What have been the most important developments in biotechnology over the last quarter-century? If you ask 29 experts, as I did for this article, you're sure to get 29 different answers.
The first thing that struck me about the responders was their optimism. Although it's tempting to present the views of this many experts in terms of "boom" and "bust," most experts preferred to accentuate the positive. Among those who mentioned failures, almost every one was qualified with something along the lines of "but it may be too early to tell."
Optimism in biotech is nothing short of amazing given, as Andy Strayer, Pharm.D., vp for clinical operations at PPD (www.ppdi.com), notes, only one in ten biotech companies is profitable. But while the failures have been many and prominent, the perception is that success far outweighs failure.
Admittedly, that generalization is difficult to prove. Biobusiness' boom and bust cycles more or less track parallel peaks and troughs for biology itself, which has generated dozens of technologies that are gorgeous in concept, but exasperating in their commercial realization. Remember antisense?
John Thompson, senior vp of corporate development at Invitrogen (www.invitrogen.com), describes the last 25 years in biotech as "a time of dynamic growth and unparalleled discovery," particularly in the fundamental understanding of how life works through such agents as DNA, genes, proteins, and cells.
The Scientific American special issue on biotechnology in 1980, and the March 1980 Time cover story on interferon caused Crawford Brown, Ph.D., CEO of Eden Biodesign (www.edenbiodesign. com), to change academic course from chemical engineering to microbiology. During these 25 years Dr. Brown notes that biotech's "sky-high" hopes to cure cancer (not to mention the common cold) are still elusive.
"Even today, as noted in the joint Financial Times/Scientific American supplement on stem cells distributed during the BIO meeting, that cycle of hype and hope continues." Although Dr. Brown believes that many of the promises of stem cell research are likely "false hopes," he predicts that "real medical and economic benefits" will come, but they could take decades.
Not everyone is so pessimistic. Michael Goldberg, general partner with Mohr Davidow Ventures (Menlo Park, CA), quotes Nobel prizewinning Prof. Paul Berg (Stanford): "Human embryonic stem cells will have a greater impact on human medicine and reduction of suffering than recombinant DNA."
Goldberg notes that Geron (www.geron.com) will soon begin clinical trials of the first human embryonic stem cell therapy, based on the work of Hans Keirstead, Ph.D., a neurobiologist at the University of California (Irvine).
Interleukin-2, which Fortune featured on its cover in 1985, was touted as "the next interferon" and a possible cancer cure but, according to Goldberg, was "a giant bust." He believes that gene therapy may be heading down the same road of long-on-promise, short on results.
Mario Elhers, M.D., Ph.D., CMO at Pacific Biometrics (www. pacbio.com), weighed in with several observations. What's in, he says, are pharmacogenomics, biomarkers, companion diagnostics, blockbuster protein drugs, theranostics, fully humanized monoclonal antibodies, RNAi, protein therapeutics, and structure-guided drug design. What's out: antisense, gene therapy, ex vivo cell therapies, cancer vaccines, high throughput screening against non-validated drug targets.
What's passed: "The era of every university professor with an idea getting $10 million to start a new biotech company. Also gone from the scene are prominent startup IPOs, naive biotech investors, and innovative early-stage R&D within big pharma."
According to Ivor Royston, M.D., Forward Ventures (San Diego), "The most significant change in biotechnology over the past 25 years has been the shift from the era of gene discovery and cloning to an era of functional genomics and systems biology."
Dr. Royston explains that in the late 1970s and early 1980s, biotechnology's major breakthrough was recombinant DNA, which led to replacement treatments like EPO, G-CSF, insulin, and human growth hormone. Today's blockbuster bio-drugs, which represent a greater understanding of biochemical disease pathways, include Gleevec, Tarceva, Avastin, Herceptin, Erbitux, and Rituxan.
"Gene-based medicine is the biggest change in biotech," says Ron Woznow, Ph.D., president of the Canadian Gene Cure Foundation (Vancouver, BC).
"Biotech is more focused today on developing healthcare products and services rather than new platform technologies. However, the transition to gene-based medicine, which depends on these innovations, will be delayed by social, legal, and ethical issues relating to privacy and who should benefit from the exploitation of the human genome."
"When they were discovered in 1975, monoclonal antibodies (Mabs) were a promising scientific tool but impractical therapies," observes Alejandro Aruffo, Ph.D., vp of global pharmaceutical development at the Abbott Bioresearch Center (www.abbott.com). "Now these agents are changing millions of lives."
Mabs, according to Dr. Aruffo, offer the best hope for patients with cancer, autoimmune diseases, and cardiovascular disease, as well as for new or emerging diseases like SARS, HIV, and other infectious diseases.
The most significant change for David Hale, president of CancerVax (www.cancervax.com), is the emergence of targeted therapeutics. "Just look at how we treat cancer today, by pumping the patient full of toxins. The approval of monoclonal antibodies like Herceptin and Rituxan in the 90s and the more recent approval of kinase inhibitors, such as Gleevec and Tarceva, have launched a specifically targeted attack on cancer.
"From cancer vaccines like Provenge and Canvaxin to angiogenesis drugs that starve tumors, the biotech industry is showing no signs of slowing down."
Our experts' views on genomics were mixed. Nate Lakey, CEO at Orion Genomics (www.oriongenomics.com), muses that it's still an open question if the gene-to-target model presumed to operate in the post-genomics age will generate the anticipated numbers of new drugs.
Many firms whose business models were based on DNA sequences as a means of uncovering drug targets to find novel drug classes have changed their businesses. Some are now diagnostics companies, while others have licensed molecules or purchased companies outright. "These firms were forced to become product companies," he adds.
Lakey also thinks the promise of cDNA sequencing (expressed sequencing tags) was not met. "ESTs underrepresent genes in genome by about 50%," he says, "and it's the wrong half as far as new drug discovery is concerned."
Not everyone is down on the genome, though. One consequence of human gene sequencing is expected to be personalized medicine and "targeted" therapies (which include a molecular diagnostic). The question is: Can the cost structure of pharmaceutical development and manufacturing support this idea? Some people think so.
"Across several disease areas, there is a great need for targeted therapeutics for patient subsets," stated Stuart Peltz, Ph.D., president and CEO of PTC Therapeutics (www.ptcbio.com).