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Metabolon s Chris Bleecher on the Future of Equilibrium for Metabolomics

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At A Glance

Name: Chris Beecher

Title: Vice President of Biochemistry and Biotechnology, Metabolon

Background: Director for Drug Development with Ancile Pharmaceuticals and Associate Director for Natural Products, Bristol-Myers Squibb — 1997-1999; Associate Professor in Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago College of Pharmacy — 1985-1997

Education: PhD in Pharmaceutical Sciences, University of Connecticut — 1985

Metabolomics, as one of the newer “-omics” fields (if not the newest — it depends on how you count) is still fairly obscure. As the name implies, it deals with the measurement of relative amounts of various metabolites in sample fluids or tissues to differentiate between states of disease, stress, or toxicity, according to Chris Beecher of Metabolon.

Beecher spoke on the first day of the Molecular Diagnostics conference in Princeton, NJ, this week, delivering what was arguably one of the more popular lectures. Pharmacogenomics Reporter decided to pull him aside to hear for ourselves a little about metabolomics, Metabolon, and equilibrium.

Can you tell me a bit about the talk you gave yesterday?

The basis of the talk is that metabolomics ... is the only side of biochemistry in which you look for the totality of biochemical pool sizes. So, within any of us, at any given time, we have metabolic pools that are theoretically in equilibrium with all the other metabolic pools. If we are normal, that is if we are healthy, then there is an equilibrium between all of these pools, and the pool sizes are consistent.

By definition, when we get sick, those equilibria are disturbed in one way or another, and that disturbance manifests itself as either a pain or a lump or [another manifestation]. But there is a disturbance in the equilibria.

So we think that by looking at metabolomics, you are making a direct measurement on that equilibrium. One can do this on the level of the organism when one looks at plasma. One can do this at the level of a tissue when one looks at a biopsy. Or one can look at it in experimental situations in either animal tissues or in vitro-grown cells or [other samples].

We have yet to find a sample that it is not applicable to.

Have you partnered with pharma companies using this approach?

We’ve partnered with virtually all of the major pharmaceuticals.

What are they most interested in concerning your approach?

I think there’s a general interest, there’s a general understanding. Conceptually, metabolomics is easy to understand. Drugs have always dealt with biochemistry—they have always dealt with altering biochemistry, generally to return to a “normal state.” Most people, when you explain to them, understand that there is some sort of equilibrium, homeostasis, that we consider healthy.

Since most are acting biochemically, most pharmaceutical companies understand where we’re headed and realize that this is a unique way to understand physiology.

Are there any disease states that they show more interest in?

I think it’s absolutely universal.

Not concentrated — as in genomics, which focuses a lot on cardiovascular states and oncology?

No.

Are there parallels between the way metabolomics is evolving and the way other targeted medicine fields have progressed?

Let me pull that question back to a much earlier phase. And that is that, in a sense, we have taken a position that metabolomics is a technology that we need to get very, very good very, very fast. So we put all of our effort into that.

And I think that one of the reasons why our datasets are really looking pretty good is that we view it very much as the early days of DNA during the genomic revolution, in which we are learning to do the equivalent of sequencing. We’re learning to do — with high accuracy — the analysis of a very complex chemical mixture that is a cell.

That is where I would draw the analogy at this moment. We’re still learning to extract the information from the sample.

How many companies or entities are doing what you’re doing?

I think there are various approaches to it, but I don’t think anybody has taken as purely a biochemical approach as we are. I’m fundamentally a chemist, and we do believe that we can literally name everything we see, ultimately.

Because we think we can name everything we can see, we think we can put it into a biochemical context. That’s a very strong argument that I don’t think I’ve ever seen anybody else make.

A lot of the meeting attendees really liked your presentation. What is the first thing that they ask you about?

I think most people immediately want to apply it to a problem that is their pet problem. Virtually everybody has some issue that has been intractable that they have always wanted to find a way of getting a solution to.

People invariably discuss their own research. It’s amazing how fast the conversations return to that.

How new is the technology?

The word “metabolomics” was actually formulated in 1999 — it showed up in press for the first time. The year 2000, there were 10 publications that used the word. In the year 2001, there were 15 or 18.

It’s a very new concept. It sort of evolved out of the concept of biochemical profiling, in which there would be no nomenclature, there would be no naming of most things — it was really sort of a pattern-matching exercise. One would look at spectra and match patterns.

Metabolomics has evolved within the last five years, primarily due to advances in mass spectroscopy and informatics.

Are there marked examples of ways metabolomics has been used, especially by drug makers?

We think our early work in Lou Gehrig’s disease, or ALS, has been very indicative of the potential to work with human populations. There will be an announcement on Thursday [that] will be a major clinical announcement.

In in vitro situations in which we are either looking at biological fluids [or] we’re examining larger aspects of the organism, or in vitro solutions that are very experimental.

We’ve been doing a lot of work in experimental animals, so we find most of the things we’re working on right now are in the areas of discovery, as opposed to the clinical arena. We think ultimately that the applications in the clinical arena will be significant.

The entrance to the clinical arena is probably more economic, in the sense that by the time you have a drug that you have invested three to four years in getting to your Phase 1 clinical trial, and you’ve invested close to $100 million by that time, you probably don’t want any new technology that can possibly gum anything up. So at the moment, we don’t get quite the same reception.

How long will it take for that to change?

I think ultimately the FDA will probably require it.

What sort of interest has the FDA shown in metabolomics?

The FDA has sponsored conferences, and continues to sponsor conferences to look at the potential in metabolomics.

The NIH actually has considered metabolomics to be in the [NIH Director] Elias Zerhouni’s roadmap [to accelerate medical discovery]. His number-three aspiration, during his tenure, ... is metabolomics. So the NIH, I think, [has] a tremendous amount of interest in its potential.

Where else do you see interest coming from?

I believe that ultimately, this will be extremely useful in healthcare in the larger sense, that is, prevention. So that one will be able to see very early on these imbalances as they are occurring. And one may use this to prevent disease.

I also believe that it will never be economically viable, but its utility in the nutrition sciences would be phenomenal.

Is it too early for you to have had any interaction with payors?

We have not. There have been some attempts, but to be honest, they were short-lived.

I assume you are still developing your platform?

Our platform is fully developed. This is the third- or fourth-generation platform, and it’s fully developed.

We are generating quantitative data that is high quality — it’s robust and generally very good.

How old is Metabolon?

Metabolon is 18 months old. In 18 months, we’ve gone from a small company to a still-small company [with about 17 employees]. But we’ve grown tremendously — we’ve been able to attract significant clientele in a number of different areas.

You must have partnered with a mass-spec company to produce your platform, correct?

We actually haven’t. There is no partnership with a mass-spec company.

What we’ve done is, we’ve taken specific machines, and modified them to fit our needs. So, it is our ability to take those machines and modify the output streams to work for us — it’s really an informatics problem more than it is anything else.

 

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