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Microarray Pioneer Ed Southern Prepares for Life after Retirement

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At A Glance

Sir Edwin Southern, Whitley Professor of Biochemistry at the University of Oxford, Department of Biochemistry.

Education:

  • 1958 — Bsc, chemistry, Manchester University.
  • 1962 — PhD, chemistry, Glasgow University

Awards and Honors:

  • Lilley Fellow, Woods Hole Laboratory 1979;
  • Biochemical Society BDH Gold Medal for Analytical Biochemistry 1981;
  • Fellow of the Royal Society 1983;
  • Analytica Prize of the German Biochemical Society 1984;
  • Herbert A. Sober Memorial Lectureship of American Society of Biological Chemists 1986;
  • Foreign Member of American Academy of Arts and Science 1988;
  • Honorary Doctorate in Medicine and Surgery, University of Padua 1988;
  • IBM Europe Prize for Science and Technology 1989;
  • Gairdner Foundation International Award for Medical Science 1990;
  • Honorary DSc University of Edinburgh 1991.
  • Miami Symposium Special Achievement Award 1994;
  • Honorary Doctor of Science, University of Lund 1995;
  • Royal Medal of the Royal Society, 1998;
  • CMB-Roche Award 1999;
  • American Association for Molecular Pathology Award for Excellence in Molecular Diagnostics 1999;
  • Sir Frederick Gowland Hopkins medal of the Biochemical Society 2002;
  • Honorary Doctor of Science, University of Uppsala 2003;
  • Knight Bachelor, Queen’s Birthday Honours List 2003;
  • ABRF award 2004;
  • Honorary Doctor of Science, University of Glasgow 2004.

Last week, microarray pioneer and Oxford professor Edwin Southern received the annual ABRF award, joining honorees Fred Sanger (1994) and Leroy Hood (2001).

For the 65-year-old Southern, the award included the opportunity to present a lecture to the annual gathering of the members of the Association of Biomolecular Resource Facilities in Portland, Ore. He spoke before an audience of 800 people, leaving the floor of the program’s trade exposition quiet as even the vendors stopped commercial activity to slip off to the auditorium to hear Southern’s remarks.

What they got was a bit of humor, a bit of gravitas, and eminence gris. He ended the lecture with advice to young scientists interested in developing technology telling them to just go for it, and “challenge attitudes.”.The advice, he said, came from “someone who has his senior-citizen’s bus pass.”

For some 45 minutes, in a baritone delivery, Southern reviewed his work in the early days of his research, 31 years ago, at a time when he activated a blotting action in his lab by using paper towels to start the absorption of nucleic acid through a gel.

Today, his said his lab is developing methods for imaging at the molecular level, integrating mass spectrometry as a label in microarray analysis, and developing new techniques for in situ manufacturing of microarrays (see related coverage, page 6).

He said he plans to retire from Oxford University, where he started as department head of biochemistry in 1985, just five years after he was promoted from research assistant to director of the MRC Mammalian Genome Unit in Edinburgh.

Southern spoke to BioArray News about what is next on his agenda as he prepares to retire from academics next year.

How did you get interested in science?

I’m not sure when it started. I had a really good chemistry teacher and he triggered my interest. I guess there is an innate personality that is drawn to science — people who tend to be a bit introspective. Science is a large part of my life. I do have other interests as well. Music — classical, and chamber music — is the main thing. I have a big garden and grow fruit trees — apples, plums, cherries, apricots. I spend a lot of time there. I have about 20-some trees. and looking after them takes quite a lot of my weekend.

Can you tell me about your childhood?

I grew up in Burnley, a small town in the north of England. My father was a typewriter mechanic, and my mother was trained as a comptometer operator — that’s sort of an accounting, calculating engine. She became a supervisor in that field. I was born just before the Second World War, so my father was away for that period. When he came back, he started this company repairing and selling typewriters and other office machines. He was sort of technically minded, always making little inventions and tools to make getting into the typewriter and doing a job on it a bit easier. He was a clever sort of chap.

Do you remember the War?

I was seven when the war finished. I remember sheltering under the table. We were never bombed where I was, but you were aware of it.

Your academic group does a lot of research. Are you constantly looking for things that have commercial potential?

No. I wouldn’t say that was always there. And, never in the academic world. When I did the blotting, I never even dreamed of filing a patent.

At this point in your career, what are your research goals?

At this stage, I’m one year from retirement. You have to retire from the university at age 67. So, I’m sort of winding down my academic activities, and winding up my involvement with the company [Oxford Gene Technology], and some other work that has to do with a charitable trust.

What is the nature of the charity?

The other trustees [are] Adrian Bird, a professor of molecular biology, and Paul Nurse, the president of the Rockefeller University. It is called the Kirkhouse Trust. We are setting up programs for crop improvement and crop research in the developing world. So I do quite a bit of traveling to India and Africa and China to set up programs. That is a new departure for me and that is something that I am really beginning to enjoy. It’s something new to do as I move out of the academic world.

How does the work that you have done apply to that?

The programs we are supporting at the moment have to do with marker-assisted selection [MAS}, so that has grown out of a mapping technology where you analyze variation in the DNA and use that to track genes in disease research in families with inherited traits. It’s applying the technology in a different sort of way.

The thing about the plant world is that you can work on a very large scale. You can do crosses, and back-crosses, and you can make recombinant-inbred strains. It’s actually a lot easier than human genetics.

What kind of horizons do you have for the work in this arena?

A classical breeding program will take probably seven to 10 years, starting from scratch. MAS can bring this down to 5-7 years. If there is already a substantial amount of the groundwork done, for example, if there is already a molecular map, or if people have created recombinant embed-strains, then the time frame is shorter.

There are very big problems, especially in Africa. There are two things — a lot of people are starving, and another thing is that, those who are not starving, are too poor to lift themselves out of rather dire straits. Both of those things have consequences. So whatever you do to improve crops can only help them to both feed themselves and lift themselves out of poverty. And, I think some of the biggest issues facing the world — political instability, overpopulation and destruction of the planet —- will be helped by the relief of poverty.

Are you dabbling with GMOs?

I have nothing against GMO work, it’s just not what we are doing at present. We are supporting marker-assisted selection, which has a number of practical applications. One objective is to bring together a number of desirable traits and put them all into one variety — this is called ‘pyramiding.’ And, so the genes that you are introducing are already present in the same species. There is no genetic manipulation in the sense of GMOs. It’s accelerated breeding.

What kind of funds does this trust have to work with?

We aim to spend approximately $1 million a year.

Let’s talk about what is in the pipeline for OGT as far as commercial technology. We wrote about Oxamer recently [see BAN 2/18/2004]. My guess is that Ryan [Egeland], the co-founder of this company receiving OGT’s support, is quite a talented scientist.

He was a Rhodes Scholar, and that’s something you don’t [achieve] without having something special, and I think he has that.

Would it be fair to call him a protégé?

No, I wouldn’t use that term. He is very much his own man. He started off with an [Oxford] MBA, and then he came and worked with me and did a PhD in two years, which is almost a record, really. He covered the whole ground — built equipment, did all the testing, wrote all the programs. He covered everything from designing and building electronics; he worked out the electrochemistry, made the oligonucleotides, did the molecular biology to show that it would work, so he is a man of parts.

Does he represent what perhaps is the very model of today’s scientist?

I think he is exceptional. What I like to see in a scientist is somebody who is prepared to turn his hand to anything. He is not afraid to take on something new, to enter a new field and learn it.

How do you assess the efforts to knit together genomics and proteomics?

I think it is difficult. It is hard to fill the gap between the two. For genomics now, a large part of it is expression analysis and the other big part of is looking at the variation in the genomes. Getting from there to function through protein expression is a very complex business because there are so many interactions. That's what people are now calling systems biology.

Do you buy into that?

To an extent, yes. It is just very hard to know where the boundaries are. The difficulty is carving out something that you can treat as a whole, and is manageable in scope. If you take a simple pathway, it tends to balloon out over time and it is very hard to know where those boundaries are, beyond which you don’t intend to include in whatever it is you are studying.

What can we expect to see from OGT?

I hope we can still contribute to the microarray field; I like to regard it as sort of a center of excellence and development.

Will you talk about technology and how you think it should be diffused?

I think it goes without saying that if you invent something that you would like to see it used as much as possible. There are some technologies where commercialization is the only way that you can get it out there and I think the microarray is a good example of that. To do it properly, it has to be done in a commercial context. So that is why, in a way, that I entered the commercial world. I am not a natural for the commercial world, as you can probably see. It will be important to keep an R&D effort going in OGT — otherwise I wouldn’t be interested in it. I think my engagement, hopefully, will be much more into the R&D side of it, not to the business side of it.

What is your filter for commercialization of technology. What is the one thing you look for?

You have to use your instincts to make a judgment. You never know when a technology is going to take off, or which ones are going to succeed. In my career I’ve had probably a dozen inventions of new technologies and only two of them have really have taken off in a substantial way. Very often what happens is that you have a wonderful new idea, spend a lot of time developing it, and somebody else comes up with something better and its displaced before it’s even born. You just have to go by your instincts and have optimism.

Are you pleased with the way that that microarray world has developed?

You are getting into dangerous territory here, actually. I’d rather not comment.

Are we going to see tangible benefits to human health from this technology as it is now?

Yes, I’m sure we will. I think there are some extremely good examples. I think the business of being able to differentiate cancer types is an extremely good example of how it will bring benefits. The hope is really that that kind of work will be consolidated into true clinical diagnostic methods. I think there is room now to make the technology more robust, more reliable, more reproducible. And to work harder on the biological side to clean up how samples are treated before being applied to the arrays. That is all going to have to be a part of it.

The FDA is quite involved. If you had 20 seconds to give them advice as they try to understand and regulate this technology, what would your advice be?

I think they are probably doing the right things, it’s all a matter of getting agreed standards, measurable standards. A lot of people are putting good efforts in that direction; there has been a tendency for people to jump in and do some quick, not very clean experiments in the field. So there is a lot of sloppy work going on out there at the present time. But I think it is improving very quickly and people have begun to understand the need for better, tidier work and it is all coming together well.

 

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