By David N. Leff

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

Did Columbus and his men inflict syphilis on the native Americans they encountered in 1492? Or did his crew catch the infection from the New World tribes they met, and bring it back to the Old World?

This question has been exercising historians and epidemiologists for half a millennium. Until recent decades produced genomic and molecular methods of identifying ancient diseases, they have had to rely on the time-honored method of examining long-gone cadaveric remains.

A 29-page, 10-article section in Science, dated May 11, 2001, on the ecology and evolution of infection, recalls: ?Until the 1980s, the only way to study the rise of diseases was to plumb the past for ancient clues. Historians parsed tantalizing passages in ancient texts such as the Bible or The History of the Peloponnesian War. Archeologists inspected skeletons for lesions and other signs of disease. Since then, researchers have figured out how to isolate ancient pathogens; recently they retrieved pathogens from Egyptian mummies and victims of the 1918 Spanish flu epidemic. And last November, French researchers reported that they had recovered DNA from Yersinia pestis ? the plague bacterium that caused the Black Death in the 14th century ? lurking inside the teeth of two people who died during the outbreak.?

?Can genes solve the syphilis mystery?? asks the Science chapter on that infection. Its ravages leave telltale scars on bones of the tribes Columbus fraternized with, yet the first records of syphilis in Europe turned up soon after he returned to Spain. But last year, excavated skeletons of monks who inhabited an English monastery, dated between 1300 and 1450, carried the same syphilitic stigmata.

Ancient DNA from pathogens is so rare that molecular paleontologists are mining a richer lode ? the genes of living pathogens. Thus, scientists at Baylor College of Medicine in Houston have sequenced the genome of Treponema pallidum, the syphilis bacterium. They note its close DNA resemblance to T. pertenue, the pathogen of yaws. This worldwide tropical skin disease, mainly of children, is transmitted not by sex but by contagious contact between lesions.

Sleeping sickness and Chagas disease, which have afflicted humans for hundreds of thousands or even millions of years, are now revealing their pathogenic pasts to computer-constructed genealogical trees. So are such Johnny-come-lately microbes as Helicobacter pylori, the stomach bacterium that causes ulcers. It was discovered in 1982. One biologist says that parents may have been passing it down to their children ever since founder humans emerged from Africa.

A phylogenetic tree of HIV-1, the most prevalent AIDS virus, constructed at the University of Alabama in 1999, indicates that this pathogen crossed the species barrier from West African chimpanzees to people around the year 1930.

Weirdest of all the ruthless microorganisms described in the May 11 Science is Wolbachia, ?perhaps the most common infectious bacterium on Earth.? Its victims are not humans but insects, in which it manipulates their sex lives to ensure its own survival.?

Blessings Of Microbial Genomics, Gene Shuffling Give Bioterrorists Curse Of Enhanced Bioweapon Deadliness

Australia suffers from a serious plague of mice (Mus musculus), so its people turned to biotechnology for relief. Whereupon two scientists, one at the Pest Animal Control Cooperative Research Center in Canberra, the other at Australian National University in the same city, set out to make a murine contraceptive vaccine by shuffling the genes of the mousepox virus.

This infectious ectromelia virus, as mousepox is known to animal virologists, belongs to the Poxviridae family, which includes vaccinia virus ? basis of smallpox vaccine ? and to the smallpox variola virus itself.

To make their mouse birth-control vaccine, the Australian team took a relatively benign strain of ectromelia, and added genes for proteins carried on the surface of mouse ova. Their idea was that cells infected by the viruses would express the proteins, causing female mice to produce antibodies against their own eggs. To maximize their construct?s effectiveness, the pair also engineered the virus to contain the gene for interleukin-4, a protein that boosts antibody production.

But by the law of unintended consequences, the IL-4 gene also shut down the T-cell arm of the animals? immune system ? rendering them unable to fight off mousepox. Previously vaccinated mice died within days.

Thus the oops factor kicked in: The Australia team had inadvertently created an unusually virulent strain of mousepox. When they saw what they had done, they suddenly realized that if a similar genetic manipulation were applied to the genomically related smallpox virus, now technically extinct on earth, it could be made even more dangerous.

That fear was not just theoretical. Smallpox is one of the prime pathogens on the most-wanted short list of biological weaponry. The others are anthrax and plague. A News Feature in the May 17, 2001, Nature titled ?The bugs of war,? puts the question: ?Could our knowledge of microbial genomics and skill in genetic engineering be used to create enhanced? bioweapons?? Its author, Carina Dennis, is a senior biology editor on the Nature staff.

Government agencies in the U.S. and elsewhere already are working on methods of detecting disease outbreaks caused by genetically engineered organisms. Perhaps the simplest way to magnify a microorganism?s wallop is to buck up its resistance to antibiotics ? something the bugs already do all too well. Staphylococcus aureus and Pseudomonas aeruginosa play the resistance card at a dizzying rate. And the Soviet Union?s bioweaponeers had clandestinely developed a form of Yersinia pestis, endowing that causal agent of plague with resistance to 16 different antibiotics.

Stenting After Angioplasty Contraindicated In Patients Carrying Gene Variant For ACE Enzyme

Described as ?the first clinical application of pharmacogenetics in cardiovascular disease,? a clinical trial of heart-disease patients harboring a gene variant of ACE ? angiotensin 1-converting enzyme ? should not receive stents (a cylindrical metal mesh) following angioplasty to unblock coronary arteries. ACE is commonly prescribed to treat high blood pressure. The study found that, contrary to standard operating procedure, stents in patients of such a genotype aggravate the occurrence of restenosis, or reblocking of the arteries.

This unexpected result is reported in The Lancet dated April 28, 2001, under the title: ?Effect of ACE inhibitors on angiographic restenosis after coronary stenting: a randomized, double-blind, placebo-controlled trial.?

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