When science goes wrong inner pages.qxd

NEUROSCIENCE: The Runner’s Brain
MORGUES ARE SPOOKY PLACES at the best of times. Evenduring the day, when knots of chattering medical students gatherround the brightly-lit dissecting tables and senior pathologists pokeat ruptured aortas or cancer-ravaged livers, they offer uncomfortablereminders of our own mortality. Not just the sight of the dead andthe disorders that killed them, but also the odour – if not the odourof death itself, then the acrid fumes of formalin, the preservative thatkeeps death’s putrefaction at bay.
At night, it’s worse. And it was night – the middle of the night – as Rebecca Folkerth stood next to a table in the morgue at the NewEngland Medical Center, Tufts University’s teaching hospital onTremont Street in downtown Boston. It was on a weekend in the latewinter of 1991. Bundled against the cold, a few late-night revellerswere still strolling the streets outside, looking for all-night Chineserestaurants or checking out the attractions of the Combat Zone,Boston’s always-open red-light district. But inside the morgue, allwas quiet, and Folkerth was alone.
Well, not quite alone. For company she had 53-year-old Max Truex, whose brain she was removing.
Folkerth was a pathologist, but not a senior one. In fact, the blonde 32-year-old had just taken her boards – the examination thatqualified her in the sub-speciality of neuropathology – a few monthsearlier. She hadn’t yet accumulated the portfolio of macabreexperiences that make pathologists such entertaining dinner guests,but this night would get her off to a good start. As she looked atTruex’s brain, she blinked, looked again, and said to herself, ‘Whatthe hell is this? This is creepy!’ Max Truex was born in Warsaw, Indiana, in 1935. His father, Russell,was a locomotive engineer with the Pennsylvania Railroad. Althoughhe drank too much, Russell was a good family man and a reliableprovider for his wife, Lucile, and their three sons, Gene, Max, and Don.
Gene was four years older than Max, so there was always a certain distance, an unquestioned division of authority andobedience, between them. With Don it was different. Don was bornonly a year-and-a-half after Max. What was worse, Max grew slowly,so already by the time he was six Don had caught up with him instature. When I visited Don in 2005 – he’s now in his late sixties, apractising dentist in Santa Barbara, California, and a running,cycling, and general fitness enthusiast – he told me that the heightissue was a major factor in their relationship. ‘It was a real sore pointfor him,’ he said. ‘When we were youngsters, it was a fight every day.
Our next-door neighbour said she thought we would never grow up,because one of us was going to kill the other.’ But it wasn’t either Max or Don who failed to grow up – it was their older brother, Gene. When he was 16, and the younger boyswere 12 and 11, the three of them were driving in the family car, withGene at the wheel. At an intersection they collided with a dumptruck, and Gene was killed.
After this tragedy, Max found himself suddenly and unexpectedly in the role of eldest son, yet with a younger brotherwho was now several inches taller than he was. What saved the twoboys from mutual destruction was sports. Gene, before his death, hadalready been running the mile in high school, and now the twoyounger boys followed his lead, taking to running and other sportswith fierce dedication and competitiveness. And in the process theybecame good friends.
Although there are exceptions, taller runners usually excel at sprinting, while smaller runners do better in endurance events. At afinal height of 5ft 5in, and a weight of 9st 3lb, Max Truex was verysimilar in stature to Ethiopians like Haile Gebrselassie, who utterlydominated world competition at 10,000 metres during the 1990s, orKenenisa Bekele, the current world record-holder at that distance.
But back in 1950, no one had set eyes on an Ethiopian runner, soMax’s modest size drew people’s attention. It encouraged them todevelop an affectionate or protective attitude toward him, as if theysaw him as a permanent child.
There were other traits that had the same effect. Although the Truexes are French in ancestry, Max had a broad, Slavic-looking facethat seemed to carry a fixed, somewhat childish smile, even when hewas running. And as he ran, he ‘skipped’ – he would frequently anderratically switch his stride, as if out of sheer playfulness. Indeed, hewas naturally good-humoured. For all these reasons, people calledhim Maxie and liked to take him under their wing. Later, whennewspapers started recording his feats, they would refer to him withpatronising titles like ‘The Little Strider.’ They described him as‘spunky’, as if his small stature was a natural handicap that only gritand determination had overcome.
In high school, Max Truex was a star athlete – he won the state cross-country championship and set a national interscholastic recordfor the mile. On account of his performances Truex was activelyrecruited by several universities, and he finally accepted a trackscholarship at the University of Southern California, where he wasdrawn by the warm climate and the school’s high ranking inathletics.
One of the people who was involved in recruiting him was USC’s assistant track coach, Jim Slosson, who became a lifelong advisor andfriend to Truex. Under Slosson’s tutelage, Truex quickly came tofocus on the long-distance events – the 5,000 and 10,000 metres –where his remarkable powers of endurance counted the most.
Success came quickly. In June of 1956, at the age of 20, Truex won the 10,000 metres at the US Olympic trials, thus guaranteeinghim a berth on the Olympic team. In October of that year, onemonth before the Games, he set his first US national record, in the5,000 metres. (He was to set four more records in that event over the following six years.) Unfortunately, he suffered a muscle injuryshortly before leaving for the Olympics, which were held inMelbourne, Australia; he competed in the 10K but did not do well.
At USC, Truex was a member of the Air Force Reserve Officers Training Corps, so in 1958, after graduating, he joined the Air Forceand served for four years as an officer at Oxnard Air Force Base inCalifornia. This base was a hotbed of athletic activity – the athleteswere given all the time they needed to train and compete. In 1959,Truex set a new US indoor record in the two-mile event. Then, in thefollowing year, he was the highest-placed American in the 10,000metres race at the US Olympic trials, again guaranteeing himself aplace on the Olympic team.
The 10K race at the Rome Olympics, in September of 1960, was probably the high point of Truex’s running career. He didn’t win – infact, he only finished sixth – but his time of 28 minutes and 50.34seconds took eight seconds off the existing US record and was aperformance which put the United States on the distance-runningmap for the first time. Just a week after the Rome Olympics, Truexiced the cake by setting a new US record in the 3,000 metres.
Truex quit competitive athletics in 1962, when he left the Air Force and entered law school at USC. He didn’t quit running,however. He ran all through his three years at law school, and he ranwhile he was working as an attorney, first in private practice inOrange County and then in the legal office of the County of LosAngeles. He lived in an apartment near Universal Studios: duringthat period he ran five, six, or seven miles daily along a footpath nextto the Hollywood Freeway. He didn’t need the spur of competition,he just loved running and the sense of fitness that went with it.
‘I told him I thought it was unhealthy to run along the freeway,’ Jim Slosson told me in a 2005 interview, and indeed it must havebeen. Los Angeles at that time had some of the worst air pollutionin the country. Truex was breathing in a truly evil brew of toxins,including carbon monoxide, particulates, ozone, and lead fromautomobiles on the freeway, as well as industrial chemicals such asthe pesticide DDT, which was being manufactured with carefreeabandon by the Montrose Chemical Corporation at its plant onNormandie Avenue. Although now banned, residues of the wind-born DDT dust can still be found in soils miles from the plant.
Even during Truex’s competitive career, there were several occasions when his running had caused him acute health problems.
He had to drop out of at least three races on account of exhaustioncaused by some combination of excessive heat and air pollution. Theworst occasion was in 1961, while he was competing in the Corridade São Silvestre, a traditional 15-kilometre race that is held everyNew Year’s Eve in São Paulo, Brazil. Although the race took place atnight, it was oppressively hot and humid. Truex was in the lead,immediately behind a phalanx of motorcycles and television trucksthat belched the combustion products of cheap South Americangasoline. He suddenly collapsed, and the next thing he knew he wasin the hospital, hooked up to an IV but losing fluids faster than theycould be pumped in. By the time he got on a plane back to theUnited States, he was fifteen pounds lighter than when he set out.
In spite of his chronic exposure to pollutants and heat stress, Truex remained in apparent good health during his earlyprofessional years. He enjoyed his work as an attorney, oftenappearing in court to argue real-estate and land-use cases on behalfof the county. And in 1973 he married.
I recently met Truex’s widow, Kay Truex De Justo, in Fresno, California, where she lives with her present husband, Michael DeJusto. She is in her late 50s, a trim-looking, well-preserved brunettewith a precise, no-nonsense style of speech that may reflect hereducational experience – she was in graduate school in English atboth USC and Massachusetts’ Brandeis University, althoughcircumstances prevented her from obtaining a doctorate at eitherinstitution.
Kay told me that at the time she met Max in the summer of 1973, she was working as a teacher in Fresno, California, the citywhere she was born, but sometimes came down to Los Angeles tovisit one of her brothers. On these visits she occasionally dated acolleague of Max’s, but it didn’t work out, and that colleague –whether out of kindness or in order to speed the end of therelationship – set up a blind date for her and Max. Although Maxwas 11 years older than she – he was 37, and she was 26 – the twohit it off right away. Within a few weeks, they went on a backpackingtrip together in the eastern Sierras, and within four months they hadmarried.
Kay loved Max’s outgoing, light-hearted approach to life and his active lifestyle. Besides backpacking, he introduced her to skiing,which took them to Heavenly Valley at Lake Tahoe, among otherlocations. Max also continued to run; soon after they married theybought a house in the Hollywood Hills, so Max was able to run inGriffith Park, a slightly healthier environment than the HollywoodFreeway.
Children were quick in coming: Gene, their eldest son (no doubt named for Max’s older brother) was conceived on their honeymoonand born in August of 1974, and their second son, John, was borntwo years later. A few months before John was born they moved to anew home in Manhattan Beach.
One evening in early 1979 when Kay was preparing dinner, she looked through the kitchen window and saw Max walking in fromthe garage as usual – but he was dragging one of his feet as hewalked. Kay didn’t think much of it; she knew that Max had injuredthat foot sometime during his running career. But it kept onhappening, and after a few weeks it became his regular style ofwalking. Then she noticed something else: when she kissed Maxgoodbye in the morning, she saw that he had failed to shave a smallpart of his face, up by one ear. Max himself noticed problems. He hadtrouble raising his arms to wash his hair in the shower, and he alsohad voice problems. On one occasion when he was on his lunchbreak, he saw an old friend across the street and tried to shout hisname but no sound came out of his throat. These symptoms alarmedhim, but he said nothing to Kay about them at the time and heminimised the significance of the symptoms that she herself hadnoticed.
A few months later, one of Max’s hands began to shake – a steady tremor that showed itself most when his arm was at rest. One ofMax’s legal colleagues noticed the tremor and recommended thatMax go see a doctor. He did so, and as a result Max was admitted toEncino Hospital. ‘They ran all manner of tests on him,’ said Kay, ‘andon Thursday of that week they told us that it was Parkinson’sdisease.’ At the time he was diagnosed, Max didn’t know much about Parkinson’s disease, but Kay was well aware that it was a progressiveand potentially fatal disorder of movement. ‘There had been a man in our church who had had it,’ she said. ‘You could just see himdiminish. I knew it was very serious.’ The central biological process that causes the symptoms of Parkinson’s disease is thought to be the death of a set of brain cellsthat produce a neurotransmitter, or signalling molecule, calleddopamine. These cells are located in a small region of the brainstemcalled the substantia nigra or ‘black substance’ – so-called becausethese cells are heavily pigmented. The cells have extensions calledaxons that run from the substantia nigra to the striatum, a structurehigher up in the brain that helps to generate body movements.
(More accurately, there are two striatums, one in the left and one inthe right hemisphere of the brain.) The tips of the axons – thesynapses – release dopamine into the striatum, and this release is vitalfor normal function.
In Parkinson’s disease, the cells of the substantia nigra gradually die over a period of years or decades, and their axons die too, so thestriatum is gradually starved of its supply of dopamine. Well overhalf of the dopamine cells have to die before the disease shows itself,however: thus, a person who experiences symptoms for the first timehas actually harboured the underlying disease process for yearswithout knowing it.
Of course, people who develop Parkinson’s disease want to know why they got the disease rather than someone else. In most cases, theanswer isn’t known. Doctors commonly describe the disorder as‘idiopathic’, meaning that it seems to develop of its own accordwithout any obvious external cause. Still, there are some clues. Inparticular, chronic exposure to pesticides, herbicides, and otherenvironmental pollutants raises the likelihood of developing thedisease. What’s more, some people have a genetic makeup thatmakes it hard for the body to break these pollutants down, and thismakes such people more likely to develop Parkinson’s disease if theyare chronically exposed to pollutants.
Truex might have been exposed to agricultural pollutants during his childhood, when he lived in a farming area, drank well water andate fish caught by his father in a polluted lake. Also, as mentionedearlier, Truex was exposed to a variety of toxic agents in his adult lifeas a result of training and racing in highly polluted air. Still, it willnever be known for sure whether these exposures were a factor in his developing Parkinson’s disease, or whether his case was truly‘idiopathic.’ The mainstay of treatment for Parkinson’s disease is the drug L- dopa. Once ingested, this drug enters the brain, where it istransformed into dopamine and thus makes up for the brain’s owndeficient supply. It is usually taken in a proprietary form calledSinemet, in which the L-dopa is combined with another drug thatprotects the body from some of L-dopa’s potentially harmful side-effects. Truex did take Sinemet, and it helped him, but it did notprevent the progression of his disease. In particular, his speech beganto be affected. He spoke too rapidly: when he was speaking in court,the court reporter would ask him to slow down, but somehow hecouldn’t. Then his voice weakened, so that it was hard to hear him inany kind of noisy environment, and he also began to slur his words.
Max’s brother Don told me that he took Max to task for ‘mumbling’– he didn’t realise that it was a symptom of his disease. ‘I said, “Max,you earn your living talking, you’ve got to talk so that you can beheard.”’ In spite of these problems, family life went on in a reasonably normal fashion. About six months after Max was diagnosed, theirdaughter, Mindy, was born. Max did as much as he could to helpwith the children. And he even kept on running. He now knew thathis disease was likely to progress, but he focused on the hope ofremaining an effective father and provider for as long as the childrenneeded him.
Unfortunately, within two years or so, his voice deteriorated to the point that he could no longer function effectively in court. Truexwanted to continue working by concentrating on office work, but thecounty thought otherwise: they retired him on a disability pension.
The pension was adequate to maintain the family’s standard ofliving, but the sudden termination of his career was a brutalexperience for an active man like Truex. He worked for a few monthsin the office of a colleague, then quit working entirely.
Gradually, the disease started to close in on him. He began to have problems driving, especially when he needed to make rapidturns of the steering wheel. He had always looked forward to beingan active role model to his children, taking them backpacking andskiing, teaching them athletics and so on, but all these things became harder and harder. His doctor frequently increased the dosage of hisdrugs or added new ones, but they never quite kept up with theadvancing disease. Max’s walking became stiff and slow, and gettingup from a chair required a great effort. He had to give up running –a terrible blow.
The Truexes thought that living in Los Angeles might be too demanding for Max, and they decided to move somewhere with aslower pace of life where he might be able to continue with activitiessuch as driving. At the urging of an old Air Force team-mate wholived in Gunnison, Colorado, they moved to that city. Both Max andKay liked Gunnison. (‘It was like being on vacation,’ says Kay.) Butthe move did nothing to slow the advance of Max’s disease. Hebegan to experience episodes of ‘freezing’, when he simply got stuckin the middle of what he was doing and couldn’t move at all. Hiswalking became unsteady to the point that he was in constant dangerof falling. The tremor in his arms worsened. And after he got intotwo car accidents in the space of two days, he had to give up drivingfor good.
Max remained under the care of his doctor in California, who juggled Max’s drugs as best he could. He was taking about 30 tabletsa day, some of them intended to treat the disease, and some tocounteract those drugs’ side-effects. As often happens with peoplewith Parkinson’s disease, it became unclear which of his drugs werehelping him and which were harming him, and so his doctor decidedto take him off all his drugs for a couple of weeks so that he couldbe ‘re-levelled’. The idea was to reintroduce the drugs one by one,while observing what effects they had. During the time that Maxwent without the drugs he stayed with Don in Santa Barbara, soDon got to see the full extent of Max’s disease in its untreated state.
‘He came unglued,’ Don told me. ‘He couldn’t do anything. Hecouldn’t even swallow.’ The re-levelling may have led to some temporary improvement, but Max soon began to go downhill again. By the mid-1980s, he washaving trouble with dressing, cutting up his food, and any other taskthat required delicate control of movement. His symptoms seemedto change from day to day. ‘If I was paralysed from the waist down,’Kay remembers him saying, ‘I would know what I could do and whatI couldn’t do, but with this I never know whether it’s going to affect my ability to walk, my ability to speak, whether I’m going to shakeor not shake, I never know which part of my body is going to go.’ Max struggled on. As his sons got to the same age as he was when he started running, so did they. Max tried to coach them, but often Kayhad to help out. Max’s friends from his college and Air Force daysrallied round. Kay recounts how one friend insisted on taking Max andhis family to Vail for a skiing vacation: ‘He said, “I don’t care how manytimes you fall, Max, I’ll pick you up.” And he did.’ Toward the end of the 1980s, when Max had been battling Parkinson’s disease for nearly a decade, things began to get rapidlyworse. As so often happens with L-dopa treatment, the drug hadbegun to lose some of its effectiveness, and even with the addition ofother drugs he was in a serious plight. Now Kay had not only to cutup his food but to lift it to his mouth, too. And his swallowing wasimpaired almost as severely as when he had been off the drugsentirely: he would choke on his food as often as he swallowed it. Maxbecame quite depressed and anxious about his future.
One person who followed this decline with great concern was his old track coach, Jim Slosson. When Slosson met Max in 1988, hewas devastated to see how this brilliant athlete had been reduced toa shuffling invalid. A little later, Slosson was having dinner with oneof his own old track buddies, a half-miler by the name of PaulIacono, and he told Iacono about Max’s illness. As it happened, Paulhad a son, Robert, who was a 36-year-old neurosurgeon with aspecial interest in Parkinson’s disease, so Paul arranged for Max tomeet him.
I visited Dr Iacono in the year 2000 at his office in Redlands, California. He was a handsome and still young-looking man withblack hair and a full, black moustache. He certainly looked to be ofItalian descent, as his name suggested. What was most memorableabout him, though, was not his appearance but his manner of speech.
He was unstoppable, and often very colourful in his choice of words.
He seemed perpetually on the brink of saying more than would bewise. An interview that I expected to last for less than an hour wenton for three hours, during which time I barely had the opportunityto get in a few questions. Various assistants and medical studentsdrifted in or drifted out during our meeting, as if to get samples oftheir boss’s oratory.
Back in 1988, Iacono was based at the University of Arizona Health Sciences Center and the Veterans AdministrationHospital, both located in Tucson. He had gone to college andmedical school at USC, and he had done further training at DukeUniversity where he had developed a special interest in theunderlying mechanism of Parkinson’s disease. ‘I was mostlygrinding on new theory,’ he told me. ‘I wrote a couple of hundredpapers when I was at the University of Arizona onneurobiological theory because I was trying to pave a new trailinto the unmarked stuff. Because the marked stuff, the dogma, isjust crap when it comes to Parkinson’s disease.’ If Iacono did write that number of papers, most of them must have remained unpublished or else they were published in minorperiodicals that are overlooked by the indexing services. But thosethat are available do attest to his iconoclastic approach to neurologyduring that period: they suggested novel causes and novel treatmentsfor a number of disorders. In a paper published in 1990, for example,he suggested that a cluster of brain cells named the locus coeruleusplayed an important role in the development of Parkinson’s disease.
The neurotransmitter used by those cells is not dopamine but arelated compound named norepinephrine (also called noradrenaline– it’s a close chemical relative of adrenaline). If true, Iacono’shypothesis would suggest treatment options quite different from thetraditional dopamine-related drugs used for the disease, such as L-dopa.
Thus, Max Truex was coming to visit a doctor with a very different mindset from the conservative neurologists who providedhis regular care. Furthermore, Iacono was not a neurologist at all, buta neurosurgeon. By that token, he might be expected to think interms of dramatic one-time solutions, rather than the painstakingmanipulation of drug dosages over months or years.
Truex’s visit was also different in the way he was treated.
Whether because he had been referred by Iacono’s father, becauseboth men had been at USC, or because Truex, like Iacono’s father,had been an outstanding runner, Iacono treated him much more as afamily friend than as a patient. He picked Truex up at the airport, forexample, and had him stay at his own home during his time inTucson.
Although Iacono may have been a radical thinker, he said that it was Truex, not himself, who pushed for radical treatment. ‘I said,“You look well-medicated, I don’t know what I can do for you,” buthe said, “No, Bob, I need something.”’ Nothing was decided on during that visit, but Truex continued to call Iacono at his home on a more or less weekly basis for about ayear. During this period, the Truexes moved to Boston so that Kaycould enter graduate school at Brandeis University – she was hopingto restart her academic career and thus bring some more money intothe family.
Truex himself seemed to be researching his treatment options during this period, because on one occasion he said to Iacono, ‘Whatabout this adrenal graft?’ This was a procedure popularised bydoctors in Mexico, who took fragments from the patient’s adrenalgland and transplanted them into the brain, near the striatum.
Adrenal gland cells produce a certain amount of dopamine, as well asother chemicals, so the thought was that they might make up for thelack of dopamine in the striatum of people with Parkinson’s disease.
It turned out that the method didn’t work – the transplanted cellsmay have survived for a while and maybe even provided some benefitduring that time, but within a few months they died, and the patientswere as bad off, or worse off, than they had been beforehand.
Nevertheless, there was a short period of enthusiasm for theprocedure right after the Mexicans published their findings in 1987,and Truex heard about it and proposed it to Iacono as a possibleremedy for himself.
Iacono knew that the adrenal transplants were not working as well as advertised, so he talked Truex out of that particular option.
But Truex still wanted something done. He kept calling and visitingIacono. After a few months of this pressure, Iacono felt that he hadto do something. So he decided that Truex should undergo aprocedure that was even more radical than an adrenal transplant – atransplant of cells from the brains of human foetuses.
Foetal tissue transplantation as a possible treatment for Parkinson’s disease had been pioneered by researchers in Sweden, ledby Anders Bjorklund. In the late 1970s, the researchers had createdan animal model of Parkinson’s disease: they treated rats with drugsthat destroyed their dopamine cells, which left the animals with a movement disorder that was somewhat analogous to Parkinson’sdisease. Then they took tissue from the substantia nigra of foetal rats– tissue that contained immature dopamine cells – and transplantedit right into the striatum of the treated animals. After a few weeks,the animals’ ability to move improved greatly; sometimes theyseemed close to normal in their behaviour. The transplanteddopamine cells had survived and matured in their new home, andthey were supplying at least some of the dopamine that the rats weremissing.
In late 1987, the Swedish group performed the same kind of transplants on two human patients with Parkinson’s disease. Thesubstantia nigra cells that they transplanted came from human foetaltissue obtained during abortions. Because the aborted foetuses wereextremely immature – just seven weeks old and an inch or so inlength – and because they were broken apart during the abortionprocedure, it took a great deal of skill for the researchers to identifyand dissect out the substantia nigra while leaving other unwantedtissues behind. But they accomplished this task successfully. Theythen drilled small holes in their patients’ skulls, passed long hollowneedles down through the cerebral cortex into the underlyingstriatum, and then pumped the foetal cells through the needles intothe striatum. The patients recovered satisfactorily from the surgery,and the researchers observed them over the following weeks andmonths to see whether the transplants had any effect.
In fact, the patients did seem to improve. Although Bjorklund’s group didn’t publicise their research immediately, word spreadthrough the neuroscience community. So Iacono heard about theSwedish experiments, and he suggested to Truex that a foetaltransplant might benefit him, too.
Truex agreed; in fact, he leapt at the idea. Kay may have been a bit more cautious, but she went along with Max’s wishes. ‘I was infavour because it was what he wanted,’ she said. And, though anobservant Catholic, she had no moral qualms about the use of foetaltissue. ‘I didn’t have a religious problem with it, because I knew thatthe tissue was going to be thrown away – it wasn’t as if people wereaborting children for this purpose.’ The next question was where and how Truex was to get the transplant. Iacono first contacted the Swedish group, hoping that they would accept Truex as a patient. They turned him down,however, because they preferred Swedish patients who they couldmonitor for long periods after the transplant. Then Iacono found outthat a group at Yale University was gearing up to perform similartransplants and was looking for volunteers. But, as it turned out, theYale group also wanted people who lived locally. A group in Englandalso turned Truex down. Iacono was stymied.
Then, in November 1988, the first American foetal transplant was performed by a team led by neuroscientist Curt Freed of the Universityof Colorado. Freed had researched the technique for years, first in rats(like the Swedes) and then in monkeys. This research was funded byfederal grants, but when he began the human work Freed had to turnto private funds because the Reagan administration, concerned aboutthe abortion issue, had banned the use of federal grants to supporttransplantations involving human foetal tissue.
For the first transplant, Freed selected a volunteer by the name of Don Nelson, a 51-year-old Denver man who had been sufferingfrom Parkinson’s disease for 19 years. As with Max Truex, Nelsonwas deteriorating fast and he was desperate to try some new therapy.
Freed obtained foetal tissue from an abortion clinic in the Denverarea, dissected out the substantia nigra and (with the collaboration ofa neurosurgeon) injected the foetal cells into the striatum on one sideof Nelson’s brain.
If the Swedes were publicity-shy almost to the point of secretiveness, Freed was the very opposite: he held a news conferenceto announce the transplant just two days after the operation, longbefore he could know whether Nelson would experience any benefitfrom the procedure. Part of the reason for his haste may have beenthat the Yale group was about to do their first transplant – it actuallytook place just a few weeks later. In the world of medical research,priority is a significant issue.
Iacono did not contact Freed to see if he would accept Truex as a volunteer. Although I don’t know the exact reason, the fact is thatFreed and Iacono didn’t get along. ‘I have no respect for Curt Freed,’Iacono told me. ‘The results he’s got have been so poor that no oneshould be continuing that work.’ And he described some of Freed’smore recent experiments, in which he did mock surgery on somepatients to establish a placebo control group, as ‘asinine and unethical.’ When I talked with Freed in 2000 – we werecollaborating on a book about Parkinson’s disease – he was equallyblunt about Iacono. He described Iacono as ‘one of the most, shall wesay, provocative neurosurgeons who has not been censured by theacademy of neurosurgery but whom everyone has said should becensured.’ Of course, this was after he learned about what happenedto Max Truex; it’s possible that he was better disposed toward Iaconoback in 1988.
In any event, Iacono said that he made great efforts to find a place where Truex could get a foetal transplant. ‘I tried all my friendsall over the world – Sweden, Britain, Japan. I tried and tried. Andeventually, after two or three years of following Max, I realised I hadto do it myself.’ Do the transplant himself? Iacono was a neurosurgeon, certainly, so he had a general expertise in brain surgery. He also had aparticular interest in Parkinson’s disease. But the handful of foetaltransplants that had been done up to that time were performed bylarge research teams at major medical centres. The teams includedbasic neuroscientists, immunologists, and neurologists as well asneurosurgeons, supported by large amounts of money from public orprivate sources. The researchers had years of practice doing thetransplants in laboratory animals before they ventured to touch ahuman being. They had studied every variable that might affect thesuccess of the procedure, such as the right age of the foetus thatwould supply the tissue, the proper technology for dissecting,handling, storing, and administering the cells, and the right kind ofdrugs to give the patients to prevent the transplanted tissue frombeing rejected. The researchers performed brain scans, usingadvanced technology, to measure dopamine function in the brains oftheir volunteers before and after the transplants. And they carriedout rigorous neurological testing of their volunteers for monthsbefore and after the transplants, so that any benefit or harm of thetransplants could be assessed. All of this was overseen by universitycommittees composed of doctors, administrators, and ethicists,whose role was to ensure that the volunteers were not exposed toundue risk, and that they were fully aware of those risks that couldnot be avoided. How was Iacono to replicate all of this, virtually byhimself, and without any funds to support the project? Iacono was based at a major medical centre – the University of Arizona Health Sciences Center in Tucson – but he would not havebeen allowed to do the transplant there, for two reasons. First, theoperation was outside his recognised area of expertise. (‘I just don’tdo stuff like that,’ was how he put it.) Second, there was a generalban on medical research using human foetal tissue at the Universityof Arizona – a state school in a very conservative state.
Iacono thought that the best way to overcome these difficulties was to do the operation overseas. He first thought of Japan, which hevisited from time to time. But his Japanese colleagues were reluctantto get involved. Then, while in Japan, he met a doctor who workedin a cancer hospital in Zhengzhou, the capital of Henan province inChina. The doctor suggested Iacono perform the transplant there:tissue from aborted foetuses was readily available, he said, andregulatory control was lax. ‘It’s no muss, no fuss in China,’ as Iaconoput it.
Travelling halfway around the world for a surgical operation is not unheard of. Plenty of people fly from faraway places to have aprocedure that is not available in their home countries. Still, whatIacono was proposing to do was very different: rather than takeTruex to an established centre of excellence where the local doctorswere experienced in the transplant procedure, he was planning totake him to what, in many people’s minds, could be considered the‘back of beyond’, and more specifically to a hospital whose staff hadabsolutely no experience in this kind of surgery. Iacono was going tohave to do almost everything himself, so if he was to succeed, heneeded to be fully prepared.
Iacono did in fact prepare himself as best he could. ‘I was learning about immunosuppression, I studied up on the embryology, I read allthe papers, and I developed my own technique – I solved millions ofproblems,’ he said. Still, he did not perform foetal-celltransplantations in animals as the other researchers had done, nordid he go and witness human foetal-cell transplant surgeries at oneof the centres that were already doing them.
One problem stood out as the most challenging. The transplantation procedure involved stereotaxic surgery – that is, theuse of a calibrated metal frame attached rigidly to the patient’s skull.
By mounting the injection needle on the frame at a specified location and angle, it could be driven into the brain a predetermineddistance and the surgeon would know that the tip was in the desiredtarget, the striatum. Iacono was familiar with the techniques ofstereotaxic surgery, but such surgery couldn’t be carried out at theZhengzhou hospital – they simply didn’t have the facilities.
Iacono thought up a fairly devious scheme to get around this difficulty. In April of 1989, he operated on Truex at the VeteransAdministration hospital in Tucson. The operation was a‘thalamotomy’ – the destruction of part of a brain region called thethalamus. This is a procedure that is sometimes done to alleviate thetremor of Parkinson’s disease, and in fact Truex’s tremor waslessened, according to Kay. But the thalamotomy wasn’t the mainreason for taking Truex into the operating room that day. Rather, itwas the ‘cover’ (as Iacono himself put it) for a second procedure thathe carried out ‘on the QT’ immediately after the first.
In the second procedure, Iacono inserted three catheters, or plastic tubes, into Truex’s brain, using the stereotaxic equipment thatwas available at the VA hospital. The tips of two of the tubes wereguided into the left and right striatum. Iacono placed the tip of thethird catheter in a ventricle – one of the large, fluid-filled cavitiesinside the brain. It was the left lateral ventricle, which is close to thestriatum on that side. This catheter was of a different design than theother two: its back end was connected to a small rubber bladder, orreservoir, that Iacono implanted under Truex’s scalp. Then he sewedup the scalp incision with all three catheters still in place. The ideawas that later, in China, he would be able to push the foetal tissuedown the tubes and he’d know that it would end up in the striatumor in the ventricle, even without stereotaxic control. The catheterswould serve as pre-targeted delivery chutes. What is more, Iaconothought that the inevitable tissue damage caused by the presence ofthe tubes would actually be beneficial to the transplant: someresearch suggested that damaged brain tissue releases chemicalscalled growth factors that encourage cell survival.
Truex recovered uneventfully from these procedures, and a couple of weeks later the two men set out for China. They flew firstfrom Tucson to Los Angeles. This was convenient for Kay, becausethe family had temporarily moved back from Boston to ManhattanBeach, where they were overseeing some work on their old property there which they planned to sell. Thus, Kay and Gene had theopportunity to come up to the airport and visit Max and Bob duringtheir layover. Max didn’t look like a typical globe-trotting tourist:besides his obvious Parkinsonian symptoms, his head was swathed inbandages to protect the locations where Iacono had drilled throughhis skull. ‘He was in pretty bad shape,’ said Kay.
At the airport, Iacono and Kay had a frank conversation. This is how Iacono recounted it to me: ‘I told Kay, “You know, I may not beable to bring him back.” And she said, “Bob, you’ve got to try …”And I said, “I may not be able to bring him back – even in a box.”She said, “Bob, please try!” So this wasn’t tiddlywinks. And I’m noTexas chainsaw murderer; I’m a very conservative neurosurgeon, bythe way.’ When I asked Kay about this, she at first denied any memory of such a conversation, but later she said, ‘I’m beginning to rememberthis ‘box’ thing. He probably did say something like that. He is verycolourful.’ The journey to Zhengzhou was a nightmare. Starting in Los Angeles, Truex and Iacono first flew to San Francisco, where theytook a China Airlines flight bound for Shanghai. But fuel suppliesran low, and the pilot had to make an emergency landing in Japan.
After a long delay they finally made it to Shanghai.
From Shanghai, they took a train for Zhengzhou. The 500-mile rail trip took 22 hours, mostly occupied by repeated hold-ups as thesteam-powered passenger train was forced to yield the track tohigher-priority freight or military trains. And there was no food.
Train travel in China was difficult at the best of times, but thesetimes were far from the best: on May 4, about 100,000 students andworkers had marched through Beijing to protest at governmentpolicies, and this unprecedented event had greatly alarmed thegovernment so the entire country was in a state of tension.
Truex had been in a bad way at the start of the trip, but by the time they arrived at Zhengzhou he was virtually immobile: he couldnot walk even a few steps. Iacono had to carry him off the train; thenhe was put on a tricycle and wheeled to a waiting car.
Neither man had ever been to mainland China before, and Iacono was unprepared for the primitive conditions that existed atthe Zhengzhou cancer hospital. There was no heat or hot water, for example, and the equipment was rudimentary. The microscopes,which were crucial for the dissection of the foetal tissue, didn’t evenhave built-in light sources. Like children’s microscopes in the West,they simply had little mirrors that you aimed at a window.
Another surprise had to do with money. According to Kay, the doctors, at the Zhengzhou hospital, or the hospital administrators,demanded a substantial fee – she thought it was in the range of$20,000 to $25,000 – to let the operation go ahead. Don said thatMax told him the fee was close to the annual operating budget forthe hospital. ‘I think they knew what they had,’ Kay commented,meaning that they had Max over a barrel. ‘Bob was a little takenaback.’ One expectation was fulfilled, however: according to Iacono, foetal tissue was readily available. ‘I’d say, “I need some things todissect, guys, because I haven’t had any practice in my country, bringme some stuff.” And it would be, “You need foetal? OK, no problem.”And a couple of hours later they’d bring me something, and I’d say,“Where did you find that?” and it was, “Oh, in the dustbin.”’ In a medical paper describing the case, Iacono said that the samples used for the actual transplantations were obtained inaccordance with US National Institute of Health guidelines, whichwould include obtaining the mother’s consent to the use of the tissuefor transplantation. Max told Don that a female gynaecologist rodethrough nearby villages on a bicycle, telling people what she waslooking for. If so, she would presumably have had the opportunity toexplain the planned use of the tissue to the women who had theabortions, and to get their agreement.
Some other research groups who were doing foetal-cell transplants, such as Curt Freed’s, made an effort to tissue-match thefoetal tissue to the recipient, at least at the relatively crude level ofthe ABO system (the system of antigens commonly known as ‘bloodgroups’, but actually present in all tissues). Iacono did not tell mewhether he did this, but it is unlikely that the Zhengzhou hospitalhad either the facilities or the expertise to carry out such an analysis.
If they didn’t, the compatibility of the foetal tissue with Truex’s owntissue would be pretty much a hit-or-miss affair. Iacono simplyassumed that the tissue would be a mismatch, and he started Truexon immunosuppressant drugs – specifically, steroids and a drug called cyclosporin. The hope was that these drugs would preventTruex’s body from rejecting the transplanted tissue, and he wouldneed to continue to take them for the rest of his life.
Having taken these preliminary steps, Iacono started the transplant procedure, which consisted of three separate operations.
On the first day, he took tissue from a foetus that he judged to be 16weeks old. It’s now known that dopamine cells from foetuses this oldsurvive poorly after transplantation – by this age, they have largely orentirely lost their ability to survive in a new host – but at the timethat may not have been so clear. At any rate, having obtained thefoetal tissue, Iacono opened Truex’s scalp and pushed fragments ofthe tissue down the implanted catheter that led to the striatum onthe right side. Then he removed the catheter and closed the scalpincision. It was a very brief operation.
A day or so later Iacono repeated the procedure, again using tissue from a 16-week-old foetus. This time he implanted thetissue in Truex’s left striatum, using a somewhat differenttechnique: he loaded the tissue into a small, spring-shaped metalcoil and pushed the entire coil down the catheter into the braintissue; then he removed the catheter, leaving the tissue and themetal coil in place.
For the final procedure, Iacono used tissue from a much younger foetus – it was 16 millimetres long, which would make it only five orsix weeks old. Strictly speaking, it was still an embryo and not yet afoetus. This age was younger than what is now considered theoptimal age for transplantation, and the tiny size of the foetal brainat that age made accurate dissection a major challenge. Anyway,Iacono dissected out the tissue he wanted, broke it up into tinyfragments, injected it into the reservoir attached to the third tube,and squeezed the reservoir to force the cells down the tube and intothe lateral ventricle. After doing so, he left the third tube andreservoir in place, because he planned to use it to take samples ofTruex’s cerebrospinal fluid at later dates.
Injecting the cells into the ventricle, rather than into the substance of the brain, was a novel and risky step. Iacono did thiswith the hope that the cells, once in the ventricle, would secretechemical ‘growth factors’ that would in turn promote the survival andgrowth of the cells he had injected into the striatum. He told me that there were animal experiments to support this hypothesis. But theventricles of the brain are linked together to form a single tortuouswaterway through which the cerebrospinal fluid circulates. Soputting cells in the lateral ventricle was rather like throwing alienwater plants into a particular pond in the Everglades: one mightexpect them to spread widely through the system, with unpredictableand possibly harmful consequences.
Iacono told me something even more remarkable about the transplants he performed on Truex. He didn’t take the foetal tissuefrom the brain region that everyone else was using – the substantianigra – even though that was the location of the dopamine cells.
‘That just shows you my contempt for the dopamine hypothesis,’ hesaid. Instead, he took tissue from a strip of the brain near themidline, running from near the front of the brain all the way back tothe medulla, where the brain narrows down to join with the spinalcord. This zone contains a diverse assortment of cells that useneurotransmitters other than dopamine. As mentioned earlier,Iacono thought that some of these other cells and chemicals playeda more central role in Parkinson’s disease than the dopamine system.
Truex came through the three procedures without any problems, and within a few days Iacono decided that it was time to go home.
But that was easier said than done. On May 20, the Chinesegovernment, in response to the increasing unrest and continueddemonstrations, declared martial law. All regular forms oftransportation were halted. ‘I had to give up all my cash and mypassport for several days,’ said Iacono, ‘and they finally dragged fourpeople kicking and screaming off a Russian turboprop [to makeroom for us]. I was at the point of tears by then. The tyres of thatplane were worn down to the Dacron. But we finally got home, andthree days later I heard that that very same plane had crashed andkilled everyone onboard.’ Kay added another detail related to her by Max: on June 4, the two men passed through Beijing’s Tiananmen Square in a pedal-powered taxi on their way to the international airport. Just hourslater, the massacre began that cost the lives of hundreds or thousands(accounts differ) of students and workers.
Truex finally rejoined his family in Manhattan Beach. He was very tired, but hopeful that the cost and exhaustion of the trip would pay off for him. And, according to Kay, he had good things to sayabout all the people who cared for him in China. In that connection,Jim Slosson added a fairly implausible detail that he supposedlylearned from either Truex or Iacono. During his hospital stay inChina, Slosson said, Truex spent his time running up and down thecorridors after the Chinese nurses. ‘The good-looking ones,’ Slossonadded, with a wink.
Before long, the family moved back to Boston. According to Iacono, Truex’s condition improved greatly over the 18 months thatfollowed the surgery. Already at six weeks his facial expressions werelivelier, and soon thereafter his speech and his gait improved. By 15months, he was able to resume normal daily activities, Iacono told me,and he even began running again in order to coach one of his sons.
Iacono described the overall improvement as ‘so dramatic.’ He did,however, offer one caveat, saying that no one had checked to see if theimmunosuppressant drugs that were used to prevent rejection of thegrafted cells might themselves have a beneficial effect on the symptomsof Parkinson’s disease. When I asked him to expand on this far-from-the-mainstream notion, Iacono clammed up. ‘I’m not going to tell youthat stuff,’ he said. ‘I have to write my own book about that.’ Iacono wasn’t alone in his belief that Truex did well after the transplant: other people who knew Truex before and after theoperation were of the same opinion. ‘There was nothing dramatic orimmediate,’ said Kay. ‘I remember, I think it was about a year aftersurgery, Bob called to see how he was doing, which he didperiodically, and I said, “You know what, I think Max is doing very,very well, because it just occurred to me that for about the last threeweeks to a month I haven’t been doing anything for him, he’s beendoing everything for himself.”’ Don Truex agreed. ‘His facial expressions were better, his speech was better,’ he said. ‘There’s no question in my mind that he wassubstantially improved.’ Jim Slosson also said that Max was betterafter the transplant.
Iacono was impressed enough with the results that he took other patients to China for similar transplants, but he performed thesurgery in a more modern hospital in Shanghai rather than inZhengzhou. He described some of these cases, including Truex’s, atseveral scientific meetings that he attended.
In the second year after the surgery, Truex visited a neurologist by the name of Raymon Durso, who is a specialist in Parkinson’s diseaseat the Veterans Administration hospital in Boston. Durso also has anacademic appointment at Boston University Medical School.
‘I think I saw him a total of three times,’ Durso told me. ‘He definitely said he was improved. However, when I went over thehistory, his doctors had, for example, added Deprenyl, and so I wasnever willing to attribute his improvement to the surgery.’ The United States’ Food and Drug Administration (FDA) approved Deprenyl for the treatment of Parkinson’s disease in thesame month that Truex received his transplants. In some patients itsignificantly alleviates the symptoms of the disease, and it can alsocause euphoria, so that a person may feel and act more upbeat evenif the physical symptoms are unchanged.
The last time Truex visited Durso was in March of 1991, a year and ten months after the trip to China. Durso says that Truexseemed quite well at that time, aside from some swelling of hisankles. Such swelling can be caused by mild kidney failure, andDurso confirmed this diagnosis by means of blood tests. Chronicmild kidney failure is a common finding in people who are treatedwith immunosuppressant drugs.
Although he seemed reasonably well to Durso, Truex evidently did not seem well to himself, because right around that same time hebegan telling Kay that he was dying. Kay didn’t take him seriously atfirst, but he was insistent. When she asked him what made him saythat, he replied, ‘I just know, I just don’t feel the same, I just know I’mdying.’ Then, over a period of ten days or so, Max began giving Kayspecific instructions concerning his death. ‘He told me about his lifeinsurance policy,’Kay says.‘He had me go into Boston and sell off somestocks that he didn’t want to cause problems afterwards, and he had mewrite down that he wanted to be cremated, and where he wanted hisashes.’He also gave Kay power of attorney for medical matters, and toldher that he did not want to be resuscitated if the question arose. Kayrealised that Max was very serious about his belief that his life wasending, even if he couldn’t verbalise the reasons.
Two weeks after the visit to Durso, on the morning of Sunday, March 24, Kay woke to find that Max was already out of bed. Shegot up and went downstairs in her nightgown, and she found Max in the living room. This is her account of what followed. ‘I askedhim if he wanted me to fix him some breakfast, but he said, “NoI’ve already had something. I’m kind of tired, I think I’m just goingto lie down on the couch for a while.” I wasn’t feeling well either,so I lay down on the other couch. The kids weren’t up yet. I wasdozing, and then I heard him moving around, and it was like hecaught himself on the arm of the couch, so I got up and I said, “Doyou need help, are you OK?” He said the strangest thing – it waslike something changed, something was going on in his head –and he said out of the clear blue, “I think I can still pee in a can.”And then he just kind of slumped. I looked up, and my son Johnhad come down the stairs and was right there. By then we were inthe doorway between our living room and our kitchen, and I saidto John, “Grab a chair quick, Dad’s going down.” So he came overand we got Max into a chair, and he kind of slumped over and itwas like he was snoring: a puff and a puff and a puff and then arush of air out of his lungs. And I said, “John, stay with Dad, I’mgoing to get dressed, I’m going to take him to the emergencyroom, I don’t know what’s happening.” And I came back down assoon as I could and said, “How is he?” John said, “Fine, Mom, he’ssleeping.” But he wasn’t sleeping.’ Kay called an ambulance, but it took 20 minutes or so to arrive.
Kay knew that Max was dead. Gene and Mindy came downstairs,and the four of them talked about what had happened. When theparamedics finally arrived and began to insert a tracheal airway, Kayremembered what Max had told her just a few days previously, andsaid, ‘He doesn’t want this.’ The paramedic said, ‘Do you havesomething legal?’ and Kay explained about her power of attorney.
Then the paramedic took out the tracheal tube and said, ‘He’s been gone for some time, it would have been much too late anyway.
I was doing it mainly for the children’ – presumably to assure themthat everything possible had been done to save their father. Theambulance crew left, after telling Kay to call a funeral home and havethem collect the body.
Even though she and the three children were in a state of extraordinary shock and grief, Kay remembered something else thatMax had told her during his final days, which was that, when hedied, she should contact Iacono because he would want Max’s brain saved for scientific study. And when Kay Truex called Iacono laterthat Sunday to let him know that Max had died, he was indeed veryeager to have Truex’s brain examined. He knew that it might bepossible to detect the presence of the transplanted cells. To show thatthese cells had survived for nearly two years after the transplantsurgery would be an important scientific finding, and it wouldprovide a partial validation for the foetal tissue treatment. There wasno reason to suspect, at that point, that the transplants had anythingto do with Truex’s death – he might easily have died from some otherunrelated condition such as a heart attack. So, after some callsbetween Iacono and Dr Durso, Kay was asked to have Max’s bodytaken to the New England Medical Center.
She did arrange for the funeral home to take him there, and Kay and the children followed the hearse in their own car. When they gotto the hospital, the staff, who had been alerted to the situation, hadMax’s body taken to the morgue, and Kay returned home. In the faceof her own and her children’s grief, she had to alert other membersof the family. She called Don, leaving it to him to break the news tohis and Max’s mother – a widow of 10 years and now the mother oftwo sons who had died suddenly and unexpectedly.
I asked Kay whether Max’s last words, ‘I think I can still pee in a can’, meant anything to her. She said that it seemed to be just arandom fragment recalled from his childhood. ‘I know that hismother had told me that she potty trained the boys by having thempee in a can,’ she said. ‘They liked the noise.’ In the regular way, brain autopsies are leisurely affairs. Within a dayor two of the person’s death, the brain is removed and placed in abucket of formaldehyde, where it sits for several days or weeks untilit has hardened sufficiently that it can be easily sliced and studied.
But this was not to be the regular way. Iacono wanted to use very sensitive chemical procedures to detect the presence of thetransplanted cells. These methods identified certain enzymespresent in those cells – enzymes that were responsible forsynthesising the particular neurotransmitters that those cellsproduced. For these procedures to work, the brain tissue had to beas fresh as possible.
Iacono said that he asked Durso to arrange for the brain to be removed that same day. Durso began making phone calls to locatesomeone who would be able to do the procedure. He tried severalneuropathologists who he knew at the Veterans Administrationhospital, but because it was a Sunday, and already late in the day, hewasn’t able to track anyone down. Then he tried to page otherneuropathologists around town, and finally, during the evening, hereached Rebecca Folkerth.
Folkerth was on the staff at the New England Medical Center, but she wasn’t on duty at the hospital that day, or even on call. ‘But Iwas one of the crazy foolish people who leave their beeper on all thetime,’ she told me. ‘I answered my page on the Sunday night and Isaid, “OK, I’ll come and do this autopsy.” It sounded like Durso washaving trouble getting anyone to help him.’ Folkerth reached the hospital around 9pm. ‘Once I got there, I got a call from Dr. Iacono,’ she says. ‘He told me the whole historyand said, “Can I ask you to take some of the tissue fresh and freezeit?” I said, “OK, fine.” It’s not the usual thing – we usually put it informalin and let it harden for a couple of weeks.’ So Folkerth donned scrubs and a face shield, identified Truex’s body, wheeled it out of the cooler, and began the procedure. First, sheplaced a block under Truex’s head, raising it a few inches to make itmore accessible. Then she took a scalpel and made a long, curvingincision in his scalp, starting behind one ear, passing over the top ofthe head, and ending behind the other ear. This separated the scalpinto front and back halves. She took hold of the front half and pulledit down over Truex’s face, and then she pulled the back half backwardand down over his neck, leaving most of his skull exposed. Then shetook a power saw and began to cut off the entire top of Truex’s skull.
Even with the power saw it was hard physical work, and it took about30 minutes. In usual circumstances, the job is often left to the diener,the technician who runs the morgue.
Having removed the skullcap, Folkerth cut the cranial nerves and the blood vessels that supply the brain, and then sliced acrossthe top of the spinal cord so that Truex’s brain was now entirelyseparated from the rest of his body. Being in its natural,unhardened state the brain was jelly-like and difficult to handle,but Folkerth placed it in a dish, took a long, broad-bladed knife, and sliced the brain as best she could into a series of slabs, eachabout a half-inch thick.
Up to now, Folkerth hadn’t noticed anything unusual about Truex’s brain. ‘But as I was cutting it,’ she told me, ‘I made thisobservation, “Gee, look at this strange stuff in the ventricles, inthe third and fourth ventricles, and in the lateral ventricles also.”I thought, “Isn’t that odd?” and I took a bunch of pictures. And Ithought, “That looks like cartilage; isn’t that weird!” Even to thenaked eye it looked like cartilage, and there were hairs – youcould see them, just eyeballing it – the gross pictures areextremely dramatic.’ By ‘gross’ pictures, she meant the pictures shetook with a regular camera, as opposed to pictures taken througha microscope. She didn’t mean that they looked gross, though infact they did.
Brains don’t usually contain cartilage or hair, of course. Nor bone or skin, which she later discovered were also present. ‘You could seethe hair shafts,’ she went on. ‘So I knew there was something verystrange about this right away. Oh, this was the most strange thing I’dever seen, and at this point it was the middle of the night. I was theonly one there, looking at this case and thinking, “What the hell isthis?” It was creepy. So here I am taking these pictures and thinkingthis is some mistake; this is a tumour – a teratoma.’ A teratoma is a tumour derived from embryonic stem cells that retain the capacity to form many or all of the body’s various tissues.
Most commonly, teratomas form in the ovary, but they can be foundin other places and in either sex. Teratomas contain a chaotic mixtureof tissues, which can include cartilage, skin, hair, bone, gut, retina,brain, glands, even teeth. It’s as if the tumour is trying to form afoetus, but without any conception of how the various tissues aresupposed to be arranged.
It looked like something similar had been happening inside Truex’s head. Lumps of glistening cartilage lined the floor of one ofthe ventricles. Part of one of the lateral ventricles was completelyfilled with a waxy, skin-like tissue. The fourth ventricle, which islocated in the brainstem near nerve centres concerned withbreathing and other vital functions, was packed full of hair and othertissues, so much so that some of the surrounding brain structureswere compressed and discoloured.
A teratoma? Folkerth knew that that was exceedingly unlikely.
Teratomas can on rare occasions occur in the brain, but if so it wouldusually be in the brain of a newborn infant or young child. A brainteratoma in a 53-year-old man would be a diagnosis of desperation.
Then Folkerth remembered the case history that Iacono hadrecounted to her – the Parkinson’s disease and the transplants. Andas she examined the brain slices further, she began to figure thingsout. In the left striatum, she found the metal coil that Iacono hadused to convey the second transplant into Truex’s brain. And she sawthe catheter that Iacono left in place after the third transplant. Thetip of the catheter was still located in the left lateral ventricle. ‘Ithought, “It can’t be a tumour; it’s the tissue they infused in there.”There was no other explanation.’ Folkerth froze some specimens of tissue for later microscopic examination, as Iacono had requested. She put other parts of thebrain in formalin. Then she reassembled Truex’s head as best shecould: She replaced the skull cap, pushed the scalp back over it, andsewed the incision roughly together. Having returned his body to amore-or-less lifelike appearance, she wheeled it back into the cooler.
The next day it was collected by the funeral home, and later it wascremated in accordance with Truex’s wishes.
This whole experience left a big impression on Folkerth, and so over the next few months she devoted a lot of her free time toanalysing the tissue samples from Truex’s brain. In the left and rightstriatum, where Iacono had deposited the tissue from the two 16-week-old foetuses, she found no surviving cells from the transplant,only scar tissue. This was consistent with findings from otherresearch groups, who have reported that tissue from foetuses this oldhas a very low chance of surviving the transplantation procedure.
Folkerth concluded that the reported improvement that Truex hadexperienced was not due to the presence of any transplanted nervecells in his brain. Either just the damage caused by the injections hada beneficial effect, which didn’t seem terribly likely, or some otherfactor, such as the new drug that Truex received, was the reason.
What about all the weird tissues in the ventricles? These presumably arose from the tissue that Iacono had dissected from thevery young, five- to six-week-old foetus and had injected into the leftlateral ventricle. Folkerth believes that Iacono mistakenly included some tissue that was not from the embryo’s brain at all – tissue fromjust outside the brain that normally would have developed into theoverlying bone, cartilage, skin, and hair. Those cells could have driftedthrough Truex’s ventricular system, found some attachment point,multiplied, and followed their own normal developmental pathway,unaware that they were now in a highly inappropriate location.
I asked Folkerth whether she thought that the blockage of the ventricular system was the cause of Truex’s death. ‘In my heart ofhearts, yes,’ she said. ‘I think that was the cause, but it wasn’t acomplete autopsy so I can’t rule out a heart attack, pulmonaryembolus, or something like that. The story that his wife told memade it sound like he had respiratory failure. I think he had gradualchanges in the brainstem [where breathing is controlled] thatcouldn’t be compensated for any longer, because we saw a lot ofchronic changes, microscopically.’ Iacono had been the initial driving force behind the autopsy, and itwould have been natural for him to participate in publishing thefindings that emerged from it. In fact, at a scientific meeting threemonths after Truex’s death, he announced that the results of theautopsy were ‘pending’. But later, Iacono seemed to lose interest inhaving the results published. And that wasn’t too surprising, perhaps,because the findings suggested not only that two of the transplantshad failed to survive, but also that the third had survived only toowell, and had quite likely caused Truex’s death.
Still, Raymon Durso and Rebecca Folkerth felt that the findings should be published, because at that time there were only one or twoautopsy studies of foetal transplant recipients, and the results inTruex’s case seemed to offer an important warning to researchers inthe field. So, after some delay, Folkerth and Durso decided to writethe paper on their own without Iacono. For the clinical details of thecase they would rely on what he had told them and what he hadreported at that scientific meeting.
After more than a year’s delay, they sent their manuscript to the New England Journal of Medicine, because that journal had alreadypublished several articles about foetal-cell transplantation forParkinson’s disease. But the manuscript was rejected. ‘That was funny,’ says Folkerth. ‘I thought this was something that wasdefinitely worthy of being in that particular journal. There seemed tobe kind of a pro-transplant point of view in the other articles theyhad published.’ What Folkerth didn’t know was that her manuscript was reviewed by Curt Freed, a major enthusiast for foetal-celltransplantation and an author of one of those ‘pro-transplant’ articlesin the NEJM. As he later told me, Freed recommended that themanuscript be rejected. The reason was a concern that, even thoughit only described what he considered a ‘therapeutic misadventure’, itcould bring the entire procedure into disrepute. (Nevertheless, Freedhas had his own setbacks with the procedure. Three years afterTruex’s death, one of Freed’s patients suffered a brain haemorrhageduring the transplant operation; he died a few weeks later.) The rejection of the manuscript caused another delay, but in 1995 Folkerth and Durso sent the manuscript to another, less prestigiousjournal, Neurology. It was accepted, and it appeared in 1996, five yearsafter the autopsy it described. Folkerth and Durso didn’t nameIacono in the body of their article. ‘I didn’t want to indict the guy, Ididn’t want to be too accusatory,’ Folkerth says. Still, they did thankboth Iacono and Kay Truex in a footnote, so anyone in the fieldwould have realised which case they were talking about.
Iacono didn’t respond to the Neurology article, or if he did his response didn’t get published. But the journal did publish a responsefrom a research team that had begun to do foetal-cell transplants atthe University of South Florida in 1993. Evidently, this team, likeCurt Freed, was worried that Folkerth’s article would throw the fieldof foetal-cell transplantation into disrepute, and they expressed theirfeelings about what Iacono had done in unusually strong language.
‘This is a case of extremely poor tissue dissection,’ they wrote. ‘Onewonders why this transplant was performed in China,’ they added,‘outside of State and Federal regulations, Institutional Review Boardoversight, and peer review scrutiny.’ ‘We should not be surprised,’they concluded, ‘that poor science leads to poor outcomes.’ Iacono never abandoned his conviction that Truex was greatly helped by his transplants, and he rejected the idea that the tissue inhis ventricular system caused his death. ‘There weren’t any signs ofincreased intracerebral pressure,’ he told me. ‘He wasn’t having urinary incontinence, he wasn’t showing signs of dementia, he wasn’tcomplaining of headaches. He was acting normally, and his wife saidhe came in and sat down and died. That just doesn’t sound like[ventricular blockage]. His death was officially signed out as a heartattack.’ (Kay says that Max’s death certificate lists only ‘Parkinson’sdisease’ and does not mention any immediate cause for his death.) A few months after Truex’s death, a memorial service for him washeld at USC; it was attended not only by family members but also bymany of Truex’s old team-mates from his college and Air Force days.
Jim Slosson was there too. As a more lasting memorial, his familyand friends endowed a college scholarship for athletes from WarsawHigh School. There is also a Max Truex Memorial interscholastictrack meet that is held in Indiana every May.
Max’s mother, Lucile, died exactly nine months after Max, on Christmas Eve of 1991. She had been in frail health, but the shockof her son’s death accelerated her own, Kay believes. Kay stayed on inBoston for a year so that Gene could graduate from high school, andthen she and the younger children moved back to Fresno, the city ofher birth. In 1993 she attended her 30th high school reunion, andthere she ran into Michael De Justo, a classmate she had been out oftouch with for decades. Within a few months they married.
During all the years since Truex’s death, neither Kay nor anyone else in the family learned what Rebecca Folkerth found in his brain– not even after her findings were published. Kay tells me that shedid have a phone conversation with Folkerth some time after herhusband’s death, but all she learned from that was that he had notsuffered a stroke. As to whatever else Folkerth said during theconversation, Kay said, ‘I could not for the life of me understandwhat she was saying to me.’ Thus it is possible that Folkerth diddescribe what she found, but did so in technical language that failedto communicate much to a layperson like Kay.
It wasn’t until the summer of 2005, when I met Kay in Fresno, that she learned about what had happened and saw Folkerth andDurso’s published report. She was of course surprised to learn thatnone of the foetal brain cells had survived, and shocked to see thephotographs of the nodules, hair, and other foetal tissues that weregrowing in the ventricular system of Truex’s brain.
Kay did take issue with one thing in the report. Folkerth and Durso, citing Kay as their source, had written in the summary oftheir report that Max had died after a ‘several-hours interval ofprogressive lethargy and breathing difficulties’ – a description thatwould be very compatible with an impairment of brainstemfunction. ‘That is completely incorrect,’ said Kay. She reiterated thatMax had not complained of tiredness until a few minutes before hisdeath, and had not shown any breathing difficulties until the verylast moments of his life. ‘I think they went back after the fact,’ shesaid, meaning that Folkerth and Durso misremembered what Kayhad told them in a manner that fit in better with their pathologicalfindings. To be fair to Folkerth and Durso, the main text of thereport does not state that Truex had breathing difficulties for hoursprior to his death, but only tiredness.
I had thought that Kay might react to what she learned with considerable hostility toward Iacono, but she didn’t – not in thecouple of hours I was with her, at least. On the contrary, she re-emphasised her belief that Iacono had acted out of good intentionsand that Max himself had urged Iacono to go ahead with theprocedure. ‘If this [report) is true, it’s very sad in a way,’ shecommented, ‘because it means that what Max set out to do to helphimself may have actually gone completely the other direction.’ Iacono stopped doing foetal transplants in 1989, after he had operated on a total of 25 to 30 patients, all of them in China. ‘Whenyou start adding up the negative aspects of foetal grafts,’ he told me,‘including the risks of immunosuppression as well as infection fromthe foetus and contamination from these other things, the risks offoetal grafts are pretty high.’ In a paper published in 1994, Iaconoargued that foetal transplantation was a less successful treatment forParkinson’s disease than another neurosurgical procedure calledpallidotomy, which involves destruction of part of a brain regioncalled the pallidum. At the time I visited Iacono he was specialisingin pallidotomy operations: he did them, as he put it, in ‘industrialnumbers’.
Some other centres, such as Curt Freed’s, continue to perform the transplants, with mixed results: about one-third of the patients havebeen greatly helped, some have seen little change in their condition,and a few have developed disabling side-effects of the procedure, such as involuntary flailing movements. In Freed’s hands, thetransplanted cells do survive, and no patients have been afflicted bythe teratoma-like growths that Max Truex experienced.
In the waiting room of Iacono’s Redlands office, I noticed a life- size portrait of a surgeon operating, with a man standing next to himguiding his scalpel. Oddly, that man was wearing neither gown normask nor gloves. It took me a moment to figure out the reason: thatman was Jesus. Iacono had become quite religious since the Truexdays, and he no longer approved of abortion or of using abortedfoetal tissue for science. ‘I went from “I don’t care what I’m doinghere with a foetal graft” to becoming a right-to-lifer,’ he said. ‘I’d seethese little guys, and after a while you realise you can tell how they’regoing to grow up and what their personality’s going to be like; youcan almost name them.’ After my meeting with him in 2000, things did not go well for Iacono. In October 2001, California’s Loma Linda UniversityMedical Center, where Iacono was doing his surgery, revoked hisprivileges, meaning that he could no longer operate there. Accordingto the California Medical Board and newspaper accounts, thehospital’s action was provoked by a laundry list of misbehaviours,starting in 1992 with an episode of ‘inappropriate language andinappropriate touching’. In 1994, Iacono allegedly used some drugsthat were not approved by the FDA. This was followed in 1998 by‘yelling and abusive behaviour toward staff ’, which earned him anofficial reprimand and six months of anger-management therapy. InMay 1999, Iacono was said to have become angry with a scrubtechnician in the operating room, and to have grabbed her hand,causing an injury. In the spring of 2000, according to the allegations,he told a nurse, within earshot of a deceased patient’s family, that shehad ‘killed’ the patient. And at some unspecified time, Iacono wasaccused of having allowed a medically unqualified nurse practitionerto drill holes through patients’ skulls.
Following the loss of his surgical privileges at Loma Linda, Iacono applied for privileges at another hospital, Desert RegionalMedical Center in Palm Springs. But, according to the CaliforniaMedical Board, Iacono falsely answered ‘no’ to a question aboutwhether he had ever had his surgical privileges suspended orrevoked. Because of this and the other alleged actions by Iacono, the Medical Board brought a formal accusation against him in 2004, andin September 2005 Iacono was ordered to surrender his medicallicence, meaning that his medical career in California was over. Twoyears later, while flying alone from Los Angeles to Mississippi, hecrashed into a mountainside in New Mexico and was killed. He was55 years old.
Why did Truex agree to participate in a project that he must haverealised was hazardous in the extreme, and which quite likely killedhim? Why did he agree to be operated on by someone who hadabsolutely no previous experience in this kind of work, in an absurdlyremote location, and without any kind of regulatory control? In part,of course, it was simply his desperate desire for relief from hisincurable and progressive illness. But also, he placed a great deal oftrust in Iacono. He was a family friend, after all. And Iacono,whatever failings he may have had, was an extraordinarily vivid andpersuasive talker. At our meeting in 2000, after lecturing me forseveral hours Iacono left the room and a medical student who hadbeen sitting in on our meeting turned to me and said, ‘You haven’tseen him at his finest. He gets very dynamic – a very charismaticfellow!’ Then Iacono popped back in and said to me, hopefully in jest, ‘My Mafia friends can track you down and cut your tongue out ifthis doesn’t work out for us.’

Source: http://www.mondaybooks.co.uk/when_science_goes_wrong/assets/When%20Science%20Goes%20Wrong%20-%20Neuroscience.pdf

Final if quest 4-5-09

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