For many years geneticists have understood the value of isogenic strains in general biomedical research as well as in genetics. Here are some examples of what they have said:
Little 1936
“Just as the purity of the chemical assures the pharmacist of the proper filling of the doctor’s prescription, so the purity of the mouse stock can assure a research scientist of a true and sure experiment…….In experimental medicine today….the use of in-bred genetic material…is just as necessary as the use of aseptic and anti-septic precautions in surgery” C.C. Little 1936
W.L Russell 1941
“. . any geneticist who samples the recent literature in such fields as physiology, biochemistry, bacteriology, pathology, cancer research, and experimental medicine in general is struck by three points. First, most of the workers who are still using animals of uncertain origin could profit by the use of inbred strains. Second, even when inbred strains are used, they are frequently not used to their full value. Third, owing to the lack of understanding of the consequences of inbreeding, erroneous conclusions are sometimes drawn from the results obtained with inbred materials.”
Strong 1952
“It is the conviction of many geneticists that the use of the inbred mouse in cancer research has made possible many contributions of a fundamental nature that would not have been made otherwise. Perhaps it would not be out of place to make the suggestion that within the near future all research on mice should be carried out on inbred animals or on hybrid mice of known (genetically controlled) origin where the degree of biological variability has been carefully controlled.” L.C. Strong
Grüneberg 1952
“The introduction of inbred strains into biology is probably comparable in importance with that of the analytical balance into chemistry.” H. Grüneberg
W.M.S. Russell and Burch 1959
Toxicity testing, as usual,…..is the scene of some confused thought, which may be delaying the exploitation of statistical methods. We have not infrequently heard the opinion expressed that, while you cannot have too much uniformity in bioassay, in toxicity tests you need a thoroughly heterogeneous mass of animals, and plenty of them. The physician, it is argued, is going to deal with patients with a very wide range of sensitivities to a given toxic action. There is a vague feeling that since this variation is quite uncontrolled, that of test animals ought to be uncontrolled too. It is a sort of high fidelity argument…..this time applied to the properties of populations. On this subject Hume has written clearly and concisely…:
“The fallacy consists in supposing that in order to obtain a broad inductive base a heterogeneous stocks should be used. It would be as if you were to estimate the value of a pocket full of silver by counting the coins, without sorting sixpences, shillings and half-crowns. The proper procedure is ,of course, to use several different lines (or preferably F1 crossbreeds), and to allow for the variance between samples; for otherwise the experimenter deprives himself of the possibility of making a relatively precise estimate of the error….”
Heston 1963
“. . . the development of inbred strains has constituted probably the greatest advance in all cancer research” W.E. Heston
A comment by the author
Although outbred stocks such as Wistar rats or CD-1 mice are widely used in biomedical research, scientists have made very little attempt to justify such use in written scientific papers. This contrast strongly with the many papers which have discussed the advantages of isogenic strains. I have written several such papers in peer-review journals. It is time for action!