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Array Pioneer Mark Schena Edits Protein Arrays Reference

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At A Glance:

Mark Schena, visiting scholar, TeleChem International

1984 - BA, biochemistry, University of California, Berkeley.

1990 - PhD, biochemistry, University of California, San Francisco in 1990.

1990 - 1999 -- Postdoctoral Research Fellow with Ron Davis, Beckman Center for Genetic and Molecular Medicine, Stanford University.

When BioArray News last spoke with Mark Schena, (see BAN 11/8/2002), the visiting scholar at TeleChem International in Sunnyvale, Calif., was celebrating the completion of his third book, Microarray Analysis (2002).

Now, some 14 months later, Schena, a microarray pioneer, is moving into the emerging technology of the protein microarray, with a new book, Protein Microarrays, slated for release on April 15 (see BAN 01/21/03).

BioArray News spoke with Schena last week to learn about the book -- which, unlike his previous book is a reference volume rather than a textbook -- and what he has learned about the field of protein arrays in this process.

You are really starting to make book writing into a cottage industry. This book really follows closely on the publication of your last one.

We were planning on having it released at the end of last year, but it was twice the size we had anticipated at 450 pages. We expected 200 to 250 pages. When the size expands, it takes a lot more editing time. We just didn't anticipate the kind of response that we would get from contributors and we ended up having to limit it to the size of the publisher's limitations. Essentially, every top lab in the world has contributed to the book.

How did you get this assignment?

Basically, [Jones & Bartlett Publishers of Sudbury, Mass., a reference and textbook publisher] contacted me and said, `You are the guy because you know the field, have attended the conferences, and are reading the literature.' They presented a good case for the need for the book and said they had gotten a lot of requests from the field. And, I had a list. So my job was to send e-mails, and contact people asking if they wanted to contribute. The response rate for the first two books was about 30 percent, getting a dozen replies back from my requests. For this, I sent out 28 invitations and got 24 affirmatives. Even after that, people in the field kept coming up and saying they would like to contribute. We had to turn away a half a dozen contributors.

Are the contributors academics, or from the commercial side?

Its about two-thirds academics and one- third commercial. There are not a lot of plugs for companies. That's an important part of the editing process: Where there is gratuitous promotion, we take it out.

But science has changed. There is so much high-level basic work required to make the products and we have found a considerable amount of intellectual content in the private sector. Twenty-five years ago, the life sciences were an academic endeavor. When I got involved, the concept of commercial science was non-existent. It's important to have the commercial presence in a high-technology field like microarrays. The tools cannot be developed in the academic community, which is just not set up to develop and market instruments and provide customer support -- those are all commercial issues. I've advocated that if you don't have the commercial organizations, you don't have a microarray field.

The field of protein microarrays is really in its early stages. How do you write a book today about such a dynamic field that will be useful in a year, or five years?

There will be important foundational content in there. The principles of protein arrays, that is timeless. Some of the other stuff -- methods protocols, content, manufacturing procedures, surfaces, and applications -that has a shelf life. But it's early enough in the field that the stuff will be interesting for about five years; that's the prediction. That is what we have seen with the DNA [array] field. One of the nice things about books is that you can include content that is hard to present in other forms. So we will present some information that is impossible to get from another source and we will have some novel content in this book. It's not Bonfire of the Vanities, but selling 10,000 copies is the target.

So, after this experience, what is your vision for protein arrays?

There are heck of a lot more people who work on proteins than on nucleic acids and we think the proteomics field is going to be substantially larger. Proteomics is more encompassing than the DNA equivalent. In proteomics, you encompass cell biology, enzymology, protein biochemistry, and protein structure. There are a bunch of fields, such as immunology, that almost work exclusively on protein.

The protein microarray field is where DNA microarrays were in 1997-1998. It's very early and there is a little bit of Braille out there. At the same time, the tools for DNA arrays can be used for the protein side of things so protein arrays have had a significant head start, where we had to invent everything from scratch [with DNA arrays]. But what is rapidly expanding is mainly on two fronts. Content, what we actually put on arrays, is expanding with the availability of recombinant proteins, monoclonal and polyclonal antibodies, purified protein domains. And, there is a rapid expansion for target molecules. On the applications side, laboratories are devising new uses every day, not only in science but also in diagnostics. On the basic research side, there is a lot of thinking about how you can reconfigure traditional assays that have been performed in cold rooms and test tubes. In diagnostics, the same thing is happening. Most diagnostics are fairly low tech and are macroscopic, using plates and large volumes of samples. We see a significant trend to miniaturizing many of the in vitro diagnostics that use antibody assays. In the private sector, there is significant technology development by people who are trying to develop tools. We have a functional set of protocols and tools. Now, the challenge is trying to expand the scope to the types of questions we use for microarrays.

Given your long experience on the DNA side of things, what is different about protein arrays?

Being involved at [the] beginning on the DNA array side of things certainly had a lot of advantages in terms of this project. By the same token, I find myself tapping into my early training. I had three incomparable mentors -- Dan Koshland, Keith Yamamoto, and, of course, Ron Davis. All three have a tremendous knowledge of protein biochemistry. I have found myself drawing on DNA and protein biochemistry knowledge that was imparted in my training. Looking forward and back was an interesting revelation for me. It become clear during the editing of the book that I was drawing on training that dated back 20 years or so.

How does this emerging technology sync up with the systems biology trend we are seeing?

I think protein fits in wonderfully in systems biology. Proteins are the ultimate purveyors of genomic information, they carry out the instructions. Protein microarrays are a high capacity assay, looking at the entire proteome. Maybe the way to think about the protein microarray is that it is an essential tool that allows researchers to look at protein function. That's new for us. People who look at DNA and messenger RNA have tended to be technology-oriented. Protein researchers, as a group, have used more traditional approaches -- and that is not to say that everyone is using sticks and stones out there. Now with the rise of protein microarrays, we are seeing a new embracing of technology by the protein community. We think microarray assays are going to be an example where the protein field uses very high technology devices to explore basic questions.

How is your microarray textbook doing? I find it ranked around 200,000 on Amazon.com compared to Terry Speed's book, which is ranked around 30,000, which I might say, qualifies it as a microarray best seller.

I had hoped [Microarray Analysis] would do a little better. The book came out early. The microarray thing is new enough that the universities haven't adopted formal courses in microarrays. But, a textbook has a longer shelf life and we expect sales to increase as universities develop courses.

I know that you have traveled extensively. Would you reflect on microarrays in global emerging marketplaces?

Overseas a lot is happening, but it is at an early stage. I tried to spend as much time as I could in the developing world and I have been spending a lot of time in China, partly because there is a lot of scientific expertise there and partly because all of us share an interest in trying to build more camaraderie with scientists and nations because in a small way a scientist can be an ambassador. The microarray field in China, Eastern Europe, and Central America is starting to expand, and is fairly advanced, not only on the basic side [but in] diagnostics. There is some activity increasing in Mexico, and in Cuba, as well as South America -- Argentina and Brazil -- and there is more and more coming over time.

Will you do another book?

I can't sit back; there are people screaming at me for other stuff. You know what happens when you have a little success in an area, it's, `Let's have more.' What is happening now is that the publishers of the earlier books are saying `let's have version two.' Maybe that's the basis of my nickname here: They call me the `visiting scoundrel.'

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