NOVA; The Case of the Frozen Addict; 1305

Oh. It began with the emergency admission of a bizarre medical case. All right. I'm just going to flash a light in your eyes and see what I saw when I went in the patient's room was remarkable. I had never seen anything like it before in my life. Here was this man apparently in his 40s. He was frozen. The key to this mystery would not be found in any medical textbook but would lead instead to the underground drug world of California. Ironically from that seedy world has come a major medical breakthrough bringing hope to millions of sufferers of a devastating brain condition known as Parkinson's disease. The case of the frozen addict. Next on nová. Major funding for No law is provided by this station and other public television stations nationwide.

Additional funding was provided by the Johnson Johnson a Beverly of companies supplying health care products worldwide and by Allied Signal technology leader in aerospace electronics automotive products and engineered material. This is in San Jose California. Something strange happened on July 16th 1982. One of the prisoners at the local jail awoke to find that he couldn't move or talk. To anyone 10:49 VMC.

We are frozen like a pillar of salt. He was rushed to the Valley Medical Center. Nothing like it had ever been seen before and the arguments broke out as to what it was were all of his sources take a look at that. George if you can hear me in there what I want you to do is to try to follow my finger very carefully with your eyes. Keep your finger just your eyes glued on my finger as I moved about a little bit as is that it can do it. You can do it. I only say in one case it was close to that a case of a very very rare disease called Wilson's disease. But this wasn't even like that. So I could see why the arguments going on. The first question that confronted us at that point was whether this man was mentally normal inside. Since there was no way to communicate we didn't know. Noticing that he could move his hand just a little. Doctors Langston and Ballard had an idea. Here it was. See if you can write the answers to some of our questions on his pad of paper and he could as George Kirylo

wrote. I can't move right. I know what I want to do. It just won't come out right. By question and answer a case history was built up and in that history was a revealing state. George Kirylo was a heroin addict. As would become clear he was the victim of a bad batch of drugs that had done irreparable damage to his brain. But his tragedy would open a new chapter in medical research. George Kirylo was just the first. His girlfriend Juanita also a heroin user was having even worse problems to a neurologist. The symptoms were very familiar. They were textbook descriptions of a very common disease of the elderly. These patients of course manifested all of the signs of Parkinson's disease. However this was a difficult diagnosis to swallow. Parkinson's disease usually occurs over the age of 50. It comes on very gradually in fact it's so

slow it's almost imperceptible most patients have had symptoms for one to two years before they actually go to a doctor that's how slow it is. In this case these were younger people. The girlfriend was in her early 30s. And it came on almost overnight. Parkinson's disease doesn't do this yet this looked like Parkinson's disease. So we had a first class medical mystery on our hands at that point. The mystery was only just beginning. That Friday. Dr. Phil Ballard left for a weekend break. He headed some 40 miles south to Santa Cruz where he had been invited to a dinner party. In this unlikely setting. He was to stumble on the next clue. At the party was another neurologist Dr. Jim tetron and soon the two of them started to talk about their cases. What Ballard heard that night was remarkable. Jim

Taproot told him of a bizarre case of two brothers from nearby Watsonville that had just been referred to him like George and Juanita. They were frozen with all of the symptoms of Parkinson's disease. David and his brother had been found by their mother lying frozen in their apartment. And there was another remarkable thing about them. They were both heroin addicts. Here we now have a totally different family different geographical location and the key both these brothers were heroin users. That identified the heroin that was the only common link between these cases. That point we went for the heroin and started trying to get samples. Langston also held a press conference to warn there were some very dangerous heroin on the street basically for fans of all motorbikes and the patients are not able to move feed themselves. Mentally we think they're OK inside.

This was the first of many encounters with the media. It's interesting to me how the involvement of the media the press really helped break this case. The first thing that happened was that we got a call the next morning from a public health nurse. And she said you know I saw you on TV last night. Channel 4 or something and you were talking about this Parkinson's like condition and I'm saying a young woman in her home and this young woman was in a psych unit a psychiatric unit for three weeks with a diagnosis I think of hysteria hysterical paralysis. She said you know she sounds just like what you described on TV last night. Do you think she could be another case. So did she is heroin. And the answer was yes and we said get her in. And we saw that afternoon it was our fifth case. And in some ways this was the most tragic young woman. She was her first summer using drugs. And we all know kids experiment. She got this stuff and she is probably the most affected.

This was Connie. And after Connie came still other cases like Toby. By the end of July there were a total of seven. How many other drug users out there on the California streets were at risk. Yes California had always had more than its fair share of drug problems. But in recent years police had come across a disturbing new trend toward. Drugs were turning up on a street packaged and sold as heroin that were not derived from the opium poppy nor from any other natural product. They came instead from underground laboratories here entirely synthetic versions of hard drugs were made some hundreds of times more powerful than heroin and it was all quite legal. Since the drugs molecular structure was different from any outlawed drug they could be made sold and used with impunity. They were to become known as designer drugs.

The heroin the George and the others took was not real heroin. It was a synthetic designer imitation. But what exactly was it. Langston collected samples and sent them out to chemists all over California like Stanford University's Ian Irwin. The police find the guilty chemical. All substances have unique chemical fingerprints by which they can be identified. Using a mass spectrometer to analyze the compound URWIN obtained the mystery substances fingerprint. He then fitted into a computer in Washington where the fingerprints of many known chemical substances were stored. He was looking for a match as expected. It wasn't heroin. But it didn't match with any of the forty thousand known chemicals on the computer or

the compound was apparently completely unknown. While Langston and his team puzzled over the mystery designer drugs unknown to them a local police investigation was closing in on a designer drug chemist. This man was the key to the operation. A suspicious list of chemicals fell into his possession. For the police. This was a big break because in reality he was an undercover narcotics agent better known today as Deputy Sheriff Dave Wendler 31. Dave Wyler turned the list over to the county crime lab. Would a local resident want with such large quantities of chemicals. Forensic scientist Jim Noras had to decide one thing. Was this the basis of a designer drug operation.

The key suspect was well known to them. Ever since a notorious incident in nearby Saratoga 18 months before when his residence mysteriously caught fire police and fire officials discovered he'd been experimenting on a vast scale making designer narcotics but they were powerless to arrest him. Now it seemed as if he might be at it again and all Noras could do legally was stage a fire inspection but the suspect was ready for them. The owner of the laboratory when confronted by the fire department first said that he was attempting to make hand lotion and also attempting to make a new type of snow cone. The chemicals that had been purchased were not appropriate to make snow cones or hand lotion most of them were very poisonous highly flammable and also very expensive. He had spent nearly ten thousand dollars to buy just the chemicals. Then the police started to hear about the frozen addicts who were turning up at Dr. Langston clinic at the Valley Medical Center. They wondered Could there be a connection. We knew that Dr. Langston had seized some samples from

patients who had been admitted. And we asked Valley Medical Center to give us those samples so that we might conduct further legal investigation. I got a call starting call from police different police groups and one in particular was Jim Norris a local Narcotics agency. And I remember that conversation quite well because he said that Dr. Langston we understand that you have some samples of this synthetic heroin and I said yes and he said well you know we'd really like some of that. We need some of that for analytic purposes in our lab. And I said Damn was being very nice and I said Damn. Well I'd really like to loan you some but you know we just have a very small amount left of what we think is a critical sample. So I'm afraid I can't do that. And remember there was a pause on the phone. And Jim said. Doctor you don't understand either you can give us the sample or I'm coming over there with some of my men and we're going to take a sample at that point I realized I'd better negotiate and I think we wound up splitting

it. The second thing I remember about that conversation. And to this day it amazes me is when I said Do you have any idea who this fellow is making this stuff. And his remark was almost casual I said oh yeah we know who this guy is. We know about this guy for two years. He was associated with his house and mysteriously blew up in Saratoga. And I said well why isn't he behind bars. And he said we can't touch him. And after he explained that to me that was the first time I'd heard about designer drugs these new synthetics that are altered. So then beyond the reach of the law he said our only hope is to get this guy on his income taxes. I was just floored. NORRIS couldn't identify the sample nor could pharmacologist Gary Henderson the inventor of the term designer drug for years Henderson had been warning of the terrifying potential of synthetic narcotics. Tiny design changes to a molecule like this can make it thousands of times more potent than morphine. It was not only dangerous but perfectly legal.

Now the real important thing from the legal standpoint is if you simply put another group in here for example regarding what it does to the activity under the old drug laws it was a new chemical and therefore not restricted. You can have all the properties of heroin look like it act like it taste like it produce all the effects and side effects because it is a new chemical and not listed on any drug list. It was strictly legal. As the search for the unknown substance continued the condition of the frozen addicts was deteriorating. Can you. Stand with. Your. Try here.

They were by now invalids quite unable to wash or feed themselves. So bad. Was there a condition that Langston decided to put them on the treatment given to sufferers of Parkinson's disease. Is the drug L-dopa. Nobody was sure if it would work but the effect was miraculous. They came back to life. Langston realized that he might be on to something big. What had begun as a drug tragedy might help unravel one of the world's major brain diseases affecting one person and 100 over the age of 60. You touch your fingers to your. L-dopa replaces dopamine a naturally occurring brain chemical without which we

would all freeze up. With own domain. The thought of lifting an arm can be translated into the act of lifting an arm. If enough of the cells making dopamine die people get Parkinson's disease. The characteristic tremor increasing rigidity and leading eventually to complete disablement. Langston realized that in the frozen Attucks this process was speeded up hundreds of times. Something in the synthetic heroin had passed into the brain and avoiding every other structure had destroyed just that small area of brain that makes dopamine the substantial Niagara. To understand this toxin might be to begin to understand Parkinson's disease. The next clue as to what that toxin was would come from the crime lab for one of Jim Norris's colleagues a toxicologist Hally Weingarten The idea that a

toxic chemical could cause a Parkinsonian state stirred a memory. Buried away in her files was an obscure article written in the late 70s. As the article revealed George Kirylo wasn't the first victim of a bad synthetic drug. There had been an almost identical case six years before. For William Langston. This article provided the missing clue for in this case the victim had known the formula of the drug he had taken. The article told the tragic story of Barry Kidston a 23 year old student from Bethesda Maryland with a long history of drug abuse. In the summer of 1976 he bought a chemistry set and in the basement of his parents house began making his own narcotics. After six months of doing this he hurried a batch on injecting himself his body froze. He couldn't speak. He developed the symptoms of Parkinson's disease. Barry was referred to the close by National Institute of Mental Health where after treatment with L-dopa

he was able to tell investigators just what he had tried to make. He. Wanted to get a drug related to Demerol. That was his favorite drug of abuse which he'd been able to get fairly readily when he was overseas and he wanted to avoid clandestine sources of supply. So he decided after looking through the scientific literature that this looked like an easy compound to make it should given the same facts as Demerol or a heroin like high without running up against the law. He was going to do this all in his own basement. It was certainly an ambitious undertaking certainly much more ambitious than most undergraduates would begin to do in their school laboratory. The drug Barry was trying to make was called pee pee chemically quite different from heroin it produced the same kind of high and was easier to make. Was this the toxin

that had given Barry Parkinson's disease. Marquis injected MPP into rats to see if they would come down with a disease. And lo and behold the rats froze up. For Markey and his colleagues back in 1977 it looked as if they were on the verge of an important discovery. But an hour or so later the rats started to unfreeze. The effect was temporary whereas Barry's condition was permanent. It was not Parkinsonism. This was a serious setback for the team of scientists now working on this unique case. But there were other possibilities.

I've started putting it together here and you can see from me. Using Barry's detailed notes and Barry's own equipment. Marquis tried to duplicate in his in IMH lab just what Barry had done. Mark the reason that Barry must have made a mistake. Used Too much heat or acid in this reaction. And there is a danger of making side products. Was this what Barry had done as Markey tried to forget all his scientific training and do sloppy chemistry. He got a lucky break. He noticed that trapped in the glassware buried in the grease. There was a small amount of powder the last remaining trace of berries last synthesis. Knowing the formula Berry had used this tiny amount was enough for Marki to analyze in a mass spectrometer. It showed that Barry had indeed made a sloppy synthesis in addition to the drug he was trying to make empty. He had also made a side product. MP t.p.

Could this be the toxic chemical. For some reason the researchers never tested pure T-P in rats. Then one day in September 1978 Barry came to the grounds of the NIH sat down under a tree took an overdose of cocaine and died. His parents gave permission for an autopsy and results removed any skepticism. The substantial Niagra of his brain was extensively damaged a substantial Niagara of a normal brain looks like this. Berrys was like a Parkinsonian brain. All the black pigment was missing. Thus in 1978 four years before George Kirylo took the bad heroin researchers had uncovered a clear link between a synthetic drug and a Parkinsonian state. Why then did no one hear of their discovery. The research was destined for obscurity. First the prestigious New England Journal of Medicine rejected the article on technical grounds. Then the Journal of the American Medical Association insisted that one of the seven authors drop out

as a condition of publication because no one would drop out. It was eventually placed in the first volume of a brand new journal psychiatry research published in Holland and it remained largely unread but three years later when Langston read this remarkable article he was struck by a powerful thought. Was it possible that the California designer drug maker had tried the same synthesis as Barry and made the same mistake. Langston read the formulas Barry Kidston had used over the phone to Kemas and URWIN who realized immediately that the same chemical synthesis was involved. Like Barry the California designer chemist was trying to make him pee pee pee. And like Barry he had used too much heat and made NBT as well. In fact he had done the synthesis so badly that some of the samples were almost 99 percent side product. Almost pure and GTP. Langston strongly suspected that TTP which hadn't been tested in rats was the

toxin but he wanted to know more. Because Barry Kidston had based his experiments on some long forgotten articles written in the 1940s. Langston went to Stanford University to read them for himself. But someone had been there first. All the articles had been razored out. It was really an eerie feeling because I had the sense I was crossing paths with this individual person and it was now part of our imagination. I had never seen that shot. He started turning to anger. After I went to additional journals because every single one had a relevant article. Then razorblade it at. The scientist bacot and I am age having heard about the California tragedy we're back in the game. Whereas Barry had been an isolated case. Now there was a virtual epidemic. Anxious to make up for lost time. They set about finding out what they had missed.

When Marki had previously tested in rats it produced a temporary paralysis but not Parkinsonism. Now he tried injecting pure MP to see if it would cause a permanent Parkinsonian state and kill cells in the substantia Niagara. To many people's surprise that had absolutely no effect whatsoever. To this day nobody has produced Parkinsonism in a rat. For one of Marcie's colleagues Stan burns. This came as no surprise from the onset he reasoned that rats were so physiologically different from humans that it would never work to test if he was toxic. You had to use an animal like a human. Another primate for example. A monkey. Burns was right in monkeys. The effect of the DP is dramatic. They freeze up and there Parkinsonism can be reversed with L-dopa. From Barry Kidston to the California addicts. They had all been struck down by the same

substance. A simple molecule produced by a piece of sloppy chemistry in MP pee. So here we've got a simple molecule that like a Nike missile goes right and past all the organs in the body skips all other areas of brain and Hone's right in this same area that is damaged in Parkinson's disease. This has a lot of implications. The first implication was that now scientists had an animal model for what had always been an exclusively human disease. Research could move forward for the first time in years. This was a godsend I mean it was even better than you would dream of in the sense of a chemical that gives systemically. That only destroys the group of cells that are responsible for the clinical manifestations of Parkinson's disease. I was not so much on a hunt for what was the causative agent to explain the cases in heroin abusers. I

wanted to find the chemical that would reproduce Parkinsonism in monkeys in particular because that would be a wonderful tool. Obviously you can't do a lot of experiments on humans. In fact you can be very few experiments on humans so that limits you tremendously in being able to study the disease and do basic research. In fact in many ways I think basic research in Parkinson's disease was almost dead in the water when this came alive. I mean where do you look. What do you do. In the teepee opened a whole new era in Parkinson's disease research scientists from all over the world started jumping on the bandwagon. The first thing that happened was that the price of MBP for experiment shot up. In 1982 the Oldridge chemical company sold five grams for $11. But two years later it was eight hundred and sixty times more expensive. It's now extraordinarily expensive in fact a bottle of empty T.P..

That was given to us by Auberge chemical company so we could do some toxicology studies. By our current estimate is worth two hundred and ten thousand dollars. We still have a Toshiba have it in a safe. The other kind of interesting figure that even worked out our chemist is that currently neuroscientists working with MP T.P. are paying approximately five times what addicts on the street paid to get this back in 1982. Now the secret of TTP was of good Langston keep up. He was a clinical neurologist in a county hospital with almost no basic research experience and no funding. Remarkably he found himself on the crest of a wave of interest both in the designer drug phenomenon and the search for a cure for Parkinson's disease. For years this had been a more of an research field. Now the various Parkinson's Foundation's rallied around to fund the new wave of research for patients like those in the Oregon chapter of the American Parkinson's Disease Foundation.

There was hope for the first time of real progress in meetings and in newsletters the message was one of optimism for research and this is for all is headed for basic research in this country and for patients with Parkinson's disease. That's good. Thank you. Parkinson's Disease is a disease of aging. The older one is the more likely one is to get it. Involved. In general we would say one person in a thousand of the general population. But since it's a disease that increases with age and over the age of 40 it's one in 200 and over the age of 60 is one in 100 and over a lifetime there's a chance in 40 of them developing the disease if you live to a normal expectancy.

Dr. Andre Barbeau pioneered L-dopa therapy back in the 1960s. People called it a miracle drug. It has the power to transform even an invalid like Conti's who without medication has no voluntary control over her movements. Again a little later when hopefully the medicine works. Now what I want to do is try to reach out and touch my finger. Try to make it a little easier. Try to just take this hand and just reach up and touch my hand. Can you do that with your fist. Just get your arm up there. Do your best. Try to get your right arm up there. Or you try. OK so you can't really do that right and I can say the tremors getting worse. Let's try it on the other side. Just try to hit my hand like a boxer. Can you do that. To try to hit my hand. L-dopa it gives her back what most people take for granted with voluntary control of her body. And you couldn't even do that a while ago. And actually that's quite fast. Good try with this hand. OK same thing. Tip of my finger to your nose.

That's what the miracle has a price. Several of them have to take medication every two to three hours just to be able to move some of them even get up at night and taken even that is not a guarantee that they're going to be right. Because with time you get these serious side effects. Connie was plagued with uncontrollable writhing movements a common L-dopa a side effect which leads to dramatic weight loss. David has suffered from this also at times David's had terrible problems with this and actually lost a lot of weight haven't you David. But how much weight have you lost because of them. Forty pounds they've actually been disabling at times and that's been our big enemy and trying to get him balance. It's a typical problem you see with Parkinson's disease you get side effects if you go up enough to be effective. You go down in the patient Phase. George the original case has another common L-dopa side effect.

Have you have any problem with the host nation status now you have them right now. Can you tell me what they're like. I'm keeping them. Do you get like let it be like a snakeskin to get you. Yeah that's the one you often have. That sounds very frightening as it is for the cases caused by MP TV and for millions of ordinary Parkinson's sufferers L-dopa isn't the final solution. In fact it can be a therapeutic trap. For the New World Wide research initiative. One pressing goal was to find alternative therapies that would allow people to move without debilitating side effects. Then a staggering development occurred that was to send some researchers in a completely different direction. One day Langston received the letter from a pharmaceutical chemist in New Jersey who had read about the discovery of MPP in the press. He reported that MPP was not new. He had worked with the

compound for years back in the 1970s on the laboratory bench then at 37 years old he noticed that things started to go wrong. His tennis game began to fall apart. His serve continually went into the net. He developed early signs of what he now realized might be Parkinsonism. Langston was horrified. This was shortly after all these calls and knowing all these scientists were getting and I thought what have we done. You know we've set the world off on using MP tape in labs and here this stuff can cause a disease. You know just from exposure. So I felt quite panicked that we might. Have done something that could be quite harmful so we immediately rushed a letter out in the New England Journal of Medicine. Describing this chemist and his case and really warning people that if you're using AMPTP be careful them in IMH. Stan Burns heard from a Danish chemist who had languished for nine years in a psychiatric ward with a diagnosis of catatonic schizophrenia.

When the story broke in the press the ex-wife of this chemist read one and said read the description and say that that's what happened to my ex-husband. She called the doctor involved who taking care of him and said I wonder whether he wasn't exposed to the same chemical. They went back at the pharmaceutical firm and lo and behold that's exactly what he had his hands on a few weeks before he developed it. And so it's really to the credit of the ex-wife that he was diagnosed and that case then became apparent this perfectly sane individual only worked with MPP for two or three weeks. It was turning out to be a very toxic chemical. Exposure by inhalation by skin contact and probably by any route I mean if you swallowed it if you injected any systemic exposure of the body it goes to the brain cells and it kills them off.

The very first man to encounter this toxic substance was its discoverer. The now retired author of the missing articles from the 1940s Dr Albert Ziering of Hoffman La Roche Laxton called in to see if he'd had any health problems. I'm glad to report he was in excellent health and a very bright man a very lively man and is what we are chatting about happy in his early experience with it when he made it. I remember he paused in the conversation and said. You know I vaguely remember. Getting a report back. That MP TB was toxic. And I said well how could that be. I said well normally we make these compounds and we send them off you know to the other part of the company. I then went to the head of the research division of this company and. He was helpful. It took some some pushing and eventually I was able to get him to read a report to me that was filed in 1960. And in fact NPT be back in the 50s had actually been tried out experimentally in animals.

The first report was on rats and AMPTP didn't do much in rats and we now know it doesn't do much in rats. However they then took it to primates actually gave it to a total of six monkeys. And in higher doses those monkeys froze up. They came rigid. Unable to move and died. More remarkably they then tried this out in humans six humans. And in what I consider the crowning. Irony of this story and this is a story full of ironies. This drug was being tried as a treatment for Parkinson's disease. While being given MP t.p two of the six people died. And Hoffman La Roche discontinued testing. Since the 1960s. Other drug companies have tested in animals for everything from heart disease to blood pressure. Did they realize its toxicity. Only the ones who expensively tested it in monkeys. And amazingly under FDA regulations that's not

required. I recently learned that current policy requires testing only in rats. You can theoretically take a new drug test and in her hands. And go straight to human trials. With empathetically this disastrous Parkinsonian state that it causes would have been missed completely because rats don't get it. So if just as happened back in the 50s you would have missed it completely by skipping over primates and I think there's a real message here and the message is that drugs before they're tried and humans should be tested for toxicity not only in rats. But in primates. And I think people are starting to look at this. If there's a moral it's that men are not nice. Drugs affect different animals quite differently. A dose of morphine that would kill a man would merely put a dog to sleep. In TPP which temporarily paralyzes a red gives a human a heroin

like high. On the other hand the side product. MP T-P which gives humans Parkinson's disease leaves a rat totally unaffected. If you're going to study Parkinson's disease and you're going to take out of the story an animal model you have to work in primates. And the reason you have to work in non-human primates is because it's qualitatively similar it's the same as in the patients with Parkinson's disease. So the findings with research are going to be be easily transferable to considering the human situation. When you get to lower animal species and I've used the example of dogs or canines the multi-system isn't the same and no longer the symptoms and signs qualitatively the same. The one half million Americans with ordinary Parkinson's disease have never injected or snorted synthetic drugs nor worked at a chemical batch. How did they get the disease. The because of Parkinson's disease has always been something of a mystery. So far no

virus has ever been violent. Recently a very large study was completed investigating whether it was a genetic inherited disease. Identical twins have identical genes. If Parkinson's disease was a genetic inherited condition then if one twin developed it you'd expect the other two as well. Yet in a study of affected identical twins all but one pair were like the brown sisters. One sister got the disease like Mary on the right the other with identical genes did not. If Parkinson's disease isn't genetic or caused by a virus that leaves the environment it is revealing that before James Parkinson described the disease in 1817 there are few convincing accounts of the condition that means it could be a disease of the industrially. It's known that prolonged exposure to manganese causes Parkinsonism among miners and

changes in mineral content of water and soil may explain why in certain Pacific islands like Guam the incidence was until recently five times that of the USA. Yet when you discount specific causes like these for the vast majority of cases worldwide across all cultures and races there is no obvious cause clinicians refer to it as idiopathic meaning unknown Parkinson's disease. Could that unknown be something in the environment. Probably for most people it gets a disease. It's something out there in the environment. Somewhere someplace. Now if you link this with the almost simultaneous discovery of a very simple molecule it can get in through inhalation exposure to the skin. You've got a pretty powerful hypothesis there that in fact it is environmental and that those of us that are getting exposed to something that there is a parody that's a chemical name. That parody things are all over the place. They're very

common. To the best of my knowledge no one has ever made a methodical search in the environment looking for P P R and B ATP like compounds. Out there in our everyday world. Are there toxins which can account for most cases of Parkinson's disease. It's a controversial theory that has divided the scientific establishment. Its proponents say that if true it might work like this. From cradle to grave our brain cells die off through natural causes at the rate of a few percent every decade to get Parkinson's disease a tenth of the cells in a substantial nitre must die. So aging alone can't account for the disease humans who get Parkinson's disease therefore must lose additional brain cells by some other means they might suffer a serious external environmental attack at some stage which kills off say about half of these nitrile cells then normal aging finishes the job when the 80 percent threshold is reached the disease begins.

So ageing is involved but ultimately the cause of the disease is something in the environment. I think the the environmental cause for Parkinson's Disease is one of the most exciting prospects to come about in the last few years out of the tepee research. I believe that it's going to be something very subtle because the epidemiology of Parkinson's Disease is that it's found really worldwide over many cultures and that's been well-documented. So it must be some substance which is common in in the fact that our own bodies are producing it or as a product of our our diet something that we can convert to an empty like substance something an intermediary metabolism something that we make. While people speculated about the cause of Parkinson's disease something quite unexpected

happened several of the research labs working on uncovered a bombshell. It turned out that surprisingly MPP wasn't quite the villain everyone had assumed. MBP by itself wasn't even toxic. The problem lay in the brain's complex waste disposal system where unwanted toxins are pounced upon by special enzymes and rendered harmless. At least that's what usually happens when it enters the brain. One enzyme in this system does something disastrous. It takes this harmless molecule and transforms it into a highly toxic one. NPP plus so toxic in fact that a chemical company had already synthesized it as an herbicide super clot super quad or MPP Plus was test marketed about 10 years ago as an herbicide. It's chemically related to paraquat which is a much much better known herbicide.

The California street drug that had caused Parkinson's disease was not itself toxic. It became toxic because the tepee in it was transformed in the brain into an herbicide. Herbicides and pesticides have been extensively used in North America for over 40 years. If such widely used chemicals are related in some way to Parkinson's disease the implications are to say the least alarming. Dr. Andre Barbeau in Canada decided to take one region Quebec as a test case to see if the incidence of Parkinson's disease could be linked with any toxins in the environment. Firstly to many people's surprise he found that far from being uniform. The disease varied sevenfold across nine different regions. It was highest in Region three. The main agricultural area the so-called breadbasket of Quebec. Then Barbeau plotted the use of pesticides in Quebec and the map was identical where there were pesticides there was Parkinsonism. This didn't prove pesticides were responsible.

Anything in the agricultural landscape might be to blame. The data showed another striking correlation. The 15 hotspots that had by far the highest amount of Parkinson's disease were all near pulp and paper mill. So a number of toxins may be involved. It may be the pesticides themselves. I'm not ruling that out but I'm not saying that is the cause. It may be the nature of the soil in the pulp and paper industry. There are about 30 different compounds being used. Some of it may get to the environment may be toxic. We're now sorting this out. We're working with pulp and paper industry and we're working with the Agricultural Department and the environmental department to identify in a very specific control area all the pollutants that are being used over the last 100 years and some you know one argument that is often given is that pesticides have only been around for 40 years. This is not true.

People were using what we call in French and they have the party which is our Saniya compounds for hundreds of years. Pesticides are just one possible cause in our industrial world. MP like substances are used throughout the chemical industry and are found in many foods and beverages and even in chewing gum and cigarette smoke. Dr. Barr those results have been met with a mixture of intense interest and skepticism. Scientists await further studies to confirm his dramatic findings. Analogy here is that a fishing versus hunting people have been looking for 100 years or more for the cause of Parkinson's disease. But they were fishing. They were looking at everything. They were focused. We now are hunting specifically looking for chemicals one or more chemicals in the environment that might play a role in Parkinson's disease. Dr. Barbours the data that I've presented is quite dramatic is that it results in other areas of research just as dramatic as was were coming in from labs all

over the world. A major breakthrough was made by scientists in San Francisco investigating the deadly transformation of empathy in the brain. They actually identify the guilty enzyme that caused the DP to become the lethal MPP plus. It was a very common enzyme known as a 0. If you could block this enzyme then he would remain harmless. And such a blocking drug was available largely scientist rush to try the obvious experiment. When you give amputee to an animal usually within hours they're. Parkinsonian they're slowed. Quiet don't move clearly affected. One dose of parceling which is an embryo inhibitor before MP t.p and these animals are doing handsprings an hour later it's so dramatic. Secondly when you look at their brains Where's the

natural neurons would be gone dead wiped out. They're totally normal. It completely prevents cell death. Quite dramatic. In the excitement. It emerged that a similar enzyme blocking drug called Deprenyl had been given to patients with Parkinson's disease. In Europe. It had fewer side effects and it seemed to help. Deprenyl seem to be slowing the progress of the disease. In fact in that article they actually concluded they were preventing nitrile cell death. So here we have the real disease. Now. That is being slowed apparently by MDO inhibitor therapy and we have MP T.P. Parkinsonism. These two together generated some real excitement. Is there the hope now for the first time we might be able to alter the course of disease if we could this comes none too soon because we're at a stage now where many neurologists are quite disillusioned with L-dopa other medications that stimulate dopamine receptors because of

all the side effects it just seems like you conker one and another one comes along. It's gotten to be a very challenging problem in neurology. A new therapeutic strategy. Altering the course of the disease could be very exciting particularly with Parkinson's Disease because the disease is so mild. When people first come in if you could halt it at that point you could give them an almost normal life. As Dr. Langston group the go ahead late last year for a Deprenyl trial. Scientists at the University of British Columbia in Vancouver announced a remarkable technical breakthrough. They had developed a method of detecting Parkinson's disease before there were any clinical symptoms at all. This California drug user has no clinical symptoms yet deep inside his brain there may be scars from the one dose even he took back in 1982. A mildly radioactive chemical is injected that will enter the brain and spread out along the dopamine pathways provided those pathways are undamaged. The positron emission tomography or

pet scanner is able to track the passage of this chemical by photographing dozens of brain sections from the bottom to the top of the brain. In a normal brain the top section looks like this. But in a Parkinsonian brain much less radioactive chemical gets through to this key motor area. What would such a dramatic contrast show up in this case. He may have no symptoms yet but his PET scan shows he is well on the way to getting the disease. We can say Parkinson's disease before it develops clinically. If we then have a way of halting further cell death. And we could intervene at that time we could literally start people on therapy before they ever got the disease and Parkinson's disease the way it would work in reality and the things that would be required would be that PET scan would have to be turned into a screening tool. Right now it's just a basic research tool. I'm told the technology is there

it's not practical yet but it could be done possibly. And one of these new therapeutic strategies to slow the progress the disease would have to work. But if both of those occur and maybe we're in the 21st century now I don't know yet but if both of those work then people could routinely go in at a certain age say you go in for your EKG heart tracing at age 40. You go in for your pet scan for your stride dope I mean at age 50 if it's normal gray. If it's down and you're on your way you start Deprenyl. And that's it. But have people who are too late for Deprenyl who already have the disease in an advanced form last who have already lost the cells and the substantial nitre what can be done for them. Perhaps one day even this might be curable. At Yerkes Primate Center. They've been trying to reverse Parkinsonism by surgically replacing the damaged substantial Nyro with new dopamine producing cells. These three monkeys have all got the Parkinsonism but after brain graft they

lose almost normal. It's much too early to know if it'll work in humans. But research is moving rapidly ahead on all fronts. I would say in the next five or 10 years there are guarantees of new information in our understanding of Parkinson's disease which are going to come from those studies they're almost predictable. Also the perspective how clinicians view Parkinson's disease in its treatment it's already changed. There are things now that are clearly due to the severity of the disease and not a chronic L-dopa treatment which in the past were blamed on chronic L-dopa treatment. It will change the way drugs are given it will change the way people understand the pathophysiology of the disease the functional disturbance it will alter and has altered the view about which chemical substances that is disturbed in the disease are important in terms of symptomatic treatment. If medical research has thrived so has the California design or drug business

underground labs have spawned a whole series of designer heroin's some of very high quality and as fast as one is made illegal new ones are designed. Authorities are now worried about designer versions of other drugs like cocaine. Last September 27 California passed state legislation outlawing the drug family that struck down George and another series based on the fentanyl molecule. Meanwhile in Washington federal hearings were held last summer and the mood was passionate. Try to imagine never being able to lose normally again never being able to raise your arm when you want it to never be able to walk to the dinner table your life permanently and forever changed. That's what it does. A designer drug bill now exists in draft form and may soon become law. And one of the suspect the San Jose Police had their eyes on after the final inspection. He and his colleagues fled. He is now in jail in Texas not for

making designer heroin but for manufacturing an illegal street drug PCP. A lawyer. He continues to deny his responsibility in the affair. But in a final twist of irony before his arrest he actually developed early signs of Parkinsonism and went to see Dr. Langston. The men spent two days together as doctor and patient. For the designer drug victim. There was little immediate hope. They live on a narrow ledge between being completely frozen and having terrible side effects. But for the millions of sufferers of Parkinson's disease around the world the future has never looked brighter. All because of the case of the frozen

addict. Or

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