Read The Faber Book of Science Online
Authors: John Carey
‘Ach, you doctors, you’re such philistines!’ she exclaimed, ‘Can you not see
artistic
development
– how he renounced the realism of his earlier years, and advanced into abstract, non-representational art?’
‘No, that’s not it,’ I said to myself (but forbore to say it to poor Mrs P.). He had indeed moved from realism to non-representation to the abstract, but this was not the artist, but the pathology, advancing – advancing towards a profound visual agnosia, in which all powers of representation and imagery, all sense of the concrete, all sense of reality, were being destroyed. This wall of paintings was a tragic pathological exhibit, which belonged to neurology, not art.
Source: Oliver Sacks,
The
Man
Who
Mistook
his
Wife
for
a
Hat,
London, Picador, Pan Book, 1986.
*
Later, by accident, he got it on, and exclaimed, ‘My God, it’s a glove!’ This was reminiscent of Kurt Goldstein’s patient ‘Lanuti’, who could only recognize objects by trying to use them in action.
This is part of an interview from
A
Passion
for
Science
(1988), a book based on a BBC Radio 3 series produced by Alison Richards. The interviewer is Lewis Wolpert, the interviewee Dorothy Hodgkin.
In 1964 the
Daily
Mail
carried a headline, ‘Nobel Prize for British Wife’. The prize was for chemistry, and had been awarded to Dorothy Crowfoot Hodgkin for research on the structure of biologically important molecules including penicillin and vitamin B12. Using the technique of X-ray crystallography she had coaxed from these molecules the minute details of their three-dimensional structure, to the extent that the exact position of each atom was known. In 1969, she went on to solve the structure of insulin.
Professor Dorothy Hodgkin, Nobel Laureate, Fellow of the Royal Society, Emeritus Professor at the University of Oxford and the first woman since Florence Nightingale to have the Order of Merit conferred upon her, was born in 1910, in Cairo, where her father, Dr J. W. Crowfoot, was in the Egyptian Ministry of Education. Both her own family and that of her husband, Thomas Hodgkin, had a long tradition of intellectual achievement and social responsibility, and she has combined her distinguished scientific career with an active commitment to the cause of world peace. She has now officially retired and I went to talk to her at her home in a small rural village about 30 miles from Oxford. She looks just like the famous portrait by Brian Organ which hangs in the Royal Society, and her hands, crippled by arthritis since she was a child, are familiar too, from the drawings by Henry Moore. We sat by the fire in the cluttered sitting room, with its faded rugs on the floor and books and pictures everywhere. She is still very active, and divides her time between writing up research papers and Pugwash, an international movement of scientists working for peace. The delight she takes in her chosen field is infectious.
X-ray crystallography is a way of studying the structure of
molecules by shining X-rays through them. The beam is scattered, or diffracted, by the atoms in the molecule and registers on a photographic plate as a pattern of spots of varying intensities. That this pattern of spots could be used to determine how the atoms were arranged in the molecule was the brilliant insight of a 22-year-old Cambridge student, Lawrence Bragg, who three years later, in 1915, became the youngest person ever to receive a Nobel prize. The technique brought about a revolution in physics and chemistry, and also, more dramatically, in biology. Not only did it make Dorothy Hodgkin’s achievement possible, but it also led directly to the solution of the structure of the genetic material, DNA.
Bragg worked with relatively simple, inorganic crystals such as salt. When the technique was applied to biological molecules, which are larger and more complicated, the diffraction patterns were, not surprisingly, also more complicated. Their interpretation became a highly skilled and immensely time-consuming occupation involving painstaking measurement, complex and lengthy calculations, and no small measure of intuition. When Dorothy Hodgkin began her research career, the ground rules for interpreting the X-ray data had still to be worked out.
Among the leaders in the field was Desmond Bernal, later to become Professor of Physics in the University of London. He was pioneering the application of X-ray crystallography to proteins, the most diverse and important chemical components of cells, at the Cavendish Laboratory in Cambridge. In 1932, after graduating from Somerville College, Oxford, Dorothy Hodgkin went to work under him. Together they obtained the first successful X-ray photograph of a protein single crystal. This was a major achievement, for not only does the skill lie in taking the actual photographs, but also in growing the crystals in the first place. It’s not a matter of following rules, but of almost alchemical skill. Dorothy Hodgkin’s future achievements were to depend both on her talent for growing suitable crystals, and on the intuitive and dogged brilliance she brought to the study of the impenetrable spots.
Two years later, she returned to Oxford. Here, just before the Second World War, Howard Florey and Ernst Chain began trying to isolate the actual antibacterial agent from the mould studied by Fleming. This fortunate set of circumstances gave her the opportunity to start work on penicillin as soon as sufficiently pure samples were available. It was a major undertaking, but by 1945 the structure was
solved. Soon afterwards, in 1948, vitamin B12, the factor which prevents pernicious anaemia, was isolated, almost simultaneously, by two British and American groups. This was a more complex molecule than penicillin, and even with the aid of one of the first electronic computers, its structure was to occupy her for the next six years. Then came insulin, a still more complicated compound, which had preoccupied her since the beginning of her career. Its chemical structure – the number and order of the chemical units from which it is composed – had been worked out by Fred Sanger, in Cambridge, in the early 1950s, and won him the Nobel prize for chemistry in 1958. But the monumental task of determining the exact configuration of the constituent atoms still lay ahead. Dorothy Hodgkin took it on.
DH
: I’m really an experimentalist. I used to say, I think with my hands. I just like manipulation. I began to like it as a child and it’s continued to be a pleasure. I don’t do very much experimental work now, but I get something of the same pleasure from going through the maps indicating the position of the atoms that result from the calculations that are carried out.
LW
: I hadn’t thought of crystallography as being an experimental subject.
DH
: Well, it does involve experiments, usually, because you often have to modify the crystal in order to get understandable results from the intensities of the reflection of the X-rays.
LW
: Now, to a non-X-ray crystallographer the reflections that you get from the X-rays look a little ordered, but it’s very hard to see any structure in them. Is it just a logical process to interpret them or is there a great deal of intuitive skill?
DH
: Of course now you can just interpret them by putting the photographs through a machine, and letting the machine place the reflections and measure their intensities and pass them into a tape full of numbers which you can put into your computer. It wasn’t like that when I was young and it isn’t what I think about. I’d start off any crystal structure operation by taking the photograph myself and looking at it and seeing straight away what there is about the structure that I can tell immediately from the distribution of the reflections on the photograph. I admit that I don’t like some modern improvements which cut out photographs almost altogether and put everything through a counter. I got a lot of pleasure myself out of just looking at
the photographs and guessing the answers even if one guessed imperfectly and wrong. Also some photographs are really very beautiful you know.
LW
: So you had a great skill in being able to go from those
two-dimensional
, ghost-like pictures to a three-dimensional object. Why were you so successful?
DH
: Well I don’t know that it requires all that skill if you know the lines on which these things work. It was a great advantage to start early. I mean one gets a certain amount of notoriety from being the first person to do things which anybody else really could have done. What I find difficult to know is why more people didn’t take up this particular method of attacking problems at the same stage as we did. It seems to me that once W. L. Bragg had taken the first step, the chemists and physicists should have realized much more than they did that this was a tremendous opportunity. But for those who came in at the early stages there was so much gold lying about that we couldn’t help finding some of it.
LW
: Your pleasure, you said, comes partly from handling crystals. Is this something that developed very early?
DH
: When I was quite young, I think I was ten at the time, I went to a small PNEU class in Beccles. PNEU stands for Parents National Educational Union, and it was founded by a Miss Mason of Ambleside to improve the education given by governesses, in a private way, all over the country. They produced small books that would enable the governesses to introduce their pupils to the different sciences in turn. So the small book on chemistry began with growing crystals, which I think is quite a common way to begin chemistry, growing crystals of copper sulphate and alum. I found this fascinating and repeated the experiments at home, when we had a home, which was the following year. My father and mother had been abroad most of the war and came home to look for a house for us to live in so that we could settle down near the local secondary school for our further education.
LW
: So you made a little laboratory at home?
DH
: Yes. I did go on crystal growing, and then, when I knew about the elements of analytical chemistry, I also used to carry out analyses on a collection of minerals. Now how I came by this is quite a nice story which perhaps illustrates the situation. My father and mother, as I said, worked abroad in the Sudan, and when I was thirteen they were just about to retire. They thought it would be interesting for us children to
see how they lived out there and so they took the two eldest of us away from school for a term to stay in Khartoum with them. We didn’t do very much in the way of lessons but my mother took us about with her to see the different things she was interested in. One of the visits that we paid was to the Wellcome Laboratories and we first of all went to the medical one. Then, next door, was geology. The geologists there had just brought some little tiny pellets of gold back, and to amuse us children, they showed us how they got these by panning the sand from the bottom of streams. Of course this started me off thinking why shouldn’t we find gold. So we went and panned the sand at the bottom of the little water channel running through our garden, and found a black shiny mineral. Now, I had already made friends with the chemical section of the Wellcome Laboratories. Its head was a particular friend of my father, Dr A. F. Joseph, whom we called Uncle Joseph. I went across to him and said ‘Please can I analyse this mineral and find out what it is?’ I guessed and told him I thought it might be manganese dioxide because it was black and shiny like manganese dioxide. So he helped me try the tests and, of course, it wasn’t manganese dioxide. It was ilmenite, which is a mixed ore of iron and titanium. After that, he gave me the proper sort of surveyor’s box with little bottles of reagents. One could carry it about the country and test for different elements in the minerals one found. It had a sample set of minerals in little tubes, so when I got home I used quite often to try out experiments and see whether I found the things in these little tubes that were supposed to be in them, according to the books. Then on his advice I bought a very large and serious text book of analytical chemistry, and continued this interest all through the years that I was at school.
LW
: So you really were a crystallographer at heart from the beginning?
DH
: Well, again, there’s a quite interesting thing about that period. You see, my mother was very much interested in my choice of subject. She approved of it. She and my father were not scientists at all, they were both archaeologists as far as they had a profession, though they were at that time working mainly in education. She bought me, amongst other things, W. H. Bragg’s books based on the subjects of his Christmas Lectures to children at the Royal Institution. If you come across them, they’re very good and still perfectly readable. One is called
Concerning
the
Nature
of
Things
and the other one is called
Old
Trades
and
New
Knowledge.
My mother was particularly interested in
Old
Trades
and
New
Knowledge.
I think she got it
because she was interested in weaving and potting and things of that kind. But the one
Concerning
the
Nature
of
Things
describes the X-ray diffraction of crystals and has in it the words: ‘by this means you can “see” the atoms in the crystals’. And so I really decided then that this was what I would do. It was very exciting.
LW
: Now when you started work you began with insulin, but you didn’t solve it straight away.
DH
: No, no, good heavens no. The first measurements on insulin, like Bernal’s first measurements on pepsin which I was a little involved in a year before, were wholly ahead of their time as far as there being any conceivable chance that we could work out the structure. We were both really totally inexperienced in even simple structure analysis at the time. We were faced with an enormously complex problem and though, right at the very beginning, Bernal suggested the way in which it could be solved, it seemed to me that no way was I, at the age of twenty-four, going to set out on that path without trying the proposed method on very much simpler problems first.
LW
: So did you abandon insulin then?
DH
: I never wholly abandoned it. I left it, yes, but in a curious way I didn’t even really leave it. I went on doing the sort of things that would eventually have to be done, but in rather imperfect ways. Very slowly and gradually during the war, doing the measurements out in this house where I brought my little child to be safe away from possible bombing. I knew they weren’t really good enough measurements to solve the structure, yet I couldn’t help going on doing them somehow. But I put my real effort, when I was back in the lab again, into soluble problems. The first one was a carryover from the work that I was doing in Cambridge with Bernal, which was concerned with finding the structure of the sterols, and particularly of cholesterol. The next one was penicillin.
LW
: Why did you choose penicillin?
DH
: Penicillin was just historical accident. The work on penicillin began in Oxford just before the war and one of my friends at that time was Ernst Chain. In Oxford we go up and down South Parks Road, and going along South Parks Road one morning I met Ernst Chain in a state of great excitement having just been carrying out the experiment that is now famous. They had four mice which they injected with streptococcus and penicillin and four mice which they had injected with streptococcus alone. One group, the last group, died and the other group lived. And, as they were trying to isolate penicillin, Ernst
was extremely excited, and said ‘Some day we’ll have crystals for you.’
LW
: Now, when you chose to work on penicillin, was it that you really cared about penicillin, or was it that here was an important molecule which offered you the pleasure of finding out its structure?
DH
: I think that both elements went into that particular operation. I mean nobody who lived through the first year or two of the trials of penicillin in Oxford could possibly not care about what it was. But also it’s difficult not to enjoy just growing the crystals.
LW
: Now, the structure of penicillin was soluble, unlike insulin which you were still holding in the background. Was that because it was simpler?
DH
: Yes, there’s all the difference in the world between working out the arrangement of atoms in the space of a small molecule in which you’ve got 16
or 17 atoms in the assymetric unit and one in which you’ve got a thousand.
LW
: How complicated, then, was vitamin B12?
DH
: That’s intermediate. That’s of the order of 100. We didn’t know it was intermediate when we started. Vitamin B12 came about through the fact that I got to know the people in the pharmaceutical industry rather well through the penicillin work, and Dr Lester Smith of Glaxo was working on the isolation of vitamin B12 just after the war. He got crystals first in 1948, within a week or two of crystals being obtained in America by the Merck Group. But to get its structure was again a long process because of the number of atoms in the molecule. The fact was, of course, at that moment we knew nothing, but nothing, about the structure, and what really held us up was just the state of computing in the world. You see electronic computers were being built, but when we started the beginning of the B12 work they hadn’t been used at all in X-ray crystallography. They weren’t really in a fit state. We did the end of the penicillin calculations on an old punched card machine and we brought this back again for the beginning of the B12 calculations. But it was very slow. A calculation which at the end of the story was taking, well, still a few hours on one of the early electronic computers, took us three months on punched cards …
LW
: At some stage you must have realized that you had talents or abilities that set you apart from your friends and colleagues. When was that?
DH
: I don’t think it was so very obvious, you know, because, in a curious way, of the sketchiness of my education. In the early period,
before the age of eleven, when my parents came home and I started secondary education, I had moved from one school, one little sort of private school, to another, and one year we’d spent actually being taught entirely by my mother, which was a very fascinating time. So when I first went to secondary school, I was rather behind, if anything. I was
terribly
behind in arithmetic, and it was only at the end of my time there, at the very end of the last year, that I was first in the form. One of the other girls was also very good indeed, and she was generally first. Actually, she did better in chemistry in school certificate than I did. She was very, very good.
LW
: So what were your special qualities? Why didn’t she go on and do all the things that you did?
DH
: I’ve always thought that her case is really a case history for the problems of girls’ education in this country. You see, a girl’s future has depended a good deal on ambition and the advice that the young get given. She just didn’t think in terms of going to a university, although there’s no reason at all why she shouldn’t have. I think in terms of the present organization, she would have done so, and would very likely have ended up in research.
LW
: Are these same attitudes reflected in the headline in the
Daily
Mail
which read: ‘British Wife gets Nobel Prize?’
DH
: Oh, I thought it said ‘Grandmother’!
LW
: But do you mind that sort of thing?
DH
: I didn’t mind that one, no. The one I was slightly worried about concerned the penicillin work. The headline on my election to the Royal Society read ‘Mother was first’. I wasn’t quite sure that my chemical colleagues would have really appreciated that.
LW
: Have you felt strongly about the position of women in science?
DH
: No. I think it’s because I didn’t really notice it very much, that I was a woman amongst so many men. And the other thing is, of course, that I’m a little conscious that there were moments when it was to my advantage. My men colleagues at Oxford were very often particularly nice and helpful to me as a lone girl. And at the time just after the war, when there was an air of liberalism abroad and the first elections of women to the Royal Society were made, that probably got me in earlier than one might have as a man, just because one was a woman.