Mammal cells make fake snider silk better The tough silk spun by spiders with

the greatest of ease has long inspired hu- man imitators. In a process not yet fully understood, spiders transform dissolved proteins in their silk-making glands di- rectly into thin, rugged filaments of vari- ous types. The most tenacious of those strands is dragline silk, which forms the resilient framework of webs. Gram for gram, dragline fiber is five times as strong as steel.

Now, a team of industrial and military scientists claims to have made artificial dragline silk that is nearly as good as the real thing. What’s more, the team’s water- based fabrication method yields artificial silk in greater quantities than ever before and avoids the environmentally unfriend- ly chemicals common in artificial fiber production, say the silk’s developers at Nexia Biotechnologies in Vaudreuil-Dori- on, Quebec, and the US. Army Soldier Bi- ological Chemical Command (SBCCOM) in Natick, Mass.

“This is way in advance of anything so far,” comments David P. Knight, a spider silk researcher of the University of Ox- ford in England.

Similar to nylon and Kevlar, genuine spider dragline silk is not only stronger than these synthetics, but it’s also at least three times as tough-which refers to how much energy it absorbs before breaking. Given those superior qualities, says Nexia’s president, Jeffrey D. Turner, manufacturers would love to mass-pro- duce the filaments for use in such items as ropes, seat belts, and bullet-proof vests (SN 3/9/96, p. 152).

However, spiders won’t stand for being herded together to create silk farms. Seeking mass-production alternatives, re- searchers have tried dissolving webs and then respinning thread from the solu- tions. They’ve also cloned silk-protein genes (SN: 2/21/98, p. 119) and inserted them into bacteria and yeast cells. No a p proach has yet produced silk quite like the real thing.

Nexia’s researchers have added a twist to the cloning tack. Instead of inserting silk genes into microbial cells, they used cells removed from cows and hamsters. In the Jan. 18 SCIENCE, they describe what happened when they put a silk-protein gene from the common garden spider Amneus diadematus into hamster cells.

They report that the cells yielded un- precedented amounts of the silk protein called ADF-3. Bacteria and yeast don’t naturally make the types of proteins in silk, which include repetitious sequences of their amino acid building blocks, notes Nexia’s Costas N. Karatzas. Nor do these microorganisms usually secrete proteins, he adds. However, the mammal cells naturally do both, a trait that Karatzas says may help explain the new experiments’ success.

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Once the hamster cells secreted ADF-3 into surrounding fluid, the researchers purified the protein and made a more concentrated solution. Next, they spun the viscous fluid into fibers by pushing it through small tubes and then stretching the resulting materials in a methanol- water mixture or pure water.

The result: silk as tough as bona fide dragline silk, albeit considerably weaker and twice as stretchy. “We’re producing fibers with properties similar to those of the spider. Nobody has been able to do that previously,” says Steven Arcidia- con0 of SBCCOM.

“It isn’t a perfect mimic,” admits Turn- er, who calls the new material a biodegradable nylon. Even so, its me- chanical quality may already be suitable for sutures and fishing line that self-de- structs if left behind in the water, he says. Also, prospects are bright for im- proving the fibers’ strength. The scien-

Bioengineered mammal cells such as cow mammary cells (inset) secrete proteins that spiders-like this member of the Araneus genus-use to spin silk.

tists plan to add other proteins to the mix, as spiders presumably do, and mod- ify how the fibers are spun. -l? Weiss

Nicotine metabolism shows ethnic bias A comparison of Latino, white, and Chi-

nese-American smokers suggests that people of East Asian descent are apt to clear nicotine from their blood more gradually than the other smokers do, thereby staving off a craving for the next cigarette.

Researchers recruited 131 smokers- 37 ChineseAmericans, 40 Latinos, and 54 whites-for the analysis. Each volunteer gave a blood sample before receiving an intravenous infusion of nicotine. The s u b stance was labeled with deuterium atoms, a heavy form of hydrogen, to make it d e tectable in the blood. After the injection, the participants provided 10 blood Sam- ples at specific intervals over the next 8 hours, then one per day for 4 days.

Nicotine is cleared from the blood by liver enzymes that convert it to its metabolite cotinine. Blood analysis showed that it took an average of 152 minutes for half the injected nicotine to degrade in the blood of the Chinese- Americans in this study. Nicotine’s half- life in whites and Latinos was 134 and 122 minutes, respectively. Slow metabo- lism of nicotine draws out its effects, says Neal L. Benowitz, a clinical pharma- cologist at the University of California, San Francisco. He and his colleagues re- port their work in the Jan. 16 JOURNAL OF THE NATIONAL CANCER h s m .

In a second test, the researchers meas- ured the smokers’ blood concentrations of cotinine. Knowing how fast each volun- teer converted nicotine to cotinine, the team could estimate how much nicotine had been inhaled in a given period and then divide that figure by how many ciga- rettes each person had smoked in that time-arriving at an amount of nicotine

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absorbed per cigarette. The calculations showed that Chinese-Americans took in less nicotine from each cigarette than whites or Latinos. This indicates the Chi- nese-Americans smoke less intensely, Benowitz says.

“The technique the researchers use for looking at [nicotine] metabolism is superb,” says Rachel F. Tyndale, a phar- macogeneticist at the University of Toronto. The work is the first to show ex- plicitly that people of Asian descent dis- pose of nicotine more slowly than others do and therefore need to smoke less to avoid withdrawal symptoms, she says.

The biological basis for the differences in nicotine metabolism could include variations in a gene that encodes an en- zyme called CYP2A6, which converts nicotine into cotinine, Benowitz says. CYP2A6 is also one of the enzymes that activate cancercausing agents called ni- trosamines that are found in tobacco smoke.

Smokers who have two fully functional copies of the CYP246 gene smoke 7 to 10 more cigarettes per day than smokers who have only one, Tyndale and her col- leagues previously reported. Other re- search indicates that some Asians har- bor more enzyme-slowing variations in the CYP2A6 gene than whites do, which could be part of the reason that Asians smoke less and get less lung cancer, Benowitz suggests. But he expects that variations in CYP2A6 will ultimately ex- plain only a portion of smoking behavior.

Psychologist Ovide F. Pomerleau of the University of Michigan in Ann Arbor agrees. What lies ahead, he says, “is ge- netic archaeology,” as scientists dig for other influential genes. -h! Seppa

JANUARY 19,2002