By Randall Osborne

SAN FRANCISCO ¿ Despite a broad lack of knowledge, biotechnology¿s bid to tailor drugs according to patients¿ genetic distinctions is making strides, said Peter Barrett, executive vice president and chief business officer of Celera Genomics Corp., of Rockville, Md.

¿We don¿t have time to [advance pharmacogenomics] in a systematic way,¿ Barrett told an audience at Allicense 99, a partnering conference here. ¿Medicine won¿t wait.¿

That¿s why so many companies have undertaken ¿parallel efforts to find clues¿ that link genetics, disease and drug response, he added.

¿We don¿t even know how many genes there are,¿ Barrett said, noting the estimates range from 50,000 to 150,000, and the relation of genes to specific diseases is hardly solid.

¿There are several hundred correlations known, but we also know that most of these diseases are caused by multiple genes, working in sequence or in concert,¿ he said. ¿So, while a lot of people want to quickly move to the post-genomics area, there¿s really a very limited understanding today of the base of our human genome.¿

Barrett spoke in a session on pharmacogenomics, which also included Elliott Sigal, vice president of applied genomics at Bristol-Myers Squibb Pharmaceutical Research Institute, of Princeton, N.J.

Sigal said Bristol-Myers finds pharmacogenomics¿ strongest potential in oncology, where ¿we have good patient, physician and market acceptance for pairing biomarkers with clinical response. Certainly, the estrogen receptors are one example, even before Herceptin,¿ the breast-cancer drug from South San Francisco-based Genentech Inc.

Herceptin, Sigal said, is a good example of ¿pairing an FDA-approved diagnostic with a therapeutic response, targeting a subsegment of a market that otherwise didn¿t exist, and then spreading out where that antibody is expressed in other tumors, and picking up other markets.¿

In an industry in which companies must put at least three new chemical entities on the market each year in order to thrive, genomics technologies clear the way, Sigal said. They are being used to ¿kill [drugs that don¿t work] early, before you get into the expensive trials.¿ They¿re also valuable ¿within clinical trials to minimize side effects and maximize efficacy, and later on in the life-cycle management, to differentiate and look for new indications,¿ he said.

Experiments with complete genetic information in other organisms are yielding results, Sigal said.

¿Of the 100 positionally cloned disease genes, 60 to 80 percent of them are represented in either yeast, worms or flies, and that percentage is likely to increase,¿ Sigal said, noting an example of pharmacogenomics in worms, as examined under a microscope.

¿You can touch the nose of a worm, and it withdraws,¿ he said. ¿If you give the worm Prozac, it¿s a happy worm, and doesn¿t withdraw. What you can do is take a colony of carefully mutated worms, and find which worms in high-throughput screening are resistant to that touch of the nose.¿

From this point, scientists may ¿rapidly isolate a pathway that confers drug resistance,¿ which then leads, in some cases, to novel targets or insights regarding the side effects of drugs, Sigal said.

Efforts Will Result In Drug Tailoring

Maria Friere, director of the office of technology of the National Institutes of Health in Bethesda, Md., introduced panel members in the session.

She said she envisions a day, 30 years from now, when patients will have chips implanted in their heads that carry their genetic information, so that when they arrive for treatment of a condition, a drug can be devised that fits the cause of disease and the afflicted person.

¿It¿s a cocktail, done immediately, based on the genetic information that has just been extracted, and here we are,¿ she said. ¿We¿re able to perform a miracle ¿ maximize the ability of the patient to get well and maximize the death of the critter [microorganism].¿

Sigal said genomics¿ march toward that goal is helped by such projects as the recently disclosed SNPs consortium, a $45 million effort to map single-nucleotide polymorphisms, which will become freely available to the public. (See BioWorld Today, April 16, 1999, p. 1.)

¿Altruism isn¿t the same thing as win-win,¿ Sigal said. ¿We have a vested interest in seeing this field accelerated, in having a reference genetic map out there that can be experimented upon, and can be leveraged by scientists to discover new predisposition clues, and we all can figure out how to work on this in the regulatory environment.¿

The Allicense conference, sponsored by San Francisco-based Recombinant Capital, concluded Wednesday, and drew more than 300 attendees. n