Victims Desperate : Alzheimer’s: Hope in THA Persists

Sometime in the fall of 1986, Joyce Beauchene began thinking about the interstate highway that slices through the family farm in South Dakota. I’m going out on that interstate, she would tell her husband, Cecil. I’m going to step in front of a big truck.

She talked of a terrible pain in her head. Like someone was in there with a hot iron, Cecil recalls. Month after month, Cecil Beauchene watched Alzheimer’s disease corrode his wife’s mind--while doctors assured him there was nothing he could do.

Then one day last summer, something heartening sputtered from the radio as Cecil was driving home from the barber shop: Paul Harvey, the conservative radio commentator, was plugging an experimental drug that he said showed promise for Alzheimer’s patients.

‘Dubious’ Ethics

The drug, called THA, had no federal government approval. But there was a way to get it--a way that Harvey conceded involved “dubious” ethics. There were pharmacists who would formulate it if doctors would prescribe it. Harvey cited one Nashville pharmacist by name.

Beauchene took Harvey’s advice. Within weeks his wife was on the drug.

“We were willing to use her as a guinea pig, I guess you’d say,” said Beauchene, a 67-year-old farmer whose education stopped after the eighth grade. “What we done here was probably make tests on our own--which maybe we shouldn’t do.”

Cecil and Joyce Beauchene are part of a nationwide underground market for THA, which splashed into the news 17 months ago when a Southern California researcher reported that it had produced dramatic improvements in a small group of Alzheimer’s patients.

Friends and relatives of patients have clamored for THA with the fervor of cancer and AIDS patients clamoring for unproved drugs. They have sought illicit sources and enlisted pharmacists’ help in bitter frustration with the federal drug-approval process.

But researchers and regulators warn that people are taking a terrible risk. The drug is unproved, and the research supporting it is under fire. THA at high doses is also known to cause serious side effects, including seizures and damage to the liver.

Black Market Feared

Even THA’s strongest proponent fears the spread of the black market.

“Someone’s going to get hurt,” said Dr. William K. Summers, the Arcadia psychiatrist who did the THA research. “Someone’s going to kill somebody. Then the hue and cry is going to be, ‘Aha! This drug killed somebody. . . .’ You cannot have casualties when you are starting off with a drug. Otherwise, you kill the drug for everybody.”

The struggle over THA illuminates the strengths and weaknesses of the system by which drugs are developed in this country: While rigorous scrutiny has kept dangerous drugs from the public, drug development and approval can now take as long as eight to 10 years.

Impatience with that process and with the U.S. Food and Drug Administration is now exacerbated by the lack of approved drugs to treat AIDS. Many dying people and their relatives increasingly believe they have a right to experimental drugs.

“You are seeing the tension between those who don’t understand the limits of science and those who are waiting to get an answer,” said Dr. Paul Leber of the FDA. “In between that is the political and social question: Should people have the freedom to take a chance?”

In many ways, the rise of the THA underground can be traced to George Rehnquist, a 65-year-old electrical engineer in Knoxville, Tenn., who noticed in 1977 that his wife, Lucille, had begun forgetting which cards had been played during games of bridge.

She became so addled that she had to retire from her job as a secretary with the Tennessee Valley Authority. At home, she began forgetting how to cook and not recognizing friends. In 1981, doctors determined that Lucille Rehnquist had Alzheimer’s.

There is no treatment for Alzheimer’s disease, the fifth-leading cause of death in the United States. It affects 2.5 million Americans and is expected to become increasingly common as the proportion of elderly in the population rises.

Nor is much known about the causes of Alzheimer’s, a progressive brain disorder that impairs thinking and behavior. Its symptoms progress over many years from forgetfulness to confusion, impaired judgment and changes in personality and behavior.

Increasingly Dependent

Toward the end, many patients spend their last years in nursing homes--fed through tubes, swaddled in diapers, lying in a fetal position. Many are completely dependent, disoriented and mute, unable to recognize people, including themselves.

Numerous drugs believed to have shown promise for treating Alzheimer’s have been tested in recent years in scientific trials--first in the laboratory, then in animals and in some cases in humans. So far, none has been proved effective in slowing or reversing the disease.

George Rehnquist, however, was unwilling to accept those facts.

The year after his wife’s diagnosis, he retired and devoted himself to caring for her. He also set out on a mission to find help--scouring magazines and journals, contacting physicians and politicians in search of some treatment or cure.

Now a THA Advocate

Rehnquist is now a zealous advocate of THA. His home computer stores a mailing list of more than 200 patients, pharmacists and physicians. He has become a one-man clearinghouse for information on THA, with a network of contacts from Canada to Costa Rica.

In January, 1982, Rehnquist says, the Lord appeared before him while he was praying. “He was in a white robe and his face was fuzzy, it was never clear,” Rehnquist recalled in a recent interview. “He just said, ‘Don’t worry. She’s going to be all right.’ ”

Three weeks later, he found himself in an optometrist’s office flipping through Health magazine. In what he believes was an act of divine guidance, his eye was drawn to a small article about Summers’ first attempt in the 1970s to use THA on Alzheimer’s patients.

Rehnquist tracked down Summers in Arcadia. He had left USC for private practice. Though Summers had put his THA work on hold, he agreed that the Rehnquists could come West to try the drug, which he had federal permission to test.

First to Try It

Lucille Rehnquist became the first patient in the study that eventually was published in November, 1986, in the New England Journal of Medicine. In that controversial article, Summers reported that THA had improved memory function in 16 out of 17 patients.

Most striking of all, Summers reported that several patients had been able to return to homemaking, golf, and even work.

The article provoked a powerful, but mixed, response.

Thousands of calls poured in to Summers’ small office in Arcadia. Receptionists answered 1,800 requests for printed information within days. Relatives of patients called universities, foundations and drug companies. One Canadian firm still gets several calls a week.

But some researchers began faulting Summers’ study. Others questioned the propriety of his application for a patent on the drug he was testing: If he could gain financially from its outcome, could Summers conduct his study with the required objectivity?

In December, the FDA began an audit of Summers’ research records, concluding later that he had repeatedly violated drug-testing rules. The agency alleged that it had found instances of missing data, biased research methods and failure to protect his subjects’ rights.

Six months later, hoping to resolve the debate, federal officials announced that they were launching their own THA study. That study, to include 300 patients in 17 centers nationwide, is not expected to produce preliminary results until late this year.

Meanwhile, pharmacists, too, had begun receiving calls.

Some came in to the Green Hills Prescription Shoppe in south Nashville, a 5-year-old apothecary where pharmacist Mark Binkley had developed a specialty in the mixing, or compounding, of hard-to-get and unapproved medications.

The practice, Binkley points out, is perfectly legal: All pharmacists are licensed to compound prescriptions. Large drug manufacturers, however, have gradually taken over that function from pharmacists, leaving many pharmacists simply dispensing manufactured drugs.

But there remain some drugs that large wholesalers do not supply. Large firms may neglect drugs that will not be profitable because they cannot be patented. Compounding is also used to tailor approved medications for unapproved uses.

For example, Binkley had compounded progesterone to treat premenstrual syndrome, as well as drugs permitted abroad for Crohn’s disease and inflammatory bowel syndrome. Other pharmacists said they had compounded experimental drugs for cancer and infections related to AIDS.

Search for an Ingredient

So in early 1987, Binkley contacted his chemical suppliers and asked them to look for a source of tetrahydroaminoacridine, the basic ingredient in THA. By summer, a Houston supply house had procured the product from a chemical manufacturer in Ontario, Canada.

The Houston firm, Professional Compounding Services of America, announced in a monthly newsletter to about 1,000 pharmacists that it was offering the chemical. Meanwhile, Binkley wrote to Paul Harvey after hearing an earlier broadcast by him about THA.

Binkley says he informed Harvey in his letter that he believed pharmacists had the right to compound unapproved drugs, including THA. On Aug. 11, Harvey conveyed that information over the air--and predicted that Binkley would be “admonished . . . for sharing that information.”

In the months after Harvey’s August broadcast, the Houston firm began supplying 34 pharmacists throughout the country, including some in Los Angeles, Chicago and most of the largest cities. Binkley alone was serving almost 30 physicians and about 50 patients.

“When a pharmacist gets a scrip, he wants to be able to fill that thing,” said Dale King, chief executive officer of Professional Compounding in Houston. “Particularly when a doctor says, ‘I have this patient, I have read the materials, and I feel there is nothing to lose’ . . . because who cares about the possibility of liver damage when the mind is being affected as it is?

“So let’s be chancy here, if I can use that word. The doctors aren’t being irresponsible here at all. They’re taking a very calculated risk.”

For Dr. Edward Stamps, it was not the first gamble.

Stamps, 69, is a retired physician from Macon, Ga., whose wife, Anne, developed Alzheimer’s about seven years ago. He says he has been “battling the government in various and sundry manners in the past four years trying to get some medication that may be of value.”

Stamps’ wife had started out on a mild mood improver. Next, they used an anti-depression drug. When that failed, Stamps took his wife to New York City and tried without success to enter her in a test of yet another experimental Alzheimer’s drug.

After that, Stamps learned about a similar drug available in Europe. He found someone to ship it, illegally, from Holland. It arrived in a bank pouch via New York City, San Francisco and Miami.

When that drug failed, Stamps learned of another experimental drug--approved for use in the U.S. only in eye preparations. Stamps persuaded the drug’s manufacturer to send him the ingredients, which he then had compounded to his specifications.

Drugs From Haiti

Next, Stamps had two more drugs shipped from Haiti--drugs that were not approved for sale in the U.S. Finally he read Summers’ journal article about THA and tried for nine months to get the drug in the United States, Europe, Mexico and Japan. He had no luck.

Last summer, a friend told Stamps about Harvey’s broadcast. Like Cecil Beauchene, Stamps contacted the pharmacist, Binkley. Because he is retired, Stamps persuaded a friend, who was a doctor and whose mother had Alzheimer’s, to prescribe THA for Stamps’ wife.

The price, Stamps said, was $2 a capsule. His wife started out on four a day.

“It was steep,” Stamps said of the cost. He ordered 1,000 capsules, anticipating that the FDA might crack down on Binkley. “I mean, hell, what’s your option? It’s your only chance, no matter what it costs.”

Similar Situation

Cecil Beauchene had the same reaction.

After hearing the broadcast, he called information in Nashville for Binkley’s number. Binkley told Beauchene he would need a prescription. So Beauchene turned for help to a doctor in Sioux City who had treated him after he had been crushed by a tractor.

Beauchene says he had to get a legal document indemnifying the doctor, who is a neurosurgeon but had no previous experience with THA. He got it notarized and gave it to the doctor, who then signed the prescription. Then Binkley mailed the drug.

Prescribing THA can be extremely risky for a doctor, Stamps observed.

“Unless doctors are pretty sure who they’re writing this for, they’re putting themselves in serious liability,” he said. “If anything goes wrong, it’s an investigational drug that the government forbids people to use. Who’s going to risk his future and entire career?”

Stamps and Beauchene report very different experiences with THA.

Stamps said he started his wife out on a schedule described in Summers’ article. After a month, blood tests showed that there were no toxic effects. But because he noticed little improvement in her condition, he gradually raised the dosage to Summers’ maximum levels.

At that point, Stamps said, his wife became violently nauseated, as though with a severe case of flu. She lost her appetite and her inclination to do anything but lie in bed and sleep.

Stamps feared immediately that it was a bad reaction to the drug. Blood tests showed elevated liver enzymes--a sign of liver damage. He discontinued the medication immediately, but it took six weeks for his wife’s condition to return to normal.

She has been unwilling to go back on the drug.

“I got into trouble with this thing and I don’t blame anybody but me,” said Stamps, conceding that a lay person handling the drug could get into worse trouble. Nevertheless, he insisted, “I think anything that offers any hope to these people should be allowable.”

Improvement Cited

Beauchene, by contrast, believes his wife’s condition has improved.

He recalled how before THA frying pans full of grease would catch fire on the stove because Joyce would forget they were there. He recalls how she would sit around the house, turn in at sundown and rarely venture out to socialize with friends at the Moose lodge.

A former bank branch manager, she could no longer add two municipal bond checks on a deposit slip. In the ticket booth at the Beauchenes’ automobile race track, she could handle single tickets. If given more than one, she was lost.

These days, Cecil Beauchene said, her memory has improved. She can remember enough to carry on a conversation. She no longer talks about suicide and the burning sensation in her head. She stays up later and likes to ride in the car with her husband.

One day last fall, Cecil Beauchene surreptitiously conducted a small test. He handed her half a dozen rent checks from tenants living on the Beauchene’s land. When he suggested that she add them up, she came up quickly with the total: $1,030.

“She has good days and bad days,” Beauchene said. “At least it doesn’t seem to be progressing.”

In the meantime, the FDA had become interested in Mark Binkley.

Word of Harvey’s broadcast, with its swipe at the agency, had filtered back to FDA headquarters in Maryland. Officials say they had also seen copies of the Houston chemical supplier’s mailing heralding the availability of THA.

In mid-September, federal and state inspectors appeared unannounced at Binkley’s pharmacy in Nashville. They said they were investigating the dispensing of THA. They inspected the pharmacy, asked for lists of suppliers and customers, thanked Binkley and left.

Two months later, they contacted him again. This time, they said they had ordered his supplier in Houston to recall from pharmacists all the THA it had supplied. Binkley considered refusing to cooperate, but then consulted a lawyer and decided to go along.

Customers Contacted

Throughout the country, pharmacists contacted their customers, gathered up their supplies and shipped their THA inventories back to Houston. They complied with the recall, several said, largely because they feared the FDA would shut them down.

“The FDA seems to want to protect the American public from ourselves, even to the point of death,” Binkley complained in a recent interview. “I think the FDA is not realizing that we’re dealing with a terminal illness.”

FDA officials say they had two objections to what the pharmacists were doing.

Under federal law, compounding is normally excluded from the law requiring registration of all manufactured drug products--as long as the work is done strictly on an individual basis and at the request of a prescribing physician.

Promoting the availability of such products is not allowed, FDA officials say. Advertising compounded products falls outside the practice of pharmacy. The Houston firm had promoted the availability of THA in its newsletter; Paul Harvey had promoted it on the air.

Not Normal Practice

“There’s a difference when someone goes outside the realm of normal practice,” said Richard Chastonay of the FDA’s drug labeling and compliance unit. The pharmacists, Chastonay said, were “going out and saying, ‘I have this new drug available.’ ”

Furthermore, researchers had temporarily suspended the federally sponsored THA study after finding liver damage in patients treated with high doses. The discovery of the potential for harming the public had prompted the FDA to intervene in the underground market.

“We are not supposed to allow drugs to enter the marketplace until we have reason to believe they work, are safe and we know enough about them to use them wisely,” said Dr. Paul Leber, head of the FDA’s division of neuropharmacological drug products. “That takes time.”

Other Arguments

Researchers, regulators and ethicists also argue that so-called investigational drugs carry a greater risk of harm than benefit: Nine out of every 10 experimental drugs tried on humans in the United States never reach the marketplace, FDA officials said.

For that reason, they say, they have an obligation to ensure that anything that is sold to the public is safe and lives up to its billing. That is essential for protecting the public from physical harm as well as economic exploitation, they say.

“I think we’ve forgotten what research is all about--not to benefit the subject, but future people,” said Arthur Caplan, a prominent medical ethicist at the University of Minnesota. “And we’ve forgotten our history and how people have been taken advantage of by outright crooks.”