Tuesday, July 17, 2007

Coley’s Cancer-Killing Concoction

On October 1st 1890, William B. Coley, a young bone surgeon barely two years out of medical school, saw one of his first patients in private practice at the New York Memorial Hospital. Although he’d only finished his residency earlier the same year, he'd already gained a good reputation and many considered him a rising star of the New York surgical scene.

The seventeen year old patient had a painful, rapidly growing lump on the back of her right hand. She had pinched the unlucky appendage between two railway carriage seats on a transcontinental trip to Alaska some months before, and when the bruise failed to heal she assumed the injury had become infected. However the bruise turned into a bulge, the pain steadily worsened, and her baffled doctors were eventually compelled to call for Dr. Coley. As a surgical man, Coley would never have guessed that this innocuous referral would take his career in a totally new direction– into an unusual branch of medicine now known as cancer immunotherapy.

At first Dr. Coley was also uncertain about the diagnosis. But as the girl’s condition rapidly deteriorated– with the lump becoming larger, more painful, and associated with the loss of sensation in some of the surrounding skin– the awful truth became apparent. She had a sarcoma, a type of cancer that affects bone and connective tissue in the body. Unfortunately, 19th century medicine offered very few treatment options.

On November 8th, Coley amputated her arm at the elbow. Although the operation appeared to go well, the girl– named Elizabeth Dashiell– developed severe abdominal pain three weeks later. Soon thereafter she noticed more lumps in her breasts and armpits, signs that the cancer was metastasizing, or spreading. She rapidly lost strength and died on January 23rd 1891, a scant three and a half months after her initial consultation, with a traumatized Dr. Coley at her bedside.

Elizabeth’s death hit the young surgeon hard. While a more experienced physician might have shrugged away the apparent failure and moved on, Coley was determined to do something. His ensuing efforts culminated in the development of a famous fluid that, for a time, appeared to promise the fulfillment of that long-held dream: a universal cure for cancer.

Coley began by poring through the hospital’s records, looking for clues from previous sarcoma cases that might lead to better treatments in the future. He soon found what he was looking for: the case of a German man who came to the hospital with an egg-sized sarcoma in his left cheek some seven years earlier. There were several attempts to excise the tumour but none of them were successful– each time the cancer came back, as aggressive as before. The final operation could only partially remove the huge mass, leaving an open wound that subsequently became infected. The unfortunate immigrant was deemed a terminal case.

Yet four and a half months later, the man was discharged with no trace of disease. Coley personally tracked down the former patient to verify that the miraculous cure had taken place. Indeed, the man was healthy and happily settled into his new life in the United States. The records showed that after the wound became infected with a commonplace bacterium, Streptococcus pyogenes, the patient went through several bouts of fever. With each attack of fever the tumour shrank until eventually it disappeared entirely, leaving only a large scar under the left ear. Coley surmised that the infection had stimulated the German’s immune system– as evidenced by the repeated fevers– and that it was this immune response that had caused the eradication of the cancer.

The story so convinced Coley that he– perhaps cavalierly– contrived to contaminate his next ten suitable sarcoma cases with Streptococcus. His initial approach was to inject a solution of live bacteria deep into the tumour mass on a repeated basis over several months. The first patient to undergo this treatment was a bedridden man with inoperable sarcoma in the abdominal wall, bladder, and pelvis. Using this experimental method, the patient was cured spectacularly. He staged a full recovery, and survived another twenty-six years before dying from a heart attack. But subsequent results were mixed; sometimes it was difficult to get the infection to take hold, and in two cases the cancer responded well to treatment but the patients died from the Streptococcus infection.

Coley’s discovery, as it turns out, was actually a re-discovery. The idea of a link between acute infection and the resolution of tumours was not new, and the phenomenon of infection-related "spontaneous regression" of cancer has been documented throughout history. A 13th century Italian saint was reputed to have his tumour-afflicted leg miraculously healed shortly after the malignant growth burst through the skin and became infected. Crude cancer immunotherapies working along similar lines to Coley’s early experiments were known in the 18th and 19th centuries, and may extend back to the time of the pharaohs. Ancient writings suggest that the renowned Egyptian physician Imhotep may have used a similar infect-and-incise method to treat tumours.

But Coley took those first important steps in dragging this old remedy into the twentieth century. After the fatalities with the ‘live’ version of his therapy, he developed an improved fluid containing killed bacteria of two different strains, Streptococcus pyogenes and Serratia marcescens. This was based on the idea that the dead bacteria would still have the immune-stimulating capability of their living brethren (in the form of purported ‘toxins’), but not share their inconvenient tendency to cause death. His invention became variously known as ‘Coley’s Toxins’, ‘Coley’s Vaccine’, ‘Mixed Bacterial Toxins’ or ‘Coley Fluid.’ The treatment was met with considerable success, with one study in 1999 suggesting that it was at least equally as effective in treating cancer as conventional modern therapies. With due care in dosing and management of the induced fever, it was also remarkably safe.

Although Coley took the concept of immunotherapy much further than his pharaonic forebears, he had no clear idea how his toxins actually worked, and the tools did not yet exist for him to find out. But given the rapid scientific progress at the turn of the last century, he reasoned that a deeper understanding of his therapy would arrive soon enough. Although the true extent of his "Toxin" success has been questioned by historians, the validity of his approach has never been seriously called into doubt. Indeed his results are regularly cited in the cancer research literature to this day.

Over the following years Coley continued to refine his technique. He determined that the toxins should be administered to patients at progressively higher doses to counter the body’s innate "immune tolerance" to the treatment. Other physicians in America and Europe also experimented with the method, and found that the toxins appeared to work just as well in a number of different non-sarcoma cancer types such as carcinoma, lymphoma, and melanoma. They could also be given intravenously some distance from the site of the tumour, and still be effective. Variations on the basic bacterial recipe and different dosing regimes were tried, depending on the individual patient and the particular cancer’s type and proliferation. Through his career Coley himself treated over one hundred patients with his concoction, and countless more were treated by other doctors.

As the fame of his fluid grew, so did Dr Coley’s stature: in 1915 he became head of the Bone Service at the New York Memorial Hospital (which later became the Memorial Sloan-Kettering Cancer Center). By the time he died in 1936, Coley’s Toxins were mentioned in a number of different surgical textbooks as a standard anti-cancer therapy.

Conventional modern medicine, however, very rarely employs Coley’s Toxins in the treatment of cancer, for reasons almost as complicated as the human immune system itself. One concern is the far-from-complete understanding of the mechanism of action; generally, doctors are reluctant to administer treatments whose workings they don’t fully comprehend. The stimulated human immune system is a whirling tempest of different physiological and biochemical responses, and even now there’s much uncertainty about how Coley’s Toxins modified this complex mechanism to better attack its cancerous target. One theory stresses the importance of the fluid-induced fever in killing the cancer cells; another considers the debris-engulfing macrophage cells to be the main players, while others consider various different immune messenger molecules– or cytokines– to be important.

The eclipsing of Coley’s Toxins also had something to do with the concurrent development of radiation therapy and, a little later, chemotherapy. Soon after Wilhelm Roentgen discovered X-rays in 1895, the possibility of using radioactivity to treat cancer was investigated. The technology was exciting, new, and developing fast along well-understood principles. Although the first results of radiotherapy weren’t all that impressive, it had the advantage of fractional doses, and once the equipment was in place it didn’t require the complicated, patient-specific preparation which was needed with Coley’s Toxins. Likewise chemotherapy was based on known scientific principles, and could be manufactured and used relatively easily.

Furthermore, both radiotherapy and chemotherapy have an immune-suppressing side-effect. Since both treatments kill the rapidly dividing cells of the immune system along with the rapidly dividing cancer cells, both can be used together if care is taken. But immune-stimulating Coley’s Toxins work entirely differently, and their effect would be cancelled out if used at the same time as high-dose immunosuppressant chemo- or radiotherapy. It became an either/or situation– and in the end, the fashionable new treatments won out over Coley’s fiddly reworking of an ancient 'natural' remedy.

So when the US Food and Drug Administration changed the status of Coley’s Toxins to that of a 'new drug' in 1963– meaning that it could only be used in clinical trials, and greatly reducing its availability– it seemed that its time had already long passed. But cancer immunotherapy does have limited applications today. Perhaps its most frequent mainstream use is in the treatment of bladder cancer; solutions containing the tuberculosis vaccine are routinely instilled into cancer-affected bladders, and are effective in causing regression of tumour deposits. It is theorized that the bladder's immune response deals with the cancer in a similar way to the whole-body immune effect of Coley’s Toxins. Melanoma, a particularly nasty type of skin cancer that responds poorly to conventional radiotherapy and chemotherapy, is sometimes treated with an immune-stimulating cytokine called interferon.

In some ways this century-old form of treatment is still a fringe area of medicine. But researchers have once again begun to probe the possibilities of immunotherapy. New antibody-based treatments like Mabthera and Herceptin are making a real difference in the treatment of common cancers like lymphoma and breast cancer. Although these therapies don’t stimulate the body’s immunity as a whole, they are based on antibody molecules which are key components of the human immune system. They show that our increasing knowledge of the molecular nitty-gritty of the body’s own defence and repair network is starting to make a real difference in the battle against cancer. One tumour at a time, such advances in modern medicine are finally vindicating William Coley and his one-hundred-year-old cancer-killing concoction.

Friday, July 13, 2007

10 things your restaurant won't tell you

1. "It's more about the sizzle than the steak."

Business is good for the restaurant industry. Americans now spend roughly half their food budget dining out, and restaurants expect revenue of more than $537 billion in 2007. That's a 67% increase since 1997.

But it's not just our collective avoidance of the kitchen that's pumping profits: Restaurants work every angle these days, using marketing psychology to get you to spend more.

At legendary Aureole Las Vegas, spandex-clad "wine angels" retrieve bottles from a 42-foot-tall spirits tower. The thinking behind the spectacle: "Anything that gets patrons' attention will get them to spend," says restaurant designer Mark Stech-Novak.

Fast-food outlets use a high-stimulus environment to maximize the source of their profit: "It encourages faster turnover," says Stephani Robson, a senior lecturer at the Cornell School of Hotel Administration. "Specifically, the use of bright light, bright colors, upbeat music and seating that does not encourage lolling."

Even menus are rigged. "We list the item that makes the most profit first so it catches your eye," says restaurant consultant Linda Lipsky, "and bury the highest-cost item in the middle."

2. "Eating here could make you sick."

The 2006 E. coli outbreak that started at a New Jersey Taco Bell and sickened more than 60 people was traced to green onions. But food-borne illness isn't the only cause for concern: In a separate December incident, 373 people in Indianapolis got sick after eating at an Olive Garden where three employees tested positive for the highly contagious norovirus.

"You don't call out (sick) unless you're on your deathbed," says freelance chef Leah Grossman. Indeed, according to a recent study, 58% of salaried New York City restaurant workers reported going to work when sick; the number is even higher for those without benefits.

"A lot of poor, transient people work in restaurants," says Peter Francis, a co-author of industry exposé "How to Burn Down the House." "They're not giving up the $100 they'd make in a shift because they're sick."

How can you protect yourself? Check inspection results, which are often posted online by local departments of public health. Or just visit the restroom; it "tells you everything you need to know about a restaurant," Francis says.

3. "Our markups are ridiculous."

It's no secret that restaurants enjoy huge markups on certain items: Coffee, tea and sodas, for example, typically cost restaurants 15 to 20 cents per serving, and pasta, which costs pennies, can be dressed up with more expensive fare and sold for $25 a dish or more. At a fine-dining restaurant, the average cost of food is 38% to 42% of the menu price, says Kevin Moll, the CEO and president of National Food Service Advisors. In other words, most restaurants are making roughly 60% on anything they serve.

It's not all gravy though. Restaurants keep only 4 cents of every dollar spent by a customer, says Hudson Riehle, the vice president of research and information services at the National Restaurant Association. The remainder of the money, he says, is divided among food and beverage purchases, payroll, occupancy and other overhead costs.

Given the slim profit margin, many restaurants rely on savvy pricing to create the illusion of value. Putting a chicken dish on the menu for $21 will make a $15 pasta dish, where the restaurant is making a big profit, seem like a bargain, says Gregg Rapp, the owner of consulting firm MenuTechnologies.net.

4. "Big Brother is watching you . . . eat."

No one likes having their every move scrutinized, but that may be just what's happening at your favorite restaurant. Cameras are popping up everywhere, from four-star eateries to the place where you grab your lunchtime sandwich.

At historic Randy's Steakhouse in Frisco, Texas, where checks average $45 to $50, co-owner Don Burks has installed 12 cameras around the premises. Of those, two pick up activity in the dining rooms, and two are aimed at the bar.

"We've had customers stand on chairs to try to take out a camera," Burks says. "But the cameras aren't even pointed at them; they're pointed at the wine rack." Their primary purpose: deterring employee theft.

At some restaurants, however, the cameras are indeed trained on the tables. At New York City's four-star Daniel, for example, four closed-circuit cameras monitor the dining rooms, offering a bird's-eye view of every plate.

"It's about maintaining a quality of service," says Daniel spokeswoman Georgette Farkas. "With the cameras, the chef can tell when each course needs to be plated and served." So much for that romantic dinner for two.

5. "There's something fishy about our seafood."

Even when you pay top dollar for a seafood dish, you might not get what you're expecting. About 70% of the time, for example, those Maryland crab cakes on the menu weren't made using crabs from Chesapeake Bay, says James Anderson, the chairman of the Department of Environmental and Natural Resource Economics at the University of Rhode Island. Because of high demand, crabs are often from other Eastern states or imported from Thailand and Vietnam. (Look closely at the menu: "Maryland-style" crab is the giveaway.)

There's also the problem of outright substitution -- inexpensive fish, such as pollack, getting passed off as something pricier, like cod. How widespread is the problem? In 2006 the Daytona Beach (Fla.) News-Journal sent fish samples to a lab to prove that four out of 10 local restaurants were pawning a cheaper fish as grouper. The same lab also checked seafood from 24 U.S. cities and found that, overall, consumers have less than a 50-50 shot at being served the fish they ordered.

What can you do? Ask where the fish comes from. "If they're not sure if the fish is from Alaska or Asia, I order the beef," Anderson says.

6. "Reservation? What reservation?"

When Timothy Dillon, 34, showed up at new Chicago trattoria Terragusto for his friend's birthday, he wasn't expecting a wait. He'd made a reservation for four, then called the day of to confirm and add one more. The restaurant told him no problem, but when the party showed up, they were met with a long wait.

"After almost an hour of standing by the bar being ignored, we ended up leaving for another restaurant," Dillon says. Terragusto says it was its first week open: "We were probably working out a lot of glitches," a spokesperson says.

As Dillon discovered, a reservation isn't a guarantee. "Overbooking is almost a necessary evil," says John Fischer, associate professor of table service at the Culinary Institute of America. Restaurants calculate their average no-show percentage for any given night, then overbook the restaurant by that much, hoping it will come out even.

How to avoid Dillon's fate? It's considered poor taste to offer a tip before you're seated, Fischer says, so if it's your first time, inquire politely after 15 minutes. But go ahead and slip the manager or maître d' $10 or $20 on the way out; it should ensure you're seated promptly next time.

7. "Our specials are anything but."

"I'm very careful about ordering my food," says Rick Manson, the owner of Chef Rick's restaurant in Santa Maria, Calif. If he orders oysters, Manson says, he'll offer multiple dishes on the menu that use oysters, "to make sure I use every one of them." Nonetheless, countless variables can leave surplus ingredients at the end of the day -- which often become tomorrow's special.

"It could be the chef legitimately wants to try out something new," says Stephen Zagor, the founder of consulting firm Hospitality & Culinary Resources. "But it could also be something nearing the end of its shelf life that needs to get out of the kitchen."

How can you tell a good special from a bad one? Watch out for "an expensive item used in a way that's minimizing its flavor," Zagor says, such as a lamb chop that's been cut, braised and put into a dish where it's a supporting player.

Pastas, stews and soups containing expensive meats are also suspect. "There's an old saying in the restaurant industry," says David A. Holmes, the vice president and director of Out East Restaurant Consultants. "'Sauce and gravy cover up a lot of mistakes.'"

8. "There's no such thing as too much butter."

Think that salmon fillet you ordered for dinner is good for you? Think again. Restaurants load even their healthiest fare with butter and other calorie-heavy add-ons. Restaurant meals average 1,000 to 1,500 calories, says Milton Stokes, a registered dietitian and spokesman for the American Dietetic Association. That's roughly two-thirds of the daily average calories recommended by the U.S. Department of Agriculture. And according to a recent study, women who eat out five times a week consume an average of 290 additional calories per day.

Though most Americans assume that fast food is the worst offender, similar fare at casual sit-down restaurants can be even more caloric. The classic burger at Ruby Tuesday, for example, has a whopping 1,013 calories and 71 grams of fat. The McDonald's Big Mac, with its 540 calories and 29 grams of fat, seems downright diet-worthy by comparison.

"We butter our hamburger buns," says Julie Reid, the vice president of culinary for Ruby Tuesday, "so we tell people if they're looking to cut calories, they shouldn't eat the bun." If that sounds less than appetizing, try splitting an entrée with someone, or order an appetizer instead of a main dish.

9. "Nice tip -- too bad your waiter won't get it."

Just because you tip your waitress 10 bucks, it doesn't mean she's going home with that money. More than likely, she'll have to pass on some of it to the people who helped her serve you: The bartender might get $2, and the busboy $3 to $5. It's called a tip pool, and it's becoming standard practice in many restaurants. "It happens often that if someone leaves a voluntary tip (for their server), a significant portion of that money is going to other people," Zagor says.

According to federal law, only employees who customarily receive tips -- wait staff, hosts, bartenders and bussers -- can participate in the tip pool. But sometimes management takes a cut. In 2006, waitstaff from the Hilltop Steak House in Saugus, Mass., won $2.5 million in damages after complaining that managers dipped into their tips.

Mandatory gratuities are also divvied up. At high-end restaurants such as New York City's Per Se and Napa Valley's French Laundry, both owned by chef Thomas Keller, the practice is called service compris.

"The 20% service charge is clearly stated on the menu, and it's equally divided among the staff," says a spokesperson for both restaurants. Though the tip pool is designed to foster a team environment among staff, for customers it means something else entirely: that your gratuity isn't specifically rewarding the waiter or sommelier who provided you with exemplary service.

10. "Never go out to eat on a Monday."

If you think that Monday, when restaurants tend not to be crowded, is a great time to eat out, think again. "You're being served all of the weekend's leftovers," says Francis, the exposé co-author. Kitchens prepare food on a first-in, first-out basis, meaning whatever is oldest gets served first. It's a way to ensure that everything on the menu is as fresh as possible.

The system works great most days, but it can run into a little glitch over the weekend. Distributors typically take Sunday off and make their last deliveries Saturday morning, which means that by Monday any food not used over the weekend is at least three to four days old. And it will be served before the same ingredients arriving in Monday's delivery.

What to do if you wish to dine out on a Monday? Ignore your instincts and go to a place that's perpetually crowded. "If you are open 24/7 and busy all the time," says New York chef Lucia Calvete, "all your ingredients are fresh all the time."

This article was reported and written by Christine Bockelman for SmartMoney.