By David N. Leff

Science Editor

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

When the surgeon general of the U.S. Public Health Service issued his historic warning, back in 1964, that cigarette smoking causes lung cancer, many youthful smokers airily kissed off that caveat. They argued that by the time they developed the disease, years down the road, medical science would have perfected a cure for lung cancer.

Despite this touching faith in oncological research, lung cancer will kill an estimated 156,900 Americans in the year 2000, according to the American Cancer Society. This body count far exceeds the expected 129,400 deaths from breast, colorectal and prostate cancer combined.

To be sure, nicotine is not the sole perpetrator of pulmonary carcinoma - not quite. Its rap sheet accounts for a mere 87 percent of that mortality, with 13 percent contracting the disease from other causes.

However, science and technology have progressed to a point where research oncologists can begin to trace the biochemical and metabolic events by which nicotine turns lungs cancerous. One recent report, in the Proceedings of the National Academy of Sciences (PNAS), dated Nov. 7, 2000, bears the title: "2'-Hydroxylation of nicotine by cytochrome P250 2A6 and human liver microsomes: Formation of a lung carcinogen precursor." Its authors are at the University of Minnesota Cancer Center in Minneapolis.

They hypothesized that, contrary to current toxicological wisdom, nicotine is metabolized by a process called 2-prime hydroxylation - (i.e., taking on board the oxygen-hydrogen radical -OH) - which eventually delivers keto and hydroxy acids to the smoker's urine. "This pathway," their paper reports, "had not been established previously in mammalian systems and is potentially significant because the product of nicotine 2'-hydroxylation (amino-ketone) can be converted to the potent tobacco-specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone - more conveniently known as NNK.

"Amino-ketone," the paper points out, "is the direct precursor to NNK, which can be formed from amino-ketone by simple nitrosation. Therefore, metabolic production of amino-ketone from nicotine potentially could provide a direct link between nicotine and lung cancer."

The co-authors developed analytical methods to quantify keto and hydroxy acids in the urine of smokers and would-be quitters who use the nicotine skin patch as replacement therapy.

"Without question," observed the paper's lead author, "nicotine replacement therapy is clearly preferable to continued use of tobacco products. Our research provides scientific evidence that nicotine products designed for long-term use, such as the so-called 'safe' cigarette, may not be safe."

Multiple Field Trials Exonerate Insecticide-Cloned Corn As Life Threatening To Monarch Butterflies

The latest - if not the last - word on the threat of recombinant corn to the monarch butterfly gives the pesticide-packing grain a verdict of not guilty. A workshop organized in mid-November by the U.S. Department of Agriculture reported on field trials it funded in Minnesota, Iowa, Maryland, Michigan and southern Ontario. Unlike earlier experiments, conducted in laboratories, these real-life studies found little or no risk to the insects on farms planting corn containing genes for insecticidal Bt (Bacillus thuringiensis). (See BioWorld Today, June 10, 1999, p. 1; and June 19, 2000, p. 1.)

Comparison of butterfly survival in conventional cornfields and plots of genetically modified (GM) grain found no significant difference. In fact, a University of Minnesota entomologist reported that the monarchs did better on the borders of a GM crop than in the nearby woods. More monarch caterpillars died near the forest than near the corn.

One explanation presented pointed out that farmers spray the milkweed, sole food source of the monarchs, while deer trample that meal-ticket weed and road maintenance crews mow it down.

Minnesota's legislature this year designated the monarch (Danaus plexxippus) as state butterfly.

The workshop's findings will be considered next year by the U.S. Environmental Protection Agency, as it reviews requests from several biotech firms to sell several varieties of Bt corn, cotton and potatoes.

BIO, the Biotechnology Industry Organization, circulated a summary of the USDA meeting to the media on November 20th.

A Prototype Malaria Vaccine, Cloned In Mouse Milk, Provided Preclinical Protection To A Primate Recipient

A malaria vaccine protein cloned in the milk of mice elicited experimental protection in a New World monkey, as reported October 30, 2000, to the 49th annual meeting of the American Society of Tropical Medicine and Hygiene in Houston.

The vaccinee was a small, large-eyed Cebidean primate, Aotus nancymai. The preclinical vaccine carried a surface protein of the malarial parasite's merozoite stage. After a mosquito bite introduces the pathogen to its human victim, and following a sojourn in the liver, the merozoite moves into the blood, where it multiplies - ready to be sucked up in the next mosquito bite.

This early stage in vivo experiment was the fruit of a Cooperative Research and Development Agreement between the National Institute of Allergy and Infectious Diseases and Genzyme Transgenic Corp., based in Framingham, Mass. The company is a pioneer in propagating therapeutic proteins in the milk of specially bred donor animals, primarily goats.

From 300 million to 500 million people a year are infected with malaria, the World Health Organization estimates, and over 1 million deaths occur, primarily among children and infants. The parasite, mainly Plasmodium falciparum - carrier of the infection - has in recent years become resistant to chloroquine, the main drug used to prevent and treat the disease. Meanwhile Anopheles mosquitoes, which ferry the pathogen to its victim, have developed resistant to insecticides. Hence the global effort to produce an efficient vaccine against malaria.