Brain trust: Local scientist, world-renowned expert reflects on half century of work with TSEs

After a half century of being on the cutting edge of transmissible brain disease research, a retired Hamilton pathologist knows when the public is being mislead about diseases such as mad cow disease. That’s what’s currently happening as the U.S. continues to react to its first reported case in a Washington state dairy cow, according to Dr. Bill Hadlow.

By ROD DANIEL Staff Reporter

http://www.ravallinews.com/articles/2004/04/21/news/news01.txt

Hadlow, who retired in 1987 from a storied, 35-year research career at Rocky Mountain Laboratories, said important information has been left out of most media reports about bovine spongiform encephalopathy (BSE), popularly known as mad cow disease.

Hadlow was one of the first scientists in the world to study what are now known as transmissible spongiform encephalopathies, or TSEs, when in 1958 as a young veterinary pathologist in Hamilton, he was sent to the Agricultural Research Council Field Station in Compton, England, to study a degenerative disease of goats and sheep known as scrapie. Hadlow said the three years he spent intensively looking at infected brain tissue under a light microscope allowed him to perfect his observational techniques in the lab and eventually led him to be considered one of the world’s foremost authorities on such neurological diseases.

"We had hundreds of infected sheep and goats, but we didn’t at the time even know if it was a disease of the central nervous system," Hadlow recalled. "It was great. We used to cut these big cross-sections of a sheep brain. They pretty much left me alone and I spent three years looking at brains."

Those early years of scrapie research were particularly productive, he said, because unlike today, there were few restrictions on the treatment of lab animals used for research.

"We had all kinds of material to work on," he said. "They used to salvage lab animals and then sell them to the meat market. I’d get the parts I needed (for research) and they’d take the rest."

After completing his three-year stint in England, paid for by the U.S. Department of Agriculture, Hadlow said he had a couple of job opportunities fall through before he decided to return to his job at the lab in Hamilton.

"My wife was pregnant and I needed a job," he said. "So in April 1961, I came back to Hamilton. It was the same job I had before; the same stuff was still in the drawer."

Perhaps wanting to capitalize on Hadlow’s new-found expertise, fellow researcher Carl Ecklund became fascinated with scrapie and encouraged Hadlow to try to inoculate mice with the disease agent which, until that time, had only been successfully injected into sheep and goats. Hadlow learned at the time, he said, that one of his former colleagues in England, Dr. Dick Chandler, had just inoculated mice with scrapie.

"That’s all we needed," he said. "They sent me over to England, and I brought scrapie brain material back in a Thermos. On Sept. 15, 1961, I first inoculated mice with scrapie at the (Rocky Mountain) lab. That started it all as far as TSE research here."

For 16 years Hadlow and Ecklund conducted an extensive scrapie study at the lab, during which time other transmissible brain diseases surfaced throughout the world. With nearly each newly discovered disease, Hadlow was summoned to look at the infected brains.

In summer of 1963 he answered a phone call to the lab from a mink rancher in Blackfoot, Idaho, who thought he had toxoplasmosis in his mink. After examining sections of the infected mink brains, Hadlow observed that the tiny holes resembled scrapie.

Hadlow suspected the Idaho mink were infected with a brain disease similar to scrapie, so he traveled to a mink farm in northern Minnesota to view other infected mink.

"I brought back brains on dry ice in containers sealed with a welding torch," he said. "They let me on the plane with them, and I brought them back here."

Using a few healthy mink, Hadlow injected them with infected brain tissue, and in 1964 the mink started coming down with the disease. Deemed transmissible mink encephalopathy, the newly discovered disease, Hadlow said, was the second example of TSEs in animals, and was suspected to have come from mink feed made from cattle infected with an as yet unidentified encephalopathic agent. The suspected cattle were mainly downer dairy cows commonly used in preparing mink feed.

In 1966 the first human TSE was discovered in an isolated population of people native to Papua New Guinea. First described in 1957, the disease, called kuru, had long caused dementia and death in the natives, but no one had been able to trace its cause.

Dr. Carleton Gajdusek described the symptoms of the strange disease in a scientific paper read by Hadlow, who noted that the symptoms resembled those of scrapie. According to Dr. Byron Caughey, currently a researcher at RML, Hadlow hypothesized to the scientific community then that such a disease could be transmitted from humans to animals.

Gajdusek proved Hadlow’s hypothesis and at the same time causally linked the deadly disease to the practice of ritualistic cannibalism engaged in by the natives. Gajdusek received a Nobel prize for his work, and many people felt Hadlow should have shared the prize, Caughey said.

Creutzfeldt-Jakob disease, Hadlow said, was the next human disease to join the ranks of the TSEs, and like kuru was found to be experimentally transmissible to chimpanzees. A "so-called" variant form of CJD, Hadlow said, is mad cow disease.

Chronic wasting disease, Hadlow said, was known to infect captive mule deer, and in 1979, Beth Williams, a graduate student in veterinary pathology at Colorado State University, looked at the brains of CWD-infected deer and saw what looked like scrapie. Almost immediately she and her major professor contacted Hadlow.

"Williams’ professor brought me brain samples of the mule deer," Hadlow said, "and gave me my first experience with CWD."

Chronic wasting disease proved to be transmissible experimentally to mule deer, mink, domestic ferrets, squirrel monkeys and goats, Hadlow said, although its source and natural mode of transmission have yet to be determined.

Apart from being another fascinating example of a naturally occurring TSE, chronic wasting disease has practical implications for management of wildlife in free-ranging populations, Hadlow said, but any human health risk it may pose has yet to be identified.

No other TSE in man or animal has gotten more world-wide publicity than bovine spongiform encephalopathy, or BSE, popularly known as mad cow disease. It was identified in England in 1986, one year before Hadlow retired from Rocky Mountain Laboratories, by British researcher Gerald Wells. Three years later, Wells persuaded Hadlow to come over to England to take a closer look at BSE.

"I went to the UK in June 1990 and looked at 110 mad cow brains from stem to stern over the summer," Hadlow said. "I went back every year for 10 years. The last time I looked at tiger brains."

Today the retired-yet-active scientist still frequently spends time in his basement with his 50-plus-year-old Lietz microscope, looking at brain tissue. His half-century-long career has allowed him to work first-hand on almost every TSE ever discovered, giving him a unique perspective on the growing family of deadly diseases.

He credits his supervisors for allowing him to do his work with little interference.

"I was singularly fortunate that no one ever told me what to do," Hadlow said. "That was always true. I had the freedom to look at what I wanted."

The news in December of the Washington dairy cow infected with BSE came as a bit of a surprise to Hadlow, but the hysteria that followed was not unexpected, he said.

"I was surprised to some extent to see the disease in this country," he said. "But I think most people don’t have an understanding of what it’s all about. It’s a fatal disease and a horrible disease; that’s why it’s of such concern."

In an attempt to lessen the "unnecessary anxiety and poorly founded concerns," Hadlow said he offers some observations for people to chew on.

To begin with, he said, BSE is a specific infectious disease of adult cattle, caused by a single, feed-borne infectious agent that originated in the UK during the preparation of meat and bone meal from rendered animal material in the 1970s and 1980s. Cattle become infected by what they eat, especially as calves in the first six months, but the disease usually doesn’t appear for three to six years. It is not contagious and does not spread from one cow to another as do some other cattle diseases.

And despite comments in the press suggesting otherwise, he said, "there is no certain evidence of maternal or vertical transmission in the strict sense of calves becoming infected before birth."

"Nor is there evidence supporting the heretical notion the BSE has arisen on its own from inherently unstable prion protein," he said, "as proponents of the prion hypothesis would have us believe can happen."

Wherever BSE has occurred in the world, he said, including North America, it has resulted from infection with the BSE agent originating from the UK. The precise conditions considered responsible for its emergence in England do not exist in other countries, including the United States and Canada, he said.

After the dairy cows in Washington and Canada were revealed to have the disease, Hadlow said he contacted the scientists in England responsible for identifying it to make sure it was indeed the same agent that had been discovered there more than 20 years ago.

The affected cows in Washington and Canada, he said, had to have been infected with the BSE agent and no other, and it was certainly not from being fed rendered products prepared in North America, unless they had inadvertently been contaminated with the BSE agent.

Moreover, he said, the diseases in the two cows cannot be attributed to infection with any of the known related agents causing spongiform brain diseases in other North American animals – scrapie, chronic wasting disease and transmissible mink encephalopathy – none of which has been linked to human disease. The disease each one brings about in cattle is readily distinguished from BSE, and with all three, neither the clinical signs nor the pathologic changes in the brain are the same as those of BSE, he said.

Hadlow said any commentary on mad cow disease should take these observations into account to give it proper perspective.

Aside from staying abreast of new research on TSEs, Hadlow has taken up a new cause – spending his time, money and effort to support the American Livestock Breeds Conservatory, searching for rare books on livestock.

With piles of hardbacks next to his desk, he’s of late been researching and compiling the history of the Conestoga horse, a breed once common in Lancaster County, Pa., which went extinct sometime after the Civil War.

"I spend most of my time reading," he said, "since I don’t watch television. I used to go over to the lab once in awhile, but now my research is confined to my basement."

Reporter Rod Daniel can be reached at 363-3300 or [email protected]