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an online version of the magazine Spring/Summer 2004
Meat Muddle Photograph of meat and cleaver by Max Boam
  Neurologist Richard Johnson is now the recognized authority on mad cow disease. From that vantage point, he can see that America’s head is in the sand.
BY Marjorie Centofanti

The hiss of the gas lamp and ping of an occasional tropical beetle on its glass were the only sounds to break the nightly hum of insects as Richard Johnson leaned back, shaking his head. A fellow neurologist at Okapa ?eld station in Papua New Guinea was some yards away, angled over his beetle collection. Johnson rested the mimeographed pages on his lap, his thoughts tethered only by the fascination of the unthinkable: cannibalism.

It was 1964, and Johnson was far from being the authority he is today on diseases caused by the deviant proteins called prions—illnesses like mad cow or the lesser known but equally fatal kuru that devastated New Guinea in the ’50s and ’60s. But what he saw and did as a new postdoc in that part of the world marked the empirical approach—being there, seeing for himself—that has since stood him in good stead. For 40 years, he’s continued to land in the thick of things, to cut to the necessary questions and help plan minimal yet telling research. It’s given him perspective on bizarre diseases. And now, it has put him close to those who plan this country’s approach to mad cow and its odd relatives.

Johnson had been in Australia on a fellowship, studying the pathogenesis of herpes, rabies and mosquito-borne viruses. But when his advisor, who headed the Papua New Guinea Health Council, found the young researcher packing for a canoe-based virus hunt in that country’s swamps, he asked, “Dick, wouldn’t you also like a week’s detour to see kuru while you’re there?”

So Johnson found a bush pilot to drop him off in PNG’s tropical highlands. “Harrowing is too kind a word for that flight,” he says. “Imagine riding a gnat.” But it was worth it to see, firsthand, a disease he’d only read about.

By day, Johnson waded through yam patches to the hilltop villages of the Fore natives. As was customary, he saw patients in the public square who’d walked or been carried there. Mostly women, they trembled and shivered without pause. In the Fore tongue, kuru means shaking. It causes loss of balance, dementia and, like the other spongiform encephalopathies such as mad cow disease, a sure death. The Fore typically died in six months after symptom onset, believing, while they could still think, that they’d been victims of sorcery.

“The situation was nothing short of astonishing,” says Johnson. “In some villages seven out of eight women would ultimately die. Kuru just annihilated the Fore.”

By night, having little else to do, Johnson thought about the disease. He agreed with New Zealander Richard Hornebrook, the other neurologist there, who acted as his guide, that kuru primarily attacks the brain’s cerebellum rather than its basal ganglia. This was a correction to the original 1957 disease description.

But those evenings, Johnson also read the field notes and monographs that two cultural anthropologists, Robert Glasse and Shirley Lindenbaum, had left behind after living with the Fore. They’d been certain that kuru spread via the ritual cannibalism that tribe members practiced on the dead.

“I remember being absolutely stunned by the idea of cannibalism,” says Johnson, “I’d never seen anything tying it to kuru. But their data were totally convincing!” Women ate the tainted brain and other body parts, unlike men, who thought such stuff would sap their strength. Kuru’s incidence varied in the same way that who-ate-what differed from village to village. Eventually, studies showed the disease was indeed spread by cannibalism.



Richard Johnson in New Guinea Richard Johnson today
> Richard Johnson in New Guinea and today.
Today, Johnson is still caught up in the spongiform encephalopathies. His opinions are sought widely. He heads the nation’s foremost committee on the topic, set up by the Institute of Medicine to advise Congress, and he is representative neurologist on the FDA’s committee. Since last December, when news of the first U.S. “mad cow” got out, he’s also been the voice for three government agencies, including the NIH. One especially full week, Johnson’s grainy bass voice graced all three of NPR’s news programs. The next morning he was on NBC, mulling over Katie Couric’s fear of frying—sausage, that is—then back at his office to answer calls from reporters.

What’s odd, Johnson admits with his broad grin, is that although every year in Hopkins’ neurology clinic he does see several patients with the prion disease Creutzfeldt-Jakob disease (CJD), he does no research on prion diseases or the agents that likely cause them.

Why, then, is Johnson so often picked to play “Mr. Mad Cow”?

For one thing, he’s done masses of lab and clinical work on infections of the nervous system. After serving as director of neurology at Hopkins for almost a decade, he stepped down in 1996 to help found the National Neuroscience Institute in Singapore. Now, he edits the Annals of Neurology. Colleagues speak of him as the “father of neurovirology.”

But as important, in the years since his session with the Fore, Johnson has stayed pressed against the window of prion disease work. He examined, for instance, the animals that NIH researchers Carleton Gajdusek and Joe Gibbs inoculated with the finely ground brains of kuru victims—the required step to prove infectious agents cause a disease.

“Joe called me and said, ‘A couple of them might be coming down with kuru. Come see what you think.’ I had a look,” Johnson says. “It was uncanny how similar the chimps were to the kuru patients I’d seen. Their tissues looked identical.” All the spongiform encephalopathies turn brains to lace.

Later, Gibbs and Gajdusek proved that CJD, like kuru, could be infectious. The work gave Gajdusek a Nobel Prize in 1976.

Still, says Johnson “nobody in the 1970s knew about prions.” We thought the ‘unconventional agents’ causing kuru, scrapie [the prion disease of sheep] and CJD were mysteriously slow-acting viruses.” But no researcher then, or now, has ever found viruses or viral antibodies in humans or animals with these diseases.




It took an unknown named Stanley Prusiner to fan everyone’s interest in prion disease. And it was Prusiner’s bumpy scientific road that gave Johnson his reputation as a level-headed observer.

Johnson had just finished a guest lecture at the University of California, San Francisco, in the early 1980s when Prusiner, a neurology resident at the time, approached and asked him to lunch. Prusiner was a bright young biochemist who groused, while they ate, about the lack of scientific rigor in scrapie studies, about the slowness at incubating the “unconventional agent” in animals and, consequently, at the delay in identifying it. “I’m going to change this whole field by getting a rapid test,” he told Johnson. The elder scientist encouraged him and the two became friends.

Prusiner did develop a quicker assay for scrapie, one that used hamsters, which sicken faster than mice. He also found a way to track characteristic brain changes before the animals’ brain tissue grew spongy. In April 1982, with unusually noisy fanfare (he’d hired a PR agency) Prusiner reported in Science that scrapie was likely caused by an odd protein—and only a protein—making it the tiniest infectious agent ever. Boil it, soak it in formaldehyde or alcohol, subject it to UV light or X-rays—actions that inactivate bacteria or viruses—and it’s still infective.

Prusiner named the protein a “prion,” for proteinaceous infectious particle (with a vowel switch for euphony). But he still hadn’t isolated prions. Sitting wide-eyed on the first new principle of disease in a century, he’d been desperate to publish. But many scientists thought Prusiner’s speculations on how the “organism” works were half-baked. And the small band of mostly British researchers who’d slogged for years looking for a slow, elusive virus they believed caused scrapie must have dreaded missing the boat.

“That was enough,” Johnson remembers, “for all hell to break loose. Editorials about the study in Nature and The Lancet were scathing.” Many science writers still consider an article about Prusiner in the popular magazine Discover the most vitriolic piece of our age about a scientist. It even included guest bashings by Prusiner’s postdocs.

Johnson watched from afar: “Stanley didn’t understand why people were so upset,” he says. Prusiner also didn’t see that, in anger at what they thought was a too-early, hyped pronouncement, some scientists had begun discounting his results. Johnson finally wrote an editorial in Trends in NeuroSciences that quietly explained why Prusiner’s research was sound. From a platform of sympathy for the unhappy researchers, he zeroed in on what riled them most: that Prusiner had had the gall to name the infectious agent before he’d isolated it!

“As a traditional virologist,” Johnson wrote, “I could question whether enough is known to adopt a formal name.” But he reminded those tempted to throw out the baby with the bath water that Prusiner was still at work and had begun presenting hard evidence that he had isolated prions.

Since then, Johnson has followed the work coming out of the prion labs that have now sprouted in the United States and—with mad cow the impetus for funding—across Europe. His recent work on HIV neuropathology at the NIH’s Rocky Mountain Labs in Montana puts him literally next door to one of the other U.S. camps of prion researchers.

But Johnson still insists he’s called to the policy committees in Washington because he’s knowledgeable and doesn’t rile anyone: “I’m older than most of these guys in research,” he says, “and I know them well.”

To his fellow scientists, however, Richard Johnson is a rare commodity: He’s seen it all and doesn’t take sides.

Q. Are fears of getting a prion disease here warranted?
A. The chance is minuscule. But people are stirred because the diseases are 100 percent fatal. Also, the long incubation period is frightening, the time bomb idea. The thought that the sausage you ate for breakfast could give you a dreadful disease 20 years from now isn’t a happy one.
Q. Is the real difficulty that we can’t spot mad cow in live animals?
A. Right. Our usual live-animal tests won’t work with prions because they’re a self-protein gone wrong. Animals don’t produce antibodies. And there’s no RNA. Still, it wouldn’t be unreasonable to follow Europe: Check all downers and all animals older than 30 months.
Q. What else would you advise?
A. We should watch what gets into the grocery store. Obviously, you don’t process brains and spinal cords. But gut and lymphoid tissue are also infective. Get rid of it! I’d hate to think what’s in scrapple. Also, we need to monitor nutritional supplements. People are out there legally selling raw ground cow brains as health pills!
Q. What worries you most?
A. Chronic wasting disease (CWD). It’s a spongiform encephalopathy of wildlife, mostly out West. Only a handful of people in this country work on it. Mad cow is transferred by feed. There’s no evidence of transmission from animal to animal. CWD is different. It apparently crosses species, from mule deer to regular deer or elk. Deer share pastures with cattle and sheep. Scary? You bet.
Q. Is this country missing cases of mad cow in people?
A. We could be. If we had a first-rate autopsy system, we’d be better off. I feel strongly we’re not going to learn if spongiform encephalopathies exist here until we do autopsies on every person dying of a chronic, degenerative nervous system disease.
Q. But isn’t a prion-disease epidemic here unlikely because we’re aware now?
A. Just because you haven’t seen something before, doesn’t mean it isn’t possible. Just in the last few months, there’s evidence CJD may be spread through transfusions and that a second strain of mad cow has appeared. With these diseases, you expect the unexpected.
 A Remedy of Errors
 Childhood Trials
 Meat Muddle
 Circling the Dome
 Medical Rounds
 Annals of Hopkins
 Learning Curve
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