WASHINGTON US accelerates investment in biomedical research

SCIENCE AND MEDICINE

NEWS Oestrogen fails to halt Alzheimer’s disease progression for women taking placebo. There was also no significant difference between the groups in measures of mood, memory, attention, language skills, motor function, or activities of daily living. Nonetheless, note the authors, “numerous publications with broadbased distribution” are supporting the use of oestrogen in women with Alzheimer’s disease to improve cognition and delay disease progression. “Such clinical practice, begun in advance of rigorous clinical trials, could be detrimental to patient outcomes”, they warn (JAMA 2000; 283: 1007–15). “The results are clear and unequivocal, but they really relate only to that specific group of women who are about 75 years of age and already have the disease”, comments Bennett Shaywitz (Yale University School of Medicine, New Haven, CT, USA). “The notion that oestrogen can improve Mouse model for neurodegenerative disorders cognition is still a very Scientists have bred a transgenic mouse strain that tenable hypothesis, and might help elucidate the earliest events in neurohas been shown in other degenerative diseases such as Alzheimer’s and studies”, he insists. “It Parkinson’s disease. The mice overexpress human might still be important ␣-synuclein, a protein originally isolated from plaques in improving cognition in brains of people with Alzheimer’s disease. The in women in midlife or mice developed intranuclear and cytoplasmic in older women without inclusions, lost dopaminergic termini in the basal Alzheimer’s disease.” ganglia, and developed motor defects. These results, And, adds Mulnard, says co-author Lennart Mucke (University of California women who have at San Francisco, CA, USA), “suggest that blocking Alzheimer’s disease the accumulation of ␣-synuclein might help prevent or should not be prevented treat Parkinson’s and related conditions” (Science from receiving oestro2000; 287: 1265–69). Jane Bradbury gen. “We know oestro-

estrogen replacement therapy neither improves cognition nor halts the decline of women with Alzheimer’s disease, report US researchers. “We were surprised and quite disappointed”, says lead author Ruth Mulnard (University of California, Irvine, CA, USA). “Given the early evidence and the epidemiological data, we thought oestrogen would really become part of the armamentarium for treating women with Alzheimer’s disease.” Mulnard and co-workers in the Alzheimer’s Disease Cooperative Study studied 97 women with mildto-moderate Alzheimer’s disease who were assigned low-dose (0·625 mg) or high-dose (1·25 mg) oestrogen or placebo daily. After 1 year, the average score on the 7-point Clinical Global Impression of Change (CGIC) scale for women receiving oestrogen was 5·1, compared with 5·0

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gen has benefits for other body systems. If it is beneficial for a woman’s heart, bone, bladder or whatever is

Ensuring a mentally fit old age?

being treated, then it should not be withheld simply because it won’t help cognitively”, she stresses. Mulnard also remains hopeful that a US trial underway in women at high risk for Alzheimer’s disease will show that oestrogen can prevent disease onset. But Thomas Chase of the US National Institute of Neurological Disorders and Stroke (Bethesda, MD, USA) argues that “it is time to move on to other things”. Past studies that suggested that oestrogen was beneficial in Alzheimer’s disease “were fairly slender, and doing a quick trial in small numbers of patients can often give funny results that are hard to reproduce”, he says. So what about the ongoing prevention trials? “This impressive negative study limits their prospects and raises the probability that they will not find a positive result”, he concludes. Marilynn Larkin

Male contraceptive pill would be acceptable to men and women

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wo multicentre surveys reveal that most men would welcome a hormonal method of male contraception. And, contrary to popular belief, most women would “trust their partners to use a ‘male pill’”. These findings, says researcher Richard Anderson (Centre for Reproductive Biology, University of Edinburgh, UK), “should encourage more drug-company involvement in male-pill development”.

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450 men in Edinburgh, Shanghai, and Hong Kong, and 493 men in Cape Town were asked about their attitudes to a male pill. Depending on the centre, 44–83% of men said that they would use a male contraceptive pill. Overall, a pill was more acceptable than an injection, which was more acceptable than an implant. Men, says Anderson, see hormonal contraception as a “longterm option, after they have had a

couple of children but before they are willing to be vasectomised”. In the second survey, a similar number of women were asked how they felt about a male pill. 65% of them thought contraception should be more evenly shared, and only 2% said they would not trust their partner to use a male pill (Hum Reprod 2000; 15: 637–45, 646–49). Jane Bradbury

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Visually induced epilepsy explained trast, the amplitude of the VEPs esults from a study of patients remained constant or even decreased, with a history of visually induced which, says Porciatti, “indicates epilepsy show that cortical activity the presence of a mechanism increases, and does not satuthat controls the response rate, with the degree of and stops it exceeding contrast in a moving a certain amplitude”. image. “This fact sugHowever, in patients gests that photosensitive with PSE, the response epilepsy may derive did not saturate with from a lack of the increasing contrast, and neural mechanisms that reached abnormally normally control the high amplitudes at amplitude of visual resmaximum contrast. This ponses to high-contrast abnormal response was patterns, which are comfound at-low-to medium mon in TV images and video temporal frequencies of games”, says researcher 4–10 Hz, which is the Vittorio Porciatti Safer cartoons in future range known to trigger (Institute of Neuroseizures, but not at higher frequenphysiology, Pisa, Italy). cies. Responses to red-green contrast A cluster of cases of TV-induced were similar in patients and controls epilepsy was reported in Japan in (Nat Neurosci 2000; 3: 259–63). 1997, when 685 children had an Kazuyoshi Watanabe (Nagoya epileptic seizure during a highly conUniversity School of Medicine, trasted scene involving flashing Japan) comments that previous VEP colours in the cartoon show “Pocket studies in Japan indicated that Monsters” (see Lancet 1998; 351: 40). “red/blue stimuli were far more effecTo find out more about photosensitive than black/gray stimuli in exciting tive epilepsy (PSE), the researchers the occipital cortex”. But despite this placed scalp electrodes over the discrepancy, Porciatti believes that his occipital and frontal cortices of 11 findings “may help in devising safer adolescents and young adults with video-generated patterns”. And, adds PSE and 12 normal volunteers. The Dorotheé Kasteleijn-Nolst Trenité participants looked at a series of sim(Instituut vor Epilepsiebestrijding, ple patterns consisting of black-white Heemstede, Netherlands), “the likeliand red-green sinusoidal gratings of hood that there is a defect in contrast different contrasts, whose colours gain control in PSE could be a key to were reversed at various temporal a better understanding of the pathofrequencies. The researchers recorded physiological mechanisms of PSE and visually evoked potentials (VEPs) as a of epilepsy in general. This knowledge function of contrast and frequency. could lead to the development of In the normal volunteers, the new, targeted anti-epileptic drugs”, amplitude of VEPs recorded from the she says. occipital scalp increased with an increase in black-white contrast of up to 20%. With further increases in conXavier Bosch

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Telemedicine used to diagnose mycetoma

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n Feb 17, clinicians in Italy reported an unusual case of occluding right-ventricular mycetoma diagnosed by telemedicine. A girl with Down’s syndrome was operated on when 10 days old because of an annular pancreas. A central venous catheter through which she received parenteral nutrition was removed after Candida albicans sepsis developed. When she was 5 months old, the girl developed right-sided heart failure, fever, and severe thrombocytopenia. Blood cultures were positive for C albicans and she was admitted to the Ospedale Civile, Foggia, Italy. Here, Giuseppe Rinaldi set up a remote real-time consultation, including echocardiography, with Maria Chirico and Dario Trose at the Giovanni XXIII paediatric hospital in Bari. A right ventricular mass, almost totally blocking the tricuspid valve, was seen and interpreted as a septic thrombus. The infant was transferred to Bari (100 miles away) where, on Jan 20, cardiac surgeon Paolo Arciprete did an emergency transatrial ventricular thrombectomy. The mass was a mycetoma—a nucleus of C albicans fungi surrounded by fluid and encapsulated by platelet thrombi. Recovery was uneventful and the girl was discharged after 4 weeks of antifungal therapy. “This case is unique”, notes Arciprete, “not only because an occluding right-ventricular mycetoma is exceptional, but also because it was diagnosed by telemedicine, and the child is well”.

Bruno Simini

Expert warns of possible poliomyelitis vaccine shortfall in 2000 isorders that first have their effect during childhood were among the topics discussed at the annual American Association for the Advancement of Science meeting (Washington, DC, USA; Feb 17–22). Stephen Cochi of the US Centers for Disease Control and Prevention (Atlanta, GA, USA) reported that there are now only two major reservoirs of wild poliomyelitis: southeast Asia and sub-Saharan Africa. In 1999 there were about 6000 cases of paralytic polio worldwide, and Cochi explained that eradication efforts are

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now being redirected to ten countries identified as “hot spots”. Half of these are “reservoir” countries with large, dense populations; the others are countries in conflict where internal strife makes it difficult to complete a vaccination programme. But, warned Cochi, an additional concern this year is the possibility that the goal of worldwide childhood vaccination will cause a shortage of oral polio vaccine. “In 1999, 147 million doses of polio vaccine were given”, he said. “That’s a phenomenal figure.” Christine Yoshinaga-Itano of the

University of Colorado (Boulder, CO, USA) reported on another way to improve the lives of children: screening for deafness in the first 6 months of life. Of 368 deaf or hardof-hearing infants, those who were diagnosed before the age of 6 months had normal-range language development at 3 years of age; those identified after 6 months were in the lowest 10% for language development. “Testing for deafness takes only 1–3 minutes, and can be done within hours of birth”, she said. Hannah Wunsch

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SCIENCE AND MEDICINE

Olives, tea, and tamoxifen—new and not so new ways to prevent cancer was epigallocatechin gallate, which xperimental compounds and occurs in green tea. This compound large-scale trials of established blocks the AP-1 signal-transduction drugs for cancer prevention were discascade involved in skin carcinogenecussed this month at Tumour sis, and according Prevention and to Steven Stratton Genetics 2000 (St (Arizona Cancer Gallen, SwitzerCenter, Tucson, land; Feb 17–19), AZ, USA), the which was also the gallate will be tested 5th annual meeting in topical creams for of the International its ability to prevent Society for Cancer cancer. Chemoprevention. Ongoing chemoRobert Owen prevention trials (German Cancer that were updated Research Centre, included the InterHeidelberg) has Better quality oil, better health national Breast found pinoresinols Cancer Prevention Study (IBIS), the in olive oil, especially in extra-virgin only trial of tamoxifen versus placebo pressings. Such phenols aggressively to continue since the US tamoxifen scavenge reactive oxidative species, trial reported a halving in the incihe said, and may partly explain the dence of breast cancers in 1998. Jack link between a low colon-cancer inciCuzick (Imperial Cancer Research dence and the “Mediterranean” diet. Fund, London, UK) explained that Another experimental food-derived 6176 women are enrolled, and that compound discussed in St Gallen Anthony Blake Photo Library

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Early steps towards a broad-based antiviral drug gp160 and the measles virus protein F0, and limits viral production. The new study shows that ␣1-PDX can also block the generation of infectious virus when applied externally to cells in culture. 8 ␮mol/L ␣1-PDX decreased the amount of infectious virus harvested by 50%; 20 ␮mol/L resulted in a 3-log reduction in HCMV titre. The potency of ␣1PDX was about ten-fold greater than current HCMV antivirals (Proc Natl Acad Sci USA 2000; www.pnas.org/ cgi/content/abstract/050504297). “If we can block virus formation without compromising the host, this approach has great potential, not only for HCMV infections, but as a broad-based antiviral that may also act against bacteria that Antisense attack on HIV-1 use the furin pathway”, says Wenzhe Ho of the Children’s Hospital of author Gary Thomas. Maxime Philadelphia (PA, USA) and colleagues report Moulard (Scripps Institute, La that gene therapy with the antisense gene Jolla, CA, USA) also welcomes antitat may be a way to block HIV-1 activation this new strategy, but warns and replication in monocytes and lymphocytes that furin inhibition could in vivo. mRNA transcribed from antitat binds impair cell viability. “Furin is irreversibly to the mRNA produced by the widely expressed, and its role HIV-1 tat gene. When introduced into in host-cell protein processing peripheral blood mononuclear cells isolated seems to be a key one”, he says. from patients infected with HIV-1, antitat “In-vivo studies, particularly inhibited HIV-1 activation and enhanced the the engineering of furin knockin-vitro survival of CD4 T lymphocytes. Antitat out mice, would be a useful DNA also persisted for many months in next step”, he adds. transduced cells and their progeny, report the

reliminary studies indicate that a protein designed to block a hostcell protein that many viruses use to process their envelope glycoproteins may limit the replication of human cytomegalovirus (HCMV). François Jean and colleagues (Oregon Health Sciences University, Portland, OR, USA) used human foreskin fibroblasts and astrocytoma cells infected with HCMV to test the effect of exogenous addition of the furin-blocking protein ␣1-PDX. This protein is a variant of ␣1-antitrypsin that contains a furin recognition sequence. Gene-transfer studies had shown that ␣1-PDX blocks the furindependent processing of HIV-1

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scientists (Gene Therapy 2000; 7: 321–28).

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the trial will stay open until the end of this year. Thus far, 96 breast cancers have occurred. Cuzick is also involved in a breastcancer prevention trial of the aromatase inhibitor goserelin versus raloxifene (like tamoxifen, a selective oestrogen receptor modulator [SERM]), and a study of tamoxifen versus the aromatase inhibitor anastrozole and a SERM yet to be decided upon. Finally, Sandra Swain (US National Cancer Institute, Bethesda, MD, USA) said that the STAR trial (tamoxifen vs raloxifene) has now accrued about 3200 women. Otis Brawley (also of the US National Cancer Institute) gave an update on the Prostate Cancer Prevention Trial—a 7-year trial of the 5-␣-reductase inhibitor, finasteride, versus placebo. The trial will end in 2003–04, and is on target for the 12 000 biopsies needed, he said. David McNamee

News in brief OK to diet while breastfeeding Deliberate weight loss by overweight breastfeeding women does not affect the growth of their infants, report US researchers. 27 breastfeeding women with a body-mass index of 25–30 kg/m2 restricted their energy intake by 500 kcal/day and did 45 mins of exercise 4 days per week. 21 similar women maintained their usual dietary intake and did not exercise more than once per week. The dieting women lost significantly more weight after 10 weeks, but the weight and length of their infants increased by about the same amount as those of the other women (N Engl J Med 2000; 342: 449–53). Eyes wide shut A UK study has shown that telephone-based triage systems may be affected by the poor understanding of medical terminology by the general public. 700 patients attending an emergency department were asked one of seven questions about the term “unconscious”. 53·5% thought an unconscious person could still hear, and 41% thought such people always had closed eyes. People for whom English was not the first language scored lower than native Englishspeakers (J Accid Emerg Med 2000; 17: 119–21).

Kathryn Senior

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FEATURE

Juan Rodés: pulling basic and clinical research together

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he describes as “a fair example” of hypertension. Says Burroughs: “One such an institute. He is the director of of Rodés’ skills has been to keep IDIBAPS (Institut d’Investigacions world leaders in hepatology in his Biomèdiques August Pi i Sunyer), team and to provide an environment which was set up in for the development of 1996. More than 250 new experts.” biomedical scientists Milestones of the are associated with past decade, notes IDIBAPS which draws Rodés, include the together basic research identification of the on genetics, cell biolhepatitis C virus and ogy, and biochemistry; the development of applied research in, for increasingly effective example, haematology, antiviral therapies; the hepatology, neurology, improved survival of cardiovascular disorpatients after liver ders, and respiratory transplantation; and disorders; research into the implementation of health services; an vaccination against the active programme for hepatitis B virus. And, health development in although he says its Integration is key to future African countries; and applicability is still a clinical trials unit. In the 4 years of unclear, he is excited about the its existence, about 1500 original potential of gene therapy for the articles have been published by treatment of liver diseases. “It seems researchers at IDIBAPS, 50% of that we are at the beginning of the them in journals within the first incorporation of a new therapy that quartile of their speciality. And, will be of great importance in a notsays Rodés, the Hospital Clinic of too-distant future.” Barcelona, which forms part of But, he says, in order to make the IDIBAPS, has one of the highest best of new advances, we need to scientific outputs of any hospital in rethink the organisation of clinical the European Union. research. He uses the current crisis in But “changing the current organiclinical research in the USA as an sation of biomedical research is not example. In that country, he explains, enough”, warns Rodés. “We also there has been a marked reduction of need major changes in the teaching of public funds for clinical projects since medicine both to undergraduates the 1970s. As a result, many physiand postgraduates.” Rodés believes cians with good training in clinical that students should be solidly investigation now do only basic trained in biochemistry, cellular and research. In Spain matters are somemolecular biology, genetics, biowhat different—a “quasi-divorce” statistics, bioethics, and the practice situation exists such that in 1995 only of evidence-based medicine. He is 10% of research units at Spanish confident that Spanish postgraduate hospitals did basic research. Worried training is excellent but is concerned about this, Rodés wants reforms initithat there are no specific biomedical ated to encourage integration of basic research programmes in Spain for and clinical research teams. He says residents. one solution may be the creation of There is one promising sign. Since institutes where clinicians, surgeons, 1980, the Hospital Clinic has encourpathologists, radiologists, and other aged several residents to become fully specialists work together to handle all involved in research for at least 1 year aspects of diagnosis and treatment of, after completion of their residency for example, liver and gastrointestinal and to eventually get a PhD degree. diseases. This “horizontal” organisa“So far the results of the experience tion, says Rodés, would improve colhave been very beneficial for the laboration between clinical and basic young researchers and the instituresearchers and between specialities. tion”, says Rodés. Now, he adds, “we The multiple problems seen in the must implement an official national centres would encourage a homogeprogramme to train the well-qualified neous but multidisciplinary scientific biomedical research professionals focus and, says Rodés, would shorten necessary to sustain IDIBAPS and the interval between the production other similar institutions”. of new knowledge and its investigation in medical practice. Rodés is already involved in what Xavier Bosch Fotograf Werner Weitzel

here is no doubt, says Juan Rodés, head of the Liver Unit of the Hospital Clinic of Barcelona, that recent progress in hepatology is a direct consequence of the incorporation of new knowledge from molecular and cellular biology into clinical practice. “Clinical investigation in hepatology has acquired a new dimension as the tools provided by basic science have become incorporated into clinical research”, he says. Rodés forecasts that genomics, proteomics, and bioinformatic technology will soon become fundamental technologies in hepatology, and “that investigations of liver diseases will increasingly involve integration of basic and clinical researchers”. “The present division of biomedical research into basic and clinical research is artificial and inappropriate”, he continues. According to Rodés, coordination of both clinical and basic research with medical practice will improve the implementation of scientific advances in the prevention, diagnosis, and treatment of diseases, and guarantee better healthcare services. Many of his ideas about how to achieve this coordination are included in the Spanish “National Plan on Research, Development and Technological Innovation 2000–2003”—Rodés was the president of the working group of the biomedicine section of the plan. Rodés studied medicine at the Faculty of Medicine of the University of Barcelona and got his PhD degree in 1967. After a training fellowship at the Hôpital Saint Antoine in Paris, France, with the hepatologist Jacques Caroli, Rodés founded the Liver Unit at the Barcelona Hospital Clinic in 1968. This unit, says Andrew Burroughs, a hepatologist at the Royal Free Hospital, London, UK, “is now the foremost clinically based centre of hepatology in the world. The quality of Rodés research”, he adds, “is attested to by his numerous publications in top gastroenterology and general clinical journals”. Much of the international reputation that Rodés has built up is a result of the work he initiated at the Liver Unit into the physiopathology of the complications of liver cirrhosis. With Vicente Arroyo, Rodés has worked on treatments for ascites (and renal dysfunction) and on the prevention and therapy of spontaneous bacterial peritonitis. With Juame Bosch, he has done world-class work on the pharmacological treatment of portal

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DISPATCHES

WASHINGTON

US accelerates investment in biomedical research

he boom rolls on in US government spending on basic biomedical research, with both Democrats and Republicans so keen for medical science that it is not even a whisper of an issue in the presidential campaign. There has been nothing like it in the sciences since the spending spree in the post-Sputnik era. Not long ago, it was different. In 1995, the third year of Bill Clinton’s presidency, the budget of the National Institutes of Health (NIH) stood at US$11·3 billion, the Newt Gingrich-led “Republican revolution” declared plans for huge spending reductions, and NIH Director Harold Varmus warned the biomedical-science community of a coming “steady state” or worse in government support. Today, NIH is running on $17·8 billion, Clinton is seeking a $1 billion raise, but Washington’s highly confident biomedical lobbies have declared the need for at least $2·4 billion more. In dealing with NIH, presidents customarily ask for less in expectation of Congress insisting on more. On the basis of past performance, the odds are that NIH will get the larger figure, as the third annual step toward a popular goal of doubling its budget in 5 years. Measured in the number of research grants for principal investigators, a count anxiously watched by biomedical researchers, NIH grew from 24 000 in 1993 to 31 000 this year. But the number of researchers supported is higher than the grant total suggests, since NIH has increased its support for centres and programmes that employ many scientists. Buoyed by the belief that in the

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new millennium, the life sciences will emulate the intellectual and economic feats of the physical sciences in the past century, government, academe and industry are in harmony on the need for expanding facilities and research. In universities across the country, from Yale to Berkeley, new laboratory buildings are springing up. From the steady-state fears of just a few years ago, the turnaround in expectations and deliveries of money for research is spectacular. Just over 7 years ago, Clinton came into office preaching the economic merits of

“There has been nothing like it in the sciences since the spending spree in the postSputnik era” industrial technology, with seeming indifference to academic research and a standstill budget for NIH. He is exiting as a benefactor of NIH and other federal agencies that are the mainstays of research in universities and hospitals. The spending is politically feasible because bountiful federal revenues from the surging economy have put the US Treasury into surplus and taken the onus away from raising government expenditures. Last year, although legally bound by so-called caps on spending, Congress and the White House exceeded the limits by shifting various expenditures into allowable “emergency” categories. The will and the money were present, and politics found a way. With a supportive constituency in a popula-

tion ageing into the disease-prone years, medical research has easily outdistanced other areas of research in building support on Capitol Hill. While boosting NIH, Clinton’s valedictory spending plan for the fiscal year that begins Oct 1 proposes catch-up increases for the National Science Foundation (NSF): $675 million, the largest increase ever for NSF, which would raise its budget to $4·6 billion. Clinton echoed the rising complaints of neglect from physicists, chemists, and others outside the charmed circle of biomedical affluence. “We have to have a balanced research portfolio”, he stated, “because the research enterprise is increasingly interdependent. Advances in health care, for example, are often dependent on breakthroughs in other disciplines—such as the physics needed for medical imaging technology, or the computer science needed to develop more drugs more rapidly, or to continue the mapping of the human genome.” Here, again, the need for money was explained in terms of medical science. The White House has adopted a new accounting method for government spending on research and development, with activities that advance knowledge—basic research, plus some applied research—bunched together in what is called the 21st Century Research Fund. By that reckoning, government spending on research rose from $29·6 billion in 1993 to $40 billion this year. Billions more are on the way for next year. Daniel S Greenberg

Plans to expand India’s “astounding” DOTS programme

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n intensive international review of India’s Revised National Tuberculosis Control Programme (RNTCP), based on Directly Observed Treatment, Short Course (DOTS), dubbed its success as “astounding” on Feb 17. “Where DOTS is not used, infectious patients are seven times more likely to die from tuberculosis”, said Arata Kochi, director of WHO’s Stop TB Initiative. RNTCP was launched 3 years after the failure of the earlier plan and now covers 14% of the population. The joint review team of 25 national and international experts

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visited nearly 100 health facilities, interviewed 1000 patients, and verified records of more than 10 000. The team found that the new strategy is twice as successful as the old one and succeeded in ensuring that drugs were made freely available to patients. RNTCP has already achieved cure rates of more than 80%, saved some 40 000 lives, and more than US$300 million already, said the review. Thomas Freiden (WHO, Geneva, Switzerland) commented that only 2–3% of people in India with tuberculosis have the multidrug resistance type, but warned against

complacency. 5 years from now, virtually incurable forms of multidrug-resistant tuberculosis could be common, thus a rapid expansion of RNTCP is is essential, he said. Every year 2 million Indians develop tuberculosis and half a million die. The disease’s cost to India is estimated to be more than $2 billion each year. Encouraged by the programme’s success and a World Bank loan of $142 million, the Indian government will expand the programme to cover half the population by 2002. Sanjay Kumar

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POLICY AND PEOPLE

Jack Straw challenged over General Pinochet’s medical report extradition to Spain on health grounds. Both France and Spain are demanding the right to arrange independent medical examinations. And, having studied the medical report, Belgian judge Damien Vandermeerch, has asserted that the former dictator is fit to stand trial. Straw’s decision has been the subject of Baltasar Garzón much controversy, especially after the leak of the confidential medical report of Pinochet to two Spanish newspapers on the evening of Feb 15. The report, along with a requirement to maintain strict

confidentiality, was faxed to the Spanish Foreign Office at 19:30. 2 hours later, a Spanish version of the entire document had been put on the websites of the ABC and El Mundo newspapers and was subsequently picked up by news agencies throughout the world. Spanish judge Baltasar Garzón, whose initial extradition request led to the general’s arrest in London in 1998, stated that the leak must have occurred before the documents arrived in his court. AP

n Feb 22, France, Switzerland, and Belgium made last-minute challenges to a medical report commissioned by UK Home Secretary, Jack Straw, on former Chilean dictator General Augusto Pinochet. On the basis of the confidential report, Straw announced in January that he was “minded to take the view that no purpose would be served by continuing the present extradition procedures” (see Lancet Jan 22, p 245, 297). However, on Feb 15, a High Court decision in London, UK, had forced to release the contents of the report to the three countries and Spain. In their challenge to Straw’s decision, the Swiss authorities have argued that international treaties do not allow the UK to bar Pinochet’s

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Sarah Ramsay, Xavier Bosch

News in brief

Italy to set tough task for drug industry

HIV vaccine initiative WHO and UNAIDS announced the creation of a new joint vaccine initiative on Feb 21. According to initiative coordinator Jose Esparza, “the new initiative provides an independent forum where everyone working on HIV vaccines . . . can identify common ground for collaboration and coordination”.

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UK analysis of racism in organ donation A report into how a racist condition was put on a UK organ donation was published on Feb 22. In July 1998, the relatives of a critically ill man agreed to donation of his organs after death only if they went to white recipients. Permanent Secretary for the Department of Health Chris Kelly found in his investigation that the organs were “wrongly accepted and passed into the system”, that three white people received the two kidneys and a liver, but that they would have received the organs anyway. But “it is clearly abhorrent that the organs should have been accepted on this basis”, he said. US medical errors On Feb 22, US President, Bill Clinton, proposed a plan to cut hospital errors by 50% in 5% years. The plan calls on Congress to legislate for an anonymous error-reporting system. Further initiatives include typed, rather than handwritten, drug prescriptions.

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rugs that have been on the Ministry in the past will not be market for more than 10 years considered. Non-application for in Italy must be re-evaluated for re-evaluation will, after 3 years, their “purported efficacy and the result in “automatic and irreappropriateness of their indicaversible” removal of the drug from tions”, according to a forthcoming the market. ruling by the Ministry of Health. 14 classes of drugs with “dubious The Ministry is due to publish a efficacy” (including “cerebrovascudecree to this effect in the lar adjuvants and neurotrophics”, near future. Within a month of “cardiometabolics”, “vasoprotecthe decree’s publication, drug tors”, “immunomodulators”, and companies will be obliged to indi“cough and colds remedies”) will cate which drug licences they be under particular scrutiny. Most intend to submit for re-evaluation. were first marketed “at a time when A formal application must follow the evaluation process was not eviwithin 18 months, which must dence based”, the Ministry said, include evidence for the drug’s adding that subsequent approval effectiveness such as randomised has often been automatically controlled trials (RCTs), metarenewed. analyses, and reviews that have Bruno Simini been published in “internationally qualified peer-reviewed journals”. And the cliniAustralia cracks down on drug promotion cal efficacy of the drug Internet-based promotion of medicines to the must be acknowledged in general public in Australia will be forbidden under a “respected international revised code of conduct for the pharmaceutical reference sources (eg, industry released last week. However, the 13th pharmacology and theredition of the Australian Pharmaceutical apeutics textbooks)”. Manufacturers Association (APMA) Code, allows Unpublished RCTs subsecurity-coded internet promotion of mitted “in the same forpharmaceuticals and gifts to doctors, provided they mat as that required by have educational and medical relevance. journals such as The “Pharmaceutical companies must not provide Lancet, NEJM, BMJ, and information on prescription products on the JAMA” and other inforInternet to the general public”, said APMA mation (eg, whether the chairman, Pat Clear. Details about drugs on the drug is marketed elseinternet should not make reference to other where in the European information sources or websites that would breach Union or in the USA) the code (www.apma.com.au). will be considered, but Amanda Tattam data submitted to the

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POLICY AND PEOPLE

US subcommittee calls for suspension of anthrax vaccination programme he US military’s Anthrax Vaccine Immunization Program (AVIP) is plagued by unstable supplies, uncertain safety and efficacy against the anthrax threat, and should be suspended until the Department of Defense (DOD) gets approval to use an improved vaccine recommended the House Subcommittee on National Security, Veterans Affairs, and International Relations on Feb 17. The damning report, entitled Unproven Force Protection, considered AVIP to be “built on a dangerously narrow scientific, medical, and industrial base”. It suggested that until a new vaccine was developed the current vaccine should be considered experimental for inhalation

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anthrax and only be used in line with FDA regulations that govern testing of a new indication. The current vaccine was designed in the 1950s and requires the patient to have six injections over 18 months and then annual boosters. As the USA has about 2·4 million servicemen and women the report suggests that AVIP “presents daunting, perhaps insurmountable logistical challenges”. Head of the Subcommittee, Christopher Shays, added that after the Gulf War “Department of Defense scientists acknowledged the vaccine caused adverse reactions and contained inconsistent amounts of the desired antigenic protein”. Despite this, DOD began, but did

not pursue, research into a safer and more effective vaccine. Meryl Nass, an internist from Freeport, Maine, USA, who has been campaigning for reform of AVIP told The Lancet: “The subcommittee acknowledged that the vaccine is unlikely to be effective against weaponised anthrax, is not safe, and is strategically a poor idea as well. Furthermore it may contribute to ‘ratcheting up’ the biological arms race”. Nass states that if the military does not halt the programme Congress’s next step should be to remove the vaccine programmes’s appropriation from the budget. Kelly Morris, Haroon Ashraf

Chinese government continues persecution of the Falun Gong sect Longxiangshan Mental Hospital, “The doctors and nurses even made which is “the biggest mental institufun of me, ‘Aren’t you practising tion in Guangxi region [and] run in Falun Gong? Let us see which is the style of a stronger, Falun prison”, said the Gong or our medhuman rights icines?’ As long as group. If the they know that I detainee does not was practising comply, the staff Falun Gong, they resort to violence would increase says Huang. the dosage of In December, medicines. The 1999, 50 sect hospital only members were allows my family held for 6 members to call Falun Gong members are closely watched weeks at the or visit me. I have Zhoukoudian Psychiatric Hospital an unspeakable feeling of pain”. near Beijing. The human rights group Huang, a 35-year-old judge for the note that although sect members were Intermediate People’s Court in Beihai, not given psychiatric treatment they was detained for 15 days in were kept in sub-human conditions. September, 1999, for “damaging social order”. A few weeks later, he was sacked and taken to the Khabir Ahmad AP

hinese authorities have sent 20 members of the banned Falun Gong sect, including teachers from Laiyang School of Medicine and doctors from Laiyang Central Hospital, to the Mental Recovering Centre in Laiyang City, in the Liaoning province, reported the Hong Kongbased Information Centre of Human Rights and Democratic Movement in China on Feb 22. Falun Gong is a blend of Buddhist and Taoist teachings. The sect’s widespread appeal led to its ban on July 22, 1999. Since then, thousands of members have been arrested and jailed (see Lancet 1999; 354: 495). Recently, authorities sent Huang Jinchun, a judge, to forcibly receive psychiatric treatment after he refused to renounce his belief in the banned spiritual movement. According to the human rights group Jinchun said:

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Gene therapy HIV scare proves to be a false alarm

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S FDA officials said on Feb 17 that there is no evidence that an experimental gene therapy vaccine given to children with neuroblastoma was contaminated with HIV or hepatitis C virus (HCV). Initial news stories reported that more than two dozen children had possibly received tainted vaccines while participating in a gene-therapy trial at St Jude Children’s Research Hospital, Memphis, TN, USA. Since a young man died in a gene-therapy trial last autumn, US gene researchers

THE LANCET • Vol 355 • February 26, 2000

have been embarrassed by a stream of reports (see Lancet 2000; 355: 634) of what seems to be serious protocol violations. This latest story made headlines across the country. St Jude’s researchers sent vaccine material for testing after learning that viral vectors used in making some vaccines did not have documentation showing them to have been properly screened for pathogens. Those tests found a “weak signal” indicating the presence of a small amount of HIV and HCV, said Laura Bowman,

who heads up the St Jude’s programme. Concerned that results were “false positives”, the researchers sent the material to the FDA for additional testing. But before the results were known, the story was leaked to reporters. “Because someone in the government did not keep the information confidential, a laboratory error was reported in the press”, said Bowman, “patients’ families ended up going through hell.” Michael McCarthy

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POLICY AND PEOPLE

ttempts to curb illegal use of opioids in developing countries are resulting in the denial of essential pain relief to cancer patients, according to the annual report of the Vienna-based United Nations International Narcotic Control Board (INCB), released on Feb 23. “People tend to forget that we are as concerned with promoting the proper use of narcotics as we are with dealing with their abuse”, said INCB Secretary, Herbert Schaepe. The report blames over-restrictive regulations and calls for governments to adopt a flexible and humanitarian approach. In some parts of the world, doctors can face long terms in jail for simple administrative errors in prescribing morphine. The report also points out that US doctors prescribe ten times more amphetamines than their European counterparts and notes, for the second year, the controversial use of methylphenidate in children with attention-deficit hyperactivity disorder in the USA. European doctors are three times more likely than their US colleagues to prescribe benzodiazepines. The experts cannot explain the trends, but note that doctors are often in the difficult position of providing pharmacological treatment for non-clinical reasons. Next year’s INCB report will focus on the general problem. Turning to drug misuse, the INCB is strongly critical of the practice in some developed countries of seeking increased protection against HIV-1 transmission by providing rooms for addicts to inject themselves. The report compares them to opium dens and warns that the practice may contravene international drug-control conventions. On a positive note, there has been considerable success in the interception of chemicals used in drug production, particularly the potassium permanganate used for processing cocaine. China is credited with intercepting more than a thousand tons on its way to illegal laboratories. However, the UNCB is pessimistic over the seriousness of Afghanistan’s Taliban government in tackling opium production. Last year, the country produced a record 4600 tons.

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Nigel Glass

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CDC head apologises again for misuse of funds

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or the second time in as many years, the head of the US Centers for Disease Control and Prevention (CDC) has been forced to explain to Congress why funds intended for research into one disease ended up being spent on other things. Last year, CDC was unable to account for about US$13 million that Congress had “earmarked” for research on chronic fatigue syndrome. This time, the Washington Post newspaper—which also broke the earlier story—revealed that $7·5 million appropriated for each of the past several years to study hantavirus had in fact been used to study other infectious diseases, including Ebola and Lassa fever. While Congressional “earmarks” are technically suggestions for how money should be spent and are not legally binding on federal agencies, government officials ignore them at

their peril. “We have got to know if the agency makes a different determination than the one directed by the Congress” on how research funds are spent, said Congressman David Obey, at a hearing before the powerful House Appropriations Committee on Feb 10. At this hearing, CDC Director Jeffrey Koplan apologised to the committee and said that the CDC is taking steps to ensure such diversions of funding will not happen again. These steps include internal and outside audits of CDC spending and replacing the head of the agency’s viral division. It will not be known until later in the year, however, if Congress will find the actions sufficient or if it will punish the agency by reducing its budget. Julie Rovner

Indian policy aims for stable population by 2045 he long-awaited National Population Policy announced by the Indian government on Feb 17, aims to stabilise the population size by 2045. The immediate aims of the policy are to address the unmet needs of the health-care infrastructure and workers, of the family-planning ser-

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UN drug board condemns morphine underuse

Education at a local level is vital

vices, and to integrate delivery of basic reproductive and child health care. The medium-term goal is to bring total fertility rates to replacement level by 2010. Currently India’s population increases by 15·5 million people each year, which means India could have a population of one billion people by May 11, 2000. The states of Bihar, Madhya Pradesh, Orissa, Rajasthan, and Uttar Pradesh constitute nearly 44% of the current total population. The population of these five states is expected to rise to 48% of the total for India by 2016. They will be targeted

by a special technology mission proposed by the Department of Family Welfare (DFW). A feature of the latest population control policy is decentralised planning and programme implementation. At village level, health-care services will be delivered through self-help groups and local governing bodies. At district and block levels private practitioners may be assigned to satellite populations of less than 5000 people to provide reproductive and child health-care services. To achieve this, an accreditation system for such practitioners will be developed by the Indian Medical Association. “This is a management paradigm shift. It’s a bottoms-up approach”, said DFW secretary Amulya Ratna Nanda. The new population policy includes a series of incentives, such as cash awards of about US$11 for the birth of a girl, though officials say there will be no coercion for limiting family size. “We are not promoting a one-child or two-child norm, but a small family norm”, declared Nanda. Local health care groups will be rewarded not for the number of family-planning operations, but for promoting the acceptance of small family unit and for achieving lower infant mortality rates. Dinesh C Sharma

THE LANCET • Vol 355 • February 26, 2000