Directed Mutation in Bacteria by Jill Abery Very occasionally an entrenched dogma within the scientific establishment is challenged, not by a crank writing in green ink from a private address, as Phillip Gething describes those offering new theories from outside academia [1], but by reputable researchers with papers even sometimes published in Nature. The reaction can be varied. In the case of Rupert Sheldrake's theory of formative causation [2], Nature unpenned the Furies and declared his book fit for burning. In the case of a French researcher's work which seemed to prove that there was something behind homeopathy [3], Nature sent in a team of debunkers including a magician. In both cases New Scientist was rather more open-minded but both subjects have since dropped out of sight. More recently Nature has published a work which strikes at the roots of modern Darwinism and raises the spectre of that old arch enemy, Lamarckism [4]. This has not raised quite such a furore mainly, I suspect, because those sufficiently roused to pen letters to scientific journals on the subject feel that they can satisfactorily explain the results without recourse to ideas of inheritance of acquired characteristics, and as the experiments only deal with bacteria there is always the let out that the results do not apply to higher organisms. However, it is precisely because of studies of the mutation rates in bacteria that biologists have come to believe that 'mutations arise continuously and without any consideration for their utility'. This has become the basic evolutionary doctrine of random variation upon which the forces of natural selection can act. In a recent experiment, Cairns et al. studied strains of bacteria which lacked the right genes to enable them to metabolise certain sugars. These strains were grown on a medium containing sugars they could metabolise; measurements of the rate of mutations which would allow them to grow on media containing the other sugars showed that the mutation rate was extremely small. Significantly, one example actually required two separate mutations, neither of which was any use by itself. Nevertheless, when the bacteria were grown on a medium containing only the sugars they could not metabolise, within two weeks they had mutated to be able to do so. The authors estimated the chances of this occurring with the 'normal' mutation rates and wrote: "That such events ever occur seems almost unbelievable,.... It is difficult to imagine how bacteria are able to solve complex problems like these - and do so without, at the same time, accumulating a large number of neutral and deleterious mutations - unless they have access to some reversible process of trial and error.... We describe here a few experiments and some circumstantial evidence suggesting that bacteria can choose which mutations they should produce." It appears that molecular biology is no longer as reductionist as it was; it is now accepted that in some genetic systems instability and extreme variability can be switched on in conditions of stress. But merely increased mutation rate, if still random, would lead to the accumulation of vast numbers of deleterious mutations, for which there is no evidence. The authors speculate about intra-cellular mechanisms which could feed back information about the success or otherwise of mutations and allow the cell to concentrate only on the advantageous ones, but it has hitherto been sacrosanct in biology that there is no mechanism for such feedback from the environment to the genome. Such processes would 'in effect, provide a mechanism for the inheritance of acquired characteristics'. It is ironic that scientists in the past have been pilloried for daring to suggest such things [5,6]. Other biologists will not yet consider the effect seriously until there is more proof, and a valid mechanism, and even then they are likely to consider the phenomenon applies only to the relatively simple chemical world of bacteria. A batch of letters to Nature [7] all made great effort to explain the heterodox results away. A further paper by another researcher [8] which gave even more suggestive results for anticipatory mutation, was again argued against in Nature [9] but Cairns had counterarguments and an explanation for the 'vehement defence' of orthodoxy his work had aroused [10]. He exhorted his readers to remember that his critics are defending what is 'an essentially negative assertion', that adaptation of an organism to its environment never precedes the genetic changes for the adaptation. Although Nature only printed the critical letters, Cairns had been contacted by other researchers with similar beliefs and in view of the fact that scientists now know "that, in the processing of biological information, almost anything is possible.... it should not be difficult for an organism to devise a way of testing phenotype (newly adapted characters) before adopting any new genotype (heritable characters). " Cairns sums up by saying: "It therefore seems almost perverse to maintain, as a matter of principle, that such a mechanism has never evolved." However these results may eventually be explained, there is no doubt that the purely mechanistic dogma of evolution by natural selection of completely random mutations leaves much to be desired. The more biologists discover about the complexity of living organisms the more there is to explain. An alternative scenario could be that our present era is one of relative stasis in which natural selection serves to keep the status quo and that evolution proceeded in catastrophic leaps at times of chaotic change. Perhaps the potential for complex feedback mechanisms between organisms and their drastically altered environment lies largely dormant and comes into play only at such times, when some means of very rapid adaptation is essential; means such as the inheritance of acquired characteristics and reinforcement through morphic resonance, of which we catch only glimpses at the present time. Though such glimpses reveal a whole new way of thought for those with the breadth of mind to accept them, the orthodox will continue to deny them while they cling tenaciously to the fragile reassurance of a belief in a non-catastrophic Universe. References 1. New Scientist 4.11.89, p. 73 2. See Workshop 4:3, p. 18 3. Nature 333, p. 787 4. Nature 335, pp. 142-5 5. A. Koestler, The Case of the Midwife Toad 6. See Workshop 4:1, pp. 11-12, on the work of Ted Steele and the inheritance of acquired immunity. 7. Nature 336, pp. 525-7 8. Genetics, December 1988 9. Nature 337, pp. 119-20 10. Nature 336, pp. 527-8 _________________________________________________________________ \cdrom\pubs\journals\workshop\w1989no2\05direc.htm