Erwin Chargaff, On the Dangers of Genetic Meddling, 1976
A bizarre problem is posed by recent attempts to make so-called genetic engineering palatable to the public. Presumably because they were asked to establish « guidelines, » the National Institutes of Health have permitted themselves to be dragged into a controversy with which they should not have had anything to do. Perhaps such a request should have been addressed to the Department of Justice. But I doubt that they would have wanted to become involved with second-degree molecular biology.
Although I do not think that a terrorist organization ever asked the Federal Bureau of Investigation to establish guidelines on the proper conduct of bombing experiments, I do not doubt what the answer would have been; namely, that they ought to refrain from doing anything unlawful. This also applies to the case under discussion: no smoke-screen, neither P3 nor P4 containment facilities, can absolve an experimenter from having injured a fellow being. I set my hope in the cleaning women and the animal attendants employed in laboratories playing games with « recombinant DNA »; in the law profession, which ought to recognize a golden opportunity for biological malpractice suits; and in the juries that dislike all forms of doctors.
In pursuing my quixotic undertaking — fighting windmills with an M.D. degree — I shall start with the cardinal folly, namely, the choice of Escherichia coli as the host. Permit me to quote from a respected textbook of microbiology: « E. coli is referred to as the ‘colon bacillus’ because it is the predominant facultative species in the large bowel. » In fact, we harbor several hundred different varieties of this useful microorganism. It is responsible for few infections but probably for more scientific papers than any other living organism. If our time feels called upon to create new forms of living cells — forms that the world has presumably not seen since its onset — why choose a microbe that has cohabited, more or less happily, with us for a very long time indeed? The answer is that we know so much more about E. coli than about anything else, including ourselves. But is this a valid answer? Take your time, study diligently, and you will eventually learn a great deal about organisms that cannot live in men or animals. There is no hurry, there is no hurry whatever.
Here I shall be interrupted by many colleagues who assure me that they cannot wait any longer, that they are in a tremendous hurry to help suffering humanity. Without doubting the purity of their motives, I must say that nobody has, to my knowledge, set out clearly how he plans to go about curing everything from alkaptonuria to Zenker’s degeneration, let alone replacing or repairing our genes. But screams and empty promises fill the air. « Don’t you want cheap insulin? Would you not like to have cereals get their nitrogen from the air? And how about green man photosynthesizing his nourishment: 10 minutes in the sun for breakfast, 30 minutes for lunch, and 1 hour for dinner? » Well, maybe Yes, maybe No.
If Dr. Frankenstein must go on producing his little biological monsters — and I deny the urgency and even the compulsion — why pick E. coli as the womb? This is a field where every experiment is a « shotgun experiment, » not only those so designated; and who knows what is really being implanted into the DNA of the plasmids which the bacillus will continue multiplying to the end of time? And it will eventually get into human beings and animals despite all the precautions of containment. What is inside will be outside. Here I am given the assurance that the work will be done with enfeebled lambda and with modified, defective E. coli strains that cannot live in the intestine. But how about the exchange of genetic material in the gut? How can we be sure what would happen once the little beasts escaped from the laboratory? Let me quote once more from the respected textbook: « Indeed, the possibility cannot be dismissed that genetic recombination in the intestinal tract may even cause harmless enteric bacilli occasionally to become virulent. » I am thinking, however, of something much more worse than virulence. We are playing with hotter fires.
It is not surprising, but it is regrettable that the groups that entrusted themselves with the formulation of « guidelines, » as well as the several advisory committees, consisted exclusively, or almost exclusively, of advocates of this form of genetic experimentation. What seems to have been disregarded completely is that we are dealing here much more with an ethical problem than with one in public health, and that the principal question to be answered is whether we have the right to put an additional fearful load on generations that are not yet born. I use the adjective « additional » in view of the unresolved and equally fearful problem of the disposal of nuclear waste. Our time is cursed with the necessity for feeble men, masquerading as experts, to make enormously far-reaching decisions. Is there anything more far-reaching than the creation of new forms of life?
Recognizing that the National Institutes of Health are not equipped to deal with a dilemma of such import, I can only hope against hope for congressional action. One could, for instance, envision the following steps: (i) a complete prohibition of the use of bacterial hosts that are indigenous to man; (ii) the creation of an authority, truly representative of the population of this country, that would support and license research on less objectionable hosts and procedures; (iii) all forms of « genetic engineering » remaining a federal monopoly; (iv) all research eventually being carried out in one place, such as Fort Detrick. It is clear that a moratorium of some sort will have to precede the erection of legal safeguards.
But beyond all this, there arises a general problem of the greatest significance, namely, the awesome irreversibility of what is being contemplated. You can stop splitting the atom; you can stop visiting the moon; you can stop using aerosols; you may even decide not to kill entire populations by the use of a few bombs. But you cannot recall a new form of life. Once you have constructed a viable E. coli cell carrying a plasmid DNA into which a piece of eukaryotic DNA has been spliced, it will survive you and your children and your children’s children. An irreversible attack on the biosphere is something so unheard-of, so unthinkable to previous generations, that I could only wish that mine had not been guilty of it. The hybridization of Prometheus with Herostratus is bound to give evil results.
Most of the experimental results published so far in this field are actually quite unconvincing. We understand very little about eukaryotic DNA. The significance of spacer regions, repetitive sequences, and, for that matter, of heterochromatin is not yet fully understood. It appears that the recombination experiments in which a piece of animal DNA is incorporated into the DNA of a microbial plasmid are being performed without a full appreciation of what is going on. Is the position of one gene with respect to its neighbors on the DNA chain accidental or do they control and regulate each other? Can we be sure — to mention one fantastic improbability — that the gene for a given protein hormone, operative only in certain specialized cells, does not become carcinogenic when introduced naked into the intestine? Are we wise in getting ready to mix up what nature has kept apart, namely the genomes of eukaryotic and prokaryotic cells?
The worst is that we shall never know. Bacteria and viruses have always formed a most effective biological underground. The guerilla warfare through which they act on higher forms of life is only imperfectly understood. By adding to this arsenal freakish forms of life — prokaryotes propagating eukaryotic genes — we shall be throwing a veil of uncertainties over the life of coming generations. Have we the right to counteract, irreversibly, the evolutionary wisdom of millions of years, in order to satisfy the ambition and the curiosity of a few scientists?
This world is given to us on loan. We come and we go; and after a time we leave earth and air and water to others who come after us. My generation, or perhaps the one preceding mine, has been the first to engage, under the leadership of the exact sciences, in a destructive colonial warfare against nature.
The future will curse us for it.
Erwin Chargaff, Science, june 1976.
Source: Erwin Chargaff, Heraclitean Fire, Sketches from a Life before Nature, The Rockfeller University Press, 1978, pp. 187-190.