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Distribution of Nets Splits Malaria Fighters
By REUBEN KYAMA and DONALD G. McNEIL Jr., The New York Times, October 9, 2007
MAENDELEO, Kenya — Veronica Njeri, 45, says she has “never healed” since losing two of her six children to malaria 20 years ago, and she still feels vulnerable. While her oldest are adults or teenagers, and have presumably built up immunity to the disease, she worries about her youngest, Anthony, who is 4.
But since hundreds of free mosquito nets came to Maendeleo, her rice-farming village in west-central Kenya, “malaria epidemics have become rare,” she said happily, even though the village sits amid stagnant paddies where swarms of mosquitoes breed.
Villages like Maendeleo are at the center of a debate that has split malaria fighters: how to distribute mosquito nets.
Recently, Dr. Arata Kochi, the blunt new director of the World Health Organization’s malaria program, declared that as far as he was concerned, “the debate is at an end.” Virtually the only way to get the nets to poor people, he said, is to hand out millions free.
In doing so, Dr. Kochi turned his back on an alternative long favored by the Clinton and Bush administrations — distribution by so-called social marketing, in which mosquito nets are sold through local shops at low, subsidized prices — $1 or so for an insecticide-impregnated net that costs $5 to $7 from the maker — with donors underwriting the losses and paying consultants to come up with brand names and advertise the nets.
“The time for social marketing of bed nets in a big way is over,” Dr. Kochi said in an interview. “It can become a supplemental strategy for urban areas and middle-income countries.”
Two years ago, social marketing was at the heart of a scandal when it was revealed that the United States Agency for International Development, or USAid, which distributes foreign aid, was spending 95 percent of its malaria budget on consultants and 5 percent on goods like nets, drugs and insecticide. Under attack from several senators championing the fight against malaria, the agency later announced that it would spend at least half its budget on goods.
Senator Tom Coburn, Republican of Oklahoma, called the new W.H.O. policy “a great move,” adding, “We knew social marketing doesn’t work.”
In practice, nothing much had been working. In 2000, a world health conference in Abuja, Nigeria, set a goal: by 2005, 60 percent of African children would be sleeping under nets. By 2005, only 3 percent were.
The theory behind social marketing, which is also used to distribute condoms and oral rehydration salts, is that the poor see more value in brand-name goods they pay for than handouts they get free, and that the trade creates small entrepreneurs.
The usual comparison made is to Coca-Cola, which reaches Africa’s remotest corners. But Dr. Kochi rejected that model, saying, “I’m not sure whether the poorest of the poor actually drink Coca-Cola.”
He argues that the insecticide-filled nets, when used by 80 percent or more of a village, create a barrier that kills or drives off mosquitoes, protecting everyone in the area, including those without nets. Individual nets tended to just drive mosquitoes next door, to bite someone else. As such, he said, nets ought to be treated as a public good, like the measles or polio vaccines, which the world does not charge the poor for.
Free net distributions are usually done in a week or two, by armies of workers who are paid a few dollars a day by the Red Cross or health ministry to cover a country or other large region. Distributions have been tried in Sierra Leone, Niger, Togo and elsewhere, sometimes in conjunction with measles shots or deworming drugs.
The new model is beginning to prevail but has not completely swept the field. Some donors still use some social marketing. Unicef, the world’s largest buyer of nets, distributed 25 million last year, of which 92 percent were given away, said its medical director, Dr. Peter Salama. The main American program, the President’s Malaria Initiative, plans to hand out more than 15 million nets by 2008, of which about 75 percent will be free, said its coordinator, Rear Adm. Tim Ziemer.
In June, Admiral Ziemer and the first lady, Laura Bush, who has made malaria her crusade, helped hand out 500,000 free nets in Mozambique and Zambia.
Social marketing may be useful during gaps between mass distributions, said Trent Ruebush, a malaria expert at the initiative and USAid. The best insecticide-filled nets last three to five years, but babies will be born in that time, or new families will move into an area. “We feel it is one of various effective ways to go,” Dr. Ruebush said.
Experiences in Kenya played a large part in persuading the W.H.O. to change its policy, said Dr. Peter Olumese, a medical officer in the agency’s malaria program.
Maendeleo, a village of about 140 mud-walled shacks with tin roofs, was part of a five-year study of 40 health districts. When it started in 2002, the only nets were those for sale in small shops, Dr. Olumese said, and only about 7 percent of people had them.
Social marketing was introduced by Population Services International, a large aid contractor. That increased coverage to about 21 percent by early 2006.
Then, late last year, the health ministry got a big grant from the Global Fund to Fight AIDS, Tuberculosis and Malaria that allowed it to hand out 3.4 million free nets in two weeks. Coverage rose to 67 percent, and distribution became more equitable. Under social marketing, Dr. Olumese said, the “richest of the poor” had 38 percent coverage, while the “poorest of the poor” — like Maendeleo’s rice farmers — had only 15 percent. After the handouts, they were about equal.
Deaths of children dropped 44 percent.
It also turned out to be cheaper, Dr. Olumese said. With consultant fees, transportation, advertising and shipping, social marketing added about $10 to the cost of each net beyond the $5 to $7 that Danish or Japanese makers charged. But even with payments to volunteers, the added cost of free distribution was only about $1.25 per net.
“There has been a paradigm shift,” Dr. Olumese said. “We need to use the momentum we have right now.”
Between the giveaways, he said, nets should be handed out free to all pregnant women and mothers who visit health clinics. Some women struggle to afford even the 10 cents per child cost of identity cards that let them visit clinics. “Asking a mother to make a decision to feed her child or buy a net is not fair,” he said.
In Maendeleo, a village elder, Benson Gacu, confirmed that price was a major impediment. “Our people are poor, and very few could afford to buy a mosquito net even for 50 shillings,” or about 75 cents, he said. “We are happy that the nets are free.”
Francis Mureithi, a local shopkeeper, said he still had some 50-shilling nets for sale because the government had given free ones only to families with children under 5.
But, Mr. Mureithi noted, sales of malaria pills were way down.
Reuben Kyama reported from Maendeleo, Kenya, and Donald G. McNeil Jr. from New York.
Essay: In a Lifetime of Sickle Cell, the Evolution of a Disease
By BARRON H. LERNER, M.D., The New York Times, October 9, 2007
Most sickle cell anemia patients do not live long enough to span generations of doctors. But Gladys Jacobs was around when I was a medical resident in the 1980s, and she is around now.
Her career — as a patient and an activist — demonstrates how the understanding of sickle cell disease has changed.
Gladys’s condition was initially misdiagnosed, as was all too common for sickle cell cases in the early ’60s. It was not until then, as the historian Keith Wailoo writes in “Dying in the City of the Blues” (University of North Carolina Press, 2001), that the disease “found its way into the public consciousness.”
When Gladys went to doctors complaining of joint aches, which were the common painful crises characteristic of sickle cell disease, she was met with skepticism. Doctors, she recalls, called her a faker.
Finally, at age 16, she went to a hematologist who diagnosed sickle cell anemia and a second blood disorder, beta-thalassemia. This combined condition may be less severe than pure sickle cell disease and probably helps explain Gladys’s longevity. (She will turn 60 in two weeks.)
But one should not minimize her list of complications. They include hundreds of admissions for painful sickle cell crises, spleen removal, shoulder surgery followed by an abscess and degeneration of the hips that has required multiple operations and forced her to use a wheelchair.
On top of all this, Gladys suffered disrespect. Too many physicians and nurses assumed she was faking symptoms to get pain medication. “The impression,” she said, “is that we are all addicts.”
Doctors’ fear of promoting drug addiction led them to underprescribe drugs to sickle cell patients — for example, insisting on checking blood tests before giving pain medications. Gladys never really cared about the test results. “I know how I feel,” she said.
Race, as Mr. Wailoo shows in his book, was central to the conundrum of treating sickle cell patients, a vast majority of whom are African-American. As one hematologist conceded, delaying the administration of pain medications has a “racial undertone.”
The frustrations led Gladys and a dozen other sickle cell patients at what is now Columbia University Medical Center to form a self-help group there in the early ’80s. Embodying the patient activism of the era, they sought to change health professionals’ perceptions about the disease. They were given a gratifying invitation from a Columbia internist and professor, Dr. Constance M. Park, to tell their histories to small groups of students.
Yet real change did not occur until medical centers like Columbia introduced pain medication services specializing in sickle cell. Enormous strides have been made in pain management, but work remains to be done. A study in the May 2007 issue of Academic Emergency Medicine reported that sickle cell patients seen in three emergency departments received pain medications 70 to 75 minutes later than recommended by the American Pain Society.
Eventually, the Columbia self-help group fizzled out. So Gladys was especially pleased last fall when her current Columbia physician, Dr. Delphine M. Taylor, asked her to speak to the entire class of 150 first-year medical students in the “clinical practice” class.
Gladys was daunted at first. Despite years of outspokenness, she is quiet and shy. In the past, she had met with just 15 students.
But she warmed to the task. In the question period, when a student asked what it was like to live with sickle cell anemia for almost 50 years, she answered with one word: “Hell.”
The students were moved. When I e-mailed them several months later to learn their impressions of the lecture, one student told me that she and others had just been discussing Gladys.
Another student, Solomon Woldu, wrote that Gladys was “an incredibly resilient and strong-willed woman” whose “sense of dignity and positive outlook left many of us students with a sense of awe.”
When Gladys finished speaking, she received a standing ovation.
Barron H. Lerner teaches medicine and public health at the Columbia University Medical Center.
In the Battle Against Cancer, Researchers Find Hope in a Toxic Wasteland
By CHRISTOPHER MAAG, The New York Times, October 9, 2007
BUTTE, Mont. — Death sits on the east side of this city, a 40-billion-gallon pit filled with corrosive water the color of a scab. On the opposite side sits the small laboratory of Don and Andrea Stierle, whose stacks of plastic Petri dishes are smeared with organisms pulled from the pit. Early tests indicate that some of those organisms may help produce the next generation of cancer drugs.
From death’s soup, the Stierles hope to coax life.
“I love the idea of looking at toxic waste and finding something of value,” said Ms. Stierle, 52, a chemistry researcher at Montana Tech of the University of Montana.
For decades, scientists assumed that nothing could live in the Berkeley Pit, a hole 1,780 feet deep and a mile and a half wide that was one of the world’s largest copper mines until 1982, when the Atlantic Richfield Company suspended work there. The pit filled with water that turned as acidic as vinegar, laced with high concentrations of arsenic, aluminum, cadmium and zinc.
Today it is one of the harshest environments in the country. When residents speak of the pit, they often recall the day in 1995 when hundreds of geese landed on the water and promptly died.
“It’s definitely an eerie place,” said Russ Forba, who directs the cleanup of the pit, now a Superfund site, for the federal Environmental Protection Agency.
But the pit itself is far from dead. Over the last decade, Mr. Stierle said, the couple have found 142 organisms living in it and have “isolated 80 chemical compounds that exist nowhere else.”
In two papers published recently in peer-reviewed organic chemistry journals, the Stierles reported finding two compounds that showed initial success in killing breast and ovarian cancer cells in lines maintained by the National Institutes of Health.
“In this test we’re just really knocking the snot out of ovarian cancer,” Ms. Stierle said, reviewing her findings. But she was quick to describe the tests as very early-stage experiments. Even if these initial results were independently replicated, she said, it would be years before any drugs could be manufactured.
“Someone in my field looks at that and says, ‘Oh, that looks juicy,’” said John Beutler, a staff scientist in the molecular targets development program at the National Cancer Institute.
The Stierles won widespread recognition in the scientific community in the mid-1990s for discovering a fungus, native to mountaintops in the Pacific Northwest, that produces taxol, which is commonly used to fight breast and ovarian cancer. The fungus was found next to yew trees, which had long been the primary source of taxol.
The couple’s results were published in the journal Science, and they were awarded 11 United States and international patents for their discovery of taxol in the fungus and for developing methods to isolate and grow it.
Then the financing they had for their taxol research from Cytoclonal Pharmaceutics came to an end. The Stierles needed something new to study, quickly. They turned to the Berkeley Pit, about a mile from their house. They persuaded the Montana Bureau of Mines and Geology to allow its Berkeley Pit coordinator to take water samples that they could use to collect microbes.
“It sure saved us a lot of money on gas,” Mr. Stierle said.
Mr. Stierle is a tenured professor at Montana Tech, but his wife gets paid only for teaching an occasional class or if there is a grant to finance her research. From 1996 to 2001 they applied for dozens of grants, but received only rejection letters. So they financed their own research, using personal savings and $12,000 in annual patent royalty payments. In 2001, they won a six-year, $800,000 grant from the United States Geological Survey.
“Their work is considered a very high-risk approach,” said Matthew D. Kane, a program director at the National Science Foundation. “It takes a long time to get funding, and some luck to find active compounds.”
Unlike scientists at large research universities, who commonly teach only one class a year and employ graduate students to run their laboratories, Mr. Stierle teaches four classes each semester at a college with 2,000 undergraduates and no major research presence.
“They’re finding lots of really neat stuff using people who don’t even have their bachelor’s degrees,” said Nicholas Oberlies, who directs the natural products laboratory at RTI International, a large nonprofit research center in North Carolina.
Meanwhile, the Stierles said, they have turned down job offers from major universities that would have tripled their salaries.
“We love Montana, and we love what we do,” said Ms. Stierle, who often wears a T-shirt that reads “I Dig Science!” around her office. “And then I look at my investment portfolio and think, ‘Oh my God, what was I thinking?’”
In return, the Stierles said, they get to witness an unfolding story of strange little creatures struggling mightily to survive. Microbes react to harsh conditions in the Berkeley Pit by switching on genes that otherwise lay dormant or by evolving through mutation and natural selection, Mr. Stierle said. Either way, they produce new chemical compounds, which the Stierles hope may benefit human health.
The couple have become intimately acquainted with the personalities of these new microorganisms. The pit’s strain of mycobacterium is a slimy, obstinate fungus that smells bad and is difficult to cultivate in a laboratory. But it has shown initial success in fighting some pathogens, Ms. Stierle said.
Then there is Penicillium rubrum, which is fuzzy and green like bread mold. “It’s sweet, it grows, and this little guy produces large amounts of interesting compounds,” she said. “It’s one of the loveliest microbes we’ve ever worked with.”
Among scientists familiar with their work, the Stierles’ talent for making discoveries in such spartan conditions generates a kind of awe.
“They have that special ability of groundbreaking researchers to ask the obvious questions, which makes all the rest of us think, ‘God, I wish I would have thought of that,’” said Kyle Strode, a chemistry professor at Carroll College in Helena, Mont., who describes himself as a friendly competitor with the Stierles.
The couple said they were negotiating privately with a pharmaceutical company to test some of the compounds they have discovered and possibly turn them into drugs. As they wait, they open another Mason jar filled with murky pit water, draw a sample and return to work.
“The pit very easily could have been a complete waste of time,” Mr. Stierle said. “We just had luck and worked our butts off. We take that first walk into the dark.”
In NASA’s Sterile Areas, Plenty of Robust Bacteria
By WARREN E. LEARY, The New York Times, October 9, 2007
WASHINGTON, Oct. 6 — Researchers have found a surprising diversity of hardy bacteria in a seemingly unlikely place — the so-called sterile clean rooms where NASA assembles its spacecraft and prepares them for launching.
Samples of air and surfaces in the clean rooms at three National Aeronautics and Space Administration centers revealed surprising numbers and types of robust bacteria that appear to resist normal sterilization procedures, according to a newly published study.
The findings are significant, the researchers report, because they can help reduce the chances of stowaway microbes contaminating planets and other bodies visited by the spacecraft and confounding efforts to discover new life elsewhere.
“These findings will advance the search for life on Mars and other worlds both by sparking improved cleaning and sterilization methods and by preventing false-positive results in future experiments to detect extraterrestrial life,” said the leader of the study, Dr. Kasthuri Venkateswaran, a microbiologist at NASA’s Jet Propulsion Laboratory in Pasadena, Calif.
Identifying and cataloging what microbes might survive sterilization is important in interpreting results of sampling missions to other planets, scientists said. If similar microbes turn up in alien samples, researchers could disregard the results as contamination and not evidence of extraterrestrial life.
NASA tries to protect its spacecraft and their delicate components from dust and bacteria by assembling and testing them in rooms that are meticulously cleaned of dust and dirt by having their air continuously filtered to reduce fine particles. People working in these rooms wear coveralls with gloves and sometimes wear face masks.
Researchers from Dr. Venkateswaran’s Biotechnology and Planetary Protection Group and the Lawrence Berkeley National Laboratory published the results of their tests in the European journal FEMS Microbiology Ecology.
Samples taken from clean rooms at the Jet Propulsion Laboratory, the Kennedy Space Flight Center in Florida and the Johnson Space Center in Houston revealed almost 100 types of bacteria, about 45 percent of which were previously unknown to science, the study said. While some were common types that thrive on human skin, such as Staphylococcus species, others were oligotrophs, rarer microorganisms that have adapted to grow under extreme conditions by absorbing trace nutrients from the air or from unlikely surfaces like paint.
Traditionally, NASA has examined clean-room bacteria by taking samples of air and surfaces and trying to culture bacteria present in the laboratory. Dr. Venkateswaran said only a small fraction of bacteria could be found this way because most grow only in their native environments.
For their tests, the researchers used a genetic testing method not employed in clean rooms before, known as ribosomal RNA gene sequence analysis, which allowed them to study and decode a genetic marker common to all bacteria. The unique sequences of each type allowed the researchers to identify a greater number and diversity of bacteria than previously detected in the rooms.
While a few microorganisms, like those common on human skin, were found at all three sites, the study discovered that each room had a bacterial community largely unique to itself. Many factors could be responsible for this diversity, the researchers said, including the differing types of air filters and cleaning agents used and the facilities’ different geographic locations.
“I was surprised by what we found,” Dr. Venkateswaran said in an interview, “and as we continue to sample additional clean rooms, we may be in for even more surprises.”
Dr. Catharine A. Conley, a biologist who is the acting planetary protection officer at NASA headquarters, said the agency had long suspected that the organisms previously detected in clean rooms did not represent the full range that were there. Current cleaning techniques kill most common microbes, she said, and the resulting lack of competition could contribute to the number and diversity of the durable survivors found by the genetic testing approach.
“We know clean rooms can be much cleaner, and some are,” Dr. Conley said, citing some used by the semiconductor and pharmaceutical industries. “The problem is the cost. They are very expensive to build and maintain.”
Spacecraft going to areas where alien life is more likely to be found, like planets or moons with identifiable water, can be sterilized by a heat method that essentially bakes them for hours. But, she said, this runs the risk of damaging components.
Dr. Conley said NASA was experimenting with different techniques, including infusing spacecraft with vaporized hydrogen peroxide or a cold plasma of ionized gas, to attack the problem.
Spacecraft contamination is not just an issue for the United States, Dr. Conley noted. All space agencies sending out interplanetary probes follow cleanliness rules from an international organization called the Committee on Space Research. These standards vary depending on the type of mission, such as one that lands on a body versus orbiting it, and the likelihood that the destination bears life.
By REUBEN KYAMA and DONALD G. McNEIL Jr., The New York Times, October 9, 2007
MAENDELEO, Kenya — Veronica Njeri, 45, says she has “never healed” since losing two of her six children to malaria 20 years ago, and she still feels vulnerable. While her oldest are adults or teenagers, and have presumably built up immunity to the disease, she worries about her youngest, Anthony, who is 4.
But since hundreds of free mosquito nets came to Maendeleo, her rice-farming village in west-central Kenya, “malaria epidemics have become rare,” she said happily, even though the village sits amid stagnant paddies where swarms of mosquitoes breed.
Villages like Maendeleo are at the center of a debate that has split malaria fighters: how to distribute mosquito nets.
Recently, Dr. Arata Kochi, the blunt new director of the World Health Organization’s malaria program, declared that as far as he was concerned, “the debate is at an end.” Virtually the only way to get the nets to poor people, he said, is to hand out millions free.
In doing so, Dr. Kochi turned his back on an alternative long favored by the Clinton and Bush administrations — distribution by so-called social marketing, in which mosquito nets are sold through local shops at low, subsidized prices — $1 or so for an insecticide-impregnated net that costs $5 to $7 from the maker — with donors underwriting the losses and paying consultants to come up with brand names and advertise the nets.
“The time for social marketing of bed nets in a big way is over,” Dr. Kochi said in an interview. “It can become a supplemental strategy for urban areas and middle-income countries.”
Two years ago, social marketing was at the heart of a scandal when it was revealed that the United States Agency for International Development, or USAid, which distributes foreign aid, was spending 95 percent of its malaria budget on consultants and 5 percent on goods like nets, drugs and insecticide. Under attack from several senators championing the fight against malaria, the agency later announced that it would spend at least half its budget on goods.
Senator Tom Coburn, Republican of Oklahoma, called the new W.H.O. policy “a great move,” adding, “We knew social marketing doesn’t work.”
In practice, nothing much had been working. In 2000, a world health conference in Abuja, Nigeria, set a goal: by 2005, 60 percent of African children would be sleeping under nets. By 2005, only 3 percent were.
The theory behind social marketing, which is also used to distribute condoms and oral rehydration salts, is that the poor see more value in brand-name goods they pay for than handouts they get free, and that the trade creates small entrepreneurs.
The usual comparison made is to Coca-Cola, which reaches Africa’s remotest corners. But Dr. Kochi rejected that model, saying, “I’m not sure whether the poorest of the poor actually drink Coca-Cola.”
He argues that the insecticide-filled nets, when used by 80 percent or more of a village, create a barrier that kills or drives off mosquitoes, protecting everyone in the area, including those without nets. Individual nets tended to just drive mosquitoes next door, to bite someone else. As such, he said, nets ought to be treated as a public good, like the measles or polio vaccines, which the world does not charge the poor for.
Free net distributions are usually done in a week or two, by armies of workers who are paid a few dollars a day by the Red Cross or health ministry to cover a country or other large region. Distributions have been tried in Sierra Leone, Niger, Togo and elsewhere, sometimes in conjunction with measles shots or deworming drugs.
The new model is beginning to prevail but has not completely swept the field. Some donors still use some social marketing. Unicef, the world’s largest buyer of nets, distributed 25 million last year, of which 92 percent were given away, said its medical director, Dr. Peter Salama. The main American program, the President’s Malaria Initiative, plans to hand out more than 15 million nets by 2008, of which about 75 percent will be free, said its coordinator, Rear Adm. Tim Ziemer.
In June, Admiral Ziemer and the first lady, Laura Bush, who has made malaria her crusade, helped hand out 500,000 free nets in Mozambique and Zambia.
Social marketing may be useful during gaps between mass distributions, said Trent Ruebush, a malaria expert at the initiative and USAid. The best insecticide-filled nets last three to five years, but babies will be born in that time, or new families will move into an area. “We feel it is one of various effective ways to go,” Dr. Ruebush said.
Experiences in Kenya played a large part in persuading the W.H.O. to change its policy, said Dr. Peter Olumese, a medical officer in the agency’s malaria program.
Maendeleo, a village of about 140 mud-walled shacks with tin roofs, was part of a five-year study of 40 health districts. When it started in 2002, the only nets were those for sale in small shops, Dr. Olumese said, and only about 7 percent of people had them.
Social marketing was introduced by Population Services International, a large aid contractor. That increased coverage to about 21 percent by early 2006.
Then, late last year, the health ministry got a big grant from the Global Fund to Fight AIDS, Tuberculosis and Malaria that allowed it to hand out 3.4 million free nets in two weeks. Coverage rose to 67 percent, and distribution became more equitable. Under social marketing, Dr. Olumese said, the “richest of the poor” had 38 percent coverage, while the “poorest of the poor” — like Maendeleo’s rice farmers — had only 15 percent. After the handouts, they were about equal.
Deaths of children dropped 44 percent.
It also turned out to be cheaper, Dr. Olumese said. With consultant fees, transportation, advertising and shipping, social marketing added about $10 to the cost of each net beyond the $5 to $7 that Danish or Japanese makers charged. But even with payments to volunteers, the added cost of free distribution was only about $1.25 per net.
“There has been a paradigm shift,” Dr. Olumese said. “We need to use the momentum we have right now.”
Between the giveaways, he said, nets should be handed out free to all pregnant women and mothers who visit health clinics. Some women struggle to afford even the 10 cents per child cost of identity cards that let them visit clinics. “Asking a mother to make a decision to feed her child or buy a net is not fair,” he said.
In Maendeleo, a village elder, Benson Gacu, confirmed that price was a major impediment. “Our people are poor, and very few could afford to buy a mosquito net even for 50 shillings,” or about 75 cents, he said. “We are happy that the nets are free.”
Francis Mureithi, a local shopkeeper, said he still had some 50-shilling nets for sale because the government had given free ones only to families with children under 5.
But, Mr. Mureithi noted, sales of malaria pills were way down.
Reuben Kyama reported from Maendeleo, Kenya, and Donald G. McNeil Jr. from New York.
Essay: In a Lifetime of Sickle Cell, the Evolution of a Disease
By BARRON H. LERNER, M.D., The New York Times, October 9, 2007
Most sickle cell anemia patients do not live long enough to span generations of doctors. But Gladys Jacobs was around when I was a medical resident in the 1980s, and she is around now.
Her career — as a patient and an activist — demonstrates how the understanding of sickle cell disease has changed.
Gladys’s condition was initially misdiagnosed, as was all too common for sickle cell cases in the early ’60s. It was not until then, as the historian Keith Wailoo writes in “Dying in the City of the Blues” (University of North Carolina Press, 2001), that the disease “found its way into the public consciousness.”
When Gladys went to doctors complaining of joint aches, which were the common painful crises characteristic of sickle cell disease, she was met with skepticism. Doctors, she recalls, called her a faker.
Finally, at age 16, she went to a hematologist who diagnosed sickle cell anemia and a second blood disorder, beta-thalassemia. This combined condition may be less severe than pure sickle cell disease and probably helps explain Gladys’s longevity. (She will turn 60 in two weeks.)
But one should not minimize her list of complications. They include hundreds of admissions for painful sickle cell crises, spleen removal, shoulder surgery followed by an abscess and degeneration of the hips that has required multiple operations and forced her to use a wheelchair.
On top of all this, Gladys suffered disrespect. Too many physicians and nurses assumed she was faking symptoms to get pain medication. “The impression,” she said, “is that we are all addicts.”
Doctors’ fear of promoting drug addiction led them to underprescribe drugs to sickle cell patients — for example, insisting on checking blood tests before giving pain medications. Gladys never really cared about the test results. “I know how I feel,” she said.
Race, as Mr. Wailoo shows in his book, was central to the conundrum of treating sickle cell patients, a vast majority of whom are African-American. As one hematologist conceded, delaying the administration of pain medications has a “racial undertone.”
The frustrations led Gladys and a dozen other sickle cell patients at what is now Columbia University Medical Center to form a self-help group there in the early ’80s. Embodying the patient activism of the era, they sought to change health professionals’ perceptions about the disease. They were given a gratifying invitation from a Columbia internist and professor, Dr. Constance M. Park, to tell their histories to small groups of students.
Yet real change did not occur until medical centers like Columbia introduced pain medication services specializing in sickle cell. Enormous strides have been made in pain management, but work remains to be done. A study in the May 2007 issue of Academic Emergency Medicine reported that sickle cell patients seen in three emergency departments received pain medications 70 to 75 minutes later than recommended by the American Pain Society.
Eventually, the Columbia self-help group fizzled out. So Gladys was especially pleased last fall when her current Columbia physician, Dr. Delphine M. Taylor, asked her to speak to the entire class of 150 first-year medical students in the “clinical practice” class.
Gladys was daunted at first. Despite years of outspokenness, she is quiet and shy. In the past, she had met with just 15 students.
But she warmed to the task. In the question period, when a student asked what it was like to live with sickle cell anemia for almost 50 years, she answered with one word: “Hell.”
The students were moved. When I e-mailed them several months later to learn their impressions of the lecture, one student told me that she and others had just been discussing Gladys.
Another student, Solomon Woldu, wrote that Gladys was “an incredibly resilient and strong-willed woman” whose “sense of dignity and positive outlook left many of us students with a sense of awe.”
When Gladys finished speaking, she received a standing ovation.
Barron H. Lerner teaches medicine and public health at the Columbia University Medical Center.
In the Battle Against Cancer, Researchers Find Hope in a Toxic Wasteland
By CHRISTOPHER MAAG, The New York Times, October 9, 2007
BUTTE, Mont. — Death sits on the east side of this city, a 40-billion-gallon pit filled with corrosive water the color of a scab. On the opposite side sits the small laboratory of Don and Andrea Stierle, whose stacks of plastic Petri dishes are smeared with organisms pulled from the pit. Early tests indicate that some of those organisms may help produce the next generation of cancer drugs.
From death’s soup, the Stierles hope to coax life.
“I love the idea of looking at toxic waste and finding something of value,” said Ms. Stierle, 52, a chemistry researcher at Montana Tech of the University of Montana.
For decades, scientists assumed that nothing could live in the Berkeley Pit, a hole 1,780 feet deep and a mile and a half wide that was one of the world’s largest copper mines until 1982, when the Atlantic Richfield Company suspended work there. The pit filled with water that turned as acidic as vinegar, laced with high concentrations of arsenic, aluminum, cadmium and zinc.
Today it is one of the harshest environments in the country. When residents speak of the pit, they often recall the day in 1995 when hundreds of geese landed on the water and promptly died.
“It’s definitely an eerie place,” said Russ Forba, who directs the cleanup of the pit, now a Superfund site, for the federal Environmental Protection Agency.
But the pit itself is far from dead. Over the last decade, Mr. Stierle said, the couple have found 142 organisms living in it and have “isolated 80 chemical compounds that exist nowhere else.”
In two papers published recently in peer-reviewed organic chemistry journals, the Stierles reported finding two compounds that showed initial success in killing breast and ovarian cancer cells in lines maintained by the National Institutes of Health.
“In this test we’re just really knocking the snot out of ovarian cancer,” Ms. Stierle said, reviewing her findings. But she was quick to describe the tests as very early-stage experiments. Even if these initial results were independently replicated, she said, it would be years before any drugs could be manufactured.
“Someone in my field looks at that and says, ‘Oh, that looks juicy,’” said John Beutler, a staff scientist in the molecular targets development program at the National Cancer Institute.
The Stierles won widespread recognition in the scientific community in the mid-1990s for discovering a fungus, native to mountaintops in the Pacific Northwest, that produces taxol, which is commonly used to fight breast and ovarian cancer. The fungus was found next to yew trees, which had long been the primary source of taxol.
The couple’s results were published in the journal Science, and they were awarded 11 United States and international patents for their discovery of taxol in the fungus and for developing methods to isolate and grow it.
Then the financing they had for their taxol research from Cytoclonal Pharmaceutics came to an end. The Stierles needed something new to study, quickly. They turned to the Berkeley Pit, about a mile from their house. They persuaded the Montana Bureau of Mines and Geology to allow its Berkeley Pit coordinator to take water samples that they could use to collect microbes.
“It sure saved us a lot of money on gas,” Mr. Stierle said.
Mr. Stierle is a tenured professor at Montana Tech, but his wife gets paid only for teaching an occasional class or if there is a grant to finance her research. From 1996 to 2001 they applied for dozens of grants, but received only rejection letters. So they financed their own research, using personal savings and $12,000 in annual patent royalty payments. In 2001, they won a six-year, $800,000 grant from the United States Geological Survey.
“Their work is considered a very high-risk approach,” said Matthew D. Kane, a program director at the National Science Foundation. “It takes a long time to get funding, and some luck to find active compounds.”
Unlike scientists at large research universities, who commonly teach only one class a year and employ graduate students to run their laboratories, Mr. Stierle teaches four classes each semester at a college with 2,000 undergraduates and no major research presence.
“They’re finding lots of really neat stuff using people who don’t even have their bachelor’s degrees,” said Nicholas Oberlies, who directs the natural products laboratory at RTI International, a large nonprofit research center in North Carolina.
Meanwhile, the Stierles said, they have turned down job offers from major universities that would have tripled their salaries.
“We love Montana, and we love what we do,” said Ms. Stierle, who often wears a T-shirt that reads “I Dig Science!” around her office. “And then I look at my investment portfolio and think, ‘Oh my God, what was I thinking?’”
In return, the Stierles said, they get to witness an unfolding story of strange little creatures struggling mightily to survive. Microbes react to harsh conditions in the Berkeley Pit by switching on genes that otherwise lay dormant or by evolving through mutation and natural selection, Mr. Stierle said. Either way, they produce new chemical compounds, which the Stierles hope may benefit human health.
The couple have become intimately acquainted with the personalities of these new microorganisms. The pit’s strain of mycobacterium is a slimy, obstinate fungus that smells bad and is difficult to cultivate in a laboratory. But it has shown initial success in fighting some pathogens, Ms. Stierle said.
Then there is Penicillium rubrum, which is fuzzy and green like bread mold. “It’s sweet, it grows, and this little guy produces large amounts of interesting compounds,” she said. “It’s one of the loveliest microbes we’ve ever worked with.”
Among scientists familiar with their work, the Stierles’ talent for making discoveries in such spartan conditions generates a kind of awe.
“They have that special ability of groundbreaking researchers to ask the obvious questions, which makes all the rest of us think, ‘God, I wish I would have thought of that,’” said Kyle Strode, a chemistry professor at Carroll College in Helena, Mont., who describes himself as a friendly competitor with the Stierles.
The couple said they were negotiating privately with a pharmaceutical company to test some of the compounds they have discovered and possibly turn them into drugs. As they wait, they open another Mason jar filled with murky pit water, draw a sample and return to work.
“The pit very easily could have been a complete waste of time,” Mr. Stierle said. “We just had luck and worked our butts off. We take that first walk into the dark.”
In NASA’s Sterile Areas, Plenty of Robust Bacteria
By WARREN E. LEARY, The New York Times, October 9, 2007
WASHINGTON, Oct. 6 — Researchers have found a surprising diversity of hardy bacteria in a seemingly unlikely place — the so-called sterile clean rooms where NASA assembles its spacecraft and prepares them for launching.
Samples of air and surfaces in the clean rooms at three National Aeronautics and Space Administration centers revealed surprising numbers and types of robust bacteria that appear to resist normal sterilization procedures, according to a newly published study.
The findings are significant, the researchers report, because they can help reduce the chances of stowaway microbes contaminating planets and other bodies visited by the spacecraft and confounding efforts to discover new life elsewhere.
“These findings will advance the search for life on Mars and other worlds both by sparking improved cleaning and sterilization methods and by preventing false-positive results in future experiments to detect extraterrestrial life,” said the leader of the study, Dr. Kasthuri Venkateswaran, a microbiologist at NASA’s Jet Propulsion Laboratory in Pasadena, Calif.
Identifying and cataloging what microbes might survive sterilization is important in interpreting results of sampling missions to other planets, scientists said. If similar microbes turn up in alien samples, researchers could disregard the results as contamination and not evidence of extraterrestrial life.
NASA tries to protect its spacecraft and their delicate components from dust and bacteria by assembling and testing them in rooms that are meticulously cleaned of dust and dirt by having their air continuously filtered to reduce fine particles. People working in these rooms wear coveralls with gloves and sometimes wear face masks.
Researchers from Dr. Venkateswaran’s Biotechnology and Planetary Protection Group and the Lawrence Berkeley National Laboratory published the results of their tests in the European journal FEMS Microbiology Ecology.
Samples taken from clean rooms at the Jet Propulsion Laboratory, the Kennedy Space Flight Center in Florida and the Johnson Space Center in Houston revealed almost 100 types of bacteria, about 45 percent of which were previously unknown to science, the study said. While some were common types that thrive on human skin, such as Staphylococcus species, others were oligotrophs, rarer microorganisms that have adapted to grow under extreme conditions by absorbing trace nutrients from the air or from unlikely surfaces like paint.
Traditionally, NASA has examined clean-room bacteria by taking samples of air and surfaces and trying to culture bacteria present in the laboratory. Dr. Venkateswaran said only a small fraction of bacteria could be found this way because most grow only in their native environments.
For their tests, the researchers used a genetic testing method not employed in clean rooms before, known as ribosomal RNA gene sequence analysis, which allowed them to study and decode a genetic marker common to all bacteria. The unique sequences of each type allowed the researchers to identify a greater number and diversity of bacteria than previously detected in the rooms.
While a few microorganisms, like those common on human skin, were found at all three sites, the study discovered that each room had a bacterial community largely unique to itself. Many factors could be responsible for this diversity, the researchers said, including the differing types of air filters and cleaning agents used and the facilities’ different geographic locations.
“I was surprised by what we found,” Dr. Venkateswaran said in an interview, “and as we continue to sample additional clean rooms, we may be in for even more surprises.”
Dr. Catharine A. Conley, a biologist who is the acting planetary protection officer at NASA headquarters, said the agency had long suspected that the organisms previously detected in clean rooms did not represent the full range that were there. Current cleaning techniques kill most common microbes, she said, and the resulting lack of competition could contribute to the number and diversity of the durable survivors found by the genetic testing approach.
“We know clean rooms can be much cleaner, and some are,” Dr. Conley said, citing some used by the semiconductor and pharmaceutical industries. “The problem is the cost. They are very expensive to build and maintain.”
Spacecraft going to areas where alien life is more likely to be found, like planets or moons with identifiable water, can be sterilized by a heat method that essentially bakes them for hours. But, she said, this runs the risk of damaging components.
Dr. Conley said NASA was experimenting with different techniques, including infusing spacecraft with vaporized hydrogen peroxide or a cold plasma of ionized gas, to attack the problem.
Spacecraft contamination is not just an issue for the United States, Dr. Conley noted. All space agencies sending out interplanetary probes follow cleanliness rules from an international organization called the Committee on Space Research. These standards vary depending on the type of mission, such as one that lands on a body versus orbiting it, and the likelihood that the destination bears life.
