The Body Hunters (5 page)

To turn the drug into a true success, though, the vast American market would have to be breached. The most likely pest that nitazoxanide might take on was a parasite called
Cryptosporidium
. Small even by parasite standards,
Crypto
wasn't even spotted by scientists until the early 1900s. The parasite burrows into cells in the intestines, reproduces rapidly, and then sheds tiny, dormant cysts that depart through the intestines, floating in sewage and pipes until taken up by another creature. In the mid-1970s scientists recognized with alarm that
Crypto
could perform this feat in human intestines as well as in animals. While parasitic infections on the whole are rare in the United States, when there are outbreaks, either
Crypto
or
Giardia
is the culprit.

In most people
Crypto
's residency in the gut provoked diarrhea for a week or two, after which it would rapidly depart, leaving the host otherwise unscathed, and functional water filtration systems generally screened out the cysts anyway.
⁷
But every now and again, when water systems failed, the parasite could wreak havoc. In 1993, severe flooding in Milwaukee triggered an outbreak that sickened over half the population, killing 100 of the weakest and most vulnerable. One of the most daunting attributes of the parasite was its defiant resistance to disinfectants: in fact, scientists
prepared pure samples of the parasite by mixing
Crypto
-infected stool with undiluted bleach.
⁸

But Romark wouldn't have to wait for periodic water department meltdowns to sell nitazoxanide for cryptosporidiosis. In immune-compromised AIDS patients crypto could be devastating. The parasite could settle in for months, even years. And the diarrhea it caused was explosive and uncontrollable. A bite of an unwashed fruit or an innocent nuzzle from a contaminated farm animal, and HIV-infected people would find themselves rushing to the toilet day and night, the great volumes of water exploding from their intestines leaving them withered and dehydrated nearly to death. So uncontrollable was the crypto-induced diarrhea that while Rossignol and Ayers scrambled for funds, wasted AIDS patients with crypto were turning up at clinics wearing diapers. If nitazoxanide might work for these patients, it could be a lifesaver.
⁹

By the mid-1990s Rossignol's company had started to test the drug in AIDS patients with crypto. They administered the drug to eighteen AIDS patients with diarrhea in Mali; four cleared the parasite.
¹⁰
When word got out to American AIDS doctors struggling with their suffering patients, they started to clamor for supplies of the drug. The FDA allowed nitazoxanide's distribution under a “compassionate use” program, whereby experimental drugs can be administered legally to patients with life-threatening illnesses if no alternatives are available. The minuscule Mali study with its four-out-of-eighteen odds hardly anointed nitazoxanide a miracle cure, but at the time the tug of HIV into the dark abyss of AIDS appeared as relentless as the tide. Patients and clinicians seized anything that might help.

Now Romark had scores of patients around the country taking its experimental compound. By carefully tracking how they fared, they might be able to use the data to garner FDA approval, especially in conjunction with data from a study of the drug about to be launched by researchers at the esteemed National Institutes of Health.
¹¹
The government docs planned to enroll sixty AIDS patients with cryptosporidiosis, randomly assign them to receive
either nitazoxanide or a placebo, wait a few weeks, and then compare their outcomes.
¹²
With its requirement that some patients crippled with crypto accept sugar pills from their doctors for weeks on end, the trial protocol was “not too friendly to people with AIDS, unfortunately,” remarked Bill Bahlman, a founding member of ACT UP New York who served on a community advisory board for AIDS trials,
¹³
but would be a surefire way of proving to the agency that the drug was effective and worthy of approval.

But the NIH didn't move fast enough. By the mid-1990s the notion of slamming HIV with multiple antiretroviral drugs had been born, miraculously beating back many of the opportunistic infections that debilitated and killed AIDS patients. Despite dramatic side effects, the difficulty of managing dozens of pills daily according to a strict schedule, and the $15,000 annual price tag for the drug cocktails, the mainstream press speculated that “this ordeal as a whole may be over,” as social critic Andrew Sullivan wrote in the
New York Times Magazine
. Was it “the End of AIDS?” as
Newsweek
magazine asked on its cover?
¹⁴
Deep in the antipodes researchers wondered whether an onslaught of antiretrovirals might vanquish crypto, too. Between 1995 and 1996 nine HIV-infected men in Sydney, Australia, rushing to the toilet with explosive crypto diarrhea between three and ten times a day, were treated with multiple antiretroviral drugs. Every single one cleared the parasite. Most gained up to thirty pounds.
¹⁵

And yet, despite the startling success of combination antiretroviral therapy, the NIH plodded onward with its placebo-controlled trial of nitazoxanide, trolling for
Crypto
-infected AIDS patients for the experiment in the spring of 1997. If the NIH trial had struck AIDS activists as unfriendly before, now it seemed downright repugnant. With the potent new therapy on offer, only the most altruistic or impoverished AIDS patients suffering with crypto would risk the chance of being given a placebo. By the spring of 1998, with only ten patients on board, the NIH was forced to abandon the trial.

Between Romark's founding in 1993 and May 1998, when the FDA advisory committee finally met to review data on nitazoxanide, everything had changed. Romark presented its data on nitazoxanide without any data from the aborted NIH trial. The committee was less than impressed. The drug hadn't cured any patients of cryptosporidiosis. The best that Romark had been able to prove was that the drug eased the diarrhea, lessening the number of trips to the toilet for a little over half of the patients who took it. Since the company had no data on how the patients who took the drug compared to others not given the drug, it was possible that even the weak salutary effect had nothing to do with the drug whatsoever, FDA advisers argued.

“We're interested in controlled comparisons,” announced the FDA's statistician, Nancy Silliman; that is, data showing how the drug works in contrast to how another drug—or placebo—works. “The interpretation of uncontrolled data,” such as Romark had presented, “is problematic at best,” she said. The only way to be able to tell for sure whether nitazoxanide worked, she and other FDA advisers maintained, was with a placebo-controlled trial such as the NIH had planned—and which was scuttled due to lack of interest.
¹⁶

Silliman's dismissive posture exasperated Rosemary Soave, MD, a cryptosporidiosis expert who had presented the data on nitazoxanide to the committee. Soave found the whole idea of a placebo-controlled trial for crypto in AIDS patients distasteful. “It was really very difficult to ask them to enroll in a trial where they would postpone getting a potentially effective agent for as long as perhaps three weeks,” she said. “This is three weeks of suffering that most patients who are in this condition and have numbered days ahead of them are really not willing to do. . . . And that is really understandable.” Placebo-controlled trials for such a dire condition, when evidence suggested that drug therapy could help, were “very difficult, if not impossible,” she told the committee. “Many physicians and patients feel it is totally unethical.”
¹⁷

But the FDA committee wasn't interested in such dilemmas, Soave said. They “didn't pay one bit of attention when I was trying to explain how tough it was for the patients,” she remembered later.
¹⁸
The committee rejected Romark's application. Perhaps the drug could be tested against placebo elsewhere, one committee member suggested. “I think consideration has to be given to the international setting,” said Johns Hopkins gastroenterologist Cynthia Sears, “where HIV is rampant and additional therapies are obviously not available in many instances.”
¹⁹

Disappointed, Soave soon moved on. There wasn't much more work to be done on AIDS and cryptosporidiosis anymore anyway, she thought. With combination antiretroviral therapy the most effective way to cure opportunistic infection, she said, “a lot of these drugs went by the wayside.”
²⁰

Romark took the blow in stride. They could still capture $100 million in sales every year if they could get the drug approved, Rossignol told reporters. All they had to do was find a new market. Crypto may have stopped being a serious problem for AIDS patients, but it was still a nuisance for the handfuls of Americans, particularly children, who caught the bug from dirty swimming pools, farm animals, or unwashed fruits. If delivered in a three-day course of sweet, strawberry-flavored syrup, nitazoxanide prescriptions might be eagerly snatched up by frustrated parents caring for intestinally challenged toddlers.

But running trials that might satisfy the FDA would be daunting in the United States. Cases of cryptosporidiosis had become rare, sporadic, and dispersed. Enrolling sufficient numbers of sickened patients would require the help of thousands of physicians across the country, each of whom might pass months if not years before seeing a single case. Romark didn't have hundreds of millions of dollars to spend on developing the drug, unlike the big pharmaceutical companies. They had $40 million.
²¹

And so Romark's hunt for bodies began. It began in Romark's home state of Florida and ended in a small, impoverished country in sub-Saharan Africa.

When the British left Zambia in 1964, the country was “little more than a hole in the ground” where copper veins had been mined, a government official remembered. Infrastructure, save whatever was required to claw out the copper, was minimal.
²²
The new government set about bringing the copper mines and farms back under Zambian control, building bridges and roads, and providing water services, free education, and free health care to a populace that would grow to ten million strong. Soon the country was one of the richest in all of sub-Saharan Africa,
²³
boasting two universities, as well as a medical school and university teaching hospital located in the dusty capital city, Lusaka.
²⁴

But the country was dangerously dependent on income from selling copper, and when copper prices collapsed while the price of the petroleum products needed to run the mines spiked in the early 1970s, the country rapidly descended into debt. By 1980, Zambia's external debt had skyrocketed from $800 million in 1970 to over $3 billion, and desperate government officials turned to the IMF and World Bank for relief.
²⁵
Over the following decades Zambia's nascent welfare state was methodically dismantled. More than 250 formerly government-run programs were sold to private investors. Farmers were cut off from government-supplied fertilizers and other subsidies. Formerly free public clinics and hospitals started to charge hefty fees, whittling the flow of patients into health care facilities by 60 percent. Tens of thousands of government workers were retrenched, as the country waited for foreign investors to sense their opportunity and invest in rebuilding Zambia.

The investors came, but squeezing a profit out of Zambia's aging copper mines and embryonic infrastructure proved trying. The new mine owners promptly closed the clinics and hospitals the government used to run for the mine workers and their families. Some, such as mining giant Anglo-American, simply cut their losses and fled. Inflation ran at 100 percent by the early 1990s. Abruptly put out of work and suddenly bereft of government support, whole towns and cities collapsed.
²⁶
By 1998, 73 percent of all
Zambians were living in poverty, and half of the populace was unable to scrabble enough food to meet their minimum requirements.
²⁷
According to UNICEF, over a fifth of all Zambians risked death by starvation.
²⁸
The flow of water and electricity to the capital city slowed to a sporadic trickle, creating conditions for paroxysms of cholera.

HIV began to spread as well. By 2003, 15 percent of the population harbored the deadly bug, including 150,000 children. The number of years Zambians could expect to live plummeted from over five decades in 1990 to less than thirty-five years by 2001, leaving the country with one of the shortest life expectancies of any country in the world.
²⁹
The combination antiretroviral therapy that had effectively stanched the AIDS epidemic in the West had yet to arrive. In 2003, at least two hundred thousand Zambians were sick enough with AIDS to require immediate therapy with antiretrovirals, but the government was able to treat only six hundred patients.
³⁰
A 2002 survey showed that 66 percent of Zambians had never even heard of antiretroviral drugs, let alone had the means to pay for them.
³¹

The country's main hospital, the University Teaching Hospital in Lusaka, was at the forefront of dealing with the AIDS crisis, tracking the epidemic, offering testing and counseling when few in southern Africa were.
³²
But its facilities were near collapse. Water and telephone services were sporadic. Shortages of medicines and equipment were so severe the hospital was deemed “nonfunctional,” as Canadian journalist and Africa correspondent Jonathan Manthorpe put it.
³³