by Liam Scheff
Crux Magazine
Winter 2004

Inside Incarnation

NYPress Orphans

30 to 50 percent

Pfizer Glaxo

Self med

3 days old

In June, 2003, I got a call to investigate a place called Incarnation’s Children Center (ICC), a Catholic orphanage for HIV-positive children in New York City. I was told that terrible things were happening there.

ICC is a home for children who test HIV-positive. Some of the children are orphans; their parents use drugs and can’t care for them. Some of the children have parents and families, but the parents have trouble enforcing the heavy AIDS drug regimen. When that happens, the city agencies bring the children into ICC, where their drug regimens are carried out without fail.

Their press page describes ICC as an “Ellis Island . . . envisioned as a sanctuary of love, a home-like nurturing residence where HIV-positive children would receive the best possible nursing and medical care while awaiting placement into foster homes.”

That didn’t sound so terrible.

ICC was also receiving federal funds for running drug trials with the children. “In 1992, an outpatient clinic for HIV-positive children was established; the same year, with funding from the National Institute of Allergy and Infectious Diseases [a subdivision of the NIH], the clinic became a sub unit of the Columbia University Pediatric AIDS Clinical Trials Unit.” In 1996, “under the direction of Dr. Stephen Nicholas, thirty-four children [were] participating in seven clinical trials . . . .”

Dr. Nicholas was listed among “The Best Doctors in New York in New York Magazine and in the 1996-97 edition of The Best Doctors in America.” ICC received government trial-funding through 2002. Dr. Nicholas has since moved to Harlem Hospital. ICC’s new medical director is Katherine Painter. She told me that children at ICC are now enrolled in clinical trials at one of a dozen area hospitals that work in conjunction with ICC. “Children participating in a drug trial undergo monitoring, testing, and supply of an experimental drug through their outpatient clinic, and we maintain that treatment here,” she said.

If I wrote for the New York Times, I would have had my story: “Noble Doctors Try New Drugs on AIDS Orphans.”

On the surface, it sounds innocuous and slightly tragic, but also heroic and perhaps hopeful. New drugs—that can’t be a bad thing, can it? AIDS orphans. Well, if anyone deserves a new drug, it’s AIDS orphans, right?

But I had doubts and lingering questions. What exactly are the “new drugs?” Do they have any effects that are deleterious? The ICC webpage listed them. It turned out that the drugs weren’t really new at all—they were old—nearly 40 years old. The primary drug used in trials at Incarnation Children’s Center is called AZT. It was developed in 1964. So, not a new drug. Does that matter? No, if the drug helps the kids. But there was a problem.

AZT isn’t a very helpful drug—unless, I suppose, you enjoy funerals. AZT has a very special use. It’s a chemotherapy drug used to kill the cells that make up living tissue and blood. It was designed in a cancer research lab in 1964 as a potent cell-killing agent called a nucleoside analogue. It works by disrupting cellular replication at the genetic level.

Our DNA is made up of four bases that combine in pairs. These line up, spiraling into a double helix. DNA codes for all our proteins; it’s a blueprint for our building blocks. AZT stops the spiral; it breaks the chain and kills the cell. Not so innocuous, after all.

AZT never got out of the lab. It was far too effective at killing cells even for short-term use. It was shelved, and no patent was filed.

In 1986, Burroughs Wellcome (now GlaxoSmithKline) was interested in entering the AIDS drug market. Recycling an old drug was cheaper than designing a new one. So AZT was brought out of storage. Test labs that ordered the drug for experimentation received it in a package bearing a skull and crossbones on a bright orange background. The label read “TOXIC. Toxic by inhalation in contact with skin and if swallowed. Target organ(s): Blood bone marrow. If you feel unwell, seek medical advice (show the label where possible). Wear suitable protective clothing.”

icc hearse

hiv negative

icc columbia presb.

icc 1

icc 2

Today, Glaxo sells AZT under the brand name “Retrovir” and as an ingredient in “Combivir” and “Trizivir.” But the warning label tells the same story:

• “Retrovir [AZT] has been associated with Hematologic Toxicity [blood toxicity], including Neutropenia [loss of neurophils, an essential component of blood] and Severe Anemia [potentially fatal lack of blood production] . . . . Prolonged use of Retrovir has been associated with Symptomatic Myopathy [muscle wasting].”

• “LacticAcidosis and Severe Hepatomegaly [liver swelling] with Steatosis [fat degeneration], including Fatal Cases, have been reported with the use of Nucleoside Analogues [AZT, 3TC, ddl, D4T] alone or in combination, including Retrovir and other Antiretrovirals (see warnings).”

The most surprising thing about AZT is that it doesn’t even claim to work:

• “Retrovir is not a cure for HIV infection . . . The long-term effects of Retrovir are unknown at this time . . . The long-term consequences of in utero and infant exposure to Retrovir are unknown, including the possible risk of cancer.”

This wasn’t so wonderful for the kids at ICC. But it was good for Glaxo. They make a lot of money with their AIDS drugs. Drugs containing AZT as an ingredient account for about one billion British pounds (over 1. 5 billion dollars) in Glaxo’s 2002 sales alone. Other nucleoside analogues provide another 470 million pounds (750 million dollars) in sales.

We know that something doesn’t have to be good for you to be profitable. Think of cigarettes or alcohol or fast-food. But it’s medication we’re talking about, not French fries. You’d think that a drug with such terrible toxicities would simply never get approved for use by the US Food and Drug Administration (FDA).

Unless, of course, the FDA approval process was easily corrupted. For example, a bad drug might get approval if a trial were heavily influenced, and even overseen, by the very pharmaceutical companies that produced the drug. That would mean that pharmaceutical reps, with a vested interest in getting the drug to market, would oversee and direct the recording process during the drug trial—or perhaps that CEOs of drug companies would go work at the FDA for a stint, approving drugs, then turn around and get back into the company.

Or perhaps doctors would be given favors—I don’t know, expensive trips, monetary rewards, that sort of thing—to be loyal to a particular product, or to review it favorably. Or that doctors fell victim to peer pressure from inside their academic community to support an ongoing paradigm, and not to rat out a bad public health policy.

But even suggesting that sort of thing is ridiculous, isn’t it? I mean, there’s no corruption in pharmaceutical-driven medicine. Is there?

Here’s a hint.

In 2000, Dr. Marcia Angell, editor of the New England Journal of Medicine (NEJM), resigned from the journal. In her parting May 2000 editorial, “Is Academic Medicine for Sale?” Angell wrote, ”[Y]oung physicians learn that for every problem, there is a pill (and a drug company representative to explain it). [Physicians] become accustomed to receiving gifts and favors from an industry that uses these courtesies to influence their continuing education . . .” She added, ”[T]he costs of the industry-sponsored trips, meals, gifts, conferences, and symposiums and the honorariums, consulting fees, and research grants are simply added to the prices of drugs and devices.”

Angell asked, “What is the justification for this large-scale breaching of the boundaries between academic medicine and for-profit industry?”

ABC News reported that in 2000 pharmaceutical companies sponsored over 314,000 promotional events for doctors—from lunches to travel weekends—at a cost of nearly 2 billion dollars.

In 2002, the new editor of the NEJM, Dr. Jeffrey Drazen, officially dropped the journal’s 190-year restriction against medical authors accepting money from drug companies. The journal’s editors claimed that there simply weren’t enough doctors who didn’t have ties to drug company money. The new policy allows review authors to accept up to 10,000 dollars a year from each drug company for “speaking and consulting fees”—with no limit on total earnings. By contrast, there are no financial restrictions placed on the researchers running the studies, who often work directly for the company whose drug is being tested.

Does money influence drug studies? ABC News reported that in a survey of independently-run drug studies, drugs were found to be safe and effective about 50% of the time. But when a drug company sponsored their own trial, the positive rating nearly doubled to 90%.

azt pregnancy	bone marrow toxicity	drugs 1	exam 1	genentech vaccine
generally healthy	gtube	gtube 2	icc baby	healthy volunteers

Even without evidence of corruption, FDA approval does not ensure drug safety. According to the US General Accounting Office, 51.5% of drugs approved by the FDA from 1976 to 1985 had “serious post-approval risks,” including “heart failure, myocardial infarction, anaphylaxis, respiratory depression and arrest, seizures, kidney and liver failure, severe blood disorders, birth defects and fetal toxicity, and blindness.”

In 1986, AZT was rushed through its FDA approval trials in record speed. Overseen and funded by Burroughs Wellcome, the trials were marred by false reporting and a total breakdown of study controls. Nevertheless, the drug was released to the market.

Subsequent independent AZT studies revealed the obvious—the drug was deadly. In English, Australian, and Dutch studies, patients on AZT developed severe anemia, requiring multiple blood transfusions just to stay alive. In the Dutch study, three-quarters of the patients on AZT died.

Well, AZT wasn’t the only drug being used at ICC. The other was Nevirapine, which is marketed under the brand name “Viramune.” And that drug . . . maybe we shouldn’t talk about that drug. Oh…might as well.

Nevirapine functions similarly to AZT. It interferes with the essential movement of genetic information in the cell. It blocks an enzyme which translates RNA into DNA.

There was a short period in research biology where it was imagined that this enzyme, called Reverse Transcriptase, only functioned in service to a particular kind of potential virus. This was quickly proven false. The enzyme didn’t belong to any particular virus or molecule. It was a part of normal, healthy cells—essential to our functioning. And Nevirapine blocks it.

Is that a bad thing? It is for people who’ve taken it whose skin has come off of their bodies. Right, well, I didn’t quite believe it myself, until I saw the European study of Nevirapine. Hands, abdomens, faces, and mouths, bursting with blood, flesh coming off like old paint steamed off a wall. The condition is called Stevens-Johnson Syndrome. Of course, those patients could have saved themselves the pain and just read the drug label (if they’d only been shown it). Here’s what it says:

• “Severe, life-threatening skin reactions, including fatal cases, have occurred in patients treated with Viramune [Nevirapine]. These have included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction. Patients developing signs or symptoms of severe skin reactions or hypersensitivity reactions must discontinue Viramune as soon as possible.”

It also warns of liver failure/toxicity. It seems that the drug can toxify the liver to such a great extent that it, well, dies: “Severe, life-threatening and in some cases fatal hepatoxicity [liver damage], including hepatic necrosis [liver death] and hepatic failure, has been reported in patients treated with Viramune.”

The other drugs used in the children’s regimen are called protease inhibitors. They have warning labels of their own, and they’re pretty painful too. Not much better, maybe worse. Doesn’t seem like much of a favor to these orphans. But these drugs—AZT and Nevirapine, protease inhibitors—aren’t just used on orphans in NYC. These are the main AIDS drugs used on people who doctors consider at risk for AIDS all over the world.

There’s been time to measure the effects of AZT. It has been given to hundreds of thousands of gay men in the US who tested HIV-positive, whether they were sick or not. United States AIDS deaths increased by thousands annually after the mass-introduction of AZT in 1987, from 11,000 in 1986 to nearly 50,000 in 1994—the height of AZT use. Sharp criticism of AZT began appearing in the press. Patients and physicians complained openly of the drug’s effects and cut doses or discontinued it altogether. The death rate declined—substantially—and before the introduction of protease inhibitors, which the industry likes to credit for the decline. Was it a coincidence? I don’t know. You can’t ask dead people what they died of. I do think it’s worth looking into.

So why were infants at ICC getting AZT? Weren’t there better solutions? ICC seemed to think so. From their published history: “Early in the epidemic, HIV disease of childhood was considered to be a down-hill course leading to death. But in the late 1980’s, before AZT was available, many very ill children admitted to ICC got dramatically better with proper nurturing and high-quality medical and nursing care.”

Why didn’t they stick with this program? Was it the government funding? Was it political pressure to get the drug approved for new markets? It certainly wasn’t the effectiveness of the drug. We don’t hear stories in the current AZT/Nevirapine era about “many very ill children” becoming “dramatically better.”

So, there were problems at ICC. But they certainly couldn’t force the children to take the drugs, could they?

drugs-v2

drugs 1

asymptomatic

azt benefit-limited

azt intolerance

Well, actually, they could. And they do.

How do they do it? It’s not pleasant to tell. Maybe you don’t want to know. Anyway, if it’s not in the New York Times, maybe it’s not important. But I had to ask.

I talked to ICC’s medical director Dr. Katherine Painter about it. She kindly provided details of the surgery given to children who “can’t take” or simply refuse the drugs. As per medical protocol, these children have a tube surgically implanted in their abdomens through which the drugs are easily administered, regardless of the child’s wishes. I wrote about it in an article called “The House That AIDS Built” and in a second article called “Orphans On Trial,” which was published in the New York Press in July, 2004.

I haven’t seen anything on it in the NY Times. But, of course, the chief writer on HIV at the NY Times is (and has been for over 20 years) a man named Lawrence Altman. And Lawrence Altman can’t write stuff like this, even if he wants to.

Altman is a former graduate of the CDC—the organization that makes the rules for how HIV patients are treated and diagnosed in this country. So, of course, Altman’s hands are tied. “All the News That’s Fit to Print” suddenly has a very clear, very unpleasant meaning.

Next time you see the headline “New AIDS Drugs for Africa” or “Noble Doctors Try New Drugs on Orphans,” what will you think? Will you ask yourself what’s behind it? If you want to find out, you’ll have to dig a little.

References and Further Reading:

• 1) “Orphans On Trial.” Liam Scheff. New York Press; July 14, 2004.
• 2) “Is Academic Medicine For Sale?” Dr. Marcia Angell. New England Journal of Medicine; May 18, 2000.
• 3) “Big Pharma, Bad Science.” Nathan Newman. The Nation; July 25, 2002.
• 4) “Death by Medicine.” Gary Null PhD, Carolyn Dean MD ND, et al. Nutrition Institute of America. November, 2003.
• 5) “Conflict of Interest?” John McKenzie. ABC News; June 12, 2002.
• 6) “AIDS; Words From The Front.” Bryan Ellison. Spin. December, 1993.