South African Sydney Brenner was awarded the Nobel Prize in Physiology or Medicine in 2002. His joint discovery of messenger RNA, and, in more recent years, his development of gene cloning, sequencing and manipulation techniques along with his work for the Human Genome Project have led to his standing as a pioneer in the field of genetics and molecular biology.
Now, one of the interesting things which happened during the time, and actually was a side-effect of all of this work, was the invention of negative staining. Now, this is a very remarkable... technology because what it did was it took electron microscopy out of the hands of the elite and gave it to the people, basically. Now in those days if you needed to do electron microscopy you needed to have a professional electron microscopist. This is someone who knew how to shadow things with uranium, and he would evaporate uranium onto these objects and put them on the machine so that you could actually visualise them. Because... of course the electron microscope can see small things but it needs contrast in order to see them and this… biological objects don't have enough contrast – you need some kind of heavy... heavier compound there, with more electrons, that is – and so shadowing was part of the profession, and these electron microscopists had to be pampered, and if you were, say, working in the life sciences you had to find a collaborator who of course exacted a very high price for this collaboration. And I started to work with… with someone called Bob Horne, who was a very interesting chap, was working with the electron micro… microscope in the solid state physics group here in the Cavendish and… and we had great difficulties in visualising these things and doing the shadowing; it was all terribly slow. So I decided – having come from a background of cytology – I would try and stain these. And… and so I knew you had to stain them with heavy metals, and so I got hold of phosphotungstic acid, and the first thing I did is I measured its pH, and I discovered its pH was three. So I said, 'I don't put biological objects into such acid conditions', so I neutralised it and I took all these pieces of virus, and I sprayed them onto this grid, and we took them over and we looked at them. Now Bob Horne said, 'That's a mess, it's a total mess; everything…' But then I saw something, and I knew immediately what it was, and I said, 'This is called negative staining'. And how did I know this? Because in my medical course I had learnt to show how you'd look at treponema. Treponema is the age… spirochaetes. Treponema is the agent that causes syphilis, and one of the things you diagnose is you put a drop on a slide and you put Indian ink in it, and you see the treponemas as white objects transmitting the lights, swimming in the sea of ink, and this is called negative staining, and this was invented in the 19th century for the optical microscope and we… and I understood that this was the exact image of this, but for the electron microscope, so with this we could produce remarkable images. And it had two effects. One is it allowed at least the electron microscopy of small objects to go. But what happened is it took all the people working in virology and gave them a tool that they could all use and really wiped out the profession of electron microscopist in a biological lab because everybody could just do it. And of course it's been the… it's been a wonderful technique, it's been developed by… by many people, but it's again… I mean, in that sense, it's… it's being able to say, 'This picture, I've seen something like this before', and of course now I know it's got to do with syphilis. Of course you can't explain to someone that this is where venereal disease comes in but it's effectively… it's the images that map on to each other.
Title: Taking the electron microscope out of the hands of the elite
Lewis Wolpert is Professor of Biology as Applied to Medicine in the Department of Anatomy and Developmental Biology of University College, London. His research interests are in the mechanisms involved in the development of the embryo. He was originally trained as a civil engineer in South Africa but changed to research in cell biology at King's College, London in 1955. He was made a Fellow of the Royal Society in 1980 and awarded the CBE in 1990. He was made a Fellow of the Royal Society of Literature in 1999. He has presented science on both radio and TV and for five years was Chairman of the Committee for the Public Understanding of Science.