(For Part 1, go here.)
Triple Helix Of Ramachandran
What is that connects skin, bones, tendons, and cartilage? They are all connective tissues and they are primarily made of protein called collagen. A protein is made of polypeptide chains. And these in turn are made of amino-acids.
The chemical components could be identified with hard work and intelligence but with relative ease, when compared to the search for the structure of the molecule.
How are these polypeptide chains, that make up the protein, orienting themselves in space?
The structure of a protein is important for understanding what it does in the biological system. So what is the shape of collagen?
Gopalasamudram Narayana Ramachandran or simply GNR, put Madras on the map of Indian science when he, along with Gopinath Kartha, proposed the triple helix structure for the collagen molecule.
The work was published in Nature magazine in 1955.
Collagen has a unique structure that consists of three polypeptide chains, each with a repeating sequence of three amino acids: glycine, proline, and hydroxyproline. These chains are twisted around each other to form a right-handed helix, and then three of these helices are further coiled around a common axis to form a left-handed superhelix.
Co-discoverer of the structure of the DNA molecule, Francis H C Crick, however, opposed the proposed structure saying that though the “idea” was “basically correct”, “the actual structure suggested by them to be wrong”.
But the model, now famous as the ‘Madras triple helix model’, was vindicated, though Ramachandran was never given his rightful place of honour for the discovery.
GNR solved the structure of collagen by analysing the X-ray diffraction patterns, from collagen samples obtained from kangaroo tail tendon, which he obtained from the nearby Madras leather institute.
Today, the name of the institute’s hall is called Triple Helix Hall, to honour the contribution of the Institute to the discovery of collagen structure.
The discovery of the collagen structure was a major breakthrough in biochemistry and biophysics, as it revealed the molecular basis of many biological functions and diseases related to collagen.
It also inspired further research on other protein structures, such as the alpha-helix and the beta-sheet, which GNR also studied using his famous Ramachandran plot.
What is the legacy of Ramachandran to the world of science? Perhaps the words of biophysicist, Dr Vijayan, summarise the achievements of the life of this seer — a life that was incredibly great in the annals of science:
G N Ramachandran is among the founding fathers of structural molecular biology. He made pioneering contributions in computational biology, modelling and what we now call bioinformatics. The triple helical coiled coil structure of collagen proposed by him forms the basis of much of collagen research at the molecular level. The Ramachandran map remains the simplest descriptor and tool for validation of protein structures. He has left his imprint on almost all aspects of biomolecular conformation. His contributions in the area of theoretical crystallography have been outstanding. His legacy has provided inspiration for the further development of structural biology in India.
Inexplicably, but perhaps not unexpectedly, he was denied Nobel Prize. But what saddens — is the way his legacy has been ignored in his own nation and even in his own home state.
Pathogens Of Sambhu Nath De
In the year 1950, out of 176,307 cases of Cholera in India, the deaths numbered 86,997. That is a fatality rate of 49.34 per cent. Fifteen years later in 1965 the fatality rate was 29.9 per cent wit 12,947 deaths.
So what happened in between?
Sambhu Nath De’s discovery happened.
Sambhu Nath discovered in 1959, the cholera toxin and its peculiar nature. Using a technique called the ‘rabbit intestinal loop model’ he isolated and identified the toxin from the bacterium. He also identified and demonstrated the method of transmission of the cholera pathogen.
This expanded our knowledge of the disease outbreaks and helped us to better our responses to the disease.
Most bacterial toxins were endotoxins. They get absorbed into the blood stream. But the toxin of Vibrio cholerae was different. This toxin stayed in the intestine and acted locally on the epithelial cells or the cells covering the inner walls of the intestines.
In other words, the toxin of Vibrio cholerae was an enterotoxin, a cytotoxin that acts locally with the wall cells of the intestine. The toxin makes the intestine to lose chloride ions and water, leading to diarrhoea.
He also showed that the toxin can be neutralised by antibodies. This in turn paved the way for vaccine development. More importantly, his work led to the development of oral rehydration salts therapy, which saved millions of lives.
So, here is a discovery that directly helped in the saving of human lives and is also scientifically innovative. Joshua Lederberg, American Nobel Laureate in medicine and physiology, nominated Sambhu Nath De twice for Nobel Prize.
Again he was denied the prize, though in 1978, he was invited by the Nobel Foundation to participate in the 43rd Nobel Symposium on Cholera and related Diarrhoeas.
Singularity Of Raychaudhuri
In 1915, Einstein came up with General Theory of Relativity (GTR). However Einstein had a problem. GTR predicted the coming up of singularities — the points where gravity is so strong that all space, time and laws of physics break down.
This for Einstein meant that his theory was incomplete. His own theory predicted that there are points where the theory breaks down at these crucial points, failing to explain the further evolution of the universe.
At the same time, GTR remains the single most efficient theory to explain the observational and experimental data.
In 1955, the year Einstein died, a young Indian physicist Amal Kumar Raychaudhuri came up with an equation, now very fundamental and important for physicists.
Called Raychaudhuri equation, it demonstrates that singularities inevitably arise in GTR.
The reason for Einsteinian inhibition was that he considered singularities as artefacts of solutions — more mathematical conjectures and could not be reality. So for him such conjectures, seemingly artificial, arising out of his theory disturbed him.
But Raychaudhuri equation elegantly makes singularities part of the property of GRT. They exist under certain conditions and are localised, as in blackholes.
Raychaudhuri equation laid the solid foundation for future developments with regard to black holes and quantum gravity. The famous Penrose-Hawking singularity theorem published in 1969 was built upon Raychaudhuri equation.
In 2020 Physicist Roger Penrose won Nobel prize jointly with Reinhard Genzel and Andrea Ghez, of which, one half of the prize was awarded to Penrose 'for the discovery that black hole formation would be a general theory of relativity.'
Amal Kumar Raychaudhuri himself, did not receive Nobel Prize.
Order Of David Bohm
Albert Einstein, had his serious reservations about Quantum Mechanics (QM) — particularly what is called the Cophenhagen Interpretation.
He viewed QM as an incomplete representation of physical reality. He wanted determinism to be back in the saddle. Many physicists embarked on this quest set out by Einstein. Among them, one of the most brilliant grail seeker was David Bohm.
David Bohm was a brilliant theoretical physicist. As a post-graduate student he had developed a theory of plasma diffusion.
It is about the diffusion of plasma in magnetic field. Today, it is one of the fundamentals of plasma physics.
He arrived independently at a theory, that had been proposed first by another famous physicist Louis De Broglie — pilot wave theory.
De Broglie had tried to overcome some of the weirdness that QM presented, like the famous Schrodinger’s cat paradox. Very simply put, if light waves have a particle aspect, then why not material particles have a wave aspect?
De Broglie wave equation is quite famous and it is the wave nature of electron — that the equation provides — is the basis of electron microscopy. Bohm arriving at the pilot wave theory independently also made improvements.
Today, De Broglie-Bohm theory, also known as the pilot-wave theory, suggests that particles are not just wave functions, as conventional QM holds, but they are particles that move in a way piloted by a wave — at quantum level.
If we know all things about the particle and its pilot wave at a particular point in time, then we can predict exactly how it will behave in the future. So, from the probabilities of QM we move to a deterministic model.
Another very important contribution of Bohm, was his improvement of the famous EPR paradox.
In the original paradox designed by Einstein, Podolsky and Rosen (EPR), position and momentum are studied. So, if one knows the position of one particle of an entangled pair, then irrespective of distance, the other particle’s position information is obtained violating the speed limit of information flow in the universe — the speed of light.
While this is all right for a thought experiment, it cannot be performed in the lab.
Bohm refined the EPR experiment. This led to it being testable in the labs.
In 1951, Bohm came up with his version of EPR thought experiment: instead of momentum and position, the spin property of the entangled particle pair is taken.
When the spin of one particle is observed, then the information irrespective of the distance, decides ‘instantaneously’ the value of the spin of other particle. This is what Einstein called ‘the spooky action at a distance’ — or the non-local nature of QM universe.
This improvement by Bohm led John Bell, in 1964, to come up with his famous ‘inequality theorem’. This would ultimately lead to the design of experiments with which a lab-version of EPR could be conducted and it vindicated QM.
John Bell and David Bohm passed away in 1990 and 1992, respectively.
In 2022, the Nobel Prize for physics was directly related to work proceeding from Bell’s inequality theorem and led to quantum information technology.
Apart from these, David Bohm's concept of the Implicate Order, though marginalised in mainstream physics, continues to elicit interest and inspire studies not just in physics — but also in philosophy, psychology and social sciences.
In 1959, David Bohm, along with his doctoral student Yakir Aharonov, published a paper on how in the quantum realm, a magnetic field can effect an electromagnetic potential on a charged particle, even though the particle is in a space where the field is null.
Today known as ‘Aharonov Bohm effect,’ it is part and parcel of Quantum Mechanics.
In 1958, he was nominated for Nobel Prize by Japanese physicist H Nakano.
According to the excellent biography of Bohm written by Olival Freire (Jr):
'from some hints in the Bohm Papers,... in 1989 Basil Hiley, Bohm’s long-standing assistant there, was asked by his head of department to send some background information in order to support Bohm’s nomination for the Nobel Prize for quantum non-locality.'
So we can infer that he was nominated for Nobel Prize, twice.
There could be many reasons for Bohm not getting the Nobel. During McCarthy era, he was dismissed from Princeton University for his left leaning. His search for a deterministic model of QM did not go well with then the dominant Copenhagen interpretation of QM and its proponent Niels Bohr. His interests in making physics part of a larger holistic worldview, also was not much appreciated by the physics community.
So what should India do?
Clearly, Nobel Prizes have their own motivation and mostly Western-centric notions in their choice. This is expected.
India can institute its own version of prizes: Sudarshan-Bohm Prize for Physics; GNR-Prize for Chemistry; Jagadish Bose Prize for Systems Science; Sambu Nath-Haldane Prize for Physiology and Medicine.
As a guiding light of the global South, India will usher in a new era of alternative recognition for science — that has the potential to become the mainstream.
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