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The transcript has been edited by Kappa, his additional comments have been added in square brackets.



Kappa interviewed by Bob Thomas
Bob

As you are probably aware, most of you anyway, Kappa is completely deaf, so I have written down these questions for him to read, and I`m speaking them out loud for the benefit of you, the viewer.

So let`s start by having your comments on your early life in Australia, and your education through to graduation at the university of Sydney.

Kappa

I was born in 1917 in Sydney, in Australia. My father was an Englishman and he became a teacher of classics and English. My mother was a hospital nurse. I began to go deaf at about the age of 10. It`s a progressive disease and you don`t know when it will stop. It`s irreversible though, and in my case it went very far indeed. I had to find something in which the loss of hearing would not be too severe a handicap, and because of Len Basser I chose chemistry.

[He was my chemistry teacher at the time and he taught many who later became famous in science, including the present President of the Royal Society, Lord May]

I started doing experiments, mostly in organic chemistry because it was so much more interesting, in my mother`s laundry at home. And so when I came to Sydney University I was already quite a good experimentalist. But there I discovered the original literature, and that was a great liberation.

The most liberating thing was the realisation that the literature wasn`t entirely correct. 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.

Bob

No, agreed. Yes!

TITLES

Kappa met Rita Harradence at Sydney University

Bob

Where did you meet Rita? And did you get married in Australia?

Kappa

When I was doing experiments in my mother`s laundry, I taught myself to blow glass. I didn`t have a proper blowpipe but I improvised one out of a Bunsen burner. And that way, I taught myself how to blow glass. Well once, I think I was in my second year, Rita broke the side tube of a Claisen flask. They were very difficult to get hold of in those days, and so she was told about me. And so she came to me, I had a proper blowpipe by that time, and so I mended this flask, and that was how we met.

TITLES

Kappa and Rita both won scholarships to Oxford.

Bob

What do you consider were your most satisfying personal contributions to the penicillin programme?

Kappa

Undoubtedly that would be the penicillamine story. At the time they were getting sufficiently pure penicillin preparation to be able to break up the molecule in various ways.

[Penicillamine was one fragment.]

The analysis indicated it only had five carbon atoms. And so Robert immediately wrote a comprehensive table of structures that it could be. But he was misled by one piece of analytical evidence that was what used to be called the C-methyl determination. The Kuhn-Roth oxidation - you boil the substance you are analysing up with chromic and sulphuric acid, and then you distil over any acetic acid that has been formed from that oxidation.

The amount of acetic acid was supposed to represent the number of methyl groups attached to a carbon atom. So because penicillamine gave hardly any acetic acid in that assay, they didn`t like any formulae that had a methyl group. But that made it very difficult, to think of a formula at all.

Bob

It would do.

Kappa

Robinson saw what he thought was the least improbable, and he asked Rita and me to synthesise it.

Well, I had to visit Manchester at about this time, and on the way up, it suddenly occurred to me that this negative Kuhn-Roth might be because penacillamine had too many methyl groups, not too few, but there were two of them interfering with each other in a gem-dimethyl as it is called. And so as soon as I got to Manchester I went to the university there. I had had a month there at some time previously, and I asked Todd if I could look in the library there. He said, of course I could. So I looked there, and there it was. Some terpenoids with gem-dimethyl groups, so they were shown to give abnormally low proportions of acetic acid in the Kuhn-Roth assay. Of course, they couldn`t show two methyls, because you can`t get two molecules of acetic acid out of that, but these didn`t even have one, it was about 0.2 or something.

And so then, as soon as I got back to Oxford I wrote Robinson a note saying penicillamine is probably this. And he said, synthesise them both. And so we did. Or at least, we gave most attention to the one we thought more probable, and quietly lost the other one.

Bob

Very wise!

TITLES

In 1975 Kappa won a Nobel Prize for clarification of the stereochemical control of enzymic reactions. Some substrates for enzymes contain carbon atoms that become chiral when one of the attached hydrogen atoms is replaced by deuterium. The enzyme processes this "labelled" compound as a normal substrate and examination of the label in the product can throw important light on the reaction mechanism. A big problem was to measure the tiny optical activity generated by replacing one hydrogen with deuterium in otherwise symmetrical molecules. Later it became possible to make methyl groups chiral by using all three hydrogen isotopes (H,D,T) and to measure the chirality without using optical rotation.

Kappa

I had the problem that it was necessary to measure somehow the optical activity, and so, looking at all the methods that were available, I could see that it was going to be nearly impossible. And so I wrote to a friend in Australia, I knew he was an expert on 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 in our time it was very much a matter of string and seccotine. 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. You have there the single centre of asymmetry, with the deuterium and the hydrogen attached to the same carbon, generating this asymmetry. And I`ve given here the two possible mirror image forms of this compound, you can see 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.

And 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, one going up like this, the other going down like that, a perfect dispersion.

Bob

Ah, that must have been something!

Kappa

I think that`s the day I remember with the most pleasure in my experimental life.

TITLES

"Throughout my entire life my wife has been my most constant collaborator. Her experimental skill made major contributions to the work."

Bob

However I understand that a particularly memorable occasion occurred one afternoon shortly after moving to the University of Sussex in 1975, when you received a phonecall from Rita to say that she`d just heard on the BBC news broadcast that you`d been awarded a Nobel prize.

Kappa

Well, 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, as usual I couldn`t hear a word of what was said. And so, also as usual, I amused myself by looking around at the audience. And it was in this sports stadium, an enormous place, it was 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. And that was the thing I remember most of all from the ceremony.

Kappa interviewed by Harry Kroto
Harry

I very much loved reading this article, and many of my questions are based on it. But I want you to feel free to talk about anything. Can you remember any specific papers which were very important in your development?

Kappa

I was particularly impressed by Emil Fischer`s papers. He is still my hero.

Harry

Which paper particularly?

Kappa

Just to take one of them at random, he found out how to make aminoacetaldehyde, by the reduction of glycine ester with sodium amalgam. Well nobody but Fischer or a fool would have tried that in the first place. But he got it to work quite well. And the experiment is so beautiful that you would never have any difficulty in repeating it. I did, as a matter of fact; I repeated it. And how he was sensitive to all the clues; you could almost see him interacting with his experiments. He is not somebody who had decided beforehand `I will take this material and I will do this, and this, and this to it`. It was more like `Let`s start with this and see how we get along. And look at what we`re doing in between`.

TITLES

"Poetry is my music".

Kappa

Mine speaks in parables to the blind.
Thine loves the same world that mine hates,
Thy heaven`s door are my hell`s gates, […]
Both read the Bible day and night
But thou readst black where I read white.

(from "The Everlasting Gospel" by William Blake)

Harry

You have a fondness for poetry.

Kappa

I use poetry as a substitute for music. I have no particular vocabulary of music in my head, but I know thousands of lines of poetry that I can recall as I like. The curious thing is that some pieces I have known for 65 years or more. And when I recall them, I find that I have sometimes improved them!

Harry

Can you say more about Blake, and anti-scientific views? That science destroys the beauty and mystery of nature.

Kappa

First, Keats 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.

I can remember quite clearly, when I first became interested in actually looking at living things, some friends and I were walking in the Blue Mountains and we stopped by the side of a river. For some reason or other I turned over onto my face and looked at the grass. I found that without moving my eyes very much I could count more than 20 different species there, all different and all beautiful in their way. Well that for me was a kind of conversion because I had never looked at things in that way before.

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

Harry

Do you have memories of sound?

Kappa

Yes, particularly people singing.

Harry

You told me that you sometimes sing to your grandchildren.

Kappa

Ah well, sometimes my grandchildren have asked me to sing, and although I`ve explained to them that I can`t sing they made me try. And apparently I can produce a melody quite accurately from something that I heard when I could hear. How that happens I don`t know. But if there is a separate store for auditory memory, mine is not very full.

TITLE

The Internet, email and databases. "Drowning in Information".

Kappa

We are wading in information at the moment. I should say, drowning. You are asked to give an abstract of your work. And in that abstract you concentrate on what you consider important about what you have done. When abstracts are compiled from that work, or when key words are chosen from that work, it is influenced by what you consider important about what you have done. Now, you are almost always wrong! And what you consider important in your paper may be, and probably is, quite unimportant to most scientists.

But that little observation that you thought you might as well shove in, and that wasn`t abstracted or key worded, that is the one that somebody else would not only think important, but sometimes, use to build progress in another direction. I read an awful lot of literature and I can put my hand on my heart and say that I have hardly ever thought important those parts of any paper I have read that the author considered important.

TITLES

The absence of scientific certainty and the importance of doubt.

Kappa

I would not like other scientists to accept what I say without checking because in my view it is the business of scientists not to believe but to check. I am against belief in anything. All we can do is to state the evidence as exactly as we can, and to confute what is manifestly untrue whenever there is an opportunity.

TITLES

"The futility of believing too much in anything" and "The dilemma of `truth`".

Harry

We see in Iran, and in some areas in the USA, fundamentalist ideologies becoming dangerously more powerful and making it difficult to do science on the basis of doubt.

Kappa

It is all about power over other people. And that has been the temptation of the priest throughout the ages! It is extremely difficult to have a continuing religion without priests of some kind.

Harry

You say, you pass this obelisk on the hillside: `I pass it nearly every day, it bears an inscription`. Can you remember the inscription? `In loving memory of the under named 17 protestant martyrs who for their faithful testimony to God`s truth, were during the reign of Queen Mary burned to death in front of the Star Inn, now the Town Hall`.

Kappa

These burnings were carried out in about the middle of the 16th century. The obelisk on the other hand was erected about 1900. The inscription was composed to keep alive the division between Protestants and Catholics. Even now, people of the same two sects are killing each other in Northern Ireland, ceasefire or no ceasefire. That constituted what I quote here as the `dilemma of truth`. I would regard that as one of the ultimate examples of the futility of believing too much in anything!

In our science, we have a pretty clean record there. People may have lost professorships for holding unpopular views, but at least we don`t burn them outside a pub!

TITLES

"Educate children to question…"

Kappa

If you educate children not to accept what they are told but to look at the evidence and, when somebody comes out with a statement, who says so? How did he know? What`s missing? What are the assumptions? What is the scale? Do the figures make sense? And hasn`t somebody changed the subject?!

Our only strength as scientists is to convince people that our ways work, and other ways do not.

Note this is the transcript for the edited interview, however more extensive archives are available from the Trust.

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Interview with Sir John `Kappa` Cornforth - Programme Transcript



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