Prion Disease
Mad Cow Home ... Best Links

Chronic wasting disease transmits to humans
Montana moves to eliminate game farm slaughter
A wonder drug that carried the seeds of death
Donor tissues: 600,000 uses a year with no CJD screening
Tissue imports pose hazards
Role of immune system in prion disease unravelled
BSE -- the epidemic continues
Europe refuses US hormone-treated beef
More tainted feed found in Belgium
French food safety agency backs ban on cow intestines

Chronic wasting disease transmits to humans

Tuesday,  May 23 2000 New York Times   SANDRA BLAKESLEE 
For further details on the Miami conference, visit the CJD Foundation
Opinion (webmaster): According to an interview conducted by the NY Times at the Miami CJD Foundation meeting, Dr. Byron Caughey at federal Rocky Mtn labs in Hamilton, Montana has shown chronic wasting disease in deer and elk has potential to cause TSE disease in humans. Prions taken from the brains of infected deer and elk are able to convert normal human prion to the protease-resistant form, a well-studied proxy for ability to transmit disease across species. The efficiency of the process is fairly low compared to human-human conversion. Caughey and coworkers have previously established that sheep scrapie has about the same efficiency as BSE in converting human.

Reportedly, M.Miller et al. of the Colorado Division of Wildlife have a paper in press in the J of Wildlife Diseases, April or July 2000 reporting that levels of detectable CWD infection have reached the staggering level of 15% of the deer in Larimer County, Colorado. A letter sent by DOW to property owners proposes to slaughter affected and unaffected animals alike by increasing permits to 60% annual kill.

While it is too late to do anything about the hundreds of thousands of hunters and others who have eaten tainted deer and elk meat, it may be possible to limit the geographic extent of the epidemic in wildlife. Back-transmission to domestic sheep and cows is another serious possibility -- here, because the prion proteins are more similar, less of a species barrier is expected compared to humans.

A veterinarian in Germany gives lethal injections to a herd with mad cow disease [Reuters]. Germany slaughters the whole herd when one of the animals is found to have had BSE. Just 6 cases of BSE have been reported.

However numerous Galloway herds have been destroyed just because they were from British ancestors. Very few British-derived cattle can still be found in Germany today. Germany examines a couple thousand cattle brains a year by histopathology but only a few dozen by immunoblotting [R. Heynkes].

Clues to Mad Cow Disease Emerge in Study of Mutant Proteins

"Now, six years after young people in Britain started dying from a human strain of mad cow disease, scientists are still struggling to understand how the disease spreads to humans, how many more will die from it and if a similar epidemic could start in the United States spread by infected deer and elk.

While there are no firm answers, clues are being discovered on an almost weekly basis as scientists explore the nature of a mysterious infectious agent called the prion. Unlike disease-causing viruses or bacteria, prions are normal proteins found throughout the body tissues of humans and other animals. But for reasons that are not at all understood, normal prions sometimes transform themselves into tiny particles that cannot be killed with boiling water, chemical disinfectants or strong radiation.

These prions, almost impossible to destroy, accumulate in the brains of infected animals and people, destroying cells and leaving spongy holes in the tissue. The most common human form of this malady, called sporadic Creutzfeldt-Jakob disease or C.J.D., seems to arise spontaneously in the brains of about one per one million people. An estimated 300 Americans, mostly over age 50, die from it each year.

But a new variant of C.J.D. now is killing young Britons who acquired the disease from eating cattle infected with abnormal prions of their own. The cattle malady, called bovine spongiform encephalopathy or mad cow disease, has infected hundreds of thousands of animals since the mid-1980's.

Two weeks ago many of the world's leading prion researchers went to Miami to meet with the families of American victims of sporadic C.J.D. and to tell them everything that was known about prion diseases.

"It was a unique medical conference," said Cecile Sardo, secretary of the Creutzfeldt-Jakob Disease Foundation in Miami, which organized the meeting, held May 7 and 8. "When scientists get together they talk technically," she said. "They rarely talk in person to families."

Of the 125 people attending, half were family members and half were medical professionals. Dr. Stephen DeArmond, a pathologist at the University of California School of Medicine at San Francisco, explained that the normal prion protein was folded in a loopy pattern resembling corkscrews. But when it misfolds and acquires ribbon-like sheets, the prion becomes deadly. When a misfolded prion comes into contact with a healthy prion, he said, it can sometimes force the normal prion to change shape. The process continues, like a nuclear chain reaction, until the brain is destroyed.

It was recently proved beyond doubt that new variant C.J.D. was a human form of mad cow disease, said Dr. Robert Will, a neurologist and director of Britain's National C.J.D. Surveillance Unit in Edinburgh. This new disease could eventually kill tens of thousands of people in Britain or, given the many uncertainties about prion diseases and long incubation periods, it may eventually die out, he said.

Thus far 56 people in Britain, 2 in France and 1 from Ireland have died of new variant C.J.D. British health officials recently found a method that might assess the scope of the epidemic, Dr. Will said. Unlike the mis folded prions in sporadic C.J.D., which are found exclusively in brain tissue, new variant prions are found in the brain, tonsils, appendix, spleen and lymph nodes. Pathologists are examining 18,000 specimens from tonsil removed in the last two decades; 3,000 tonsils have been tested but the results have not been made public, Dr. Will said.

One of the biggest mysteries is why the new variant form of the disease attacks young people, Dr. Will said. The British victims were 13 to 53 years old, whereas sporadic C.J.D. affects much older people. Dr. Will said that one possible explanation was the widespread use of "mechanically extracted meat." After meat is removed from the carcass, he said, it is compressed with a machine not unlike an automobile crusher used in wrecking yards. Bone comes out one end and a meat-like goo at the other end.

This "meat" was once widely used in baby food and institutional school meals, Dr. Will said. It was fed to children all over the country, but the link between eating the food and getting the disease has not been proved.

No cases of new variant C.J.D. have been found in the United States, said Dr. Lawrence Schonberger of the Centers for Disease Control and Prevention. There have been a few instances of deaths of younger Americans from C.J.D., but tests of their brain tissue showed that they had sporadic forms of the disease, he said.

But according to Dr. Michael Hansen, a researcher at Consumers Union in Yonkers, deer and elk in several western states are experiencing a growing epidemic of a prion disease called chronic wasting disease.

In Larimer County, Colo., 15 percent of deer are infected, Dr. Hansen said. Some experts fear that many hunters and their families have almost certainly been exposed to the misfolded proteins from eating infected deer and elk meat, Dr. Hansen said. But it is not known if the deer version of the disease has been transmitted to humans.

Such transmission is possible, said Dr. Byron Caughey, a senior investigator at the Laboratory of Persistent Viral Diseases of the Rocky Mountain Laboratories in Hamilton, Mont. Results of experiments, to be published soon, show that the misfolded deer prion can, in a test tube, convert normal human, sheep and cattle prions into deadly prions. The rates are very low, he said, but conversions can occur.

At the end of the meeting, family members told researchers horror stories about how their loved ones had been told, wrongly, that they had Alzheimer's disease or got no satisfactory diagnoses at all. Many said that local pathologists, fearing prions, would not carry out brain biopsies and that some morticians had refused to embalm the bodies of C.J.D. victims.

Families are confused and angry, said Mel Steiger, an engineer from Salt Lake City, whose wife died of sporadic C.J.D. They want to know if there is an environmental factor, and, he said, they worry that officials in the United States are not doing enough to monitor the situation."

Montana moves to eliminate game farms

20 May 00 Stan Frasier  
Montanans Against the Domestication and Commercialization of Wildlife MADCOW
"Game farming commercializes the last remnants of the great wild commons, it seeks to privatize what is held in trust by all of us, it domesticates the wildness we sought to preserve, and it trivializes what is exceptional...The things we value die inside the woven wire of game farms." Jim Posewitz, Orion-the-Hunter's Institute.

The June 2000 issue of The Atlantic Monthly will carry an article called "The Money Game," by Hamilton writer Hal Herring about game farming and captive shooting. In the article, Hal quotes a California man named Mike Ferrari who paid to shoot an elk on the Big Velvet Elk Ranch in Darby, Montana.

". . . I'm sitting here right now looking at that animal on my wall, and it just doesn't mean very much to me," Ferrari says. Ferrari also tells of game ranch hunts in Texas called a Texas Grand Slam, "where you shoot all the species of sheep, and some of these animals, you have to honk the horn on the truck to make them get out of the way." Ferrari no longer shoots game farm animals.

The group is currently collecting signatures to get a game farm reform initiative on the Montana state ballot. It will stop captive shooting and stop licensing of any new game farms. They need to collect 20,000 signatures by June 23 to qualify for the Nov election. Donations can be sent to:

MADCOW
PO Box 5841
Helena, MT  59604

Game Farm Reform Petition Resubmitted, Approved; Sportsmen Group is again Gathering Signatures

May 18, 2000.  Contacts:
 Gary Holmquist, (406) 273-7862 Stan Frasier (406) 443-3424
 Stan Rauch (406) 642-6639} Dave Stalling (406) 721-8258 
 John Kober (406) 458-0227
HELENA---Despite recent attempts by the game farm industry to undermine its citizen initiative, Sportsmen for I-143, spearheaded by Montanan¹s Against the Commercialization and Privatization of Wildlife (MADCOW) is once again gathering signatures to place a game farm reform initiative on the November ballot.

"Our goal is to reform the game farming industry and protect our public wildlife and hunting heritage," said MADCOW President Gary Holmquist. "We want to keep the wild in wildlife, and keep the hunt in hunting by prohibiting new licenses and ending the captive shooting of penned animals in Montana."

MADCOW had begun to gather signatures last week, but its effort were temporarily derailed when the special legislative session passed Senate Bill 7, signed into law by Gov. Marc Racicot, placing a temporary moratorium on new game farm licenses until a test is developed to detect Chronic Wasting Disease (CWD) in live deer and elk. Since the new law amends the state statutes that MADCOW hopes to change through its initiative, the validity of the initiative was in question. Although game farmers claim the new law prevents the spread of CWD, MADCOW President Gary Holmquist said the law does nothing to stop the occurrence and spread of the deadly disease, since it does not prohibit the movement of game farm animals in and out of the state, which is how disease spreads, nor does it require double fencing on game farms to keep wild elk and deer from making contact with potentially diseased, domestic animals.

"The new law was pushed through the legislature for one reason--to derail our efforts," Holmquist said. "Although game farmers deny it, their true intent was made quite clear in a May 8 letter that game farm attorney Mark Taylor sent to the Attorney General¹s office, stating that SB 7, if signed into law, would make our petition invalid--although he discounted such intentions in front of two legislative committees. This new law is a legislative smokescreen for the industry that fails to address the real threats of game farming. It merely shows the need for the people of Montana to step up and take measure to protect our public wildlife by supporting I-143. "

Last Friday, MADCOW reworded its petition in accordance with the new law and resubmitted it for state approval. The new petition met state approval on Monday, and MADCOW has forged ahead with signature gathering. A total of 19,862 signatures from five percent of voters in at least 34 legislative districts is needed by June 23 to place Initiative I-143 before voters next fall.

"With the backing of the Montana Bowhunters Association, The Montana Wildlife Federation, the Montana Chapter of the Wildlife Society and other sportsmen, conservation and wildlife groups throughout the state, we¹ve got the network in place to quickly gather signatures and place this initiative before the citizens of Montana for a vote," Holmquist said. "A recent survey conducted by Montana Conservation Voters reveals that more than 70 percent of Montanans believe game farms should be banned or more tightly regulated---this initiative provides Montanans a voice and opportunity to protect our public wildlife."

If passed, I-143, also known as the Game Farm Reform Initiative, would prohibit the issuance of any new game farm licenses, prohibit the shooting for profit of captive big game animals such as deer, elk, mountain goats or antelope, and prevent the transfer or sale of existing game farm licenses. The initiative would not affect the licensing of existing game farms.

According to Holmquist, the initiative is needed to protect Montana¹s public wildlife and fair-chase hunting heritage. "Deadly diseases such as chronic wasting disease, tuberculosis and cryptosporidium increasingly emanating from these so-called alternative livestock operations are only part of the driving force behind this initiative," he said. "Other serious, well-documented threats of this industry to our wildlife and hunting heritage include loss of habitat, escape and hybridization, the privatization of wildlife, the creation and expansion of commercial markets for the parts of vulnerable wildlife and the bankrupt image of hunting portrayed by the captive shooting operations. Game farming erodes our hard-earned, long-standing American principles of wildlife management based on the public ownership of wildlife, a ban on commercial markets for vulnerable wildlife, allocation of hunting by law with equal opportunity for all citizens, and a ban on the frivolous killing of wildlife."

MADCOW¹s concerns that the unethical shooting of penned, domestic animals creates a negative perception of hunting and fuels the fires of the anti-hunting movement is shared by the Montana Bowhunters¹ Association (MBA), which recently pledged its backing of the initiative. "A long-standing major concern of our membership is the game farm industry¹s practice of shooting penned game farm animals under the guise of hunting, which is completely contrary to Montana¹s treasured and honored hunting heritage," said MBA President Mark Baker. ŒOur desire is for the game farm reform initiative to be on the November ballot so all of the voting citizens of Montana will finally have their say on the game farm issue."

Holmquist said if people are interested in signing a petition or helping to gather signatures they can contact him at (406) 273-7862. Or, they can learn more and print out a copy of the petition from the group¹s website at: www.macow.org.

"Game farming is far too serious a threat to the future of Montana¹s wildlife for us, as citizens, not to make a citizen effort to control the problem before it gets beyond control," Holmquist said. "The Montana Department of Fish, Wildlife and Parks has already spent more than a million of sportsmen-generated dollars to license, monitor, test for and eradicate disease, and otherwise protect our public wildlife from this highly-subsidized industry. It¹s time to reform game farming and protect the public wildlife and ethical, fair chase hunting we Montanans cherish."

A wonder drug that carried the seeds of death

21 May 00 LA Times by Emily Green 
Comment (webmaster): Approximately 8100 people received the hormone described below (some batches of which were contaminated with CJD) but only 6000 people were ever notified by the govenment. Due to this article, over 100 of the remaining 2100 affected people have requested further information.

People who have not been contacted by the CDC and wish to be found should contact Lawrence Shoenberger at 404-639-3091.

If they want to speak with other people exposed growth hormones in an advisory group, contact Mr. Tam Fry at the Child Growth Foundation, UK telephone....011-44-208-995-0257 no later than 1:00 p.m.Eastern time.
To contact the federal institute with responsibility for the program, the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health. Contact person:

Jane Demouy
tel 301-496-3583
NIH  31 Center Drive MSC2560  
Bethesda, Maryland  20892-2560.

Growth hormone used since the mid-1980's is synthetic and cannot be contaminated with CJD though it may carry other risks. The Endocrine Society has further information.

"In 1958, an American scientist managed to do what nature had failed to. He made a dwarf grow. For the first time, man had harnessed human growth hormone. By 1963, while technically still an experimental drug, the hormone was being supplied free of charge by the National Institutes of Health to pediatricians across America. For the next 22 years, the drug was administered to more than 8,000 stunted children.

It worked. The children grew--collectively, more than a mile. They went on to become soldiers, doctors, journalists and secretaries. They married and had children. But then, decades after taking the hormone, a small but steady succession of recipients began to develop strange symptoms.

First they lost their balance. In the case of a 32-year-old foot surgeon from Brooklyn, N.Y., Dr. Stacey Crair, she suddenly started toppling over. As a child, Crair had received growth hormone treatment for 12 years. Nearby on Long Island, a water safety engineer named Mike Nofi remembers that his 30-year-old wife, Wendy, suddenly started feeling like "she was on a boat." She had received growth hormone for six years.

Soon they began to stagger and drool. Their personalities changed. Within months they were in comas. Their brains were turning to sponge. They had Creutzfeldt-Jakob disease, or CJD, a human variant of the so-called mad cow disease. CJD is incurable. The agent that causes it is unknown. How they got it, however, was clear. They had been infected by contaminated hormone. Twenty other hormone recipients in the United States have also died from CJD, and the toll continues to rise.

But the NIH has not apologized, or even helped with the care of victims. Having investigated the debacle, the NIH has insisted for the last 15 years that the deaths were unforeseeable.

"It was an experimental treatment, and people signed informed consents," NIH spokeswoman Jane Demouy said recently.

[This is a contemptible lie -- the NIH knows full well that families were not informed about the risk of CJD transmission, even though NIH knew this was a risk. This is the complete opposite of informed consent. -- webmaster]

However, The Times has unearthed British court documents showing that the deaths were not only foreseeable, they were foreseen. The NIH lab called in to investigate the deaths in 1985 had been warned of the danger of contamination seven years earlier.

Moreover, a body of research shows that a safer method for processing the drug had been available from the inception of the program. But scientists under contract to the NIH chose a cheaper, less labor-intensive method.

Shown the documents, Demouy said the NIH involvement was limited to funding the program. [NIH invariably oversees programs that it funds. -- webmaster]

"Physicians around the country administered the hormone. Decisions regarding the program were made more than 35 years ago, and the people involved are deceased or retired. In 1985, when it was learned that three patients who had received human growth hormone had contracted CJD, distribution of human growth hormone [from cadavers] was ended."

Today human growth hormone is synthetic, and safe. So it is easy to forget how crude its early forms were--or that it was an important medicine. A sign of how fast its development has been is that, at the turn of the 20th century, the word "hormone" did not even exist. Endocrinology--the study of the network of glands that produce hormones responsible for growth, sexual maturation, reproduction and digestion--was a new science.

Early research was brutal but effective. Experimenting on animals, mainly dogs, scientists in Europe and North America deduced what endocrine glands did by surgically removing the organs and seeing what happened. Usually the dogs died.

In 1921, a University of Toronto team found not only that removal of a dog's pancreas caused diabetes but also that injecting the dog with pancreatic extract appeared to cure the disease. The extract contained the lifesaving hormone insulin. Within a year, insulin from the pancreases of cows was being injected into diabetic children. The first American recipient went on to live to the age of 74 and came to describe the hormone as "unspeakably wonderful." [Today, people who injected British insulin during the BSE crisis are not allowed to donate blood in the US, for fear of nvCJD transmission. -- webmaster]

Plundering the pituitary gland proved a good deal trickier. Located behind the bridge of the nose, the bean-size organ was difficult to remove without killing the test animal. By the 1950s, however, not only had scientists managed this, but it had also become clear that the pituitary was home to a complex cache of hormones governing growth, maturation and reproduction.

The first pituitary hormone to receive the insulin-style extraction treatment was human growth hormone. But unlike insulin from cattle, bovine growth hormone had no effect on people. Scientists needed human pituitary glands to make people grow. They would have to look to morgues.

In 1958, a Boston-based researcher named Maurice Raben at the Tufts University School of Medicine produced another first. A 17-year-old boy, whom Raben had experimentally injected with human growth hormone, grew 2.1 inches in 10 months.

For parents of stunted children, this offered precious hope: Their children might be spared lives as dwarfs. But then they were asked to wait. Dwarfism wasn't diabetes. It wasn't life-threatening. Unlike insulin, human growth hormone was not seen by drug companies as commercially viable.

Almost immediately, the most enterprising parents enrolled their children in small trials, very like the first Raben experiment. Even then there were not enough pituitaries for steady production of the growth hormone. Some parents turned organ scavengers, personally petitioning hospitals and morgues for pituitary glands from cadavers.

By 1963, pressure from parents, pediatricians and endocrinologists had become so intense that the NIH stepped in. It formed the National Pituitary Agency out of Baltimore's Johns Hopkins University. The agency would organize collection and redistribution of the glands to three universities for processing into growth hormone: Emory in Atlanta, Tufts in Boston and Cornell in Ithaca, N.Y.

Soon, the NIH was guardian of a sweeping experimental drug trial. For 22 years, from 1963 to 1985, it supplied the hormone to 8,157 children nationwide and to about 50 foreign-born children who came to America for treatment.

For the first 14 of these years, the largest seat of hormone production was at Emory, supervised by Alfred E. Wilhelmi. A former Rhodes scholar, he was at the peak of a charmed career. He had received a doctorate from Oxford University in England and taught at Yale before moving to Emory. Soon to become president of the Endocrine Society, he was the NIH expert of choice.

But more advanced work was going on in Sweden, at the University of Uppsala, where chemists had observed problems with the human growth hormone being extracted using Wilhelmi's method; it caused immune responses and was far from pure. The Swedes, by contrast, had developed a method to produce hormone that was 95% pure. It did not spark immune response and appeared to be more potent in inducing growth. The difference was part effort--the Swedes took a much more labor-intensive approach to gland collection and storage--and part technology--they filtered their drug using a process called Sephadex gel filtration.

Wilhelmi chose not to use the filter. "Wilhelmi's philosophy was that the material was human protein, and human protein cannot harm human beings," said Albert Parlow, a Harvard-educated biochemist who was at Emory at the time.

The result was that the NIH supplied thousands of American children with a drug that could have been pure, but wasn't. In 1969, Wilhelmi unveiled what he described as an "improved method" for hormone extraction. But the improvement was in yield, not purity. The resulting hormone was, Wilhelmi wrote in the Journal for Clinical Endocrinology, "clinically useful and . . . may be purified further for chemical use and immunochemical studies."

Put more simply, this meant that Wilhelmi regarded the hormone as safe for children but in need of further refinement for use in experiments.

Another believer in the acceptability of clinical grade hormone was Anne Stockell Hartree, an American-born biochemist then on staff at Cambridge University in England. She co-wrote the 1969 Wilhelmi paper announcing the "improved" hormone and was using the method to process the hormone being employed in an almost identical program in Britain.

By 1973, both Wilhelmi and Hartree were facing questions. A member of the British hormone program's steering committee raised concerns about the safety of the drug. Wilhelmi replied: "We have been preparing hGH since 1958 in increasing quantities, and in all that time there has never been a complaint of that kind of contamination. . . . We are presently going to modify our procedure to include a step of filtration on Sephadex G-100, and this, I think, will provide further assurance of removing virus from the system."

The Times could find no record that Wilhelmi or Hartree ever used the Swedish-style Sephadex filtering.

The method wasn't officially adopted until after Wilhelmi's retirement in 1977. That year, the NIH put hormone production out to bid. The winner was Parlow, by then a research professor of obstetrics and gynecology at the UCLA School of Medicine. Written into his proposal was strict incorporation of Swedish-style protocols. The same year, British purification was moved from Hartree's lab to one that also began filtering the drug.

Even so, for the next seven years, Wilhelmi's confidence in his method seemed justified. As he had once observed to those questioning his methods, nobody seemed to "have caught anything."

But in March 1984, in the English cathedral town of Winchester, that changed. What began as an off day for a 22-year-old woman quickly escalated into an international public health crisis. Alison Lay, a secretary at a local Barclay's bank, noticed that her balance was unsteady. "She progressed from not being able to go to work," recalls her mother, Mavis Lay, "to not being able to feed herself and not being able to walk without help." On Feb. 12, 1985, eight days short of her 23rd birthday, Alison Lay died from CJD. When she was 2, surgery to remove a brain tumor had also taken out her pituitary gland. To compensate, between the ages of 10 and 14, she had received more than 550 injections of human growth hormone.

Unbeknown to the Lays, CJD cases were also being recognized in young people in the U.S.: a 22-year-old in Buffalo, a 34-year-old in Dallas, a 21-year-old in San Francisco. All had received human growth hormone.

CJD is among the rarest of diseases, striking about one in a million people per year. It is rarer yet in the young. Of more than 3,000 cases recorded in international literature, before 1985 only nine were in patients younger than 30. The typical age was between 55 and 65. But when autopsy results from the first four hormone recipients came in, the average age was 25.

Alarms blared. After an urgent meeting on April 20, 1985, the NIH suspended the National Pituitary Program. The anguished reaction of University of Virginia pediatrician Robert Blizzard was typical. He wrote British colleagues: "Just an hour ago I left a meeting at NIH and I am very depressed. . . . I realize full well the implications of this worldwide--both for investigators and for patients. The implications are tragic."

By June, programs had been stopped in Belgium, Finland, Greece, the Netherlands, Sweden, Britain and Australia. An estimated 27,000 children worldwide had been given the drug. In the U.S., the Centers for Disease Control and Prevention in Atlanta was brought in to track down the 8,157 American recipients.

Meanwhile, the NIH switched hats from overseer of the program to its own accident investigator. Sponsor of the hormone program had been the National Institute of Diabetes and Digestive and Kidney Diseases. Assessing the disaster fell to a sister institute, the National Institute of Neurological and Communicative Disorders.

A pediatrician there, Dr. Daniel Carleton Gajdusek, had received the Nobel Prize for physiology or medicine in 1976 for his work on CJD. In 1968, he had published in Science magazine an article showing that CJD was transmissible through exposure to infected brain tissue.

However, the man who would lead the institute's investigation was Gajdusek's colleague, Dr. Paul Brown, then establishing himself as a world-class epidemiologist on the spread of CJD. When the first CJD case appeared in a growth hormone recipient, Brown thought it was a coincidence. Then, as other cases rolled in, he became convinced that the hormone was the culprit. He began systematically testing remaining stocks of the drug. "One of the lots that was inoculated did in fact transmit disease to an animal," he told The Times.

It took Brown six years to publish an estimate of how many glands infected with CJD might have entered the system. By 1991, the official estimate was 140. As shocking as this seems in retrospect, Brown takes pains to stress that, at the time, too little was known about CJD. "Before 1985, nobody had any idea it [the hormones] would be contaminated," he said.

That is where American knowledge stood for the next 15 years. It was regrettable, but unavoidable. Nobody could have known. Except, it emerges, someone did. In reviewing the documents generated during the 1996 British human growth hormone trial, The Times found a paper trail between the British government and the NIH. Its existence had remained unknown in America and its significance unrecognized in Britain.

The man who raised the alarm was not a Nobel laureate, not a neurologist, but a specialist in an obscure disease of sheep: veterinary geneticist Alan Dickinson, founder of the Neuropathogenesis Unit at the University of Edinburgh in Scotland. Dickinson specialized in the sheep form of CJD, called scrapie. In decades of experimentally infecting mice with scrapie, he had observed that the pituitary glands became both infected and infectious.

On Oct. 5, 1976, nine years before the first cases of CJD appeared, Dickinson called to warn the British Medical Research Council of the danger posed by its growth hormone program. "My intrusion came after the sudden realization that they were using human pituitaries," he said.

But it was only four months later, after Gajdusek reported that CJD could be spread by surgical instruments, that curiosity among the British officials was roused. Even so, a member of the British pituitary program took more than a year to write Gajdusek, seeking his opinion about Dickinson's warning. By then Gajdusek was traveling abroad. [They might have telephoned. The head of Gajdusek's NIH lab, Dr. CJ Gibbs, was not travelling and readily available. -- webmaster]

On May 8, 1978, a visiting Australian pathologist named Colin Masters answered on his behalf. Masters echoed Dickinson's warning: "It would be reasonable to expect that the pituitary gland and/or surrounding tissue taken from a case of CJD disease would be contaminated with the virus."

At Masters' invitation, the British then forwarded the purification protocols to the NIH for review. But there is no record that Masters ever made good on his offer to evaluate either the Swedish or Wilhelmi methods for their ability to remove CJD contamination. And in spite of the now-acknowledged danger, neither the British nor the Americans moved to exclude the use of glands from organ donors who had died of CJD. Nor did Masters warn the NIH's National Pituitary Program.

Masters subsequently returned to Australia, where he is now head of the Australian National CJD Surveillance Unit at Melbourne University. Asked why he did not relay the warning, he responded, "Presumably the people who were running the pituitary programs should have been aware of the warnings that were being sounded in the medical press."

Both Brown and Masters were in Gajdusek's lab at the NIH. But, while Brown insists that the danger of CJD contamination was unforeseeable before 1985, to the mind of Masters, it was too obvious to mention.

By 1979, the British were worried enough to give Dickinson money to test the Swedish protocol for its ability to eliminate CJD. Pituitaries were deliberately infected, then purified and injected into test mice. The Wilhelmi-Hartree method, however, was not tested. In 1982, Dickinson had his answer: The Swedish method appeared to be safe. [This is typical of CJD research then and now: no one wanted a scandal from the Wilhelmi-Hartree method failing to remove infectivity and so the study wasn't done. Someone would have to face the patients. -- webmaster]

The results were not published for three years. Both Dickinson and the British hormone program sponsors were sensitive to the potential for a scare. But in the wake of Alison Lay's death in 1985, the results showing the Swedish method's safety were seen to have a calming effect. They were published in the same issue of the Lancet as her case history. [In other words, the report on the death was held back until a reassuring study could be co-published, a study that deliberately avoided the issue of Wilhelmi-Hartree infectivity. -- webmaster]

The drug appeared safe for children, including 4,000 Americans, who had received the drug after 1977, the year Parlow took over production and insisted on the filtration. The other roughly 4,000 American children treated before 1977 with hormone from Emory, Tufts and Cornell no longer needed Dickinson to test the drug on mice. They were the mice, and it was official: The drug was potentially deadly.

After the Lancet report, in September 1985, Brown reported on the three American deaths in the New England Journal of Medicine. America faced, Brown wrote, the "ominous possibility of a burgeoning epidemic" of CJD.

Public displays of concern about a potential epidemic of CJD were one thing. Doing something to help the victims proved to be another. When Wendy Nofi first descended into madness between July and November 1995, her husband, Mike, sought assistance from the NIH. "I was in contact with the NIH when she first got sick," he said. "I told them I wanted to keep apprised. I haven't received one thing."

The Crairs say they too were rebuffed. "We called the NIH to seek help, but we received no counseling, no support whatsoever," said Stacey's sister, Lisa Crair. "At first we couldn't even get a doctor who would take Stacey on."

By 1996, Gajdusek's lab was in turmoil. In March, as the laureate addressed a scientific meeting in Europe, the mad cow crisis erupted in the Britain. The next month, Gajdusek was arrested in Maryland on charges of child molestation. Found guilty in April 1997, he served a year of an 18-month sentence and then left for France.

Mike Nofi had his wife placed on a feeding tube in a rest home. It took her 2 1/2 years to die. The Crairs nursed Stacey at home for four years.

Both Lisa Crair and Mike Nofi are now lost in legal battles that they say they neither relish nor understand. Crair's lawsuit has been thrown out of court over legal technicalities in three states where the hormone was processed. Nofi has been given leave in New York state courts to sue numerous doctors, technicians and every university that handled the hormone--even Parlow's UCLA lab, the very place that in 1977 cleaned up the hormone.

But Nofi is not suing the NIH. According to Pamela Liapakis, former president of the Assn. of Trial Lawyers of America, the agency enjoys what the legal profession calls "sovereign privilege" and is exceedingly difficult to sue under federal tort law.

In Britain, however, outraged families did sue the government. In 1990, an English lawyer named David Body tracked Dickinson down in a drafty stone house outside Edinburgh, where he had been living in retirement for three years. Body then represented three of what are now 34 families of British hormone victims. He was going to try something nobody had ever done successfully in Britain: sue the Department of Health in a personal injury case.

He needed an expert witness. After interviewing Dickinson, Body realized that he could "never put him on the stand." The scientist was frail and prone to severe migraines. But he typed out a statement that both outlined the state of knowledge about CJD 25 years ago and recounted his 1976 warning about the risk of contamination.

In July 1996, the court decided against the British government to the tune of more than $7.5 million. Anyone treated with the potentially contaminated hormone after Dickinson's warning was issued would be compensated. Damages are now even going to the "worried well." [This is an insulting term that belittles the situation of recipients -- no data argues they are well. -- webmaster]

Although Alison Lay's death sparked the 1985 crisis in Britain, her parents were excluded from the settlement, because their daughter was treated before Dickinson sounded the warning. "At least in this country we did have the trial," said Mavis Lay. "And the government admitted that it was at fault and caused the deaths.'

By the time of the trial, Hartree had returned home to Nashville. She refuses all contacts with the media, lawyers and hormone recipients. In her absence, the British judge concluded that Hartree's failure to use Sephadex was, by analogy, "a commercial decision: quantity before quality."

The court stopped short of finding the government negligent in the preparation of the hormone. "In the English claims, the issue of purification became secondary to the policy failures," said Body. "I'd like to see purification explored further in the United States."

The more time that passes, the more difficult this will be. In 1994, at the age of 84, Wilhelmi died at his home in Atlanta. However, Parlow, his former colleague who upgraded the purity of the NIH hormone, said clear "warning bells" were ignored.

Describing the early hormone, he said, "It was painful on injection. This signaled impurities." That was confirmed by a second side effect. "Ten to 15% of the kids treated developed antibody formation," said Parlow. "Though this is not life-threatening, it is not a good thing, and it means that there is something wrong with the product."

In addition to the 22 Americans who have died from Wilhelmi-era hormone, CJD has killed five New Zealanders and one Brazilian who received pre-1977 American hormone. In Britain, 34 people have died, and the global toll stands at more than 125. The Centers for Disease Control says the rate of CJD cases among hormone recipients worldwide is increasing to 2 cases a year from 1.

* * *
Tracing the Growth Hormone
1901-05: The word "hormone" coined
* * *
1921: Creutzfeldt-Jakob disease (CJD) discovered in Germany.
* * *
1925-45: Growth and reproductive hormones found in the pituitary
glands in the brains of animals
* * *
1958: Maurice Raben at Tufts University School of Medicine in
Boston spurs 2.1 inches of growth in a dwarf by injecting him with
human growth hormone extracted from pituitary glands taken from
the brains of cadavers
* * *
1963: The National Institutes of Health takes up sponsorship of
the National Pituitary Program.
The largest seat of production is the lab of Alfred E. Wilhelmi,
head of the biochemistry department at Emory University in Atlanta.
Swedish scientists notice that American growth hormone causes
immune reactions and publish an alternative method for making the
drug.
* * *
1968: NIH doctor Daniel C. Gajdusek writes in Science magazine
that CJD is transmissible via infected brain tissue. *
* * *
1976: Edinburgh-based veterinary geneticist Alan Dickinson
warns the British government that its pituitary program might spread
CJD.
* *
1977: Wilhelmi retires. The NIH moves production of human
growth hormone to the UCLA lab of Albert Parlow, who begins
filtering the drug. The British hormone program also switches from
the Wilhelmi protocol to the Swedish extraction method.
* * *
1978: Dickinson's fears of CJD contamination in the hormone are
passed to Gajdusek's lab at the NIH. In May, a visiting Australian
pathologist replies on NIH letterhead that pituitary glands could be
contaminated with CJD. But he does not pass the warning to the
NIH's own pituitary program. *
* * *
1985: Alison Lay, a hormone recipient, dies in Britain. Three
unidentified American recipients also die. The NIH suspends the
human growth hormone program. Paul Brown of Gajdusek's lab is
called in to investigate. He warns of a potential "epidemic" of CJD.
* * *
1991: Brown and others report in the Journal of the American
Medical Assn. that 8,157 American children received the drug and
that as many as 140 glands infected with CJD may have entered the
system.
* * *
1996: A class-action lawsuit on behalf of hormone recipients is
brought against the British government. A London high court awards
the plaintiffs $7.5 million.
* * *
2000: The CJD death toll among American recipients of pre-1977
unfiltered hormone stands at 22. The Centers for Disease Control
and Prevention in Atlanta reports that the incidence of CJD in
hormone recipients is rising from one case a year to two.

NIH epidemiologist Paul Brown was called in by the human growth hormone program to investigate the CJD contamination in 1985. Ever since, he has insisted that nobody could have foreseen the dangers. But newly discovered letters show that in 1978, a colleague in Brown's own lab acknowledged the danger and failed to alert the hormone program.

Department of Health, Education, and Welfare
Public Health Service
National Institute of Health
Bethesda, Maryland 20114

May 8, 1978

It would be reasonable to expect that the pituitary gland
and/or surrounding tissue taken from a case of Creutzfeldt-Jakob
disease would be contaminated with the virus. Therefore, it would
seem advisable that tissue obtained from any patient with CJD
{or any other dementing illness) not be used in preparations for
human use.
 

Opinion (webmaster): This is an excellent in-depth article. It is worth mentioning that sephadex columns were used by every lab in the world purifying protein in 1965, it is not a little-known Swedish technology. Little effect ongworth hormone yield would occur. It sounds like there was not even an adequate ultra-centrifuge step in the crude extract of Wilhelmi or Hartree. There would be a great many other extraneous but active hormones in a crude pituitary extract, in addition to any prions.

The story does not make clear that many children did not have pituitary problems to begin with and received little or no benefit from the program, which was and is aggressively marketed (kickbacks) through pediatricians to parents who are told a short child is not normal, when of course human heights have a standard gaussian distribution. This was never really about pituitary dwarfism but rather experimental molecular cosmetic surgery -- and that would account for 95% of the use today.

Things aren't that different now for corneal transplants either: "neither the British nor the Americans moved to exclude the use of glands from organ donors who had died of CJD."

Note Dickinson, who was quoted last week as claiming to have evidence that spreading fertilizer on fields led to horizontal transmission of BSE, is described in the story as having retired 13 years ago as " living in a drafty stone house outside Edinburgh ... frail and prone to severe migraines." In other words, no experiments have been conducted on cow manure (though horizontal transmission of BSE remains a very real possibility.

Colin Masters, who made several controversial statements last week about the supposed low risk of surgical transmission at an Australian hospital, was already in fine form by 1978.

It is also interesting to see the long delays in publication: "In 1982, Dickinson had his answer... The results were not published for three years. Both Dickinson and the British hormone program sponsors were sensitive to the potential for a scare..... It took Brown six years to publish an estimate of how many glands infected with CJD might have entered the system. By 1991, the official estimate was 140."

Then as now, no one wants to look at a random autopsy series to determine the actual incidence of incipient CJD. This is far higher than clinical CJD because many people die of cancer or heart attacks before displaying CJD symptoms.

And talk about coincidences: "the results showing the Swedish method's safety were seen to have a calming effect. They were published in the same issue of the Lancet as her case history. After the Lancet report, in September 1985, Brown reported on the three American deaths in the NEJM."

Donor bodies milled into growing profits

By Stephen J. Hedges and William Gaines Chicago Tribune Opinion (webmaster): An estimated 600,000 people a year in the US receive a donated tissue transplant from a predatory unregulated industry according to this story. How many of the donors had CJD? It is very unlikely that any screening takes place, except possibly for the odd case of clinically diagnosed CJD. These of course represent a small fraction of total infectious pre-clinical individuals.

Little-regulated industry thrives on unsuspecting families

Jim Bardsley lives in White Oak, Ga., and runs two businesses. One sells catfish. The other sells human body parts. Bardsley has had the catfish farm for just two years. But he was one of the first to jump into the human body parts trade 14 years ago, eventually starting three non-profit tissue banks and a for-profit company, all to ship body parts to scientists for a fee.

He said he is proud of his contribution to science. He's also not shy about making money: His current non-profit earned $1.5 million last year, a fraction of the lucrative body parts business in America.

Many who followed Bardsley into the tissue trade also cashed in while removing, processing and selling cadaver parts for use in everything from knee replacements and cosmetic surgery to the testing and manufacture of new drugs, a Tribune investigation has found.

Huge markups in prices and a lack of federal regulation have attracted a wide range of individuals, tissue banks and for-profit companies benefiting from transactions that begin with an act of generosity’ a grieving family's decision to donate the tissue of a deceased loved one.

The allocation of hearts, livers and other vital organs is so critical to saving lives that the federal government closely regulates their use. Yet federal and state governments pay scant attention to what is done with tissue, which is a medical euphemism for bones, skin, veins, corneas’ anything that isn't a healthy organ.

One body can yield more than 130 pieces of tissue once it is extracted, sterilized, cut up, packaged and sold. The total worth of all the usable tissue in a body is more than $230,000. Because not all the tissue from a single donor is usually taken, the average market yield per cadaver is closer to $80,000, industry executives say.

Just what happens to that tissue has stunned families who believed they were helping others in need. Skin that could help burn victims is sold to companies as ingredients in products that help cosmetic surgeons enlarge penises, stretch sagging chins and puff lips.

Knee tendons that take just a few minutes to snip out of cadavers are popular with sports medicine doctors and can fetch $2,500 each. Valves are cut out of donated hearts, frozen and sold as transplants for more than $7,000 each.

Those prices seem to defy the 1984 National Organ Transplant Act, which prohibits the buying and selling of tissue and organs. The body parts business, though, banks on a gaping loophole in the act: It allows agencies to recover the "reasonable costs" of collecting human material.

Tissue banks, brokers and for-profit companies use that vague language to set their own prices for the tissue they collect and sell. No federal agency polices the seeming abuse of the "reasonable cost" clause.

"The problem that you find is that lots of guys just view this as a commodity," said David Kessler, a former commissioner of the U.S. Food and Drug Administration, which focuses on tissue safety, but not pricing. "My sense was, if certain guys weren't in this business, they'd be in concrete."

To meet the demand, local tissue and organ banks compete and even pay for access to hospitals, morgues and hospices where they can find families willing to donate a deceased loved one's remains.

Some tissue is also imported by U.S. companies, a practice that has resulted in diseased tissue being used in transplants here. Surplus tissue from American donors, meanwhile, is shipped overseas, even though donor families often believed the tissue would help someone in their own community.

The altruism of donation is further clouded by the complicated relationships that have developed between the non-profit and for-profit companies in the tissue business. Though donor families give a relative's tissue to a non-profit tissue bank, some of those groups turn around and sell the tissue to for-profit companies. It is not unusual for the non-profit and the for-profit to have supply agreements, processing contracts and formal partnerships.

Revenues of the nation's 10 largest non-profit tissue banks and organ banks dealing in tissue totaled $230 million in 1998, the last year for which figures are publicly available. Two years prior to that, those same organizations reported revenues of $183 million. Revenues for four leading for-profit tissue companies were $173.3 million last year.

"It's standard for the tissue handlers to commercialize their services," said Lori Andrews, a professor who specializes in medical ethics at the Chicago-Kent School of Law. "One of the main points is that people who donate organs or tissue, or even provide it for diagnostic tests, have no idea that someone has used it as a business. It has become the raw material for products."

Most donor families are unaware of the brisk business in body parts when a tissue bank approaches them. Full disclosure of what donation really means is rare; pressure to donate is not.

Donald Pierini of Chicago is still outraged at the way the tissue business treated him just a few hours after his father's death six years ago, and by what it did with his tissue after it was removed After suffering a heart aneurysm, Donald Pierini Sr. was rushed to Halifax Hospital in Daytona Beach, Fla. His son and wife of 40 years, Rita, were with him, and they stayed with his body at the hospital. Then came the request for donation. Donald Pierini recalled a nurse pressing the family, telling them the tissue bank was waiting and needed an answer.

The younger Pierini doesn't remember anyone ever asking for tissue’ only organs’ though FDA records show that the University of Florida Tissue Bank did extract bones from his father's body. From there, the bones were sent to a for-profit company, Biodynamics International Inc., also a Florida company, which then sent them to Germany for processing before they were distributed in the U.S.

Those details were never explained to the family, Pierini said. "You expect someone to be sensitive to what's going on," Pierini said, "instead of being worried about some kind of business."

FDA officials say they are more concerned with the safety of tissue than the burgeoning market for it, possible violations of the federal prohibition of profiting from human body parts or the way tissue is solicited.

"You have to realize that our focus in regulating the tissue banks is to prevent the spread of communicable diseases," said Steve Masiello of the FDA's Center for Biologics, Evaluation and Research. "Insofar as actions are necessary, we're going to be leaning toward recalls or orders, so that we can identify and remove any products from the market."

The FDA requires tissue banks to screen donors for disease and assign each donor a distinct number. The agency published a Tissue Action Plan in 1998, but it has yet to adopt its own proposals, including ones that would require the registration of products made with human tissue and of the nation's estimated 300 tissue banks. Agency officials say they have been delayed by their expanding responsibilities in regulating other fields, such as biotechnology and gene therapy.

In a December 1997 audit, the U.S. General Accounting Office, the investigative arm of Congress, noted the inherent risks posed by the FDA's inaction.

"The agency has no universal registry of tissue facilities currently operating in the United States," the report found. "As a result, FDA could not disseminate to all tissue banks critical information in a public health emergency that might affect the safety of transplanted tissues."

The FDA's own regulations allow it to prosecute individuals "when there is documented evidence of fraud, gross violations, a hazard to health and/or continuing significant violations." But the agency has never sought a criminal case against a tissue bank operator, despite past instances of apparent fraud and potential health hazards. Usually, errant operators are just given written reprimands.

There are signs, though, that the industry is beginning to consider new, self-imposed regulations following revelations of unethical practices reported by the Orange County Register in Southern California. The American Association of Tissure Banks is considering ways to inform donor families that tissue is sometimes processed by for-profit companies. The group, which represents 69 tissue banks and processors, also plans to poll its members to determine if there is a shortage of skin for burn victims.

Association President Richard Kagan said that the good done by tissue transplants is overshadowed by tissue banks' violations of public trust. "There are situations where a non-profit tissue bank takes advantage of the donation process," he said. "We have got bad players, just like there are bad lawyers and bad doctors."

And, the newspaper has reported, the Orange County Eye and Tissue Bank now is offering families the option of designating donated skin for cosmetic surgery.

The business of tissue banking begins even before someone dies. The first step is finding donors. Besides arrangements with hospitals, coroners and medical examiners, organ and tissue banks sponsor school and community campaigns to encourage people to donate.

Every state has a program that asks drivers to designate themselves as "donors" on their licenses. In Illinois, 4.7 million residents had signed up as donors by 1999, according to the secretary of state's office. (Depending on the year, an Illinois driver's license might provide the option of "entire body" or "any organ or tissue" but drivers also can designate specific body parts.)

But organ and tissue banks still need to get consent from the dead person's next of kin before they remove body parts. Organ donation has been one of the great medical success stories and has long drawn support from Illinois politicians. Former Gov. Jim Edgar took up the cause while serving as secretary of state. George Ryan, the current governor, did the same. Today, Secretary of State Jesse White urges residents to become donors.

Ryan's high-profile role in that effort is a good example of how the bid to increase tissue donation is subtly folded into the dramatic appeal for lifesaving organs. "Currently, thousands of people in Illinois and around the country are in need of an organ and tissue transplant," one pamphlet issued by Ryan reads. "Without it, many will die."

That is true of organs, but most tissue is not lifesaving. Farther down, the brochure states that, "The National Transplant Act of 1984 established full and equal access to donated organs and tissue for all potential recipients." But the act only addresses the fair distribution of organs, not tissue. Just who gets tissue, how, and at what price is left up to the tissue banks and hospitals that buy and sell it.

In Illinois there are three main tissue banks. The Regional Organ Bank of Illinois (ROBI) extracts’ or harvests’ tissue. It also is the federally designated organ procurement organization, or OPO, for the central and northern part of the state. The American Red Cross extracts tissue from donors throughout the state, but does not harvest organs. In southern Illinois, St. Louis-based Mid-America Transplant Services harvests tissue and organs.

By federal law, every hospital in America must notify the OPO in its area when a death occurs. The requirement was instituted in 1998 to increase the availability of organs for transplant. Hospitals that accept Medicare payments are required to arrange for donation with a local tissue bank.

Organ and tissue agencies often pay hospitals or county morgues for use of the facilities where they harvest tissue and for any equipment they might use. In Cook County, as in many counties in the state, Medical Examiner Edmund Donoghue gives ROBI free use of a room in which to extract tissue once it gets consent from the deceased's family.

The tissue harvest can last one to two hours. Technicians typically extract leg and hip bones; Achilles tendons; the internal structure of the knee, including several important tendons; leg veins; skin, usually removed from the deceased's back; the corneas; and the whole heart, which will yield valuable valves. Metal, wood or plastic rods are placed in the body to give it shape for open casket funerals.

At ROBI, and at many other organ banks, tissue collection is a growing segment of the donation business. In 1999, ROBI recovered tissue from 565 donors and organs from 276 donors. Two years earlier, it had 420 donors who gave tissue, and 252 for organs. Ultimately, tissue donated in Illinois can end up in the possession of a for-profit company. But that shouldn't dissuade donors, state officials say.

"The cosmetic use is not a problem in Illinois," said Sue Altman, director of the Illinois Secretary of State Organ Donor Program. "I have been assured that none of the tissue from Illinois goes into those products." ROBI and Mid-America ship tissue on dry ice by air to AlloSource, a non-profit tissue processing consortium that is jointly owned by ROBI, Mid-America, the Donor Alliance of Denver and the San Diego Regional Tissue Bank.

In Denver, AlloSource treats the tissue by sterilizing and shaping it into usable parts for transplant. It returns a portion of processed bone and other tissue to its member tissue banks, depending on local need. The rest goes to hospitals in other cities, or to Progressive Medical, a St. Louis medical supply distributor, according to Jeff Sandler, AlloSource's president.

AlloSource also grinds up some of the donated bone it receives to make AlloGro, a surgical bone-growth powder that is used in bone grafts. The agency sells some of the tissue it receives to for-profit companies. One of those firms, Regeneration Technologies, Inc., shapes bones into dowels that are used in back surgery.

Two other AlloSource customers, Gensci Regeneration Service, Inc. of Canada and Wright Technology Co. of Arlington, Tenn., use AlloGro as an ingredient in their own bone powder compounds, which are then sold to surgeons and hospitals, according to the companies.

Across the country, an estimated 600,000 people a year receive a donated tissue transplant. Tissue is used in a variety of transplant procedures, some of which dramatically improve patients' lives. They include the insertion of bone pieces in ruptured backs, leg veins in bypass surgery and valves for troubled hearts.

Once tissue is donated, though, there is no guarantee where it will end up. It may help someone with a dire medical need, or be used in dental work or cosmetic surgery. It may stay with a non-profit tissue bank, or end up at a for-profit company.

Donated skin may have found the most questionable use. Lifecell Corp., a New Jersey company, pays tissue banks for skin and uses it to make a burn treatment product, Alloderm. Plastic surgeons, though, have found it useful for face lifts and lip enhancements. Some doctors even use Alloderm to enlarge penises, a procedure that can cost as much as $8,000.

Doctors in New York, Beverly Hills, Ireland and Argentina are among those who advertise the use of Alloderm for cosmetic purposes. In Las Vegas, Dr. William Canada said he uses Alloderm for several procedures, including penis enlargements. "In cosmetic surgery, if someone else has it done, it's frivolous," Canada said. "If you have it done, it's not."

Lifecell has had dramatic success with Alloderm, its main product. Revenues grew from $4.9 million in 1997 to $7.2 million in 1998 and $11.9 million last year. A square-foot sheet of Alloderm costs $4,000, doctors say. It comes packaged in slices very much like American cheese.

Another company, Collagenesis, Inc., makes a product called Dermalogen, a gel that is used by cosmetic surgeons who insert it under the skin to remove wrinkles and frown lines.

In a report filed with the Securities and Exchange Commission, Lifecell said that it doesn't promote the cosmetic use of Alloderm and that if potential skin donors found out, they might not want to donate.

"We didn't think of these applications," said Dr. John Harper, vice president for clinical development. "Surgeons came to us and told us how they had discovered different uses. It's not within our power to tell the doctor what to use it for."

Though it is illegal to buy and sell organs, tissue banks have made good use of the loose language in the law, which declares that no tissue or organ can be exchanged for "valuable consideration."

Tissue banks and other companies in the tissue business try to avoid running afoul of the law by charging "processing costs," which are supposed to cover the costs of extracting and handling the tissue. Along the way, these processing fees can inflate the price of tissue and pad revenues.

Hearts not good enough for use as transplants are sold by tissue banks to one of several tissue banks and companies, including Cryolife of Atlanta, for about $1,500. The two usable valves are removed, frozen and sold as transplants for more than $7,000 each, according to Cryolife's public financial disclosures.

Whole knees are sold to processors for about $4,000, tissue bank directors say. The knee parts, including tendons, are worth double that when they are packaged and sold retail to hospitals. Patellar tendons, a 2-inch strip of tendon snipped from the knee, are sold for up to $2,500 apiece, according to a Cryolife Vice President Roy Vogeltanz. They are a popular fix for knees torn in sports injuries.

How do companies such as Cryolife, whose shares are traded on the New York Stock Exchange, manage to make money on a product that can't be bought or sold? Vogeltanz said that no profit is derived from the tissue, but that profit is built into the processing fee.

"Federal law prohibits buying and selling tissue," Vogeltanz said. "It does allow companies to bill hospitals to get their fee for service back out."

The FDA has declined to sort out the legalities of these transactions, but even some in the tissue bank industry argue these fee arrangements appear to violate the spirit of the law. These insiders point to the wide variation in tissue prices from tissue bank to tissue bank, company to company, city to city. The rules of supply and demand are setting the price, they say, just as in any other business.

"Why is there a change in price between Boston and Nashville and Des Moines and Los Angeles?" asked Kagan, the tissue bank association president and a burn doctor. "As far as tissue banks go, a guy might distribute a patellar tendon in his own back yard for $2,000, but $5,000 elsewhere. So what did he do for the $3,000? The service charge should reflect the service, not the market."

A 1995 court case offers a glimpse at the profits behind the body parts business. The case involved Biodynamics International Inc., which sued the FDA after federal inspectors held up shipments of tissue the company was importing into the U.S. An affidavit from a company executive reveals that 650 "units" of tissue were drawn from 45 American donors.

"The cost of recovery and processing these tissues is approximately $120,000 and has already been paid," said an affidavit from David Nichols, a company vice president. "Biodynamics expected to realize approximately $156,000 in revenue on the distribution of these tissues."

Another shipment of 1,500 units taken from 31 donors, Nichols wrote, was still in Germany ready to be imported. The company had spent $300,000 to procure and process that tissue, he wrote, and it expected to earn $360,000. A federal judge ruled in favor of Biodynamics and allowed the shipments into the U.S. Biodynamics officials, like those at Cryolife, argue that the profit is in the processing fee and not the tissue.

The public sees organ and tissue donation as a charitable act. Inside the business, though, the line between doing good and making money gets blurred. Sometimes it can disappear altogether.

Earlier this month, Robert Hoffmann submitted his letter of resignation as the head of the agency that collects and delivers vital organs in Wisconsin. Hoffmann ran the agency for the last 25 years out of the University of Wisconsin Hospitals and Clinics. Hoffmann quit after university officials learned that he was being paid by Allograft Resources of Wisconsin, Inc., a tissue bank that Hoffmann helped create and that received donated tissue from the university hospital.

In 1996, Hoffmann arranged to have the tissue that was harvested from hospital patients delivered to the American Red Cross. In return, the Red Cross paid him personally for those services, university officials said. Two years later, several Red Cross employees, aided by Hoffmann, set up their own non-profit tissue bank, Allograft Resources.

The new tissue bank replaced the Red Cross as the recipient of the hospital's tissue, and Hoffmann continued to receive a fee, according to Lester Pines, Hoffmann's attorney. Hoffmann violated university rules by not disclosing his outside source of income. He has vowed to pay the $86,000 in fees to the university for "organ donation education," Pines said.

Allograft Resources sent donated bone and skin to two for-profit tissue companies: Regeneration Technologies in Florida and Lifecell, which makes Alloderm. RTI President Jamie Grooms and another RTI executive sat on Allograft's board of directors.

RTI is one of the tissue industry's most aggressive for-profit players. It was formed by the non-profit University of Florida Tissue Bank in 1998, and it recently bought out the non-profit Georgia Tissue Bank to increase it tissue supply. Grooms said the company hopes to go public within a year.

"We're just being up front about it," said Grooms. "If I had my way, everybody would be a for-profit." RTI is a still a small player compared to the nation's largest tissue bank, the non-profit Musculoskeletal Transplant Foundation (MTF) of Edison, N.J.

MTF's promotional literature states that it was "established by surgeons and teaching institutions." In fact, it was established in 1987 by Osteotech, Inc., a New Jersey company that wanted to make money by processing tissue. Back then, company officials said, Osteotech couldn't convince non-profit tissue banks to give it tissue to process; the non-profits blanched at the notion of someone making money from tissue. So it started its own non-profit, enlisting university doctors to help.

Since then, MTF, backed by several million dollars in loans from Osteotech, has developed a network of 27 "member" tissue and organ banks. Company executives say MTF, which realized revenues of $105 million in 1999, is no longer reliant on Osteotech. But MTF remains one of Osteotech's largest providers of bone, corporate records show. Osteotech , whose shares are traded on the Nasdaq stock exchange, has seen its revenues climb from $44.8 million in 1997 to $59.2 million in 1998, and $75.6 million last year.

Jim Bardsley understands how running both non-profit and for-profit body parts businesses can have its advantages. Non-profit organizations are exempt from federal and state taxes, and "none of the earnings of the organization may inure to any private shareholder or individual," according to the federal Internal Revenue Service. The IRS notes that charitable groups must serve a community purpose.

For-profit companies face a simpler, if more costly existence. They have to pay taxes, but they are free to attract investors, float stock, pay returns to shareholders and make money. As human tissue has been commercialized, more for-profit companies have started to process and sell it, and more non-profit agencies have begun acting like commercial companies.

"You can set up a non-profit like a business operation, and that's basically a flaw in our system," Bardsley said. Some non-profits and for-profits even share the same office space. That's how it works in Jim Bardsley's small corner of the industry.

His current non-profit, the Anatomic Gift Foundation, was established in 1992. At the time, Bardsley had rolled up $70,000 in debts, all of it on credit cards. He was employing his wife, father and brother (a second non-profit would also employ his brother's wife), and paying them good salaries. He and his wife alone took in more than $115,000 that year, according to Internal Revenue Service non-profit filings.

AGF was started originally, he said, to procure fetal tissue, a controversial sidelight of the tissue business that most operators stay away from. Fetal tissue is usually received from abortion clinics. It is used, among other things, in Parkinson's disease research.

Soon, Bardsley discovered a promising new product line: liver cells. A University of Pittsburgh doctor had found a way to isolate the cells and implant them in patients waiting for whole liver transplants. The new cells latch onto the liver and extend the life of the patient. The beauty of the business, Bardsley said, was that the liver didn't have to be perfect. Plenty of cells could be taken from a small section of most livers.

Bardsley founded a new company. This time it was a for-profit: the Human Cell Culture Center, which extracts and markets the cells. And he started to pay organ banks for their livers.

The livers were sent directly to the University of Pittsburgh doctor, who kept some for his research and processed the rest into cells for Bardsley. At first, the "processing fee" charged by organ banks for each liver was about $500, Bardsley said. "But then they realized there was a market in the things, and prices jumped to over $3,000. Some people even started paying more, up to $7,000 a liver." The only reason for the price increase, Bardsley said, was the new market for previously unusable livers.

The big drug companies, including Abbott Laboratories, Pfizer Inc., Hoffman-LaRoche & Co. and 30 others, were all on Bardsley's client list. Until then, they had been using animal livers to test the toxicity of new drugs; human liver cells were a much more reliable gauge. Bardsley struck a $1 million, two-year contract with BioWhittaker Corp, a Maryland company that markets cell lines.

But Bardsley said that increased competition and the high price of livers is forcing him out of the cell business. "There's a lot of crazy things going on out there," he said. "There's a tremendous amount of economic pressure on the medical advances that have to be developed. Investors are pouring money into this stuff. And it all comes back to the raw material."

People like Mary Berkey of San Antonio are introduced to the nuances of the body parts industry when they are at their most vulnerable. She believed what the public service ads told her, that donating organs and tissue could help someone in need.

When her husband, Murray, died of a heart attack in 1997, she got a call from Southwest Tissue Services. "You can imagine the state I was in," she recalled. "But I told them, 'Yes, take whatever you need if it will help someone else."'

Southwest Tissue harvested Murray Berkey's bones, tendons and skin and then distributed them to a for-profit San Antonio company, Bone Bank Allograft, for sale to hospitals.

The FDA ordered a recall of Murray Berkey's tissue in the fall of 1998. It took that action after learning from a Southwest employee that the tissue bank had distributed Berkey's tissue even though lab tests showed that he had been exposed to hepatitis B.

Southwest closed in late 1998, after the FDA cited it for repeatedly distributing tissue that lab tests had shown was contaminated. "It's not right that someone should make money off of it," Berkey said. "I know there are fees involved and all, but it's not right."

Opinion (webmaster): A tissue donor industry web site has some interesting snippets. From the fact or fiction section relevent to screening of donors for CJD:

"Does a history of medical illness or advanced age will automatically eliminate your chance for becoming a donor.

No. "Age limits for organ donation no longer exist and at the time of death, qualified medical personnel will review medical and social histories to determine donor suitability on a case-by-case basis. "

And there are other ways you can help the tissue donor industry besides giving them $230,000 worth of your body parts for resale:

"Put an organ & tissue donation bumper sticker on your car. Wear a t-shirt, hat or even shoelaces with a message about donation - it¹s a great conversation starter."

"Put posters on bulletin boards or in windows of laundromats, libraries, doctors¹ offices, grocery stores and fast-food restaurants in your community. "

"Make a financial contribution to national or local efforts to educate the public and increase organ and tissue donation. Contact the Coalition on Donation or your local coalition for details."

Tissue imports pose hazards: Deadly contamination found in shipments from abroad

May 22, 2000 By Stephen J. Hedges Chicago Tribune Staff Writer 
The laboratory run by Dr. Alvero Duenas was not what it appeared to be. Each day the neonatal intensive care unit at the University of Valle Hospital in Cali, Colombia, received a call from Duenas' small non-profit agency, In Vitro, to see whether any babies had died prematurely.

Hospital workers said they thought Duenas, a retired university professor, was using the babies' kidneys for research. But after an assistant collected the kidneys, Duenas reduced some of them into a slurry of frozen cells and then shipped the vials to the U.S., where they were used to make Abbokinase, a $277 million-a-year anti-clotting drug sold by Abbott Laboratories of North Chicago.

Federal inspectors uncovered the kidney source in 1998 when they made a routine visit to BioWhittaker Inc., the Maryland company that took delivery of the cells from Duenas and sold them to Abbott. They halted the shipments after they found that kidneys were in mislabeled containers, that they weren't properly tested for disease, and that there was no proof the parents of the dead babies had given permission for the kidneys to be removed.

Abbott has stopped making Abbokinase, and BioWhittaker has suspended kidney shipments from Colombia. But the harvesting of dead infants' kidneys in Cali shows the wide reach and questionable practices associated with an expanding international supply of human body parts.

The body parts business in the U.S. has grown in the past decade from a small-time, community endeavor into a sophisticated medical industry, one that generates hundreds of millions of dollars in revenue each year. Increasingly, those businesses have turned to overseas markets, both as a source of body parts and as a market for exports.

Food and Drug Administration import records show heart valves and veins arriving from France and Canada, cartilage from Italy. Skin is shipped in from Denmark, South Africa and Japan. Heart arteries arrive from Russia. The tissue is used for research and transplants. Cells are used in the testing and manufacture of drugs. Exports of surplus bone donated to U.S. tissue banks are similarly brisk, according to tissue bank operators.

Like many aspects of the tissue industry, the import and export of human body parts, skin and corneas have been largely hidden from public view. The families that consent to tissue donation often think it will be used for transplants to help others in their community. There is no federal requirement that tissue banks disclose to families just what will happen to the tissue they collect. No federal agency watches over exports.

The FDA, which has been reluctant to aggressively regulate the domestic tissue market, has focused more attention on imports into the U.S., with some of its most notable actions coming in response to tainted tissue from overseas. Agency inspectors must approve all imports, and businesses bringing tissue into the U.S. must show it is disease-free and was given with the consent of the donor's next of kin.

The FDA relies largely on the veracity of the importer's documents, because it can't review donor records to check whether the tissue was properly screened and donated.

The dangers of the international trade in human body parts are demonstrated in a series of tragedies and mishaps involving tissue imports during the past decade. These episodes also shed light on a little-known and fast-expanding international business, one that is as much about making money as it is about helping people in need.

Karen Bissell first began to feel odd in June 1998. The back of her head hurt. Her vision would blur. Her legs and neck ached. Bissell was 39, an energetic woman who had played in the high school band, owned a motorcycle and served a stint in the Army. "She kept saying: 'I'll be OK, Mom. Don't worry, I'll get better,"' recalled Eleanor Bissell, Karen's mother. She never did.

Two months after she started feeling numb, Bissell was forced to leave her job as a finance administrator at the U.S. Department of Agriculture in Miami to return home to Denver. She alighted from the plane in a wheelchair, legally blind and very afraid. She died five weeks later.

The cause of death was Creutzfeldt-Jakob disease, which is similar to so-called mad cow disease. Because it may be borne in meat, any CJD-like death raises an alarm for health officials. As they delved into Bissell's medical history, those authorities fixated on a piece of brain-lining tissue transplanted into Bissell's neck six years earlier. The material, called dura mater, is the membrane that encases the brain and spinal cord. It is often transplanted to repair the breach neurosurgeons make in the patient's own dura mater to access the brain and neck.

In 1992, Bissell had an operation after she learned she suffered from an Arnold-Chiari malformation, a condition in which the head puts undue pressure on the spinal column. It is treatable, and doctors implanted a piece of donated dura mater to repair their incisions.

The dura mater, health officials say, came from Biodynamics International Inc. of Florida, which received it from its German partner, Pfrimmer-Viggo GmbH. Pfrimmer-Viggo had taken the tissue from the body of a German man who had suffered from a series of maladies, including brain disorders, officials say.

"He had all kinds of diseases," said Richard Hoffman, chief epidemiologist for the Colorado Department of Health and Environment. "He had heart disease [and] ... some kind of neurological disease. By any standards in the screening of donors, any patient with neurological diseases should be excluded."

Biodynamics, which has since changed its name to Tutogen Medical Inc., was cited after a 1990 FDA inspection for shortcomings in the screening of tissue donors by its German business partner. The FDA found that tissue from donors in newly independent Estonia, Lithuania and Russia was taken without family consent and was not properly checked for disease.

The FDA reported these manufacturing deficiencies to the company, but it took two years, until November 1992, for the agency to follow up with another inspection at Biodynamics in Germany. This time, the FDA concluded that "approximately 80 percent of all dura mater received and used has not been tested for conformance with serological specifications, i.e., hepatitis A, HIV."

The company says those problems were corrected long ago, and that its tissue was not the culprit in Karen Bissell's death. "We definitely have the deepest sympathy for the family," Tutogen President Manfred Krueger said. "But we strongly disagree with any conclusions that that woman was infected by any dura mater. She was born with a severe brain damage, and she was probably treated all her life on that brain disorder."

Bissell's family angrily disputes that. "That's not true at all," Eleanor Bissell said. "She had no brain damage. She was perfectly fine. When she was about 32, she started having numbness in her hands and feet." There were no complications afterward, she said, until the onset of CJD in the summer of 1998.

In 1999, Tutogen voluntarily issued a recall for all the dura mater it had distributed before 1994. It got back only four pieces. Company officials say they don't know how much had already been transplanted. There have been no other reports of adverse reactions to the transplanted dura mater, though health officials note that it can take 16 years for the disease to manifest itself.

Karen Bissell's relatives say they weren't told about the use of donated dura mater before Karen's surgery, the possible risks involved or the synthetic alternatives that are available. "It's the most horrible thing you can imagine going through," Eleanor Bissell said. "The hard part is knowing that it could have been prevented."

Imported dura mater had been associated with illness and fatalities before. More than 50 deaths worldwide have been linked to the late-1980s importation of a dura mater product called Lyodura, made in Germany. In February 1987, U.S. health authorities discovered that a 28-year-old Connecticut woman had developed CJD after getting a transplant of Lyodura.

Soon, other possible Lyodura-related cases of CJD were reported in Germany, Italy, Japan, New Zealand, Spain, Britain and the United States. As part of their investigation, officials with the U.S. Centers for Disease Control and Prevention in Atlanta found that manufacturer B Braun Melsungen AG was taking all of its donated dura mater and processing it together.

"They put it in a bucket, a huge bucket," said Dr. Ermias D. Belay of the CDC's division of viral and rickettsial diseases, who has investigated both the Lyodura and Tutogen cases. "They processed it together as a batch. All you need is one infected piece and it can infect all the other pieces."

B Braun Melsungen changed its processing method. But 57 people who received Lyodura grafts from the older tissue died from CJD, including the Connecticut woman and one other U.S. resident, according to the CDC. Most of the deaths occurred in Japan.

The CDC concluded that "an international outbreak of CJD associated with a single brand of dura mater graft is larger than previously recognized and that recipients of contaminated grafts may remain at risk for CJD for at least 16 years following receipt of grafts."

In the U.S., the dura mater problems were left largely to the CDC to investigate. Last October, a year after Karen Bissell's death, the FDA issued new dura mater guidelines. They call for businesses selling dura mater to keep detailed records of the donor's medical history and brain autopsy, and they provide special instructions for processing dura mater, including how to sterilize it. The guidelines, which apply to domestic and imported dura mater, don't have the same power as a federal regulation, making it harder for the FDA to enforce them.

In 1992, the Sklifosovsky Research Institute in Moscow became the source of a human body parts pipeline that delivered more than 5,600 pieces of tissue from 228 Russian cadavers to tissue banks and hospitals throughout the U.S. When a U.S. tissue bank executive expressed concerns about the safety of that tissue, FDA officials opened an investigation. What they found astonished them.

FDA case files reviewed by the Tribune offer a glimpse at just how lucrative, and potentially disastrous, the Russian tissue trade was. The pipeline flowed from the office of Dr. Valery Khvatov at Sklifosovsky, according to FDA investigators. In 1992, Khvatov arranged for a friend in Los Angeles, a dentist, to become his U.S. import agent, FDA records show.

Khvatov, according to tissue receipts, was charging $5,000 for each shipment of bones and tendons from the hips, knees, legs and feet. In an interview, Khvatov denied personally benefiting from the tissue trade. "It's a fairy tale," he said. "If I were taking cash, my own side would put me to jail." The institute, however, was receiving fees for shipping, he said.

Once the tissue was in the U.S., tissue banks would take the bones and charge $5,000 to $10,000 for different parts of the processed tissue‹up to $30,000, or six times Khvatov's wholesale price, for all of the tissue, according to FDA investigative summaries.

Records show that most of the tissue went to Allotech of El Paso, Texas. It distributed 3,000 pieces of tissue, according to an FDA investigative report. Two San Antonio businesses, Transplant Technologies Inc. and International Tissue Services, bought bone from Allotech, FDA records show. From those outlets, the Russian tissue was shipped to hospitals and tissue banks in 30 states, Puerto Rico and Mexico, FDA records show.

Khvatov also worked with a company called Flark Medical in Miami Beach, brought in more tissue and sold it to a tissue bank in San Diego, FDA records show. When FDA investigators researched the company in early 1994, they reported Flark's estimated annual income was $240,000 from the tissue business. Khvatov and his U.S. liaisons assured tissue banks that the cadavers were tested for diseases. But the FDA, with the help of the Pennsylvania Regional Tissue Bank, bought some of the Russian bones and found them to be contaminated.

"The samples were tested and found to be remarkably hepatitis positive," said David Kessler, who was FDA commissioner at the time and is now dean of Yale University Medical School. "We were getting the medical records, but they were all forgeries."

Those medical records often were incomplete, investigators found, and they were always in Russian. Few tissue banks in the U.S. bothered to have them translated. What's more, records showed that families of the deceased Russians were never asked for permission to take their bones.

Russian officials told the FDA that tissue can be taken from bodies there without permission. That meant no relatives were asked whether the deceased donor had used drugs, had contracted diseases such as AIDS or had engaged in "high-risk" behavior. Such questions are routinely asked of donor families in the U.S.

In late 1993, the FDA ordered a recall of all the Russian tissue, saying the tissue banks "lacked documentation about the donors' relevant medical history relative to ... hepatitis B, hepatitis C, or human immunodeficiency virus [HIV] infection." The tissue banks recovered about 90 percent of the Russian bone during the recall, FDA officials say. That still left 500 pieces of bone in circulation, and almost 100 were used in transplants, the FDA determined. There is no evidence to date that anyone has become ill from a Russian bone transplant.

The Russian case spurred the FDA's most forceful effort to regulate tissue. Kessler issued an emergency rule in 1993 that required U.S. tissue banks to screen all domestic donors and to give each donor a distinct number that would allow the agency to track the tissue. Importers also were required to get an FDA inspector's approval for each shipment based on paperwork showing that the tissue had been tested and is disease-free. In 1998, these became formal regulations.

The FDA took no legal action against those involved in the Russian imports, other than ordering recalls and issuing warning letters. FDA regulations, however, don't require doctors to tell patients about recalls. Some within the FDA wanted to pursue criminal charges, but that had never been done before. The Justice Department was reluctant to build a case, and the FDA at that time had few laws and regulations on tissue to cite for criminal charges.

The paperwork that accompanies imports isn't always a guarantee that the goods are safe. Imported cells like the ones produced in Cali by Dr. Duenas don't fall under the tissue regulations, but the FDA standards for testing are similar.

Since the early 1990s, Duenas had been shipping kidneys from Cali, each with documents purporting to show that all the FDA's procedures had been followed. Only in 1998 did FDA inspectors determine that the forms didn't fully explain how the kidneys had been screened for disease, just who gave the consent for the donation and what had caused the death of each infant.

Duenas, in an interview, said he formed In Vitro in 1990 and ran it from the university. BioWhittaker, he said, provided him with two machines to store the cells, as well as disease-testing kits and $70,000 a year, of which $48,000 was used to pay two employees.

Dead babies weighing 1 to 3.3 pounds yield the most useable kidney cells, he said. A tissue sample from one baby could fill anywhere from eight to 20 pinkie-size containers of kidney cells. Shipments of about 100 such containers were made to BioWhittaker two to five times a year, he said.

Duenas said he was gathering kidneys for his own research, and sending the leftover cells to BioWhittaker. "Do we throw the remaining cells in the sink?" he asked. "We get so many we can't use them all."

Duenas said he did not tell his colleagues he was shipping cells to BioWhittaker because "The culture is not right." Anti-American sentiment is strong in Colombia, he said, and word of his exports could have put him at risk.

Abbott ceased production of Abbokinase after the FDA questioned the safety of the Cali cells used in the drugs. BioWhittaker declined to discuss the Cali imports. But the company and Abbott have argued in letters to the FDA that the cell collection was done properly and was safe.

"Informed consent in Spanish was obtained prior to cell donation," said Rhonda Luniak, Abbott spokeswoman. "The medical information about the donor's mother was recorded, and extensive screening and testing was done."

A visit by a Tribune reporter to Duenas' lab and the sites where he collected the neonatal kidneys, however, raises questions about what was happening in Cali. University of Valle hospital workers say parental consent was not sought. Several parents, they said, had even complained about the two incisions in their babies' backs when they picked up the bodies for burial.

"We don't ask if they'll let us take a sample," said Maria Eugenia Rojas, a university hospital social worker. "But if they ask us for the cadaver immediately or if they ask us not to sample, we respect that" and don't take the kidneys. After the FDA halted the kidney imports, activity at Duenas' lab fell off and eventually stopped, hospital workers say.

As for Abbott, Luniak said it has "terminated our procurement of cells from outside the United States, and we are committed to finding a domestic source." If that source is found, she said, Abbokinase may return to the market by the end of 2001.

The export of tissue is scrutinized less than importation, and donor families in the U.S. usually have no idea that part of their loved ones may be going overseas.

U.S. doctors, for instance, prefer not to use the bones and bone powder of some elderly donors, but the same items are in demand in some foreign countries. And so, trying to increase revenue, some tissue banks seek elderly donors for tissue export. But donor records and interviews with families who donated a deceased relative's tissue reveal that tissue banks often don't inform families that parts of their loved one's body could end up in another country.

"My husband was not [registered as] an organ donor, and I did it against his wishes," said Linda Johnson of Orange, Calif., whose husband, Dennis, died five years ago. "And now I know I'm getting my comeuppance. "I did the moral thing to help other people, and then to find out they sent it to Europe."

Dennis Johnson's case was indeed just one of dozens in which tissue banks channeled the bones and tendons they harvested to Biodynamics International, which shipped them to its German plant for processing, and then sent them back to the U.S. for sale to hospitals, doctors and other outlets.

When told of the overseas trade, most donor family members interviewed by the Tribune were distressed.

Dorothy Newberry of Ocala, Fla., was among them. She agreed to donate her husband Arthur's tissue when he died in 1994. The University of Florida Tissue Bank representative called and told her that the tissue "could be used to do research to help other people, possibly save someone's life," she recalled. Newberry gave her consent. "I was so upset at that point, it was more, 'OK, let's go, because we've got to get to the funeral parlor. ...' There was just so much, it was a little overwhelming."

The tissue went to Germany and back without her knowledge. "They never said it was going to leave the country," she said. "The part that is troubling is if they're just making a profit for their own benefit. I mean, charity begins at home."

BSE -- the epidemic continues

1 May 00MAFF, excerpts from a 37 page report pdf
... 2. In Great Britain the number of suspected BSE cases placed under restriction in 2000 up to 30 April was 734 compared with 1,232 in the same period in 1999. A graph showing the progress of the BSE epidemic is attached at Figure 1. This shows the cases of BSE by month of clinical onset where the date of clinical onset is known. The numbers of suspect cases and diagnoses as at 30 April are provided in Table 1.

3. Of the 734 animals restricted in Great Britain in 2000 to 30 April, 678 animals were reported as having been slaughtered. There are 34 animals for which slaughter has not yet been reported and 22 had restrictions lifted due to alternative diagnosis. Of the animals slaughtered, there have been 328 cases where BSE was confirmed (972 confirmed cases at the same time in 1999) and 62 cases where BSE was not confirmed, with 288 diagnoses still outstanding. These figures are summarised in Table 1a.

4. In Northern Ireland the number of suspected BSE cases placed under restriction in 2000 up to 30 April was 8 compared with 3 in the same period in 1999. Of the 8 suspects, BSE has been confirmed in 1 animal to the end of April compared to 3 in the same period in 1999. There is no evidence to suggest the decline in the epidemic is not continuing and the increase in the number of suspects is believed to be as a direct result of the action outlined in paragraphs 5 and 6 below. The numbers of suspect cases and diagnoses as at 30 April are provided in Table 1. ...

7. Although a few cases still occur in older animals, most are in animals born after the ban on the feeding of ruminant proteins to ruminants was introduced on 18 July 1988 in GB and 11 January 1989 in Northern Ireland. Table 2 and Figure 2 show the number of cases of BSE in animals born after the 1988 ban by month and year of their births in GB. Up to 30 April 2000, BSE was confirmed in a cumulative total of 224 cases born after the 1989 ban in Northern Ireland (219 at the same time in 1999).

8. Additional information relating to cases restricted during 1999 and 2000, is included in Table 3 and 4. Table 3a and 3b summarise the confirmed cases first placed under restriction in 1999 and 2000 respectively by age at clinical onset where known; and Table 4a and 4b lists these cases by region/county in the United Kingdom.

9. At 30 April a total of 183 suspect animals born after 1 January 1996 (176 in Great Britain and 7 in Northern Ireland) have been restricted as BSE suspects. So far, of the 138 animals reported as having been slaughtered, BSE has been confirmed in only 1 animal (born January 1996) and not confirmed in 120. Further information is included in Table 5.

nvCJD Cases

10. The latest figures, published by the Department of Health on 5 May 2000, as at 28 April 2000, show a total of 68 definite and probable cases of vCJD. Details are set out in Table 6. Year vCJD probable vCJD probable deaths vCJD deaths Total still alive awaiting post-mortem confirmed*
1995        -                  -                  3           3
1996        -                  -                  10          10
1997        -                  -                  10          10
1998        -                  -                  17          17
1999        -                  1                  12          13
2000+       10                 1                  4           15
Total                                                         68
[includes 3 probable cases where neuropathological confirmation will never be available]

Suspect cases born after the feed ban of 01 January 1996

24 May 2000.  See MAFF for text and charts and recent BSE publications 
"In view of the additional measures taken in 1996 to prevent transmission of BSE there is considerable interest in whether or not BSE suspects born in 1996 or later have been investigated and confirmed. While these are important, it has to be recognised that throughout the epidemic MAFF veterinary officers have always been presented with suspects of any age, but showing neurological symptoms which could be attributable to BSE. We do not rule out BSE simply because the suspect is considered too young. We have to bear in mind that the youngest confirmed case was only 20 months of age, and this would not have been recognised if BSE had been ruled out on the basis of age.

The following table summarises the outcome of investigations into suspicion of disease in cattle born in 1996 or later. They are just part of the greater effort, but have been presented in this way at the request of the European Commission so that it can monitor the effectiveness of the 1996 measures, and our efforts to test that effectiveness by investigating disease in animals born in this time period.

(1) Total restricted Only cases showing clinical signs suspicious of BSE are placed under restriction. Some suspects reported by owners will not on close examination justify service of restrictions. This total does not include animals submitted post mortem by the owners for differential diagnosis, or cases identified as part of a post mortem survey.

(2) Restrictions lifted: Some cases, having been placed under restriction on suspicion of BSE may later recover, or the veterinary surgeon, MAFF veterinary officer and farmer will arrive at an alternative diagnosis. Restrictions are therefore lifted.

(3) Not yet notified: Suspects under restriction but slaughter has not yet been notified to HQ

(4) Total slaughtered: Compulsory slaughter only takes place when suspicion of BSE on the part of the veterinary officer becomes belief that the suspect is actually affected with the disease. While in many instances the two are synonymous, and will take place on the same day, some cases may present only some of the signs typical of BSE. Subject to considerations for the welfare of the animal, and the health and safety of those who have to handle a potentially dangerous cow, slaughter may not take place until one or more further clinical examinations have been completed. Where initial signs are very slight, a delay of several months is possible.

(5) BSE confirmed: For the reasons given below, confirmation is significantly in arrears of restriction and slaughter.

(6) Diagnosis pending: Slaughtered cases for which there is yet no final diagnosis. After slaughter, brain tissue is removed for examination by a laboratory of the Veterinary Laboratories Agency and results are passed to headquarters at Page St, London for eventual confirmation. Because of the delays due to laboratory examination and to the movement of paper from Animal Health Offices to Page St, London, there is always a significant lag between slaughter and the provision of a final outcome. This may affect cases slaughtered during the current year and even some of those slaughtered at the end of the previous year. The delay between slaughter and confirmation may be some 6-8 weeks for routine cases but could be considerably longer in cases where additional tests or further on-farm investigations are requested.

EU, citing scientific findings, to continue ban on hormone-treated beef

24 May 2000 United Press International
The European Commission Wednesday continued its ban against U.S. hormone-treated beef, citing an EU scientific panel assertion that some growth-promoting hormones used in the cattle are a health risk to humans and bear out EU concerns they could promote cancer.

The EU has been wrestling over ban since the 1998 World Trade Organization ruling that the EU needed more scientific evidence to back up its ban. Without any such evidence, the WTO had ruled, it must allow U.S. beef imports.

But Wednesday's statement declaring the ban will continue, said the scientific panel findings allow the EU to maintain its "chosen high level of protection." A WTO arbitration panel ruled in 1998 that the EU's ban on hormone-treated beef imports is illegal and last year the WTO allowed the United States and Canada to slap about $24 million in sanctions per year in retaliation on EU goods for beef producers' loss of trade.

The EU also announced proposals Wednesday that it said sought to end the long-running dispute. Based on the studies, the Commission proposed that the EU council and Parliament adopt legislation, which is expected to be in force by July 1, 2001, to permanently ban one natural growth-promoting hormone, 17B-oestradiol, while maintaining a temporary ban on five others, including two natural hormones progesterone and testosterone and three synthetic hormones, zeronol, trenbolone acetate and melengestrol acetate.

"We believe that this will bring us into line with the panel findings to finally resolve the panel's decision,'' said EU Commission spokesman Anthony Gooch said. "We need to base ourselves on legislation and we're doing this on the basis of scientific evidence,'' Gooch said.

Gooch said that the EU plans to ask the WTO panel to lift the sanctions because its import ban will be based on scientifically-supported legislation. The issue has long been contentious. The U.S. nearly one year ago imposed $117 million of retaliatory tariffs against specified EU products, including certain French cheeses, Danish ham, and certain chocolates.

American trade negotiators claim U.S. beef producers and exporters have lost up to $202 million yearly because Europe has declined to comply with the WTO order that the EU accept the beef.

Noting that the amount of U.S. beef fed growth hormones accounts for 95 percent of U.S. beef exports, The National Cattlemen's Beef Association claims the ban has cost much more -- as much as $500 million yearly. Earlier this year, charges arose that the U.S. cattlemen were sending over hormone-fed beef despite the ban.

"We would like to see the basis of the new information. As far as we know, there is no new scientific evidence,'' a U.S. official, who asked not to be named, said.

The Times of London reported British food inspectors told the British government "U.S. federal food inspection service had falsely certified the export of meat -- beef, pork, and horse -- to the EU since May 1999." The U.S. Department of Agriculture disputed the inspectors' findings and criticisms.

EU ministers say the ban must stay in place because of scientific concerns of cancer and also raised concern about possible damage to children's immune systems.

And, in March, the British Broadcasting Corporation reported other concerns about U.S. hormone-treated meat -- or any U.S. meats, for that matter. The report cited fears that some US laboratories were unable to detect hormone traces in meat, and that some farmers used hormones without veterinary supervision and without following manufacturers' instructions.

More tainted feed found in Belgium

Sat, May 20, 2000 By RAF CASERT  Associated Press Writer
One year after the dioxin crisis forced the wholesale destruction of meat and dairy products, the government shutdown 200 farms Saturday, hoping to prevent the distribution of cancer-causing pollution in the food chain.

Farm Minister Jaak Gabriels said 205 farms were under investigation for taking fodder from a company where animal feed contaminated with cancer-causing PCB was discovered. The pollution was 925 times above the legal limit.

"This is very serious and we are doing our utmost to contain the pollution," said Gabriels. So far, there were no indications contaminated meat had reached consumers. "The good thing is we were quick to react," reducing chances it had spread far," said Gabriels. Earlier this month, routine tests showed PCB in the fodder company Bauduin-Cambier, in Feluy, 25 miles south of Brussels.

PCB pollution has similar effects on human health as dioxin. The dioxin scandal hit Belgium in May 1999, when the government announced that high levels of the cancer-causing chemical had been discovered in eggs, meat and dairy products. The fear led to a wide range of products being pulled from the shelves, causing the biggest food safety scandal in Europe since the 1996 Mad Cow crisis in Britain.

Belgian food was banned all over the world and exporters have been trying to shore up confidence in Belgian exports ever since. Belgium instituted a series of control mechanisms to avoid a repeat of the damaging crisis and Gabriels said the early warning tests had been instrumental in containing the crisis. The government said it had carried out some 3,000 tests on fodder companies since last year's scandal.

Of the affected farms, 147 raise cattle, 48 breed horses and 7 produce pigs. A poultry farm and two pet food producers make up the total. Unlike last year, when Belgium was extremely slow in warning the European Union it was faced with a dioxin crisis, Gabriels said his services had already approached the EU headquarters with information.

Dioxin contamination of feed and food

Lancet 2000; 355: 1883 
M Neuberger, R Grossgut, J Gyimothy, J Leibetseder 
A preventive action limit for dioxins in feed for broiler chickens and pigs was set to 2 pg toxic equivalents/g feed in Austria. This limit was effective in the detection of feed contamination from an imported mineral additive [kaolinite], and in the prevention of food contamination according to WHO tolerable daily intake.

In 1998, WHO experts lowered the tolerable daily intake (TDI) to 1-4 pg toxic equivalents (TEQ) per kg bodyweight, and recommended that every effort be made to reduce exposure to the lowest possible level.1 More than 90% of human exposure to polychlorinated dibenzo-p-dioxins and polychlorinated furans (PCDD/Fs) is from food, mainly animal fat. Chloracne and other chronic symptoms have been reported in Japan from rice oil, and in Spain from olive oil contaminated with PCDD/Fs. Recently, the Belgian government failed to be re-elected because it had provided very late information on food contamination from animal feed. Contamination was first discovered in chickens. About 8 litres of used polychlorinated biphenyl ended up in an 80 tonne batch of recycled fats used in production of 32,000,000 pounds of animal feed. In the first sample from a dead hen analysed for PCDD/Fs, 958 pg TEQ/g fat were found.

The member states of the European Union were faced with the difficult task of tracing the contamination and setting prelimiary standards to protect consumers from additional body loads, without knowledge of transfer rates from feed to food. Austria, the first country to lower PCDD/F emission standards, set preventive action limits for feed.

Comment (webmaster): This issue of Lancet had a number of good articles on dioxin, including one on abnormal sex ratios in children of the survivors of the exposion at Seveso, Italy, where a pesticide factory released a collossal 32 pounds of dioxins (many billions of doses) into the surrounding town.

Role of immune system in prion disease unravelled

Thu, May 18, 2000 By Maggie Fox, Health and Science Correspondent, Reuters
Scientists on Thursday said they had fresh insights into how the immune system is involved in the spread of mad cow disease, and that the discovery could provide a route to an eventual treatment. But they stressed that any treatment for the deadly and incurable brain illness is a long way away, and that they are only just beginning to understand how proteins that cause mad cow disease spread.

Mad cow disease, known formally as bovine spongiform encephalopathy (BSE), raged through British herds in the 1980s and is still found in the occasional European herd. It has spread to humans, causing a deadly brain illness called variant Creutzfeldt-Jakob Disease (vCJD) that has killed more than 50 people in Britain.

Doctors do not yet know whether a human epidemic is waiting to break out, as the incubation period for the disease can last decades. They believe people became infected by eating contaminated beef. BSE, CJD and related diseases such as scrapie are caused by prions -- which are normal brain and nervous system proteins -- that have mutated into an unusual form.

Charles Weissmann of the Imperial College School of Medicine in London and colleagues at Biogen in Cambridge, Mass., and the University of Zurich in Switzerland have worked to find ways to prevent the mutated prions from spreading through the nervous system. Writing in the journal Science, they said prions seem to be produced by immune cells in the spleen known as follicular dendritic cells (FDCs).

These FDCs need the help of other immune cells, called B cells, to mature and stay alive. These B cells carry on their surface a signaling molecule called a lymphotoxin. Weissman's team found a way to de-activate this lymphotoxin in mice and said it stopped the build-up of prions in the spleen.

Although prions cause disease in the brain, they are transmitted elsewhere, usually by eating infected food. They survive digestion and get to the spleen, where they travel to the lymph glands and, Weissmann said, along the nerves. "It is like an amplification," he said in a telephone interview. He said the spleen, which produces immune system cells, is rich in nerves, and researchers believe the prions get into the nerves there, travel to the spine and then to the brain.

"We call it the domino theory," he said. Nerve cells carry normal prions, and the mutated ones are somehow able to convert them into the disease-causing form. No one knows what role normal prions play in brain cells, and mice bred to lack the proteins seem normal in every way.

Weissman's team was able to stop the amplification step by giving the mice a lymphotoxin receptor, which seemed to soak up the lymphotoxin from the B cells. This, in turn, stopped them from nurturing the FDCs that produce the prions. Weissmann stressed that the research was highly experimental and done only in mice.

"I think this is fraught with problems because obviously even in mice it only works well if you block the FDCs (right) after infection," he said. "The question really is how do you know someone has got a dose of infectivity?" But the researchers said their findings could eventually lead to a way to treat people for CJD.

French food safety agency backs ban on cow intestines

Thu, May 18, 2000 AP WorldStream
France's food safety agency on Thursday said it backed a proposal to ban the sale of cow intestines and other innards as part of the battle against bovine spongiform encephalopathy, known as mad cow disease. In a statement, the agency, known as AFSSA, said it also supported tighter controls on the sale of cow brain and spinal tissue. The agency called for more research into human consumption of cow, sheep and goat products.

The announcement comes amid fears over the spread of mad cow disease in France. Authorities recently said that new tests were to be carried out across the country this year. Thirty-one cases of mad cow disease were detected in France in 1999, up from 18 in 1998. Agriculture Minister Jean Glavany conceded last month that a "mysterious, third way" of spreading the disease was suspected by French officials, who had previously thought it was passed from cow-to-calf or through animal-based feeds.

The animal parts called into question by the proposed ban are used in the preparation of certain regional specialties and are considered delicacies in France. If taken up by the government, the ban would pose a direct threat to French butchers and the country's processed meats industry. It would affect animals born before May 1, 1999.

A study published Thursday in the French newspaper Le Monde said that French butchers sell an estimated 20,000 tons a year of pork delicacies and other products encased in cow intestine.

France has resisted pressure from both Britain and the European Union Commission to drop its embargo on imported British beef, arguing that not enough was known about mad cow disease for the ban to be lifted.

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