishment of a committee under the auspices of the National Institutes of Health. This committee was empowered to draw up a system of biological-containment procedures and recombinant-DNA recipients which could be assigned to any experiment whatsoever.

The committee that was appointed consisted of fifteen biomedical-research directors. Both the composition of the committee as well as the guidelines they adopted were criticized by the Genetics and Social Policy group of Science for the People, among others, for violating the spirit of the Asilomar meeting.5 As a result the committee was instructed to reexamine original guidelines and resubmit specific proposals. 

Finally on December 4 and 5, 1975, the committee adopted a set of guidelines which will in all likelihood be the working guideline. 

The moratorium on active research, consideration of the risks involved, and establishment of guidelines for such research which others have dubbed unprecedented, are considered by the Genetics and Social Policy Group of Science for the People to be publicly misleading. Such actions appear to have been taken to ensure the welfare of the general public, yet the public was neither informed, consulted, nor educated. The research directors have a vested interest and involvement in their own experiments. Can they be counted on to take full responsibility? If these experiments were to be put on trial, why then were the experimenters allowed to act as prosecutor, judge, and jury? The progress of dangerous gene implantation experiments has suffered inconveniences but has not been deterred. 

In their zeal to answer fascinating scientific questions, the research directors failed to open debate. Experts in related fields such as epidemiology and public health, occupational health and safety, and microbial ecology, who might have contributed to discussions of dangers inherent in such experiments, were not consulted. Neither were the laboratory workers, who actually perform the experiments, allowed to participate despite the fact that they are exposed to the greatest risks. The general public, neither informed nor consulted, is also exposed to the risks involved in recombinant-DNA experiments and should not abnegate responsibility. And it is precisely because such experiments are being conducted in the public interest with public money that the public should be educated about the pros and not deluded about the cons. Substances such as radium, asbestos, thalidomide, vinyl chloride, and dieldrin which appeared completely beneficial at the time of their introduction have become intentionally or accidentally destructive of human life and the environment. Today, molecular biologists are in a position to benefit from the lessons of our technological present and not to contribute to the inventory of tragic results of the past.

A large question mark in gene implantation is that the common bacterium of the human intestine and throat, E. coli, acts as recipient for all newly transplanted genes. The practitioners maintain that: (1) the containment apparatus will not allow the escape of the implanted bacteria into the environment, (2) even if some escape, they have been so extensively crippled that they are unable to persist outside the laboratory, and (3) these bacteria are unable to exchange genes with other bacteria as normally occurs, so that the implanted genes cannot be transferred to healthy bacteria. These ideas are supported by research into the genetics of bacteria at the molecular level, but the Genetics and Social Policy group feels the dangers are sufficient to warrant extensive tests to insure that unwanted, foreign genes don’t end up in the bowels of unsuspecting passers-by.

It has been assumed that these physical-containment facilities will be adequate although there has been no mention of thoroughly testing them before the more dangerous experiments are attempted. In fact the number of reported acquired infections in laboratories with special containment facilities have been around 1650 in the last 30 years. There have been 423 cases of infection and 3 deaths in 25 years at the U.S. Army Biological Laboratories at Ft. Detrick, Maryland, alone. 

Even if the bacteria employed to receive the gene implants are crippled as required, there remains a finite possibility that they may persist outside of the laboratory. Cultures of crippled bacteria ready to receive gene implants may readily be contaminated with healthy bacteria. These healthy bacteria, containing gene implants, may readily spread to the environment. Although such events are unlikely, over many years they may become a distinct probability. E. coli have been chosen because of convenience to the experimenters, not because of public safety. Another bacterial recipient could be developed which is much further removed from the human biosphere. If the committee truly had the interests of the public at heart it would have insisted on a bacterial recipient that was humanly remote. The cold fact remains that the proposed safeguards have not been validated. In view of these uncertainties it would seem safe and prudent to proceed with what are generally agreed to be the less dangerous implants. However as the guidelines now stand virtually any recombinant-DNA experiment can be performed.  

What then are the real dangers of these artificially constructed bacteria? The answer is somewhat rhetorical as well: we don’t really know. This alone should be cause for trepidation. It would be easy to construct horror stories about bacteria gone berserk, or powerful biological toxins implanted into the genes of ubiquitous human-inhabiting bacteria thus constructing novel biological bombs, etc. For every fairy tale which ends with, ”and they lived happily ever after,” an equally disastrous scenario can be painted. 

It would be highly desirable to construct a bacterium in which the gene for insulin biosynthesis had been implanted. Such bacteria could supply insulin cheaply in virtually unlimited amounts. However insulin in greater than minute amounts is a deadly poison, and were E. coli harboring an active gene for insulin biosynthesis to gain admittance to human intestinal tracts the results would swiftly be fatal. Here then is a highly desirable candidate for gene implants, all the more so being a potential financial boon, which could easily have undesirable consequences. The pharmaceutical industry would be extremely interested in construcing an insulin-producing bacterium. However, containment problems on a large industrial scale are compounded enormously. Historically the health and safety of the American worker have not been of prime concern to American industry, nor in academic scientific circles for that matter. Will it be possible to maintain a low level of risk in large-scale industrial operation? Who will write and enforce the guidelines? The NIH guidelines apply only to academic research, yet private industry stands to profit greatly. The stresses involved in maintaining safe containment conditions openly tempt flagrant violations.

Electron micrograph of human chromosome 12.

Therefore all workers, academic or industrial, potentially exposed to hazards of gene implants ought to be organized to both educate and protect themselves. Local safety committees, like the new Biology Health and Safety Committee at MIT, should be organized and should include lab technicians, custodial people and clerical workers. The formation of such committees is mandated by the NIH guidelines themselves. However, unless workers organize themselves actively these committees will be composed entirely of research directors, who have little or no interest in safety. It is up to each and every one of us to insure that our rights are observed. 

Decisions about which research projects should be pursued are matters of public policy, and the general public must become involved. These are financed by public tax money, spent for public welfare, and all of us have a right to a say-so. Senator Kennedy of Massachusetts is convening a public meeting of the Senate Health Subcommittee on Genetic Research and Bioethics which will hopefully discuss and propose legislation aimed at precisely these questions. The Genetics and Social Policy Group of Science for the People hopes the American taxpayer gets a fair hearing at this conference, and that in the future all such public-welfare decisions cease to be open to only ranking professionals in their exclusive fields. 

The Genetics and Social Policy Group notes the irony of the current situation. In the name of improving human health, newer and more potent threats to human health are being developed. It is unclear that these genetic technologies have been developed in response to national needs or whether they are simply the interests of professional scientists who make their livings with such developements.

FURTHER READING

Allen, Garland E., Genetics 79, 29-45 Supplement, part II. Proceedings of the 13th International Congress of Genetics.

>>  Back to Vol. 8, No. 2  <<

REFERENCES

  1. Nature 257, 637 (1975).
  2. Wade, N. Science 190, 1175 (1975).
  3. Psychology Today, June 1974,  p. 30.
  4. Newsweek, January 12, 1976,  p. 50.
  5. Genetic Engineering, press release. November 26, 1975. Science for the People. 16 Union Square, Somerville, MA.