Canada, for $3.

The first ever Official Traveller's Guide to Canada is available now.

This guide gives you everything you want to know.

Cities. Tours. Outdoor adventures. Events. Shopping. M<yor tourist attractions. Plus a complete listing of the toll-free telephone numbers to get free literature on the type of vacation you choose.

Just call 1-900-773-2300 for only $3. Hear about fabulous Canadian vacation ideas, plus receive free this beautiful travel book (a $5 value) .

Call now to get the information you need to plan a great trip to Canada.

Call today. 1-900-773-2300

AJW' $3. charge will be applied '0 you,phlme bill. Only J 8 ),ears and older may call.

Want to brush up ona foreign language?

With Audio-Forum's intennediate and advanced materials, it's easy to maintain and sharpen your foreign-language skills.

Besides intennediate and advanced audio-cassette courses - most developed for the U.S. State Department - we offer foreign-language mystery dramas, dialogs recorded in Paris, games, music, and many other helpful mate­rials. And if you want to learn a new language, we have beginning courses for adults and for children.

We offer introductory and advanced materials in most of the world's languages: French, Gennan, Spanish, Italian, Japanese, Mandarin, Greek, Russian, Portilguese, Korean, etc. - 191 courses in 56 languages. Our 19th year.

Call 1-800-225-5400 for FREE 36 page catalog, or write:

aUDIC·':CRUm® Room E620, 96 Broad Street, Iford, CT 06437 (203) 453-9794

118 SCIENTIFIC AMERICAN June 1991

Clot Spotter Does a test for fibrinogen predict risk of heart disease?

A: if blood pressure, cholesterol , cigarette smoking and weight were not enough, here comes

another potential risk factor for heart disease: fibrinogen. This blood-clotting factor circulates through the body on the lookout for any lesion in need of repair with a clot or scab. But lately the protein has been showing up in studies that link high levels of it to heart dis­ease and stroke.

"There is a great deal of interest in fibrinogen as a risk factor," acknowl­edges John C. Hoak , director of hema­tology at the National Heart, Lung and Blood Institute in Bethesda, Md. But, he adds, the plethora of studies making the correlation may be raising unwar­ranted suspicions. It is still undeter­mined whether elevated fibrinogen lev­els actually cause heart disease or are simply associated bystanders.

The scientific uncertainty has not de­terred Henry L. Nordhoff, president and chief executive officer of American Bio­genetic Sciences (ABS), a tiny biotech­nology company on the campus of the University of Notre Dame in Indiana.

"Fibrinogen should be on a routine physical," he asserts, citing independent studies done in the U.S., U.K . and Swe­den, which conclude fibrinogen is a risk factor that should be a target of routine screening-and perhaps therapy.

Nordhoff happens to be developing a rapid, highly speCific test for fibrino­gen. He hopes a major diagnostic com­pany will license the test, trade named Cadkit, which has been designed to run on the high-volume automatic ma­chines found in clinical laboratories. A bedside version that works on whole blood is also under development. It could be used to monitor heart-attack patients receiving or being considered for clot-dissolving therapy.

One of the studies that puts the onus on fibrinogen is the same one that fingered cholesterol. The Framingham study, which since 1948 has tracked the heart health of residents in the Mas­sachusetts town, measured fibrinogen levels just once, in 1968-among 1,315 people free of cardiovascular illness. It has since found that "if we follow peo­ple long enough, those with higher fi­brinogen values are at greater risk for atherosclerotic problems," says William B. Kannel, lead researcher for the Fram­ingham study.

The classic way of measuring fibrino­gen is with functional assays that add

Starting from Scratch

G ordon Bell is clearly a man after the hearts-and businesses-of aspiring entrepreneurs. In the 1970s he led the design team that built the VAX superminicomputer at Digital Equipment Corporation

in Maynard, Mass. That work helped Digital blossom from a midsize compa­ny into one that IBM had to reckon with. Since then, Bell has had a hand in some 20 start-ups, most of which have tried, with varying degrees of suc­cess, to build computer hardware.

Now Bell is trying a different kind of start-up, one that aims to guide other start-ups through infancy. He has developed what he calls a diagnostic, a col­lection of questions he thinks could help fledgling entrepreneurs. Bell's ap­proach is outlined in his recent book, High-Tech Ventures (Addison-Wesley), which reads a bit like a Dr. Spock guide for young companies. Among his questions: Will the company need fewer than three technical breakthroughs to make its product? Do the designers have a manufacturing strategy in mind? Will the product still be trendy when the company seeks additional funding?

Yet building a successful start-up is still more of an art than a science. Some consultants may disagree with Bell's priorities, even on elements as standard as a business plan. Bell argues that such a plan should serve as a dynamic blueprint for the company. In contrast, Edward B. Roberts, a profes­sor at the Sloan School of Management at the Massachusetts Institute of Technology, suggests in his recent offering, Entrepreneurs in High Technolo­gy (Oxford University Press), that his studies reveal few relationships be­tween high-tech start-ups, their initial plans and their later performance.

So far, Bell says, Japanese managers have been more intrigued by his ap­proach than have U.S. venture capitalists. All Bell hopes is that his pointers will steer some entrepreneurs away from the pitfalls he has encountered. As he wryly observes: "In hardware engineering, Ohm's law and Maxwell's equations pale in importance and influence next to Murphy's law." -Elizabeth Corcoran

© 1991 SCIENTIFIC AMERICAN, INC

thrombin to a blood plasma sample . . Thrombin converts fibrinogen to fibrin, the main component of insoluble clots. The faster a clot is formed, the more fi­brinogen is deemed present. A newer testing approach uses monoclonal anti­bodies, but the clotting process releas­es breakdown products that can con­fuse these immunochemical assays.

ABS is betting on a new production technique to manufacture monoclonal antibodies, which the company claims are much more specific to fibrinogen. Instead of isolating antibody-produc­ing cells from normal laboratory mice, ABS creates its antibodies in mice that have been immunologically isolated for generations.

Because these mice, which the com­pany has licensed from Notre Dame's Lobund Laboratory, have developed very few antibodies on their own, the response is highly specific when they are injected with a specific antigen-in this case, human fibrinogen. ABS says that one in 48 spleen cells from these mice produced antibodies to fibrino­gen, compared with one in 60,000 cells from normal mice. The cells are then cultured to provide commercial quanti­ties of the antibody. "Antibodies made this way seem better able to 'see' the dllference between fibrinogen and fi­brin," explains Paul E. Gargan, director of protein biochemistry at ABS.

Given an accurate test, patients with high fibrinogen levels could mini­mize other risk factors, such as smok­ing, Nordhoff says. They might also be candidates to receive fibrinogen-reduc­ing drugs, he suggests. A number of medications on the market reduce fi­brinogen, although they were not devel­oped to do that specifically, including beta blockers for high blood pressure.

So begin administering fibrinogen­lowering drugs? "God, no," says Greg Vercellotti, an associate professor of medicine and hematology at the Uni­versity of Minnesota and an expert in clotting. Fibrinogen is an acute-phase reactant that increases with inflam­mation, he says, "so you'd wonder if the patient had a hidden cancer or infection."

Framingham's Kannel acknowledges that no one really knows how elevated fibrinogen levels could cause heart dis­ease, but he suggests possible mecha­nisms: with more fibrinogen around, it is more likely a clot will form; higher levels also could be a measure of the activity of lesions and the body's ef­forts to repair them. "The Significance of rising or falling levels of fibrinogen is a continuing saga in research," Kan­nel notes. ABS would like to write itself into the story. -Deborah Erickson

The brilliant new book from

Slo»hOD Jag Gould is "illuminatIng,

instructive and fun to read!'· From frogs that use stomachs as brood pouches to Voyager's photos of Uranus, from scientific racism to the current mania over dinosaurs, the new book by the bestselling author of Wonderful Life is his "finest to date." - ·Publishers Weekly

The best way to a man's stomach ... NordicTrack

World's best aerobic exerciser.

NordicTrack duplicates the motion of cross-country skiing, what most experts agree is the most efficient and effective aerobic exercise.

It burns more calories in less time than any other kind of exercise machine. Up to 1,100 calories per hour according to fitness experts.

Besides burning calories it strengthens the heart, tones the muscles and improves stamina. And it's much less stressful on the body than running and high-impact sports. Working out on NordicTrack also boosts creativity and productivity and lowers stress, making you feel as good as you look.

It's time to change the spare tire.

Unlike most in­home exercisers, NordicTrack works all the major muscle groups of the body including the arms, legs, buttocks, shoulders and yes, even stomach.

So what are you waiting for> Call NordicTrack today.

I 1-800-328-5888 WoFl I I 0 Please send me a free brochure I o Also a free Videotape 0 ViiS 0 Beta I Name I I Street ------------

City ______ State __ Zip __ I

I Phone ( I NordicTrack, Dept 320Fl L

_141CJ�h�1�N�haska, � �8_ ..J

SCIENTIFIC AMERICAN June 1991 119 © 1991 SCIENTIFIC AMERICAN, INC