Dorothy Hodgekin and the structure of insulin

Source: stevepb (via Pixnio)
Dorothy Hodegkin was a pioneering chemist behind the discovery of insulin's structure and her work is used by many researchers today.

By Holly Giles | Deputy Editor 

Diabetes is a common condition that causes the level of sugar in the blood to become too high as the body is unable to process sugar in the diet. Individuals with this condition are either not able to make any insulin (type 1) or cannot make enough insulin or the insulin it does make is unable to work properly (type 2). Insulin is the hormone which processes sugar in the diet, meaning this cannot be controlled and blood glucose levels keep rising and can lead to a condition called hyperglycaemia. 

Whilst this is a lifelong condition, affected individuals are able to keep their condition under control by taking measured amounts of artificial insulin. This builds on the work of key chemist Dorothy Hodegkin who was awarded the 1964 Nobel Prize in Chemistry for solving the anatomic structure of molecules using X-ray crystallography. 

Dorothy Hodegkin (born in 1910) was always interested in chemistry and was accepted to study it at the University of Oxford in 1928. During this course she used X-ray crystallography which is used to determine the anatomic structure of a crystal by shining X-rays onto different points of the molecule and using the diffractions of the rays which bounce off to calculate its structure. 

After graduating she went on to establish an X-ray laboratory at the Oxford University Museum of Natural History, where she began her work on insulin. This was always her focus but in 1939 it was put to one side when she was asked by her colleagues at Oxford to determine the structure of penicillin. 

Over the course of the following 6 years she completed this task and had described the arrangement of the atoms in the molecule in 3D. Hodgkin recognised this research as a vital war effort to enable antibiotics to become more efficient. This was revolutionary at the time as the largest molecule to ever be determined using this technique and led to Hodgekin being elected to the Royal Society in 1947. 

In the mid 1950s Hodgekin discovered the structure of vitamin B12, which led to her winning the Nobel Prize in 1964. She was then made a member of the Order of Merit, Britain’s highest honor for achievement in science, the arts and public life. 

She continued working on insulin, which required more advanced techniques in order to deduce its structure, but was able to complete this goal in 1969 when she and a team of researchers revealed insulin’s structure. 

Despite this glowing portfolio, Hodegkin overcame her own challenges being diagnosed with rheumatoid arthritis aged 28. Describing the initial symptoms of her condition she said: “I found I had great difficulty and pain in getting up and dressing. Every joint in my body seemed to be affected”. This pain continued to the point where she was forced to wear slippers as her ankles were so swollen. Despite this pain and difficulty moving she continued her work which required meticulous movements, even having her laboratory modified to enable  her to continue her work. Hodgkin was dedicated to the pursuit of research and her work is still used by researchers today. 

At her memorial service, her long-time collaborator and colleague, Max Perutz said of her:

“She radiated love: for chemistry, her family, her friends, her students, her crystals and her college… Her love was combined with a brilliant mind and an iron will to success, regardless of her frail and later severely crippled body. There was magic about her person”. 

There is currently no cure for type 1 diabetes and most patients manage by calculating the amount of sugar consumed and injecting the required dose of insulin into their bodies. Research is ongoing to try and make this process less invasive of patients and one such effort is the use of glucose-responsive insulin which is able to turn on when it’s needed and turn off when it’s not, allowing patients to take a daily pill that could adapt to their needs. Whilst this may sound like the stuff of science fiction, research for this is ongoing. It is hoped that when blood glucose levels are low, a binding element prevents the insulin from working. As glucose levels rise, the binding element is degraded, freeing insulin to work and lower glucose levels to normal. 

The Juvenile Diabetes Research Foundation (JDRF), a type 1 diabetes charity and funder of diabetes research, is currently investigating this idea by funding nine projects across the world which are all working towards this goal. One of these projects is based in the UK, at the University of Birmingham, where they are developing the capsule material for the insulin to go in. The project is described by JDRF as “a bit like a bath bomb in water, (that) would break up in the presence of high glucose levels, releasing the pockets of insulin”. 

Explaining the challenges of the project, Lead Researcher Dr John Fossey, said:

“Glucose is one of many sugars. It’s very easy to make a molecule that recognises any sugar, but very difficult to make one that can differentiate between two different types of sugar, such as glucose and fructose”. 

“The next big challenge for our team… is to exploit the glucose sensitivity we have discovered and take the glucose sensing technology to the next level in terms of insulin delivery. It’s perhaps ten years away, but we hope our work will translate to clinical use to manage insulin levels for people with diabetes, particularly children”. 

The possibility of smart insulin could not be achieved without the basic structure provided to us by Hodgekin and her team. It is due to her “determination” and “iron will” in the face of adversity that we are able to make the advances that we can see happening today.


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