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This article was originally prepared for the online magazine TNTY Futures. Written by Daniel Drell (U.S. Department of Energy) and Anne Adamson (Oak Ridge National Laboratory), it speculates about how genetic advances sparked by the Human Genome Project may affect the practice of medicine in the next 20 years.

The first phase of the ambitious international effort to determine the entire sequence of the human chromosome set is virtually complete. Human Genome Project scientists plan to finish the human sequence by 2003, along with a database of the most common sequence variations that distinguish one person from another. This knowledge base, freely available to any interested person over the Internet, will revolutionize biology and medicine. But how? What will be different 20 years from now because the human genome was sequenced?

Only time will prove the accuracy of the following predictions, but here is a list of some effects we might expect in 2020.

More Effective Pharmaceuticals

A virtually complete list of human gene products will give us a vast repertoire of potential new drugs. From 500 or so drugs in 2000, at least six times this number will have been identified, tested, and commercialized in 2020. All will be manufactured by recombinant DNA technology so they will be "reagent-grade pure," just as human insulin and growth hormone are today.

Your medical record will include your complete genome as well as a catalogue of single base-pair variations that can be used to accurately predict your responses to certain drugs and environmental substances. This will permit you to be treated as a biochemical and genetic individual, thus making medical interventions more specific, precise, and successful. In addition, the increased power of medicine to predict susceptibility to specific diseases will allow you to alter your lifestyle to reduce the likelihood of developing such diseases or to be treated with preventive or disease-delaying medicine.

Treatment failures occasionally happen today with drugs for hepatitis C infections, antihypertensives, and certain anti-depressants (selective serotonin reuptake inhibitors like Prozac). In the next 15 to 20 years, more effective drugs will be developed, and doctors will test individual genetic profiles against panels of drugs available for a specific condition and choose the treatment with the greatest potential benefit.

Today, some 100,000 people die each year from adverse reactions to drugs, and millions of others must bear uncomfortable or even dangerous side effects. We see such current examples as heart-valve abnormalities from diet drugs, muscle damage from some hormone-regulating drugs, and nervous system effects with certain types of anti-depressant medications. As genes and other DNA sequences that influence drug response are identified, we can expect the number of toxic responses to drop dramatically and most side effects to be eliminated.

Societal Implications

Another consequence of greater knowledge about individual variation is more disturbing, and we may face some unpleasant consequences unless society makes some hard choices. These considerations include the likelihood that your medical information will be available to others not in the medical profession--your insurer or employer, perhaps. Employers may have a strong motive to learn about your risks of developing certain conditions and to avoid hiring you or restrict the kinds of work you may do.

Genetic Testing, Therapy

Although now plagued by technical difficulties, gene therapy for single-gene diseases will be routine and successful in 20 years. Certain aberrant disease-associated genes will be replaced with normally functioning versions, and several hundred diseases will be curable. Neonatal genetic testing for these treatable conditions will be routine.

Some of the mysteries of early embryonic development will be solved. We should know the timing of expression of most, perhaps all, of the human gene set. We may have learned how to direct differentiation so that a desired cell type or even relatively "simple" organs and parts of more complex organs can be grown for transplantation. In 2020, we will have made substantial progress towards true "cloning" of certain organs, but many difficult technical steps will remain before successful cloning of a heart or liver.

As genetic testing using DNA sequence becomes more common, less expensive, and more accurate, it will be used commonly and reliably in cases of mistaken identity, false or misattributed paternity, and the identification of missing persons. Misguided attempts to ascribe behavioral tendencies to a person's genes will cause many problems, not least for the courts that must resolve disputes when an individual's behavior and actions conflict with laws. Should society (via the courts) interpret behavior as a consequence of free will or as influenced by genetic constitution? At what point does society mitigate responsibility or punishment?

Understanding Life

On the brighter side, an inevitable consequence of the genome project will be a much greater understanding of fundamental biology. Already, some three dozen organisms (mostly one-celled microbes) have been completely sequenced. The fruit fly, the latest organism to be sequenced, is being used to model the essential features of human disorders such as Parkinson's, making possible a powerful genetic approach to garnering knowledge about diseases as well as to developing more effective treatments. In 2020, perhaps 1000 complete genomes will be in hand. Besides furnishing insights into evolution, this vast repertoire of new genes and their products can be explored for their potential in solving challenging problems such as environmental cleanup.

We will fitfully and slowly gain some insights into biological complexity. In 2020, we will know how to build a functioning cell capable of free-living existence. We will understand certain pathways used by this simplest cell, but there still will be unanswered questions about it. We will be virtually no closer than we are today to the mysteries of such true "emergent" properties as intelligence in complex multicellular organisms.

Challenges

So the Human Genome Project will have vast and largely positive impacts on people living in 2020. Of the various predictions noted above, the last two are the most profound because the most powerful and momentous impacts come from fundamental knowledge, usually in unforeseen ways. As this astonishing treasure trove is introduced into society, we need to be alert to challenges and misuses of the knowledge about ourselves. Society as a whole, not just genome scientists, must address these considerations. It has to be all of us. [Daniel Drell (DOE) and Anne Adamson (HGMIS)]

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