The future of proteomics

Bill Snyder
Published: February, 2003

Tony White
Applera’s Chairman and CEO
Among the scientists, business leaders and government officials who led the successful effort to sequence the human genome were two officials of Applera Corp., the parent company of the Applied Biosystems and Celera groups. Michael Hunkapiller, Ph.D., former president and general manager of Applied Biosystems, pioneered development of the automated machines that made it possible to unravel the human genetic code. Tony White, Applera’s chairman, president and CEO, was a guiding force behind the creation of Celera Genomics and its race with the publicly funded Human Genome Project.

In 2002, Lens magazine editor Bill Snyder interviewed White and Hunkapiller about the challenges facing the field of proteomics, the growing need for collaboration between government, universities and private companies, and the potential impact that the debate over stem-cell research may have on scientific progress.

Lens: What are the next advances that are about to happen? What will market and medicine look like in 10-15 years?

Hunkapiller: I think a lot of the drugs that are coming on the market now have come about because of a more thorough use of tools that allow in-depth analysis of the biology underlying the choice of targets and the choice of molecules that interact with those targets. I think we will see drugs coming to market at a more rapid pace.

What is clear is that when people are given drugs now, there tends to be a mix of beneficial effects for some people and harmful effect for others, and no effect at all for a third group of the population. One thing that will happen as we get a better understanding of all the biochemical pathways that may be impacted by a particular therapeutic compound, we can begin to do drug development in a way that maximizes the positive and minimizes the negative effects of some of those compounds. We will be able to target exactly the right disease-causing agent with the right drug as opposed to more of a hit and miss approach, which is what has somewhat characterized past efforts.

Understanding the underlying biology also can help us understand the preventive measures to take against disease. Most of the diseases that have a genetic underpinning also have a big interaction with the environment that can trigger those diseases. If we understand the underlying biology, we can begin to understand how to deal with preventive measures as well as the therapeutic ones.

Lens: Should there be a “big science” project to move the field along?

White: I certainly believe that with the exception of a situation where a research program might require a very large, centralized capital expenditure or capability, a decentralized research program is going to be better for everybody -- one like we have today, where the government provides grant money to the individual researcher at the laboratories, rather than bringing the money into one big centralized center. I’m not sure that would work very well.

These research programs tend to have a boss and whatever that boss thinks is the right science, is the only science that gets done, as opposed to under the grant mentality, where there are a lot of ideas coming up from different places. I think you get better science. You get more diversity and you get more for your money.

Lens: What challenges must be overcome to achieve the fruits of proteomics?

Michael W. Hunkapiller, Ph.D.
Hunkapiller: A lot of the technology efforts up until now have been to design systems that allow people to study an individual out of an entire population. The human genome project was to do that essentially.

One of the challenges now is to develop tools that go beyond just looking at the overall blueprint. Scientists now want to look at the individual differences among large populations of individuals to help identify changes that might lead to disease or to identify why some individuals remain healthy. The tools that are required to look at those differences across a large number of individuals are pretty substantial, as opposed to tools used to decipher the basic blueprint of life.

The main issue is reducing the cost of the technologies to a level that is affordable to perform these studies on a large number of people. The technologies that will allow large-scale studies are available, but they are currently somewhat cost prohibitive. I think the same issue applies to the proteomics industry.

On top of that, there is the challenge of making the technology cost effective to do a complex study of both protein structure and function in a broad survey sense, which has not been done yet. It requires development on the one hand, and invention on the other. Science and technology have a good way of playing off of each other, and coming up with solutions to these kinds of challenges.

Lens: If Congress, in an attempt to reduce the cost of pharmaceuticals, makes it easier for generic drugs to get to market, would this have an impact on drug discovery?

White: If you consider a complete cessation of all research and development an impact, I would agree.

I don’t see why a right-minded public company would spend anything on developing a drug if they weren’t going to be able to have patent protection around it. It costs a billion dollars or so to develop a drug. Most companies are not inclined to do that so that somebody can steal it from them.

As a matter of principle, patent protection in pharmaceutics is just as important as it is in any other commercial endeavor.

Lens: What are the barriers beyond the science – financial, political, and social?

Hunkapiller: I would certainly say that the stem cell issue and the ethics surrounding that could easily become one of the bigger obstacles to understanding how some of these biological systems work and, more importantly, figuring out ways of translating that knowledge into practical benefits.

It is one of the areas in which the potential for using a lot of this information in a pretty dramatic way to impact people’s health would seem to be pretty astounding, and I personally would hate to see the politics of that override the benefit of it.

White: I guess I’d put it another way. I think the stem cell debate was a very instructive one, in that you took a scientific initiative, and it was kidnapped by people with a different agenda. I’m not favoring either side. I’m simply saying that people with other social agendas try to insert themselves into science in fairly ignorant ways.

Cloning is another one. Leave it up to the people who want to alarm society, and who want to take their own agenda and insert it into the scientific debate, absent an educated public they’ll get away with it.

People need to be better informed about this science before they start talking. Unfortunately, that is not the way politicians typically work. They usually start talking and somewhere along the way they find out what they’re saying.

Hunkapiller: I’d add a second area where I think the complication of some of this knowledge has been put into a debate in which people with different agendas have captured the media attention as well, and that’s in the whole area of genetically modified food.

To some degree, one can understand the concern. I think that a lot of the companies that started to use the technology went about it not in an inappropriate manner, but they may have chosen the wrong first targets. The big seed companies that were also big herbicide companies tended to promote the use of the technology in a way that would foster their interest as opposed to highlighting the benefit for the public.

We can argue about whether we need corn that is resistant (to insects), but if we go to third-world countries where nutrition is a key to survival, having crops there that provide vitamins the population could not get otherwise is a pretty big deal. And people there, I think, would laugh at the arguments that go on in the U.S. and some countries in Europe.

I think is a disservice to the public at large to lump the less than stellar use of science with the cases where it is obviously beneficial. And I think that sometimes the media misses the distinction between those two things.

“One of the challenges now is to develop tools that go beyond just looking at the overall blueprint. Scientists now want to look at the individual differences among large populations of individuals to help identify changes that might lead to disease or to identify why some individuals remain healthy. The tools that are required to look at those differences across a large number of individuals are pretty substantial, as opposed to tools used to decipher the basic blueprint of life.”
Michael W. Hunkapiller, Ph.D.
Lens: Is collaboration between academia and industry important for the development of the field of proteomics and for drug development, and, if so, why?

White: It’s valuable. I think the key is that everybody has to know what they want to get out of the relationship, and if the relationship can be structured so both parties can accomplish what they want to accomplish, it’s a good thing.

Hunkapiller: It’s a tradeoff. The academic world has a mission to create new knowledge and make that available for other people to build upon. Companies have an imperative to increase value for their shareholders. Certainly where those missions are in concert, there is synergy between the two, and an opportunity for fruitful collaborations, such as when basic discoveries are developed into practical applications to help people.

Clearly one has to be mindful of the fact that there occasionally are conflicts in determining what are the goals. Mechanisms have to be in place to minimize those conflicts. But the university system is a source of a lot of basic knowledge that is applied towards practical applications. Congress recognized that a long time ago, by fostering within the biological area programs that push universities to get some of their basic discoveries into the commercial world.

Lens: There is growing concern that industry affiliation represents a potential financial conflict of interest for university-based researchers, one that threatens to jeopardize the public trust in their integrity and honesty. What do you do to avoid conflicts of interest, and ensure that industry-academic collaborations succeed?

Hunkapiller: We tend to do collaborations with universities during what I would call the pre-competitive development or the basic discovery stage in the technology field. We try to make sure through our relationships with academia that we have access to developing technologies. We do not tend to push for exclusive access because exclusivity, I think, can tilt over frequently into problems with the relationship.

It becomes trickier when one is dealing with later-stage development issues, and that can become a bigger challenge publicly in some of the drug development efforts. One just has to be very careful to make sure there is full disclosure, as to who pays for development costs and who reaps the benefits of those developments.

Lens: How can your company balance the need to keep stockholders happy with the need to do good science?

White: I don’t see the conflict. We have to do good science to stay in business, so I think the best thing we can do is make to sure we have informed shareholders. We spend lot of time communicating with them, trying to make sure they understand our strategy and our plans and the basis for our scientific endeavors. We spend a lot of money, a quarter of a billion dollars a year, on research and development. That is the nature of our business. If we didn’t do it and we didn’t do it very well, we wouldn’t last.

We chose to be in field that is technology intensive, and so we have a risk profile that is different than if we were developing the next generation farm tractor.

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