Pathogenetic tales

A little over twenty years ago, a group of scientists assembled in Asilomar, California, to consider the consequences of the newly invented techniques of genetic engineering, or recombinant DNA, as it later came to be called. There was in place a moratorium recommended by scientists and which we, working for the UK's Medical Research Council, had been instructed to heed by the Secretary of the organization. It was then that I came to appreciate the depth of the distinction between chastity and impotence, which I had used some years previously to convince my supervisor, Sir Cyril Hinshelwood, that bacteriophage resistance arose by mutation in E. coli, a process he seriously doubted at the time. The outcome is the same, but the reasons are profoundly different. Fortunately, at Asilomar, scientists voted to terminate the moratorium, and, in exchange, offered to proceed cautiously and try to find conditions for the safe practice of gene manipulation. This occupied the attention of many able scientists for several years thereafter. If nothing were to survive from that decade other than the proceedings of committee meetings, the reports of commissions of enquiries, press reports and books, future historians would convince themselves that a new religious cult suddenly appeared first in California, later sweeping the world with intricate theological works that encompassed not only everything on earth but future human evolution as well. Eventually a scheme was produced in the US, the NIH guidelines, parts of which were plainly absurd. For example, the guidelines required that the pathogenicity of the organism providing the DNA be taken into account; thus DNA from the malaria plasmodium required higher containment for cloning than DNA from Tetrahymena. Nobody was allowed to consider how the original pathogenicity might be reconstituted from a bunch of DNA clones, and, if one took this seriously, lion DNA would need more stringent containment than pussycat DNA, lions being much more pathogenic for humans than their domestic cousins. It took quite a long time to convince people that the best way to deal with a dangerous virus would be to clone it and lock it up in E. coli or lambda bacteriophage rather than working with the virus itself. All of this generated a discussion of what could be called artificial pathogenesis. Could we create, intentionally or by accident, entirely new elements that were worse than anything found in nature? I wrote a paper on this subject …