Designer Drugs

Science 85, March 1985 Magazine Work

By slightly altering molecular structures, underground chemists are cooking up substitutes for heroin and other drugs.

The new drug was designed to look exactly like heroin. It was diluted with lactose, the milk sugar used to cut heroin, and it was packaged in balloons, just like heroin. It also mimicked heroin's euphoria. When a dealer unveiled it to southern California heroin users in December 1979, he even called the powder China White, the street name for the finest Southeast Asian heroin, and he charged a comparable price. Any confusion between his drug and the real thing was strictly intentional.

The dealer did a brisk business, but three days after Christmas he permanently lost two of his customers, both Orange County men in their thirties. One was discovered comatose in a motel room and ticketed DOA at the hospital; the other died in his bathroom shortly after coming home from work. Heroin paraphernalia--needle, syringe, white powder--was found alongside both men, whose bodies bore the telltale needle marks of heroin mainlining.

Yet when forensic scientists screened the corpses for evidence of narcotic poisoning, they found no trace of heroin. Nor did tests of the white powders and syringe residues found near the victims yield any known drug. "We were frantic,' said Robert Cravey, head of toxicology at the Orange County sheriff's office. "Here people were dying after injecting a white powder which looked like lactose to us. We were unable to isolate any active ingredient.'

Two and a half years later, a different heroin-like drug struck 42-year-old George Carrillo. He was taken to the Santa Clara Valley Medical Center in San Jose, California, where he lay drooling in his bed, unable to speak. If assisted he could walk slowly but only with a stooped gait. About a week later, his girlfriend Juanita Lopez, 31, entered the hospital suffering rigidness and palsy. Physicians William Langston and Philip Ballard were inclined to diagnose Parkinson's disease, but that neurological disorder afflicts only the elderly.

Carrillo and Lopez's problems had started over the Fourth of July weekend when they shared multiple doses of a powder they called new heroin. After Carrillo injected a dose, he hallucinated, something that had never happened to him before. Within days both suffered stiffness and slurred speech. They were not alone. Two brothers in Watsonville, 50 miles to the south, became paralyzed after they took injections of new heroin.

Since China White's debut in 1979, the drug has killed over 65 heroin users and is now killing at the rate of two a month in California alone. New heroin has given seven users severe brain damage indistinguishable from Parkinson's disease, and more than 200 other users of new heroin may eventually come down with the same paralysis that is crippling George Carrillo.

From the outset researchers knew that both "designer drugs' had been made to look like heroin. They also suspected that both drugs had been synthesized in clandestine laboratories. It wasn't until the drugs were identified that their most important designer feature was revealed: The drugs were completely legal. For until a particular drug is classified as a controlled substance by the state or federal government, that drug remains legal both to make and to use.

China White and new heroin were not the first synthetic drugs to come from a clandestine lab--not by a long shot. Such labs have been illegally synthesizing LSD, PCP, amphetamine, methaqualone (Quaalude), and other drugs since the mid 1960s. Even legal, designer versions of these drugs are not unique. But China White and new heroin did mark the first time anyone had made and sold legal heroin substitutes on a large scale.

The legality of the designer drugs is only one of many powerful economic incentives working to make them the future drugs of abuse. These drugs are extraordinarily cheap to synthesize. Less then $ 500 worth of chemicals and equipment can produce a cup of China White worth $ 2 million on the black market. And it takes only a modicum of laboratory experience to make the stuff from recipe. Theoretically, a single chemist could produce the equivalent of the entire world's supply of heroin without growing or harvesting a single opium poppy. And the designer market is not limited to heroin. Underground chemists can modify the molecular architecture of almost every drug on the illicit market to create legal substitutes. Why should organized crime continue to import heroin from Asia and cocaine from South America when they can make cheap and legal designer versions of them within our borders?

As the designer drugs move from their California testing ground to the rest of the country--and there is no reason to believe that they won't--they may well topple America's 70-year-old policy of drug control and spark a public health disaster of overdose deaths, poisonings, and addiction.


In 1980, as the deadly China White syndrome spread from Orange County up the coast to Monterey County and west to Arizona, another 13 users died in mysterious overdoses. Informants insisted that the powder was also being sold as "synthetic heroin.' Heroin can be synthesized from scratch, but high cost and low yield make that route impractical. More likely, the chemist behind China White had come up with a heroin substitute. In late 1980, several China White samples were forwarded to the Drug Enforcement Administration's (DEA) elite Special Testing and Research Laboratory outside of Washington, D.C., where the task of identifying the drug fell on Theodore Kram, Donald Cooper, and Andrew Allen.

Ideally forensic chemists have several grams of material to work with and reliable reference standards to turn to. Special testing had neither. They were given several samples, the largest of which weighed 200 milligrams, less than an aspirin tablet, and told that it was killing heroin users. From the 200 mg sample, they extracted about one mg of the suspected active ingredient in China White and examined it with a nuclear magnetic resonance spectrometer, a device that identifies the position of atoms in a molecule. This method revealed several molecular subunits and enabled the special testing team to sketch a rough draft of the drug's structure. Further analysis indicated that China White was a mixture of two compounds with molecular weights of 149 and 350. The lighter molecule was easy to piece together; its odd weight implied at least one nitrogen atom, and the subunits generated by the spectrometer suggested a compound called propionanilide. "We assumed that propionanilide must have been formed as an impurity in the synthesis of the active ingredient, but we ruled it out as a possible cause of death because of its low toxicity,' said Donald Cooper.

Next they searched Chemical Abstracts, a roster of known chemical compounds, for a drug whose structure would match what they knew about the heavier molecule. They settled on 3-methyl fentanyl, a powerful analgesic that was invented and patented in the early 1970s but never marketed. Later, when they compared the analytical data of pure 3-methyl fentanyl with that of the China White sample, they made a minor correction and reidentified China White as alphamethyl fentanyl.

Alpha-methyl fentanyl and 3-methyl fentanyl are analogs, or chemical cousins, of fentanyl, each differing from the parent compound by the attachment of a single methyl group. (See diagram, opposite page.) Fentanyl is a synthetic narcotic sold as Sublimaze by Janssen Pharmaceutica and used regularly as an anesthetic in major surgery. Drugs from the fentanyl series are excellent heroin substitutes because they work just like heroin to block pain and cause euphoria by binding to opiate receptors in the brain. Because of this binding ability, these synthetic opiates also display cross-tolerance and cross-dependence with heroin. A high-dosage user of one can switch to a comparable dosage of the other without overdosing, and the two drugs are interchangeable in relieving the craving and withdrawal of opiate addiction.

By January of 1981, the DEA disclosed China White's true chemical identity. The fact that alpha-methyl fentanyl has never been marketed commercially and the presence of the propionanilide impurity convinced the DEA that China White was coming from a clandestine drug lab. Under federal drug law, a compound is legal to make, own, and use until it is scheduled as a controlled substance. Alpha-methyl fentanyl's designer wrinkle, a methyl group attached to a particular site on the molecule, differentiated its structure just enough from the controlled fentanyl to make it as legal as table salt. "You could walk around with a shopping bag full of it and nobody could do anything to you,' said Robert J. Roberton, chief of the State of California's Division of Drug Programs. The DEA quickly filed the paperwork to start the scheduling process.

Even though the deadly nature of the drug was thoroughly publicized, California heroin users continued to die. A state of California research grant to detect alpha-methyl fentanyl in these victims made Gary Henderson's laboratory a China White clearinghouse. Henderson, a professor of pharmacology at the University of California at Davis, has studied the fentanyl series of drugs for over a decade, and it was he who coined the term designer drug.

Until Henderson investigated the China White cases, it was widely assumed that overdoses from poorly cut batches of the drug were killing users. It was a sound hypothesis. Both fentanyl and alpha-methyl fentanyl are some 20 to 40 times stronger than heroin and infinitesimal doses of the drugs, 40 to 80 micrograms (a microgram is a thousandth of a milligram) can induce heroin-like euphoria. An aspirin tablet, by comparison, weighs over 300,000 micrograms. Surgical doses of 200 micrograms of fentanyl are generally safe, but at higher levels the drug represses the breathing reflex and patients must be put on artificial respirators. Henderson estimates that 300 micrograms of either fentanyl compound would be enough to shut down respiration and kill a novice user who had not built up a tolerance. "Just a few extra crystals of alpha-methyl fentanyl in the injection would be enough to cause an overdose,' he said.

When Henderson examined China White powders, he fully expected to see samples containing those deadly "few extra crystals' of alpha-methyl fentanyl. Instead he found the samples to be fairly uniform in concentration, containing only 50 to 80 micrograms of the drug in each standard street dose. This was enough to cause euphoria but well below the lethal dose. Nor did the blood levels of victims reflect massive overdoses. In almost every case, the blood levels were on par with dosages in the 50 to 80 microgram range. "Users shouldn't have been dying from these low levels, but they were,' said Henderson.

Just how China White causes death remains a mystery, but Henderson has found a group of users who are taking massive doses of the drug--and surviving. Since 1981, drug users who insisted they were addicted to heroin but whose urine showed no sign of the opiate began turning up in California methadone clinics. The urine samples were forwarded to Henderson, who found substantial amounts of China White in them. In some cases, the levels of China White were 50 times higher than those found in victims presumed to have overdosed. Henderson points to these cases as evidence that overdose deaths are a rare occurrence. "The most overdose-prone users are heroin novices and "chippers,' occasional users who have lost their tolerance to opiates,' he said. The safest users seem to be those who have boosted their tolerance with large, steady diets of heroin or China White. The high number of China White urines from methadone clinics makes him think that thousands of drug-tolerant California users --up to 20 percent of the state's estimated 100,000 addicts--might be regular users of one of the fentanyls.


In 1982 a paralyzed George Carrillo became the first of several victims of new heroin to wind up under William Langston's care at the Santa Clara Valley Medical Center in San Jose. Because some of his patients referred to their drug as synthetic heroin, Langston believed that new heroin might be alphamethyl fentanyl. He persuaded one of the victim's relatives to give him a sample of the drug for analysis and immediately sent a portion of it to Henderson. Henderson, however, was unable to detect any form of fentanyl in it.

Langston had no idea how widespread the use of new heroin might be, but the minute he made the connection between the drug and Parkinson-like paralysis, he issued a public announcement warning heroin users of the drug's dangerous side-effects. That recruited three more new heroin users suffering from the same symptoms: stiffness, impaired speech, rigidity, tremors. These parallels tempted Langston to diagnose Parkinson's disease, even though the diagnosis made no sense. Symptoms of Parkinson's arise whenever the brain's supply of dopamine, a neurotransmitter, is interrupted. If the brain is short on dopamine, neural signals that instruct muscles to work get lost or blocked, resulting in the very problems Langston's patients were experiencing. No one knows exactly what causes the disease, but it strikes almost exclusively the elderly-- one in 100 between the ages of 60 and 65. George Carrillo, Juanita Lopez, and the others were much too young to have Parkinson's.

Carrillo suffered in his bed for over a week before Langston decided to treat his paralysis with L-dopa, a drug the brain converts to dopamine that has been used to treat Parkinson's disease since the 1960s. "When I gave him L-dopa the reaction was amazing. It was like melting a block of ice,' said Langston. Lopez also responded to the L-dopa therapy as did the others who had been paralyzed by new heroin. Within days they were able to walk and speak intelligibly. As long as they remained on substantial doses of this medication, they were able to function. But without it they would freeze up, just like victims of Parkinson's disease.

Langston had also sent a sample to Halle Weingarten of the county crime laboratory. Weingarten couldn't determine exactly what the powder contained, but she did detect a substance very similar to meperidine, a narcotic painkiller marketed under the trade name Demerol. As with the fentanyl drugs, users of compounds from the meperidine family can develop the same tolerance and dependence patterns that they do with heroin.

Meanwhile, an informant who insisted on anonymity contacted Deputy Sheriff Dave Weidler and sent him the packing list for a shipment of chemicals he believed were being used to make drugs at a house in the county. Deputy Weidler turned the list over to James Norris of the county crime lab, who compared it to the meperidine-like drug Weingarten had just analyzed. Norris concluded that the packing list described enough raw materials to produce tens of kilograms-- hundreds of thousands of doses--of such a drug.

Deputy Weidler was ready to raid the house, but without probable cause that a crime was being committed, no judge would issue a search warrant. While it is a crime for an unlicensed individual to make meperidine, no laws proscribe the synthesis of meperidine-like drugs or the chemicals for making them unless they are controlled substances. So the sheriff's office enlisted the fire department to conduct a fire inspection of the house, with Weidler in tow, to get a look at what was going on inside.

The lab's operator met the fire department at the door and graciously consented to an inspection, commenting that he was merely experimenting with methods to make snow cone flavorings and moisturizing creams. Laboratory equipment and clean glassware were set up, but nothing was being synthesized at the time. Fire department authorities advised the lab operator that the chemicals constituted a fire hazard and gave him 24 hours to remove them, which he did. Authorities, however, did spy a container of powder and pinched a sample of it during the inspection. Later analysis of the sample revealed a meperidine-like substance identical to that found in new heroin.

The big breakthrough came when Halle Weingarten recalled the parallels between the new heroin case and an article she had read in the journal Psychiatry Research in 1979, three years before, which described a 23-year-old student from Bethesda, Maryland, who had come down with Parkinson's symptoms after using his own home-brewed opiate substitute. The student had intended to make MPPP, an analog of meperidine, which like alpha-methyl fentanyl has never been distributed commercially.

National Institute of Mental Health doctors had successfully treated the student with L-dopa but couldn't figure out what, specifically, there was in his drug that was causing the symptoms as they had no sample to work with. NIMH attempted to duplicate the student's method of making MPPP, but rats injected with their concoction failed to develop Parkinson's symptoms. In 1978, after the student died in a cocaine-related death, the NIMH study came to an end but not before the link to Parkinson's disease was strengthened by evidence gathered in an autopsy of the student's brain. In classical cases of the disease, extensive cell death occurs in the substantia nigra, a crucial dopamine pathway. NIMH researchers found identical damage in the student's brain.

Weingarten told Langston of the case, and he then searched Stanford University's library for more information on MPPP. He discovered instead that all the relevant articles on MPPP's synthesis had been razored out of the journals, the sure sign of an underground drug manufacturer at work. Langston forwarded samples of new heroin to Ian Irwin, a chemist at Stanford, who identified the MPPP in them. But Irwin also found substantial quantities of a substance called MPTP. He experimented with the synthesis of MPPP and found that MPTP could be generated as a by-product if either excess heat or acid was applied, a mistake an inexperienced or unscrupulous chemist might make. Perhaps the chemist behind new heroin had rushed the drug's synthesis and contaminated it with MPTP, and this chemical was causing the strange paralysis by destroying its users' brain cells. In 1983 NIMH researchers confirmed that MPTP was a powerful neurotoxin when they succeeded in inducing Parkinson's disease in monkeys by injecting them with a few milligrams of the chemical.

The Bethesda student never shared his drug with anyone, so he was the sole victim of his sloppy chemistry. But how many others in San Jose had taken the snow-cone chemist's new heroin? How many would be afflicted with the paralysis? Langston dispatched two of his students to local methadone clinics in search of possible users. Follow-up interviews eventually located more than 200 people who reported that they might have taken the drug.

If so, these users may yet be stricken with the disease. The substantia nigra gradually deteriorates in the course of normal aging, yet Parkinsonian symptoms don't appear until one has lost 80 percent of those cells. "Suppose people using this drug lost 50 percent of their substantia nigra cells in two or three doses--which is not at all improbable,' said Langston. "If they start out with a 50 percent loss, then they could cross that 80 percent mark in five to 10 years, as normal aging proceeds, so we might be seeing a wave of Parkinson's disease in young people in coming years.' The federal Centers for Disease Control is now assisting Langston in locating the people who might have used new heroin so their health can be monitored.

Fortunately, after Langston's warning went out, new heroin all but vanished from San Jose. But for George Carrillo, Juanita Lopez, and five others the warning came too late. L-dopa therapy is no panacea. Doses of it must be finely calibrated to work. Too much of the drug causes adverse reactions; too little fails to relieve symptoms. Over time the drug becomes less effective in reversing the paralysis, which leads to death from infections or malnutrition.


In 1981 alpha-methyl fentanyl, or China White, killed only one person. But the drug remained in plentiful supply, so the Drug Enforcement Administration went ahead with the scheduling process to classify the drug as a controlled substance. The DEA guessed that as soon as the drug became illegal the chemist would spin off another of the more than 200 known analogs of fentanyl to keep a legal heroin substitute in his inventory. From this list of analogs, DEA Special Testing synthesized 26 of the most likely. "The next one we saw wasn't one of them,' said Andrew Allen. In May 1981, a full four months before alpha-methyl fentanyl became a scheduled substance, the Los Angeles Police Department acted on a lead that a shipment of China White was being sent down from northern California. They seized a package that turned out to be para-fluoro fentanyl.

Para-fluoro fentanyl's appearance stunned the DEA because, unlike alphamethyl fentanyl and MPPP, it has never been written up in the open literature. Most lab operators are content to make illicit drugs from formulas found in underground drug cookbooks or handed down to them by friends. The enterprising few who make designer varieties of amphetamine, PCP, and the hallucinogens usually crib the formulas from scientific journals, just as MPPP's was. The synthesis of a novel compound like parafluoro fentanyl proved that a talented chemist was at work. "I would guess that the fellow behind the fentanyls is a graduate student or a college grad in chemistry,' said Donald Cooper.

Because para-fluoro fentanyl was not illegal, its owners had to be set free. Had they asked for the return of their drug, the police would have been legally obliged to do so. For unknown reasons, this analog, which differs from fentanyl by a single fluorine atom, never again appeared.

In 1982 China White fatalities rebounded back up to seven. Another 13 died in 1983, and over 30 in 1984 as four new designer fentanyls, two of which are thousands of times more potent than heroin, hit the street. To date none of the new analogs has been scheduled and no lab has been seized. "I doubt very much if the guy who made China White has a lab set up,' said Henderson. "Most likely he made a few grams of the drug-- millions of doses--and then shut up his shop. Or maybe he made all the analogs at once and is parceling them out one at a time.'

Since the passage of the Harrison Narcotic Act of 1914, America's policy of drug control has been predicated on interdicting organic drugs from abroad. By blocking Asian heroin, South American cocaine, and Mexican marijuana at the border, the government has sought to cut the supply of drugs and drive up the price, hoping that this would reduce drug use. This policy has met some success, but it has also established an environment in which designer drugs can flourish. If labs start making designer heroins in earnest and dealers switch to these drugs, the country could quickly be awash in cheap, legal heroin substitutes, perhaps leading to an epidemic of addiction and overdose.

The heroin market is not the only one vulnerable to this sort of encroachment. The cocaine market is also wide open. A cocaine study by a team at Yale University in 1979 found that cocaine sniffers were unable to distinguish cocaine from a local anesthetic. Already a few enterprising souls have made and sold crude powder preparations containing stimulants found in over-the-counter medications. Completely legal, these cocaine substitutes have such names as Coco Snow, Crystal Caine, and Synth Coke. Even more potent substitutes are possible, though, based on the amphetamine molecule. A sufficiently dedicated chemist could tinker with amphetamine to make a legal "synthetic cocaine.'

"These new drugs are without a doubt one of the most complex challenges to drug control we've ever faced,' said Gene Haislip, DEA deputy assistant administrator for diversion control. In late 1984, Congress gave the DEA a new weapon to combat designer drugs-- emergency scheduling powers. Normally it takes six months to a year to schedule a new drug. The new powers allow the DEA to ban designer drugs with the stroke of a pen and a year to justify the action. But aggressive scheduling may only accelerate the proliferation of designer drugs as chemists unleash new legal analogs every time the government prohibits one. The analog possibilities are endless; nature has provided the molecular patterns for millions of potential drugs of abuse, and the slightest modification, like that of fentanyl, can produce a potent and legal drug. When asked how many fentanyl analogs are possible, Henderson shrugs his shoulders. "That would be a good question for a graduate student to write a paper on. Perhaps hundreds. Maybe thousands.'

Even if the government were to find a way to outlaw designer drugs before the fact, we could still be awash in synthetic drugs. Since the mid-1960s, police have closed over a thousand labs producing illegal drugs and handed out stiff sentences to the chemists, but that has not prevented billions of doses of these drugs from pouring onto the black market. PCP tells the story in a nutshell. When this lab-made drug first made its appearance in Los Angeles in 1965, it was dismissed as a California fad. From its California toehold, however, PCP spread across the country and around the world. Escalating penalties against it have not kept it from becoming one of the most ubiquitous street drugs.

The most surprising thing about designer drugs like China White and new heroin is not that they have appeared on the drug scene, but that it has taken so long for them to appear. The chemical signature of impurities found in China White have led Henderson and the DEA's Donald Cooper to believe that only one chemist is currently behind China White, but both think that it is only a matter of time before imitators set up labs. Given the enormous profits to be made, such a move is almost a certainty. When these designer drugs arrive in full force, we may well experience the deaths, overdoses, and poisonings of China White and new heroin on a national scale.


The Parkinson's Connection

The link between MPTP, the contaminant discovered in new heroin, and Parkinson's disease kicked off a new round of research in a field that was moribund for decades. When L-dopa therapy was developed in the 1960s, scientists abandoned basic Parkinson's research and focused their efforts on finding new drugs for treating the disease's debilitating symptoms. In the last two years that trend has reversed, and MPTP may be far better remembered as a tool for exposing the underlying cause of the disease.

By injecting laboratory animals with MPTP, scientists at the National Institute of Mental Health found that they could induce irreversible cases of Parkinson's, something no other drug had reliably done before. This "animal model" for Parkinson s, which already has helped generate an effective MPTP antidote, enables researchers to study the disease's mechanisms in detail.

MPTP, it now appears, is not directly responsible for the destruction of the brain cells that results in Parkinson's. Groups at the University of California at San Francisco, Rutgers Medical School, and NIMH find that the brain uses MPTP as a raw material to produce whatever toxin actually does the damage. After MPTP is administered to monkeys, it is metabolized by a brain enzyme, first to a chemical called dihydropyridinium ion and then to MPP+, both charged, oxidized versions of MPTP. When these chemical reactions are experimentally blocked, MPTP circulates in the brain, doing cells no harm. This evidence has shifted attention from MPTP to MPP+. Tests show that MPP+ alone does cause cell damage but not the sort of selective damage to the substantia nigra observed in animals given MPTP or in classical cases of Parkinson's disease.

The San Francisco team has come up with an untested hypothesis that dihydropyridinium is more directly responsible for the death of brain cells than either MPTP or MPP+. Their thinking goes like this: The substantia nigra is rich in both the neurotransmitter dopamine and neuromelanin, a byproduct of dopamine. Perhaps one or both of these substances interacts with dihydropyridinium in the substantia nigra to generate the cell-killing chemical. The problem with the theory is that other parts of the brain are rich in similar neurotransmitters, but they seem to be immune to the ravages of MPTP. New MPTP studies are now being framed to identify the end product that does the actual damage.

MPTP first caught William Langston's attention when it was found in his patients' new heroin. But in fact, MPTP has been around for decades. Major chemical supply houses sell small quantities of MPTP as a building block for other industrial chemicals. Even MPP+ was developed in the 1970s as a herbicide, though it was never marketed. Fortunately, contact with MPP+ cannot cause Parkinson's. Though this chemical forms when MPTP is metabolized, MPP+ itself cannot enter the brain from the outside. Research into MPTP, however, has unearthed other suspicious cases of Parkinson's. In 1970, for example, a chemist synthesizing MPTP for a drug company was stricken with the disease at a premature age. New safety guidelines for handling MPTP are now being developed.

Ironically, MPTP and Parkinson's research have come together once before but from the opposite direction. While tracing MPTP's history, Langston found that in the 1950s scientists from Hoffmann-La Roche Inc., a pharmaceutical company in New Jersey, tested MPTP as an anti-Parkinson's disease drug in both animals and humans. According to Langston, two of the six humans who rook the chemical died during or shortly after the research project, and two monkeys given MPTP were struck with Parkinson-like rigidity. Hoffmann-La Roche researchers failed to connect the monkey's symptoms to Parkinson's disease, and they abandoned the experiment.

That MPTP can cause Parkinson's disease is certain, but that doesn't explain how millions of people who have neither taken a tainted narcotic nor handled the industrial chemical have contracted the disease. One theory has it that the brain creates an MPTP-like toxin of its own in the course of normal aging. A competing theory holds that the disease is environmental in origin, a contention which history supports. The first time that the palsy and paralysis typical of Parkinson's disease was recognized as, a disease in its own right was during the industrial eras. Could MPTP be an unnoticed pollutant of the industrial revolution in England? As Stanford chemist Ian Irwin points out, when heat and three common industrial chemicals--alpha-methylstyrene, formaldehyde, and methylamine--come together, they can spontaneously generate MPTP. So common are these chemicals in industry that MPTP could be an unwanted byproduct of manufacturing processes. This theory, however, doesn't account for the incidence of the disease outside industrial areas. Parkinson's strikes older people in both rural and industrial settings.

Whether the genesis of Parkinson's disease is neurochemical, environmental, or both, its secrets are being pried loose by MPTP.