A Doctor’s Posthumous Vindication


Peter Gleason was a psychiatrist who devoted much of his professional life to caring for what government officials call “underserved populations.” He would have been thrilled to learn that on Dec. 3 in New York, a three-judge panel of the U.S. Court of Appeals for the Second Circuit issued a ringing opinion that vindicated the conduct for which he was indicted and arrested in 2006.

Unfortunately, Gleason did not live to see this welcome reversal of the federal government’s crusade against him and the promotion of Xyrem—a drug widely used by physicians, including Gleason, to treat a number of medical conditions beyond what the federal Food and Drug Administration approved it for. Hounded for years, he saw his career and finances ruined by the relentless war waged against him by FDA bureaucrats and Justice Department prosecutors. Gleason committed suicide on Feb. 7, 2011.

The doctor’s troubles stemmed from lectures he gave attesting to the efficacy of Xyrem, a pharmaceutical originally developed for use in narcolepsy but found by physicians to be effective against a number of conditions, including fibromyalgia and chronic fatigue syndrome. The FDA had not given formal approval for these so-called “off-label” uses since the manufacturer had not submitted an application covering those ailments.

Obtaining FDA approval for a new drug is time-consuming and expensive. Once a drug is approved for a certain use (which its FDA-approved “label” describes), physicians often discover, through use of the drug as well as through further research and field experience, other conditions for which the drug is a safe and effective remedy. Manufacturers rarely go through the FDA approval process for such additional uses of already-approved drugs due to the expense. FDA regulations forbid them to promote these “off-label” uses.

Yet such uses are widely practiced by experienced physicians. They know, for instance, that Neurontin, approved to treat seizures, can also relieve neuropathic, or nerve, pain. Avastin, approved to limit new blood-vessel growth in tumors, ameliorates age-related muscular degeneration. Aspirin is widely deemed a miracle drug because of its uses beyond pain relief, largely discovered by trial and error.

Unlike manufacturers, physicians are not restricted by federal law from prescribing an FDA-approved drug for an off-label condition. They are perfectly free to communicate the results of their experience to fellow physicians, or to publish in medical journals. Such communications have long been recognized to be protected by the physicians’ professional prerogatives and free-speech rights.

So how was it that Gleason was indicted on a conspiracy charge of communicating to his fellow physicians that he found Xyrem effective for off-label medical conditions such as chronic pain and bipolar disorder? Gleason, it turns out, often revealed his experiences with Xyrem to audiences of physicians during paid appearances at events sponsored by its maker, Orphan Medical—a common practice within the medical community. The prosecutors’ convoluted legal theory was that even if Gleason himself was free to recommend Xyrem, he had lost his First Amendment right to communicate his medical knowledge because he had become an agent of sorts for the manufacturer and “conspired” with employees of the company, who had to stick to promoting only FDA-approved uses.

No wonder Gleason was shocked when he found himself surrounded and handcuffed by six federal agents who were waiting for him at a train station on New York’s Long Island on March 6, 2006. When prosecutors could not convince Gleason to cooperate against the drug manufacturer—he did not feel that either he or Orphan Medical had violated the law—they indicted him, triggering a downward spiral that wreaked havoc on his medical practice.

Gleason was not a wealthy man, but whatever assets he had accumulated during his working life were placed in limbo when the feds included in the indictment a “criminal forfeiture allegation.” This sought to force him to turn over to the government “any property, real and personal, that constitutes or is derived, directly or indirectly, from gross proceeds traceable to the commission of offenses.” Virtually all of Gleason’s income and assets were derived from his medical practice. Thus prevented from hiring private counsel of his choice, he required free legal representation from the Federal Defenders Service, tasked with representing indigent defendants.

The ordeal of fighting a federal indictment, a daunting process even for the wealthy, exhausted Gleason, with whom I corresponded when I included his case in a book I was writing about how federal bureaucrats and prosecutors go after innocent defendants for innocuous behavior. He grew increasingly dispirited and finally decided to accept an offer that he felt he could not refuse. He pleaded guilty to a misdemeanor alleging his conspiracy with Orphan Medical and was sentenced to one year of probation and a $25 fine.

But Gleason’s career was ruined and his pride decimated. He had difficulty holding a hospital or clinic job, and his medical license was placed into question. He was despondent the last time I spoke with him, and he subsequently took his life by hanging himself.

Just under two years later, Gleason’s posthumous vindication was achieved by his co-defendant, Alfred Caronia, a sales representative for Xyrem’s manufacturer, Orphan Medical (later acquired by Jazz Pharmaceuticals JAZZ -0.21% ), who had refused to make a deal with the feds. With the aid of aggressive legal counsel and the “friend-of-the-court” backing of two public-interest organizations, Mr. Caronia won the point that Gleason had many times argued to anyone who would listen: The First Amendment protects the right of physicians, drug manufacturers, sales representatives and anyone else who wishes to convey truthful, factual information about the beneficial uses of drugs in the relief of illness and pain.

What the appeals court affirmed in ruling for the defendants on Dec. 3 seems so obvious now. But it’s too late for Peter Gleason. And too late for the feds to apologize, if they were so inclined.

Mr. Silverglate, a Boston lawyer, is the author of “Three Felonies a Day: How the Feds Target the Innocent” (Encounter Books, 2009).

A version of this article appeared Dec. 26, 2012, on page A13 in some U.S. editions of The Wall Street Journal, with the headline: A Doctor’s Posthumous Vindication.


Fake pharmaceuticals

Bad medicine

The world’s drug supply is global. Governments have failed to keep up

Oct 13th 2012 | ABUJA AND WASHINGTON, DC | from the print edition



PATIENTS expect drugs to be safe. But even in supposedly well-run health systems, they can be useless—or deadly. Tainted steroids from a compounding pharmacy (one which mixes its own drugs) near Boston had killed 11 people with fungal meningitis and sickened more than 100 as of October 10th. A contaminated blood thinner, heparin, was linked to 149 American deaths in 2007-08. This year it emerged that some vials of the cancer medicine Avastin contained no active ingredient.

No one knows exactly what share of medicines are fake, ill-made, stolen or diverted. But bad pharma is a global problem, which national drug-safety agencies are struggling to contain. It particularly afflicts countries where officials are bribable, health systems lax and consumers desperate. In Nigeria, Africa’s largest market for medicines, a survey by the World Health Organisation (WHO) in 2011 found that 64% of antimalarial drugs were fake. Over 70% of drugs consumed in Nigeria are imported from India and China, widely seen as the biggest source of fakes. Paul Orhii, of Nigeria’s drug agency, blames “a shambolic system and porous borders”.

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Salesmen have peddled worthless cures for millennia. But the 21st century is turning into a golden age for bad drugs. In Boston, the fungal meningitis spread because of poor oversight. Price pressure encourages even well-intentioned drugmakers to cut corners. For criminals, fake pharma is lucrative and the penalties are usually low. Indeed, the drug supply-chain is a cheat’s paradise.

Raw materials come from one place and are processed into active ingredients in another. Pill-fillers and coating come from other sources. Manufacturing and packaging may be separate. To reach the dispensary, the drug passes through distribution chains (and may be repackaged). In America 80% of drugs’ active ingredients come from abroad (drug imports there more than doubled from 2002 to 2010, accounting for 40% of finished medicine).

This creates a regulatory nightmare. In the heparin case Chinese suppliers replaced the main ingredient with a cheaper, dangerous substance that still passed authentication tests. The fake Avastin apparently hopped from Turkey to Britain to America, with help from a Canadian online pharmacy. Do-gooding attempts may backfire, too. The WHO has a “prequalification” scheme that authorises cheap, good drugs for aid programmes. But Roger Bate of the American Enterprise Institute, in a paper published in July, found that 7% of such drugs in his sample failed.

Attempts abound to stem the scourge. The latest raids in Operation Pangea (an international police campaign against illegal online pharmacies) involved 100 countries and shut down more than 18,000 online pill-pushers. But such pharmacies are not necessarily the villains: they often sell real drugs (at low prices); and many fakes are on sale from reputable offline outlets.

Some poor countries think that rich ones simply want an excuse to bust their generic drug industries. Rows about the definition of “counterfeit” have crippled the WHO’s International Medical Products Anti-Counterfeiting Taskforce, or IMPACT, launched in 2006. Now new working groups are mulling the meaning of SFFC (“spurious/falsely-labelled/falsified/counterfeit”) drugs. It may add another “S” for “substandard”. Pirates are not trembling.

Most other international efforts are moving slowly, says Mr Bate, author of a book called “Phake”. To punish counterfeiters more harshly and speed information-sharing, 18 European countries signed the Medicrime convention in 2011. But only Ukraine has ratified it. The G8 group of rich countries published a wordy declaration in May, but has done little since.

For years governments and companies have talked about “track-and-trace” systems to identify and authenticate medicines. Though the technology exists, countries cannot agree what to use. Different firms hawk their own schemes; regulators disagree about what should be tracked.

My pills, not yours

So individual states are taking their own steps. Nigeria has spearheaded an impressive counterattack, which by some counts has brought the share of fake medicines down from around half to a tenth in five years. One means is TruScan, a cheap hand-held spectroscope that allows officials to spot fakes at the point of import (America, Germany, Sweden and Canada now use this, too). Nigeria has also deployed a scratch-off label system, in which users text the revealed code from their phones to verify the product before consuming it. But the scheme is voluntary and so far only a few firms are using it.

China, concerned for the reputation of its drug-export trade, has staged big seizures of fakes (detaining nearly 2,000 people in August). It executed its top drug official in 2007 for approving untested medicine in exchange for bribes. India has commissioned feasibility studies of track-and-trace technology from Wipro, a software and services giant. The government talks of better manufacturing standards, but exhortation has yet to lead to action.

America’s Food and Drug Administration (FDA), the world’s biggest drug-safety agency, has steadily reached beyond the country’s borders. Since 2008 it has opened offices in China, India, South Africa, Jordan, Mexico, Belgium and other countries. A recent law sets higher penalties for counterfeiters and allocates money for the agency to inspect more factories overseas. But even the FDA admits it cannot police the world’s drug supply alone.

Drug firms often make better enforcement partners than governments do. John Clark, security chief for Pfizer, a pharma giant that makes Viagra, likes to tell a story about a man caught selling fakes who asked an undercover agent first if he was with “the Feds”, then whether he worked for Pfizer. His firm employs former police, investigators and customs officials all over the world. Usually it builds about 80% of a case, then hands it to local law-enforcers.

Yet, as officials fiddle, the problem grows. In January 2009, 81 countries noted counterfeit versions of 20 Pfizer drugs. As of July 2012, 106 had found 60 such fakes. “Counterfeiting is like a balloon filled with water,” says Nigeria’s Mr Orhii. “You push it on one side but when you remove your hand, it bounces back even stronger.”

Dr. Liston: Fastest surgeon

Before anesthesia, speed was essential to minimizing pain and improving odds of survival.

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Imagine lying on a table in a old-school operating room. Faces stare down at you from the viewing galleries above, and your leg throbs with pain from a broken bone — infection is just starting to set in. The door opens and three men in blood-stiffened aprons walk in, carting a collection of knives and saws. Two of them grab your shoulders and arms and pin you to the table. The third picks out one of the knives from the cart.

“Time me, gentlemen,” he calls out to the gathered spectators. “Time me.”

The man grabs your leg and begins to cut just below the knee. He continues to hold onto your leg as one of his lackeys gets a tourniquet around it. To free his cutting hand, he clasps the bloody knife in his teeth and picks up a saw. He cuts back and forth through the bone, drops the severed leg into a bucket filled with sawdust, and sews you up, to the applause of the men sitting in the wings. As promised they’ve timed the whole procedure — from first incision to clipping the loose threads on the sutures — at just two and a half minutes.

The man who just flew through your amputation with apparent reckless abandon was Dr. Robert Liston, one of the finest surgeons of the time.

Dr. Richard Gordon, a surgeon and medical historian, calls Liston the “fastest knife in the West End.” His style may have seemed careless, but in the age before anesthesia, speed was essential to minimizing the patient’s pain and improving their odds of surviving surgery. Slower surgeons sometimes had pain-wracked and panicked patients wrestle free from their assistants and flee from the operating room. Only about one of every 10 of Liston’s patients died on his operating table at London’s University College Hospital. The surgeons at nearby St. Bartholomew’s, meanwhile, lost about one in every four.

Liston’s quick hands were so sought after that patients sometimes had to camp out in his waiting room for days waiting for their turn to see him. Liston tried to see every last one of these patients, no matter their condition. He especially loved treating those cases that his fellow surgeons had dismissed as beyond help, which earned him a reputation among colleagues as being showy.

Occasionally, Liston’s speed and showmanship actually were a hindrance to his operations. Once, he took a patient’s testicles off along with the leg that was being amputated. His most famous (and possibly apocryphal) mishap was the operation where he was moving so fast that he took off a surgical assistant’s fingers as he cut through a leg and, while switching instruments, slashed a spectator’s coat. The patient and the assistant both died from infections of their wounds, and the spectator was so scared that he’d been stabbed that he died of shock. The fiasco is said to be the only known surgery in history with a 300 percent mortality rate.

Liston had more going for him than just a quick and (mostly) steady slice, though. He was a highly-regarded surgical instructor and prolific inventor. Some of his creations, like the “Liston splint” and “bulldog” locking forceps, are still around today. He also published two medical texts, The Elements of Surgery and Practical Surgery.

Towards the end of his career, Liston made medical history and performed a surgery that made his nimble hands obsolete in Britain. From that point on, pain would no longer be a hurdle to successful surgery, and speed wouldn’t be the surgeon’s greatest asset.

In 1846, Liston received a patient named Frederick Churchill, whose right knee had been causing him terrible problems for years. None of the treatments he’d been given before had worked, and now the only option was amputation. The day of the surgery, Liston walked into the operating room and, instead of grabbing a knife and asking his audience to time him, he pulled out a jar. Ether, American dentists and doctors had recently demonstrated, could be used as a surgical anesthetic. “We are going to try a Yankee dodge today, gentlemen,” Liston told the crowd, “for making men insensible.”

Liston’s colleague, Dr. William Squire, administered the anesthesia. He held a rubber tube to Churchill’s mouth so he could inhale the ether, and after a few minutes, he was out. Squire placed a handkerchief laced with more of the stuff over Churchill’s face to keep him that way, and then Liston began the operation.

A mere 25 seconds later, the amputation was complete. Churchill roused a few minutes later and reportedly asked when the operation was going to begin, to the amusement of the audience.

Further use of ether in Europe’s operating rooms revealed its drawbacks. It irritated surgeons’ lungs, caused vomiting and other side effects in patients and, in some windowless rooms where surgery was performed by gaslight, ignited and caused fires. Anesthetics would continue to improve and become more common in medicine, but Liston wouldn’t get to see much of their progress. He died in a sailing accident less than a year after Churchill’s surgery, still the fastest knife London had ever known.

This post originally appeared on Mental Floss, anAtlantic partner site.