By David N. Leff

Editor¿s note: Science Scan is a roundup of recently published biotechnology-relevant research.

Malignant melanoma represents only 5 percent of all skin cancers in the U.S., but it accounts for 75 percent of all deaths ¿ some 6,900 a year, and counting. In recent years, 25,000 new cases occur annually. In white males, the reported incidence of melanoma rose 124 percent between 1973 and 1991. This rate of increase leads all other cancers, including lung cancer in women.

Melanoma¿s prime risk factor appears to be sunshine beating on susceptible skin surfaces, perhaps aggravated by depletion of the protective ozone layer in the atmosphere. The most reliable treatment to date is surgical removal of suspected melanotic skin blemishes before they have time to strike inward, via bloodstream and lymph channels, to metastasize lethally in visceral organs. Chemotherapy and immunotherapies (e.g., interleukin-2) are under clinical study, as are vaccines against melanoma antigens, but so far the disease seems to be winning.

¿Advanced melanoma,¿ reports a paper in the current Proceedings of the National Academy of Sciences (PNAS) dated Nov. 23, 1999, ¿remains a prime example of poor treatment response that may, in part, be the consequence of activated N-Ras oncoproteins.¿ The PNAS article, authored by research dermatologists at the University of Vienna, Austria, bears the title: ¿Novel Ras antagonist blocks human melanoma growth.¿

The Ras protein is expressed by the ras oncogene, which is abnormal in 25 percent of human cancers. When normal, it regulates multiple signaling pathways that control cell division; aberrant, it signals cells to go on dividing indefinitely. The Viennese co-authors speculated that ¿a pharmacological approach that curtails Ras activity may present a sensible approach to inhibit melanoma growth.¿

They tested this concept by pitting a recently discovered antagonist of Ras against human melanoma cells in SCID mice. The antagonist, code-named FTS, dislodges Ras from its membrane-anchoring sites on malignant cells, thus blocking its signaling and transforming effects. The team¿s results showed reduction of activated Ras protein in those tumor cells, which inhibited their growth. ¿Our findings,¿ the paper concluded, ¿stress the notion that FTS may qualify as a novel and rational treatment approach for human melanoma and possibly other tumors that either carry activated ras genes or rely on Ras signal transduction more heavily than nonmalignant cells.¿

Chickens Are Closer To People Genomically Than The Mice That Model Human Diseases

At the zoo, you¿ll find the birds and beasts housed and exhibited, as in Noah¿s ark, ¿after their kind.¿ That is, elephants here, reptiles there, monkeys elsewhere, and so on. But there¿s no one place that groups the various life forms that populate the major animal models of laboratory research. Their cage labels would read:

¿ Fruit fly (Drosophila melanogaster);

¿ Round worm (Caenorhabditis elegans);

¿ Zebrafish (Brachydanio rerio);

¿ African clawed toad (Xenopus laevis);

¿ Mouse (Mus musculus);

¿ Rat (Rattus rattus);

¿ Chick (Gallus domesticus);

¿ Human (Homo sapiens).

Of all these critters, the main workhorse, of course, is Mus musculus ¿ the mouse. This compliant animal pinch-hits for every human disorder from cancer to schizophrenia. Now it turns out that of all the above-listed stand-in biological specimens, one comes closer to the human genome than does the mouse. A research report in Nature dated Nov. 25, 1999, intimates that people may have more in common with chickens than with mice. It¿s titled: ¿The dynamics of chromosome evolution in birds and mammals.¿ Is authors are molecular geneticists at Scotland¿s Roslin Institute, which gave the world Dolly, the cloned sheep.

The authors mapped the large-scale organization of the domestic chicken¿s genome, and found that its chromosomal organization shares more features with H. sapiens than does the mouse. All three life forms descend from a common ancestor that lived around 300 million years ago. Then the rodent genome began evolving much faster than the lineages leading to people and chickens. Mice diverged from humans 100 million years ago.

The co-authors conclude: ¿Now we can start to use comparative gene maps derived from selected species for the systematic reconstruction of ancestral vertebrate genomes.¿

To Invade Target Cells, HIV Relies On Two Human Co-Conspirators In Inside Job

Like a convict snatching a prison guard¿s keys through the bars, the AIDS virus has hijacked a human protein to force its way into target cells it aims at infecting. That protein, cyclophilin A ¿ ubiquitous in eukaryotic cells ¿ has been known as a co-conspirator in HIV¿s assault on the human cells, but its role in the attack was unclear.

Now an article in the fortnightly journal EMBO, dated Dec. 1, 1999, and published by the European Molecular Biology Organization, reports that HIV-1 co-opts cyclophilin A from cells at the time it buds, then flaunts the protein on its surface. Thus exposed, the human bull¿s eye lets the virus grab onto the surface of the human cells it has in its cross hairs ¿ with the help of heparin, a human carbohydrate.

The EMBO paper is titled ¿Host cyclophilin A mediates HIV attachment to target cells via heparins.¿ Its authors are scientists at the Scripps Research Institute in La Jolla, Calif. The paper¿s senior author, Phillipe Gallay, pointed out, ¿To date, the only protein on the surface of HIV-1 known to mediate HIV-1 entry, the HIV-1 envelope protein (gp120/41), is derived from the viral genome. We are particularly excited about this finding because cyclophilin A is not encoded by the viral genome, and thus cannot directly mutate in response to antiviral selective pressure, unlike the virus¿s own envelope protein.¿