Hodgkin and Kraepelin

You may be wondering at this stage how many women have actually received the Nobel Prize.

Precious few.

The most famous, needless to say, was Marie Curie, who with her husband Pierre won the Physics Prize in 1903 for their discovery of radium, only two years after the Nobel Foundation was established. Marie, in fact, was the first woman to win any Nobel Prize, just as she had been the first woman in history to teach at the Sorbonne. She won the Chemistry Prize, too, in 1911.

In 1964 the Nobel Foundation conferred its Chemistry Prize on Dorothy Crowfoot Hodgkin (1910-94). It was the fourteenth time a Prize had been awarded to a woman, in this case “for her determination by x-ray techniques of the structures of biologically important molecules”. Those crucial molecules included penicillin, cyanocobalamin (vitamin B₁₂) and insulin.

Let us have a look at Hodgkin’s work on vitamin B₁₂.

In the late 1920s the American physician William B. Castle had done research on the cause of pernicious anaemia, which in those days was usually fatal. He discovered that two substances were involved: one that is produced in the body (which he called “the intrinsic factor”, still known in medicine as “intrinsic factor”, these days without the the) and one that is supplied in the diet (“the extrinsic factor”, which today we call vitamin B₁₂). Intrinsic factor, a glycoprotein generated in the gastric juices, forms a complex with vitamin B₁₂ that remains intact, so protecting the vitamin from digestion as it passes through the gastrointestinal tract and facilitates its absorption into the body via the small intestine.

Without enough vitamin B₁₂, the body is unable to synthesize DNA properly. In turn this affects red blood cell maturation in the bone marrow (the cells divide but their nuclei remain immature). In other words, B₁₂ avitaminosis (deficiency) — and therefore pernicious anaemia — is due to decreased B₁₂ absorption rather than a poor diet, in contrast to iron deficiency, say.

Vitamin B₁₂ was isolated in 1948, and later that year Hodgkin got an opportunity to take on the task of determining the precise configuration of its constituent atoms when the Glaxo laboratories sent some crystals to Oxford University, where she did most of her research.

It took her eight years. Penicillin had been a complex molecule to analyse in 1944-5, but vitamin B₁₂ was far more challenging, having about 100 atoms to penicillin’s 17, though no one knew that when she began. Using an electronic computer, Hodgkin was the first person to apply its capabilities to X-ray crystallography. But because computers were in their infancy each calculation took several hours.

Eventually Hodgkin was able to reveal the structure of vitamin B₁₂, and other researchers began applying themselves to the challenge of synthesising it. These days it is administered via intramuscular injection, obviously because a pill taken into the stomach would defeat the purpose of absorption.

Like Rosalind Franklin, Dorothy Hodgkin maintained a lifelong passion for her chosen field of X-ray crystallography, but of course she was working in this line of work nearly two decades before Franklin. Indeed, when she began her research career, the ground rules for interpreting X-ray data had still to be worked out. Often it was largely experimentation, and in many cases she had to grow her own crystals, photograph them, then interpret the photos. If no solution emerged, she would have to start again.

Unlike Franklin, however, Hodgkin had no trouble fitting in with her male colleagues, whom she later described as having been “particularly nice and helpful to me as a lone girl”. During her career at Oxford she did a large amount of teaching and tutoring, and is remembered as very encouraging to younger scientists in the field. One of her students, incidentally, was a certain Margaret Roberts, later Thatcher, the only British prime minister to date with a degree in science. (Mind you, some have noticed her failure, despite her education, adequately to support scientific research — but that’s another story, best ignored in Bikwil).

In 1957 Dorothy Hodgkin helped found the Pugwash Conference on Science and World Affairs, and became a tireless worker for world peace.

Her hands, crippled by arthritis from a young age, have become famous by dint of being drawn by the most prominent sculptor of the 20th century, Henry Moore.

Pernicious anaemia, then, is now readily dealt with, thanks in part to the labours of Dorothy Hodgkin. Management of the disease involves a monthly injection of vitamin B₁₂ that has to be continued for life. Most patients improve quickly, although the inability of the stomach to produce intrinsic factor persists. One of the long-term effects of untreated pernicious anaemia is a sort of dementia, the symptoms of which are also eased by the regular B12 shots, though the neurologic damage is seldom fully reversible.

To date, of course, the news is not nearly so good with the most common form of dementia, Alzheimer’s disease.

Just as with the recent prominence given to Parkinson’s Disease because of the problems of actor Michael J. Fox, Alzheimer’s came to the world’s attention because of publicity in the 1980s surrounding the case of a film star. Rita Hayworth (1918-87) suffered from the disease for the last 15 years of her life. Alzheimer’s, however, had long been known among the medical fraternity, having been described as early as 1901 by the Munich neuropathologist Alois Alzheimer (1864-1915) after whom the disease is named.

Many fear-provoking maladies have been named after the doctors who first described them — such as Barrett’s Oesophagus (Núman R. Barrett, 1903-1979), Bright’s Disease (Richard Bright, 1789-1858), Down[’s] Syndrome (J. Langdon Down, 1828 - 1896), Hodgkin’s Disease (quite a separate Hodgkin, this one being Thomas Hodgkin, 1798-1866), Huntington’s Chorea (George Huntington, 1850-1916), Parkinsonism (James Parkinson, 1755-1824) — but none has captured the broad public imagination as apprehensively as Alzheimer’s. Currently, it affects 3% of the world’s population by age 75 and its incidence doubles every 5 years up to age 95.

As is often the case, though, it was not the doctor in question who named Alzheimer’s disease. Originally, in a lecture, Alzheimer called it merely “a peculiar disease of the cerebral cortex”. Shortly afterwards the condition became known as “presenile dementia” (or “premature dementia”), but in 1907, at the suggestion of Emil Kraepelin, it was given the designation it bears today.

Kraepelin (1855-1926) was a German psychiatrist who was born in Neustrelitz and educated at the University of Würzburg. He also studied in Leipzig under Wilhelm Wundt (the founder of modern psychology, 1832-1920). In 1891 he was appointed Professor of Psychiatry at Heidelberg University, and later (1903) to a similar post at Münich University, where he also directed a clinic.

Ardently driven by the belief that mental and psychological problems have a physical basis (namely deficits in structure or neurobiological functioning), Kraepelin inevitably imparted a quality of medical diagnosis to subsequent psychological methods. Many people misapply this flavour even today by using terminology that includes phrases like “mental illness”, “treatment of patients” and “curing mental disease”.

But by treating psychology as a physical science, Kraepelin did advance its technical capabilities at that time, and the pioneer achievements that followed from his approach were numerous.

Two investigations he carried out, for example, were an analysis of the fatigue process and a study of the effect of alcohol on the mind. It was he who coined the terms "neurosis" and "psychosis", and after analysing thousands of case histories established the clinical pictures of dementia praecox, now known as “schizophrenia”, and of manic-depressive psychosis, more commonly called “bipolar disorder” today. It was Kraepelin, too, in fact, who first explained the fundamental distinction between those two illnesses. He has also been called “the father of modern psychopharmacology”.

These individual researches and others were ultimately incorporated into his most significant contribution to the field, which was his classification system of psychological disorders, published in 1896. The first comprehensive nosological (disease classification) system for psychology, it incorporated all that he and other researchers had learnt during the 19th century in the differentiation of a multitude of psychological symptoms.

Rejecting the theory of unconscious mental activity proposed by the psychoanalytical school, Kraepelin concerned himself solely with diagnostic taxonomy. He classified mental diseases in terms of their cause, symptoms, course, final stage, and pathological anatomical findings, and his book was so influential that in Kraepelin’s lifetime that it ran to nine editions and became for many years the standard psychology textbook. It served in fact as the foundation for the Diagnostic and Statistical Manual (DSM) and the International Classification of Diseases (ICD), which are the standard reference texts used by psychiatrists today.

(This essay will be concluded in the next issue.)