- THE FIRST MILLENIUM
1933 – USA
‘‘The Mechanism of Mendelian Heredity’ (1915), ‘The Theory of the Gene’ (1926)’
Starting with Mendel’s laws of segregation and independent assortment, Morgan investigated why there are far fewer chromosomes – the long thread-like structures present in the nucleus of every living cell, which grow and divide during cell splitting, – than there are ‘units of heredity’. Morgan could not see how these few chromosomes could account for all the changes that occur from one generation to the next.
Mendel’s ‘factors of heredity’ had been renamed ‘genes’ in 1909 by the Dane Wilhelm Johannsen.
When the organism forms its reproductive cells (gametes), the genes segregate and pass to different gametes.
Since it had been separately established that chromosomes play an important part in inheritance, then groups of genes had to be present on a single chromosome.
If all the genes were arranged along chromosomes, and all chromosomes were transmitted intact from one generation to the next, then many characteristics would be inherited together. This implicitly invalidates Mendel’s law of independent assortment, which dictated that hereditary traits caused by genes would occur in all possible mathematical combinations in a series of descendants, independent of each other.
Experimental evidence often seemed to back-up the mathematical forecasts for characteristics present in descendants that Mendel had suggested; Morgan felt that the law of independent assortment could not accurately model the process of arriving at the end result.
He began his experiments with the fruit fly, which has just four pairs of chromosomes, in 1908.
He observed a mutant white-eyed male fly, which he extracted for breeding with ordinary red-eyed females. Over subsequent generations of interbred offspring, the white-eyed trait returned in some descendants, all of which turned out to be males. Clearly, certain genetic traits were not occurring independently of each other but were being passed on in groups.
Rather than invalidating Mendel’s law of independent assortment, a simple adjustment was required to unite it with Hunt’s belief in chromosomes to produce his thesis.
He suggested that the law of independent assortment did apply – but only to genes found on different chromosomes. For those on the same chromosome, linked traits would be passed on; usually a sex-related factor with other specific features (such as, the male sex and the white-eyed characteristic).
The results of his work convinced Morgan that genes were arranged on chromosomes in a linear manner and could be mapped. Further testing showed that, as chromosomes actually break apart and re-form during the production of sperm and egg cells, linked traits could occasionally be broken during the exchange of genes (recombination) that occurred between pairs of chromosomes during the process of cell division. He hypothesised that the nearer on the chromosome the genes were located to each other, the less likely the linkages were to be broken. Thus by measuring the occurrence of breakages he could work out the position of the genes along the chromosome.
In 1911 he produced the first chromosome map showing the position of five genes linked to gender characteristics.
In 1933 Hunt Morgan received the Nobel Prize for Physiology.
1865 – Austria
‘Law of Segregation: In sexually reproducing organisms, two units of heredity control each trait. Only one of such units can be represented in a single sexually reproductive cell’
‘Law of Independent Assortment: Each of a pair of contrasted traits may be combined with either of another pair’
These laws laid the foundation for the science of genetics.
The biologist Lamarck (1744-1829) had proposed a theory of inheritance of acquired characteristics and had suggested that inherited characteristics are influenced by environment. Mendel planted an atypical variety of an oriental plant next to a typical variety – the offspring retained the essential traits of their parents, which meant that the characteristics that were inherited were not influenced by the environment. This simple test led Mendel to embark on the path that would lead to the discovery of the laws of heredity.
Mendel’s aim was to discover ” a generally applicable law of the formation and development of hybrids “. He addressed this by studying the effect of cross-breeding on seven pairs of contrasting characteristics of Pisum sativum, a strain of pea.
His work on peas indicated that features of the plant; seed shape, seed colour, pod shape, pod colour, flower colour, flower position and stem length; were passed on from one generation to the next by some physical element. He realised that each characteristic of a plant was inherited independently, and that the ratios of plants exhibiting each trait could be statistically predicted.
A common assumption in Mendel’s time was that when two alternative features were combined, an average of these features would occur. For example, a tall plant and a short one would result in medium height offspring. For seven years Mendel kept an exact record of the inherited characteristics of 28,000 pea plants, taking great pains to avoid accidental cross-fertilization; then he applied mathematics to the results. These quantitative data allowed him to see statistical patterns and ratios that had eluded his predecessors.
From his analysis he found that certain characteristics of plants are due to factors passed intact from generation to generation.
Mendel observed that individual plants of the first generation of hybrids (crossbred plants) usually showed the traits of only one parent. The crossing of yellow seeded plants with green seeded ones gave rise to yellow seeds; the crossing of tall stemmed ones with short-stemmed varieties gave rise to tall-stemmed plants.
The factors determining a trait are passed on to the offspring during reproduction.
Mendel worked out that the factors for each trait are grouped together in pairs and that the offspring receives one part of a pair from each parent.
Contrary to the popular belief of the time, these factors do not merge. Any individual pea always exhibits one trait or the other, never a mixture of the two possible expressions of the trait; only one trait from each pair of factors donated by the parents would be expressed in the offspring, although there are four possible combinations of factors.
This is now described as Mendel’s law of segregation.
An offspring inherits from its parents either one trait or the other, but not both.
He decided that some factors were ‘dominant’ and some were ‘recessive’ and was able to conclude that certain expressed traits, such as yellow seeds or tall stems, were the dominant ones and that other traits, such as shortness of stem and green seeds, were recessive. It appeared that the dominant factors consumed or destroyed the recessive factors – but this could not be the case, as the second generation of hybrids exhibited both the dominant and recessive traits of their ‘grandparents’. Across a series of generations of descendants, plants did not average out to a medium, but instead inherited the original features (for example, either tallness or shortness) in consistent proportions, a ratio of 3:1, according to the dominant factor.
The 3:1 ratio would apply because the dominant factor would feature whenever it was present.
He also noted that the different pairs of factors making up the characteristics of the pea plant ( such as the pair causing flower colour, the pair causing seed shape and so on ), when crossed, occurred in all possible mathematical combinations. This convinced him that the elements regulating the different features acted independently of each other, so the inheritance of one particular colour of flower was not influenced, for example, by the inheritance of pea shape.
This is now described as Mendel’s law of independent assortment.
He first articulated his results in 1865 and in 1866, which was shortly after Darwin’s ‘Origin of Species’ appeared, published them in an article ‘Versuche über Pflanzen-Hybriden’ (Experiments with plant hybrids).
No one before him had attempted to use mathematics and statistics as a means of understanding and predicting biological processes and during his lifetime and for some time after, his results were largely ignored.
Around the time of Mendel’s death, scientists using ever improving optics to study the minute architecture of cells coined the term ‘chromosome’ to describe the long, stringy bodies in the cell nucleus.
|The seven traits studied in peas|
|TRAIT||DOMINANT TRAIT||RECESSIVE TRAIT|
|Type of seed surface||smooth||wrinkled|
|Colour of seed albumen||yellow||green|
|Colour of seed coat||grey||white|
|Form of ripe pod||inflated||constricted|
|Colour of unripe pod||green||yellow|
|Position of flowers on stem||axial||terminal|
|Length of stem||tall||short|
‘There is doubt as to the probity of this Jesuit scholar, some claiming that his data was falsified whilst others argue that it is accurate’
Pilgrim, I. (1984) The Too-Good-to-be-True Paradox and Gregor Mendel. Journal of Heredity,#75, pp 501-2. Cited in Brake,M.L. & Hook, N. Different Engines – How science drives fiction and fiction drives science
1923 – Toronto, Canada
Early research had shown that there was almost certainly a link between the pancreas and diabetes, but at the time it was not understood what it was.
We now know a hormone from the pancreas controls the flow of sugar into the blood stream. Diabetics lack this function and are gradually killed by uncontrolled glucose input into the body’s systems.
Banting believed that the islets of Langerhans might be the most likely site for the production of this hormone and began a series of tests using laboratory animals.
After successfully treating dogs – showing signs of diabetes after the pancreas had been removed – with a solution prepared from an extract from the islets of Langerhans, Banting’s team (Best, MacLeod and Collip) purified their extract and named it insulin.
Human trials successfully took place in 1923 and dying patients were restored to health. The same year, industrial production of insulin from pigs’ pancreas began.
In the Second World War Banting undertook dangerous research into poisonous gas and was killed in an air crash while flying from Canada to the United Kingdom.</p
1931 – USA
‘A framework for understanding the electronic and geometric structure of molecules and crystals’
An important aspect of this framework is the concept of hybridisation: in order to create stronger bonds, atoms change the shape of their orbitals (the space around a nucleus in which an electron is most likely to be found) into petal shapes, which allow more effective overlapping of orbitals.
A chemical bond is a strong force of attraction linking atoms in a molecule or crystal. BOHR had already shown that electrons inhabit fixed orbits around the nucleus of the atom. Atoms strive to have a full outer shell (allowed orbit), which gives a stable structure. They may share, give away or receive extra electrons to achieve stability. The way atoms will form bonds with others, and the ease with which they will do it, is determined by the configuration of electrons.
Earlier in the century, Gilbert Lewis (1875-1946) had offered many of the basic explanations for the structural bonding between elements, including the sharing of a pair of electrons between atoms and the tendency of elements to combine with others to fill their electron shells according to rigidly defined orbits (with two electrons in the closest orbit to the nucleus, eight in the second orbit, eight in the third and so on).
Pauling was the first to enunciate an understanding of a physical interpretation of the bonds between molecules from a chemical perspective, and of the nature of crystals.
In a covalent bond, one or more electrons are shared between two atoms. So two hydrogen atoms form the hydrogen molecule, H2, by each sharing their single electron. The two atoms are bound together by the shared electrons. This was proposed by Lewis and Irving Langmuir in 1916.
In an ionic bond, one atom gives away one or more electrons to another atom. So in common salt, sodium chloride, sodium gives away its spare electron to chlorine. As the electron is not shared, the sodium and chlorine atoms are not bound together in a molecule. However, by losing an electron, sodium acquires a positive charge and chlorine, by gaining an electron, acquires a negative charge. The resulting sodium and chlorine ions are held in a crystalline structure. Until Pauling’s explanation it was thought that they were held in place only by electrical charges, the negative and positive ions being drawn to each other.
Pauling’s work provided a value for the energy involved in the small, weak hydrogen bond.
When a hydrogen atom forms a bond with an atom which strongly attracts its single electron, little negative charge is left on the opposite side of the hydrogen atom. As there are no other electrons orbiting the hydrogen nucleus, the other side of the atom has a noticeable positive charge – from the proton in the nucleus. This attracts nearby atoms with a negative charge. The attraction – the hydrogen bond – is about a tenth of the strength of a covalent bond.
In water, attraction between the hydrogen atoms in one water molecule and the oxygen atoms in other water molecules makes water molecules ‘sticky’. It gives ice a regular crystalline structure it would not have otherwise. It makes water liquid at room temperature, when other compounds with similarly small molecules are gases at room temperature.
One aspect of the revolution he brought to chemistry was to insist on considering structures in terms of their three-dimensional space. Pauling showed that the shape of a protein is a long chain twisted into a helix or spiral. The structure is held in shape by hydrogen bonds.
He also explained the beta-sheet, a pleated sheet arrangement given strength by a line of hydrogen bonds.
He devised the electronegativity scale, which ranks elements in order of their electronegativity – a measure of the attraction an atom has for the electrons involved in bonding (0.7 for caesium and francium to 4.0 for fluorine). The electronegativity scale lets us say how covalent or ionic a bond is.
Pauling’s application of quantum theory to structural chemistry helped to establish the subject. He took from quantum mechanics the idea of an electron having both wave-like and particle-like properties and applied it to hydrogen bonds. Instead of there being just an electrical attraction between water molecules, Pauling suggested that wave properties of the particles involved in hydrogen bonding and those involved in covalent bonding overlap. This gives the hydrogen bonds some properties of covalent bonds.
1922 – while investigating why atoms in metals arrange themselves into regular patterns, Pauling used X-ray diffraction at CalTech to determine the structure of molybdenum.
When X-rays are directed at a crystal, some are knocked off course by striking atoms, while others pass straight through as if there are no atoms in their path. The result is a diffraction pattern – a pattern of dark and light lines that reveal the positions of the atoms in the crystal.
Pauling used X-ray and electron diffraction, magnetic effects and measurements of the heat of chemical reactions to calculate the distances and angles between atoms forming bonds. In 1928 he published his findings as a set of rules for working out probable crystalline structures from the X-ray diffraction patterns.
1939 – ‘The Nature of the Chemical Bond and the Structure of Molecules’
Pauling suggests that in order to create stronger bonds, atoms change the shapes of their waves into petal shapes; this was the ‘hydridisation of orbitals’.
Describing hybridisation, he showed that the labels ‘ionic’ and ‘covalent’ are little more than a convenience to group bonds that really lie on a continuous spectrum from wholly ionic to wholly co-valent.
Pauling developed six key rules to explain and predict chemical structure. Three of them are mathematical rules relating to the way electrons behave within bonds, and three relate to the orientation of the orbitals in which the electrons move and the relative position of the atomic nuclei.
As carbon has four filled and four unfilled electron shells it can form bonds in many different ways, making possible the myriad organic compounds found in plants and animals. The concept of hybridisation proved useful in explaining the way carbon bonds often fall between recognised states, which opened the door to the realm of organic chemistry.
X-ray diffraction alone is not very useful for determining the structure of complex organic molecules, but it can show the general shape of the molecule. Pauling’s work showed that physical chemistry at the molecular level could be used to solve problems in biology and medicine.
A problem that needed resolving was the distance between particular atoms when they joined together. Carbon has four bonds, for instance, while oxygen can form two.It would seem that in a molecule of carbon dioxide, which is made of one carbon and two oxygen atoms, two of carbon’s bonds will be devoted to each oxygen.
Well-established calculations gave the distance between the carbon and oxygen atoms as 1.22 × 10-10m. Analysis gave the size of the bond as 1.16 Angstroms. The bond is stronger, and hence shorter. Pauling’s quantum .3-2. explanation was that the bonds within carbon dioxide are constantly resonating between two alternatives. In one position, carbon makes three bonds with one of the oxygen molecules and has only one bond with the other, and then the situation is reversed.
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1953 – UK
‘The self reproducing genetic molecule DNA has the form of a double helix’
The structure explains how DNA stores information and replicates itself.
The helical strands of DNA (deoxyribonucleic acid) consist of chains of alternating sugar and phosphate groups. Four types of base – adenine (A), cytosine (C), guanine (G) and thymine (T) – form the rungs of the DNA ladder, which can only be linked by hydrogen bonds in four combinations: A-T, C-G, T-A, G-C.
The DNA code is based on the order of these four bases and is carried from one generation to the next. The sequence of base pairs along the length of the strands is not the same in DNAs of different organisms. It is this difference in the sequence that makes one gene different from another.