News: Gates Takes On Malaria

30 October 2005

San Francisco--Bill Gates is going after bugs in a big way--but not the computer kind. Today, the billionaire co-founder of Microsoft and his wife, Melinda, announced that their philanthropic foundation is giving $258.3 million to researchers to help fight the parasites that cause malaria. It is the single biggest donation from a charitable organization to fight malaria ever given.

"Deaths from malaria have doubled over the last 20 years," Gates said during a teleconference call. "It's a tragedy that the world has done so little to stop this disease that kills 2,000 African children every day," Gates said.

Forty percent, or $107.6 million, of the new funding will go to support clinical trials of a prototype vaccine aimed at protecting children against severe malaria, which is under development at GlaxoSmithKline's GSK Biologicals unit, in Rixensart, Belgium. The Bill & Melinda Gates Foundation has earmarked another $100 million for efforts to speed development of drug treatments for patients already suffering from malaria. And $50.7 million will go to develop insecticides and other techniques for controlling mosquitoes.

In the teleconference call with Gates, Glaxo's chief executive, Jean-Pierre Garnier, said he has no illusions that the company will make money by developing a malaria vaccine. "I do it because it's the right thing to do and because it's an exciting adventure for our scientists," Garnier says.

Even so, the malaria research could have some positive upside for Glaxo's commercial products, particularly for future versions of "pandemic" vaccines--drugs that could be used to protect people against new and virulent influenzas, such as the avian flu. Here's why: Key to the success of a malaria vaccine is a so-called "adjuvant," a formulation that primes the immune system to respond to a vaccine. Glaxo researchers are hopeful that the work they are doing on malaria adjuvants will pay off as they develop vaccines for future pandemic illnesses.

Taking on a challenge as scientifically and emotionally appealing as creating a malaria vaccine is also a great recruiting tool, Garnier says. "I have top-notch scientists coming to work for Glaxo who won't work for other big pharma companies," Garnier asserts, because they want to work on problems like malaria. Glaxo's competitors include companies such as Pfizer and Schering-Plough.

Having someone else foot the bill doesn't hurt, either. In recent years, large pharma companies have sharply curtailed many research programs that once explored pharmaceuticals for treating diseases that largely afflict impoverished people. For instance, only 13 out of 1,223 new medicines marketed by major drug companies between 1975 and 1997 could be used for tropical diseases, according to Doctors Without Borders.

Malaria research has been particularly squeezed. Although work on a malaria vaccine had gone on for years at SmithKline Beecham (which became GlaxoSmithKline following a merger in 2000), corporate managers considered scuttling the program as recently as 1999 to cut costs. The program survived largely because its leading researcher pledged to find outside grants to supplement his budget--a move then unheard of in the pharmaceutical industry.

In 1999, the Gates Foundation awarded its first grant supporting malaria research. Prior to the grants announced today, the Gates Foundation had, since 1999, already put more than $250 million toward malaria research efforts. That makes them big spenders. According to a study slated to be released on Monday by a nonprofit group, the Malaria Research and Development Alliance, total research and development spending on malaria totaled $323 million in 2004. More than half of that money was given by just two groups-- the U.S. National Institute of Allergies and Infectious Diseases and the Bill & Melinda Gates Foundation.

Even so, trying to create a vaccine against a parasite is a daunting task. Vaccines aim to provide the body with lasting immunity against a disease and so are seen as the most cost-effective way to safeguard against illness. Yet science has yet to produce a commercial vaccine against any parasite, living organisms that can adapt and change with startling agility.

Last year, a team of researchers in Mozambique and at GlaxoSmithKline published the results of a clinical study of a prototype malaria vaccine, involving 2,000 children. They found the vaccine (administered with its specially designed adjuvant) cut the risk of malaria by 30% for children overall and reduced the risk of the most fatal versions of malaria by 58%.

Ripley Ballou, Glaxo Vice President of Clinical R&D Early Development, says that the new money will support the development of more widespread clinical trials, which will take place over the next two to three years. Glaxo expects to try the vaccine formulation in approximately 17,000 young children in at least six countries throughout Africa.

If the trials go smoothly, a malaria vaccine could be ready for widespread use by 2011, says Melinda Moree, director of the PATH Malaria Vaccine Initiative, a nonprofit created in 1999 by the Gates Foundation to accelerate such research and development efforts.

Other multinational companies are also getting involved in fighting malaria. For instance, Exxon Mobil, which has 5,000 employees in 20 countries throughout Africa, kicked off its own antimalaria programs in 2001. Steven C. Phillips, who directs the program, says that although he supports research programs aimed at developing a vaccine, companies must also use existing medical therapies and countermeasures to save lives. "The global community shouldn't underestimate the complexity of developing a vaccine," Phillips says.

Garnier predicted that other pharmaceutical companies will follow Glaxo's lead in doing work on widespread diseases that afflict impoverished people. "Companies will come to this because you have people like Bill Gates around the table," Garner said. "Bill has reinvented philanthropy and made it a can-do enterprise."

http://www.forbes.com/sciencesandmedicine/2005/10/30/malaria-gates-philanthropy-cz_ec_1030malaria.html

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Forbes: Chutzpah Science

Even the Gates Foundation would run out of money if all it did was buy vaccines. So now it's going about inventing them, too.

Stefan Kappe is a bug-killer. Every week in a tiny, humid room (nicknamed The Swamp) at the nonprofit Seattle Biomedical Research Institute, Kappe and his colleagues slit open between 2,000 and 3,000 mosquitoes to collect the microscopic parasites that cause malaria. By knocking out a gene essential to the parasite's development, Kappe hopes to create a vaccine against malaria. It's an audacious goal--no one has ever made a commercial vaccine that protects against any parasite, much less malaria, which threatens 40% of the world's population. Half a billion get the disease every year and more than a million die of it.

In late June Kappe was one of 43 principal scientists to win a chunk of the multiyear Grand Challenge awards, funded largely by the Bill and Melinda Gates Foundation. The Gates Foundation has set aside $450 million for the project, while the Wellcome Trust and the Canadian Institutes of Health Research are chipping in another $31.6 million. The goals for all the projects are breathtakingly grand: Give a child a vaccine without using a needle. Make vaccines that don't need to be refrigerated. Make plants that grow in dry climates more nutritious. Genetically modify mosquitoes so they can't spread diseases such as malaria and dengue virus. "These [projects] probably wouldn't get funded by the National Institutes of Health," says Richard Klausner, director of global health at the Gates Foundation and formerly director of the National Cancer Institute. "They're too risky, too ambitious. And that's exactly what we wanted."

Bill Gates' $28.8 billion foundation is more than double the size of the runner-up, the $11 billion Lilly Endowment, and the projects it has taken on are supersize. On the top of the agenda: battling the diseases that plague developing nations. The Gates Foundation has already pledged $1.5 billion to bring routine vaccines to the poorest children around the world. Now Gates wants to push scientists to create a more powerful arsenal.

To put together its list of 14 "challenges," a panel of scientists sifted through recommendations from 1,000 researchers--from biochemists to mathematicians--around the world. Grant winners will have to invent technology on a deadline. Miss a milestone and the money stops. That hardheaded approach makes the applications more like business plans than traditional research programs, Klausner says.

Such research also represents a healthy half-step between pure academic research and for-profit development. "It's good to try things that stretch the university a bit toward providing products in situations where the commercial world won't," says Nobel Laureate David Baltimore, who also serves as president of the California Institute of Technology and has won a $13.9 million Gates grant. The grantees pledge to make their technologies available at no or little charge to developing nations, though they retain marketing rights in developed markets.

When Florence Wambugu, founder of A Harvest Biotech Foundation International in Kenya, heard about the Gates grants, she immediately thought about three packages of sorghum seeds sitting in cold storage in Des Moines, Iowa. A cousin of corn, sorghum is a staple for half a billion people worldwide, even though it lacks much nutritional value. Five years ago Pioneer Hi-Bred International (a subsidiary of DuPont) figured out how to slide a critical gene from corn into sorghum to make a variant with more lysine--an essential amino acid. The researchers published their work, then filed the details (along with 200 seeds) in cold storage. The sorghum market simply wasn't big enough for Pioneer, says Paul Anderson, research director of DuPont crop genetics.

But Wambugu, who remembered the project from past discussions with Anderson, wanted those seeds. She called Anderson and asked if Pioneer would help her foundation develop better sorghum for African farmers. Wambugu and Anderson worked on their joint proposal for 20 months, ultimately winning $16.9 million from the Gates Foundation. Pioneer agreed to further nutritional enhancements to the sorghum strain, to train African scientists, and to donate the know-how (and seeds) from its earlier work. Wambugu has created a network of allies in Africa that will develop new crops as well as coax governments to okay the use of bioengineered seeds.

Delivering a drug via inhalation--that challenge inspired Harvard professor David Edwards to found a company in 1997. The novel delivery mechanism has commercial potential in treating diabetes, since prosperous countries are full of diabetics. Eli Lilly & Co. and Alkermes (which now owns the technology) are trying out inhaled insulin on 1,000 patients.

How about the same method to deliver vaccines, sparing the costs of refrigeration and needles?There's scant commercial potential here, but there's a need. In 2003 Edwards started the nonprofit Medicine in Need to develop the technology, which is very tricky. You have to dry the vaccine without killing the cells in it, and you have to make the particles small enough to be inhaled but not so small that they are exhaled. Edwards and his collaborators are getting a $7.6 million Gates grant.

Caltech's grant was for finding a way to equip the body to fight a disease that it may not be prepared to tackle, such as AIDS. Most vaccines and therapies try to bulk up the body's existing defenses, say, by boosting the immune system. Baltimore wants to rewrite the body's disease-fighting instruction manual. He aims to take hematopoietic stem cells--the bone marrow cells that form blood cells in the body--and reprogram them by adding genes that direct the cells to produce unnatural antibodies. So far he and his colleagues have primarily demonstrated that they could help mice beat tumors this way. "This approach is such a leap beyond where we are today," says Baltimore.

Malaria is a classic example of a disease that pharmaceutical companies are reluctant to tackle. The parasites that cause malaria go through four major developmental stages, some in humans and some in mosquitoes. Most experimental malaria vaccines target the mature parasite as it is wreaking havoc in a patient's blood. Kappe's $13.5 million grant, by contrast, aims to stop the equivalent of teenage parasites while they're developing in the human liver.

In his insect swamp, Kappe develops a culture of red blood cells with malaria parasites that lack a key gene for development. The mosquitoes feed on the blood, absorbing the parasites. After the parasites have matured further, Kappe harvests them to build a mouse vaccine. Although the parasites can't develop further (and so can't cause malaria in the mice), they do excite the immune system. Kappe is using his grant to begin human trials.

His colleague in Africa, Patrick Duffy, won a $19 million award to pin down which forms of malaria are most deadly to children, and Dominic Kwiatkowski at Oxford University got a $16.4 million grant to explore which variations in the human genome protect some people from ever contracting malaria.

"These grants are different from standard research programs, which are about learning, not about producing things," says Baltimore. "The Gateses have made a commitment to seeing that something gets done."

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Forbes: Ride the Light

Silicon Always Wins

On The Cover/Top Stories

Teaching silicon new photonic tricks promises a huge boost in getting data out of a computer

In his lab at Sun Microsystems' San Diego Physical Sciences Center, Ashok Krishnamoorthy is surrounded by big numbers: looming powerful computers that can crank through a trillion operations per second. But what commands his attention these days is something very small: a prototype silicon chip, only a few millimeters on a side, that works like a magic gateway between muscle-bound computers.

Although still a hatchling, this so-called silicon photonic chip, devised by a Carlsbad, Calif. startup called Luxtera, could mark the beginning of a new Internet era when computers will be able to tap into huge reserves of data, no matter where they are situated, as easily as they now retrieve data from their own hard drives. "It will mean that distance truly won't matter anymore," says Arno Penzias, a Nobel laureate and one of Luxtera's venture backers. "Wherever you are, you can share in all the world's information."

Big promises come in small packages. Luxtera's chip is neatly hidden inside a component that looks like a gold-covered mint wafer. Metal pins along three sides both secure the piece to a circuit board and deliver streams of bits to the silicon device. On the fourth side of the component is a plug that resembles a telephone jack. Krishnamoorthy slides a bundle of fiber-optic threads into the plug. One thread is attached to a laser.

As the pins deliver bits sent from another computer, the laser pumps a steady stream of light into the chip. Inside, a modulator works like a tiny shutter, imprinting the bits onto the incoming laser light. The light signals do a victory lap in the device, then head out on a path that runs parallel to the one they came in on. The signals spill onto an optical fiber, then travel another 20 meters before reaching a detector, a chip that transforms the light signals back into electrical ones. "We've been working with Luxtera for almost a year now," says Krishnamoorthy. "I have personally tested the modulators to 10 gigabits a second." That's fast enough to send a DVD movie in four seconds.

Silicon photonics aims to solve what has become one of the huge bottlenecks in the information age, the movement of data in and out of computers. For the past 40 years computer chips have grown faster as designers have marched steadily to the drumbeat of Moore's Law, roughly doubling the number of transistors on a swatch of silicon every two years. By shortening the distance electrons travel, they've made chips go faster. But like an automobile pulling out of the driveway, electrons that venture outside a chip must follow some path--usually copper--to reach their next destination. Intel's top-of-the-line Pentium 4 runs at 3.7 gigahertz and relies on a souped-up "bus" that is about a quarter of that speed.

Designers have invented clever shortcuts for electrons, like Sun's recent approach for nudging separate chips closer together and zapping data between them. But radically improved performance calls for the use of photons, or particles of light, which are 250,000 times lighter than electrons and can fly in close formation, squeezing lots of data into a small space. Telephone companies spent the 1990s ripping out copper lines and replacing them with optical fiber and expensive networking gear to turn digital signals into light waves. This was never a cheap trick, though, depending on compound semiconductors such as indium phosphide and gallium arsenide, which don't enjoy the mass-manufacturing economies of silicon, the mainstay of the computing universe.

"Silicon always wins," points out Cary Gunn, a cofounder and vice president of Luxtera. If optical devices could be built in silicon, the cost of communicating data would fall.

Silicon is finicky about light. Tickle compound semiconductors with enough electrons and they spit back photons (the telecom industry uses them for its optical magic). In the 1980s Eli Yablonovitch, now a professor at UCLA, invented something called photonic crystals, which manipulate light much like transistors shuffle electrons around. Key to building useful photonic crystals, however, was carving tiny structures into semiconductors.

In the late 1990s, after nine years in the Air Force, Gunn wound up in graduate school at the California Institute of Technology working with Axel Scherer, one of the world's experts in building very tiny electronic and photonic structures. By then the enormous manufacturing muscle of the silicon chip industry had pushed the size of key chip components down to roughly 100 nanometers--a quarter of the wavelength of infrared light, which is widely used by the telecom industry. Only at these tiny dimensions can engineers manipulate the electrons buzzing within silicon to change its photonic properties. "That turned the corner," says Yablonovitch, who cofounded Luxtera with Gunn and Scherer. The challenge was to train silicon to modulate laser light fast enough to keep up with the data pouring in from computers.

Scores of inventions had to fall into place. (All told, Luxtera has filed for more than 75 patents; 15 have been issued so far.) The central idea of the modulator depends on the fact that light travels at different speeds through different materials. (Put a pencil in a glass of water and the pencil looks bent because light travels more slowly through water than through air.) Light traveling through silicon usually moves only a third as fast as it would in a vacuum. At the nanoscale level, Luxtera engineers figured out how to tune silicon by applying voltage and thus make light move more sluggishly.

Within the Luxtera chip, light is split along two paths, and the twin beams are nudged out of synch with each other by the modulator, acting upon incoming data. When the beams recombine, they either make a bigger wave or cancel each other out. This way the modulator stamps data onto the light.

Figuring out how to funnel as much light as possible from a laser into the tiny modulator structure is another part of Luxtera's secret sauce. The company also saved enormous trial-and-error time by using a complex modeling program built by two Caltech undergraduates that simulates how light and electrons interact in three dimensions. (They sold it to Luxtera in exchange for founder's equity.)

The timing of the telecom bust helped, too. In November 2001 Luxtera's venture capitalist tapped chip industry veterans, including Alexander Dickinson, who got his start with optical devices at Bell Labs. Minutes after Dickinson signed the papers that gave Luxtera $7 million in seed capital, Gunn bought $2 million worth of test equipment for $200,000 in a fire-sale auction at Nortel. Since then Luxtera has raised another $24 million in venture funding.

That 10 gigabits a second is only a starting point, says Dickinson. Adding light signals of different wavelengths, like creating extra channels, will multiply performance. Shrinking component sizes will also speed the modulator.

Intel researchers are working feverishly on their own silicon photonic components, including modulators, which operate at 4 gigabits a second. Those could be commercial devices by the end of the decade. Last December the Defense Advanced Research Projects Agency kicked off a four-year program to build integrated electronic-photonic devices. "This is potentially a very disruptive technology," says Jagdeep Shah, who manages the Darpa program. "We're sort of like at the early stage of integrated circuits."

Essential to holding down costs is using the same manufacturing tools and factories used to make cheap PC chips. Luxtera is relying on Freescale Semiconductor to build its chips, and in the past 12 months Freescale has been sliding Luxtera's designs right into the standard manufacturing line for the PowerPC chips that go into a range of devices, including Apple computers. David Mothersole, chief technology officer of Freescale's networking business, expects to be making samples for Luxtera's first customers by the end of this year. Although the startup plans to make money by selling its chips to computer systems manufacturers, its director of marketing, Gabriele Sartori, is a staunch advocate of spreading the new technology through licensing.

Luxtera's growing fan club also includes Michael Fister, formerly with Intel and now chief executive of Cadence Design Systems, the leading maker of chip-design software tools. "Demand for high-speed interconnects is strong," he says. "There's good reason to be intrigued with this technology, and Luxtera is definitely worth watching."

Lighten Up

Luxtera's chip speeds data out of another chip by printing electrical signals on light waves. Here's how it works:Laser light is fed through tiny waveguides and split into two silicon channels. Meanwhile, a stream of bits from a microprocessor is fed into an electronic driver, which applies voltages to the silicon corresponding to the bits, changing the phase of the light. The two waves recombine to form distinctive peaks and valleys. The light can travel any distance via fiber-optic cables and then be converted back into electronic signals.


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News: Saving The World From Real Viruses

25 January 2005

SAN FRANCISCO-- When Microsoft co-founder Bill Gates set out his vision for the future in his first book, The Road Ahead, back in 1995, he imagined computers at everyone's fingertips. These days, he has a much more fundamental vision: vaccines for every child.

Today, the Bill and Melinda Gates Foundation is announcing that it will give $750 million over the next ten years to the Global Alliance for Vaccines and Immunization to help pay for vaccines for children in developing nations. The government of Norway is chipping in another $290 million to GAVI.

"The Gates Foundation's goal is to reduce the inequities in health between rich and poor countries," says Melinda Gates, co-founder of the foundation. In 2002, 1.4 million children under the age of 5 died from preventable diseases, including measles, diphtheria, polio and tetanus, she points out. "Every one of those deaths is totally unacceptable when we have an affordable and effective means to prevent those deaths," she adds.

In 2000, the Gates Foundation gave a $750-million, five-year grant to help start GAVI, a private-public partnership aimed at significantly boosting vaccination rates in developing countries. So far, the program has been a success: By the end of 2003, GAVI had provided routine immunizations for 4 million children, hepatitis B shots for 42 million children, and immunization against yellow fever and Haemophilus influenzae type B for 8 million children. In Uganda alone, routine immunizations rose to 81% of all children in 2003, from 53% in 2000.

"That original grant was the largest grant we've made in world health, and yet we can say very strongly that we've never made a better investment," says Bill Gates. All told, GAVI estimates that it has saved 670,000 lives.

But even a billion dollars doesn't go a long way when you want to vaccinate the entire world. Bill Gates points out that GAVI aims to vaccinate 90% of the children in the world's poorest countries by 2015, a task that will cost between $8 billion and $12 billion. So far, nine nations, including the United States, have ponied up another $870 million to support GAVI. Gates says that he has been talking to the leaders of England and France about establishing an "international finance facility" that will help developing nations get funding to pay for vaccines.

"GAVI has made the transition from a startup to something that really works," says David Fleming, director of global health strategies at the Gates Foundation in Seattle. The foundation felt that it was important to give the same dollar amount--$750 million--as it did five years ago, but to acknowledge that GAVI will need more funding sources to widen the sweep of its vaccination program, he says. The Gates money has demonstrated that the program can effectively vaccinate millions of children, and that kind of track record should make it easier to attract new donors, Fleming adds.

In the past, all kinds of roadblocks have stopped vaccines from reaching children in need, Fleming says. It's hard to deliver the right medicine to the right clinic. Too frequently, rural clinics lack the refrigeration and other equipment needed to store temperature-sensitive vaccines. To run effective immunization programs, Fleming says, GAVI has taken a business-oriented perspective: It analyzes the capital investment needed (to provide transportation and refrigeration of vaccines), in addition to forecasting the demand for vaccines and likely supplies. "You can really think of the delivery of immunization as a business," Fleming says, "but instead of profit, our bottom line is 'lives saved.'"

At the same time, GAVI works closely with the governments of countries receiving its support to develop business plans for how to spend the money. "GAVI is a model for donor assistance," said Yoweri Museveni, president of Uganda, in a statement. "We as a nation have the flexibility to determine how to best spend funds to achieve results. Some ask, 'what works?' in foreign aid--here is your answer," he said.

That businesslike perspective has been a boon for pharmaceutical firms such as GlaxoSmithKline (nyse: GSK - news - people ) and Merck (nyse: MRK - news - people ). "GAVI plays an important role by providing a steady understanding of what the market for vaccines will be," notes Debbie Myers, director of external government affairs and public partnerships for Glaxo.

Even though Glaxo and others have had vaccine development projects for decades, immunization had fallen off the international public health agenda before GAVI, Myers says. Donors became focused on other health issues, and vaccination rates began to slip. Countries like Sierra Leone and the Congo, where roughly 85% of the children received the basic tuberculosis vaccine in the mid-1980s, saw that percentage slip down to one-third of the population by the late 1990s.

"GAVI and the Gates Foundation got vaccines back on the radar screen," Myers says. Bill Gates seems intent on keeping it there. At the annual World Economic Conference--the glitzy confab of world leaders in Davos, Switzerland, which begins on Wednesday--Gates is devoting his time to talking about poverty and the developing world. He is slated to appear on two panels on the subject. Among the other panelists are former U.S. President Bill Clinton; Thabo Mbeki, the president of South Africa; and musician Bono, who is also outspoken on world poverty.

"There are many ways to look at the impact of GAVI," Gates says. "The supply chain for vaccines is handled better. It's driven innovation. But most importantly, it's saving lives."

http://www.forbes.com/healthcare/2005/01/25/cz_ec_0125gates.html

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Book Review: Eyeing the Flash

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Memoir of a scam artist reads like another trick

Reviewed by Elizabeth Corcoran

Sunday, January 16, 2005

Eyeing the Flash: The Education of a

Carnival Con Artist

By Peter Fenton

SIMON & SCHUSTER; 244 PAGES; $23

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Peter Fenton has spent most of his life telling beguiling stories. His memoir, "Eyeing the Flash: The Education of a Carnival Con Artist," reveals how many of his early tales were based on deception. But what about the memoir itself? It doesn't take long to suspect that this con man can't quite ever tell the truth.

"Eyeing the Flash" is a story of how a kid learned to pull off scams. As he tells it, Fenton was a shy teenager in the Detroit suburbs during the 1960s, with an alcoholic father and a talent for adding numbers. He becomes charmed by a slick teen named "Jackie" whose family runs low-budget carnivals. Jackie teaches Fenton a grab bag of card tricks and simple cons. Together, the boys run a casino in Jackie's basement lair, cheerfully ripping off their fellow students and the occasional teacher. Fenton blossoms into a card shark, and proudly learns to dress like a one-trick pimp. Fenton is shocked -- shocked! -- to learn that Jackie is ripping him off, too. But eventually, Fenton gets the chance to scam his teacher. All's well that ends well, and in the end they troop merrily off to college or, in Jackie's case, Wharton School of Business.

Or so Fenton says.

There's a disclaimer at the beginning of the book that "names and certain identifying characteristics" of pretty much everybody in the book have been changed. Fenton captures the weird flavor of the era, portraying it as an alcohol-laced, puke-covered joyride. But if you believe that the details he describes from 40 years ago are genuine, I suspect he also has a bridge he'd like to sell you.

What does ring true is Fenton's enthusiasm for scamming people. Four years and scores of scams into their friendship, Jackie tells Fenton that he's looking for a way out of the carnival business and has plans to go to college and get a job on Wall Street. Fenton is incredulous. " 'As far as I'm concerned, becoming an agent (who helps run scams at the carnival) is the best thing that's ever happened to me,' " Fenton tells Jackie. " 'I feel great when I'm working a mark, putting one over on him. Even a 10-year-old kid.' And at that moment, I understood why: ... I was constitutionally suited to being an a -- carny."

Jackie gives Fenton a copy of John Scarne's "Complete Guide to Gambling" (a genuine best-seller) and begins to teach him the basics. Many of the scams are numbingly simple: The "Duck Pond" features a circular basin with a water jet and a flotilla of rubber ducks that circle through the basin, passing through a tunnel. Each duck has a number painted on its underside that corresponded to a "flash," or prize. Customers (a.k.a. "marks") pull out a duck and collect their prize. Most of the flash is cheap stuff. Customers see the carny working the booth put the duck with the Big Prize -- say, a television set -- into the water. What the mark inevitably misses: The carny makes sure that the Big Prize duck disappears into the tunnel, never to reappear.

What shines through the carnival patter, however, is Fenton's contempt for the people who fall for his tricks. "All marks are dummies, who'd stare in drop-jawed fascination at a spinning hubcap if admission were free. Marks were drawn to the midway by cheap thrills and danger. I was just giving them what they came for."

The final chapter is written with the pacing of a made-for-TV movie: Fenton and Jackie confront each other in a "Bust Out," a daylong contest to see who can pocket more money by running a series of scams. Each has small triumphs and flops and, of course, our narrator ultimately carries the day with the biggest scam of all.

After the showdown, however, the book sputters to a close. Jackie, we're told, went to Wharton. (Or maybe he didn't. Even Fenton doesn't seem to know.) Fenton heads to the University of Michigan, where he's bored after 24 hours. He then heads off into the sunset to search for more carnivals. There are no big morality lessons here, no analysis of what the experience means. He just moves on.

Curious readers will discover from the author's biographical statement that Fenton eventually wound up writing for the National Enquirer for 15 years. He's written two other books, including one that lists 100 or so sensational headlines and challenges readers to guess which ones are "real" (as in, printed in the Enquirer) and which are Fenton concoctions. (Predictably, it's nearly impossible to tell them apart.)

Calling "Eyeing the Flash" nonfiction seems a silly pretense. Like all the scams Fenton ran during his carnival career, this story probably has threads of truth woven into a background of hyperbole -- but only Fenton knows for sure. As a work of fiction, the book features characters too ambiguous and underdeveloped to be compelling. If you feel nostalgic for the tawdry aspects of the late 1960s, you might enjoy this. But if you pay for the book, remember that nothing makes Fenton happier than pocketing the money of the mark in front of him. •

Elizabeth Corcoran is a contributing editor for Forbes magazine.

http://sfgate.com/cgi-bin/article.cgi?file=/c/a/2005/01/16/RVGL1AM1OS1.DTL

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