Advancing Epigenetics Towards Systems Biology

Dorothy Crowfoot Hodgkin

Deciphering atomic hieroglyphs

Name: Dorothy Crowfoot Hodgkin
Nationality: British
Lived: 1910-1994
Fields: Biophysics, biochemistry and crystallography
Claim to fame: Pioneer in the field of crystallography; discovered the structure of several biological molecules

Insulin has transformed the lives of millions of diabetics around the world. Without Dorothy Crowfoot Hodgkin’s (1910-1994) pioneering and patient efforts – over a period of  some 35 years – to decipher this crucial hormone’s structure, its full potential may still not have been realised. All this was made possible by Crowfoot’s co-discovery and  development of X-ray crystallography as a critical method for studying natural molecules.

Scientific excavator

Dorothy Crowfoot was born in 1910 in Cairo, where her father worked at the Egyptian Education Authority at a time when Egypt was still part of the British empire. Not long after her birth, the family moved to  Sudan where her father became the director of both education and antiquities. In fact, he so loved archaeology that he became a keen archaeologist after his retirement. Her mother was also an enthusiast and became an authority on early weaving techniques. Despite Dorothy’s love of chemistry, this passion for antiquity was transferred to their daughter and, just before going to university, she considered taking up archaeology full time after attending a dig with her parents in Jordan. Fortunately for physics and chemistry, she utilised her archaeologist’s bent for digging deep under the surface to piece together the structure of biological molecules.

Runs in the family

In 1937, by which time she was an established research fellow, Dorothy married the historian Thomas Hodgkin who was a bohemian, bon vivant and political activist. Like her, he had a passion for history and, with his interest in Africa and the Arab world, he spent time in such places as Palestine and Ghana. The couple had three children. Their daughter also inherited the history gene and went off to Zambia to teach the subject. One of Dorothy’s greatest scientific and political mentors was fellow chemist Professor John Desmond Bernal who was a communist (until 1956), and greatly influenced her life both scientifically and politically. Both unassuming and passionate, Dorothy cared greatly about issues of social inequalities and peace.

Crystals are a girl’s best friend

While most young children have vague dreams of becoming doctors or simply famous, Dorothy Crowfoot – who became fondly known as “the cleverest woman in England” and a “gentle genius” – became interested, at the age of ten, not only in chemistry but also in the study of crystals.
Large stretches of her childhood were spent apart from her parents who sent their children to school in the UK while they remained in Africa. In 1921, she entered the Sir John Leman Grammar School in Beccles, Suffolk, travelling abroad frequently to visit her parents in Cairo and Khartoum.
From 1928 to 1932, Dorothy studied at Somerville College, which was also known as “bluestockings college”, at Oxford University. After attending a special course on crystallography, i.e. the study of the arrangement of atoms in solids, she decided to specialise in the emerging use of X-rays in this field. For that reason, she went to Cambridge in 1932, to study with J.D. Bernal. From 1934 onwards, she spent her entire research career at Somerville College, Oxford. In 1956, she became University Reader in X- ray Chrystallography.

High-protein science

Dorothy dedicated most of her research career to mapping the structure of proteins and other biological substances. Insulin was her toughest and most rewarding challenge. The complex and multifaceted hormone captured her imagination because of the intricate and wide-ranging effect it has on the body. It took her and her team 35 years, between 1934 and 1969, to improve X-ray crystallography sufficiently to map out the complexity of this hormone.
“I used to say the evening that I developed the first X-ray photograph I took of insulin in 1935 was the most exciting moment of my life,” she wrote in the British Medical Journal in 1971. “But the Saturday afternoon in late July 1969, when we realised that the insulin electron density map was interpretable, runs that moment very close.”
In addition, Dorothy became a Wolfson research professor of the Royal Society in 1960 and was present at the inception of the International Union of Crystallography in 1946.

Scientific achievements

There was a time when there were plenty of theories about the structure and function of microscopic molecules, but few hard facts. It is difficult to understand what you cannot see, and that explains why Dorothy Crowfoot dedicated her life to unlocking the complex structures of molecules at the atomic level.
She was not only a trailblazer in X-ray crystallography – which was critical in determining the structure of DNA and other biological molecules – but she also created the field of protein crystallography. In fact, she is widely seen as being the scientist who most transformed crystallography from an art form into an indispensable scientific tool.
Among her most influential discoveries were her confi rmation of the theoretical structure of penicillin. Her decades-long pursuit of insulin must count as one of the most dogged quests in modern science. For her description of the structure of the vitamin B12, she received the Nobel Prize for chemistry in 1964.