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For (almost?) every scientific fact that we know, there used to be a different theory that seemed to explain the same phenomenaBefore Mendel's laws were discovered (and much later accepted) genetic inheritance was considered to be comparable to the mixing of liquids. Many people literally believed that this substance was actually blood; for others blood was a metaphor for liquid-like mixing, with no limit on the degree of dilution. Unlimited dilution was the key assumption, not which specific liquid was mixed. As an illustration of how widely this was believed, please consider one of the most intelligent criticisms made against Darwin's theory of evolution (which, please notice, was itself a replacement of earlier theories of evolution!). I refer to the criticism by a famous engineer whose name looks as it if it were not spelled correctly: Fleeming Jenkin (Yes! It really was spelled that way.). He was one of the engineers most responsible for early undersea cables. His objection to evolution by natural selection was that dilution would prevent continued evolution of any characteristic that deviated very much from the average. For example, extreme height might result in leaving many offspring, but if those offspring had offspring by individuals of average height, then the effect would be diluted and the advantage lost. This has often been called "The Swamping Argument". Unfortunately, the hypothetical example Jenkin used was not height, but skin color, and his discussion of the issue sounds (and was) racist. Nevertheless, his reasoning is regarded by experts as having been correct. In other words, were it not for the "lumpyness" and non-dilution of genes, which Mendel discovered, Darwin's mechanism of natural selection could not work. Neither Mendel nor Darwin realized this connection; if they had, then Mendel's research would have become famous in his own time. Darwin took Jenkin's objection very seriously, and thought perhaps it disproved natural selection as a workable mechanism for evolution. So did many other good scientists of the time. Wikipedia has a good biographical sketch of Fleeming Jenkin., but does not understand the swamping argument. It doesn't depend on thermodynamics. It was not inherently racist. And given what people then assumed about inheritance being like mixing of liquids, it was a valid argument against Darwin. Furthermore, breeders of animals and plants were already aware of the phenomena that Mendel discovered, except he was the first to be quantitative about it. Breeders had two main concepts; "throwbacks" and "fixation of characters". When trying to breed "pure-bred" dogs, horses, pigeons, you name it, sometimes they would cross two brown dogs and get a few spotted dogs or a few white dogs, or something different, among a litter. They noticed that these unwanted few tended to be about a quarter of those produced (if there were any odd ones, then these odd ones would be about 1/4 of the total number), and they noticed that the odd ones looked like grandparents of the litter. Furthermore, they even noticed that there were some odd properties that occurred more often among males (in other words, they even knew about sex-linked recessives). Darwin actually discusses such observations in "The Origin of Species". He couldn't quite figure out what they meant.) What Mendel did, and it was plenty, was actually to count large numbers of offspring, and exactly quantitate a well-known phenomenon. Mendel's concept of recessiveness of genes is the mirror image of throwbacks – another way of talking about the same fact, which is that genes can be present in what amounts to a concealed form, but then become expressed again in a later generation. The animal and plant breeders also knew that if you kept inbreeding for 3 or 4 generations, just those individuals that had the phenotype you want, then you could completely "fix" an inherited character. Next, please notice that genetic linkage is ALSO a flat contradiction to Mendel's laws. When linkage was discovered, scientists had the choice of deciding that Mendel was wrong, or deciding that he had been basically correct, but linkage was a special case, and that they should try to quantitate the degree of deviation from Mendel's laws. Later, T. H. Morgan (who was an embryologist, not a geneticist) and others had the brilliant idea of deducing locations of genes on chromosomes, based on linkage. Before they could get to that point, people had to realize that chromosomes were the locations of genes, and that chromosomes differed from each other. The key breakthrough was that sea urchins developed abnormally whenever there was an uneven distribution of chromosomes in an early mitosis. This was discovered by embryologists, and its meaning for genetics was recognized only slowly. Incidentally, polytene chromosomes in flies were discovered in Russia in the 1890s, and reported in a Russian-language journal, which didn't get read and noticed by geneticists until around 1930. It was a big advance for geneticists to be able to "see" genes on chromosomes, but they had already figured out most of what polytene chromosomes now allowed them to see directly. So you should learn Russian! The science of genetics was a triumph of indirect reasoning. Researchers figured out that genes existed as units, arranged like beads along string-like chromosomes, and cleverly deduced the locations of each particular gene based on frequencies of changes in linkage ("crossing over") and many other facts. The molecular basis of all these facts was discovered much later, and also by indirect methods. One of the criticisms made against Mendel in his time was that he didn't know the chemical nature of the semi-hypothetical units whose existence he had deduced, nor did he know the chemical cause of dominance or recessiveness. These same objections were made against Morgan, and against all the early geneticists. Biochemists of the time were the main opponents of the conclusions of Avery, and of Hershey, that DNA was the genetic material. The historical development of genetics as a science depended completely on the willingness and skill to reason carefully about genes, long before the time was ripe to discover that genes were made of DNA. This historical development was consistently criticized and held back by chemists, and by others who claimed that it shouldn't be possible to figure out how a mechanism works until you know what chemicals it is made out of. It is ironic that many molecular geneticists criticize other subjects for "not being molecular enough". I challenge any student to name any phenomenon related to cell biology, genetics or embryology, which they think has always been correctly understood, and about which they think that the facts now in the textbooks are not replacements for some prior theory, that was taught as fact to students 10, 25, 50, a hundred or two hundred years ago. There may be some real examples. What I have written above is meant to show that Mendel's Laws are not an example. They were preceded by mistaken (but very plausible) ideas about mixing of blood. The conceptual history of genes is very complicated. The 2 best books on the history of genetics are by Carlson and by Sturdivant. The latter author made the first genetic map as an undergraduate research project. The concept of clones was applied to asexual reproduction of plants by cuttings and shoots. Most groves of aspen trees are clones. Then nuclear transplants were made in frogs by Briggs & King in 1952, but didn't get much public attention until repeated in mammals. Cloning of genes is a special case of "transformation", as used by Avery, and begun by Griffith in 1928. Clonal selection of lymphocytes was originally proposed by Jerne as selection among antigens, but Burnet realized cloning of antibody-producing lymphocytes would make more sense, etc. Monoclonal antibodies were an unexpected result of testing which cell's genes would continue to be expressed when 2 were fused. So every concept and method has its history, which is seldom if ever a straight line. Kuhn was right.
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