History of genes
For centuries and even millennia, philosophers and scientists have understood the concept of heredity, in humans as in animals. This notion was intimately linked to the idea of generations, based on the reproduction of individuals and characterized in most cases by physical similarities between parents and children. But what concerns humans and animals also concerns plants. It is indeed through botanical discoveries that genetics would be born, thanks to the works of an Augustinian monk of the XIXth Century. But before talking about him, let us mention the origin of the word ‘genetic’. The word gene takes its root in the ancient Greek, where génos (γένος) means the race, which comes from the word gignomai (γίγνομαι), which means to engender, to become. Today, genetics refers to the study of the transmission of hereditary traits and gene function. But, as we will see in this episode, and as it was the case for stress, the creation of the term “genetics” would occur after the beginning of the work that will concern it. Indeed, William Bateson, a British biologist, proposed in 1906 that the Chair created for him at the University of Cambridge be named “Genetics” to designate the science of heredity and variation. The Chair was finally named “Chair of Biology” but the idea was well and truly established. The following year, Bateson succeeded in making his idea real by renaming the 3rd International Conference on Plant Hybridization to the 3rd International Conference on Genetics. A small victory for him, which marked the beginnings of genetics as the official terminology.
However, it is possible to begin the History of Genetics with René Antoine de Réaumur, a French physicist and naturalist of the first half of the 18th century. Reaumur used to study a particular family where one of the children had six fingers. He noted that this particularity had been inherited by some descendants of the family. A few years later, in 1745, Pierre Louis de Maupertuis put forward the hypothesis that mothers and fathers have an equal influence on heredity. In his treatise Varieties in the Human Species, Maupertuis stated: “The children are usually like their parents, and the varieties with which they are born are often effects of this resemblance. These varieties, if one could follow them, might have their origin in some unknown ancestor. They are perpetuated by repeated generations of individuals who have them and are erased by generations of individuals who do not have them. But what is perhaps even more surprising is, after an interruption of these varieties, to see them reappear; to see the child who resembles neither his father nor his mother, born with the features of his grandfather. These facts, marvelous as they are, are too frequent for them to be revoked in doubt.” The notion of heredity was therefore the subject of hypotheses and fairly accurate evidence from the eighteenth century.
But it would be necessary to wait until 1866 to witness new advances in the field of what would later be called genetic. In fact, that year, Gregor Mendel, a Catholic monk from the former Austro-Hungarian Empire (in the present Czech Republic) published a very detailed dissertation, entitled Experiments on Plant Hybridization. In this dissertation, Mendel disclosed the findings of his nine years of experimentation, which are now known as “the Mendel Laws.” This document is considered the founding act of classical genetics. During those nine years, Mendel had in fact studied peas grown in his Augustinian monastery. While making hybrids, he understood that a hereditary character can exist in different versions, dominant or recessive. Mendel thus established the laws of the transmission of certain hereditary traits. But what is surprising is that, at first, he did not try to work on heredity. Mendel was looking for a law on which to base the phenomena of hybridization. His “Hybrid Development Act”, he said, reflected only certain hybridization phenomena. But surprisingly, Mendel’s dissertation would not arouse the curiosity of the scientists of his time, and it would take nearly 35 years to witness a renewed interest and a rehabilitation of his discoveries. In 1900, three botanists would indeed ”rediscover” the laws of Mendel. They are the Dutchman Hugo de Vries and the Germans Carl Correns and Erich von Tschermak. These three scientists in fact, through their experiments, made more or less the same conclusions as Mendel, even if it is possible to think that they themselves based their work on the Augustinian monk’s findings.
But during this period of 35 years, another discovery is also to be underlined and it came from Friederich Miescher, a Swiss biologist of the second half of the XIXth century. In 1871, he published an article mentioning his discovery of nuclein, a phosphate-rich substance that he discovered in the nucleus of cells, and which is more commonly called today Deoxyribonucleic acid, or more simply DNA. Miescher was working at the Hope-Seyler laboratory in Germany at the time, where the study of cells was the priority. His task was to define the composition of the lymphoid cells, and it was by working on this subject that he managed to isolate this new molecule. His first idea was that nucleins were the molecules of heredity. Moreover, Oskar Hertwig and Eduard Strasburger, respectively embryologist and botanist, after meticulous analyzes made under the microscope and theoretical reasoning, would deduce in the 1880s that the nucleus of cells is indeed the seat of heredity.
At about the same time, the American Walter Sutton and the German Theodor Boveri developped the chromosome theory of inheritance. Here, what is interesting to note is that these two scientists worked on their own. Boveri was studying sea urchins and found that all chromosomes needed to be present for embryonic development to proceed properly. Sutton worked on grasshoppers, and his work showed that an individual’s chromosomes are composed of maternal and paternal chromosome pairs that separate during gamete formation (oocytes / spermatozoa) and “may constitute the physical basis of the Mendelian law of heredity.” Their work therefore explained and confirmed the mechanisms of Mendelian inheritance, and they would both leave their name to this theory now called “the Boveri–Sutton chromosome theory.” Their theory, however, was challenged for a few years, before being confirmed by Thomas Hunt Morgan, an American embryologist and geneticist. In 1915, Morgan indeed confirmed this theory through his work on Drosophila (fruit flies). He discovered for the first time a Drosophila with white eyes, whereas they are normally red, and led hybridization experiments that would confirm the basis of the chromosome theory of heredity. Three years later, Morgan and a member of his team, Alfred Sturtevent would succeed in establishing the first “genetic maps” that locate genes along chromosomes, while working on Drosophila, always. Thomas Hunt Morgan would later be awarded the Nobel Prize in Physiology or Medicine in 1923 for his work. It also seems important to emphasize Morgan’s strong influence in the progress of genetics at that time.
In 1927, Herman Joseph Muller, who began his career as a student of Morgan, discovered that X-rays can induce mutations or genetic alterations, which greatly improved the accuracy of genetic maps, and provided the first estimate of the number of genes present in the body. This would be his greatest discovery and it earned him a Nobel Prize in Medicine in 1946. It is also interesting to note that Muller was not in good terms with Morgan and Sturtevant, He reproached them for not giving him the recognition he thought he deserved with regards to his participation and influence on the work of the team. He also chose, at a later stage of his career, to use his work and his emerging fame to draw attention to the risks of radiation.
In 1944, three Americans, Oswald Avery, Colin Munro MacLeod and Maclyn McCarthy, formally demonstrated that DNA is THE molecule carrying hereditary information. To do this, they modified an experiment by Frederick Griffith, a British physician and bacteriologist. In particular, Griffith demonstrated that pneumococci killed at very high temperatures could transmit some of their characters, including virulence, to non-virulent strains of live pneumococci. And our three Americans, and more specifically Avery, demonstrated that DNA is responsible for this transmission.
The following notable developments would come from the United Kingdom, and more specifically from Francis Crick, James Dewey Watson and Rosalind Franklin. In 1953, Crick and Watson presented their work, which uncovered the double helix structure of DNA. A discovery that would earn them the Nobel Prize in Medicine in 1962. But Rosalind Franklin, would not be awarded this award. And it is necessary to ask why. Indeed, thanks to her work on X-ray radiography of the DNA structure, Rosalind Franklin had contributed greatly to this discovery. Probably discriminated by her mere status of grant holder at King’s College London, and probably because she was a woman in the 50s, she was never quoted or recognized by Crick and Watson, especially when their speeches of acceptance of their award at the Nobel Academy. Specifically, Franklin had not worked directly with Crick and Watson. It was in fact Maurice Wilkins, a British physicist, who had had access to Franklin’s conclusions, and who sent them to Crick and Watson, and the rest of the story, you know it. Wilkins was the only one who had the ‘elegance’ of emphasizing Rosalind Franklin’s prominent role in this discovery in his speech.
Now, let’s move to France and focus once more on a trio, composed of Prof. Raymond Turpin, and Drs. Jérôme Lejeune and Marte Gautier. This trio was interested in what was called at the time, quite clumsily, ”Mongolism.’’ Turpin had for twenty years or so the idea that what is now called Trisomy 21 or Down syndrome was linked to a chromosomal anomaly. Marte Gautier, who had joined the department of Prof. Turpin as Head of Clinic in 1956, established and transmited microphotographs of chromosomes of people with Down syndrome to Jerome Lejeune, who then studied these photographs under a microscope. In 1958, he counted 47 chromosomes instead of the usual 46, noting the presence of a small additional chromosome on the 21st pair. For the first time in the history of genetics, a link was established between a disability and a chromosomal anomaly.
A few years later, still in France, another trio would, this time, bring one of the greatest contributions to molecular biology. André Lwoff, Jacques Monod and François Jacob, all three researchers at the Institut Pasteur, made several discoveries concerning the genetic control of the synthesis of enzymes and viruses. Discoveries that would allow them to receive the Nobel Prize in Medicine in 1965. I quote the website of the Institut Pasteur, which on the occasion of the 50th anniversary of the trio’s receipt of this award, made a focus on this discovery in 2015: “[They] have discovered that our genes are not consistently expressed over time, but that they are regulated – that is, activated or repressed – very finely to meet the needs of our organization. Why digestive enzymes are not produced constantly, but only after a meal? Why does our immune system, under normal conditions, only start when the body is being threatened by pathogens? To these questions, their discovery finally brought an answer.
As you have understood, from year to year and from decades to decades, progress in genetics occurred more and more rapidly. In 1967, the first DNA synthesis of a virus was performed by the American trio Arthur Kornberg, Mehran Goulian and Robert Sinsheimer.
Five years later, the first gene transfer and cloning experiment in Escherichia coli was done by Paul Berg. Escherichia coli is a bacterium that represents 80% of the cells present in our digestive tract and harmless in the vast majority of cases. The era of genetic engineering had just begun, and in 1978 Werner Arber, Daniel Nathans and Hamilton O. Smith discovered the restriction enzymes that can cut DNA molecules at specific locations. Their discovery would earn them a Nobel Prize in Medicine. Arber was the one who discovered these enzymes in the 1960s, which showed that the phenomenon called “controlled modification of the host” was due to a modification of the DNA and that it served to protect the host from foreign genes. Hamilton Smith confirmed Arber’s hypothesis, while determining the chemical structure of the regions of DNA cut by the enzyme. And finally, Dan Nathans built the first genetic map using restriction enzymes by cutting the DNA of a monkey virus.
It is therefore on this date of 1978 that we will stop this podcast, or almost. Of course, advances in genetics have continued since then. For example, the birth of the “Human Genome Project” in 1986, whose goal was to understand, detect, prevent and attempt to cure genetic diseases. In 1995, the mapping of the human genome was made public, which allowed an acceleration in genetic diseases research. In 2003, the sequencing of the human genome was completed and established that humans have nearly 25,000 genes. A little more than 150 years after the publication of Mendel’s dissertation, genetics has grown remarkably, and its most eminent contributors have often been awarded a Nobel Prize in Medicine. The sequencing of the first genome lasted 10 years and cost about $ 2 billion. Today it costs 1,000 euros and takes about 15 days to complete. Yet, many advances are yet to be discovered. Genetics has indeed offered the search for new leads and continues to try to change the treatment of many diseases.
- Histoire de la génétique et de l’amélioration des plantes, André Gallais, Editions Quae
- https://fr.wikisource.org/wiki/V%C3%A9nus_physique/page_6 Pierre Louis Moreau de Maupertuis, Vénus physique, SECONDE PARTIE, Chapitres I – IV Variétés dans l’espèce humaine.
- De Mendel à l’épigénétique, l’Histoire de la génétique par Jean Gayon, Institut de France – Académie des Sciences – https://www.youtube.com/watch?v=lQdRPuq5ZwY