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Simon Goldbard on His New Biotech Venture and the Use of Primary Cells in Drug Discovery

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At A Glance

Name: Simon Goldbard

Position: Founder and CEO, Movi Global

Background: Co-founder and vice president of product development, Vitra Bioscience, 2001-2005; Head of research and product development, Applied Imaging; Co-founder and director, Genet Corporation; PhD, immunology, Iowa State University


Over the course of his career, Simon Goldbard has had his hands in the technology development, founding, and/or IPO of three biotech companies. During this time, his interests have ranged from genomics and nucleic acid hybridization, to tissue culture, oncology, and drug discovery.

Most recently, Goldbard co-founded and served as vice president of product development for Vitra Biosciences, the Mountain View, Calif.-based biotech that was trying to commercialize a novel multiplexed cell-based assay platform called CellCard. Vitra was forced to close its doors late last year due to a lack of VC cash, but just this week had its core technology acquired by Serologicals (see related story, this issue).

In the meantime, Goldbard has founded Movi Global, another biotech startup based in Mexico that strives to be a CRO of sorts for US-based biotechs and pharmas. He also published a review paper calling for the increased use of primary cells in drug discovery and development [Current Opinion in Drug Discovery & Development, 2006 Jan; 9(1): 110-6]. Cell-Based Assay News caught up with Goldbard this week to discuss the paper and his newest venture.

Tell me about the work you're doing now with Movi in Mexico.

We're working on several fronts in the biotech industry in Mexico, which as you can imagine is financially a lot more viable than the US. There is a lot of technology, and a lot of good talent there that's been underutilized, especially in the biotechnology and biology fields. I'm bringing a lot of the R&D and production from American companies into Mexico. It's a little bit different from outsourcing — you can do a lot more with your money, and that allows us to do things that we couldn't do in the US before — especially in areas like pre-clinical studies, reagent development, and reagent production and manufacturing. It's more like a virtual biotechnology company, and we partner with American companies. In one instance, we're making specific reagents for a company that does screening of different enzymes. We also do a lot of cell line production and chemistry.

A lot of companies are very wary about going to India and China. People are not that willing to go to China — they're going kicking and screaming, if you ask me. They are only going there if they think they can sell into the Chinese market. But they're not trying to sell to the Chinese market — they would much prefer to do things closer to the US market.

Also, in India and China, intellectual property is not well protected, as opposed to Mexico, which is part of the Patent Cooperation Treaty, and also where, through NAFTA, intellectual property is very well respected — as well as [it is] in the US. That attracts a lot of attention from the companies we're talking to, because it never occurred to them to go to Mexico. Labor is as cheap as in China, but [Mexico is] closer, and the IP is protected, and there are a lot of American- and European-trained scientists there. There is really a lot of talent there. Essentially, you can do a lot more things with your money. For instance, if you want to go into primary cell production, it's a lot cheaper to do that. And then you can go into animal testing and do a bunch of other things that are prohibitively expensive in the US, such as working with stem cells — which also have some political implications [in the US], but not in Mexico. So we're doing contract research and contract manufacturing with pharmaceutical and biotechnology companies. We're manufacturing instrumentation for biotechnology, like dispensers, automated microscopy, and things like that. This is an effort that is also partially supported by grants from the Secretary of Commerce in Mexico.

So you still have an interest in the use of primary cells in drug discovery?

Absolutely.

Was the Current Opinion in Drug Discovery & Development article written while you were with Vitra still?

I started it while I was at Vitra, and finished it with Movi.

What are some of the major factors that have limited the use of primary cells in drug-discovery applications?

There are several of them. The major factor, to me, seems to be variability. People are very worried that they can't reproduce day-to-day experiments with the same group of cells, which is a natural concern. This was one of the things we were trying to address with the CellCard system, by trying to use fewer cells, and therefore get more out of it, and [cut down on] variability. Miniaturization of primary cell assays is not going forward, though, as much as one would expect. That's still a big problem.

The second factor is availability. There are just a few reliable places where they're willing to sell cell lines to you, and they're still limited in the number and type of cell lines that they will sell to you. We've also had some interesting experiences in the past, where we used the same cell line in different experiments and got different results. I'll give you a specific example: adipocytes. [At Vitra], we used adipocytes from different commercial sources, and got different results in the same assays with the same drugs. So depending on where I was getting [the cells], I was getting different results, which is very unsettling. That represents a problem from a quality control standpoint, but it also gives you pause as to how people isolate adipocytes. It makes you wonder, for example, are they really adipocytes, or are they something like pre-adipocytes? All of those things give people a lot of reasons to not use them, because you know that with transformed cell lines, all these issues disappear — HeLa cells are HeLa cells, pretty much.

The corollary of all of that is money — it's expensive. Having said that, one of the fastest growing areas in biotech is how to efficiently transfect cells. I've now met two or three different companies that are all in the cell transfection business, and they're talking about primary cells, specifically. But transforming primary cell lines is difficult. Transfecting transformed cell lines is not a big deal anymore — there are very well-established technologies to do that, and the rates are very good. The problem with primary cells is that the transfection reagents are very toxic. When you work with primary cells, you can transfect cells and kill half of them — that's one of the biggest problems. There are now companies, though, that have developed other methodologies, like electroporation, to efficiently transfect primary cells. The reason for that is that people want that technology. People are starting to see that it is necessary. One of the things I wrote in the [Current Opinion in Drug Discovery & Development] paper is that they need better disease models than are currently available. It doesn't make much sense to me that if you're doing diabetes research, you transfect CHO cells with your genes of interest, and then screen those, because you're doing it in kind of a vacuum. It makes a lot more sense to do this on adipocytes, where the rest of the cellular machinery is in there. People are coming to that realization, and it's a hard spot for them, because it's very difficult for them to do those experiments. That is what is generating many of these companies that are dedicated exclusively to the efficient transfection of primary cells. I think that's going to move the whole field forward, and make people more aware that something has to be done to provide these cells in bigger quantities.

Is the increased disease relevancy the major benefit of using primary cells, or are there other benefits?

That's the major benefit. A second benefit could be that they are more native targets. They're less artificial reagents, so to speak. Therefore, if you're also looking at toxicology, it's really important, because a compound can be relatively safe on transformed cells, but it would have really raised a red flag if it started killing primary cells. There are lots of examples of that. We started mixing transformed cell lines with primary cell lines at Vitra, and we saw that effect. It stands to reason that at some point — and the earlier the better — you want to use primary cell systems.

Is miniaturization the answer to more widespread adoption of primary cells in drug discovery?

I think miniaturization is definitely one of them. The other one is isolation techniques. For example, the isolation of adipocytes still requires a large amount of adipose tissue. There are culture techniques — primary cells, in general, take longer to attach when isolated, and therefore, the mortality in the initial steps is very high. As a clinical example, if you run an amniocentesis test, in the first three days, ninety percent of the amniocytes die, and the last ten percent you end up utilizing. It's no different with other primary cells. You start with a big mixture of primary cells, and you end up with very few of them, and that costs you a lot of money. If somebody could find a way to prevent the mortality in the initial steps, that could increase your efficiency ten fold. That's what happened with amniocytes — since the development of Chang media, which is now used worldwide to culture amniocytes, it made a huge difference, and amniocentesis became a viable test, because this media was so effective in retaining the good cells. Hopefully something like that can be accomplished with the rest of the primary cells.

As the use of cell-based assays increases in drug discovery, it stands to reason that there could be a lucrative market for reliable primary cell suppliers…

Yeah, you would think so. You would think that a company like Cambrex would be able to increase revenues here. And that's one of the reasons they were interested in working with Vitra (see CBA News, 6/6/2005). Cambrex, I think, is more interested in selling the reagents in and around the cells, rather than the cells themselves. I think it's a little more profitable to sell the media and some of the reagents that enable tests on primary cells. That's one of my interests in Mexico. I think it's easier to set up infrastructure in Mexico to collect primary cells. It's less competitive, and probably cheaper to set up an operation like that, and then export the cells. This is something that can be done very well from other parts of the world, but it's more difficult. There is a company in Spain called Advancell, and they're in Barcelona, and compete straight up with Cambrex. They sell adipocytes and other cell lines. Their problem is that it's very difficult to ship live reagents from Barcelona into the US because it takes too long. There are no direct flights, so they have to go through Madrid, and that takes another day, so that's now three days. Now, shipping from Mexico is the same as in the US — you can do it overnight, so that's one of the major advantages.