Sponsored by the U.S. Department of Energy Human Genome Program
Human Genome News Archive Edition
Human Genome News, November 1990; 2(4)
A group of prominent scientists met with pharmaceutical industry representatives to discuss the Human Genome Project's impact on health care at a September 30 satellite meeting to Genome Sequencing Conference II. The meeting was convened to:
In his opening remarks, Mark Pearson (E. I. du Pont de Nemours and Company) said that mapping genes and other markers leads to identification of disease loci; sequencing DNA identifies drug targets; and knowledge of molecular mechanisms allows rational design of a new generation of therapeutics.
J. Craig Venter (NIH National Institute of Neurological Disorders and Stroke) pointed out that the 50,000-100,000 genes to be identified by the Human Genome Project are potential targets for pharmacological intervention. The drug industry will therefore be the first group to begin applications-oriented interpretation of genome data.
In generating this data, the Human Genome Project is continuing the basic biological research agenda started in the 1940s of understanding function by studying structure. Technical advances are making possible the complete molecular dissection of genes so that their functions and interactions can be clarified, noted Robert Cook-Deegan.
The genome project is now considered to be feasible because of the development of and improvements in sequencing technologies, recombinant DNA techniques, restriction fragment length polymorphism mapping methodologies, and the polymerase chain reaction. Walter Gilbert (Harvard University) pointed out that published DNA sequence (human and nonhuman) has been increasing annually by 60% since 1975. At that rate, he predicted, an amount equivalent to a human genome will be sequenced by the year 2000.
Francis Collins (University of Michigan) noted that deducing the origins of some single-gene diseases required years of work. The underlying causes of multigenic diseases-such as heart disease, diabetes, high blood pressure, and cancer-will be even more difficult to decipher. Genome project data, he asserted, will lead scientists to an understanding of the etiologies of these diseases. The pharmaceutical industry, by applying these data, can play a major role in alleviating the effects of these multigenic diseases or in eradicating them.
Scientists present agreed that the Human Genome Project will revolutionize the study of medicine and stimulate the creation of the next generation of drug therapies. Pearson suggested that new modalities, including viruses and structural elements that recognize precise cell surfaces, could be used to target drugs to disease-affected tissues without affecting the rest of the body.
Drug therapies currently are far less than 100% effective, in part because of individual genetic differences; sequence data will elucidate these variations to allow improved precision in the design of drugs and drug trials and in the prescription of therapeutics. Gilbert said that patient response to drug therapies would be predictable and that side effects could be anticipated and minimized.
Michael Hogan (Triplex Pharmaceuticals) noted that some members of the industry are demonstrating that it will be possible to proceed directly from DNA sequence data to pharmaceutical development without waiting until the end of the genome project. In a revolutionary approach to drug design, information from project databases will allow the design of oligonucleotide drugs that directly bind to target DNA duplexes. Oligonucleotides would occupy the major groove in the target duplex and could modulate transcription of that region.
Leroy Hood (California Institute of Technology), Eric Lander (Massachusetts Institute of Technology), Gilbert, and Pearson spoke of using DNA sequence databases to predict 3-dimensional protein structure and function. A finite number of structural motifs (4000-10,000) based on sequence homologies are believed to dictate protein function; this information can be used to design therapeutics that work at the protein level, a traditional avenue of drug design.
A concern of attendees was that medical education in genetics lags far behind current knowledge. Delineating disease etiologies has evolved from an early emphasis on transmitted diseases to the current stress on diseases with origins in intermediary metabolism. Participants agreed that medical schools should teach future doctors about the genetic causes of disease.
Some researchers suggested that drug companies may be slow to apply information gained through the Human Genome Project to the introduction of new pharmaceuticals and other medical technologies. Large companies, they said, may be burdened by high costs, past successes, and an overpowering bureaucracy. Pearson stated that molecular genetics will provide tools for finding new drugs; he is optimistic that a cooperative atmosphere will flourish among industry leaders in this search. Others speculated that smaller, venture-capital firms may be first to apply genome project information to important applications in the health-care field. Gilbert stated that the pharmaceutical companies that apply the information first will produce the most benefits for themselves and for health care.
The meeting was sponsored by Parke-Davis Pharmaceutical Research Division of Warner Lambert and organized by Venter and Jack B. McConnell (retired Director of Research, Johnson & Johnson). Cochairs were Venter and Pearson. The meeting, which featured 7 speakers, was attended by nearly 70 pharmaceutical and genome project representatives.
Reported by Betty K. Mansfield
HGMIS, Oak Ridge National Laboratory
The electronic form of the newsletter may be cited in the following style:
Human Genome Program, U.S. Department of Energy, Human Genome News (v2n4).
The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.
Published from 1989 until 2002, this newsletter facilitated HGP communication, helped prevent duplication of research effort, and informed persons interested in genome research.