Justiça e censura

Os jornais saem esta semana denunciando a série de ações de fiéis da Igreja Universal do Reino de Deus contra reportagens que saem nos jornais. Alegam que as séries visam criar um custo e uma complexidade para a defesa, com o intuito de prejudicar a liberdade de imprensa.

Segundo o portal Comunique-Se, a Editora Abril irá entrar com várias ações contra a minha série - uma de cada jornalista, uma da própria Abril. Não tenho departamento jurídico pessoal para me defender. Nem recursos financeiros para enfrentar ações prolongadas.

Se a Abril quisesse apenas questionar a série, bastaria uma ação.

Qual a explicação que se pode dar a essa estratégia de múltiplas ações?

enviada por Luis Nassif

Sobre o Reuni

Naomar de Almeida Filho

Folha de S.Paulo, 6.2.2008

Por que só os alunos lutam contra a reestruturação da universidade pública? Forças reacionárias predominam no movimento estudantil?

O REUNI é um ambicioso programa de expansão e reestruturação do sistema federal de educação superior, parte integrante do PAC da Educação. Foi concebido para duplicar a oferta de vagas públicas no ensino superior, com um orçamento de R$ 7 bilhões aplicados em cinco anos. Por razões ainda mal-entendidas, o Reuni sofreu intensa oposição de parte do movimento estudantil. Houve tumulto e violência em reuniões de conselhos universitários; reitorias foram invadidas; várias ocupações somente terminaram mediante mandados judiciais de reintegração de posse.
De nada adiantou. No prazo, todas as instituições federais de ensino superior (Ifes) aderiram ao Reuni e apresentaram propostas comprometendo-se a alcançar, ao final do programa, taxa de conclusão de 90% e relação aluno/professor de 18/1. Convém registrar que o indicador da taxa de conclusão, aparentemente inalcançável como média geral, na verdade incentiva o aproveitamento de vagas residuais por mobilidade interna ou externa. Por outro lado, a relação aluno/professor pode incorporar estudantes de pós-graduação, obedecendo aos critérios de qualidade da Capes.
Trinta anos depois da expansão resultante da reforma universitária de 1968, o crescimento da rede federal de ensino superior, no final dos anos 1990, foi iniciativa das universidades públicas e caracterizou-se por uma estratégia institucional de criação de fatos consumados. A universidade abria cursos novos ou ampliava a oferta de vagas sem contar com docentes, instalações, recursos financeiros; só depois se buscava criar as condições mínimas para tanto. Esse tipo de crescimento pode ser chamado de "autonomia-sem-apoio". Nessa fase, as Ifes submeteram-se a vigoroso ajuste, que, otimizando recursos humanos e materiais, conseguiu ampliar a relação aluno/professor do patamar de 7/1 para quase 12/1.
A segunda onda de expansão ocorreu no primeiro governo Lula, liderada pelo ministro Fernando Haddad. A principal característica dessa fase foi a interiorização da universidade brasileira, como atendimento emergencial a demandas históricas de populações e regiões representadas por lideranças político-partidárias. Nesse caso, os fatos consumados eram criados pelo governo federal, pouco respeitando a autonomia das Ifes. Por esse motivo, pode-se dizer que se trata de crescimento tipo "apoio-sem-autonomia". A estratégia institucional predominante baseava-se em implantação de cursos simultaneamente à contratação de docentes e à realização dos investimentos necessários. Nessa fase, o financiamento tem sido realizado durante a expansão de atividades da universidade.
O Reuni inaugura uma terceira fase de expansão do sistema universitário federal. Agora temos um modelo de crescimento da educação superior que, por um lado, respeita a autonomia universitária, acolhendo propostas específicas elaboradas por cada uma das instituições participantes do programa. Por outro lado, pela primeira vez, aplicação de recursos de custeio, investimentos, modelagem pedagógica e contratação de docentes e servidores são feitos antes da expansão de atividades e de vagas. A modalidade de crescimento "apoio-e-autonomia" parece em tese o melhor dos mundos. Não obstante, algumas questões precisam ser consideradas.
Primeiro, o Reuni implica planejamento estratégico de atividades das Ifes, obrigando-as a pensar o futuro de curto e médio prazo. Em segundo lugar, os apoios vinculam-se ao atendimento de metas pertinentes, supervisionado por sistemas de avaliação. Enfim, o REUNI representa um poderoso indutor de eficiência institucional e de qualificação pedagógica.
Desse modo, ao reduzir a enorme dívida social do ensino superior, implica enorme potencial de revalorização do campo público da educação. Nesta conjuntura, em todas as IFES, dirigentes acadêmicos, encorajados por incentivos gerenciais e financeiros do MEC, decidem mudar a universidade; docentes e técnicos, inspirados em tendências contemporâneas, elaboram novos modelos de renovação curricular; servidores, antevendo melhores condições de trabalho e valorização do serviço público, engajam-se ao processo. Porque somente os alunos, representados por uma minoria (pois a omissão da maioria estudantil não os exime da responsabilidade política), resistem às mudanças e lutam contra a expansão e reestruturação da universidade pública brasileira?
Será que, hoje, forças reacionárias e conservadoras predominam no interior do movimento estudantil?

---

NAOMAR DE ALMEIDA FILHO , 55, doutor em epidemiologia, pesquisador do CNPq, é professor titular do Instituto de Saúde Coletiva e reitor da UFBA (Universidade Federal da Bahia).

Uma decisão de grande responsabilidade

Marco Antonio Raupp

O Estado de S.Paulo, 10.2.2008

Na terça-feira próxima, sob a presidência da ministra Dilma Rousseff, reúne-se o Conselho Nacional de Biossegurança (CNBS), para apreciar recursos da Anvisa e do Ibama contra decisões da Comissão Técnica Nacional de Biossegurança (CTNBio). É importante que se reafirme para a sociedade civil a qualidade científica e tecnológica dos membros da CTNBio. São nomes da mais alta relevância, reconhecidos nacional e internacionalmente pela excelência da pesquisa que desenvolvem, muitos deles propostos pela Sociedade Brasileira para o Progresso da Ciência (SBPC). Esses cientistas se dedicam a avaliar as solicitações encaminhadas às quatro áreas de atuação da comissão: ambiental, vegetal e saúde humana e animal. Trata-se de trabalho constante e dedicado, que muitas vezes acaba sendo questionado não pelo mérito da decisão, mas pela falta de informação ou por razões ideológicas. Recentemente, o ministro de Ciência e Tecnologia, Sérgio Rezende, fez um balanço muito positivo dos trabalhos da CTNBio no último biênio. Esse trabalho, no entanto, vem sendo sistematicamente contestado por organizações não-governamentais (ONGs), principalmente quanto às liberações comerciais, e o próprio ministro destacou que o governo acompanha os numerosos recursos judiciais interpostos contra algumas decisões da CTNBio. A mais recente envolve o milho, contestado pelas ONGs e agora por setores do governo ligados aos Ministérios da Saúde e do Meio Ambiente.

O milho é uma das mais importantes fontes de alimento no mundo. Na cadeia produtiva de suínos e aves se consomem de 70% a 80% do milho brasileiro. O Brasil é o terceiro maior produtor mundial, com produção de aproximadamente 35 milhões de toneladas (em 2005), atrás somente dos EUA (282 milhões de toneladas) e da China (139 milhões). No País é plantado em duas safras e cultivado em quase todo o território nacional - 92% da produção se concentra nas Regiões Sul (47%), Sudeste (21%) e Centro-Oeste (24%).

Nos últimos anos, os insetos da ordem Lepidoptera (lagartas) se têm tornado pragas limitantes na cultura do milho no País, com danos de até 34% na produção desse grão. Com o aumento da área cultivada na chamada safrinha (3 milhões de hectares) o problema se agravou. Em algumas áreas são necessárias dezenas de pulverizações com inseticidas num único ciclo da cultura. O Brasil é o terceiro maior consumidor de defensivos agrícolas do mundo. Temos, hoje, 142 agrotóxicos registrados para milho, 107 só para lagartas. Já existem vários casos de resistência pelo uso constante e indiscriminado de inseticidas na cultura do milho no País. Além disso, um dos fatores que mais afetam a saúde dos agricultores no Brasil é o uso de defensivos agrícolas, altamente agressivos, responsáveis pela intoxicação de 1 milhão de pessoas anualmente, além do lixo tóxico resultante do descarte das embalagens.

Um dos produtos aprovados pela CTNBio é o milho modificado para resistir ao ataque das lagartas. Esse milho transgênico, cultivado e comercializado na União Européia e em mais 13 países - Argentina (desde 1998), Austrália, Canadá, China, Japão, Coréia do Sul, Filipinas, México, África do Sul, Suíça, Taiwan, Uruguai e EUA (neste último, desde 1995) -, expressa uma proteína responsável, especificamente, pela morte das lagartas, sem efeito tóxico para outros insetos, como abelhas, besouros ou joaninhas. Essa proteína é idêntica à encontrada em bactérias do solo que são pulverizadas nas culturas há mais de 40 anos, técnica amplamente utilizada pelos agricultores orgânicos. Outro processo em discussão é o do milho que ganhou um gene que o torna resistente a herbicida produzido por uma bactéria de solo, permitindo a eliminação de plantas daninhas com menor agressão ao solo no processo de aragem, além de outras vantagens. É importante ressaltar que nenhuma dessas variedades causou dano algum ao meio ambiente, aos animais ou aos seres humanos. No Brasil, exaustivos experimentos controlados no campo provaram sua inocuidade para o ambiente.

Somando os aumentos na renda de todos os agricultores que adotaram um dos seis principais cultivos transgênicos, o ganho mundial em dez anos foi de US$ 26,85 bilhões. O total de ganho em cada país variou de acordo com o número de cultivos e com a taxa de adoção da nova tecnologia. Os EUA foram o país que obteve maior ganho, quase US$ 13 bilhões em dez anos, e a Argentina, US$ 5,5 bilhões. A nossa participação no ganho mundial foi de apenas 5% e se deve ao fato de o País produzir, em grande escala, apenas soja tolerante a herbicidas.

Em ganhos ambientais se prevê que, em dez anos, a adoção do plantio de soja transgênica economizará 42,7 bilhões de litros de água, 300 milhões de litros de óleo diesel, com redução de emissões para a atmosfera de aproximadamente 1 bilhão de toneladas de dióxido de carbono, o equivalente a plantar 6,8 milhões de árvores. Para algodão e soja se estima uma redução de uso de mais de 77 mil toneladas de agrotóxicos. A nossa indústria é a mais prejudicada com o ingresso de sementes piratas, em razão da demora na adoção de sementes transgênicas.

Apelamos ao CNBS que não dê provimento aos recursos interpostos, reconhecendo que existe uma lei aprovada pelo Congresso Nacional (Lei 11.105/05) que atribui somente à CTNBio a responsabilidade de deliberação sobre organismos transgênicos e seus derivados. Anvisa e Ibama são órgãos de fiscalização, e não elaboradores de políticas de Estado.

Parte da cultura contra os transgênicos tem raízes obscurantistas e está causando muitos danos à ciência e à economia brasileiras, bem como ao meio ambiente, pelo uso indiscriminado de defensivos agrícolas. A sociedade tem de se posicionar de forma esclarecida, sem emoções, levando em consideração a qualidade técnico-científica do parecer e a credibilidade desses brasileiros que se dispõem a trabalhar para manter a rigidez de critérios na emissão de laudos fundamentados em ciência, não em crenças.

MEDICINE

Combating Impervious Bugs

Richard P. Novick^*

Science 15 February 2008:

Staphylococcus aureus has always been a serious human pathogen, and during recent decades it has become more serious owing to its acquisition of antibiotic resistance. In the past few years, a new strain of methicillin-resistant S. aureus (MRSA), known as USA300, and its close relatives, have emerged that are not only resistant to antibiotics but are more virulent and highly contagious. MRSA is presently spreading throughout the world, in hospitals and also in community settings where people are in close contact (1-3). Indeed, in the United Sates, MRSA infections now account for more deaths each year than AIDS (4). But two reports, by Corbin et al. on page 962 in this issue (5), and by Liu et al. in Science Express (6), are cause for some cautious optimism about new therapeutic approaches to treat such infections.

Both studies describe possible strategies for interfering with the ability of S. aureus to thwart attacks that are mounted by the immune system during infection. Bacteria defend against lethal reactive oxygen species (ROS) produced by neutrophils, immune cells that are mobilized to sites of infection. Corbin et al. show that calprotectin, a wellknown mammalian calcium-binding protein, chelates manganese (Mn²⁺), which the bacterium requires for growth and for detoxifying ROS. Liu et al. report that certain cholesterol- lowering drugs have an entirely unexpected activity against S. aureus--blocking synthesis of staphyloxanthin, the pigment that imparts the organism's characteristic color (aureus means "golden" in Latin) and also chemically detoxifies ROS.

Staphylococcal infection is an especially serious health threat in individuals with weakened immune systems, impaired circulation (as with diabetics), and surgical wounds. In deep-tissue sites, staphylococci can be lifethreatening, even in otherwise healthy individuals. Staphylococcal abscesses form when the host immune system recognizes certain bacterial products, including cell wall components and chemotactic (neutrophil-attracting) enzymes (7). The host mounts an aggressive inflammatory response, walling off the infected area by forming a meshwork of fibrin protein packed with neutrophils and other immune cells. Neutrophils take up (phagocytose) bacteria and kill them with ROS and other lethal agents. In defense, staphylococci deploy cytotoxins and enzymes to degrade host tissue and kill neutrophils and other cells. Neutrophils, however, continue their antibacterial activities posthumously (see the figure). Upon lysis, they release bactericidal ROS as well as DNA that forms a network to entrap bacteria (8). Bacteria respond by secreting potent nucleases to degrade the DNA. Staphylococci also produce substances that detoxify ROS, including staphyloxanthin and superoxide dismutase. Although the role of staphyloxanthin seems clear (9), that of calprotectin seems complex.

Raging battle. S. aureus and immune cells (neutrophils) use an arsenal of agents and enzymes to mount and combat infection. Nonantibiotic-based therapeutics may focus on the functions of calprotectin and staphyloxanthin. CREDIT: ADAPTED BY P. HUEY/SCIENCE

Calprotectin is a calciumbinding heterodimer that constitutes about 40% of the soluble cytoplasmic protein of a neutrophil. Its widespread biological roles include signaling to other immune cells after tissue damage and/or inflammation (10) and, as Corbin et al. show, defending against bacterial infection by chelating Mn²⁺. Because this cation is a required trace element, its depletion could simply inhibit bacterial growth, as the authors observed in vitro. Moreover, mice with calprotectin deficiency had abscesses with higher bacterial loads and about three times the amount of Mn²⁺ as did those in wild-type mice. But bacteria can grow in tissues and form abscesses in the presence of low natural concentrations of Mn²⁺, so it seems more likely that abscess attenuation is due to the effects of Mn²⁺ depletion on bacterial defenses against ROS. Mn²⁺ is also an essential component of bacterial superoxide dismutase A, which inactivates ROS enzymatically (11).

However, the situation may not be quite so simple, because staphylococci express catalase and other antioxidant enzymes that are repressed by Mn²⁺ through a regulatory protein, PerR (12). Thus, calprotectin could enhance the expression of these enzymes, thus enabling bacteria to counter the effects of ROS, even when the Mn²⁺ concentration is low. The effects of iron (Fe²⁺) in bacteria complicate matters further. Fe²⁺ drives the Fenton reaction, which converts hydrogen peroxide (H₂O₂) to the highly bactericidal hydroxyl radical (13); but Fe²⁺ also relieves PerR repression of the catalase gene, katA. This induces the synthesis of catalase, which destroys H₂O₂ and blocks the Fenton reaction. Therefore, katA and the other genes under the control of PerR may help counter ROS even if Mn²⁺ concentration is high (14). Because the relative effects of these various reactions in an abscess are unknown, and the prediction that adding excess Mn²⁺ would negate the calprotectin-dependent antibacterial effects of neutrophils was not examined, more work is needed to reveal how chelation of Mn²⁺ by calprotectin attenuates a bacterial infection.

As for detoxification of ROS by the pigment staphyloxanthin, nonpigmented staphylococci are rapidly killed by neutrophil-generated ROS and consequently are deficient in skin abscess formation in mice (9). Liu et al. show that similarities exist in the biosynthetic pathways of staphyloxanthin and host cholesterol. Remarkably, presqualene diphosphate is an early intermediate in both pathways. Liu et al. determined that the structure of CrtM, the staphylococcal enzyme that catalyzes presqualene diphosphate synthesis, resembles that of mammalian squalene synthetase. Moreover, the staphylococcal enzyme is inhibited in vitro by cholesterollowering drugs that block squalene synthetase. The authors further show that these cholesterol- lowering compounds attenuated a systemic murine infection by a pigmented strain of S. aureus infection (though a nonpigmented strain was not examined).

Blocking ROS detoxification by inhibiting staphyloxanthin synthesis and chelating Mn²⁺ may be attractive, new antistaphylococcal treatments that do not involve conventional antibiotics. However, some unanswered questions give pause. The strategy of removing an essential nutrient to combat infection is one previously proposed by Mahan et al. (15), who found that bacteria unable to synthesize purines were avirulent because the in vivo supplies of purines were insufficient to support bacterial growth. Whether one could reduce an essential trace metal to a concentration low enough to block bacterial growth without also compromising the functions of host cells remains to be seen. It is also a matter of concern that nonpigmented S. aureus are often isolated from abscesses and other infections. For translation to the clinic, both strategies warrant further examination.

References

1. A. D. Kennedy et al., Proc. Natl. Acad. Sci. U.S.A. 105, 1327 (2008).
2. R. J. Olsen, K. M. Burns, L. Chen, B. N. Kreiswirth, J. M. Musser, J. Clin. Microbiol. 0.1128/JCM.02029-07 (2008).
3. B. A. Diep et al., Ann. Intern. Med. www.annals.org/cgi/content/full/0000605-200802190-00204v1 (2008).
4. E. A. Bancroft, JAMA 298, 1803 (2007).
5. B. D. Corbin et al., Science 319, 962 (2008).
6. C.-I. Liu et al., Science 14 February 2008 (10.1126/science.1153018).
7. S. Tyski, S. Tylewska, W. Hryniewicz, J. Jeljaszewicz, Zentralbl. Bakteriol. Mikrobiol. Hyg. A 265, 360 (1987).
8. V. Brinkmann et al., Science 303, 1532 (2004).
9. G. Y. Liu et al., J. Exp. Med. 202, 209 (2005).
10. M. E. Bianchi, J. Leukoc. Biol. 81, 1 (2007).
11. M. H. Karavolos, M. J. Horsburgh, E. Ingham, S. J. Foster, Microbiology 149, 2749 (2003).
12. M. J. Horsburgh et al., Mol. Microbiol. 44, 1269 (2002).
13. B. H. Bielski, Philos. Trans. R. Soc. London B Biol. Sci. 311, 473 (1985).
14. M. J. Horsburgh, E. Ingham, S. J. Foster, J. Bacteriol. 183, 468 (2001).
15. M. J. Mahan, J. M. Slauch, J. J. Mekalanos, Science 259, 686 (1993).

DRUG-RESISTANT TUBERCULOSIS:

In South Africa, XDR TB and HIV Prove a Deadly Combination

Robert Koenig

Science 15 February 2008:

Since the 2005-2006 outbreak of extensively drug-resistant TB in KwaZulu-Natal, health experts have been grappling with how to detect and treat the disease

Tricky diagnosis. X-rays, like this one taken in Port Elizabeth, show TB infection, but tests to distinguish normal from drug-resistant TB can take weeks. CREDIT: KARIN SCHERMBRUCKER/AP

CAPE TOWN, SOUTH AFRICA--A gaunt man with dark, deep-set eyes nods toward the uniformed security guards at the gate and the nurses who wear double-thick "respirator" masks when they make their rounds. The cheerless ward, surrounded by a 3-meter fence, is "more like a prison than a hospital," he says. "Many patients are depressed; they don't want to be here," the chief nurse tells a visitor as a TV soap opera drones in a nearby room.

That feeling is understandable. The two dozen men and women in the isolated ward are undergoing harsh and possibly futile treatment for the often lethal, contagious, and stigmatized disease that has brought them to Brooklyn Chest Hospital: extensively drug-resistant tuberculosis (XDR TB). The emergence over the past 2 years of the disease--which is even more difficult to treat effectively when patients are coinfected with HIV, as many are--is posing complex medical, ethical, and scientific issues in South Africa, the site of the largest and deadliest XDR TB outbreak to date. Last year, more than 500 cases of XDR TB were diagnosed here, and the total number was probably far higher.

On the medical front, the challenges include treating an infection that resists even last-ditch medications and finding the best ways to prevent hospital transmission of the disease (see sidebar, p. 897). Among the research challenges are identifying new drug targets and rapid diagnostics, as well as investigating the molecular evolution of the TB strains that led to the emergence of this new threat. The main ethical quandary is the extent to which hospitals can or should isolate XDR TB patients against their will or force them to take potentially lifesaving yet toxic drugs--perhaps for years.

Few warning signs
In August 2006, researchers made headlines at the annual AIDS meeting in Toronto, Canada, with a report that a new strain of TB, apparently resistant to almost all known drugs, had emerged in South Africa. The cases had been detected in 2005-2006 in the poor, mainly Zulu community of Tugela Ferry in South Africa's KwaZulu-Natal (KZN) Province; nearly all the victims were also coinfected with HIV. Especially alarming was the fatality rate: 52 of 53 patients had died within a median of 16 days after being tested for TB (Science, 15 September 2006, p. 1554).

XDR TB caught health care workers off guard and sparked fears of a new wave of "killer TB" outbreaks--especially in countries with high rates of HIV infection--that could jeopardize the progress in global TB control. The outbreak provided a "wake-up call," says Mario Raviglione, director of the World Health Organization's (WHO's) Stop TB Department, which had first discussed the emergence of XDR TB of Tugela Ferry and elsewhere at a meeting in May 2006. WHO quickly formed a global XDR TB task force that soon made recommendations for dealing with the threat. These include better TB and HIV/AIDS control and stricter management of drug-resistant TB, as well as better laboratory services and more extensive surveillance.

Although the Tugela Ferry outbreak was startling, XDR TB wasn't brand-new. Sporadic cases had been reported in the United States, Latvia, Russia, and elsewhere; WHO and the U.S. Centers for Disease Control and Prevention in Atlanta, Georgia, had first defined the strain in a March 2006 article. Nor was the new bug totally unexpected, given the poor record of treating TB in many countries. After multidrugresistant (MDR) strains of TB surfaced a couple of decades ago, some scientists had warned, it was only a matter of time before new strains, resistant to even more drugs, would emerge.

MDR TB first garnered widespread attention in the 1990s, when researchers and clinicians around the globe began identifying an alarming number of cases that were resistant to at least two of the four standard drugs used to treat TB. Suddenly, the already arduous task of treating TB became even more difficult and expensive. MDR TB can take as long as 2 years to treat, compared with 6 to 8 months for drugsensitive TB. Costs run 3 to 100 times higher, depending on the country and the drug-resistance pattern. WHO now estimates that of the 8 million cases of active TB diagnosed each year, more than 400,000 are MDR. Cases tend to be concentrated in regions where inadequate healthcare services make it harder to ensure that patients can follow the lengthy drug regimen.

Resistance can arise when patients fail to complete their therapy, thereby giving the TB bacteria an opportunity to mutate to evade the drugs. That's why a cornerstone of TB therapy has long been directly observed treatment-short course (DOTS), which focuses on supervised adherence to a fixed combination of anti-TB drugs. However, DOTS does not require drug-resistance testing, meaning that many undiagnosed MDR TB patients have been treated by an ineffective DOTS drug regimen that may have allowed those MDR TB strains to develop even further drug resistance. To help address that problem, WHO in March 2006 began recommending what's called the "DOTS-Plus" protocol--which calls for using second-line TB drugs for people with confirmed or presumed MDR TB--for some high-incidence countries.

"The major challenge is to see that TB patients stay on the treatment regimen," says Karin Weyer, head of the TB program at South Africa's Medical Research Council (MRC). Lindiwe Mvusi, who heads the South African Health Department's TB Program Directorate, estimates that at least 20% of the country's MDR TB patients are defaulting, making it more likely that some may eventually end up with XDR TB. Because XDR TB is resistant to most of the second-line drugs that are used to treat MDR TB (including fluoroquinolone-category medications as well as either amikacin, capreomycin, or kanamycin), clinicians have few options, other than trying older drugs or new combinations of drugs.

Paul van Helden, co-director of the Centre of Excellence in Biomedical TB Research at Stellenbosch University, questions whether the DOTS drug protocols are always the best approach in high-incidence TB countries such as South Africa. He believes more investigations are needed to determine the best mixture of drugs to treat MDR and XDR TB in different regions.

At this point, no one knows exactly how many cases of XDR TB there are globally, because most go undiagnosed and are not reported. WHO recently estimated that XDR TB may infect about 27,000 people a year in at least 41 countries. But this is just an educated guess, based on a percentage of the MDR TB cases diagnosed each year. Later this month, a new WHO report will give a more detailed picture of the spread of drug-resistant TB.

Flash point at Tugela Ferry
In retrospect, it's not surprising that the 2005-2006 outbreak occurred in KZN Province, which includes areas of extreme poverty. Although for centuries tuberculosis has been called The White Plague, in South Africa it is predominantly a disease of black Africans, a byproduct of poverty, poor health care, and--perhaps most perniciously--a high HIV infection rate. About 5.5 million South Africans are HIV-infected, about 11% of the population, with the highest infection rate in KZN. The combination of drug-resistant TB and HIV is especially dangerous because the weakened immune systems of HIV-infected persons make them more vulnerable to TB and also more difficult to treat.

The Tugela Ferry outbreak was detected when doctors at Church of Scotland (COS) Hospital began investigating the unexpectedly high mortality rate among TB-HIV-coinfected patients. Drug-sensitivity tests revealed that not only was MDR TB rampant, but even more patients had the superresistant XDR strain. Before then, few clinicians tested for drug resistance because it was expensive and time-consuming. That has changed over the last 2 years; today, many South Africans who test positive for TB are started on first-line drugs while being tested for drug resistance.

Isolation. The new XDR TB ward at Brooklyn Chest Hospital in Cape Town is guarded around the clock and surrounded by a high chain-link fence. A patient who tested positive for XDR TB awaited treatment at a rural hospital in Tugela Ferry in 2006 (right). CREDITS (LEFT TO RIGHT): WESTERN CAPE DEPARTMENT OF HEALTH/SOUTH AFRICA; REUTERS/MIKE HUTCHINGS

Since the initial reports, a total of 217 XDR TB cases have been found in Tugela Ferry, with a mortality rate of 84% between June 2005 and last March. Paul Nunn, the TB-HIV and drugresistance coordinator at WHO's Stop TB Department, calls the Tugela Ferry outbreak "the worst of its kind" worldwide, in terms of the number of cases, fatality rate, and the high ratio of XDR to MDR cases.

Was Tugela Ferry the harbinger of other severe XDR TB outbreaks or an anomaly resulting from an unusual convergence of risk factors? Gerald Friedland of Yale University School of Medicine--whose research group reported the outbreak at the 2006 AIDS conference as part of its collaboration with physician Anthony Moll's COS hospital staff and other institutions--worries that interlinked HIV and XDR TB epidemics could "create a firestorm" in many South African communities. He argues that the current South African statistics are unreliable and the extent of the problem underestimated because "there has been a marked underreporting of XDR TB."

But other TB experts, including Weyer and Mvusi, regard Tugela Ferry as atypical, in large part because its mortality rate has not been matched anywhere else in South Africa. Mvusi says there were 183 confirmed deaths from XDR TB in South Africa last year, but 342 XDR TB patients were still under treatment--giving hope that some cases can be managed. Although the Eastern Cape and KZN provinces had the most XDR TB cases, the strain has been found in all nine South African provinces. Many of those XDR TB patients were HIV-infected and many others had defaulted on TB drug regimens.

Searching for origins
In the wake of the Tugela Ferry outbreak, scientists have been using molecular fingerprinting techniques to analyze thousands of old, frozen TB samples to try to reconstruct the history of XDR TB's emergence in South Africa. At the University of KwaZulu-Natal, A. Willem Sturm's team discovered that XDR isolates of the KZN strain had existed undetected as far back as 2001. About 9% of the province's 2634 MDR TB cases had actually been XDR infections.

XDR isolates dating back to 2001 were also found in western South Africa, where biologists at Stellenbosch University's TB research center are conducting a retrospective analysis of thousands of TB samples. They are also cooperating with the Broad Institute and Harvard School of Public Health in Boston to sequence and compare the genomes of several drug-resistant TB strains isolated here (Science, 9 November 2007, p. 901).

Meanwhile, other groups are searching for faster and cheaper ways to detect XDR TB, as well as new drugs to treat it. Testing for resistance to second-line drugs can take up to 2 months using the standard techniques, by which time patients may have been treated with the wrong drugs.

In South Africa and elsewhere, clinical trials of new, molecular-based tests for drug resistance are already under way by MRC, in cooperation with the Foundation for Innovative New Diagnostics in Geneva, Switzerland. If WHO validates the results, approval seems likely for a German firm's test that can quickly detect MDR TB and is being modified to detect XDR TB. Other groups are also testing their own molecular-based techniques.

Drugs for treating XDR TB are much further away, although several trials are under way. For now, doctors prescribe older TB drugs such as capreomycin and ADT that have not been used in typical second-line drug regimens.

Despite the daunting challenges, there is some reason to hope that XDR TB patients can be effectively treated, if not cured. In contrast to the Tugela Ferry outbreak, Iqbal Master, chief of medicine for drug-resistant TB at King George V Hospital in Durban, says two-thirds of the 133 XDR TB patients who were in King George V Hospital during 2007 were still alive at the year's end. Researchers in Latvia suggest that up to 30% of XDR TB cases that are not HIV-infected could be effectively treated. That is good news for patients but poses problems for medical officials who must decide whether and how to separate XDR TB patients from others during the lengthy treatment period.

The isolation debate
"We were caught off guard by XDR TB," concedes Marlene Poolman, the deputy director for TB control at the Western Cape province's health department in Cape Town. No cases were diagnosed until the end of 2006, and the following year, the number of XDR TB admissions at Brooklyn Chest Hospital soared to 72. "Virtually overnight, we had to convert an empty ward into a new XDR unit." The chain-link fence and 24-hour guards were added in October after several patients left the hospital and had to be returned under court order.

Involuntary isolation or confinement of XDR TB patients is controversial, allowed in some nations only if the disease is found to pose an immediate threat to public health. WHO recommends separating XDR TB patients from others, especially in regions with high HIV prevalence, and South Africa's health department has adopted that policy.

But even high fences and guards at some specialized TB hospitals in South Africa haven't kept all patients inside. In December 2007, 20 XDR TB patients and 28 MDR TB patients in another ward cut a hole in the fence and fled a TB hospital in Port Elizabeth. A month later, eight of those patients had not returned, despite court orders.

Mvusi says overcrowding at some hospitals and clinics, especially in high-incidence areas such as KZN, has made it difficult to separate XDR TB patients. King George V Hospital had a waiting list of 120 drug-resistant TB patients at the end of last year. Many of those were being treated as outpatients.

Master says the caseload is challenging the health care system. If patients with M(X)DR TB survive their entire 2-year treatment regimens and still test positive for drugresistant TB, Master asks, "What do you do then? You can't put everyone in the hospital for an indefinite period."

RETROVIRUS MEETING:

Back-to-Basics Push as HIV Prevention Struggles

Jon Cohen

Science 15 February 2008:

BOSTON--At the big annual AIDS conference held in the United States, new drug studies once dominated the agenda. But last week at the 15th Conference on Retroviruses and Opportunistic Infections (CROI), treatment took a back seat to prevention. Many powerful anti-HIV drugs now exist, but few attempts to obstruct HIV infection have succeeded. Results presented at CROI, which ran from 3 to 6 February, continued the string of bad news and prompted much soul-searching about how to invigorate the ailing vaccine search. A few sessions did, however, relieve some of the gloom with reports on new ways to stop HIV's spread from mother to child and new insights into how HIV causes an infection and destroys the immune system.

Vaccine researcher Ronald Desrosiers, head of the New England Primate Research Center in Southborough, Massachusetts, sparked debate by criticizing the funding priorities at the U.S. National Institutes of Health (NIH) in Bethesda, Maryland. NIH devotes nearly one-third of the roughly $600 million it spends annually on AIDS vaccine research to developing and testing products in humans, yet, Desrosiers asserted, no product now under development has "any reasonable hope of being effective." "Has NIH lost its way in the vaccine arena?" asked Desrosiers, who argued for more basic research. "I think it has." (ScienceNOW, 5 February: sciencenow.sciencemag.org/cgi/content/full/2008/205/1.)

The beleaguered AIDS vaccine field took a serious hit last September, when researchers halted a clinical trial of a promising AIDS vaccine after an interim analysis revealed that it offered no protection against HIV. More disconcerting still, some evidence suggests that preexisting antibodies against an adenovirus strain, Ad5, used in the Merck and Co. vaccine to carry HIV genes, may somehow have made people more susceptible to the AIDS virus (Science, 16 November 2007, p. 1048). Data from Susan Buchbinder, an epidemiologist at the San Francisco Department of Public Health in California and co-chair of the study, offered some reassurance that the vaccine did not cause harm. Circumcision protects men from HIV, and uncircumcised men with high levels of Ad5 antibodies appear to have become infected more readily. "The effect of circumcision seemed at least as strong if not stronger than Ad5 [antibodies]," said Buchbinder. Although it's difficult to unravel cause and effect in post-hoc analyses, Buchbinder said: "I don't think at the end of the day that Ad5 was associated with increased infection."

In another blow to the prevention field, Connie Celum of the University of Washington, Seattle, revealed unexpected results from a study aimed at reducing susceptibility to HIV infection by treating preexisting infection with herpes simplex virus-2 (HSV-2). Infection with HSV-2, which causes genital ulcers, makes a person two to three times more vulnerable to HIV infection through sex. In a multi-country study involving more than 3000 people, Celum found that treatment with the anti-HSV-2 drug acyclovir did not reduce HIV transmission. Over the course of 18 months, 75 people who received acyclovir became infected with HIV versus 64 who received a placebo. "This is a surprising, disappointing, and important result," said Celum. "Many people thought this was going to be a slam dunk."

Gutsy virus. Several studies suggest that the AIDS virus causes immune "activation" by destroying Th17 cells, a CD4 subset that resides in the gastrointestinal tract and secretes "defensins" that prevent bacteria from entering the bloodstream and lymph nodes. CREDIT: ADAPTED FROM GUIDO SILVESTRI/UNIVERSITY OF PENNSYLVANIA

Celum said the problem wasn't linked to a failure to take acyclovir and that the treatment did reduce genital ulcers--although not as much as in earlier trials. That means intervention might work with a more powerful anti-HSV-2 drug or an effective HSV-2 vaccine, she said.

On a more positive note, two studies of thousands of HIV-infected pregnant women in several developing countries showed for the first time that anti-HIV drugs given to their babies could prevent transmission of the virus through breast milk. "The data are very exciting, but there are caveats," said Michael Thigpen of the U.S. Centers for Disease Control and Prevention in Atlanta, Georgia, which sponsored one of the studies. Babies can develop resistance to the drugs, which can limit treatment options if they do become infected.

Some intriguing data came from studies of a new type of immune actor, discovered just 2 years ago, called Th17 cells. HIV targets and destroys CD4 white blood cells; Th17 cells are a subset of CD4 cells that secrete interleukin-17. Three labs reported that in monkeys and humans, destruction of Th17 cells in the gut make it "leaky," allowing gut microbes, or pieces of them, to flood into the bloodstream. The researchers contend that this turns up the immune system, "activating" CD4 cells that then prematurely die or become targets for HIV themselves. In one study, said Barbara Cervasi, a postdoc in Guido Silvestri's lab at the University of Pennsylvania, Th17 cells were profoundly depleted in the gastrointestinal tracts of HIV-infected people and SIV-infected macaques--species that both develop AIDS--but not in SIV-infected sooty mangabeys that suffer no harm from that virus. "People assume that high [HIV or SIV levels] lead to activation," said Silvestri. "What if it's the opposite and activation causes the problems?"

In the final session, George Shaw of the University of Alabama, Birmingham, reported that his group had sequenced the HIV envelope gene in 102 recently infected people. HIV-infected people carry many genetic variants of the virus, but a single one established an infection and dominated in 80% of the subjects, Shaw and co-workers found. Although other studies have shown that a "bottleneck" occurs in sexual transmission of HIV, allowing few viruses to infect, this is the first study to clarify just how few. Four other new studies have had similar findings, said Shaw.

Shaw, who hopes to discover and target HIV variants that are especially good at transmission, said this work is good news for vaccine researchers. "If all you've got to deal with is one virus," said Shaw, "surely it shouldn't be so difficult to develop a vaccine."

O trote nas Universidades

Por Hilano Carvalho

Nassif,

O que você acha do trote nas universidades ? O que você achou do caso do estudante de direito em Ribeirão Preto que, drogado, invadiu um posto e atropelou um frentista ? O que se passa na cabeça dos universitários e estudantes em geral ? Estou estarrecido !

enviada por Luis Nassif

Polícia pede prisão de estudante que atropelou frentista em Ribeirão

Exame preliminar diz que o jovem pode ter ingerido bebida alcoólica; no carro foram encontrados seis frascos de lança-perfume, um deles estava vazio

DA FOLHA RIBEIRÃO
DA FOLHA ONLINE

A Polícia Civil de Ribeirão Preto (314 km de São Paulo) pediu ontem à Justiça a prisão preventiva do estudante de direito Caio Meneghetti Fleury Lombardi, 19.
A bordo de um Vectra, ele invadiu um posto de gasolina, bateu em um carro que estava sendo abastecido e atropelou o frentista Carlos Pereira Silva, 37. O acidente aconteceu por volta das 22h de segunda-feira.
Segundo a polícia, Lombardi tinha acabado de sair de um trote universitário e pode ter usado lança-perfume -no carro dele havia seis frascos do entorpecente, um deles vazio.
O boletim de ocorrência foi lavrado no 1º Plantão Policial, como lesão corporal culposa em acidente de trânsito, e informa que o exame médico preliminar constatou que o rapaz poderia ter ingerido bebida alcoólica. Anteontem, após analisar as imagens gravadas pelo circuito interno de TV do posto de gasolina, a Polícia Civil afirmou que pode mudar o indiciamento de Lombardi.

Acidente
Ainda de acordo com a polícia, o rapaz atravessou o canteiro da avenida Independência e entrou direto no posto. Na invasão, arrancou a bomba de gasolina, bateu em um Corsa que estava abastecendo e em seguida atropelou o frentista, que ficou preso sob o carro. Logo depois, o estudante tentou fugir, mas foi impedido por pessoas que estavam no posto. Ele foi ameaçado de espancamento.
A reportagem tentou ouvir o estudante, mas ele não foi encontrado. Seu advogado, Eduardo Sandoval de Melo Franco, disse que só falaria com a imprensa no decorrer das investigações.
Ontem, o frentista permanecia internado em estado grave no Hospital das Clínicas da cidade, cuja assessoria informou que ele está sedado e respira com ajuda de aparelhos. Silva sofreu queimaduras e traumatismo craniano.

Shutting off genes stops cancer cells from growing but leaves healthy cells unharmed

Erika Check Hayden

Gene signatures (top) result from multi-gene analysis (middle) of cancer-cell survival (bottom).SCIENCE

Geneticists have identified genes that are normally present and that seem to be key to the growth and survival of specific cancers. The finding, from a ‘functional-genomics’ screen of human cells, could offer new drug targets for blitzing tumours.

In an alternative approach to the traditional search for oncogenes (rogue genes that can turn normal cells into tumours), two teams of US scientists publish support this week for what they call the “non-oncogene addiction” idea: that a tumour relies heavily on certain normal cell pathways, and that drugs disabling gene products in those pathways could be deadly to cancer. The teams, led by Stephen Elledge of Brigham and Women’s Hospital in Boston, Massachusetts, and Greg Hannon of Cold Spring Harbor Laboratory in New York, designed a method to knock down thousands of genes relatively cheaply and quickly.

The method uses ‘short hairpin RNAs’ (shRNAs) — pieces of RNA that can be designed to target and shut off specific genes. In two papers^1,2, the teams describe how they introduced thousands of shRNAs that target normal genes into colon cancer cells, breast cancer cells and healthy breast cells. Dozens of the shRNAs slowed or stopped the cancer cells from growing, but didn’t impair the healthy cells, which could point the way to new cancer drug targets.

“It will take time and money to sort out which of these are the best drug targets, but the important thing is that we are finding them,” Elledge says.

'Welcome advance'

Oncologists say that drugs against oncogene products, such as Novartis’ Gleevec (imatinib) and Genentech’s Tarceva (erlotinib), have been a welcome advance for patients with cancer. But because patients often develop resistance to the drugs, they are not cures, says Gary Schwartz of New York’s Memorial Sloan-Kettering Cancer Center. “Everyone’s looking for the next Gleevec, but even though these targeted drugs have been exciting, they have not had the overwhelming impact we would have hoped for,” says Schwartz, who is trying to find funding for a clinical trial of a drug that inhibits a normal cell-cycle pathway³. Early clinical trials of the drug indicate that it may operate best in a ‘therapeutic window’ in which it is more harmful to cancer cells than to healthy cells, Schwartz says.

Elledge and Hannon say that their work will complement two large projects aiming to spur development of more drugs like Gleevec and Tarceva, which target mutations involved in certain blood and lung cancers. Both projects involve sequencing the genomes of cancer cells to find more oncogenes and help scientists understand the biology of cancer. One — the The Cancer Genome Atlas — began in December 2005, and is expected to cost $1.35 billion over 9 years. The other is led by scientists at the Wellcome Trust Sanger Institute in Cambridge, UK.

The team has long contended that the sequencing studies have a low “bang for the buck” — they are quite costly and will require detailed follow-up studies to sort out the mutations that drive cancers from those that are merely along for the ride. Their work is, by contrast, cheap and easy enough to be done in a single laboratory. And they that say their “functional” approach, which looks at the behaviour of cancer cells in response to certain triggers, might be a quicker path to new drugs.

“The sequencing becomes the easy part — the longer road is going to be to figure out what it all means in functional studies.”

Elledge and Hannon have found growing support for their argument, even among scientists using the sequencing approach. Bert Vogelstein, co-director of the Ludwig Center at Johns Hopkins School of Medicine in Baltimore, Maryland, says that his own studies highlight the need for the cancer atlas to fund some functional-genomics work. “What’s clear now that wasn’t clear at the beginning of The Cancer Genome Atlas is the complexity and heterogeneity of the mutational signatures that are going to be found in most cancers,” says Vogelstein, who demonstrated such complexity in a 2006 study on breast and colorectal cancers⁴.

“The sequencing becomes the easy part — the harder and longer road is going to be to figure out what it all means in functional studies,” Vogelstein says. “I believe some well-thought-out combination of those two approaches is likely to be the best way to progress.”

• References

  1. Schlabach, M. R. et al. Science 319, 620-624 (2008).
  2. Silva, J. M. et al. Science 319, 617-620 (2008).
  3. Fornier, M. N. et al. Clin. Cancer Res. 13, 5841-5846 (2007). | Article | PubMed | ChemPort |
  4. Sjöblom, T. et al. Science 314, 268-274 (2006). | Article | PubMed | ISI | ChemPort |

Prizes Eyed to Spur Medical Innovation

John Travis

MAASTRICHT, THE NETHERLANDS--If the World Health Organization offered a $10 billion award for a malaria vaccine, would that persuade major pharmaceutical companies to go after the prize? Could a $100 million prize encourage development of a reliable, cheap, and fast diagnostic assay for tuberculosis? And would those monetary awards prove to be the cheapest, or fastest, way to achieve such medical innovations?

Provocative questions such as those were at the core of a 2-day workshop^* here last week addressing whether prize incentives can stimulate the creation of new drugs and therapies. For some speakers, prizes offer a chance to spur medical research on neglected diseases, including those that strike people in developing nations who can afford little health care. Others took a more radical view: A national or global medical prize scheme could eliminate drug patents, stimulate drug development, and lower escalating health care costs. "A prize is a [research] incentive, the same way a monopoly is an incentive," says James Love, director of the think tank Knowledge Ecology International (KEI) in Washington, D.C.

Prize-worthy. Noting the long history of scientific and technological prize contests, James Love argues that a national scheme of awards for medical innovations should replace drug patents.
NOTABLE AWARDS	AMOUNT	GOALS	WINNER
Napoleon's Food Preservation Prize (1795)	12,000 francs	Ease food-supply problems for invading armies	Nicolas François Appert's canning process (1809)
Ansari X Prize (1995)	$10 million	Private, crewed reusable spacecraft	SpaceShipOne (2004)
Methuselah Mouse Prize (2003)	$4.5 million fund	Extend longevity or slow aging of mice	Multiple winners
Prize4Life (2006)	$1 million	Biomarker for ALS	No winners so far

CREDIT: (IMAGE) HERMAN PIJPERS/UNU-MERIT

Cosponsored by KEI and UNU-MERIT, a research and training center run jointly by United Nations University and Maastricht University, the workshop drew several dozen economists, intellectual-property specialists, public-health officials, and drug-development experts to discuss a concept that's attracting more attention. For example, U.S. Senator Bernie Sanders (I-VT) has introduced a bill, the Medical Innovation Prize Act, written with Love's help, that would replace medical patents with an estimated $80 billion annual award fund. Although the bill is unlikely to go anywhere now, Sanders hopes to get a Senate hearing this year to publicize the concept. "There is growing interest and political feasibility for trying prizes in a variety of contexts," says Stephen Merrill of the U.S. National Academies, who recently examined how the U.S. National Science Foundation could set up a prize system to stimulate innovation (Science, 26 January 2007, p. 446).

Prize contests have long been used to steer efforts toward particular discoveries or technological accomplishments, and they're becoming popular again (Science, 30 September 2005, p. 2153). One well-known early success was the British government's 18th century prize to find a way for seafarers to gauge longitude. More recently, the $10 million Ansari X Prize for a private, reusable, crewed spacecraft prompted an estimated $100 million to $400 million in space-flight research before Burt Rutan's SpaceShipOne won it in 2004.

Although perhaps not as prevalent as technology competitions, medical prizes are attracting sponsors. Pierre Chirac of Médecins sans Frontières said at the meeting that his group was considering an award for the desperately needed TB diagnostic test. And in 2006, Prize4Life, a nonprofit group founded by a patient with amyotrophic lateral sclerosis (ALS), announced a $1 million prize for a biomarker that can track the fatal disease's progression--a key for any drug development. Prize4Life hopes to launch two more contests, including a $2.5 million prize for a treatment that proves effective in a common mouse model of ALS.

Such modest awards pale in comparison to the mammoth prize system Love advocates through the Sanders bill. Financed annually with 0.6% of the United States's gross domestic product--about $80 billion at the moment--the Sanders plan would give annual awards to medical innovations based on the health impact for the nation--assessed using a measurement known as quality-adjusted life years that gauges improvements in life expectancy. Instead of the government granting patents to a company, a board that would include business and patient representatives, as well as government health officials, would each year judge any new products and award their developers a share of the fund.

At the Maastricht meeting, intellectual-property specialist William Fisher III of Harvard Law School argued that prize schemes have some advantages. Patents, said Fisher, guide medical research away from vaccines, which may require at most a few doses per person but arguably have the most health impact, and toward treatments for the rich and the development of "me-too" drugs, copies of an already successful drug with just enough differences to be patentable. "Prizes can offset all three" of those biases, he says.

PhRMA, a trade group in Washington, D.C., that represents pharmaceutical and biotech firms, has strongly criticized the Sanders bill as a step toward socialized medicine. And yet it is intrigued by new incentives, if the patent system stays intact. "It's an interesting idea to add prizes for neglected diseases to the existing system," says Shelagh Kerr of PhRMA, who attended the workshop.

Prize incentives are, however, unlikely to sweep the medical research world. Philanthropic and patient groups may offer new awards, but governments may be more cautious. "We're no longer in the Longitude Prize era. We pay scientists many millions to do research," says David King, former science adviser to the U.K. government. "How do you decide how much money to award?" adds economist Aidan Hollis of the University of Calgary in Canada, noting that governments typically don't know in advance what social value a medical treatment will have.

The workshop itself offered an ironic morsel of evidence that prizes are not perfect incentives. Organizers offered a €1500 award for the best paper on using monetary prizes to stimulate private investment in medical research, but no entries have been submitted thus far. The contest has now been extended to mid-April.

^* "Medical Innovation Prizes as a Mechanism to Promote Innovation and Access," 28-29 January.

Lifting the Veil on Traditional Chinese Medicine

Richard Stone^*

DALIAN, CHINA--Genome, proteome, metabolome … herbalome? In the latest industrial assault on nature's biochemical secrets, a Chinese team in this seaside city is about to embark on a 15-year effort to identify the constituents of herbal preparations used as medications for centuries in China.

The Herbalome Project is the latest--and most ambitious--attempt to modernize t raditional Chinese medicine (TCM). The venerable concoctions--as many as 400,000 preparations using 10,000 herbs and animal tinctures--are the treatment of choice and often the only recourse for many in China. In the 1970s, TCM tipped off researchers to qinghaosu, a compound in sweet wormwood whose derivatives are potent antimalaria drugs. But TCM's reputation has been blackened by uneven efficacy and harsh side effects, prompting critics to assail it as outmoded folklore. "TCM is not based on science but based on mysticism, magic, and anecdote," asserts biochemist Fang Shi-min, who as China's self-appointed science cop goes by the name Fang Zhouzi. He calls the Herbalome Project "a waste of research funds."

Hoping to rebut TCM critics, Herbalome will use high-throughput screening, toxicity testing, and clinical trials to identify active compounds and toxic contaminants in popular recipes. "We need to ensure that TCM is safe and also show that it is not just qinghaosu," says Guo De-an, who leads TCM modernization efforts at the Shanghai Institute of Materia Medica and is not involved in Herbalome. Initial targets are cancer, liver and kidney diseases, and illnesses that are difficult for Western medicine to treat, such as diabetes and depression.

The Dalian Institute of Chemical Physics (DICP), one of the biggest and best-funded institutes of the Chinese Academy of Sciences, won a $5 million start-up grant to develop purification methods; the Ministry of Science and Technology is reviewing the project with a view to including it as a $70 million initiative in the next 5-year plan to start in 2010. A planning meeting will be held at a Xiangshan Science Conference--China's equivalent of a Gordon Research Conference--in Beijing this spring.

Several TCM power players have thrown their weight behind the initiative. "It's the right time to start this project," says chemist Chen Kai-xian, president of the Shanghai University of Traditional Chinese Medicine. Herbalome should appeal to pharmaceutical firms, as it could identify scores of drug candidates, says Hui Yongzheng, chair of the Shanghai Innovative Research Center of Traditional Chinese Medicine.

In many parts of the world, traditional medicine recipes are handed down orally from one generation to the next. But in China, practitioners more than 2000 years ago began to compile formulations in compendia. Although in major cities Western medicine has largely supplanted TCM, many Chinese still believe in TCM's power as preventive medicine and as a cure for chronic ailments, and rural Chinese depend on it. "For most of us, when we feel unwell, we want to take TCM," says chemist Liang Xinmiao of DICP.

Medicine man. Liang Xinmiao's Herbalome Project aims to identify active ingredients and toxins in thousands of traditional Chinese preparations. CREDIT: R. STONE/SCIENCE

Since the Mao Zedong era, the government has strongly supported TCM, in part because it was too expensive to offer Western medicine to the masses. It remains taboo for Chinese media to label TCM as pseudoscience. "Criticizing TCM is unthinkable to many Chinese and almost like committing a traitorous act," says Fang.

Proponents insist that TCM has much to offer. But for every claimed TCM success, there are reports of adverse effects from natural toxins and contaminants such as pesticides. Dosages are hard to pin down, as preparations vary in potency according to where and when herbs are harvested. Quality can vary from manufacturer to manufacturer and from batch to batch. "That's why many people don't trust TCM," says Guo. In the modernization drive, quality control is a paramount concern.

Herbalome intends to take modernization to a whole new level. The initiative is the brainchild of Liang, who believes many TCM recipes are effective. "The problem is, we don't know why it works," he says. The main hurdle is the complexity of the preparations. As an example, Liang shows a chromatograph of Hong Hua, or "red flower," a preparation applied externally for muscle pain. In many samples chemists deal with, one peak usually represents one compound, Liang says. But for Hong Hua, each peak is many compounds, and fractionating these yields more multicompound peaks like nested matryoshka dolls. Hong Hua is composed of at least 10,000 compounds, says Liang: "We know only 100."

Faced with such complexity, "we must invent new methodologies," says Liang. "This is the battleground of the Herbalome project." For starters, his 45-person team at DICP is developing new separation media. Herbs will be parsed into "multi-components": groups of similar constituents. To determine which substances are beneficial or toxic, his group plans to devise Herbalome chips in which arrays of compounds are screened for their binding to key peptides. The expanded Herbalome project would involve researchers at many institutes in China and abroad.

Herbalome has potential pitfalls. One is a concern that Western companies will develop blockbuster drugs--and walk away with the spoils--by modifying compounds identified by the project. To counter this possibility, says Guo, "we're encouraging scientists not to rush to publish and do structure modifications [to identify drug candidates] first." Teams would then apply for patents on groups of similar structures.

Not all practitioners embrace TCM's demystification. "Some are afraid that the traditions will be lost," says Chen. But Hui says that modernization is necessary "to reconcile the knowledge-oriented, deductive process of Western medicine with the experience-oriented, inductive process of TCM." Fang has a different take: "Can you marry astrology and astronomy, alchemy and chemistry? It never works."

Hui insists that TCM can coexist wi th Western medicine. Liang hopes his Herbalome project will prove Hui right.

Unesp lança site sobre o escritor Machado de Assis

A Unesp colocou no ar, em caráter experimental, o site www.machadodeassis.unesp.br para marcar o centenário da morte do escritor Machado de Assis (1839 - 1908).
O projeto traz uma biografia do escritor carioca e apresenta, na íntegra, os jornais e revistas com os quais ele contribuiu durante a segunda metade do século 19. Estão disponíveis as publicações "O Futuro", periódico literário, "Marmota Fluminense", jornal de moda e variedades, "Semana Ilustrada", "Diário do Rio de Janeiro", "Jornal do Povo" e "A Saudade".

SP tem 2º caso de morte por suspeita de reação a vacina de febre amarela

Mulher de 79 anos morreu na capital paulista na segunda quinzena de janeiro

A Secretaria da Saúde do Estado de São Paulo confirmou ontem o segundo caso de morte no Estado por suspeita de reação adversa à vacina contra a febre amarela. Uma mulher de 79 anos que havia recebido uma dose da vacina na capital paulista morreu na segunda quinzena de janeiro. O nome dela não foi divulgado.
Segundo Clélia Aranda, diretora da coordenadoria de controle de doenças da Secretaria da Saúde, as investigações feitas até agora pelo governo estadual não detectaram que a paciente tivesse alguma doença que contra-indicasse a vacina. Ela afirmou ainda que a paciente não iria viajar.
"Nós acreditamos que existam algumas condições individuais que façam com que umas pessoas tenham reações mais exacerbadas do que outras", disse.
De acordo com ela, não há restrição de idade máxima, apenas para "baixo" -crianças com menos de seis meses não podem tomar a vacina.
Já o infectologista e professor da Unifesp Celso Francisco Granato disse que, a partir dos 60 anos, é maior a chance de acidente vacinal. Mas caso o paciente vá viajar para uma área endêmica, a vacina é indicada.

Notificações
A morte da paciente de 79 anos em São Paulo foi uma das 24 notificações de reações adversas no ano no Estado, número que já supera o total do ano passado. "Geralmente são aplicadas de 400 mil a 450 mil doses por ano, mas em 2008 já foram 730 mil", disse Clélia.
Em 2008, além do caso divulgado ontem, também morreu a enfermeira Marizete Borges de Abreu, 43. Ela tinha ao menos três contra-indicações para a vacina: era portadora de lúpus -uma doença auto-imune-, usava corticóide continuamente e não pretendia viajar para áreas de risco.
Marizete era enfermeira-chefe da UTI do Hospital Geral de São Mateus (zona leste) e foi vacinada no dia 17, em uma Unidade Básica de Saúde.
Amostras de sangue das duas pacientes foram enviadas para investigação no Instituto Adolfo Lutz, que determinará se os casos foram realmente de febre amarela vacinal.
Além das duas mortes, outros quatro pacientes foram internados no Estado com meningite, dores musculares e icterícia após tomarem as vacinas. Atualmente, há apenas um internado na região de Bauru.
Segundo a Secretaria da Saúde, só deve se vacinar quem for viajar à região amazônica (para áreas de mata e florestas) e os Estados de GO, TO, MT e MS.
Até o dia 29 de janeiro, o Ministério da Saúde havia registrado 47 ocorrências de casos suspeitos, todos em processo de investigação. Destes, 21 pacientes foram hospitalizados. O ministério não divulgou o número de casos de óbito.
(MÁRCIO PINHO)

O caso revista Veja

No nono capítulo da série sobre a Veja, falo sobre a primeira tentativa de "assassinato de reputação" perpetrada pela revista, depois do advento da era Dantas. O alvo? Eu mesmo (clique aqui).

Os demais capítulos da série podem ser acessados a partir do primeiro (clique em cada título para acessar).

Capítulo 1: Os Momentos de Catarse e a Mídia.

Capítulo 2: A mudança de comando na Veja

Capítulo 3: A guerra das cervejas

Capítulo 4: O caso André Esteves

Capítulo 5: O caso COC

Capítulo 6: Os primeiros ataques a Dantas

Capítulo 7: Os assassinatos de reputação.

Capítulo 8: O quarteto de Veja.

Capítulo 9: Os primeiros trabalhos.

PS - Os capítulos sairão de terça a sábado.