Chromosome theory of inheritance

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The chromosome theory of inheritance states that the material carriers of inheritance are in the cell nucleus . Walter Sutton and Theodor Boveri founded the theory from 1902 onwards through microscopic observations.

Empirical Findings

Oscar Hertwig (1875) and Eduard Strasburger (1877) observed that fertilization involves two successive processes: the fusion of the germ cells and the union of the cell nuclei. In 1888 Heinrich Wilhelm Waldeyer introduced the term chromosomes for the stainable nucleus. In 1882, Walther Flemming described the principle of the constancy of the number of nuclei during cell division (commonly known as mitosis ), and Theodor Boveri and others observed the halving of the number of nuclei during the development of germ cells. The concept was described by August Weismann in 1885 under the term germline . From 1905 onwards, Farmer and Moore called this process meiosis (reduction division).

Empirical evidence

The chromosome theory was empirically confirmed by the work of Thomas Hunt Morgan, A. Sturtevant and Hermann Josef Muller in 1911 and 1919: "The genes are strung on chromosomes like pearls on a string". The above conclusions from the empirical observations have always been controversial. In Germany in particular, the reductionism of the Morgan School was long rejected (Goldschmidt).

Early development of the chromosome concept

The assumptions include:

  • the observation of the union of the cell nuclei during the fusion of the germ cells by Hertwig and Strasbourg in 1875/77,
  • the discovery of the constancy of the number of nuclear bodies during cell division ( mitosis ) by Flemming in 1882,
  • the introduction of the term chromosomes for nuclear bodies by Waldeyer in 1888,
  • the observation of the halving of the number of nuclear bodies in the formation of germ cells by Theodor Boveri and others in 1904/05
  • the introduction of the term meiosis by Farmer and Moore in 1905 for this process.

All of these observations are incorporated into the concept of the germline . August Weismann introduced the term in 1885, and it says that the only constant material element in the succession of organisms over the generations is the nucleus of the germ cells.

Development in the first half of the twentieth century

In order to preserve the modern concept of the structure and function of the chromosomes, however, the introduction of further concepts is necessary. This includes the following elements:

  • The order of the genes on the chromosome
  • The material structure of genes
  • The alternative between DNA and protein
  • X-ray spectroscopy of DNA and the polymer concept
  • Radiation genetics and Muller's concept of "Like-with-Like-Attraction"
  • Max Delbrück: the gene as an atomic association
  • The virus gene theory
  • The theory of the chemical bond
  • Genes and metabolism
  • Early attempts to understand gene structure in terms of gene expression
  • Watson and Cricks attempts to understand gene structure in terms of DNA replication

The order of the genes on the chromosome

First of all, the observation was made that the inheritance factors, which Johannsen called genes from 1909 on, are localized in a special way on the chromosomes. From 1911 onwards, Thomas Hunt Morgan and his students demonstrated, through experiments with the Drosophila fruit fly , that the genes on the chromosomes are lined up like “pearls on a string”.

The material structure of genes

The next problem arose from the question of the material structure of these factors, which are located on the chromosomes. In the twenties of the twentieth century there were about ten different concepts. Only two of these have subsequently proven to be correct: the genes have something to do with DNA , and they are made up of atoms . The connection between these two assumptions was initially not at all in the focus of the scientists who had dealt with it.

The alternative between DNA and protein

It has long been clear that chromosomes consisted of a “mixture” of proteins and DNA. In the twenties, the basic structure of DNA was clarified as consisting of four bases with a sugar and a phosphate group. Since proteins consisted of up to twenty different amino acids, DNA was considered unsuitable for carrying the genes. Today one would say that scientists believed that DNA was “under-complex”, too simply constructed for such a complicated function. The DNA was just an uninteresting molecule. This also influenced the work of Oswald Avery , who demonstrated in 1944 that the transforming principle in the conversion of harmless to infectious variants of pneumococci was DNA. Avery was not believed because he correctly stated that his DNA samples were about five percent contaminated with protein: any critic would have immediately said that the contamination was the transforming principle. About ten years later, Hershey and Chase published their work on bacteriophages , in which the proteins were labeled with radioactive sulfur and the DNA with radioactive phosphorus. The phosphorus fraction was found in the infected bacteria, which proved that DNA was the transforming principle. This was believed even though the sulfur contamination was 20 percent.

X-ray spectroscopy of DNA and the polymer concept

Nonetheless, DNA research was carried out in isolated cases as early as the 1920s. As early as 1926, scientists in Hermann Staudinger's laboratory in Freiburg carried out the first X-ray spectroscopic examinations with DNA, without success. In 1938 the scientist Florence Bell produced the first fully meaningful X-ray spectroscopic image of DNA molecules in the so-called wool research laboratory of William Astbury . The double helix structure of DNA could easily have been derived from it. Due to the beginning of the war, the findings were forgotten. However, there were a number of problems with these findings. The idea that simple molecules could unite to form complex ones was very controversial. Staudinger fought for years against the resistance of all specialist colleagues for his concept of polymers. Physicists in particular did not believe that a polymer could exist. Again, the background to this assumption is intricate. In 1913, the physicist Max von Laue developed the method of X-ray spectroscopy in Arnold Sommerfeld's laboratory in Munich. The principle behind this is the diffraction of X-rays by crystals, which proves two assumptions: X-rays are light and crystals are made up of atoms. The theory for this observation came from the British physicist William Lawrence Bragg . A detail of this theory is the concept of the unit cell. Unit cells have a certain size and it can be calculated that there is only room for about 20,000 hydrogen atoms. This measure was considered to be the maximum size for a molecule. This justified the scientists' doubts about the concept of polymers . So that genes could be a polymer was considered physically implausible until well into the 1930s.

Radiation genetics and Muller's concept of "Like-with-Like-Attraction"

In the year of quantum mechanics , 1927, a student of Thomas Hunt Morgan , Hermann Joseph Muller , made a sensational discovery. He found that mutations in Drosophila could be induced by exposing the larvae to X-rays. The idea that light and life, quanta and genes have something to do with each other was born. The idea electrified the quantum physicists, so that Werner Heisenberg , Niels Bohr , Pascual Jordan , Linus Pauling , Erwin Schrödinger and many others commented on it. The age of radiation genetics was born. The most spectacular idea, however, came from the discoverer, Hermann Joseph Muller, himself. He developed the car attraction model of the genes. This idea was justified by the observation that when cells divide, the chromosomes move towards and away from each other and that there is an exchange of chromosome parts with one another. Muller postulated that a new physical law would take effect, and advocated this idea until the 1940s.

Max Delbrück: the gene as an atomic association

The concept was wrong, of course, but you couldn't prove or disprove that at the time, it was just attractive. Muller represented his ideas at numerous lectures that took him to Berlin as well as Moscow. A young physicist, Max Delbrück , works there in Nikolai Timofejew-Ressowski's group at the Kaiser Wilhelm Institute for Brain Research in Berlin-Buch. In 1935, together with Karl Günther Zimmer, he published the “Green Paper” or the “Three Men Work”. In this publication (“About the nature of gene mutation and gene structure”) the authors advocated the thesis that genes consist of an “atomic association” of around 1000 atoms. The work was sent by the authors in the form of free copies and went largely unnoticed. Erwin Schrödinger received it in 1944 in his booklet “What is Life?” And claims, with reference to Delbrück, that the physical problem of genes has been solved. Genes are made up of molecules. In a subordinate clause, he referred to chromosomes as "aperiodic crystals", which can be interpreted as a paraphrase for an irregular polymer.

The virus gene theory

Research into the connection between genes, atoms and DNA has other aspects that are important for understanding the subject. In the early 1930s, John Desmond Bernal applied to the Cavendish Laboratory. He then made a very remarkable experiment there, the results of which he published in 1943 together with his colleague Fankuchen. The two succeeded in producing the first X-ray spectroscopic images of crystallized tobacco mosaic viruses. Unfortunately, this work was largely ignored in its time due to the turmoil of the war. The importance of the experiment is enormous. Viruses had been isolated since around 1920, and the perfectly correct notion that viruses and genes are related came about at the time as virus-gene theory. H. viruses were thought to be genes. Bernal's pictures would have been a sensation in this context if they had the right audience. They refuted the assumption of Niels Bohr from his essay on "Light and Life" from 1933 that one must kill organisms in order to be able to investigate their last secrets on the atomic level, one must therefore regard life as an "elementary fact" that is physical not ultimately to be cleared up.

The nature of the chemical bond

Another important strand of research, which took its first approach during this time, was the elucidation of the question of what holds atoms together in molecules. Although London and Heitler had already presented their concept of the resonance orbital for the chemical bond in 1928, these investigations were intensified in the following years. One of the pioneers was Linus Pauling . Together with his colleague Brockway, he worked as a visiting scientist at IG Farben in Höchst and BASF in Mannheim in 1934 . At that time he used unique instruments (electron diffractometers) to measure bond lengths in simple organic molecules. He was initially able to summarize his work by stating that methane has a tetrahedral structure, and in 1939 he published the "nature of chemical bonds" in a book of the same name. Linus Pauling was a very hardworking chemist. He clarified the peptide bond in the 1940s and became world famous for it. Even during his lifetime he was considered a legend, a genius. He is one of the few scientists besides Frederick Sanger to have received two Nobel Prizes. Of course, Pauling also tried his hand at DNA and genetic models, but more on that later.

Genes and metabolism

The final part of studying genes is metabolism. Archibald Garrod published his work on alkaptonuria in 1909 . He showed three things: The cause of this disease is a metabolic disorder, it is inherited by a gene, and the metabolic defect is based on a chemically "impossible" reaction. The idea that genes could be responsible for chemical reactions that cannot be replicated in the laboratory was born. About ten years later Muriel Whaldale published her work on the genetics of anthocyanins (flower pigments ) in snapdragons. However, only the work of Tatum and Beadle from the 1940s with slime molds (one-gene-one-enzyme hypothesis) provided definitive information about the fundamental nature of the effect between genes and metabolic processes.

Preliminary summary: the situation around 1950

This means that all the essential results that were collected up to around 1950, the eve of the DNA double helix, can now be summarized:

  • Genes sit in the chromosomes like pearls on a string.
  • They are made up of atoms, possibly in the form of a polymer.
  • There are two candidates for this polymer: DNA or protein.
  • The mechanism by which genes produce traits is puzzling but linear: gene - enzyme - trait.
  • The nature of the gene molecules is almost certainly not a mystery: they consist of normal chemical compounds.
  • Even if it is not yet clear which molecule genes represent, it has been empirically proven that all candidates can be physically examined: Viruses, DNA and proteins can be visualized, chemically prepared and purified using X-ray spectroscopy. Their nature can be explained in principle.

Early attempts to understand gene structure in terms of gene expression

The first attempts to elucidate this connection were models in which it was assumed that the DNA was a single-stranded molecule, the bases outwardly wound around a protein strand (the chromosome). The three-dimensional structure of the bases should therefore represent a kind of stamp template for the formation of enzymes. As a result, Linus Pauling presented a DNA model in the early 1950s that consisted of a triple helix with bases pointing outwards. The intention to propose a mechanism that explains the connection between gene and enzyme (in today's terminology, gene expression) is obvious. The only problem was: the model is wrong.

Watson and Cricks attempts to understand gene structure in terms of DNA replication

The way to the right model is still a detour. Erwin Chargaff presented his observation of the base ratios under the heading of complementarity. The term was misleading. Watson and Crick recognized around 1952 that DNA is a double helix with the bases inside. But that wasn't the definitive structure. They first built models with a base pairing of bases of the same name (i.e. a parallel double strand), based on the Muller car attraction model. Their intention was to propose a mechanism for gene duplication (in our terminology, DNA replication). So they chose a base pairing on the principle of similarity pairing, just as Muller put it: like with like attraction. Even after her encounter with Chargaff, it was not clear how to bring about a “complementary” base pairing. Only the contribution of her colleague Donohue, who redefined the three-dimensional structure of the DNA bases, made it possible to position the hydrogen bonds in such a way that an anti-parallel double strand was possible. Another woman works with DNA in Maurice Wilkins' laboratory. Rosalind Franklin's diffraction patterns of DNA provided the empirical evidence for Watson and Crick's assumption.

supporting documents

  1. ↑ Junker, Geschichte der Biologie, p. 85f: “The inheritance and thus the continuity of organisms in evolution are based, according to Weismann's model, on the 'continuity of the germplasm' (Weismann 1885), i. H. on the continuity of the hereditary parts of the egg and sperm cells (germ line). "

swell

  • Theodor Boveri 1902: About multipolar mitoses as a means for analyzing the cell nucleus . Negotiations of the Physical-Medical Society Würzburg (New Series) 35: 67–90.
  • Friedrich Miescher 1871: The composition of the pus cell. In Hoppe-Seyler (Ed.) Medical-chemical investigations. Pp. 441-460.
  • Alfred H. Sturtevant 1913: The linear arrangement of six sex-linked factors in Drosophila, as shown by their mode of association. Journal of Experimental Zoology 14: 43-59.
  • WS Sutton 1903: The chromosomes in heredity. Biological Bulletin Marine Biol. Lab. Woods Hole 4: 231-251.
  • August Weismann 1885: The continuity of the germplasm as the basis of a theory of heredity. Fischer, Jena.
  • Farmer JB & Moore JES (1905): On the meiotic phase (reduction divisions) in animals and plants . QJ Microsc. Sci. 48, 489-557.

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