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Head of Bio-Rad's Proteomic Business Talks About Company's Strategy


Brad Crutchfield
Vice president and group manager
Bio-Rad’s Life Science
Name: Brad Crutchfield
Position: Vice president and group manager of Bio-Rad’s Life Science business, 2004 to present
Background: BS in physiology and nutritional biochemistry ,University of California at Davis, 1985

During the past year, Bio-Rad significantly ramped up its presence in the proteomics industry by first purchasing ProteOptics, which gave it a platform for the functional analysis of proteins, and then agreeing to acquire Ciphergen’s proteomic tools business, including its SELDI platform.
ProteoMonitorrecently caught up with Brad Crutchfield, who oversees Bio-Rad’s protein-related business, to talk about the company’s ongoing strategy in that sector and its plans for Ciphergen.
It seems like Bio-Rad is really looking to build up its proteomic and protein-related business. Can you comment on some of the recent acquisitions in that space and what you’re looking for when you’re considering such a deal?
For Bio-Rad, we look at the workflow, the kinds of data that are going to be needed to allow the specific understanding of a protein, and, therefore, gene expression. These tools really come in a workflow. And in our case, we have a strong, 50-year experience in the area of protein separation. And now what we’ve been building on is ways of doing that faster with microfluidics and more reproducibility. We certainly felt that the multiplex array, or the liquid chip multiplex array approach, which we call Bio-Plex, was the key element of looking at protein expression, even the isoforms of a particular protein. So that particular product line has been out and we’ve invested heavily [in it] and will continue to do so.
But then you get to some holes in the process and a number of our customers indicated that there needed to be a very convenient way to look at how proteins interact with their neighbors or with other cellular components and that had to be studied through a protein-protein interaction. It could not involve any outside contamination, i.e. a dye or some sort of marker, and so really the technology that we centered on was surface plasmon resonance in terms of label-free detection. And that product we developed with a small Israeli company that had some interesting technology to allow us to do our gradient or a grid and do so in a way that was more accessible to a wider range of people. Some of the high-throughput surface plasmon resonance instruments had been at price ranges that only a few core labs would be able to afford.
Our philosophy is to bring the technology as close to the person who’s asking the biological question [rather] than having to have it shipped off to a core lab. So we came out and helped develop this product. We ended up acquiring the company [ProteOptics] although in the end, most of the development was [with] our funding as well. So ProteOptics became part of the team. They are referred to internally as the Haifa innovation center. They developed and launched the product. In fact, our product is out on the market. We are shipping it at this point, and the demand is very, very high.
The second element to this really comes down to this idea of protein identification, and again, there are a number of technologies centered around mass spec to allow specific proteins to be identified. However, it’s a very complex process to get to there. We’re looking at opportunities to offer the product that Ciphergen has and tuning that product to make it a very good protein fingerprint instrument that allows in clinical research the opportunity to look at normal and diseased states and look for particular markers or potential biomarkers that could be used for diagnostic purposes, or in themselves [provide] a better understanding of how protein expression in that particular disease state is impacted.
Clearly in the case of the Ciphergen product, the SELDI product, it’s a very powerful tool and it’s very ideally set up for protein discovery or protein fingerprinting. It’s particularly useful in the clinic or when you’re trying to compare samples or do differential protein expressions in different states. The next step, or next evolution of that, will be the capability [to go back to] use the power of a MALDI technology to actually identify that through peptide fingerprinting and using databases, go back and say, ‘OK those two proteins are up- and down-regulated, this is exactly what they are.’
And that’s going to take a second-generation product that we’re working on and will be part of the Ciphergen business unit for us.
During the most recent earnings conference call, your CEO, Norman Schwartz, said that he sees more business opportunities on the protein side of the business and less so on the genetics side. What did he mean by that, and what has caused this reversal?
I think in general, it’s really our customers. The human genome represents the document, effectively a map. And the question is, how quickly can we take that information and turn it into useful information, i.e., how the cell works. And it’s a very complex mixture of how gene regulation works within the cell and how other factors like microRNA impact and control and modulate gene expression. And then to the extent that you’re looking at protein expression, how does that get modulated? These proteins, which are in a sense coded for, are all nice, but then if you have five different isoforms, depending on the level of glycosylation or phosphorylation, you have completely different situations in the cell.
I think what Norman Schwartz meant is that we have a series of products now that really put us in the position, and this is no longer molecular biology kits where somebody can clone and move along, like the gateway process, not that those are not important. What you’re talking about is a series of platforms that are going to drive success in this market. And that’s what we feel we have to do. Our approach is really around the total solutions and the total solution is close to the end user or the person asking the question. And that means that by getting the engineering done in a way that the instrument can be provided at a price level that is more affordable for labs or groups of labs. And then the necessary reagents and software and all the things that allow answers to come out of these things.
Is the life science industry seeing proteomics reaching a new stage as a viable science to base a business on?
Yeah, I think it is. I think that proteomics’ initial view owed its basis from the genomics, and there was a belief that there was a brute force solution to it. At some point in sequencing the human genome, somebody was able to do the math and say ‘Hey, all we need is 1,600 machines working around the clock for the next four years and we’re going to get it.’
And of course the technology improved and got faster, but the problem with proteomics is it’s just very, very difficult to do that. And in fact, I really don’t like the word ‘proteomics.’ I think what we’re trying to look at is protein expression analysis, and protein expression analysis is getting to be a viable option for understanding drug discovery or drug interactions and is also a viable process that ultimately could yield potential clinical diagnostics.
But the key, though, the absolute key, is it cannot be the expert users, it cannot be just the core facilities, and it cannot be the five or six well-funded genome centers that are going to drive this. This is going to be driven because we’re asking complex biological questions, and the people who ask those questions, the customers who are asking those questions and are going to solve them with these tools, that’s where the discoveries are going to come [from]. I don’t believe that there’s going to be some national initiative that’s going to drive all this. It’s too complex and there are too many angles for this all to be done under some sort of Herculean effort that’s being globally managed.
Is it going to come from the clinical side or the ground-level researcher?
I think it’s more ground-level researcher, but you’re going to see the opportunity for this to move into the clinical labs fairly quickly. In the case of SELDI technology, it is a great discovery tool for protein markers. Coincidentally, it’s exactly the same detection tool that you would put into the clinic, and that’s currently the plan and that is Ciphergen’s ongoing plan as we take over the rest of the business, and we’ll certainly support them on that.
A few years back, a lot of companies jumped into proteomics. Why didn’t Bio-Rad?
If you look out in our industry, we’re somewhat unique. We have a fairly diverse product line, we’re very vertically integrated and we made a very strong decision in the end that we would not run out and try to throw something together until we could validate how well it worked. And we have been working very hard and have validated and made a very good 2D array generation capability, and then we obviously have a very strong capability for people who blot and look at very specific elements of a protein expression map.
The elements that we looked at and felt where we could add value were in the area of multiplex immunoassay. Multiplex immunoassay is no different from anything else in the sense that you’re trying to look at multiple proteins, and do so in some cases under [a] constraint — in a mouse model, where you don’t have a lot of serum to work with but you want to test 10 or 15 different cytokines or phosphoproteins. We made that available and that project has been out and has been very, very successful.
Why didn’t we jump into mass spec? We had partnered with Micromass. That was our original approach. In the end we found that that just didn’t work, and we did not feel that we wanted to be in the mass spec business. And today, we are not interested in being in the mass spec business.
What we’re interested in [doing] is providing appliances that allow our customers to be successful, appliances where our customers may not really care how they work — they are just tools to give them answers to get to the next step. And that’s kind of where we felt Ciphergen had brought the technology, for lack of a better word, mass spec technology. And so we realize it has a certain capability and we have already plans to take it to the next level as far as the capability for true protein identification.
If a customer is looking for a full function mass spec for a core facility, they have a number of choices to go. But if a customer is looking for a mass spec that’s tailored for their applications for protein identification and the workflow of them trying to understand some aspect of the cell, then I think we have the right answer.
You touched upon some of the R&D that you want to do with the SELDI instrument. Can you give me some more details?
The existing product right now will need to be evolved to offer the kind of capabilities that one would expect.
Is that your way of saying that Bio-Rad is aware that there have been problems with the instrument and criticism about its accuracy, and that this is something that the company’s going to have to address?
Yeah, and I think it’s the difference between a company that’s small-time and desperate to get as much success under their feet because they’re under the gun financially, i.e. Ciphergen. I think they did a good job. I think there were probably examples where they oversold the instrument. In the end, this product does a very, very, very good job of giving general protein fingerprints and those protein fingerprints can be very, very useful in multiple stages to help identify potential markers. We are not selling a mass spec. The SELDI product that they have will be marketed and sold by Bio-Rad with the tool that we have. They all kind of go together and we’re going to be making that argument.
The next-stage instrument — and that doesn’t mean that we’re going to get rid of the product that exists today — [is] for those customers, who choose to take it to the next level, they want to say ‘OK, fine, I have these five spots. I want to know exactly what those proteins are.’”
What kind of update can you give me on the Ciphergen deal?
The acquisition is proceeding on plan. We would expect that some time in the next two to three weeks, we would get all the necessary clearances with the shareholders and Nasdaq and we’re very confident that on Nov. 1, the signature will occur, the deal will be done and the Bio-Rad sales and marketing force worldwide will be brought to bear to support the Ciphergen customers that have it and really begin to roll out our marketing strategy.
Was there any discussion of Bio-Rad buying Ciphergen’s entire business, including the diagnostic business?
That really wasn’t an issue for us because they perceived that most of the value right now [is] around these ovarian cancer markers that are currently in the clinic with Quest, and anybody who knows anything about ovarian cancer knows that this is one of those deadly ones where there’s really no effective screening point.
That being said, they have a team of people who are really focused on that and they believe that in the near future that that product will make it into the lab. And what it essentially means is it validates the SELDI technology as a discovery tool as well as a diagnostic tool.

Now, we may choose to help support them and expand that technology into the clinics worldwide. Obviously we have a very large clinical diagnostic group that could step up and do that.

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