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Blackstock Tells How His Proteomics Path Led Inevitably to Big Pharma

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AT A GLANCE

Name: Walter Blackstock

Age: 54

Position: Vice President, Technology, and a Founder of Cellzome UK

Prior Experience: Served as Worldwide Director for Proteomics, GlaxoSmithKline. Founded Cell Map Incubator Project within Glaxo Wellcome in 1998 to study protein-protein interactions using mass spectrometry.

In the first of a two-part interview, Walter Blackstock discusses his entry into proteomics and his work at Glaxo Wellcome in functional proteomics. In the next issue of ProteoMonitor, Blackstock will describe why he left Glaxo, and his current work at Cellzome.

QHow did you first get involved in the field of proteomics?

AMy origins are in natural product chemistry. I’m a chemist by training and in this area you usually have so little material to work with that mass spectrometry was a natural characterization tool. From a very early stage I was shown how to operate a mass spectrometer so I could do my own work, and I found this quite congenial. I’ve always taken the view that the diversity of nature is a lot more interesting than the diversity of man, and the protein side for me represented the biggest challenge of all.

I’ve been involved in protein mass spectrometry for the past 10 years at least. In 1993 about five groups around the world more or less worked out simultaneously that you could characterize proteins from a rather limited set of numbers derived from mass spectrometry. At that point it became apparent that the ability to characterize proteins rapidly was now a real possibility.

QHow did you get involved with Glaxo Wellcome?

AWhen I finished grad school, I did postdoctoral work in Zurich and in Glasgow, and then I had rather a checkered background because I tended to move on after five years — I’ve had quite a lot of jobs. I worked with Hewlett-Packard for five years and I’ve been in small startup companies. But most of my time I’ve been with Glaxo [because] it was just following on from my interest in mass spectrometry. [Pharma companies] were the people who had the money to buy mass spectrometers and the people doing interesting work in this area. If you add both of those requirements together it inevitably drives you — or did in those days anyway — towards pharmaceutical companies.

QHow did your group at Glaxo contribute to proteomics?

AFirst of all I’ve been fortunate to work with some very talented people. One of the contributions we have made was to try to distinguish between the various flavors of proteomics and to articulate the notion of functional proteomics. It’s the application of proteomics to the study of protein-protein interactions rather than the use of proteomics for studies of protein expression. We come from the view that proteins in the body do not function alone, [but rather] almost always as a part of molecular machines composed of many proteins. We set up a group within Glaxo Wellcome called the Cell Map group, and published on this notion [of functional proteomics] that has now been adopted quite generally. I suppose we were one of the first groups to articulate this notion.

QWhat kind of tools did you use?

AThe principle tools behind it were mass spectrometry combined with the power of genome databases, but it was [also] the integration of low flow rate HPLC with mass spectrometry. In many cases it’s not a case of buying an instrument off the shelf and plugging it in and away you go. There’s a little more to it than that and this integration of low flow rate HPLC and mass spectrometry is an illustration of that.

QIs there a particular technology you’re interested in seeing developed?

AI have an interest in protein chips, but I’m not sure which way this whole area is going. I suspect it’s the venture capital people who see an analogy with DNA chips, and therefore by definition protein chips must be a good thing. That’s easy to say. It’s extremely difficult to implement. If you want to take [proteomics] into the diagnostic market, or want to go for really high-throughput you can’t do this by mass spectrometry, partly because the throughput is not adequate and partly because the expense is just totally disproportionate. [The impetus for developing protein chips] is really looking for a way to make that transition between a high-tech approach and a very low-tech approach appropriate for the mass market or diagnostics.