We may not be so lucky next time

Beyond safety, however, some scientists say the real question is “Does the vaccine work?” The Pentagon says it does. It points to studies showing that the vaccine was 88 percent effective in monkeys after 100 weeks. Government scientists point to other studies showing that 62 of 65 vaccinated monkeys subjected to lethal challenges of inhaled anthrax survived while all 18 unvaccinated monkeys died. The Defense Department further defends the vaccine by pointing to a study of at-risk wool-mill workers showing the vaccine to be 93 percent effective.

But Dr. Meryl Nass isn't convinced and states, “You won't see me getting in line for the vaccine.” Nass, who has written extensively on the use of anthrax for bioterrorism, stated during Congressional testimony in 1999 that claims of effectiveness based on the monkey studies are questionable. First, although there are numerous strains of anthrax, only one strain was used to infect the monkeys. In addition, Nass points out, in a study of vaccinated guinea pigs, one-half of the animals died after exposure to 27 of 33 strains of anthrax. She also notes that what works in monkeys may not work in humans.

Even the highly touted wool mill study has raised as many questions as it answered. Doctors from the National Naval Medical Center and the U.S. Army, writing in the Archives of Internal Medicine point out that the wool-mill worker study included so few cases of inhaled anthrax (most had the skin form of anthrax) that it was impossible to determine whether the vaccine provided any protection against inhaled anthrax—even though it clearly reduced the cutaneous, or skin form, of the disease. Experience with another vaccine suggests there may be good reason for concern. A vaccine under development for plague had to be abandoned in 1999 when it was found that, although it did reduce the skin form of the disease transmitted by flea bites, it failed to protect against its highly lethal, inhaled form.

A 2000 report by the House's Government Reform Committee highlighted these concerns. The committee concluded: “At best, the vaccine provides some measure of protection to most who receive it. Just how much protection is acquired, by whom, for how long, and against what level of challenge are questions the [Defense Department] answers with an excess of faith but a paucity of science.”

Despite scientific uncertainty and technical problems, the Pentagon has poured over $126 million into its exclusive relationship with BioPort, causing Reform Committee members to conclude that the Defense Department is “captive to old technology and a single, untested company.”

Questions about financial conflicts of interest have also dogged BioPort. Critics have asked why a start-up company with no track record was given a multimillion-dollar contract. They also wanted to know why, when BioPort nearly went belly-up, the Pentagon doubled the sole-source contract from $25.7 million to $49.8 million while simultaneously reducing the contracted number of vaccine doses from 7.5 to 5.3 million. A central concern is the cozy relationship between BioPort and the Pentagon (one of BioPort's top guns is the former chairperson of the Joint Chiefs of Staff, Admiral William Crowe).

Dr. Barbara Hatch Rosenberg, a biological arms-control expert with the Federation of American Scientists, argues, “Admiral Crowe has no expertise in anthrax vaccine. His only role is to secure a contract and that's not a position that should go to an insider. It appears to be a conflict of interest.”

Commenting on the revolving door between government officials and industry that can lead to mega-buck contracts while too often giving short-shrift to the public interest, Jerome Hoffman, Professor of Emergency Medicine at UCLA, notes, “Although industry routinely tries to convince us that its motives are philanthropic, its primary agenda is, and pretty much has to be, to maximize its own profits.” Dr. Hoffman doesn't believe that people expect anything different. But he points out that we do expect our government to put the public's interest first. “But the pharmaceutical industry is one of the leading ‘contributors' to both political parties, and there are a lot of indications—from the ‘industry-friendly' directives to the FDA (Food and Drug Administration) to the blanket rejection of price controls on medications which are far more costly here than anywhere else in the world, to the dance between Bayer and Secretary Thompson over the price of Cipro—that our government values corporate interests over any other.”

America for Bayer, Bayer for America

Although Cipro was initially touted as the only cure for anthrax, some doctors were puzzled by the claim. After all, a number of drugs, including penicillin and doxycycline, are not only effective, but also are far cheaper, and in most instances, safer than Cipro. Further, doctors have extensive experience treating anthrax with penicillin and doxycycline, but virtually no experience with Cipro. So, how did Cipro come to be the drug that Tom Brokaw would hold aloft while telling viewers, “In Cipro we trust?”

In part, the answer has to do with initial uncertainty about the anthrax spores and whether they had been genetically engineered to be resistant to older antibiotics. However, according to some physicians, that concern should not have been a green light to endorse Cipro since there was virtually no experience with the drug in human anthrax.

Another part of the answer rests in the ability of Bayer, Cipro's manufacturer, to file for Food and Drug Administration approval for use in treating anthrax. Although, doctors can legally prescribe medications that have not won FDA approval for a specified condition (called “off-label” prescribing), there can be significant advantages to having FDA approval, as the anthrax scare so clearly showed. In a very savvy move in 2000, Bayer applied for FDA approval to use Cipro to treat anthrax. What many people didn't realize was that while Bayer won that approval (and penicillin and doxycycline remained unapproved), it was not because Cipro was clinically superior to penicillin or doxycycline, but because Bayer could afford the enormous costs associated with winning FDA approval. Smaller companies that manufacture generic drugs, such as penicillin, may be unable to underwrite such costs. Following the anthrax scare, the government expedited approval for penicillin and doxycycline and the Centers for Disease Control modified its recommendations to doctors, indicating that both of these drugs were acceptable treatments for anthrax following initial use of Cipro.

Although it appeared that sufficient supplies of antibiotics were available for the anthrax scare, questions of profiteering quickly arose. Bayer president and CEO, Helge Wehmeier argued that the company already cut their wholesale prices for Cipro from $1.77 to 95 cents per pill. But Cipro, which raked in over $1 billion in U.S. sales in 2000, cost U.S. patients as much as $5 per pill—while generic versions sell in other countries for 10 cents per pill.

According to a Wall Street Journal report, 3 U.S. drug makers are willing to sell generic Cipro for 40 cents per pill and note that they would still be turning a profit at that price. For its part, Wehmeier claims, “Bayer is fully committed to supporting America in its war on bioterrorism.”

Testing For Serum Parsnip Levels

During this flu season, hospital emergency departments have been besieged with worried patients wondering if they have anthrax. At this writing, the Centers for Disease Control report that they are still receiving roughly 25-50 requests for anthrax testing per week. With the filing of a $37 million lawsuit against doctors who sent an anthrax victim home, mistakenly thinking he had the flu, doctors are also shaking in their boots. They ask how they can be expected to tell which of the several hundred thousand patients with flu symptoms could actually have anthrax.

Making matters worse, some doctors are giving advice ranging from bad to ludicrous according to some experts. Dr. Isadore Rosenfeld writing in the November 12 issue of Parade magazine told readers that they should ask their doctor for Cipro or doxycycline if  “…you find yourself surrounded by people who, suddenly and for no apparent reason, have come down with what is seemingly the flu…”

However, such paranoia-inducing comments fly in the face of reason, according to other doctors. Robert Solomon, MD, vice chair of the Department of Emergency Medicine at Ohio Valley Medical Center in Wheeling, West Virginia asks, “One wonders if Dr. Rosenfeld would consider that this is the flu season and that might be the reason patients have flu symptoms?”

Unfortunately, however, since early anthrax and flu have so many similar symptoms and since anthrax cultures can take up to several days to yield results, some doctors heaved a sigh of relief on November 5, when the Mayo Clinic and Roche announced in a press conference that they had jointly developed a new test that could diagnose anthrax in just 30 minutes. The new test relies on polymerase chain reaction (PCR) that can detect minute amounts of the anthrax bacillus in a blood sample.

Without this test, some emergency doctors warn that flu season will be hell this year. “This new test should be assessed by the appropriate federal agencies and made available ASAP,” according to Meryl Nass. “There are several [tests] that look pretty good, including the Mayo test,” adds Nass. She believes PCR tests could rapidly screen out the majority of hoaxes, leaving a manageable number of specimens to be tested further, to confirm that they are truly positive.

Indeed, the claims made by Roche and the Mayo Clinic seem impressive. Franklin R. Cockerill, III, MD, the Mayo Clinic microbiologist who led the anthrax test development team claims that the test is 100 percent accurate when anthrax is present. However, his claim is based only on test tube studies, and he acknowledges that no human studies with the Roche test have been concluded that would allow scientists to assess the test's accuracy in humans. Therefore, until human studies are completed, Dr. Cockerill recommends that the PCR test be used in conjunction with conventional culture-based testing methods.

Another problem with the Roche PCR test is that it can't deliver on the very thing doctors say they want most; the ability to reassure patients who don't have the anthrax. That's because even if the test can accurately identify patients with anthrax in their blood, such identification may come too late. According to Dr. Richard Meyer, bioterrorism laboratory director with the Centers for Disease Control, “We don't know enough about when anthrax appears in the bloodstream to be certain that sample collection after the onset of symptoms will be useful.” Since anthrax is sequestered in the lungs and surrounding lymph nodes during the initial phases of infection, some fear that by the time anthrax appears in the blood, it may be too late to help the patient.

Solomon questions Roche's claims of 100 percent accuracy noting that there is no example of anything in medicine that is 100 percent accurate in humans. “The PCR test is based on test tube studies, and if you have 100 percent accuracy in a test tube study, that's wonderful. But it tells you absolutely nothing about how it will perform in humans. Even if the test is highly accurate—and there is much reason to doubt it will be—it won't always be right. If you can't assuage a patient's fears in a way that's intellectually honest then it is deceitful to hold out a negative test result as reassurance. If we're going to order the test knowing it will almost always be negative, because almost no one will have anthrax anyway, then all we're doing is pretending the reassurance is from the test rather than because of the extraordinarily low prevalence of the disease. If that's all we're doing, then a test for parsnip poisoning will serve the purpose quite nicely.”

A recent CDC report lends weight to Dr. Solomon's concerns. In comparing a commercial PCR test made by Idaho technologies, when six environmental samples grew anthrax on culture, a PCR assay was only able to correctly identify anthrax in two of the instances. On the other hand, of eight samples identified as positive by PCR, only two were positive by culture. Several possible explanations for the test's inaccuracy were given including possible contamination, splitting of samples and errors in methods of sample collection and preparation. In addition, it was noted that PCR could identify spores that were killed or non-viable, showing a positive result, while cultures would be negative.

Given such problems with anthrax prevention and testing, some doctors have suggested that patients get the flu shot. A microbiologist—not a physician—interviewed for a PBS show on bioterrorism weighed in with the idea that the “patriotic” thing to do is for all citizens of the U.S. to get the flu vaccine this year so doctors could tell who had the flu and who didn't. However, Solomon scoffs at the notion that such an approach is useful for reassuring patients noting, “The flu shot is only 70 percent effective in preventing influenza. This would leave a large group of people more, not less, worried that they have anthrax when they develop flu symptoms.” Others recommend testing for the flu when patients develop symptoms. But Solomon dismisses this strategy as well stating, “Of all the patients who present with flu symptoms, only half will actually have influenza. Of those patients, many will not test positive for it in the lab. So most patients with flu symptoms will not have a positive test for influenza. This will leave another group of people panic-stricken.”

Roche has announced that for its “contribution” to the war against bioterrorism, they are donating free tests to a number of labs. But some see this as a cynical way to promote a questionable test. The tests will sell for $50 to $60 a piece and can only be run on Roche's LightCycler machine that lists at $57,000.

Industry Response To Bioterror

The 19 percent profit margin enjoyed by the pharmaceutical industry is the highest of any industry, eclipsing the 5 percent median profits of all Fortune 500 firms. Hoffman remarks, “When a drug company can make a product that is both profitable and life-saving, it's a win-win situation for everybody. But any time it comes to a choice between the public health or profits, drug companies can and must sacrifice the former for the latter, because like all corporations they see their ultimate responsibility as being to their stockholders.

“The recent dance between Bayer and the government over Cipro shows this quite clearly. Both sides—and a mostly uncritical media—pushed the image of Tommy Thompson heroically twisting Bayer's arm to get a great price, and Bayer going along, albeit just a bit reluctantly, as a ‘good corporate citizen.' But while this was all happening, Thompson's Department of Health and Human Services was trying to hush up the fact that its ‘discount' price was more than twice as much as it was paying the same company for the same pill in another government program. Of course all these prices are far greater than what it would cost for a generic version of ciprofloxacin, and even more compared to what it costs to produce the drug—providing Bayer with a huge profit to go along with its public relations success. When the next public health crisis arises, why should we expect industry—or our government—to behave any differently?”

Although many believe that profit incentives fuel medical innovation and scientific excellence, critics believe that science itself may be deformed by financial conflicts of interest. Hoffman comments, “Unfortunately, since so much money is riding on the interpretation of scientific studies there is an enormous tendency to inflate both the level of evidence, and its significance. That may be why we seem to discover a great new cure for some terrible disease almost every day—only to find out, over and over again, that very little has changed.

“When scientists are funded by industry, the results tend to favor their sponsor disproportionately,” states Hoffman. “While it is impossible to do perfect science, the more that a researcher brings conflicts of interest to the work, the more likely it is that the research itself will be tainted. If we really want to put the public health first, we shouldn't tolerate a system whereby the majority of work on medicines is paid for directly by the pharmaceutical industry, to whom the researchers are beholden.”

What can be done? Hoffman states, “There are many possible alternatives to having a drug company fund the grant, supervise the project, and own the data. I won't even raise the question of whether we would be better served by a national health care system, for drug manufacturers as well as for physicians. But why not at least require, for example, that a proportion of sales revenues—no more than they currently spend—be placed in a central pot, to be administered to scientists by the National Institutes of Health, without any direct tie to the companies?”

What does Hoffman think it would take to make needed changes? “It is up to us—the citizenry, not just physicians—to demand that government look out for the public interest and not the corporate bottom line. We may have lucked out this time, because anthrax is hard to spread, but we'd better think hard about fundamental changes if we don't want to be so dependent on luck in the future.”                      Z

Jeanne Lenzer is a freelance journalist.