Science Highlights-2000 February 2001 (Continuing the series of annual reviews, with slightly different titles, starting with 1995) Genome Mapping: Last year's explosive progress in identifying individual human genes and their mutations is causing a profound change in the science of medicine, from "diagnosis" to "risk prediction", where even prospective parents may learn before conception of risks to their offspring. Gene mutations arise either spontaneously or by inheritance. The "parkin" gene is now firmly associated with a rare form of PD (CSRs AUG, SEP), and I expect shortly we'll have similar warnings for many if not all autogenic disorders, and a political storm over the ethics of such warnings. Drugs: The atypical neuroleptic clozapine is useful against psychoses (e.g., hallucinations), in PD because it doesn't worsen motor symptoms, but users must be monitored for liver damage. And now, it seems to incur a risk of heart damage as well. The search for a substitute continues to dissappoint (JAN, NOV). Recent trials of the COMT inhibitor tolcapone (Tasmar), which also was restricted because of rare but serious liver damage, seem to indicate an attempt to restore confidence (MAR, JUN). Pig cell transplants: Despite encouraging trials and no instance of retroviral infection, the debate over safety continues. At least one firm plans to breed certified pigs as a source of graft tissue, and ethical questions also are being raised. (APR, MAY, NOV) Smoking appears to be genuinely protective against PD, but only in subjects having the right genetic makeup (NOV). Coffee also is neuroprotective (JUN, JUL, DEC). Early diagnosis of PD (before appearance of motor symptoms) or its latent risk may be possible by means of various scanning techniques using MRI or SPECT (JUL, SEP, OCT, DEC). Pallidotomy was shown by controlled trials to be safe and effective, but benefits fade after a few years (OCT). PD is more than loss of dopamine cells in the substantia nigra; it definitely includes several types of cognitive impairment, and neurotransmitters other than dopamine (DEC). Although known to be valuable for nerve regeneration, GDNF failed in its first human trial because it didn't reach the desired site in the brain. But the makers are trying again, (in monkeys) with a retroviral mode of delivery (DEC). Quibble: As a hallmark of PD, Lewy bodies are often discussed in symposia and seminars, where my confidence in the speaker's acuity is routinely destroyed when he calls them "Louie" (as in the pop song "Louie, Louie") bodies. Please! The name "Lewy" is properly pronounced "lay'-vhee". Cheers, Joe -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013