Roth et al. (2006) recently summarized this problem, describing the results of Cairns and colleagues in-depth and provided alternative explanations. Dean & Hinshelwood (1960) and Grant & Hinshelwood (1964) measured the appearance of lactose-fermenting (Lac+) colonies on Petri dishes with non-lactose-fermenting mutants of bacteria including E. coli. Lac− cells formed Lac+ colonies

over days, which was attributed to the bacteria having ‘learned’ or having been ‘trained’ to utilize lactose from extended exposure (Hinshelwood, 1946; Dean & Hinshelwood, Gefitinib order 1964, 1966). Of course, it was mutation, selection, and overgrowth. The wrong overall model was that bacterial cells, being relatively simple, did not require genes, but could have metabolism governed by a series of metastable states, readily described by a series of parallel differential equations (Dean & Hinshelwood, 1966). The results fit the model. While these ideas might have been innovative at the time of Hinshelwood (1946), the explanation was recognizably wrong by the time of Dean & Hinshelwood’s (1966) extensive development of the ideas. Dean & Hinshelwood (1966) were familiar with Obeticholic Acid supplier the new microbial

molecular genetics, but reluctant to explain their results in that manner. Hinshelwood also attributed the development of antibiotic resistance to training or learning (Hinshelwood, 1946; Dean & Hinshelwood, 1966). His ideas were generally recognized as wrong by the late 1950s. It might have been thought that Lamarckian arguments about microbiology would have ended then. However, Clostridium perfringens alpha toxin Gorczynski and Steele published a series of beyond the fringe reports on inheritance of acquired immune tolerance. One appeared in Nature (Gorczynski & Steele, 1981) only 2 weeks before Peter Medawar (whose 1960 Nobel Prize was for demonstrating and explaining the mechanism of acquired immune tolerance) and colleagues (Brent et al., 1981) submitted a debunking report

to the same journal. They stated that inheritance of acquired immune tolerance ‘has been faulted by every critical test’ and the ‘experiments executed hitherto to corroborate the Lamarckian interpretation can be faulted’. Why did Nature knowing this was a major problem publish the first report? It should have been stopped. Several years later, again in Nature, Cairns et al. (1988) measured the mutation from Lac− to Lac+ in E. coli cells and found the appearance of mutations continuing over days, only in the presence of lactose. This led to the conclusion that the bacterial ‘cells may have mechanisms for choosing which mutations will occur’. That was a beyond the fringe conclusion. Over the next two decades, Cairns occasionally published additional supporting reports (Cairns & Foster, 1991).