Reason Magazine - Topics > FDA

My Dog Ate My Prozac

mriggs@reason.com (Mike Riggs) — Mon, 14 Jul 2008 12:15:00 EDT

The New York Times reports that we're more like our dogs—or, they're more like us—than we might want to admit. Our dogs are overweight, neurotic, and depressed:

Allan pointed to Max, who was lying on the floor and staring at his tail. He looked angry at it, disturbed by it. “You can see the pressure building in his psyche until he’s ready to explode,” Michelle said. And then he did: Max jumped to his feet and lunged. His jaws snapped, catching only air, and he spun counterclockwise in place, an accelerating blur of fur and teeth and frustration. Tail-chasing is normal—except that Max did it daily, often for hours on end. “He’s like a junkie needing a fix,” Allan said. “At times he can’t not do it. He goes berserk.”

Pet owners can buy meds to treat anything from compulsive disorder (as in the case of Max, above) and obesity to separation anxiety disorder. And as with humans, the drugs are accompanied by therapy:

[S]cientists in an expanding field known as behavioral pharmacology say that the combination of new drug therapies and progressive training techniques can solve problems that in the past almost always resulted in euthanasia.

Seeing as a dog's life is worth considerably less than a human's life, I wonder if the FDA approves drugs for animals in a shorter period of time than it does for humans?

reason's FDA archive here.

From The Three Musketeers to the "Testicle Festival"

baylenl@hotmail.com (Baylen Linnekin) — Wed, 11 Jun 2008 17:00:00 EDT

In Alexandre Dumas’ foodie classic The Three Musketeers, main character D’Artagnan and his three associates wager with a rum-swilling, goose-fat-eating Swiss mercenary and his ragtag mates: the musketeers will go to the Bastion Saint-Gervais (which D’Artagnan had made a bloody mess of the night before) and enjoy a boozy picnic breakfast, under threat of gunfire, for at least an hour without ceding ground. The winner would enjoy “a dinner for eight...with no limits on the menu.”

In fact, the musketeers stood their ground, drank, ate, chatted, and killed about two dozen bad guys.

Earlier this month I attended the fourth annual Duckathlon in New York City, thanks to an invitation from event founder and host D’Artagnan, seller of foie gras and other fine foods. In the Duckathlon, billed as an epic food battle among four-chef teams from top New York City-area restaurants, squads competing against each other earn points by taking part in what D’Artagnan calls a twenty-event “gastronomic obstacle course” that sends competitors on “an action-packed tour” of area dining hot spots.

I realized only after seeing its numerous team culinary events that the Duckathlon is just slightly less impressive a foodie challenge than the one Dumas dreamed up more than 150 years ago.

Baylen Linnekin recently sat down with Reason.tv to discuss the Duckathlon, "culinary freedom," and the notion that cooks and customers, not bureaucrats, should decide on what they can and cannot eat. Click on the video above to watch, or follow this link to Reason.tv

The Culinary Paradox

There is probably no better place in America to hold an event celebrating and defending haute cuisine—and the chefs who cook it—than in New York City. The city is home to many of the best restaurants in the country.

But New York City is also a burgeoning food nanny state, boasting many new regulations that would seem more at home in, well, France.

Two years ago, a city councilor briefly considered attempting to ban foie gras, but thought better of it. But that was the last time New York’s restaurant cops showed anything resembling restraint.

Since then, the city has also banished trans fats from restaurant kitchens and forced chain restaurants to display calorie totals, in large type, alongside every menu item. The city, which claims the menu regulation "will help guide informed and healthier food choices," apparently didn’t find it relevant that this information was already available online and in handouts available in each chain restaurant.

The real pleasure of the Duckathlon is this culinary paradox—a troublesome attack by the state on what people eat that is playing out here and in California, Chicago, and many of this country’s bastions of gastronomy. I wanted to know what these foodies—chefs, suppliers, and journalists—think about what is effectively a fight to keep food legal.

Many at the center of the paradox, including some of the best New York City’s kitchens have to offer, are critical of bans that impact what some consider to be staple foods.

“They’re trying to change doughnuts,” a chef at Daniel, one of the city’s (and the country’s) top restaurants, laments when I asked him about the city’s trans fat ban. “I mean, doughnuts are good. They’re great the way they are.”

The Event

D’Artagnan, a twenty-four-year-old, New Jersey-based company, bills itself as “the favorite food purveyor of chefs.” If you’ve ever bought foie gras, guinea hen, or wild boar bacon from an upscale grocer, chances are you have eaten D’Artagnan products.

Owner Ariane Daguin, who like Dumas’s D’Artagnan hails from France’s Gascony region, drew her inspiration for the Duckathlon from a French wine competition.

"I always dreamed of doing something close to what they have in Paris, the Marathon des leveurs de coude,” she tells reason. “Where you go to all the St. Germain cafes, and you drink at every café, and you are in a team formation. Except I wanted it to be more gastronomic."

Though a culinary challenge and promotional event first, Daguin also sees the Duckathlon as an opportunity to push back against the food police, calling it a “counterbalance to people who are trying to limit our choice in food and life.”

The Challenge

The Chelsea Market, near the edge of the Meatpacking District, was home to this year’s event—though D’Artagnan kept the site secret to all but competitors and press, no doubt to discourage the appearance of foie gras protestors who, like pretentious cockroaches, seem to materialize only where excellent food is served.

Most of the twenty Duckathlon events took place at restaurants and bars immediately around the market. The challenges were often as surreal as those faced by D’Artagnan and his fellow musketeers. In the Saucisson Fan-Dangle, contestants donned hoop skirts and—in repeated squats—blindly maneuvered an especially phallic sausage, tied at the waist, into the opening of a milk jug as many times possible within a two-minute time limit.

I found Scott Gold, blogger and author of a recently published meat paean, The Shameless Carnivore: A Manifesto for Meat Lovers, manning the Testicle Festival challenge. Gold, a Brooklyn resident, defends meat eating, and staunchly opposes foie gras bans. Still, he supports the city’s menu-labeling requirements, and isn’t so sure where he stands on the city’s trans fat ban.

“As far as banning trans fats, I don’t know if that’s such a great idea,” Gold tells reason. “But then again, trans fats are useless. I don’t see any reason, as long as you’re cooking decent food, that you should have trans fat at all.”

The tenor of Gold’s comments is echoed by Josh Ozersky, who edits the Grub Street food blog for New York magazine.

“I don’t think, in its upper reaches, New York City is a food nanny state at all,” says Ozersky, also author of the recently published The Hamburger, to reason. “It’s closer to a sybaritic free-for-all.”

Ozersky and Gold are probably both right. The city’s worst food laws don’t really impact those in the “upper reaches” who choose to eat subjectively “decent food.”

So while the city has hundreds of outstanding restaurants, each likely claiming thousands of devoted customers, it also has millions of residents who can’t afford (or be bothered) to eat in them. Those people instead frequent the inexpensive chain restaurants city regulators target.

New York City might be foodie heaven, but if you’re an eater rather than a gastronome, regulators are increasingly futzing with your food. The food really under fire in New York City right now is not that eaten by, for example, billionaire Michael Bloomberg—whose mayoral manse chefs competed at the Duckathlon—but by everyday diners.

Still, the vigilance of Daguin, her staff, and Duckathlon participants is as important as it is admirable.

“In a small little way,” Daguin says, “I hope it’s paving the way to more freedom.”

It is. She is. While groups like the New York State Restaurant Association have rightly challenged New York City bans in court, Daguin brings together the people who love to buy, sell, cook, and eat great food.

At best, it’s a budding movement. At worst, it’s still a lot of fun. And if nothing else, Daguin has again reminded her allies and foes alike that D’Artagnan is willing to occupy the bastion simply to ensure the continued promise of a good meal.

Full disclosure: After writing a few thousand kind words about foie gras in a magazine piece last year, the nice folks at D’Artagnan first sent me an enthusiastic email, and followed that up by sending me the occasional free shipment of foie gras and other foods. I happily devour each one.

Cigarette Flavoratism

jsullum@reason.com (Jacob Sullum) — Wed, 11 Jun 2008 13:00:00 EDT

For years I've argued that a bill authorizing the Food and Drug Administration (FDA) to regulate tobacco products is bad for consumers. I've said the Family Smoking Prevention and Tobacco Control Act, which Congress is once again considering, would stifle competition, raise prices, reduce variety, block the flow of potentially lifesaving information, and impede the introduction and promotion of safer tobacco products.

Such arguments have attracted remarkably little attention, given that consumer protection is the main rationale for FDA regulation. Now I realize my mistake: I should have said the bill was racist.

In my defense, I did not realize until recently that the bill was racist. Then again, neither did the people making that argument.

Take Joseph Califano, who has been a vociferous opponent of smoking since he served as Jimmy Carter's secretary of health, education and welfare. Despite his longstanding interest in the issue, it seems Califano never got around to reading the tobacco bill, which was first introduced in 2004, or at least did not notice a provision he now deems outrageously discriminatory.

Califano told The New York Times his eyes were opened by Louis Sullivan, secretary of health and human services under George H.W. Bush, who called him to complain that the bill bans all cigarette flavors except menthol. It's not clear why Sullivan only recently got riled up about this provision, which anti-smoking activists have been murmuring about for years.

It may have had something to do with a May 13 New York Times story headlined "Cigarette Bill Treats Menthol With Leniency," which reported that "some public health experts are questioning why menthol, the most widely used cigarette flavoring and the most popular cigarette choice of African-American smokers, is receiving special protection as Congress tries to regulate tobacco for the first time." The front-page article quoted William S. Robinson, head of the National African American Tobacco Prevention Network, who explained that his organization and other anti-smoking groups had gone along with the menthol exemption because it was necessary to placate Philip Morris, the only major cigarette maker supporting the bill.

Philip Morris sells a lot of menthol cigarettes, but the flavors forbidden by the bill are offered only by its competitors. The bill's flavoritism is of a piece with its general tendency to help the industry leader maintain its market dominance.

But Robinson was willing to live with the Philip Morris-favoring menthol compromise until two weeks after the Times story ran, when he announced that his group had withdrawn its support for the bill because "our constituents across the country are just livid." In a June 5 op-ed piece published by The Atlanta Journal-Constitution, Califano, Sullivan and Robinson explained the source of that anger.

"This loophole especially undermines the health of African-Americans," they said, since 75 percent of black smokers prefer menthol brands, compared to 32 percent of white smokers. "The bill blatantly discriminates against African-Americans."

In a June 4 letter that was also signed by five other former health secretaries and one former surgeon general, Califano et al. urged Congress to ban menthol cigarettes. Since the rationale for banning flavored cigarettes is that kids like them, the letter said, the menthol exception "sends a message that African American youngsters are valued less than white youngsters."

There are other ways to look at it. Given that white menthol smokers outnumber black menthol smokers by three to one, maybe this isn't such a black thing after all. Alternatively, since the bill allows blacks to smoke the cigarettes they prefer, a freedom it does not allow whites who like clove cigarettes or Camel Cremas, you could argue that it discriminates in favor of blacks.

People who want to ban flavored cigarettes, of course, believe that letting smokers have what they want is a hostile act. But if so, the fact that the bill allows tobacco companies to continue selling the non-mentholated cigarettes overwhelmingly preferred by whites suggests that it blatantly discriminates against European Americans.

Wilhelm Reich: 50 Years in Hell and/or Heaven

bdoherty@reason.com (Brian Doherty) — Mon, 05 Nov 2007 12:08:00 EST

Psychoanalyst Wilhelm Reich had his books burned by the U.S. government in the 1950s and died in prison 50 years ago, in prison basically for refusing to agree with the FDA that his work and devices had no medical value. The Boston Globe notes the opening of his personal paper archives at Harvard, and a possible trend in revival of interest in and furthering of his research.

The Wilhelm Reich Museum.

A devotee's history, with links.

A skeptic's analysis of Reich, with links.

The FBI on Reich.

Robert Anton Wilson's harrowing and wonderful play, Wilhelm Reich in Hell.

I operated a cloudbuster once. I cannot authoritatively state whether it had any effect on the weather.

More on the Abigail Alliance

rbalko@reason.com (Radley Balko) — Sat, 11 Aug 2007 00:46:00 EDT

Just to clarify this post, I didn't mean to imply that there is a right to medication that someone else must provide. Only that you should have the right to transact with a willing vendor to access lifesaving medication. The ruling says no—that the federal government may in effect allow you to die in order to protect you from drugs that may not work (note that this isn't even an issue of safety, only efficacy). If anything at all is still covered by the Ninth Amendment (and alas, it seems that nothing is), I would think it would be the right to allow yourself the chance to save your own life.

Also, I neglected to link to our own Kerry Howley's excellent feature on the topic from our August/September issue.

Protecting Us to Death

rbalko@reason.com (Radley Balko) — Fri, 10 Aug 2007 13:38:00 EDT

Cato's Roger Pilon dissects the D.C. Circuit Court of Appeals decision last week denying a right to potentially lifesaving drugs that are still under review by the FDA.

The Ninth Amendment makes a rare guest appearance.

The Milk Club

jsamuel@reason.com (Juliet Samuel) — Thu, 09 Aug 2007 17:30:00 EDT

The NYT wrote yesterday of a rising trend of illegal substance use, outlawed by the FDA for twenty years, but used by half a million people in the U.S. The product is raw milk—straight from the udder, just as the cow intended. Currently, most milk in the U.S. is pasteurized, which involves heating it to temperatures at which nasty bacteria (E. coli, salmonella, etc) break down, then cooling it down again and bottling it up. According to raw milk drinkers, the process gets rid of its “rich” taste and beneficial bacteria. But it’s often the only legal way to buy and sell milk:

While its sale for human consumption is illegal in 15 states, New York is one of 26 where it can be bought with restrictions. The chief one is that raw milk can only be sold on the premises of one of 19 dairy farms approved by the state. Clandestine milk clubs, like the one Mr. Milgrom-Elcott joined, are one way of circumventing the law, and there are others.

And the market is growing:

In 2000, the Organic Pastures Dairy Company in the San Joaquin Valley near Fresno became California’s first raw milk dairy with certified organic pasture land. This year its co-founder, Mark McAfee, expects it to gross $6 million — up from $4.9 last year.

It's legal within California, but the only way to ship it across states lines without inciting the FDA’s wrath is to label it as pet food. Admittedly, despite its “natural” appeal, raw milk might not be perfectly healthy (“In 1938, for example, milk caused 25 percent of all outbreaks of food- and water-related sickness”), but it’s hardly the FDA's place to snatch bottles of milk from the hands of full-grown adults.

Dying for Lifesaving Drugs

khowley@reason.com (Kerry Howley) — Wed, 25 Jul 2007 12:00:00 EDT

Ten years ago, doctors drilled a hole into John Gotschall's skull, inserted two catheters, and pumped a poison into his brain. Using a child's morphine pump, the team of neurosurgeons pushed diphtheria toxin into Gotschall's temporal parietal lobe over a period of four days. Eight weeks later, they did it again, reusing the same cavity and pumping in a slow stream of tissue-killing fluid.

Gotschall was not well. Shortly before he invited a team of surgeons to experiment with his cerebral tissue, the 44-year-old municipal worker had plowed his car into a snow bank on a Baltimore street. When he woke up at the hospital, doctors told him he'd had a seizure at the wheel. An MRI revealed the cause of that seizure: a tumor deeply embedded in his brain tissue. There are different grades of brain tumor, many of them slow-growing. Gotschall had glioblastula multiforma (GBM), brain cancer in its most aggressive and deadly form, and he likely had only months to live.

Gotschall's physicians initially ordered chemotherapy and radiation, the same weapons with which doctors have fought cancers for decades. Neither worked. After he exhausted the standard options, he started searching for nonstandard ones. His neuro-oncologist pointed him to a group of doctors at Johns Hopkins and a drug in development called TransMID. TransMID had survived Phase I testing, in which researchers evaluate a medication's safety and appropriate dosage, and was then in Phase II, in which researchers begin to evaluate efficacy. Gotschall finally caught a break: He qualified for entrance into the trial. Along with 43 other patients, Gotschall would have a chance at a radical new treatment that might add years to his life.

TransMID is a Trojan horse: The drug attacks the tumor under the pretense of a gift. Tumors feed on iron they absorb from surrounding tissue, and the drug delivers deadly, iron-wrapped diphtheria toxin straight to the site of the disease. The method is meant to be more precise than scooping out the cancerous tissue, a technique that can be as clumsy as its cringe-worthy name, debulking.

The treatment proved immediately effective in the most dramatic way possible. Gotschall's tumor simply vanished. TransMID's newest poster child, he touted the treatment on CBS Morning News. "It is dramatic," Gotschall's neurosurgeon, John Weingart, told CBS. "I mean, there is no question that this is an unbelievable response."

Ten years later, TransMID is still not available to the public. About 18,500 Americans will be diagnosed with GBM this year, and the median patient will survive 14 months. Treatment has not advanced significantly in the last 20 years, so GBM victims will be offered more of the same: chemotherapy, radiation, and when possible, surgery. TransMID entered Phase III tests, meant to confirm efficacy and monitor the drug's side effects, last year. But most currently diagnosed GBM patients probably will never know about the drug, and most of those who do find out about it will not qualify for trials. If TransMID ever does go to market, these patients will be dead by the time it gets there.

For as long as there are lifesaving drugs in development, there will be dying patients undaunted by the dangers of an unapproved treatment. But within the strictures of the current regulatory regime, very few patients--mainly those who, like Gotschall, meet the criteria for clinical trials--are granted the freedom to risk their lives in the face of certain death. Consider the conditions for admission to the TransMID trial. "The tumor has to have grown 25 percent since the patient's last MRI, but it has to be under five centimeters," explains Patrick Rossi, a physician employed by Celtic Pharma, TransMID's manufacturer. "It can't have grown into the ventricles or the brain stem. The patients have to have failed every other treatment: chemo, radiation, stereotopic radio surgery, any kind of oncology agent, grandma's soup, voodoo, you name it."

To terminally ill patients who do not qualify for such trials, and typically cannot receive drugs until they are deemed effective by the Food and Drug Administration (FDA), this obsession with clinical control can appear deadly and cruel. As TransMID trickles through the FDA pipeline, GBM continues to kill thousands of Americans every year. Most patients who don't meet the criteria for admission to clinical trials will not be granted the right to risk their lives with a developmental treatment.

Since the 1960s, when randomized, double-blind clinical trials became a standard requirement for bringing new drugs to market, clinical researchers have confronted the chaos of disease with the trappings of a regimented, uncompromising order. Drug trials are rooted in centralized authority: trial slots are numbered, subjects handpicked, control groups maintained, patients monitored. Maintaining this level of precision requires not only the cooperation of willing test subjects, but the coercion of the general population. To preserve pristine testing conditions, the federal government curtails our freedom of exchange and our right to take risks. Ailing individuals and drug companies are prohibited from trading in unapproved drugs, and terminal patients forbidden to experiment outside a clinician's watch.

This approach to drug testing is rife with serious ethical problems, but the preconditions for meaningful change are mind-boggling. The current clinical trial regime is cemented in place by legal restrictions that prevent patients from waiving their rights to sue and a regulatory regime that resists even incremental change. Alternatives to the standard placebo-controlled, closed clinical trials exist, but guarantees that such trials will lead to a drug's approval do not. A system meant to facilitate innovation in drug development is itself resistant to change.

With billions of dollars on the line, the clinical trial industry has never been more powerful. But in an age of increasing patient autonomy, the walls surrounding the drug testing system are under assault like never before. An organization called the Abigail Alliance for Better Access to Developmental Drugs is suing the FDA, claiming a constitutional right to trade in lifesaving pharmaceuticals. The group wants to crack open the system, to give patients and their doctors the right to choose between taking experimental, often dangerous drugs and dying untreated.

To the dismay of the medical establishment, bioethicists, and many groups representing cancer patients, a federal appeals court has ruled in the alliance's favor. As the case continues to wend its way through the courts, doctors, researchers, and even patients warn that the suit could bring the drug development process to a screeching, lethal halt.

Resurrection and Insurrection
The FDA runs on $1.5 billion a year, while the global clinical trial industry is worth roughly $10 billion. The Abigail Alliance, based in its founder's home in Fredericksburg, Virginia, subsists on $50,000 a year in donations. Its one full-time employee is Frank Burroughs, father of the late, eponymous Abigail.

Burroughs, now in his sixth year of advocacy, has lost many of his most important co-members. After last year's ruling in the alliance's favor, the FDA argued that the group no longer had legal standing to sue it, since none of the patients who had signed the original affidavits were still members. They were all dead.

The alliance launched its assault on the FDA in 2001, right after 21-year-old Abigail Burroughs died while fighting for access to developmental treatment for head and neck cancer. In 2003, Frank Burroughs and his pro bono lawyers at the Washington Legal Foundation, a public-interest litigation group, filed a federal lawsuit in D.C. They maintain that terminal patients have a constitutional right to lifesaving experimental drugs that have passed the first phase of FDA testing--the phase that establishes the safety and tolerability of a treatment. The right to self-preservation through access to experimental drugs, the alliance argues, is a substantive due process right, implicit in the Fifth Amendment principle that no person may be deprived of life, liberty, or property without due process of law. The Supreme Court has used substantive due process reasoning, which is highly controversial among legal scholars, to recognize unenumerated constitutional rights to abortion, to private sexual activity, and to send children to private schools. The Abigail Alliance argues that it also protects the right of terminally ill patients, acting on a doctor's advice, to obtain potentially lifesaving medication when all other alternatives have been exhausted.

The group's complaint was dismissed, but last year a three-judge panel of the U.S. Court of Appeals for the D.C. Circuit overturned that decision. "A right of control over one's body has deep roots in the common law," Judge Judith Rogers concluded in the majority opinion. "The prerogative asserted by the FDA...impinges upon an individual liberty deeply rooted in our Nation's history and tradition of self-preservation."

The appeals court decision drew little attention, but the media coverage it did attract was almost uniformly negative. "A court makes up a right," snarked the Washington Post editorial page. A June 2006 article in The New Republic said the court's logic would put us "back in the snake-oil days," and The Journal of the American Medical Association lamented "a new era of unapproved drugs."

The FDA sought a rehearing by the D.C. Circuit, and a 10-judge panel heard the arguments of both sides in March. No matter how the court rules, the Abigail Alliance expects its legal battle to end in the Supreme Court.

After Burroughs, the man who spends the most time promoting the Abigail Alliance's cause is a geologist named Steve Walker. In December 2000, Walker and his wife of 20 years--Jennifer McNeillie, also a geologist--were in the process of adopting a child abroad. The two had paid an agency, were looking at pictures, and were preparing to go to Russia to make their final arrangements. Before they got there, Jennifer was diagnosed with Stage 4 colon cancer. At 45, she was told she had a slim chance of making it to 50.

McNeillie's bleak prognosis coincided with a flurry of promising research in colon cancer treatment. Three new drugs, Erbitux, Eloxatin, and Avastin, were in development, and McNeillie decided that the risks of being a test subject were worth taking. She would wait years, her cancer progressing, for the chance to try one. There were no Eloxatin trials in progress at the time, and Erbitux and Avastin trials were both closed to new enrollment. "The drugs were simply unavailable," says Walker. "We couldn't get into the trials."

In September 2002, a bedridden McNeillie was finally admitted into a small Erbitux trial. "The drug resurrected her," says Walker. "We went skiing in Colorado. We went hiking." Without the drug, cancer cells that lined McNeillie's stomach would appear, expand, leak fluid. McNeillie would blow up like a balloon every four days and have to go to the hospital, looking six months pregnant, to be drained through a catheter. On Erbitux, her worst side effect was a rash. She went back to work.

Six months after she started taking the drug, doctors spotted a new tumor on her colon. By the rules of the trial--rules set to ensure the FDA would accept the results--McNeillie could no longer participate. No trial meant no drug. When Walker pleaded with McNeillie's physician to keep dispensing the drug, the doctor pleaded back: Giving out more Erbitux could mean giving up his license to practice medicine.

Determined to dig up more Erbitux, Walker spent six weeks shuttling between the drug's manufacturer, ImClone, and the FDA. ImClone responded quickly, offering to set up an entirely new trial just for McNeillie so her treatment would conform to protocol. It took ImClone 10 days to set up the trial. The FDA then delayed for two and a half weeks, mulling approval. "This is to give the same drug the same way by the same doctor," says Walker. "During this time my wife is dying. She is tremendously suffering." At the same time, Walker was trying to get his wife into an Avastin trial. She didn't qualify.

Six weeks after she'd been kicked out of the trial, McNeillie was given a dose of Erbitux. She passed away after six months on the drug, in June 2003. Eight months later, the FDA deemed Erbitux and Avastin safe and effective treatments for colon cancer.

The Abigail Alliance has collected many such stories. There is David Baxter, a high school student suffering from colorectal cancer, denied admission to trials for a promising drug because he was too young to qualify. He died at 17 in 2001. Alita Randazzo, also suffering from colorectal cancer, spent years flying to France to get Eloxatin, which had been approved there but not yet in the U.S. When Eloxatin stopped working, she was told by her doctors that her last hope was Erbitux. Trials for Erbitux had closed. She died in 2002, still fighting for access.

A Hard ACT UP to Follow
Enraged patients have jolted the FDA into action before. In New York in 1987, protestors from the AIDS Coalition to Unleash Power (ACT UP) hanged an effigy of FDA chief Frank Young on Wall Street. Activists complained that AIDS drugs were too slow in being approved and too expensive when they went to market. A year later ACT UP brought 1,000 protesters to the FDA's headquarters, vowing to shut the agency down. The FDA stayed open, and 180 protesters were arrested.

Graced with voluminous media coverage, AIDS activists found their confrontational tactics rewarded. AZT had been rushed through the process before the activists showed up at the FDA's doors, the protease inhibitor Saquinavir was approved three months after it was submitted for approval, and a similar drug, ritonavir, was approved 24 hours after an FDA panel recommended that it be allowed on the market. It was as if they'd slipped the FDA a massive dose of Adderall.

In the early 1990s, under congressional pressure to reform, the FDA introduced "fast track" regulations to speed review of certain drugs and complex "expanded access programs" through which terminally ill patients could potentially receive medication. In 1997 then-President Clinton signed the Food and Drug Modernization Act, part of which allowed individual patients to request access to developmental drugs.

But many of the gains applied exclusively to AIDS patients, and from where Burroughs is standing, even the systematic reforms appear inadequate. Setting up an expanded access program, he argues, is such a bureaucratic nightmare that the program is "essentially inoperative." The process involves a significant amount of paperwork for the patient's doctor, who may not be aware of drugs in development; the pharmaceutical company, which has no real incentive to participate; and the FDA, which is not known for its alacrity in tackling administrative tasks. Drugs aren't eligible for such programs until late in the clinical trial process. Still, such programs do exist and they are occasionally utilized. Two patients have won the right to try TransMID through such a program.

As the heyday of activism passed and the AIDS movement matured, pressure for radical change began to wane. The Abigail Alliance is no ACT UP, and Walker and Burroughs look with envy upon the group's ability to jam drugs through the FDA bureaucracy. "Originally, we tried to get support from the AIDS community," Burroughs recalls.

"But we didn't. They had won their victory." The 1980s marked the first time dying patients had risen against the FDA, and no movement of similar strength has emerged since.

In its fight against a sclerotic system, the AIDS community had a major advantage: It actually was a community. Organized around civil rights, supported by the political left, noticed by the mainstream media, AIDS patients formed a vocal, recognizable class. "Contrast that with the class of patients who are terminal," says Walker. "There are hundreds of cancers. These people have nothing in common. By the time they're sick, they have no way of connecting to anyone else. They don't have time to go to meetings and lobby the FDA. The only thing they have in common is that the FDA stands in their way. And sometimes they don't even know that."

It's more than a lack of organization that plagues the alliance. Groups representing the victims of deadly diseases are often vocally opposed to its agenda. The American Society of Clinical Oncology submitted an amicus brief in the alliance's pending case-in support of the FDA. In a September 2003 press release, Fran Visco, head of the National Breast Cancer Coalition, announced that a victory for the Abigail Alliance would "undermine scientific research and impede our search for answers that will help everyone." The Leukemia & Lymphoma Society, the National Childhood Cancer Foundation, and the National Patient Advocate Foundation have all voiced their intention to side with the government.

‘Piles of Bodies'
While Burroughs and Walker believe they are tearing down senseless bureaucratic obstacles, their opponents charge that the Abigail Alliance is trying to hijack drug development the world over. Clinical trials have been the primary way the medical establishment obtains information about drug efficacy for the last 50 years. To its detractors, the alliance seems prepared to cripple an ever-evolving body of pharmaceutical research. In the interests of a few patients suffering now, it is willing to cause an untold amount of damage to patients yet to be diagnosed.

Trials conducted in the United States are the most rigorous in the world, consisting of three distinct phases, typically involving thousands of patients. Only 11 percent of drugs that enter clinical trials are ultimately approved, and the numbers are markedly worse for cancer drugs. Anyone who argues for the unencumbered right of patients to take developmental cancer drugs must grapple with the fact that 94 percent of them will not work.

To sift the pharmaceutical gold from this vast bed of chemical silt, drug companies need some type of trial system, and for trials they will need patients. Trials are typically randomized, meaning that some patients will receive the treatment and others will not. If patients could simply obtain the medicines they wanted, they would have little incentive to enter the clinical testing lottery.

"How do you take a rational person and get that person to enroll in a double-blind, randomized clinical trial?" asks Steve Walker. "How do you get people to do that? You give them no other choice. They're not lives worth saving. They're lives worth using. If you can't get into the trial, they can't use your life. They need two piles of bodies."

Mindful of medicine's dependence on test subjects, the alliance isn't asking that all patients get access to development drugs. It's asking that patients already denied admission to trials--patients like Abigail Burroughs and Jennifer McNeillie--be able to buy the drugs they're denied. And even this concession, argue their opponents, would dismantle the clinical trial system.

The amicus brief submitted by the American Society of Clinical Oncology argues that if people who didn't qualify for trials had access to drugs, patients would have an incentive to appear ineligible. Their physicians could easily help them game the system by, say, ordering a round of chemotherapy, which disqualifies patients for many Phase II and Phase III trials.

By that logic, Abigail Burroughs had to be denied treatment to protect the integrity of the clinical trial process. Terminal patients who cannot gain admission to trials still must be prevented from receiving developmental drugs, lest future patients refuse to submit themselves to randomized testing. "They need test subjects," says Walker, "and patients are their only resource." Pull even a single thread, and the whole information-aggregating web unravels.

This conflict has a way of pitting those without any hope of survival against those with some chance at life. Take David Welch, co-founder of the successful software company Telco Exchange. In 2004 doctors found a tumor the size of a lemon in Welch's left frontal and left temporal lobes. The 38-year-old chose to be aggressive, pursuing a treatment so risky that three review boards rejected his request to have the operation performed at their hospitals. The treatment was successful, and Welch, now on his 19th round of chemotherapy to keep the remaining cancerous cells at bay, is unambiguously positive about the operation and his right to risk it.

Welch might seem the typical Abigail Alliance booster, eager to argue for the right to experiment in the face of death, but he is deeply ambivalent. "I medically inherit what has been given to me," he says. "Statistically, I've got a time line of five to six years. The more time I buy, the more time I have for clinical trials to play out. I'm still open to arguments, but I fail to see how we can change the process without breaking it down."

Welch also argues that even if pharmaceutical companies were allowed to sell their drugs prior to approval, they have strong incentive not to do so. Anything that happens to a patient taking a drug in development could later be used to argue against approval, halting manufacture and denying that drug to future patients. And under current FDA regulations, patients cannot waive liability for negligence. Whether they want it or not, patients must have the right to sue, which means they may never be given the chance to take a risk. If the Abigail Alliance wins its case, it will face additional legal battles.

There is a serious argument to be made that the entire clinical trial system is antiquated, that it is time to stop counting piles of bodies and to start using more sophisticated measures of drug efficacy. Biomarkers, substances whose presence in the body indicates a particular disease state, could provide objective evidence on how a drug is working on a particular patient. As such measures improve, the need for placebos may lessen. "Clinical trials are very cumbersome," says Thomas Garvey, a gastroenterologist and former FDA supervisor who has designed thousands of clinical trials. "Although they are not the be all and end all. The science is evolving and getting better."

A March 2005 editorial in The Wall Street Journal advocated scrapping placebo trials for cancer patients altogether, giving everyone access to the drugs, and using advanced statistical methods to measure patient progress versus the typical survival rate for a particular cancer. This is the kind of change the Abigail Alliance hopes for, but more incremental changes are already in play.

In an attempt to increase flexibility and reduce approval times, some pharmaceutical companies have begun to conduct what are known as "adaptive" trials. Standard trials are blinded: The findings remain secret from researchers until each phase of the trial is over, and they are conducted on general populations of patients with similar conditions. Even after a standard trial has ended, it can be difficult to know which patients within a population will respond most positively or suffer the most severe side effects from a particular drug.

Alternatively, adaptive trials allow researchers to analyze and respond to data as it comes in, personalizing treatments and assessing how patients with particular characteristics respond to particular dosages. Researchers can tweak the trial design as they move forward, perhaps dropping a method of treatment that proves unpromising or adding more of one type of patient that seems to be responding well. Trial flexibility may prompt shorter approval times and allow companies to sort good drugs from bad more efficiently. "It's a slightly less restrictive straitjacket," says Walker.

Drug development needs to move in lockstep with the regulatory regime, and the FDA has signaled its openness to new trial design with its "critical path initiative," a program meant to jump-start the process of moving toward more sophisticated clinical trials. Its stated goal is to "bring new scientific discoveries--in fields such as genomics and proteomics, tissue engineering, imaging, and bioinformatics--to bear on product development."

While the agency's potential for change is heartening, the critical path initiative is widely acknowledged to be under-funded and lacking in institutional support. For the foreseeable future, the system will be one that pits David Welch against Abigail Burroughs, information gathering aimed at helping future patients against current patients' desire to live. Dying people will be treated as data points; other dying people desperately want those data.

The View From 40,000 Feet
In February the Food and Drug Law Institute, a D.C. nonprofit that promotes education on law and public policy, held a colloquium on the Abigail Alliance's lawsuit that illustrated just how far outside the medical consensus the alliance and its supporters really are. The colloquium included high-profile lawyers, a specialist in pharmacoeconomics, and Arthur Caplan, one of the world's most prominent bioethicists. The only panelist clearly in favor of the alliance's position was Scott Ballenger, the alliance's lawyer.

Most of the panelists expressed profound discomfort with the Abigail Alliance's rights-based argument and its challenge to the regulatory structure. Caplan argued that terminally ill patients are desperate and therefore may be more in need of the FDA's paternalism than other classes of patients. The panelists spoke of caution, of "giving pause," of balancing risk between patient and society.

After hours of staid presentations and speeches before an audience of 100, Steve Walker approached the mike as an audience member. "You're all approaching this topic from 40,000 feet," he charged, launching into an impassioned retelling of his wife's decline. The panelists looked nervously at their colloquium booklets. The moderator, shifting in her seat, looked torn over whether to cut him off.

Such are the P.R. challenges of the Abigail Alliance. As lawyers, medical professionals, and bureaucrats debate the optimal regulatory structure, Walker and Burroughs want to supplement abstractions with anecdote, to replace talk of test subjects with stories of dead wives and daughters. But when they trade the language of clinical science for that of loss and bereavement, they can come off as too invested to be reasonable and too emotional to merit response. In the heavily risk-averse culture of the FDA bureaucracy, talk of rapid, radical change isn't even countered. It's just ignored.

Even more than the regulatory barriers, this deep-seated fear of disorder works against the alliance's agenda. "I don't have a right to fly somebody'sexperimental airplane," reasoned BruceChabner, clinical director of the Cancer Center at MassachusettsGeneral Hospital, Boston, in the August issue of the New England Journal of Medicine, "so why should I have the right to somedrug that a company has dreamed up?" In defending the status quo, Chabner apparently did not pause to consider that cancer drugs, as opposed to airplanes, are unlikely to fall out of the air and kill passersby. Nor are people typically forced to choose between flying an "experimental airplane" and certain death. The right to self-medicate is considered so absurd that incoherence passes for analysis in respected medical journals, while opposition is treated as hysteria.

Things weren't looking much better on March 1, the day the alliance defended its case, for the second time, before the U.S. Court of Appeals for the D.C. Circuit. Scott Ballenger began by stating the alliance's claim: that "terminally ill, mentally competent adult patients have a due process right to informed access to potential lifesaving investigational new drugs determined by the Food and Drug Administration to be sufficiently safe for expanding human trials, where there are no alternative government-approved treatment options."

"That's an awfully specific right," barked Judge David Sentelle, less than a minute into Ballenger's argument. "I may have gotten a thin copy, but I had a hard time finding it in my copy of the Constitution."

The FDA argues this very specific right has been "gerrymandered," its boundaries improbably stretched and manipulated to fit the alliance's very specific demands. In order to disrupt the existing legal framework as little as possible, the alliance has settled upon a narrowly defined right to lifesaving pharmaceuticals. "We have described the contours of the right in terms of the present regulatory regime," says Ballenger, "and we're not trying to destroy it." The alliance concedes to the FDA that it has a compelling state interest in protecting the integrity of the clinical process. It concedes that the FDA has the right to deny dying people drugs that have not yet been subjected to Phase I testing. But it still claims this very narrow right is implicit in the concept of due process.

If terminal cancer patients do have a constitutional right to lifesaving drugs, the limits of that right are hard to discern. What does it mean to be "terminally ill," after all, and where is the line between a lifesaving drug and a life-prolonging one? Could a suicidal cancer patient claim she has a constitutional right to marijuana in order to ease her pain? Does it make any sense to say a fundamental right hinges on the FDA's determination that a drug has passed Phase I testing? And if not, what does that say about the Controlled Substances Act, the Supreme Court's recent rulings on medical marijuana, and the FDA's role as medical gatekeeper?

Although the Abigail Alliance has chosen not to assert a broader right of individual autonomy, the narrow right it claims seems to imply profound change to U.S. law. "Wouldn't the right you're asserting here also apply, then, to the right to therapeutic cloning, or to organ purchase?" Judge Brett Kavanaugh asked a few minutes into Ballenger's oral argument. "Don't we have to take into account the repercussions of what you're asking for here?"

This is a slippery slope, and it alarms supporters of the status quo. Once you argue that the government has no authority to deny Jennifer McNeillie access to cancer drugs, that she has a constitutional right to accept a certain level of risk, it becomes difficult to know where the agency's authority stops and her autonomy begins.

Staying Power
John Gotschall's glioblastoma disappeared for five years after TransMID, the Trojan horse, tricked the tumor into absorbing it. Meanwhile, the drug lumbered along its tortuous road to approval. GBM is a relatively rare disease, and TransMID has a tiny prospective market. Celtic Pharma's Rossi estimates testing has cost more than $600 million so far. And during the last 14 years, the drug has cycled through no fewer than nine pharmaceutical companies in three countries. Every time TransMID's backers are bought out, as often happens in the industry, Rossi needs to justify the enormous costs of clinical testing to new owners with new priorities. Time and time again, an acquisition or merger has left the drug without funding, at which point Rossi cries, pleads, and eventually brings the dead drug back to life. He casts his relationship to TransMID as something out of Night of the Living Dead. "My colleagues call me George Romero," he jokes.

In January of this year, Rossi was busy scouring the globe in search of eligible tumors. The planned Phase III trial would require 363 patients, of which Rossi had found only half. But in February TransMID met with yet another obstacle. Celtic Pharma decided to terminate Phase III testing "on commercial grounds," citing the unlikelihood that the drug would meet efficacy requirements in the late-stage patients it was testing on. TransMID's future is once again unclear; Celtic may undertake new trials in patients with early-stage tumors, sell TransMID to yet another sponsor, or terminate the drug's development altogether. The 143 patients already enrolled in Phase III testing will have to petition the company if they want more of the drug.

As drug approval progresses in fits and starts, patients are liable to fall into the gaps. When Gotschall's tumor returned in 2002, Phase II of the clinical trials had concluded, and production of TransMID had been halted during a merger. There was simply no new drug to give him.

Rossi petitioned the FDA for permission to dispense some TransMID left over from Phase II, but the FDA would not grant permission to use the remaining drug without potency and stability analyses. TransMID's backers ordered the relevant tests. When those results were in, Rossi reapplied for permission. The process took over 3 months. "By the time we got approval to use the Phase II material," recalls Rossi, "they gave John only days to live." Gotschall finally got the treatment, his tumor rapidly growing. He died six months later.

In the nexus between men like Gotschall, who surrendered himself to the whims of researchers, and Abigail Burroughs, who never got the chance, lie uncomfortable truths about drug experimentation and patients. At the very least, men like Frank Burroughs and Steve Walker force us to acknowledge what we give up by insisting on the cold order of randomized trials; they cast the trade-off in the starkest of terms, because the lives of people they loved were part of what was traded. Whereas patients once had the right to treat their bodies as laboratories, their selves as subjects, the right to experiment on individuals is no longer the province of the individuals themselves. Patients fight for the right to be test subjects for others, and consider themselves lucky to be chosen.

At the end of our last long interview, after Walker delivered his usual hyperarticulate assessment of the cruelty of the clinical trial system, capped off with another description of his wife's final days, his voice grew suddenly weary. "God, I hate talking about this," he said quietly. Patients of the present and future should hope he keeps talking. Perfect information comes at a cost. And as Walker keeps reminding researchers who don't want to listen, that cost does not fall on everyone equally.

Kerry Howley is a senior editor of Reason.

Also These May Ye Smoke: Of Those That Are Clove-Flavored...

jsullum@reason.com (Jacob Sullum) — Wed, 18 Jul 2007 07:22:00 EDT

Cigarette smokers with bohemian pretensions can breathe a fragrant, spicy sigh of relief: The bill that would authorize the FDA to regulate tobacco products, which originally prohibited all cigarette flavors except tobacco and menthol (ostensibly to help repel underage smokers), now makes an exception for cloves as well. The change supposedly was prompted by complaints from the Indonesian government, which said banning imports of clove cigarettes while permitting the sale of domestically produced menthol brands would violate America's free trade commitments. Another factor may have been Philip Morris's recent introduction of clove-flavored Marlboros in Indonesia. Although Philip Morris, the only tobacco company that supports the FDA bill, says it "has no plans" to sell clove cigarettes in the U.S., it hardly seems a coincidence that the two cigarette flavors permitted by the bill are ones it uses, while the banned flavors (which include vanilla, chocolate, cinnamon, and orange) are used by its competitors.

Anti-smoking activist Michael Siegel reports an even funnier change to the bill: Tobacco companies would be forbidden to tell their customers that cigarettes are regulated by the FDA, lest the public mistakenly infer that cigarettes are safe. The bill's sponsors explain why it's necessary to stop cigarette makers from making statements that are indisputably true:

If manufacturers are permitted to state or imply in communications directed to consumers that a tobacco product is approved or inspected by the Food and Drug Administration or complies with Food and Drug Administration standards, consumers are likely to be confused and misled. Such a statement could result in consumers being misled into believing that the product is endorsed by the Food and Drug Administration for use or in consumers being misled about the harmfulness of the product because of such regulation, inspection, approval, or compliance.

Siegel, who has long opposed the bill in large part because he thinks it would have precisely this misleading effect, comments:

Apparently, the only way this legislation will work is if we trick people into thinking that the FDA does not regulate cigarettes....

What kind of cockamamie regulatory scheme depends upon the public not knowing about that scheme in order to avoid severe public health consequences?

How sensible can a regulatory approach be if we need to hide from the public the very fact that the regulatory scheme is in place?...
That is how foolish this legislation is. So foolish that we need to infringe upon the companies' First Amendment rights in order to make sure that the public doesn't catch wind that the legislation is in place.

Sunscreen Screening

jsullum@reason.com (Jacob Sullum) — Mon, 09 Jul 2007 07:02:00 EDT

The Environmental Working Group rates 786 varieties of sunscreen available in the U.S., based on both effectiveness and potential health hazards. It concludes that "only 17% of the products on the market are both safe and effective, blocking both UVA and UVB radiation, remaining stable in sunlight, and containing few if any ingredients with significant known or suspected health hazards." The EWG provides separate ratings for effectiveness and safety, so if you're not worried about, say, possible allergic reactions to the fragrance in L'Occitane Immortelle Very Precious Fluid (SPF 40)—which rates a 7 on the "health hazard" scale but a 0 on the "sun hazard" scale (meaning it's highly effective)—you can still see how well the product blocks ultraviolet light.

Interestingly, despite its extra-cautious attitude regarding unconfirmed hazards, the EWG faults the Food and Drug Administration for preventing the U.S. sale of sunscreens that have long been available in Europe. Some of these products are especially effective at screening out UVA light, which does not cause sunburn but may pose a more serious skin cancer risk than UVB light does. The EWG prefers them to similarly effective FDA-approved alternatives that contain nano-particles, which it says "raise potential concerns":

Micronized and nano-scale zinc oxide and titanium dioxide in sunscreen provide strong UVA protection, and are contained in many of our top-rated products. Repeated studies have found that these ingredients do not penetrate healthy skin, indicating that consumers' exposures would be minimal. Studies on other nano-scale materials have raised concerns about their unique, toxic properties. FDA has failed to approve effective UVA filters available in Europe that, if approved here, could replace nano-scale ingredients.

At the same time, the EWG criticizes the FDA for allowing sunscreen manufacturers to make misleading claims such as "blocks all harmful rays," "waterproof," and "all day protection." The agency has been dragging its feet on sunscreen safety standards for decades. Meanwhile, the misleading claims have prompted class action lawsuits in California. Although I don't know the details, in principle this seems like an appropriate response: Companies should be held liable for selling products under false pretenses, but in this case the loss to any one consumer is too small to make individual suits cost-effective. While the FDA dithers, the threat of civil judgments and the educational efforts of independent groups such as the EWG can help protect consumers from fraud and steer them toward the best products.

Backtracking Our Way to Safety

rbailey@reason.com (Ronald Bailey) — Fri, 18 May 2007 15:12:00 EDT

Thousands of cats and dogs may have died from eating pet food made with wheat gluten and rice protein from Chinese companies that had deliberately contaminated their goods with melamine. Melamine is an ingredient in plastic that is used to make Melmac dinnerware, among other things. The melamine had evidently been added to boost the nitrogen content of the gluten and rice protein. Nitrogen content is often used as a marker for high protein content in food ingredients.

Hot on the heels of this contamination episode came reports that a poison, diethylene glycol, shipped from China as glycerin had been mixed into cold medicines in Panama. As many 100 people may have died from taking this adulterated drug. Diethlyene glycol is an ingredient in antifreeze and causes acute kidney failure when drunk. As an historical note, in 1937, diethylene glycol was mixed with the nasty-tasting antibiotic sulfanilamide in an elixir sold by the Massengill Company in the United States. Over 100 people died from taking it, and the scandal led directly to the passage of the 1938 Food, Drug, and Cosmetic Act, which increased FDA's authority to regulate drugs.

In the wake of the melamine contamination, CNN's own anti-globalist rottweiler Lou Dobbs, wondered, "Why in the world is the United States importing Chinese food?" And Dobbs was not alone. In a column entitled, "The Price Of Imported Food Is Too High," conservative Eagle Forum founder Phyllis Schafly darkly speculated, "Maybe China's poisoning of our pets will be one offense too many to tolerate."

Poisonous pet food and medicinal ingredients are a big problem. So what should be done about them? The most popular response from Congressional committees has been to advocate more money for a bigger FDA budget and more FDA food inspectors. Currently, the FDA inspects about 2 percent of food shipments from China. Another proposal is to create a centralized federal food safety agency. Even Daniel Griswold, director of the libertarian Cato Institute's Center for Trade Policy Studies acknowledges that "the U.S. retains full rights and sovereignty to inspect any imports on the grounds of public health and safety."

However, Griswold cautions against any hasty moves toward a general ban on food imports from China. "A knee-jerk effort to shut down imports from a specific place is the wrong way to go," says Griswold. Food safety is not just a foreign trade issue. He points out tainted spinach came from California and impure meats were shipped from Nebraska. "The place of origin of adulterated products is not as important as the fact they are entering food and drug supply chains," says Griswold.

More food safety inspectors might help, but not even the most ardent food safety activists are demanding that all food imports be inspected by government agents. Our best check against food adulteration and contamination is the self-interest of private companies backed up by government muscle when necessary. If Chinese companies earn a reputation as unreliable suppliers, American manufacturers will go elsewhere. "Chinese companies must clearly understand that their standards need to be higher if they want to export to the U.S. market," says Griswold. "Otherwise there will be a real price to pay for falling short of high standards."

As for now, food and drug manufacturers will work back down their supply chains to figure out how to improve their in-house safety procedures. In fact, this is already being done by pet food manufacturers who are planning to hire private laboratories to check imports to make sure that they are the right products and that they meet quality standards. Many large American companies have already established transnational quality assurance systems. After some initial reluctance to deal with the matter, the Chinese food safety authorities have detained officials from the two companies who shipped the adulterated gluten and rice protein. FDA inspectors in China found the facilities of the two companies shut down. Less happily, the supplier of the poisonous diethylene glycol is still being investigated.

The most effective way to address food and product safety issues is greater transparency. Cheaper information technology is already making it possible for companies (and inevitably governments) to mark and trace the provenance of all products and ingredients through their supply chains. All products will one day be accompanied with records tracing their origins from mines, forests, fields, oceans through factories and shippers to final consumers. Companies will immediately flag any break in the chain of provenance and demand that suppliers authenticate their goods. If that's not forthcoming, they will call the regulators in. My prediction is that such a comprehensive and largely private product tracing regime will evolve and be in place in the next ten years. In a decade or so, Americans will not have to give a second thought about whether their food and drugs come from Salinas or Shanghai.

Ronald Bailey is Reason's science correspondent. His book Liberation Biology: The Scientific and Moral Case for the Biotech Revolution is now available from Prometheus Books.

Discuss this article online.

Is Antidepressant a Misnomer?

jsullum@reason.com (Jacob Sullum) — Thu, 19 Apr 2007 11:30:00 EDT

A research review in this week's Journal of the American Medical Association finds a risk of increased "suicidal ideation" in children and adolescents taking antidepressants half as big as the already small risk the FDA cited when it ordered scary "black box" warnings for the drugs three years ago. A.P. reports:

The researchers analyzed data on 5,310 children and teenagers from 27 studies involving the antidepressants Prozac, Paxil, Zoloft, Celexa, Lexapro, Effexor, Serzone and Remeron. They found that for every 100 treated with antidepressants, about one additional child experienced worsening suicidal feelings above what would have occurred without drug treatment. In contrast, the F.D.A. analysis had found an added risk affecting about two in 100 patients. There were no suicides in any of the studies.

SSRI boosters argue that the FDA's daunting label has resulted in more deaths by scaring doctors away from antidepressants that would have prevented suicides. That may be true, but this review shows once again that the benefits of antidepressants, like their risks, are overrated:

The new analysis found that antidepressants worked best when used to treat anxiety. They worked moderately well in treating obsessive-compulsive disorders. They worked less well, though still effectively, in treating depression....
In the studies involving depression, 61 percent of patients improved while on antidepressants. But 50 percent of depressed patients taking dummy pills also improved.
Among young patients with obsessive-compulsive disorders, 52 percent improved on antidepressants, compared with 32 percent who improved on dummy pills.
And in the studies of anxiety disorders, 69 percent improved on antidepressants and 39 percent improved on dummy pills.

If antidepressants work better in treating anxiety than in treating depression, and if they relieve depression only a little better than a placebo, antidepressant is something of a misnomer, isn't it? Prozac et al. may be even less effective than these numbers suggest: Skeptics (including psychologists, who do not enjoy the legal privilege of prescribing antidepressants) argue that the physiological side effects of antidepressants may tip off some subjects that they are getting the real thing, knowledge that could create an enhanced placebo effect that may account for the improvements attributed to the drugs. Then again, as Maia Szalavitz has argued in Reason, the clinical trials may underestimate the potential effectiveness of antidepressants because they throw together people who benefit dramatically with people who don't respond at all.

Miracle Fruit Revisited

rbalko@reason.com (Radley Balko) — Sat, 31 Mar 2007 10:04:00 EDT

My friend Jacob Grier hosted another Miracle Fruit party a few weeks ago. A Wall Street Journal reporter was there, and wrote up the story:

Within minutes of consuming the berries, guests were devouring lime wedges as if they were candy. Straight lemon juice went down like lemonade, and goat cheese tasted as if it was "covered in powdered sugar," said one astonished partygoer. A rich stout beer seemed "like a milkshake," said another.

I was there, too. And my second Miracle Fruit experience was even a little better than the first. Reporter Joanna Slater did a bit of digging on the regulatory hang-ups of the fruit, too:

Miracle fruit remains in a kind of regulatory limbo in the U.S. It's perfectly fine to grow and sell it, because the Food and Drug Administration doesn't require prior approval to sell fresh fruits, though it can intercede if it suspects problems. The trickier part comes when people try to use it as an additive in other foods. That's when regulators start asking questions.

Two American entrepreneurs, Robert Harvey and Don Emery, tried this route back in the 1970s but the venture ended in heartbreak. Their initial focus was on products for diabetics, but some of their financial backers, which included Reynolds Metals Co. and Barclays Bank PLC, had a loftier goal. "They were interested in replacing half the sugar industry in the world," Mr. Harvey says.
Mr. Harvey figured out how to turn miracle fruit into a dried powder and then a tablet. His company, Miralin Co., explored making everything from chewing gum to a miraculin-coated drinking straw. It developed recipes for diabetics which assumed people would pop a miracle-fruit tablet before eating the results.
Reynolds, now part of Alcoa, then owned the Eskimo Pie brand of frozen snacks and suggested trying miraculin-coated ice pops. In the summer of 1974, a group of Harvard Business School students conducted ice-pop taste tests on Boston playgrounds, giving children a choice between regular ice pops and miraculin-coated ones. The children preferred the latter by a wide margin, Mr. Harvey says.
That same year brought a big setback: The FDA sent a letter calling miraculin a "food additive" requiring years of testing. The letter effectively scuttled the venture, which was on the verge of selling products and wasn't prepared to spend money on extensive testing. Miralin filed for bankruptcy and fired 280 employees. It's only in the past five years that "I'm able about to laugh about this instead of crying," says Mr. Harvey, now 75 years old, who went on to a lucrative career making blood pumps used in heart surgery.

Grier has much more here. He also explains how you can order your own.

Free the Miracle Fruit!

rbalko@reason.com (Radley Balko) — Thu, 08 Feb 2007 08:19:00 EST

My friend Jacob Grier has created an online stir with his post about the wonders of the Miracle Fruit.

It's a small, red berry from West Africa with a strange and wonderful property: It makes sour things taste sweet.

I tried one over the weekend, from the same batch Jacob tried. You put the thing in your mouth, chew it, and slosh it around so it coats your tongue. I then bit into two lemon wedges, and ate them both. I chewed them like candy. They tasted like sweet lemonade.

The secret is a glycoprotein called Miraculin (yes, that's actually what it's called) that attaches itself to your taste buds. No one seems to be quite sure how it turns sour and bitter to sweet. The effect lasts for about 90 to 120 minutes.

The fruit is heavily marketed in Japan, where it's used in fruit form, in powder form, and now that scientists have figured out a way to isolate Miraculin, in tablets. Some chefs there have constructed low-cal deserts around the use of the fruit. Wired News reported last December that there's even Miraculin-infused lettuce in the works.

In Japan, the Miracule Fruit is particularly popular among diabetics and dieters. Those are two very large (sorry) and growing markets in the U.S. It's also used to help leukemia patients get back their appetites, and to make bitter medicine more palatable. All this would seem to mean a great market for the stuff in America. So why can't U.S. consumers get any?

It seems that the FDA banned the fruit under mysterious circumstances in the 1970s. I've seen speculation on various websites that it may have had something to do with the sugar industry, or with the fact that aspartame was working its way to FDA approval at about the same time. There's been little written about why the fruit was banned, only that the prohibition appears to have been sudden and unexpected. It came on the eve of one compnay's plan to roll out a major marketing campaign.

The Miracle Fruit has been used for centuries, now. And there have been quite a few studies of it, with no known ill-effects, other I guess than that it could potentially cause something toxic to taste better than it should. That hardly seems like a reason to ban it.

Seems like something the FDA ought to revisit, particularly with the uptick in diabetes cases over the last several years.

Life, Death, and Red Tape

rbalko@reason.com (Radley Balko) — Mon, 15 Jan 2007 13:13:00 EST

Earlier this month, a Santa Cruz, California family inadvertently ate some poisonous mushrooms they'd collected in a nearby woods. The "death cap" mushroom they ate is often fatal, and there's no antidote approved for use in the U.S.

The doctor on call at Dominican Hospital did a search on Google Scholar, and found that in some parts of Europe, intravenous administration of an extract from the milk thistle plant had been used to effectively treat poisoning from this particular variety of mushroom.

Enter the FDA. The treatment isn't approved in the United States. So the doctors next embarked on a harrowing battle with various bureaucracies to get the drug to the U.S. from the manufacturer in Germany in time to treat the family.

The good news is that they succeeded, and managed to save five of the six patients.

Story here .

Roll Over, Rover, and Left Pfizer Take Over

gillespie@reason.com (Nick Gillespie) — Sun, 07 Jan 2007 08:57:00 EST

Yet another sign--in an endless series--that we are living in a post-Rapture world:

The world's first weight-loss drug for dogs has been approved by the US Food and Drug Administration (FDA).
Slentrol, made by the pharmaceutical giant Pfizer, is intended to significantly reduce the appetite and increase fat absorption in canines.
The FDA's head of veterinary medicine said the drug was a welcome addition to animal therapies because of an apparent increase in dog obesity in the US.
Americans own 65 million dogs and almost 40% of US households have one.
According to the FDA, veterinarians generally define a dog that weighs 20% more than its ideal weight as obese.
Surveys have found that approximately 5% of dogs in the US are obese, and another 20-30% are overweight, it says.

It'll cost between $1 and $2 a day. Given the amount saved on food, who knows, maybe it's a boon for pet owners (and where's the feline version, which is just waiting for a Garfield ad campaign?). More here.

Of greater concern to all of us should be the slowdown in new drugs coming to market, which seems to partially due to well-known FDA regulatory red tape and dubious decisionmaking by pharmaceutical companies.

Drug Brakes

rbailey@reason.com (Ronald Bailey) — Fri, 08 Dec 2006 17:27:00 EST

Ever since Congress helped speed up the Food and Drug Administration’s rate of drug approvals in 1992, critics have complained that the relatively quick approval times put patients in danger. So when Merck’s Vioxx was shown to cause heart attacks in 2004, a chastened agency slowed the process considerably. In September The New York Times reported that the 2005 approval rate was the slowest in a decade.

So what’s the correlation between approval times and drug safety? According to a 2005 report by the Tufts University Center for the Study of Drug Development, there isn’t one.

Researchers say the percentage of drugs withdrawn for safety reasons was 3.2 percent in the 1980s, rose slightly in the ’90s to 3.5 percent, and fell in the new century to 1.6 percent. And approval time for drugs that are later withdrawn for safety reasons is not appreciably shorter than the average approval times for all drugs.

The good news is that the dangerous drugs are withdrawn from the market much sooner than used to be the case. The average time between government approval and subsequent safety withdrawal has dropped from 3.7 years in the 1980s to just 0.7 years today.