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Donald Michie

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Experimenting on mice and working with Peter Gorer
Avrion Mitchison Scientist
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I'd heard a student of Peter's called Darcy Wilson. He was just- a Canadian- he was just leading in Oxford the time that I started. And he gave a talk on the homograph reaction from the point of view of what it looks like. And he'd be cutting sections. And he had noticed that- This wasn't Darcy Wilson, this was Darcy somebody else. No, no, sorry. Did I say Darcy Wilson? Yes. But you meant- Sorry I'm getting the name muddled up. He was Darcy- Darcy Hart? No. A different Darcy. He disappeared from- he's not- I could probably find out his name. No, it's okay. But at any rate, he had observed that skins grafts filled up with lymphocytes at the time of rejection, so it was a reasonable guess that the lymphocytes have something to do with it. So I set out to try to test that idea. And, not wanting to do it all with skin grafts, partly because actually I wanted to cut out a little bit of territory for myself apart from the- this very strong grouping, in Birmingham. So I thought that the way to do it would be by transplanting tumors. That wasn't an entirely original idea, not at all. Because, in particular, a scientist called William Woglom in America had published papers on tumor transplantation and had noticed that, in mice, they grew for a bit and then they shrunk with about the same timing, as we by that time you knew the skin was being rejected. So that seemed a more- an easier assay. So I used to- I got a hold of a tumor which would be transplanted in one strain of mice, and I learned to mince up the tumor with- Peter told me that. I said, I had this great lump, what shall I do with it? Oh well, get a pair of iris scissors, that's scissors which have a half-curve in them, and just go on chopping until you've got a mince which you can take out in a cannula, which is what I did. And then you push the cannula under- under the mouse's skin, and lo and behold, in about six days you get a little lump, and if it's the same inbred strain that turns, by day 10, to quite a big lump. But if you put it into a foreign mouse strain, you can see the same little lump there at day 6, but by 10, day 10, there's nothing- it's been rejected. So using that as an assay, I then tried transferring blood and blood cells and that didn't work. I learnt how to- I went to visit Peter Gorer in London who had been, himself, a kind of- I don't think he was labelled a student of Jack's, but he'd been close to Jack, partly sharing the same political opinions and partly because Jack had encouraged him and that was his, Gorer's, entry into science to- to try to test the idea that blood groups were- the word- the term used then was primary gene products. They were close to what the- the gene made. And in particular, you had two different genes, or two different blood groups, human or animal, would express both of them. And, the rules of transplantation that had been worked out by- in America, by people in the Jackson Lab in America, and particularly by its founder, the rules of transplantation between hybrids and parents supported that view. So, at Jack's- with Jack's encouragement- And Jack, I think, first proposed the hypothesis that these were primary gene products; Gorer had set out to test it by making antibodies and he'd done that. He verified that, and that went on to- that was the beginning of the definition of the H2 locus. It's now called the histocompatibility locus of mice, and he had done that by- Gorer had done that by going to Bar Harbour and one, doing a great experiment, two, getting married to, I think, the personal assistant of C. C. Little, the founder. And that made him a more humane person. So, where was I? Yes. He taught to bleed mice and I thought, well, if he's right there should the antibodies there. But that didn't work, so- There were no antibodies. Well, there were antibodies that Gorer had shown. Right. You could show the antibodies with some difficulty. It was not very easy text, but you could show there were antibodies. But if you transferred the serum that didn't work. Didn't speed up the rejection. Right. And then I went on to make the same minces I'd been making with tumors. I was making minces out of lymph nodes and those did transfer immunity.

Avrion Mitchison, the British zoologist, is currently Professor Emeritus at University College London and is best known for his work demonstrating the role of lymphocytes in tumour rejection and for the separate and cooperative roles of T- and B-lymphocytes in this and other processes.

Listeners: Martin Raff

Martin Raff is a Canadian-born neurologist and research biologist who has made important contributions to immunology and cell development. He has a special interest in apoptosis, the phenomenon of cell death.

 

 


Listen to Martin Raff at Web of Stories

 

 

Duration: 5 minutes, 43 seconds

Date story recorded: June 2004

Date story went live: 24 January 2008