By David N. Leff

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

Two widely disparate facts of life on earth came into common focus last week:

¿ Mice (Mus musculus) are too distant genomically from humans (Homo sapiens) to serve as useful animal models of disease. Nonhuman primates are too expensive, and hard to come by.

¿ More and more wild mammals are threatened with extinction, as their natural habitats shrink worldwide.

Both these seemingly insoluble issues have just achieved a limited degree of success - thanks to gene cloning. To wit: In Oregon, a transgenic rhesus monkey (Macaca mulatta) was born with a foreign gene transferred into its genome. And in Iowa, a domestic cow gave birth to a live gaur (Bos gaurus), the giant wild ox of Southeast Asia. Its creators described it as the first endangered species to be cloned.

First Transgenic Primate - 'ANDi' By Name

The birth of the trail-blazing cloned monkey three months ago was reported in the current issue of Science, dated Jan. 12, 2001. The paper's title: "Transgenic monkeys produced by retroviral gene transfer into mature oocytes." Its authors are reproductive biologists, headed by Gerald Schatten, at the Oregon Regional Primate Research Center in Beaverton.

Their proof-of-principle DNA transfer experiment introduced a jellyfish-derived gene that encodes green fluorescence protein (GFP), which glows when expressed. It's widely used by researchers to track and monitor genes of interest in organisms, including plants, frogs and mice.

The co-authors attached their GFP gene sequences to a genetically modified moloney retrovirus vector. They inserted this construct close to the yolks of 224 mature rhesus eggs, then followed up with injections of sperm into the cytoplasm of those oocytes. Fifty-seven percent (126) of the 224 starter embryos developed past the four-cell stage, and 40 of them were transferred to the wombs of 40 surrogate mother monkeys.

Five pregnancies produced three healthy male babies, but only one clearly carried the heterologous GFP gene sequence in his genome. And no part of him glowed green. Although not expressed, the presence of the GFP transgene was confirmed in hair, blood, umbilical cords, placentae, cultured lymphocytes, cheek epithelial cells and urogenital cells passed in urine. Two other fraternal twins, which miscarried halfway through the 150-day gestation period, did evince green-glowing hair follicles and toenails..

Schatten and his colleagues named this transgenic youngster "ANDi," standing for "inserted DNA" in a reverse transcribed direction. Their Science paper makes the point, "Although only one live offspring is shown to be transgenic, we cannot yet exclude the possibility of transgenic mosaics in the others. We have neither demonstrated germline transmission nor the presence of transgenic sperm; this must await ANDi's development through puberty in about four years." Presumably, the gene will persist in his progeny and future generations.

The article concluded, "Nonhuman primates are invaluable models for advancing gene therapy treatments for diseases such as Parkinson's and diabetes, as well as . . . vaccines, including HIV."

Gaur, First Endangered Species, Cloned

A press statement on Friday, Jan. 12, 2001, recorded the birth - and death - of "the baby bull gaur, Noah, the first successful birth of a cloned animal that is a member of an endangered species." Robert Lanza, vice president of medical and scientific development at Advanced Cell Technology Inc. (ACT), in Worcester, Mass, made the announcement that Noah was born at 7:30 p.m. on Monday, Jan. 8, 2001, but died within 48 hours of clostridial enteritis, a common infection of bovine newborns.

The cells from which Noah was created originated from a male gaur that died of natural causes at five years of age. At his autopsy, skin cells were taken and frozen for eight years, then thawed and cloned. Forty embryos were transferred into cross-species cows, and eight viable pregnancies detected.

Only the 80-pound calf Noah was brought successfully to full term. He was delivered at Trans Ova Genetics in Sioux Center, Iowa. Noah's genome was deemed to be 99 percent wild gaur, with the remaining 1 percent coming from the mitochondria of his domestic surrogate mother cow.

"Despite this setback," Lanza observed, "the birth of Noah is grounds for hope. We still have a long way to go, but as this technology evolves, it has the potential to save dozens of endangered species." (See BioWorld Today, Oct. 10, 2000, p. 1.)

In Quest For Golden Eggs, Can Chickens Take Over As Mankind's Best Friend?

A "Leading Edge" editorial in the January issue of the journal Lancet Oncology takes up the trans-Atlantic issue of whether industry or academia will win the race to clone the common chicken. The prize is to create a flock of cloned transgenic fowl that will churn out human monoclonal antibodies and other cancer-related pharmaceuticals in their egg whites - in therapeutically viable quantities and at low cost.

The smart money is laying bets that the first products through the starting gate will be two antibodies - one against melanoma , the other a promoter of apoptosis. The biggest hurdle, the editorial writers foresee, is not technological difficulty but proprietary secrecy.

The commentary points out: "If flocks of cloned transgenic chickens laying the pharmaceutical equivalent of golden eggs are really a viable proposition, the benefits to the winning team could be enormous. Perhaps it is the very richness of the prize," it continues, "which leads to the only downside to this story, and that is the growing reluctance to share knowledge. Multidisciplinary collaborations between academic institutes and biotech companies all over the world are obviously desirable and very necessary."