Submitted By Barry Coyne '59

 

Meeting the Challenge: Upgrading Our Downtown

 

By Barry-Lee Coyne '59

 

Salem, OR, where I currently live, is thousands of miles away from my birthplace of Brooklyn and Jamaica HS, where I got my early training as a civic activist.

However, over half a century later, that passion for "making things happen" remains as strong as ever.    Salem is somewhat more conservative and so the art

of building coalitions is that much more challenging.

 

The name Salem is derived from the Hebrew word for peace - Shalom.  Many of our local people never made that connection.  I decided to do my best to help

fill that gap in a visual way: creating a public art mural.  Some tagged me as a well-meaning visionary, but I was determined to see that vision materialize.

 

At first I wrote to our former mayor, Janet Taylor.  She liked the basic idea but urged me to create a vehicle to move it forward.  This I did by bringing together

the arts community and several pro-peace organizations.  We met in a local coffeehouse starting in mid-2009.  Then we invited guest speakers ranging from the

founder of a suburban mural society to a high school art chairmen to a police officer handling graffiti problems.  Our goal was to involve youth in planning the

design.  We saw this project as one to unify the larger community.

 

Our first roadblock was an obsolete law which bunched together public art and wall sign advertisements.  Both were subject to very restricted size.  We were able

to persuade our city council to pass a new statute that permitted murals of any size, to be reviewed in advance by a new public art commission.  Then we looked

around for a downtown site to beautify.  Our first choice was the coffeehouse where we met.  However, our hopes were dashed when the properietor expressed

strong doubts based on fear of graffiti.  By this time, we had located a talented artist who worked in mosaics rather than paints.  Still, he resisted our proposal.

 

That building was next door to the local YMCA, just down the street from our State Capitol.  That was a prime location.  Ironically, the Y had a new administration

and was already planning a facelift.  Our artist did a power-point of her past achievements and they were impressed.  The art association link would do outreach

to local schools to participate.  What was missing was the money for the lead artist and the materials we would need to puchase.

 

From having Zero in funds, the only way was up.  These were the steps we took:

      -- We obtained a $4000 grant from our state's art commission;

      -- Next a statewide peace organization donated another $1500;

      -- Various churches and individuals contributed and helped;

      -- In a matter of months, we had gathered a $12,000 budget.

 

In addition to the artwork, poetry was recruited.  Our state's poet laureatte, Paulann Peterson, wrote a short but poignant poem that was woven into mosaic.

Two giant mandelas emerged as part of the design, along with a flowing river sandwiched between two large trees, one with human faces and the other with

wild animals.  The inference was that we had to live in harmony to make peace into a reality.  

 

A dedication took place last August.  We staged a street party, replete with speakers, musicians, and dancing.   Salem had finally become of age.  This has

resulted in new momentum to upgrade a blighted bus terminal nearby and seek out a public university campus for the downtown area.  However, our 40-ft.

Peace Mosaic remains the newest landmark in town. 

 

To get a glimpse, go to: www.salempeacemosaic.org.  Perhaps your town also needs a similar booster shot.

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(Mr. Coyne invites comments at: luckycoyne@yahoo.com).

 

 

Submitted by Bernard Edinger '59

Remember Laura Kirchman '59

Bernie found this Article in Science Magazine and received Laura's permission to share it with us.

 

 

She’s not the only prion doubter, but her voice is by far the loudest. In part that’s because she’s safe. Long a tenured profes- sor at Yale, Manuelidis still commands vast lab space she no longer uses. Her unpopu- larity among top prion scientists leaves her unfazed. “What can they do to me?” she says. “If I don’t say it, nobody’s going to say it.”

Beginnings

In her youth, Manuelidis aspired to be a poet. She enrolled at Sarah Lawrence Col- lege, a small liberal arts school outside New York City known for its strong focus on the arts and literature. Her older brother, with whom she’d always been close, was attend- ing Harvard Medical School at the time. “He said, ‘I don’t see any want ads in The New York Times for poets. ... How long are you going to be a parasite on Mom and Dad?’ ”

Manuelidis considered this problem and settled on medical school as an alternative. “My brother said, ‘Why don’t you become a nurse?’ and I said, ‘Why don’t you become a nurse?’ ” she remembers. “He wanted a normal sister.”

In medical school she knew from the start that she would focus on the brain, hoping to cure schizophrenia. Manuelidis had been deeply affected by college sum- mers spent volunteering at Waltham State Hospital outside Boston, where she says patients were rarely seen by physicians. (“I looked in the charts” to find out.) They were so heavily drugged that they reeked of Thorazine, an antipsychotic drug. “I saw people with frontal lobotomies,” she says. “I felt there was a certain arrogance in med- icine. It was very good to see before I went to medical school.”

Manuelidis embraced pathology, encouraged by a supportive department chair. Another draw was her neuropatholo- gist husband-to-be, a confirmed bachelor when she met him. Their relationship was scandalous, she says. They lived together openly and threw large parties at his house attended by many of her friends.

The two began exploring a class of deadly diseases called transmissible spon- giform encephalopathies (TSEs), so named because once symptoms surface, the brain turns into spongy tissue with alarming speed. TSEs in people are rare; the most prevalent, sporadic Creutzfeldt-Jakob dis- ease, strikes about one person in 1 million each year. A curious feature is that TSEs, like viral diseases, can be passed from one animal to another by injecting affected brain tissue. TSEs also have a long latency period in animals. The first guinea pigs

Elias Manuelidis exposed to TSE thrived for 500 days before getting sick.

But the virus, if there was one, was elu- sive. Some experiments indicated that there couldn’t be a virus at all. A radiobiologist named Tikvah Alper showed in the 1960s that blasting infected tissue with radia- tion didn’t destroy its ability to infect. And exposing tissue to high heat failed to pre- vent transmission of a TSE called scrapie, which kills sheep and goats. Strategies that annihilate the usual viruses didn’t do much to halt disease.

In the early 1980s, Prusiner began to advocate a different theory to explain where the “transmissible” in TSEs came from. The answer, he argued, was a particle he called a prion, in effect the first infectious pro- tein. The evidence, “one has to admit, was very shaky” to start, Aguzzi says. But the work slowly advanced. Prusiner reported that purifying bits of scrapie-laden brain down to their infectious components always left behind a protein that resisted chemi- cal breakdown, suggesting it might be mis- folded. In 1985, the gene that generates the prion protein was cloned, and researchers were shocked to discover that the healthy prion protein, PrP, was naturally abundant in the brain tissue of normal people.

Aguzzi became convinced of the prion hypothesis in the early 1990s, when he was working with prion biologist Charles Weissmann, then at the Institute of Molecular Biology in Zurich, and

saw that mice genetically engineered to lack PrP didn’t get sick when injected with infected material. This suggested to Aguzzi that the disease is transmitted by a misfolded PrP pro- tein and that it targets healthy PrP in the brain and turns it toxic, killing neurons. “That was really the tipping point” for me, he says.

Another tipping point came when Prusiner won the Nobel Prize in phys- iology or medicine in 1997 for “his discovery of prions—a new biologi- cal principle of infection,” the Nobel Committee announced. “Numer- ous attempts to disprove the prion hypothesis over the past 15 years have failed,” Prusiner declared in his Nobel lecture on 8 December of that year, shortly before accepting the prize in Stockholm, Sweden. For him, the case was settled.

Days after the award was announced, Manuelidis shared her blunt assessment with The New York Times. “My fear is that debate

NEWSFOCUS is going to be stifled,” she told a reporter.

“That’s the problem with Nobel prizes. If people feel everything is decided, you can’t possibly risk going against the grain.” Man- uelidis keeps a yellowed clipping of that arti- cle pinned up outside her office door.

Prusiner’s Nobel came as fear of TSEs was running high. In 1995, the first person died of what would later be called variant Creutzfeldt-Jakob disease (vCJD): a ver- sion of the neurological ailment, trans- mitted by eating beef from affected cows. Panic ensued, especially in the United Kingdom, where 175 people were eventu- ally diagnosed as having the lethal disease. But uncertainty about its cause hasn’t been “an impediment to making sensible public health decisions,” says David Asher, chief of the laboratory of Bacterial and TSE Agents at the U.S. Food and Drug Admin- istration (FDA). Governments simply took steps to keep meat from sick cows out of the food supply. Recently, cases of vCJD have dropped, and fear has subsided.

Battle lines

In the years since Prusiner won his Nobel, even some who have wavered on the prion hypothesis say that evidence has mounted steadily in its favor. About 10 years ago, neuroscientist Claudio Soto, who trained in Chile and is now at the University of

www.sciencemag.org SCIENCE VOL 332 Published by AAAS

Nobelist. The views of neurologist Stanley Prusiner, at the Nobel Prize ceremony in 1997, are now dogma in the field.

27 MAY 2011 1025

CREDIT: JONAS EKSTROMER/AP

NEWSFOCUS

Texas Medical School at Houston, devel- oped a new technology called protein mis- folding cyclic amplification (PMCA). As its name suggests, PMCA is designed to boost the concentration of prion protein in a sample and eliminate living cells (along with viruses they may contain). To test for infectivity, researchers run samples of brain homogenate through PMCA and inject the concentrated product into mice. Because the mice get sick, many believe this points to prions as the infectious culprit.

The results have been difficult to argue with. Bruce Chesebro, who has long been on the fence about the prion hypothesis, is leaning in its favor. Chief of the Labora- tory of Persistent Viral Diseases at the U.S. National Institute of Allergy and Infectious Diseases, based in Montana, Chesebro now says, “PMCA suggests it may not be a virus” that triggers these maladies.

Biochemist Jiyan Ma of Ohio State Uni- versity in Columbus and his colleagues reported online in Science on 28 January 2010 (http://scim.ag/prion_ma) that mix- ing PrP with various lipid molecules, which force it to misfold, and then injecting the mixture into the brains of healthy mice gave them prion disease. “The data show that pri- ons exist,” says Surachai Supattapone of Dartmouth College, who published one of the landmark experiments in a 2007 issue of the Proceedings of the National Academy of Sciences (PNAS). “That’s I think now clear.” And, he adds, prions are “not viruses.”

This all sounds unambiguous, but even backers of the prion hypothesis admit to some gaps in the evidence. Misfolded PrP is sometimes found in noninfectious tissue, and sometimes it is not found in tissue that can infect other animals. Brain homogenates from people and animals afflicted by prion disease—even prion diseases from the same species—can have wildly different effects when injected into animals, including genet- ically identical ones. Some develop symp- toms after a few months, others not until years later. Prion supporters attribute the variation to different “strains” of PrP, sug- gesting that the protein can misfold into dif- ferent chemical conformations that have different levels of toxicity. Not everyone buys it.

Another festering worry, Manuelidis and some others say, is that prion experiments are easily contaminated. Anyone examining the brains of animals with TSEs risks wind- ing up with the infectious agent on their equipment, Chesebro says—on their test- tube racks, their benchtops, the hoods under which they work for protection. Although

Family ties. Laura and Elias Manuelidis built their careers together, and their family—here in 1967 with their infant son Manoli.

great care is taken to keep stray bits of brain tissue at bay, there isn’t an airtight solution short of switching to a new lab each time. What does this mean, practically speaking? If an unidentified infectious agent exists, it could be a stealthy actor even in the best- controlled experiments.

The Ma study, many argue, has come the closest to definitively proving the prion hypothesis. Researchers synthesized mis- folded PrP in the lab, injected it into nor- mal animals, and watched them develop symptoms of TSEs. But no one has repli- cated this result. Instead, researchers often use genetically engineered mice that over- produce healthy PrP because they develop symptoms faster once infected. This makes for cheaper and easier experiments. Normal

mice can take an eternity to show symp- toms. It “might take longer than the life span of the mouse,” Aguzzi says. “So it helps to have an overexpresser.”

Casting a long shadow over the field is Prusiner, who is as tight-lipped in public as Manuelidis is loquacious. He almost never talks to the press and declined, through his correspondence manager, to be interviewed for this article.

Minority views

Asking Manuelidis to elaborate on her prion skepticism can be an exercise in frus- tration. Encouraging her to talk is not the problem—but grasping her case against prions isn’t easy. Manuelidis is aware of this. “I can’t think in a straight sentence,” she says, soon after parking her low-slung Mazda convertible and sitting down for dinner at a Portuguese restaurant. “My brain goes into literature.”

Many prion biologists—even some with questions about the current dogma— are disappointed by the evidence she’s turned up. In 2007, Manuelidis published a paper in PNAS, describing small viruslike particles in TSE-infected tissue but not in uninfected samples. That’s a correlation, however, not proof that the particles are causing disease, Chesebro says. “I’m sym- pathetic of her battle,” he notes. “I wish she were more convincing.”

Weissmann, Aguzzi’s colleague, who’s now at the Scripps Research Institute in Palm Beach, Florida, has been both friend and foil of Manuelidis over the years and was the only one to mention her unprompted in conversation. (More often there is a long pause after her name is brought up.) “The work itself is sound; she’s done some inter- esting work with cell cultures,” Weissmann says. “But then she tries to force it into the

viral hypothesis,” going through “contortions” to interpret the data. His language is nearly identical to Manuelidis’s descriptions of the work of the “prion cabal.”

Manuelidis and others say she has paid a price for holding so tightly and so publicly to her virus theory. She describes a prominent prion scientist walking out when she took the lectern at a meeting, and another screaming at her in a room full of people. Anonymous reviews of her papers have some- times been caustic and personal, she says. “She’s had a very tough time scientifically, but she also has many friends and allies,” says Robert

Minority view. Viruslike particles cluster as small circles inside a large bundle, while PrP protein (labeled by large black dots) scatter nearby. Manuelidis discovered the particles and says they’re likely causing prion diseases.

1026 27 MAY 2011 VOL 332 SCIENCE www.sciencemag.org Published by AAAS

CREDITS (TOP TO BOTTOM): COURTESY LAURA MANUELIDIS; L. MANUELIDIS ET AL., PNAS 104 (6 FEBRUARY 2007)

Somerville, who studies TSEs at the Roslin Institute at the University of Edinburgh in the United Kingdom. He’s known Manueli- dis since 1980 and considers himself a good friend. “The divisions run perhaps deeper in our field than others and are longer lasting. Which is sad, really—it can be difficult to have a useful, constructive discussion.”

Like Somerville, Asher of FDA worries about the path prion biology has taken. “I’m still left with this nagging concern that the abnormal protein, important though it may be, has not been demonstrated to be the infectious agent,” he says. “The field has been very forgiving of failures of the prion hypothesis to predict things that are found in the laboratory.” Asher also complains that prion studies are almost never repeated— scientists just move on to a new one. And, he says, papers that fit the dogma are more readily published than those that do not.

Maurizio Pocchiari, a neurologist at the Istituto Superiore di Sanità in Rome, agrees that siding with the vocal majority can cer- tainly help one’s career. “If you are aligned with the prion hypothesis, it is very easy to publish, ... [and] it’s easier to get a good result” experimentally, he thinks, thanks partly to the genetically modified mice churning out PrP that are so popular.

Pocchiari is another member of the Manuelidis fan club. He disagrees that a conventional virus is lurking behind TSEs, believing it would have been found by now—but he isn’t satisfied with the protein-only dogma, either. “We now are pretty aware that when we try to purify infec- tivity, we purify the pathological prion pro- tein, but we also purify something else,” he says. “There is a something else, ... [but] we have no idea what we are looking for.” Some, like Somerville, wonder about a “virino,” a small viral particle that doesn’t code for pro- teins on its own and acts in conjunction with PrP. Virinos fit the bill in part because of their size, which is useful because of long- ago studies suggesting that nothing as large as a virus was hiding in TSE-infected tissue. But virinos are a concept invented to fit the experimental data that haven’t been found anywhere else. Then again, many argued before the prion theory took hold that prions shared this feature, too.

Tenacity

If there is a virus behind TSEs, how could it have stayed hidden for so long? Isolat- ing these tiny snippets, Manuelidis argues, is just plain difficult because copies are so scarce, even in brain tissue where disease concentrates. Most people disagree with

her, but not everyone. “The fact that we can’t detect it is, I would argue, not a statement of what’s present or not, but maybe more a statement about our abilities as scientists to discover it,” Somerville says. Asher hopes that Manuelidis will continue her work with the viruslike particles she identified in the 2007 PNAS paper. “Far too little has been done with it,” he says.

Manuelidis perseveres, working near the morgue in the basement of the sur- gery building, where she’s been since the mid-1970s. The labs are old; her husband’s off ice remains largely untouched. Like everywhere else, precautions against infection were an after- thought when they first began this work. “My husband was deter- mined you had to feel the stuff; nobody put on gloves and then [we] ate lunch,” Manuelidis says. A guinea pig injected with CJD that mysteriously didn’t get sick was christened Harold and lived for 12 years in the lab’s biohaz- ard facility. Manuelidis acciden- tally squirted herself once in the eye with an infectious brain sam- ple and took out a $1 million life insurance policy for 10 years for her two sons. She never devel- oped the disease, reinforcing her view that TSEs are not particu- larly virulent and may need to be injected or ingested in large quan- tities for someone to get sick.

In the late 1990s, Manuelidis began downsizing her lab, frus- trated by how grueling her strug- gle for money had become—a shift that began after Prusiner’s Nobel, she says. Now she has three recent Yale undergraduates working for her, as they bridge time between college and medical or grad- uate school. Her students learned the prion gospel in biology class and are fascinated by what, to them, is a new controversy. They’re not sure where they stand. As they tell it, Manuelidis doesn’t push them. “The data doesn’t seem to contradict” the virus theory, says Terry Kipkorir, a thoughtful 2010 graduate who grew up in Kenya and slouches at a desk, a blue stocking cap on his head. Kipkorir and the others are looking for viral particles in infected tissue and trying to determine which components are infec- tious. But “I don’t want to dismiss the prion theory” either, he says. If there’s one thing he’s realized as he ends an academic year in Manuelidis’s lab, it is to prize autonomy. “I

NEWSFOCUS don’t think I’m going to work under a lot of

direction” going forward, he says. Manuelidis attributes the slow pace of her

never-ending virus hunt to technical chal- lenges and a shortage of money. She has the same CJD grant from the National Insti- tutes of Health that she’s had for more than 30 years; it now brings in $539,000 a year, nearly $200,000 of which goes to Yale for overhead costs. Multimillion-dollar awards— the kind that allow you to work with hundreds of animals—are not in her future, she thinks.

Should they be? The same researchers who lament how incomplete her work is say

no. “To be quite frank, I don’t think it’s worth funding,” Weissmann says. “In the 19th cen- tury, there were still people who thought that life could originate from boiled hay. These people just die out—there’s always fewer and fewer of them.” He believes that Manuelidis will never relinquish a theory to which she’s held tight for decades, no matter what story the data tell.

Asked if letting go would be hard for her, Manuelidis is unambiguous. “No, no,” she says. “All I know is that my experiments don’t show” that prion protein is causing dis- ease. She’s hopeful now that she’s on the cusp of something new. “I think I can crack this stuff,” she says.

–JENNIFER COUZIN-FRANKEL

Under attack. An MRI shows the brain of a 17-year- old who later died of variant Creutzfeldt-Jakob disease, with the infection destroying his thalamus (in red).

www.sciencemag.org SCIENCE VOL 332 27 MAY 2011 1027 Published by AAAS

CREDIT: SIMON FRASER/PHOTO RESEARCHERS INC.

 

 

 

From Bernard Edinger '59

 Dear Stanley and Larry,

First: Congratulations on organizing a fabulous reunion. I'm sorry that in the extraordinarily heady atmosphere of the event, I wasn't able to congratulate nyou personnally - or even see where you were - but it was fantastic!

As you may have seen, I today submitted a few personal photos of the reunion and of a small "pre-reunion reunion" held in NYC a couple of days before the Melville festa.

Dare I do it again and sumit a tidbit on my activities for the Alumni column? You guys decide:

I took advantage of my coming across from France for the reunion to organize another working trip for my Association of French Defense Correspondents in the U.S.

Three colleagues came across the Atlantic and joined me for two and a half days at the United States Military Academy in West Point, N.Y., and two days in Red Bank, New Jersey, with a U.S. Marines reserves unit getting ready to ship out to Afghanistan.

Both visits were exceptional. Please find attached a photo of the West Point Superintendant, Lieutenant General David Huntoon, kindly answering our questions (I'm on the right).

Best regards and look forward to attending the next (60th ?) anniversary reunion.

Bernard Edinger, Paris, France (Class of '59)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Is it possible that I am the only person feeding news to the JHS Alumni site? I can’t believe that among the multitudes which we were from three classes, I’m alone still doing something worth reporting? Or perhaps it’s because I worked as a journalist virtually all my life and an old saying about newspeople is that they never really retire and keep on hammering away stories until the nails are hammered into the box putting them away!
  
Anyway, I just spent a week in the West African republic of Niger as an instructor in a media training workshop for officials of UNICEF, the United Nations Children’s Emergency Fund, trying to help this impoverished nation.
  
Some three million people living in areas of Niger mostly along the southern edge of the Sahara Desert (from among a total population of 13 million) are threatened with starvation within months unless it either rains, or the world comes to their help with food and medicine. There has been a general lack of rain for agriculture for at least a decade, largely as a result of global warming, and things are unlikely to improve.
  
Our job was to try to give tips to doctors, public health specialists and other UNICEF officials on how to explain the situation to visiting journalists in order that they should come away and write sympathetic copy which will lead donors to come to the aid of the local population, one of the world’s poorest.
  
To compound a miserable situation, more than three-quarters of the country (the largely desert North) is apretty much a no-go zone because of the presence of  armed bands, some of which are connected to al Qaida.
  

The attached photo was taken at a hotel in the capital Niamey, overlooking the Niger River (no swimming – there are hippos around - not to mention multiple tropical diseases!), at the end of a work day with Jeremy Toye (on the right) the head of the media training firm which hired me. Jeremy is a former colleague from Reuters news agency and we had not seen each other since the Fall of Saigon in 1975!
  

 
  

Bernard Edinger
  
   Since my retirement from Reuters news agency, I have been active in the Association of French Defense Journalists since I covered defense matters and several conflicts (Yom Kippur War in 1973, Fall of Saigon in 1975, Soviet entry into Afghanistan in 1979, Balkans in the late 1990s) during my time at Reuters (1969-2001).

I now organize study trips around the world for the association allowing full-time active journalists to meet key defense figures and visit interesting places and military installations and units. I've organized two trips to the US, two to Israel and one each to Britain and to Germany.

The latest trip I organized and accompanied (I'm the tour guide too) was to the U.S. in June where we were received by General David Petraeus, head of Central Command at his headquarters in Tampa, Florida, and also visited Fort Bragg, the home of the Special Forces.

Please find attached a photo of General Petraeus greeting me as head of the visiting French press delegation.

I hope it's not too presumptueous to submit this but it certainly was interesting. As you know, General Petraeus (sometimes referred to as "King David") is America's foremost and best known military leader today with some in the American press believing that he has very high political ambitions for the future if he succeeds in Afghanistan after  making very notable progress in Irak.

Best regards

Bernard