History of Science - 14
History of Science-14.
Matthias Schleiden-(1804-1881).
Theodor Schwann-(1810-1882).
Rudolf Virchow-(1821-1902).
Walther Fleming-(1843-1905).
Edouard van Beneden-(1846-1910).
August Weismann -(1834-1914).
Hugo de Vries-(1848-1935).
Gregor Mendel-(1822-1884).
Thomas Hunt Morgan-(1866-1945).
Friedrich Miescher-(1844-1895).
Phoebus Levene-(1869-1940).
Fred Griffith-(1881-1914).
Erwin Chargaff -(1905-2002).
Gilbert Lewis-(1875-1946).
Svante Arrhenius-(1859-1927).
Linus Pauling-(1901-1994).
Lawrence Bragg-(1890-1971).
Max Von Laue-(1879-1960).
Rosalind Franklin-(1920-1958).
James Watson-(1928-).
Francis Crick-(1916-2004).
We are the most complicated thing that we know about in the entire universe.
Life as we know it, is a manifestation of the ability for atoms,
to form a complex variety of large molecules.
The exact size of a lump of matter, needed to destroy the complexity,
on which life as we know it depends, is determined by the different strengths.
of electromagnetic and gravitational forces.
The electrical forces that hold molecules together,
are 10 to the power of 36 times stronger, than the gravitational forces,
that try to crush molecules out of existence.
When atoms are together in a lump of matter, there is no overall electric charge,
because each atom is electrically neutral.
Each atom is essentially on its own, when it comes to withstanding gravity,
through the strength of QED.
The strength of the inward gravitational force on each atom,
in the lump of matter, increases with the addition of every extra atom.
The amount of mass in a sphere, with a certain density,
is proportional to the cube of the radius.
The strength of the gravitational force falls off in accordance,
with the inverse square law.
Gravity on the surface gains on electric forces,
in accordance with two thirds power.
This means, since 36 is two thirds of 54,
that when 10 to the power of 54 atoms are together,
in a single lump, gravity dominates,
and complicated molecules are broken apart.
Imagine starting out with a set of objects made up of 10 atoms, 100 atoms,
1000 atoms and so on.
Each lump containing 10 times more atoms, than the one before.
The twenty fourth object would be as big as a sugar cube.
The twenty seventh would be the size of a large mammal.
The fifty fourth would be the size of the planet Jupiter.
The fifty seventh would be the size of the Sun.
In the Sun, even atoms are destroyed by gravity,
leaving a mixture of nuclei and free electrons, called a plasma.
On this logarithmic scale people are almost exactly halfway in size,
between atoms and stars.
The thirty ninth object would be the size of a rock, 1 km in diameter.
The realm of life forms like ours is between,
the lump of sugar and lumps of large rocks.
This is the realm Charles Darwin investigated, in the theory of evolution.
The basis for the complexity of life, depends on the chemical process,
at a deeper level.
We now know that DNA is the key component of life.
The origin of species was published in 1859.
The understanding of evolution went backwards, during the rest of the 19th century.
One reason was the problem of timescales required for evolution.
This was resolved only in the twentieth century, by an understanding of radioactivity.
The second reason was Darwin did not fully understand the concept of heredity.
This became clear only in the twentieth century.
Darwin’s own ideas of heredity was presented in 1868.
He gave it the name ‘Pangenesis’.
His idea was that every cell in the body, contributes tiny particles,
which are stored in the reproductive cells, to be passed on to the next generation.
The model also incorporated the idea of blending inheritance.
This says that when two individuals combine to produce offsprings,
the offspring represent a blend of the characterises of the parents.
This runs completely against the basic tenet of evolution by natural selection,
which requires a variation among individuals to select from.
Blending inheritance would produce a uniform population, in a few generations.
Darwin revised his thinking many times and was leaning,
more and more towards the Lamarckian position.
His opponents argued that evolution could not proceed by a series of tiny steps,
since intermediate forms would not be viable.
The example given was a proto giraffe, with a neck longer than a deer,
but too short for it to browse on treetops.
The Englishman George Jackson suggested that evolution,
required sudden changes in body plan, from one generation to the next.
This in effect would mean a deer giving birth to a giraffe.
Darwin was on the right lines, when he highlighted the importance of individual cells,
and reproductive cells, to carry information from one generation to next.
The role of cells as the fundamental component of living things,
became clear only in the end of 1850’s.
The realisation was driven largely by improved microscopic instruments.
Matthias Schleiden proposed in 1838, that all plant tissues are made of cells.
A year later Theodor Schwann, extended this to animals, in effect all living things.
Rudolf Virchow was a professor of pathology in Berlin.
He published a book in 1858, which explicitly stated,
that every cell is derived from a preexisting cell.
He applied this doctrine to his field of medicine, suggesting that disease,
is the response of cells to abnormal conditions.
He showed that tumours are derived from pre-existing cells.
This proved immensely fruitful in many ways,
and produced an explosion of interest in the study of cells.
Virchow however opposed the germ theory of infection.
He also rejected the theory of natural selection through evolution.
Microscopic techniques was able to show the structure of cells,
as a bag of watery jelly, with a central nucleus.
They were so good that in late 1870’s, both Hermann Fol and Oskar Hertwig,
independently observed the penetration of the sperm into the egg.
They worked with sea urchins,
which have the invaluable property of being transparent .
They observed the two nuclei fusing to form a single new nucleus.
In 1879, the German scientist Fleming discovered,
that the nucleus contains thread like structures.
These threads came to be known as chromosomes.
The Belgian Edouard van Beneden observed in the 1880’s ,
the way in which chromosomes were duplicated and shared,
between the two daughter cells, when a cell divided.
August Weismann, pointed out in the 1880’s that chromosomes,
were the carriers of hereditary information.
He observed two kinds of cell division.
In growth and development, all the chromosomes in a cell are duplicated,
before the cell divides.
Each daughter obtains a copy of the original set of chromosomes,
during cell division.
In cell division that produces egg or sperm cells, the chromosome is halved.
The full set of chromosome is restored, when two cells fuse,
to create the potential for the development of a new individual.
Weismann showed that the cells responsible for reproduction,
are not involved with the other processes in the body.
The cells that make-up the body are not involved,
with the manufacture of reproductive cells.
Darwin’s idea of Pangenesis was proved to be wrong.
Lamarckian’s idea that outside influences from the environment,
directly causes variations, from one generation to another, could also be ruled out.
Dutch botanist Hugo de Vries, worked with plants, to gain an insight into the way,
characteristics are passed from one generation to the next.
In 1889, he published a book, where he suggested,
that the characteristics of a species,
must be made up from large number of distinct units.
Each unit due to a single hereditary factor, which was passed on,
from one generation to the next, independently of the others.
He gave the hereditary factors the name of ‘pangenes’.
After Weismann showed, that the whole body is not involved in producing,
these hereditary factors, the ‘pan’, was dropped,
giving the familiar modern term,’gene’.
The term was first used by Dane Wilhelm Johannsen, in 1909.
In the 1890’s De Vries carried out experiments, where he recorded,
the way in which particular characteristics, such as colour of its flowers,
could be traced down the generations.
In 1899, De Vries was ready to publish his findings.
Before publishing, he carried out a survey of scientific publications.
He discovered that almost all his conclusions about heredity,
had been published already, by a Moravian monk, Gregor Mendel.
Mendel’s work was published in 1865.
Other scientists also came to similar conclusions.
The genetic basis of heredity was firmly established.
Gregor Mendel is credited with the first discovery of this concept of genetic heredity.
Mendel’s work was ahead of its time, and made little sense on its own,
until people had actually seen and worked on chromosomes.
Mendel was a monk, and also a trained scientist.
He was born in 1822, in Moravia.
He was an intelligent child, but came from a poor farming family.
The family exhausted its financial resources,
in sending the bright young man to school.
University education was beyond his financial means.
In 1843, Mendel joined the priesthood, in a monastery of St. Thomas in Brunn,
as the only means of furthering his education.
The Abbot of the monastery was in the process,
of turning the monastery into a leading intellectual centre.
The priest included a botanist, an astronomer, a philosopher and a composer,
all with a high reputation.
Mendel completed his theological studies in 1848.
He showed such ability, in 1851, at the age of 29,
he was sent to the university of Vienna.
He studied experimental physics, statistics, probability, atomic theory of chemistry,
and plant physiology, in a short period of 2 years.
He returned to the monastery as a teacher.
In 1856, he began an intensive 7 years study,
of the way heredity works in pea plants.
He studied about 13000 plants individually, and traced its descendants,
like a family tree.
Mendel pollinated each plant, dusting pollen from a single known individual plant,
on to the flowers of another single known individual plant.
He kept careful records of all these experiments.
Mendel discovered that there is something in the plant, which we now call genes,
that determines the properties of its overall form.
The genes come in pairs.
In one example, there is a gene S, which results in smooth seeds, and the gene R,
which results in rough seeds.
Any individual plant will carry one of the possible combinations like SS, RR or SR.
Only one of the genes in a pair, is expressed in the individual plant.
It is known as the phenotype.
If the plant carries RR or SS, they produce rough or smooth seeds.
If it carries the combination RS, we might expect half the plants to have rough seeds.
This is not the case.
One gene is dominant, and the other is recessive.
When RR plants are crossed with SS plants, 75% of the offspring has smooth seeds,
and 25% has rough seeds.
This is because there are two ways to make RS, SR and RS.
S is the dominant gene and R is the recessive gene.
In the next generation the individuals are evenly distributed among four genotypes,
RR, RS, SR, and SS.
Only RR has rough seeds.
Mendel actually carried out the experiments, to the grandchildren plants and beyond.
Mendel showed conclusively that inheritance works,
not by blending characteristics of the parents,
but by taking individual characteristics from each one.
By the early 1900’s it was clear that genes are carried on chromosomes,
and chromosomes come in pairs, one inherited from each parent.
We now know, in the kind of cell division, that makes sex cells,
these pairs are separated, but only after chunks of DNA, are swapped between them.
This makes new combinations of genes, to pass on to the next generation.
Mendel’s discoveries were not appreciated at that time.
In 1868,Mendel was elected as Abbot of his monastery.
His new duties gave little time for science.
His plant experiments was abandoned, when he was 46 years old.
He died in 1884.
Mendelian laws of inheritance, was rediscovered in the beginning of the 20th century.
This combined with the discovery of chromosomes,
provided the keys to understanding, how evolution works, at the molecular level.
American scientist Thomas Hunt Morgan was born in 1866.
He came from a prominent family.
His great grandfather Francis Scott Key, wrote the U.S. National anthem.
Morgan had doubts about the ideas of Mendelian inheritance.
He did experiments to prove that Mendel’s law, was at best a special case,
that applied to only a few simple properties of particular plants.
He chose to work with the fruit fly, Drosophila.
There was a great advantage in working with fruit flies.
They produced a new generation, every two weeks,
compared to a year, of Mendel’s plants.
Each female lays hundreds of eggs at a time.
By pure luck it turned out that Drosophila, have only 4 pairs of chromosomes.
This made Morgan’s experiments much easier.
One pair of chromosomes, had a particular significance,
as it had to do with sexual reproduction.
There is a distinct difference in the shape of the reproduction chromosomes.
From these shapes they are known as X and Y chromosomes.
In females, the chromosomes carry the XX pair, while the males carry XY pair.
A new individual must inherit the X chromosomes from the mother.
It could inherit either the X or the Y from the father.
If it inherits a X, it is a female.
If it inherits a Y, it is a male.
Morgan found that a variety of flies, had white eyes instead of usual red.
Careful experiments showed, that the gene related to the colour of the eyes,
must be carried on the X chromosome, and that it was recessive.
If the variant gene was present in the single X chromosome, they had white eyes.
A variant gene is called a allele.
In a female the relevant allele had to be present on both X chromosomes,
for the white eye, to show up, in the phenotype.
Morgan’s work established that chromosomes carry a collection of genes.
During the process that makes sperm or egg cells, paired chromosomes are cut apart,
and rejoined to make new combinations of alleles.
Genes that are far apart in the chromosome, are more likely to be separated,
when this process of crossing over, and recombination occurs.
Genes that are close together rarely get separated.
This provided the basis for mapping the order of genes in the chromosomes.
Morgan published, The theory of gene, in 1926.
He received the Nobel prize for his work, in 1933.
He died in 1945.
Evolution by natural selection only works when there is a variety,
of individuals to select from.
Morgan showed that the constant reshuffling of genetic possibilities,
provided by the process of reproduction, encourages diversity.
It also explains why it is so easy for sexually reproducing species,
to adapt to changing environmental conditions.
In humans there are about 30000 genes that determine the phenotype.
Over 93% of these genes are homozygous.
This means they are the same in each chromosome of the pair.
7% of them are heterozygous.
This means there is a chance that there are different alleles for that particular gene,
on the paired chromosome of an individual, chosen at random.
These different alleles have arisen by the process of mutation.
They sit in the gene pool, having little effect, unless they confer some advantage,
on the phenotype.
Mutations that cause a disadvantage, soon disappear.
This is what natural selection is all about.
2000 pairs of genes come in at least two varieties.
This means that there are 2 to the power of 2000 ways, in which 2 individual people,
could be different from one another.
This is a spectacularly large number.
It means that no 2 people on Earth are genetically identical.
Twins are exceptions, since they share the same genotype,
and come from the same fertilised egg.
No two people who have ever lived, have been exactly the same as each other.
This gives some indication of the variety on which natural selection operates.
Swiss bio chemist Friedrich Miescher was the scientist, who took the first steps to discover,
åthe double helix structure.
He worked as a physiology professor in Leipzig, from 1872.
Miescher was interested in the structure of the cell.
Virchow had laid down the doctrine, that living cells are created only by other living cells.
Miescher decided to investigate the human white blood cells, known as leucocytes.
They had an advantage of being available, in large quantities,
from the pus soaked bandages, from a nearby clinic.
It was known at that time, that proteins were the most important structural substance,
in the body.
Miescher found that the watery cytoplasm, which surrounds the nucleus,
was rich in proteins.
Further studies showed that there was something else present.
Miescher was able to isolate the nuclei for his studies.
He analysed the composition of the nucleus, and found that it was significantly different,
from that of a protein.
He called the substance as ’nuclein’.
It had carbon, hydrogen, oxygen, and nitrogen, like any other organic molecule,
but it also had phosphorus, unlike any protein.
By 1869, Miescher confirmed that this substance was present in other tissues,
and in cells of yeast.
He published his work in 1871.
Miescher continued his research on nuclein.
He used sperm cells from Salmon.
The sperm cell is almost all nucleus, since its sole purpose, is to fuse with the nucleus,
of a egg cell, and contribute hereditary material, for the next generation.
Miescher pointed out that structural proteins, from the body, must be broken down,
and converted into sperm.
He found that nuclein was a large molecule, which included several acidic groups.
In 1889, one of his students introduced the term, nucleic acid.
Miescher failed to appreciate that nuclei could be the carrier of hereditary information.
In 1885, Oskar Hertwig wrote that nuclein is the substance responsible for fertilisation,
and transmission of hereditary characteristics.
American biologist published similar findings in 1896.
The building block which gives its name to DNA is ribose.
Ribose is a sugar whose central structure consists of 4 carbon atoms,
linked with a oxygen atom in a pentagonal ring.
Other atoms like OH, are attached to the corners.
The second building block is a molecular group containing phosphorus,
and is known as phosphate group.
Phosphate group act as links, between ribose pentagons, in an alternate chain.
The third building block comes in five varieties, called bases.
They are known as guanine, adenine, cytosine, thymine, and uracil.
They usually referred with their initials as G,A,C,T,U.
The ribose pentagon gives the overall molecule its name, ribonucleic acid, or RNA.
An almost identical type of molecule was identified in the 1920’s,
in which the sugar units have one less oxygen atom.
It is called deoxyribonucleic acid or DNA.
RNA contains the bases G, A, C, and U.
DNA contains the bases G, A, C, and T.
This discovery reinforced the idea, that nuclein, was just a structural molecule.
This held back a proper understanding of its role in heredity.
Russian born American scientist, Phoebus Levene,
was a member of the Rockefeller institute.
He played a leading part in identifying the way building blocks of RNA was linked together.
He identified DNA in 1929.
He made a mistake which, thanks to his prestige, unfortunately had a wide influence.
His mistake resulted from analysis of large amount of nucleic acid.
When this was broken down, it turned out to contain almost equal amounts of G,A,C, and U.
This led him to conclude that nucleic acid was a simple structure,
made up of 4 repeating units.
This idea became known as the tetranucleotide hypothesis.
Instead of being tested, this hypothesis became a dogma,
accepted by many other scientists.
Proteins were known to be more complicated molecules,
made up from a large variety of amino acids, linked together in different ways.
This reinforced the idea that all the important information in the cell,
was contained in the structure of proteins.
Nucleic acids were considered as simply providing a supporting structure,
that held the proteins in place.
It was thought that a molecule like GACU, repeated many times,
contains very little information.
The British scientist Fred Griffith was a medical officer in the ministry of health, in London.
He was investigating the bacteria that causes pneumonia.
He had no intention of investigating heredity.
Bacteria reproduces faster than fruit flies.
It goes through many generations in the matter of hours.
It could show changes in a few weeks, that would be revealed by fruit flies over many years.
Griffith discovered that there are two kinds of pneumococci.
One was virulent, and caused a disease which was often fatal.
The other produced little or no ill effects.
Griffith found that the dangerous bacteria, could be killed by heat, and injected into mice,
with no ill effects.
When the dead bacteria was mixed with the non lethal variety,
the mixture was almost as virulent, as the dangerous bacteria.
Griffith died before the importance of his work could be realised.
This discovery triggered a change of direction by American scientist Oswald Avery,
who was working on pneumonia, in the Rockefeller institute since 1913.
Avery and his team investigated the way in which one form of pneumococci,
could be transformed to another form, in their experiments.
They found by growing a colony of non lethal pneumococci,
along with dead cells of the virulent strain, was sufficient to transform,
the growing colony, into the virulent form.
Something was passing from the dead cells, into the living pneumococci,
being incorporated into their genetic structure.
But they did not know what it was.
It took until 1944 for Avery to identify the chemical substance responsible,
for the transformation they observed.
They proved that the transforming substance was DNA, and not protein as widely assumed.
But they did not identify DNA with genetic material.
Erwin Chargaff was born in Vienna, in 1905.
He received his Phd in 1928.
He joined the Columbia university in 1935.
Chargaff realised that DNA molecules must come in great variety of types,
with a more complicated internal structure.
Using the new techniques of paper chromatography, and ultraviolet spectroscopy,
he was able to show that the composition of DNA is the same within each species,
but differed from species to species.
He suggested that there must be as many kinds of DNA, as there are species.
He also found there is a degree of uniformity, underlaying the complexity of DNA.
The four different bases of DNA come in two varieties.
Guanine and adenine are members of chemical family called purines.
Cytosine and thymine belong to a chemical family called pyrimidines.
He published what is known as Chargaff rules in 1950’s.
It said the total amount of purines is always equal to the amount of pyrimidines.
The amount of adenine is the same as the amount of thymine.
The amount of guanine will be the same as the amount of cytosine.
These rules are a key to understand the famous double helix structure of DNA.
To appreciate how this structure is held together,
we need to understand the developments in chemistry, following the quantum revolution.
Quantum physics was able to explain the patterns found in the periodic table of elements.
It gave insight why some atoms link up, with other atoms to make molecules,
while some do not.
It depends on the way energy is distributed among electrons in an atom.
It is always in such a way to minimise the overall energy of the atom.
The idea was clear even in Bohr’s model of the atom.
Bohr originally thought that electrons were tiny hard particles.
The important difference after the understanding of quantum theory,
was that they were spread out entities.
Even a single electron can surround an atomic nucleus, like a wave.
The quantum properties of electrons, allow only a certain number of electrons,
to occupy each energy level, in an atom.
We can imagine this as corresponding to different orbits around the nucleus.
This model is not strictly accurate, but serves to understand the concept.
The different energy states are known as shells.
Several electrons may occupy a single shell.
Full shells have the maximum number of electrons allowed.
These are favoured over partly filled shells.
The shell nearest to the nucleus allows for two electrons.
The second shell allows for eight electrons.
The third shell allows eight electrons.
A hydrogen atom has a single proton, and a single electron.
The shell allows for two electrons, which is the desired level.
Hydrogen therefore links up with other atoms, to share an electron in the first shell.
In H2, one electron is shared by two hydrogen atoms.
Helium has two electrons in the first shell, which is the desired energy state.
It does not react with other atoms.
Lithium has three protons and three electrons.
Two of them occupy the first shell.
One electron occupies the second shell.
This is why lithium is either to share one lone electron with other atoms.
It is highly reactive and has similar chemical properties to hydrogen.
The number of protons in an atom, is the atomic number.
Neon has 10 protons and 10 electrons.
2 electrons are in the first shell, and 8 electrons are there in the second shell.
Neon is an inert gas, like helium.
This is why there is a repeating pattern of chemical properties for elements,
8 units apart, in the periodic table.
Sodium has an atomic number of 11.
It has 2 electrons in the first shell, 8 in the second shell,
and a lone electron in the third shell.
It has similar chemical properties to lithium, whose atomic number is 3.
American scientists Gilbert Lewis, in 1916, developed the idea,
of bonds forming between atoms, as they shared electrons, to form full shells.
It is known as the covalent bond.
It is important in describing carbon chemistry, that lies at the heart of life.
Carbon has 6 electrons, 2 in the first shell and 4 in the second shell.
It shares an electron with 4 hydrogen atoms, to form CH4.
If an atom has 5 electrons in the outer shell it strives to make 3 bonds to fill the shell.
If it had 3 electrons, it could make only 3 bonds, though it might want to make 5.
4 bonds is the maximum any atom can make.
This is why carbon is an excellent compound maker.
Carbon has the potential to produce a wide variety of complex molecules.
Another type of bond is the ionic bond.
The Swedish scientist Svante Arrhenius was one of the scientist who developed this idea.
He received a Nobel prize in 1903 for this.
Sodium has two full inner shells, and a lone electron in the third shell.
Chlorine has 17 electrons, in two full shells, and a third shell of 7 electrons.
If a sodium atom gives up 1 electron to a chlorine atom, it satisfies both,
as the outer shells would be complete for both atoms.
This arrangement leaves sodium with a positive charge, and chlorine with a negative charge.
The resulting ions of sodium and chlorine are held together,
by electric forces in a crystalline array which acts like a sodium chloride molecule.
Molecules of sodium chloride do not exists as independent units, like CH4 does.
In quantum physics, things are seldom clear cut and straight forward.
Chemical bonds are a mixture of covalent and ionic bonds.
Some bonds are more covalent, and some are more ionic.
The bond models are helpful to imagine the molecules.
In 1920’s, Schrodinger published his quantum mechanical wave equation.
In 1927 two German scientists used this mathematical model,
to calculate the change in the overall energy of two hydrogen atoms,
which combine to form one molecule of hydrogen, with a pair of shared electrons.
This agreed with experiments, to measure the amount of energy required,
to break the bond of a hydrogen molecule.
Later experiments proved that in atoms and molecules, the arrangement of electrons,
are most stable, when they have the least energy.
This was crucially important in making chemistry a quantitive science, at the molecule level.
It provided evidence that quantum physics applies in general,
and in a precise way to the atomic world.
American scientist Linus Pauling, put all the pieces together,
and made chemistry a branch of physics.
He got his degree in chemical engineering in 1922.
He got his Phd in 1925.
This was the time that Broglie’s idea about electron waves was gaining attention.
Pauling worked briefly with Bohr, Schrodinger and Bragg.
William Bragg and his son Lawrence, are key figures in the story of discovery,
of the structure of DNA.
William Bragg graduated from Cambridge in 1884.
He worked for a year with JJ Thomson.
He worked on alpha rays and X-rays.
He developed the first X-ray spectrometer, to measure the wavelength of X-rays.
In 1923, he was appointed director of the Royal Institution.
William Bragg had the dream of using X-ray diffraction to determine the structure,
of complex organic molecules.
His son Lawrence Bragg, graduated in mathematics in 1908.
On his father’s suggestion, he switched to physics and graduated in it, in 1912.
When he was a research student, news came from Germany, that Max Von Laue,
observed the diffraction of X-rays by crystals.
This is exactly equivalent the way light is diffracted in the double slit experiment.
Since the wave length of X-rays are much shorter than light,
the slits had to be much smaller.
It turned out that the spacing between layers of atoms, in a crystal,
is just right to do the job.
This established that X-rays are a form of electromagnetic waves,
with shorter wave lengths.
Von Laue received the Nobel prize for this in 1914.
Lawrence Bragg worked out the rules, to predict where the bright spots,
in a diffraction pattern would be produced, when a beam of X-rays,
with a particular wavelength, struck a crystal lattice,
with a particular spacing between atoms, at a particular angle.
This established that X-ray diffraction could be used to probe the structure of crystals.
Lawrence Bragg came up with what is known as Bragg’s law.
By measuring the spacing of the bright spots in the pattern,
one could determine the wavelength of the X-rays, if the spacing of the atoms,
in the crystal was known.
If the wave length of the X-rays was known, one could measure the spacing between atoms,
in a crystal.
It was this work that showed, in sodium chloride, there are no individual molecules,
but an array of sodium and chlorine ions, arranged in a geometric pattern.
William Bragg and Lawrence Bragg, published the book,
X-rays and crystal structure, in 1915.
Both of them received the Nobel prize for their work.
Lawrence Bragg, was 25 years old, was the youngest, to receive the Nobel prize.
They were the only father and son team, to share the Nobel prize.
Lawrence Bragg succeeded Rutherford, as head of the Cavendish lab.
He became a director of the Royal institute till he retired in 1966.
Linus Pauling learnt about X-ray crystallography from the book written by the Bragg’s.
He carried out his own determination of crystal structure in 1922.
He became a professor in Caltech in 1931.
He published a set of rules for interpreting the X-ray diffraction patterns.
Lawrence Bragg had already developed the same rules, but Pauling published it first.
It is now known as Pauling’s rule.
Lawrence Bragg was not pleased, and a rivalry developed between them.
In 1931, Pauling published a great paper, The Nature of the Chemical Bond.
By 1935, he felt he had a complete understanding of the chemical bond.
He moved on to understanding the structure of complex organic molecules, like proteins.
At that time DNA was not regarded as a complex molecule.
The structure of proteins yielded to a two pronged investigation.
One was the understanding of the chemical bond,
of how the amino acid subunits of proteins, fitted together.
X-ray crystallography helped to understand the overall shape of the molecules.
Only certain arrangements of subunits was allowed by chemistry.
Only certain arrangements of subunits could produce the observed diffraction patterns.
Combining both, one could build a model of biomolecules.
A lot of hard work was involved to reveal the structures of important biomolecules of life.
Pauling and other scientists over the next 40 years,
revealed the structure of many biomolecules, like haemoglobin, insulin, and myoglobin.
This had significant impact on human healthcare.
The existence of hydrogen bonds highlights the importance of quantum physics,
to the chemistry of life.
It illustrates the way the quantum world differs from our everyday world.
Scientists knew that it is possible to form links between molecules,
that involve a hydrogen atom, as a kind of bridge.
Pauling wrote about the hydrogen bond, which was weaker than a normal covalent bond,
or ionic bond in 1928.
In 1930, he revealed how hydrogen bonds form bridges between water molecules in ice.
Along with a colleague he applied the idea to proteins.
To appreciate hydrogen bonding, we have to visualise a proton in a cloud of electric charge,
representing the electron.
When the hydrogen atom is involved in forming a bond,
with an atom such as oxygen, the cloud of charge is pulled towards the other atom,
leaving only a thin covering of negative charge, in the hydrogen atom.
Hydrogen has no other electrons to conceal the positive charge of its proton.
This will attract any nearby atom, which has a preponderance of negative charge.
Oxygen in a water molecule gains extra negative charge, from its two hydrogen atoms.
The positive charge on each of the two hydrogen atoms can link,
with an electron cloud of another water molecule.
This gives ice, a very open crystalline structure, with a low density.
This makes ice float on water.
Pauling made the idea of hydrogen bond, into a precise, quantitive science.
In proteins, when long chain protein molecules fold up into compact shapes,
they are held in their shapes by hydrogen bonds.
This was a key insight, since the shape of the protein molecule is vital to its function.
The hydrogen bond can be explained only in terms of quantum physics.
Our understanding of the molecular basis of life,
came after our understanding of quantum mechanics.
The combination of understanding, how the subunits of proteins, can fit together,
and the X-ray diffraction patterns produced by molecules,
led to the determination of the basic structure, of a whole family of proteins.
These proteins were a fibrous kind, found in hair and fingernails.
The scientist William Astbury, showed that globular proteins, such as haemoglobin,
and myoglobin, are made of long chain of proteins.
These are called polypeptide chains, that fold up as balls.
Pauling’s team identified the basic structure of fibrous protein in 1951.
They showed that this structure is made up of long polypeptide chains,
wound around one another, in a helical fashion.
It is like the strands of string, that are wound together to make a rope.
Hydrogen bonds play an important role in holding the coils in shape.
The world of biochemistry was overwhelmed, when his team published the papers,
laying out in detail the alpha-helix structure of fibrous proteins.
This led to other scientists thinking about helices, for other biological macro molecules.
What was important in Pauling approach, was combining the X-ray data, model building,
and a theoretical understanding of quantum chemistry.
Many scientists including Pauling worked on discovering the structure of DNA.
The American Scientist James Watson did his post doctoral scholarship,
in Cambridge in 1951.
He worked with another scientist Francis Crick.
Crick was inspired by a book, What is life?, published by Erwin Schrodinger in 1944.
Schrodinger did not know that chromosomes were made of DNA.
Schrodinger called chromosomes an aperiodic crystal.
Schrodinger suggested that information could be stored in terms of letters of the alphabet.
With three alphabets we could store 88,572 different words.
Crick was working on X-rays studies of Polypeptide and proteins.
He was interested in the structure of DNA.
Rosalind Franklin worked on the X-ray diffraction of DNA.
A team led by Maurice Wilkins also worked on the model for DNA.
Watson attended a talk given by Rosalind Franklin.
Building on the work on other scientists including Pauling,
Watson and Crick came up with a model for DNA.
This involved strands twining around one another, with a nucleotide bases, A, C, G, and T.
The model was embarrassingly bad, and was not received well by other scientists.
In a conversation with a mathematician John Griffith, Crick tossed out the idea,
with the nucleotide bases in the DNA, might fit together somehow,
to hold the molecules together.
Griffith worked out that adenine and thymine could fit together,
linking up through a pair of hydrogen bonds.
Cytosine and guanine could fit together with a set of 3 hydrogen bonds.
Crick did not appreciate the importance of this pairing.
He also did not appreciate the relevance of hydrogen bonds.
He also did not know Chargaff’s rules.
In 1952, Chargaff visited Cavendish lab, and was introduced to Crick.
He mentioned to Crick, that DNA always contains equal amounts of A and G,
and equal amounts of C and T.
This combined with Griffith’s work, clearly suggested that the structure of DNA,
must involve pairs of long chain molecules, linked together by AG and CT bridges.
Linus Pauling came up with a model which had a triple helix structure,
with three strands of DNA wound around one another.
Crick and Watson realised that this model was not correct.
Watson took a copy of Pauling’s paper to show it to Wilkins.
Wilkins showed Watson a print of Franklin’s best photographs, without her knowledge.
It was this picture, which could be interpreted in terms of helical structure,
plus the Chargaff’s rules, and the relationship worked out by John Griffith,
that enabled Crick and Watson to produce the famous DNA model, in 1953.
The model had a double helix, with the entwined molecules held together,
by hydrogen bonds, linking the nucleotide bases.
Franklin was thinking along very similar lines to Crick and Watson.
She was ready to publish her own version of the double helix structure,
when the news came about Crick and Watson’s discovery.
Three papers were published in April 1953, in ‘Nature’ about the DNA model.
One was by Crick and Watson, one by Wilkins and colleagues,
and one by Franklin and Gosling.
The paper by Franklin and Gosling represented a completely independent discovery,
of the structure of DNA.
Rosalind Franklin did not get the credit she deserved.
She died in 1958 from cancer, possibly caused by her work with X-rays.
Crick, Watson and Wilkins shared the Nobel prize in 1962.
A combination of bases, A, C, G and T makeup the single strand of DNA.
Crick and other scientists, discovered that the genetic code is actually written in triplets.
These triplets are combinations like CTA or CGC.
Each triplet represents one of the 20 amino acids.
Amino acids are the building blocks of proteins.
From the DNA a string of 3 letter codons is copied into a string of RNA.
In RNA thymine is replaced with uracil.
The messenger RNA acts like a template to manufacture proteins in the cell.
Proteins are a string of amino acids linked together.
When enough protein is produced, RNA is disassembled and its components are reused.
How the cell knows when and how much protein to produce, is yet to be explained.
Another important feature of the DNA double helix, is that the two strands,
in terms of their bases, are mirror images of one another.
A on one strand corresponds to a T and the other strand.
C on one strand corresponds to a G and the other strand.
During cell division, one strand goes to each daughter cell.
The second strand is built up using correspondence bases.
The genetic code of DNA is reproduced in each daughter cell.
This process provides a mechanisms for evolution.
During cell division, while copying DNA there are occasional mistakes.
This does not matter much in growth cells.
In reproductive cells, the cell division provides for only half the DNA, in the daughter cells.
There is more scope for copying the errors.
This is partly due to the extra processes involved in crossing over and recombination.
When the resulting sex cell, fuses with the partner, it develops into a new individual.
This gives a chance to express the mistakes in copying.
In most cases the resulting changes may not be significant.
In rare cases, the DNA copying error produces a gene,
that makes it better suited for the environment.
This makes it amenable for natural selection and Darwinian evolution.
From 1960’s onwards, scientists investigated the genetic material of humans,
and other species.
It became gradually clear, how closely we are related to the African apes,
who Darwin himself regarded as our closest living relatives.
By late 1990’s it had been established that human beings share 98.4%,
of their genes with chimpanzees.
Studying fossil evidence of related species, can be used as a kind of molecular clock.
It tells us that the chimpanzee and gorilla lines, split from the common stock,
just 4 million years ago.
A small genetic difference between ourselves and chimps,
suggested that important differences must be there,
in control genes that regulate the behaviour of other genes.
The human genome project completely mapped, all the DNA in every chromosome in 2001.
It lists all the genes in terms of strings of codons.
It is still not known what most genes actually do.
The genome map suggests that there are about 30,000 genes.
The 30,000 genes are capable of making at least 250,000 proteins.
The number of human genes is only twice that of a fruit fly.
It is clear that the number of genes alone does not determine,
the nature of the body they build.
The number of genes we have does not explain the way,
in which we are different from other species.
The few genes which are different in us, are affecting the way the other genes operate.
All species have the same genetic elements.
The mechanism of DNA, RNA and protein synthesis, is same in all species.
We have all evolved from primordial forms of life on Earth.
This puts in perspective our place in the scheme of life.