By David N. Leff
Editor's note: Science Scan is a roundup of recently published biotechnology-related research.
A medical verdict of genital herpes is a life sentence. So, for that matter, is the common cold sore or fever blister.
Both acts of mayhem to the skin are the work of the herpes simplex virus. HSV type 1 hits the lips; HSV 2 zeros in on the genitalia, male and female. Between its recurrent bouts of infection, the sexually transmitted type 2 hibernates in the sacral nerve ganglion, a viral safe haven slightly north of the human tail bone.
Four to seven days after sexual contact passes along the infection, a slight tingling itch in the vaginal or penile area telegraphs HSV-2's impending hit. This takes the form of small clustered blister-like vesicles, which turn into open, painful ulcers. They clear up in about 10 days, and yield to antiviral shots, pills or creams. But sooner or later, the virus will strike again and again, all through life.
Absent a definitive cure, what's needed is an effective, inexpensive vaccine to immunize a body against HSV-2, which infects one in five adults in the U.S.
Immunologists at The Johns Hopkins University in Baltimore, teamed with plant microbiologists at the Monsanto Co.'s Agracetus campus in Middleton, Wis., have constructed and successfully tested such a topical, mucosal vaccine in vivo. Their report in the December 1998 issue of Nature Biotechnology bears the title: "A humanized monoclonal antibody produced in transgenic plants for immunoprotection of the vagina against genital herpes."
The co-authors' humanized monoclonal antibody (Mab) targets HSV's glycoprotein B. This immunogenic protein allows the virus to infect its human victims' cells. They inserted the genes expressing this immunoglobulin into soybean plants, which duly expressed the antibody in quantity.
Immediately after injecting the Mabs into the vaginas of eight mice, the team inoculated the animals with pipettefuls of HSV-2 virulent virus. As their paper reports, "After delivery of the inoculum, the pipette was moved in and out four times to simulate the stirring action of coitus."
At the same time, they performed a parallel experiment with conventionally produced mammalian Mabs. Their paper reports "that vaginal delivery of the plant antibody and mammalian-cell-culture-expressed Mab provided similar levels of protection against [infection]," and added, ". . . the ability to produce Mabs in transgenic plants allows high-capacity production (tons) of Mabs, and dramatically reduces cost."
Besides these benefits, the report pointed out, "Because of their potency, Mabs can be applied in small volumes, allowing this method of woman-controlled protection to achieve the goal of being undetectable to partners."
Molecule Largely Responsible For Making Cholesterol In Body Also Guides Sex Apparatus Formation In Embryo
Among the weight-conscious and heart-anxious, cholesterol has a bad rap.
To be sure, under its black hat, this steroid plays a sinister hand in the buildup of atherosclerotic plaque that leads to coronary artery disease. But under its white hat, cholesterol is vital to the construction and well-being of cells throughout the body. In fact, it's the most abundant steroid in animal tissues.
One of cholesterol's master builders is an enzyme known as HMG-CoA reductase. Besides catalyzing an essential step in cholesterol synthesis, it turns out that HMG-CoA reductase has at least one other job — in the body's embryonic development.
The title of a paper in the current issue of Nature, dated Dec. 3, 1998, spells this out: "HMG-CoA reductase guides migrating primordial germ cells." Its authors are developmental geneticists in New York University Medical Center. Instead of mice, they used fruit flies (Drosophila melanogaster). This is not all that far-out. That particular stretch from fly to human is highly conserved throughout evolution.
The co-authors point out, "In many animals, including mammals and Drosophila, primordial germ cells [PGCs] form a region of the embryo separate from the somatic portion of the gonad." That is, the very early-stage cells destined to form testes and ovaries start out in embryonic reproduction at sites remote from the ultimate physical location of these sexual organs.
That's where HMG-CoA reductase comes in. The co-authors showed that it's highly expressed in somatic gonadal tissue, and serves as a guide, or beacon, to bring in the distant PGCs to their ultimate target.
Mummified Man, Preserved In Alpine Glacier For 5,300 Years, Dosed His Ills With Organic Therapeutics
Alternative medicine wasn't known five millennia ago, because conventional medicine didn't exist.
Yet a man trudging across the snowy Tyrolean Alps between present-day Austria and Italy medicated himself on his journey with antibiotics and anti-diarrheal drugs.
This was the mummified Ice Man, now celebrated on TV worldwide, and the subject of meticulous international medical and anthropological investigation. The closest he comes to biotechnology is suggested by a brief communiqué in the current Lancet, dated Dec. 5, 1998. It's headed: "5,300 years ago, the Ice Man used natural laxatives and antibiotics."
The author is Luigi Capasso, in the department of anthropology at Italy's National Archeological Museum, in Chieti.
Examination of the mummy's lower bowel revealed that he suffered from a still-common intestinal nematode, Trichuris trichiura, now better known as the whipworm. This particular form of helminth is thought to infest fully half the population of many countries today. The slender parasite runs 30 to 50 millimeters (about 1 to 2 inches) in length, and can coat the nether reaches of the colon from wall to wall.
Its symptoms, which obviously afflicted Ice Man on his travel, feature diarrhea, anemia, emaciation and painful abdominal distention.
Among the many objects he carried were two walnut-sized, cork-like lumps, each pierced and tied with a leather thong. These turned out to be the woody fruit body of a bracket fungus (Piptoporus betulinus), which is rich in organic therapeutics. One active compound is agaric acid, a powerful purgative. Others are a series of oils that are toxic to most multicellular life forms, but also act as antibiotics against mycobacteria. *