By Kim Coghill
ARLINGTON, Va. - The Human Genome Project holds a promise for understanding the heredity contribution for nearly all diseases, said Francis Collins, director of the NIH's National Human Genome Research Institute in Bethesda, Md.
Collins, among other speakers Thursday at the Second Annual National Congress on the Future of Genomics, Biotechnology and Pharmaceuticals in Medical Care, addressed the highly publicized Human Genome Project and how its outcomes will impact the future of medicine.
"Virtually any disease except trauma will have some hereditary contribution if you look hard enough," Collins said. "Even an infectious disease like AIDS has some genetic contributors that have an effect on whether you become ill after exposure to a particular viral or bacterial agent. So whatever disease you are interested in unraveling, genetics offers a very powerful set of tools to peer into the most primary basis of what is going on in that condition."
The international Human Genome Project was initiated 10 years ago and to date has "achieved all of its milestones on or ahead of schedule," Collins said. "The ultimate goal of genomics is to develop therapies that you couldn't have with another strategy."
The Human Genome Project has a goal of producing a complete sequence without gaps and a 99.99 percent accuracy by 2003. It also expects to have discovered 1 million single nucleotide polymorphisms (SNPs) - human genetic variations - by the end of the year.
In June, Rockville, Md.-based Celera Genomics finished the first assembly of the human genome, having sequenced 99 percent of it, while the Human Genome Project assembled a working draft of the genome's sequence. The accomplishments mean the two research groups know the location and order of the letters of genetic code along the chromosomes, but they don't yet know the function of specific genes. (See BioWorld Today, June 27, 2000.)
The project has confirmed by evidence 38,000 predicted genes. Estimates of how many genes there are range widely, from around that amount to several times as many. Researchers continue to concentrate on discovering which genes cause disease and developing therapies to treat genetic diseases such as heart disease and cancer.
"There will be discoveries made, but it will be a long time in coming before those results translate into medicine," said William Haseltine, chairman and CEO of Human Genome Sciences Inc., of Rockville, Md. Haseltine, also a conference speaker, addressed "Turning the Knowledge of the Human Genome Into Effective Therapeutic Advances."
"For the most part, they once again address the question of why," he said. "We have genetic predispositions, but what can we do to treat those diseases? Those are very different questions. We know 1,000 causes, we maybe know 10 cures."
Haseltine's company focuses most of its drug discovery efforts on the human genes that produce substances - signaling, or secreted, proteins - that control the behavior of human organs and cells.
"The question now before us is no longer what are the genes, but what do the genes do that have a practical medical consequence," Haseltine said.
In 1993-94, Human Genome Sciences and SmithKline Beecham plc, of London, collaborated on a drug for osteoporosis. "We asked a series of anatomical questions," Haseltine said. "Where is the gene located? What is its relative abundance? Is it like anything we've seen before? What does it do in the body?"
He said the approach was not based on genetic differences, but "based on an intelligent hypothesis of how the anatomy of a gene, the physical substance of a gene, ,relates to normal physiology which can improve the medical outcome."
Discoveries Will Lead To Intervention
Based on technology available today, Collins said if you asked him whether you were at risk for Alzheimer's, he likely could tell you. "No one is very interested in knowing that for obvious reasons. The diagnoses in the future will be most useful if there is an intervention."
But during the next 10 to 30 years, Collins predicted that genetic testing will be available for up to 10 to 12 conditions and there will be interventions available to reduce the risks.
By the year 2010, Collins said that primary care providers driven by the availability of genetic tests and patients interested in receiving that information should find that they are starting to practice genetic medicine. "We will have to work hard to prepare them for that because most will have not had any formal training in this field, and that is a major agenda item that we are pursuing right now."
For example, Collins said pre-implantation diagnosis, which will allow anyone to choose embryos that are free of genetic disorders, will undoubtedly expand in its availability. "People will begin to consider using this not only for severe diseases, but for milder and milder conditions. That is part of the debate about the appropriate limits about this kind of technology."
In the year 2020, Collins predicted that technology being developed today will enable scientists to develop gene-based designer drugs that will enter the market for a long list of diseases. "Others may say the 2020 prediction is too conservative, and I certainly hope so."