6 September 2006

Master of the molecules

When John Cornforth discovered chemistry as a young man gradually going deaf, he discovered a means to understand the world through sights and smells. The Australian later went on to win the 1975 Nobel Prize for Chemistry.
Master of the molecules

John Cornforth as he was in 1975, when he won the Nobel Prize for Chemistry Credit: Nobel Foundation

The day was warm and sunny. Lying beside a river in Australia’s Blue Mountains a young man turned away from the bright sunlight, and stared at the vegetation on which he lay. With his nose close to the turf, how many different plants could he see? Five, no ten, fifteen, twenty…the bounty of nature. But instead of merely accepting it, as so many might, he also began to wonder about how the plants were made and how they functioned; about what Dylan Thomas once described as “the fuse that through the green stem drives the flower”.

The same fuse also fired an unquenchable curiosity about the natural world in the young John Cornforth. At one level it was a pleasant bush walk with friends. At another, it was also the beginning of a sixty-year journey to many insights into the multi-dimensional world of atoms and molecules, and to a shower of science’s most distinguished awards.

John Warcup Cornforth, known to his friends as “Kappa”, was born on September 7, 1917, in Sydney, the second of four children.

As a child, the attack of a crippling ear disease gradually deprived him of his hearing, leaving him by the time he was 20 unable to hear but beset by a permanent tinnitus, or ringing in his ears. Focussing his powers of concentration, imagination and clear thought in spite of the painful distraction, Cornforth developed a profound insight into aspects of both nature and human nature which was to lead him eventually to the pinnacle of scientific attainment, the Nobel Prize itself.

Part of Cornforth’s childhood was spent in Sydney and part in the pleasant rural surrounds of Armidale, in New South Wales, where his later fascination for understanding the natural world underwent a gradual awakening.

“Looking back at the time, some seventy years ago, when the love of science took hold of me, I think of no big event but of many small things that influenced me,” he recalls.

“As a child I read books and learned lessons, but I did not have much curiosity about the natural world. This began to change when I looked at the stars. In Australia, where I grew up, the skies were often clear. I learned to recognise the stars and constellations, and I chose a book about astronomy for a school prize in 1931. The stars are there, you cannot change them, you can learn about them only by measuring their positions and analysing the light that comes from them … I did enter science through astronomy.”

At Sydney Boys’ High School a gifted chemistry teacher, Len Basser, captured and inspired Cornforth’s eager mind, encouraging him both to think and to experiment. His deafness was coming on gradually, and chemistry soon seemed to him a profession that he could pursue in spite of it.

Fired with enthusiasm by Basser’s teaching, Cornforth constructed a small chemistry laboratory at home, in his mother’s laundry, and was conducting his own experiments with a sense of growing absorption and fascination that never deserted him. “At the time one could buy small amounts of many common chemicals and I made a little laboratory at home, with improvised equipment, to study chemical reactions. I soon discovered that the organic chemicals were the most interesting. With the help of a textbook on practical organic chemistry I made many preparations, using cheap chemicals to prepare those that were too expensive to buy.

“This was more satisfying than astronomy: you could change things by your own effort. At that time I was rapidly losing my hearing, so I suppose that the work attracted me also for its impact on the other senses: the beauties of crystals and distilled liquids, the colours of dyes, and smells both good and bad.

Cornforth was coming to see himself as a craftsman of the fundamental components of nature. “As a carpenter or carver learns to work with the grain of wood or bone, I learned that each substance has its own nature and can be easy or difficult to handle according to the procedure chosen. I began to see experiments as I see them now, not only as procedures to answer questions or to make compounds but as opportunities to observe what happens and to learn from mistakes.”

Bright and focused, John Cornforth was well ahead of his years at school and entered Sydney University at the age of 16. By that time he was quite unable to hear any lecture, and the most important event for the budding chemist was suddenly to gain access to an Aladdin’s cave of knowledge – a rich and fascinating library of chemical literature. He learned from handbooks and journals. Many of them were in German, which he did not know. So he found a German dictionary and looked up each word until he understood them all. Cornforth says that reading the original scientific literature helped him to become a scientist because it showed the evidence behind the things that he was being taught – and some of this evidence was wrong.

“The most liberating thing was the realisation that the literature wasn’t entirely correct,” he says. “It gave me quite a shock at first, and then a thrill. Because I can set this right! And always, and ever since, I’ve relied upon the primary literature exclusively. I don’t believe a word I ever read in any textbook. I began to see science as a continuous process of discovery and correction, and myself as a part of this process.”

During his time at university there came a second moment of revelation, this time on the bush walk with friends. “One morning we were resting beside a river. I turned over so that my face was close to the grass and I began to count all the different kinds of plant that I could see. There were more than twenty of them, all different, each beautiful in its own way.

“For me this was a kind of conversion, because I had never looked at things in that way before,” he recalls. “This was really the beginning of my curiosity about living things. I brought back from these walks some fruits – wild grapes, and some berries with a bitter taste – and took them into the laboratory and extracted pure compounds from them. This was not a very good way to study the chemistry of life, but I began to be interested in the life sciences and to read biological text books. At that time they mostly described and classified things that nobody understood. But later, when I started to work with life scientists, I could understand their viewpoints and could use my chemistry to solve problems that interested us all.

“After that experience I started, according to orthodox chemistry, to look at what constituents of plants I could extract. It was the usual thing in those days – anything that you could distil or crystallise you would go for. It meant of course that you were throwing away 99.5 per cent of the rest of the material which is just as interesting, but there was no way of getting into.”

Cornforth was enthralled by his growing wonderment at the sheer breadth and complexity of chemistry. “All this time I was learning more and more – as I still do – about the detail of chemistry. There is so much detail that you cannot keep it all in your head, although it is very helpful to know how to look for it. What you can do is to form in your mind a pattern of what is possible and what is not possible in chemistry. This helps you to make new compounds and to understand new reactions and structures.

“When the literature, or one of your own experiments, presents you with a new fact, you compare it with the pattern in your mind. Often the new fact fits into the pattern easily, and reinforces it. But sometimes, the fact does not fit. Then you check, and sometimes you find that a mistake has been made. But if there is no mistake, you must change your pattern to fit the new fact, and you learn more about your science on these occasions that at any other time.”

Science for John Cornforth begins with curiosity. “You ask questions, you read what other people have written, and then you begin to find ways of answering your own questions. You never stop learning. All the time, everything becomes more interesting and beautiful the more you understand it. And best of all, you become part of a great company of people, all over the earth, who share your curiosity and your search for truth and who will share their knowledge with you whenever they are allowed to do so.”

For him, knowing the fundamentals of how something was made or worked never detracted, but rather magnified its wonder: “Keats once said that Newton’s explanation of the rainbow killed the beauty of it for him. And perhaps there were people before him. But for me, what I know about nature simply enhances the beauty of it. And I am rather sorry for the people who look at a flower and don’t understand anything at all about what is going on.”

In 1937 he graduated with first-class honours and the University medal. After a year of post-graduate research he was awarded an 1851 Exhibition scholarship to work at Oxford with Robert Robinson, who was later to nominate his gifted colleague for the Nobel prize.

Only two of these prized scholarships were given in Australia each year. The other went to a fellow student, Rita Harradence, also of Sydney and also an organic chemist. They had met for the first time after she had had a small accident with a valuable piece of laboratory equipment, a Claisen flask – which were hard to come by in those days.

As a keen improviser of equipment, Cornforth had adapted an old Bunsen burner tube and taught himself to blow glass. By this stage he’d earned a bit of a reputation as a glass blower and equipped himself with a proper blowpipe for the job. One of Rita’s friends suggested she get him to perform the repair, which he duly did.

It was the beginning of a remarkable lifetime partnership, in which Rita became his co-researcher in the chemistry lab, his ears and often his interpreter in communicating with others, and in 1941, his wife and the mother to their three children.

“Throughout my scientific career my wife has been my most constant collaborator. Her experimental skill made major contributions to the work; she has eased for me beyond measure the difficulties of communication that accompany deafness; her encouragement and fortitude have been my strongest supports,” he says.

“War broke out as we journeyed to Oxford and after completing our work (on steroid synthesis) for doctorates we became part of the chemical effort on penicillin which was the major chemical project in Robinson’s laboratory during the war. We made contributions, and I helped to write The Chemistry of Penicillin, the record of a great international effort.”

After the war ended, he returned to this interest: finding a reaction for the synthesis of the sterols, a fatty kind of chemical. His close collaboration with Robinson continued after he joined the scientific staff of the Medical Research Council and worked at its National Institute, first at Hampstead and then at Mill Hill. By 1951 they were able to complete, simultaneously with Robert Woodward, another Nobel laureate, the first total synthesis of the non-aromatic steroids.

This was the beginning of what Cornforth recalls as the richest and most fulfilling period of his career, for the spirit and feeling between colleagues even more than for the discoveries these yielded. He later recalled: “I spent sixteen of the best years of my life in an extraordinary place, the National Institute for Medical Research, and I know to what extent scientific advances are the product of an ambience created by many people, not just the few who tend to have the best ideas … At the National Institute for Medical Research I came into contact with biological scientists and formed collaborative projects with several of them, in particular George Popják [with whom] I shared an interest in cholesterol. At this time Konrad Bloch was beginning his work on the biosynthesis of the sterols and Popják and I began to concert experiments in which the disciplines of chemistry and biochemistry could be applied.”

In 1962 Cornforth and Popják and left the Medical Research Council and became co-directors of the Milstead Laboratory of Chemical Enzymology set up by Shell Research. Their project was the study of how biological catalysts – enzymes – are affected by the spatial configuration of the molecule. His work at Milstead led directly to the 1975 Nobel Prize in Chemistry.

Some substances that the enzymes act upon are left or right-handed in their molecular structure. Knowing the ‘handedness’ or stereochemistry of the chemical reveals a lot about how the enzyme and its substrate are likely to react with each other.

The problem was identifying whether a molecule leaned to the left or right. Cornforth tried replacing one of the attached hydrogen atoms with deuterium, a heavier version of hydrogen. But then he needed to measure how this substitution had altered the way light interacted with the molecule to identify the molecule’s handedness.

“I had the problem that it was necessary to measure somehow the optical activity and, looking at all the methods that were available, I could see that it was going to be nearly impossible. So I wrote to a friend in Australia [who] was an expert in optics and I asked him whether there was anything in the pipeline for measuring very small optical activity.

“He said: go to the National Physical Laboratory, they’re evolving a prototype there. It was a marvellous instrument – but …it was a lash-up of all kinds of components. Well, we did our biochemistry and our chemistry, and we got two specimens of mono-deuterio succinic acid…[in which] the molecules are mirror images of each other. So we had a few milligrams of each of these, and we also had a third specimen which we had much more of, which was made from a product in which we were sure of the stereochemistry.

“We took all these three specimens along to the NPL at Teddington, and there, with this Heath-Robinson apparatus, they did the optical rotations. They came out most beautifully. The two dispersion curves of these two compounds were mirror images of each other.

“I think that’s the day I remember with the most pleasure in my experimental life.”

Then came another memorable day, when, shortly after Cornforth had moved from Shell to the University of Sussex in 1975, his wife Rita telephoned to tell him she had just heard it announced on the BBC news that he had been awarded a Nobel prize for the work. “I was quite surprised. I had estimated my chances at about one in three. I knew that Robinson had put me up for the prize.

“As for the ceremony, I couldn’t hear a word of what was said. And so, as usual, I amused myself by looking around at the audience. It was in this sports stadium, an enormous place, because the town hall was being refurbished, but I could see, in the darkness of the auditorium, these flashes of bright light. They kept on like this, and I couldn’t make out what they were. And finally I realised all the women were wearing their jewels, and that was what was causing the flashes of light. That was the thing I remember most of all from the ceremony.”

Memorable for others was Cornforth’s brief yet powerful speech of acknowledgement on behalf of himself, his fellow laureate, Vladimir Prelog and their colleagues: “That our work has been considered worthy of such distinction is a great satisfaction to us both; but I think that we derive equal satisfaction from the sense of being two in the great company of those who approach the truth.

“In a world where it is so easy to neglect, deny, corrupt and suppress the truth, the scientist may find his discipline severe. For him, truth is so seldom the sudden light that shows new order and beauty; more often, truth is the uncharted rock that sinks his ship in the dark. He respects all the more those who can accept that condition; and in returning thanks tonight we are saluting all those who make our load lighter by sharing it.”

Julian Cribb is a science journalist and Adjunct Professor of Science Communication at the University of Technology Sydney.

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