View Professor Frank Gibson (1923-2008)'s photo gallery
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Professor Frank Gibson was interviewed in 1993 for the Interviews with Australian scientists series. By viewing the interviews in this series, or reading the transcripts and extracts, your students can begin to appreciate Australia's contribution to the growth of scientific knowledge.
The following summary of Gibson’s career sets the context for the extract chosen for these teachers notes. The extract covers his experiments that use mutants to look at metabolic pathways in bacteria, and his dramatic discovery of chorismic acid. (Chorismic acid is a substance used in the production of a number of different organic molecules, including three amino acids.) Use the focus questions that accompany the extract to promote discussion among your students.
Frank Gibson was born in 1923 in Melbourne, Victoria. In 1937 he started work in the Bacteriology Department at the University of Melbourne. In 1939 he moved to the newly created Bacteriology Department at the University of Queensland as a technical officer.
At the beginning of 1947 Gibson returned to the University of Melbourne, from where he earned his BSc in 1949. During this time he began his first independent research, on the mode of action of bacterial antibiotics and how they might work by acting as metabolic analogues.
Gibson was awarded an Australian National University scholarship to study for a doctorate at Oxford. His work on the biochemistry of amino acids included the use of normal and mutant bacterial cells, resulting in the completion of a DPhil in 1953.
On Gibson's return to Australia in 1953, he took up a senior lecturership at the University of Melbourne. It was during this time that he and his research group discovered chorismic acid occurred.
In 1967 Gibson took up the Chair of Biochemistry at the Australian National University's John Curtin School of Medical Research. He continued to explore the biochemistry of chorismic acid and its many, and important, metabolites.
Since retiring in 1988, Gibson has continued collaborating with colleagues on projects using computers to study the structure of various proteins.
Gibson was elected to the Fellowship of the Australian Academy of Science in 1971 and to the Fellowship of the Royal Society London in 1976.
You re-established your link with Melbourne, which had been an important place for a long time.
Yes. I enjoyed Oxford and developed good links there. But some time before I was due to leave, I had two letters. One was from Syd Rubbo, saying that Frank Fenner was intending to offer me a job but that he also wanted to offer me one. (These were the halcyon days when you were offered jobs.) Frank Fenner was offering me a job as a Fellow in the John Curtin School of Medical Research, in Canberra; Syd Rubbo’s job was back in Melbourne as a senior lecturer. Because I like teaching and also because virology – which is what Frank Fenner’s department was concerned with – was a bit of a foreign field for me, in 1953 I went back to Melbourne.
You went back on to related pathways. Tell us about your ‘one Saturday morning’ experiment.
Well, it did things, even if they were all the wrong things. I was interested in one-carbon transfers, having been working with that in Oxford. I had an idea that anthranilic acid could be converted to indole, which is a step on the tryptophan pathway known because of the use of mutants. That ostensibly is an addition of one carbon atom. In Oxford I did an experiment where I added serine to anthranilic acid and showed that indole was formed. So I thought, ‘Ah, I will go with this. I can go back and work on the same general area, studying one-carbon transfers.’
When I did the same sort of thing in Melbourne and did the controls, I found that if I used glucose and ammonia I got just as much indole formed as if I had serine present. That showed me I never used the library, or I would have discovered that that was not the way indole was made – Yanofsky had shown some time earlier that it was made by the addition of a five-carbon ribose fragment to anthranilic acid. But the interesting thing was that it meant that by incubating glucose and ammonia with a mutant that was blocked after indole, you could get indole formed. It allowed you to study the whole pathway. You could look for mutants with other compounds being produced.
Was this drawing on your early work on antibiotics?
Yes. Initially I was interested in whether antibiotics inhibited any steps in the pathway. From the early work on the acridines I was very interested in the motive action of antibiotics, and also the book by Work and Work on the basis of chemotherapy had a big influence on me. We spent quite a lot of time mucking around with antibacterial action. It didn’t really get very far – it was a diversion, I suppose – but it did lead us on to really thinking about the biochemistry of the pathway. We then started to isolate mutants which were forming various compounds. We would generate the mutants, in the sense that you treat them with a mutagen and then look for mutants which will grow on some media and not on others. It was fun, especially in those days when there were plenty of novel mutants to be found.
Tell me more about that way into the pathway, Frank.
We were interested in the early part of the pathway. There had been a lot of work done by Davis and Sprinson in two groups working in the United States, and the pathway was starting to be established. It was known that there was a so-called common pathway which led from carbohydrate and branched out to three different amino acids, phenylalanine, tryptophan and tyrosine, and then possibly to para-aminobenzoic acid and possibly to folic acid. The big mystery was where the pathway branched.
We started to study the pathway, using mutants blocked at various points near where the branch-point might have been – eventually deciding that if we could make a multiple mutant, blocked all the way round the branch-point compound, that should pile up. In theory it wasn’t possible to do that – the reasons get a bit complicated – but we did the experiment the best way we could and found that a compound did pile up. We extracted the compound into ether, looked at the spectrum and knew we had a new compound being formed. Great jubilation.
Was the discovery of that the greatest moment of all?
Yes. There have been some good ones, but seeing that was one of the best because it came in so dramatically. One minute it wasn’t there, and next minute there was the spectrum in front of your eyes.
I remember very distinctly that Margaret was the one who actually ran the spectrum. Soon after that she became ill and had to leave the lab, and then I spent a lot of time trying to isolate the compound. I wasted a tremendous amount of time. Because no-one had ever found it before and everything, I thought it must be so labile that it had to be treated very delicately, very gently, or it would break up. So I ran all sorts of exotic columns. I remember doing some very dangerous things like, in a very poorly ventilated room, running columns of powdered sucrose and ether. Safety committees would never let you do things like that now.
Anyway, I lived through that, and eventually found that you could put the compound onto ion exchange columns and get it off, provided you did things very quickly and cold, even though it was unstable. It spontaneously broke down into one of the intermediates in phenylalanine biosynthesis and also into para-hydroxybenzoic acid. Getting this compound opened up a Pandora’s box: we could look at the pathway to the three amino acids and so on. We knew para-aminobenzoic acid (PABA) probably came from that compound, and we were able to show that. Then we started to look at other compounds also, and later in Canberra we did a lot more.
Why was the compound called chorismic acid? I must say I love that name.
My father-in-law, a clergyman in the Church of England, was a Greek scholar. I wrote to him outlining the situation – that we had a pathway and a branch-point – and he suggested several words from a Biblical quotation which I think has to do with St Barnabas and the young St Luke. That they ‘parted asunder’ was the important thing, and he suggested ‘apochorismate’ or ‘chorismic’ or words like that. I chose ‘chorismic’, because ‘apo’ has chemical connotations and one could confuse it.
And it is in the biochemistry literature for all time.
Yes, I assume so. It would be a bit hard for anyone to pirate it now.
Select activities that are most appropriate for your lesson plan or add your own. You can also encourage students to identify key issues in the preceding extract and devise their own questions or topics for discussion.
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