Dorothy Hodgkin is possibly the greatest British female scientist. A bold claim, but what makes her so great? As May 12th was the 100th anniversary of her birth, I thought I’d take a little look at the achievements that mean Dorothy Crowfoot Hodgkin is the only British woman to receive a Nobel Prize in Chemistry and is rightly revered by the Royal Society- who award a research fellowship in her name, and even included her in the set of commemorative stamp as part of their 350 year celebrations (you really know you’ve made it then).
A picture of the New Hodgkin stamp produced to celebrate the Royal Society's 350th anniversary
Quite frankly, Dorothy Hodgkin helped develop and revolutionise an entire branch of science- Protein crystallography. As a small molecule crystallographer myself, I have often taken small pot-shots at our ‘large molecule’ friends, but there is no getting away from the fact that Protein crystallography is at the forefront of biological research today, being instrumental in driving the development of new pharmaceuticals and therapies.
To quote Isaac Asimov’s Biographical Encyclopaedia of Science and Technology (a gripping read), ‘For her doctoral labours, she studied the X-ray diffraction of crystals of the digestive enzyme pepsin. That fixed the direction of her interests and she spent her later professional life on the determination of complex organic structures through X-ray diffraction’. And you can’t get more complex than proteins.
The structure of Penicillin
During the second world war, Hodgkin set about determining the molecular structure of penicillin, which had recently been isolated. The importance of this cannot be overstated as the final results produced in 1948 meant that for the first time, science knew the exact geometrical relationship between the different atoms in the penicillin molecule. Up to then, other analytical techniques could provide information about what atoms were present in the molecules, but not exactly where they were and how they were orientated relative to each other. Synthetic chemists had the tools for building molecules at their disposal and knowing the three-dimensional make-up of penicillin meant it was much easier for them to make penicillin in the laboratory, and indeed tweak the atomic make-up of the molecule which has led to the wide array of penicillin derived antibiotics we have today.
This was the first time an electronic computer was used in this way, although the computer itself would probably be unrecognisable from today’s machines, being the size of a medium sized building and with all the information needing to be input via reams of punch cards that were transferred across the university by wheelbarrow. This new application of computers, coupled with the relatively new science of X-ray crystallography, revolutionised the future synthetic and analytical approaches of chemists and biochemists.
The structure of Vitamin B12
Having sorted out penicillin, Hodgkin turned her attention to Vitamin B12, which was ultimately to lead her to a Nobel Prize. Up to now Hodgkin had had a pretty good idea of what she was working with, in terms of the atoms that were present in the molecules she was studying, and the molecules themselves were relatively small, being in the order of tens of atoms.
Vitamin B12 provided a much bigger challenge, however, as there was virtually no chemical information available and the hundred or so atoms present in one molecule meant that previous techniques for analysing the results were no longer usable. Hodgkin and her co-workers developed many new techniques, still utilised today, that allowed the full structure of B12 to be elucidated, a feat unachievable by any other means. This work was hugely important and led to many medical applications, such as the treatment of megaloblastic anaemia.
Hodgkin continued to work on B12 and its biological activity, and in 1964 was awarded the Nobel Prize in Chemistry ‘for her pioneering and inspired work on the structures of biologically significant molecules using X-ray diffraction techniques’.
Churning along in the background to all this was insulin. Hodgkin had been given some small crystals of insulin in 1934, a moment which changed the direction of her research to determining it’s crystal structure. It took 35 years to get there but eventually, in 19, she and her research group reached their goal. The presentation of this structure to the scientific community led to a virtually complete understanding of insulin’s activity and behaviour in the body, and has ultimately led to much improved treatment for diabetes.
Insulin
To quote Max Perutz, himself a Nobel Prize winner, ‘She will be remembered as a great chemist, a saintly, gentle and tolerant lover of people and a devoted protagonist of peace’.
Much of this information has been gleaned from a fantastic biographical memoir of Dorothy Hodgkin, written by Guy Dodson (10.1098/rsbm.2002.0011)
joshuahowgego
railwaybecks
ross
bethanlowder
robellisatlantic
