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Haseltine Gets Down and Dirty with Biology

William Haseltine is a party pooper.  

While others are celebrating the near completion of a working draft of the human genome, Haseltine, chairman and CEO of Human Genome Sciences (Nasdaq: HGSI) dismissed the accomplishment as more conceptual than scientific. 

“The human genome, from my point of you,” said Haseltine, “is not useful for medicine.” 

It is this view, in part, that three years ago drove a rift between Haseltine and Craig Venter, the iconoclastic researcher who spearheaded the private-public race to sequence the human genome. The two had teamed up in 1992—HGS was the exclusive commercial beneficiary of Venter’s not-for-profit Institute for Genomic Research, with a first crack at practical applications of TIGR’s research.

Their differences were not purely scientific. They also disagreed on where genomics is headed as a business. 

Haseltine, 55, was trained by James “Double Helix” Watson and had by the 1980s achieved a reputation as a brilliant Harvard AIDS researcher.   He has founded seven companies since 1981, each in a different are of medicine.

He also has a reputation as an extravagant art collector and of living the high-life. The medieval and renaissance art adorning the walls of HGS headquarters in Rockville, Md., exude the sense that the work done here transcends all else.  

In 1991 he married socialite Gayle Hayman, a George Balanchine-trained ballet dancer and cosmetic entrepreneur of Giorgio of Beverly Hills and Giorgio perfume fame.   Together they hosted glamorous dinner parties for celebrities and corporate moguls.  

Venter too was at the threshold of fame and fortune, but had a different vision.

Both were interested in mining the human genome for commercial value. Venter wanted to sequence the genome. But Haseltine wanted to start a pharmaceutical company. 

Venter, fond of referring to his company Celera as the Bloomberg of genomics, positions his company as a dot-com-age information-provider. The company, which gave the public sequencing project a run for its money, now lures subscribers to its annotated sequence databases. 

Haseltine, however, insists that the tools and service businesses will eventually burn themselves out. 

“It’s very, very simple,” he said in an interview with GenomeWeb. “If you’re selling tools or selling services, yes, you can have a business. Yes, it can be successful. No, it cannot have, over a long time, a high growth multiple. So, I would say 90 percent of the businesses that call themselves genomic—even more than that—are in a low, long-term growth sector.” 

And despite analyst predictions that genomics companies will need to enlist the marketing prowess and sales force of big pharmaceutical companies to bring products to the consumer, Haseltine is not satisfied with the paltry pittance royalties provide.  

He has bigger plans than that. “Our goal from the day I became involved, which is the day this company actually got its structure, was to become a global pharmaceutical company that manufactures and sells the products we discover,” he said. 

The only big pharma partnerships HGS is interested in, he said, are those in which profits are split right down the middle. 

“We’re in the pharmaceutical sector because that’s where the money is,” said Haseltine. 

So far HGS is one of only two companies with genomics-derived products in clinical trials. Amgen is the other.

These HGS drugs include epithelial-cell promoter Repifermin, also known as Keratinocyte Growth Factor-2, and Mirostipen, or Myeloid Progenitor Inhibitory Factor (MPIF), a human protein that may reduce the toxic effect of anti-cancer treatments on blood-forming tissues in bone marrow. 

The drugs are proteins, notoriously unstable molecules that need to be administered through injection, making them difficult to use as drugs.

But through its acquisition of Principia Pharmaceuticals for $120 million in stocks last week, HGS has gotten a hold of a technology that allows protein drugs to remain in the bloodstream for several days.

Yet unlike many in the sector, Haseltine shuns the hype of pharmacogenomics, or personalized drugs, referring to it as “a limited form of mass hysteria.” 

Nevertheless, the current buzz in genomics is about genetic differences. Genetic differences will tell us who is predisposed to disease and perhaps suggest lifestyle changes aimed at prevention.

Genetic differences, or genotyping, will also usher in a new age of diagnostics. And companies such as Sequenom (Nasdaq: SQNM), Orchid (Nasdaq: ORCH), and Third Wave among many others are counting on the idea that miniscule genetic differences—SNPs, or single nucleotide changes in a single gene—will be the key to understanding and treating disease.

Instrument providers are also jumping into the market, with several toolmakers envisioning genomic diagnostic tools small enough to use in a doctor’s office. 

Once again, Haseltine is the party pooper.  

“First of all, nobody can afford to develop ten drugs for the same disease,” he said. The regulatory pathway for each is too complex, too long, and too costly.  

Secondly, “this concept, which is so prevelant in genomics, is deeply flawed and off-center and isn’t where genomics makes its contribution,” he said. “Humans, after all, are more similar than they are different.” He therefore favors one drug for one disease for all people. 

For instance, insulin from one individual’s gene is used for everybody; a growth hormone from one individual’s gene is used for everybody. “We are made from totally interchangeable parts.”  

So instead, Haseltine views genes as simply a part of the human anatomy—much like the heart, lungs, or a single cell. HGS studies these genes as physiological components of biological pathways and seeks drugs that intervene or enhance these pathways. 

And although he uses sophisticated computer algorithms in seeking out these drugs, Haseltine challenges computer scientists who believe that bioinformatics will replace traditional biology.

Bioinformatics can guide you in the right direction, said Haseltine. But “because biology has happened by completely random natural selection, it is not a predictable system,” he said. So ultimately you need to enter the wet world of experiments. “You have to get down and dirty with biology.”


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