LITMIR.BIZ

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Darwin needed some mechanism to replenish the variation that was being washed out of populations by blending. His answer was to embrace the discredited Lamarckian theory of inheritance of acquired characteristics. In the 1868 edition of The Origin of Species, Darwin proposed that parts of the body threw off minute particles congregating in reproductive cells to be inherited by the offspring. These bits, or gemmules, were held to transmit characteristics acquired during an individual’s lifetime and thereby provided a new source of variation to offset the loss of variation by blending. The gemmules theory had more than a whiff of desperation about it and did much to discredit Darwinism in the latter half of the nineteenth century.

      GENES

      Two years before the 1868 edition of The Origin of Species, an obscure monk working in an Augustinian monastery in Brünn had discovered and published the right answer to Darwin’s problem. Born into a peasant family in Silesia, Gregor Mendel joined the monastic life to escape poverty. In the monastery garden, Mendel crossed pea plants and carefully recorded the inheritance of parental traits – such as round or wrinkled peas – in those hybrids he generated. He demonstrated that, contrary to expectations, discrete characteristics such as the shape of the pea seed did not blend in crosses. Instead they bred true – were unchanged when they appeared in subsequent generations – though sometimes skipping a generation. To account for his peas, Mendel proposed that organisms contain within them discrete factors, passed unaltered from one generation to the next. We now call Mendel’s discrete factors, genes. This was the exactly the answer Darwin needed – genetic variation would not be lost during sexual reproduction but emerge, unscathed by its passage, in each generation.

      Darwin died in 1882, completely unaware that the work that would rescue his seriously flagging theory was languishing in the Linnaean Society library, the very place his own theory had been triumphantly unveiled. Even more tragically, Mendel died in obscurity in 1884, his revolutionary work unknown or forgotten. It was not until 1900 that three botanists, Hugo de Vries, Carl Correns and Erik von Tschermak, independently rediscovered his experiments. Working on the inheritance of variation in plants, they were each finding evidence for discrete patterns of inheritance. Searching the literature for any related similar work, independently each came across brief references to Mendel’s publications and immediately realised their significance. Mendel was posthumously recognized as the father of modern genetics. Mendelian genetics went on to revolutionize twentieth-century biology and medicine.

      The early twentieth century saw the fusion of Darwinian evolutionary theory (his original rather than the Revised Version) and Mendelian genetics in what has come to be known as the neo-Darwinian synthesis. In 1901 De Vries published the first volume of his Mutation Theory, in which he proposed that evolution occurs by discrete steps or mutations that were rare chance modifications of Mendelian genes. These mutations were the source of the variation for Darwinian natural selection and evolution. Evolutionary theory was, at last, complete.

      But what were genes? What were they made of? How were they inherited? How were they modified? In 1901 nobody had any idea. The first real clue did not come until 1945 when the bacteriologist Oswald Aver/s experiments at New York’s Rockefeller Institute, demonstrated that genetic characteristics could be transferred from one bacterial cell to another, simply by transferring a chemical called deoxyribonucleic acid, or DNA. Avery purified DNA from some bacterial cells which produced a capsule (a slimy protective layer made of strings of sugars that surrounds the bacterial cells). He found that if he added it to cells that didn’t produce a capsule then some of them would be transformed into capsule-producing bacteria. It appeared that the genetic information, the gene for the capsule, was made of DNA and could be transferred from one bacterial cell to another simply by transferring the DNA chemical.

      However, not everyone was convinced of the significance of Avery’s demonstration that DNA encoded bacterial slime. DNA was considered an unlikely vehicle for heritable information. Different species were assumed to have different genes but DNA isolated from different species appeared identical. The prevailing opinion was that genes were made of the protein. It was easy to show that different species had different proteins. Proteins contaminated all preparations of DNA, so many scientist’s believed that it was the contaminating proteins in Avery’s experiments that had transferred the genetic information. When in 1944, the quantum physicist Erwin Schrödinger (of whom much more later) published his book, What is Life?, he went along with the prevailing genes as proteins hypothesis.

      However, in the early 1950s Alfred Hershey and Martha Chase’s experiments proved that genes were made of DNA. They demonstrated that when a virus infects a bacterial cell, it injects its DNA but not its protein into the host cell. After infection, the bacteria become transformed to make the bacteriophage proteins. So the genes encoding those proteins must have been injected with the bacteriophage DNA. Genes must be made of DNA.

      DNA was quickly accepted as the genetic material, but it was unclear how genetic information was stored within it. The overall chemical composition of DNA was already known – it was composed of a simple sugar (deoxyribose), phosphate groups and roughly equal quantities of four types of nucleic acids, each made up of carbon, nitrogen and hydrogen atoms. But the profound problem remained – how do these chemicals store the information for the shape of your nose? This was answered by Watson and Crick’s structure.

      THE DOUBLE HELIX

      The intertwined DNA molecule has become such a strong cultural icon today that it is hard to realise just how unobvious its structure was in the 1950s. Both laboratories racing for a solution initially got it wrong. Linus Pauling of the California Institute of Technology (CalTech) was perhaps the greatest chemist of the twentieth century. He had already discovered proteins contained helical regions so it was hardly surprising that he proposed a helical structure for DNA. However, he wrongly proposed a triple helical structure.

      James Watson was an American scientist who came to Cambridge’s Cavendish Laboratory to learn protein biochemistry. However, his real interest was DNA and at Cambridge he teamed up with the Englishman Francis Crick to solve the structure of that ‘most golden of all molecules’.² Watson and Crick’s first stab at a structure for DNA was (like Pauling’s) also a triple-stranded helix. The pair rashly invited the UK experts on DNA, Maurice Wilkins and Rosalind Franklin, to the unveiling of their putative structure. Wilkins and Franklin had travelled from King’s College, London to view the new model but felt their trip had been wasted when it took just a few minutes for Franklin to spot crucial flaws in the triple helix. After a hasty, tense lunch, the King’s Group rushed off to catch their train home.

      News of this débâcle soon reached Sir Lawrence Bragg, chief of the Cavendish laboratory and Watson and Crick were instructed to turn their attentions to less challenging molecules. The pair decided to continue surreptitiously with their model-building. Their approach used wire models representing the chemical groups to build (quite literally) a structure in three-dimensional space that, they hoped, would represent DNA’s actual structure. But how could they know whether their structure was correct? The key was Rosalind Franklin’s X-ray crystallography data – which was essentially an X-ray of the DNA molecule. The problem, according to Watson, was the difficulty they experienced getting a look at the data over the shoulder of the allegedly overly secretive Franklin. Yet between the lines of Watson’s very readable account, The Double Helix, you can read something of the cultural landscape that forged Franklin’s diffidence. Watson’s describes his female colleague:

      ‘Though her features were strong, she was not unattractive and might have been quite stunning had she taken even a mild interest in her clothes. This she did not. There was never lipstick to contrast with her straight black hair, while at the age of thirty-one her dresses showed all the imagination of the English blue-stocking adolescents.’

      There is unfortunately no record of Franklin’s opinion of the good looks and dress sense of her male colleagues. Some inkling of her likely feelings may be garnered from Watson’s account of a particularly frank exchange of views between himself and ‘Rosy’ which ended with her bearing

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