Companies customarily communicate a quarterly earningsreport to their shareholders and potential investors. Here isBioWorld's learning report, an overview of salient scientificadvances in biotechnology during the first quarter of 1993,keyed to reports in BioWorld:

Three areas of applied research -- cancer, neuroscience andAIDS -- led the field in January, February and March:


-- "Co-stimulation" was the buzzword in three separate journalreports describing a new strategy for enhancing killer T cellresponse to a tumor's own antigen. In Berkeley, Seattle andBoston, a genetically engineered protein, B7, supplied the extrakick in tumor-bearing mice.

-- Another T cell-boosting ploy, developed at Israel'sWeizmann Institute of Science, and just licensed to BaxterInternational, in effect transfers an antibody's tumor-huntingprowess to the cancer-killing T cells.

-- Instead of T cells, the National Cancer Institute's Ira Pastanengineered a bacterial toxin to destroy his murinemalignancies. He hitched this lethal payload to a monoclonalantibody specific for a tumor antigen, and is on the point ofstarting clinical trials.

-- NeoRx Corp. of Seattle coupled its tumor-targetingmonoclonals to cell-slaying radioactive isotopes. But to avoidthe "innocent bystander" effect that stray radiation will alsoslaughter healthy cells, the company announced a"pretargeting" tactic, whereby it injects the antibody first. Onlyafter this fully attaches to all available tumor cells does theisotope follow.

-- San Diego-based Agouron Pharmaceuticals Inc.'s protein-structure-based designer drugs essentially starve their tumortargets to death by inhibiting their synthesis of thymidylatesynthase, essential to cancer cell proliferation. FDA approvedhuman testing of one such compound, beginning in February.

-- Closer to root causes, histopathologist A. J., P. Klein-Szantosat Philadelphia's Fox-Chase Cancer Center discovered that, atleast in nude mice, a known carcinogen in tobacco smokewreaks a specific base-pair mutation in the gene for p53, aknown tumor-suppressing protein. This mutant acts as astrong, cancer-promoting oncogene.


As the quarter ended, two announcements thrilled the world ofneuroscience:

-- After a decade of false leads and futile failures, theHuntington's Disease Collaborative Research group announcedthat it has located the HD gene, on the tip of chromosome 4. Thegroup is headed by James Gusella of Massachusetts GeneralHospital, who in the early 1980s discovered the gene markersmaking it possible to predict susceptibility to HD.Simultaneously, Canadian researchers in Toronto andVancouver reported they had identified "a strong candidategene" for HD.

-- At the same time, again after 10 years of hard labor, aBritish team isolated the gene for human glial growth factor.This subtle protein blazes the trail for an embryo's advancingneuronal network, and sheaths the neurons on myelin.Cambridge NeuroScience Inc. took the British discovery,expressed the gene, and has begun to test it in rats.

-- Regeneron Pharmaceuticals announced March 30 that it hadbegun a large, pivotal Phase III clinical trial of its recombinanthuman ciliary neurotrophic factor to treat Lou Gehrig disease,amyotrophic lateral sclerosis (ALS).

-- A scant four weeks earlier, researchers at Boston'sMassachusetts General Hospital and Northwestern University inChicago reported that they have identified the putative genefor a familial form of ALS. Located on the long arm of humanchromosome 21, it encodes copper-zinc superoxide dismutase(SOD). This chemical generates free radicals that are suspectedof destroying motor neurons.

-- Smuggling pharmaceuticals past the blood-brain barrier intocerebral cells is a holy grail of neuroscientists. Now, amultinational task force, including Alkermes Inc. of Cambridge,Mass., reports that nerve growth factor, linked to a transferrin-receptor-specific antibody, and injected into the bloodstream,showed up in medial forebrain tissue, where it displayedbioactivity.

-- Other groups are using adenovirus expression vectors toferry genes across the blood-brain barrier, and encode theirprotein products in the central nervous system. Ronald Crystalof the National Heart, Lung and Blood Institute injected thevirus, carrying a gene for alpha-1-anti-trypsin into thecerebrospinal fluid of animals, and obtained secretion of theproduct in cells lining the brain ventricles.


A full-court press of research companies and institutions madeonly incremental progress toward therapies and prophylaxisfor Acquired Immune Deficiency Syndrome.

-- A prototype peptide AIDS vaccine, artificially synthesized byUnited Biomedical Inc. (UBI) of Hauppauge, N.Y., got FDA'sPhase I green light. It is the first of a growing gamut of suchvaccines, under development by numerous companies, to reachthe stage of human testing. UBI's prototype vaccine has eightpeptides from the V3 loop of the HIV envelope, a primary sitefor antibodies to neutralize the virus.

-- At the other extreme from artificial synthesis, TherionBiologics Inc. of Cambridge, Mass., is developing a Harvardresearcher's attenuated live-SIV (simian) virus for a humanAIDS vaccine. The SIV version protected six rhesus monkeysfor two years from infection challenge.

-- Scientists at Genelabs Technologies Inc. of Redwood City,Calif., have a patent-pending way of tracking previouslyundetected levels of HIV at every stage of infection. Theirtechnique claims to be 60,000 more sensitive than currentmethods in measuring a patient's viral load. Such levelscorrelate with stage of disease and efficacy of treatment.

-- Viral levels in HIV-positive patients with latent (pre-symptomatic) AIDS are higher in lymphoid tissues thanelsewhere in the body, said reports from the NIHImmunoregulation Laboratory. This means that anti-viraldrugs should be given before their helper T cell counts decline,and that other treatment strategies need re-thinking.


Over-arching these disease-oriented advances (and others toonumerous to mention) this past quarter are two signal stepstaken by the incoming Clinton administration, which willbenefit biotechnology science policy across the board:

-- As almost his first act in office, the new president lifted theban on fetal-tissue research on Jan. 22, two days after hisinauguration.

-- In naming Jack Gibbons, until now director of theCongressional Office of Technology Assessment, to be hisscience adviser, President Clinton has done the biotechnologyindustry a very good turn, according to a range of opinions. Forexample, Bill Small, director of the Association of BiotechnologyCompanies said, "Jack Gibbons is a very smart guy, and I thinkhe's going to be a terrific asset to the (biotechnology) industry."

(c) 1997 American Health Consultants. All rights reserved.

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