Implantable Glucose Sensor World Precision Instruments World Precision Instruments About thIS MANuAl .1 Notes and Warnings .2 INStruMeNt deScrIPtIoN .2 Parts list .2unpacking .2 oPerAtINg INStructIoNS .3 conditioning the Sensor .3Preparing Solution for calibration .3calibrating the IgS100 .3 SeNSor cAre ANd MAINteNANce .5 Storing the Sensor .5Maintaining the Sensor .5Sterilizing the Sensor .5
p914 Under fire:
p916 Rebel with a
NIH scientists say cause: Transgendered
they feel punished researcher Ben Barres of proof for fertility for the misdeeds of fights for women in a few colleagues.
Threat of pandemic brings flu drug back to life With an effective avian influenza vaccine production capacity to the limit. But Relenza, Other influenza drugs, such as amantadine, have nowhere on the horizon, health officials are which was the first neuraminidase inhibitor already been rendered ineffective against bird flu scrambling for ways to head off a pandemic. on the market, claims only one percent of the by misuse (Nature 435, 1009; 2005).
Governments have been purchasing millions of growing flu drug market. The drug has suffered "In a pandemic situation, resistance is a major doses of Roche's Tamiflu, but would that alone from lackadaisical marketing efforts, according concern," says University of Wisconsin virologist be enough to head off a pandemic? Should other to a lawsuit that Biota, which gets a percentage of Yoshihiro Kawaoka, who led the study in Japan. drugs be stockpiled? Are other drugs available? sales, is bringing against GlaxoSmithKline.
He adds that Relenza has not been used widely The influenza drug Relenza, available since Relenza has also been unpopular in part enough to judge its potential for creating resis- 1999, had been a footnote to Tamiflu but, after because it must be breathed in with an inhaler. tance. "It has been underestimated," he says.
glowing reports in August of its relative effective- GlaxoSmithKline is considering repackaging Meanwhile, Biota is conducting phase 1 trials, ness, has jumped back into the spotlight.
Relenza as a shot or nebulizer to increase sales.
boosted by a $5.5 million National Institutes of Relenza, marketed by GlaxoSmithKline, and Relenza is at least as effective as Tamiflu and Health grant, of a neuraminidase inhibitor that Roche's Tamiflu both bind to the active site of the has fewer side effects, including nausea and could be taken only once a week—compared virus' neuraminidase protein, rendering the virus headaches, according to an article published with twice a day for Relenza and Tamiflu.
unable to escape its host cell and infect others.
13 August (Lancet 366, 533–534; 2005). The
But will any—or a combination—of the In August Germany announced it would buy report, based on data compiled from the drugs help? A pandemic virus would require 1.7 million doses of Relenza as part of its bird companies' clinical trials and from subsequent quick access to the drugs. After the first few flu preparedness strategy. "Germany's purchase studies, also says there is no evidence of days of infection, says Graeme Laver, whose shows that countries are starting to take a resistance to Relenza, compared with resistance work led to the design of neuraminidase balanced view of influenza preparedness," says levels of up to 18% in those taking Tamiflu inhibitors, "you may be able to stop the Simon Tucker, head of research at Melbourne- (Lancet 364, 759–765; 2004). The researchers virus, but the immune response would likely
based Biota, which developed Relenza.
recommend stockpiling both.
kill you." To prevent misuse of the drugs, he Bulk orders of Tamiflu from the UK, France The Tamiflu resistance data are based on stud- adds, they should be sold in tandem with an and other countries to cover 20% or more ies in Japan, which in past years has consumed influenza diagnostic test.
of their population are pushing Roche's nearly 75% of the drug's worldwide supply. David Cyranoski, Tokyo
Room to roam: With unpredictable migratory routes, the H5N1 virus—which has caused the death or destruction of more than 150 million birds in
southeast Asia—is spreading toward Europe. Kazakhstan, Russia, Mongolia and Tibet are the latest to register cases.
* As of 20 August 2005.
NATURE MEDICINE VOLUME 11 NUMBER 9 SEPTEMBER 2005
Drug firms vow to tone down consumer advertisements
In an attempt to deflect Congressional regulation, against a flood of print out and people taking drugs the pharmaceutical industry has announced and broadcast advertising that are more dangerous voluntary measures that would temper the tone prompted by a loosening and less effective than they of consumer-directed drug advertisements. The of FDA regulations in 1997. seem to be," says Sidney move comes amidst growing public distrust of Spending on ads grew from Wolfe of Public Citizen, a the ads, and tighter regulatory scrutiny.
$965 million that year to liberal watchdog group.
The US Food and Drug Administration (FDA) $4.1 billion in 2004, accord- Wolfe says the FDA has recently doubled the number of warning ing to IMS Health, a market should be given the power letters it sends to pharmaceutical companies research firm.
to impose large fines on about false or misleading ads. The agency also As the number of ads has companies that make false announced in August that it intends to conduct grown, so has the public's dis- or misleading commer- a comprehensive review of its advertising trust of them. According to a cials, rather than the letters regulations for the first time in a decade.
February poll by the Kaiser it now sends, demanding US Food and Drug Administration The guidelines, detailed 2 August by the Family Foundation, 18% of After being warned about ads for that they immediately pull Pharmaceutical Research and Manufacturers respondents said they could Zyrtec, Pfizer is changing the way it offending ads. As of 31 of America (PhRMA), ask the group's member trust ads "most of the time," promotes its drugs.
July, the agency had sent 27 companies to more accurately convey drug ben- compared with 33% in 1997.
warning letters this year, up efits and risks in their direct-to-consumer ads. In an effort to improve the ads' public image, from 24 in all of 2004.
Two companies also made independent deci- the PhRMA guidelines call on manufacturers But Jack Calfee, a resident scholar at the con- sions to rein in their drug ads. Bristol-Myers to cease ‘reminder' ads—which name drugs servative American Enterprise Institute in Wash-Squibb on 13 June announced that it would but not their uses or risks—and to target ads ington, says the ads provide patients with impor-not launch consumer ads for one year after a to appropriate audiences, for instance by not tant information that neither the government medicine is introduced, allowing the company airing television ads for erectile dysfunction drugs nor physicians are equipped to disseminate.
time to first educate physicians. Pfizer said until children are asleep. They also suggest that Republican Senator Charles Grassley, who on 11 August that it would improve its ads to companies should educate doctors about new chairs the Senate Finance Committee, has better communicate risks and reinforce the drugs before launching consumer ads.
introduced legislation that would require ads doctor-patient relationship. It also promised Critics assailed these steps as inadequate and for new drugs to be vetted by the FDA during to invest as much in a campaign addressing insisted that more government power is needed the first two years they are on the market. By important public health issues as it typically to regulate the ads. "As long as there is no one out contrast, Grassley noted, the PhRMA guidelines spends on ads for a branded drug.
there cracking the whip on drug companies, you provide "not a single guarantee for consumers." The industry is responding to a backlash will have these dangerous, misleading ads going Meredith Wadman, Washington, DC
Loss of grants review board leaves Australian scientists wary
Grants given by Australia's primary funding
way various agencies are run, and recommen-
medical research called for the creation
agency for basic research will go through one
ded that the agencies be governed either by a
of an NHMRC board to streamline the
less step on their way to approval, a move
chief executive or a board—but not both.
agency's administration, and recommended a
scientists say will leave the process vulnerable
The government says eliminating board
substantial increase in the agency's budget.
to political whim. The nation's medical
review will expedite the grant-approval
Commissioned in October 2003, that
and health funding agency is also to be
process. But John Mullarvey, chief of the
report was not released until December 2005.
restructured, but biomedical researchers are
Australian Vice-Chancellors' Committee,
Researchers were frustrated by the report's
in the dark as to the possible outcome.
says it will compromise the integrity of the
late release, amidst speculation that the
The Australian Research Council
process. "There will be less transparency in the
government wanted to deflect attention from
administers about US$420 million in
decision-making process," he says.
a recommendation to increase funding for
competitive grants each year. Following
Snow Barlow, president of the Federation
peer review of grant applications,
of Australian Scientific and Technological
Researchers say the NHMRC should
recommendations are passed along to the
Societies, based in Canberra, adds that the
not be forced into one of the two models
board—made up of leading community,
board functions as a critical buffer to political
proposed by the government report, given
industry and academic representatives—
interference. "There is a dangerous potential
the agency's diverse roles in funding, policy
before being sent to the agency's chief
for loss of independence," Barlow says.
making and regulation of research areas,
executive, and then to the federal science and
The National Health and Medical Research
such as reproductive technology. "There is
education minister for final approval.
Council (NHMRC), the nation's major
a sound argument given the range of roles
But on 15 July, the government announced
funding agency for biomedical research, is
of the NHMRC for having a tailored model
plans to dissolve the board, effective early in
also up for an overhaul. But the government is
that recognizes these specific functions," says
2006. The agency's chief executive, currently
guarded about the details. "The minister is still
Christine Bennett, chief executive of Research
Peter Høj, will report solely to the minister.
considering," says a ministry spokesperson.
Australia, an independent organization that
The decision follows last year's government-
In December 2004, a government-
promotes investment in medical research.
commissioned report, which examined the
commissioned review of investment into
Carina Dennis, Sydney
VOLUME 11 NUMBER 9 SEPTEMBER 2005 NATURE MEDICINE
Skeptics demand duplication of controversial fertility claim
When Jonathan Tilly claimed in March 2004 by chemotherapy, a genetic mutation or both. In Baby steps
that stem cells could replenish the supply of each case, the recipient ovaries gained fluores- eggs in a mammalian ovary, experts in the field cent green egg cells. Bone marrow transplants First evidence that stem cells in mice replenish the egg supply of adult mouse ovaries.
(Nature 428, 145–150; 2004).
balked. But his claim in July that those stem also restored oocytes, although more slowly. But cells may reside not in the ovary but in the bone whether those eggs can be fertilized to produce First embryo from in vitro fertilization of an egg retrieved from a frozen-thawed ovarian marrow, and that they might circulate in blood, fluorescent offspring is yet to be determined. tissue transplant patient; implanted embryo did not result in pregnancy.
(The Lancet 363, 837–840; 2004).
has shocked critics into downright disbelief.
That result would largely mollify the critics.
Tilly's new work posits that stem cells in the Tilly's work also hints that the ovary may alert Birth of a baby boy conceived through in vitro fertilization with sperm that had been bone marrow can travel through the blood to the bone marrow when oocyte numbers run low. frozen for 21 years.
(Hum. Reprod. 19, 1448–1449; 2004).
regenerate oocytes in a mouse ovary (Cell 122,
The expression of a gene marker used to track 303–315; 2005). His group at the Massachusetts bone marrow stem cells fluctuates with the Boston-based Extend Fertility freezes eggs for future use. Nearly 130 women have General Hospital has found that mice with mouse's estrous cycle and disappears altogether since banked eggs at about $15,000 each; birth rates hover around 20%.
barren ovaries that received blood transfusions when the ovaries are removed. The researchers began producing new egg cells suggest that ovaries send an unknown molecular Woman who received a fresh ovarian tissue transplant from her identical twin sister delivers a girl.
signal to regulate egg development.
(N. Engl. J. Med. 353, 58–63; 2005).
The study challenges the "Therapeutically, such a factor would be a gold long-held view that mam- mine to increase the oocyte stockpile or jumpstart Baby girl born to a woman who received a transplant of her own ovarian tissue, which was frozen before her treatment with sterilizing chemotherapy mals are born with a limited new egg production," says Tilly, adding that if the (N. Engl. J. Med. 353, 318–321; 2005).
number of eggs that declines work translates to humans, it could lead to ways to with age. Among experts, it prolong women's fertility or delay menopause.
Evidence that oocyte stem cells in mice reside in bone marrow and travel through blood.
(Cell 122, 303–315; 2005).
has inspired, at best, cautious But talk of human implications frustrates optimism and, at worst, vehe- critics who say the work must first be reproduced. ment denial. But it is also challenging the field "Relieving menopause is a long jump forward," to reexamine one of its most sacred dogmas.
says Jeffrey Chang, a reproductive endocrinolo- Because the work raises fundamental "There are so many inconsistencies between gist at the University of California, San Diego. questions, five years is too long, experts say. the first paper and this one, it makes it very Chang says he appreciates the research, but "it's But the work's controversial nature may make difficult to believe in these findings," says David important not to over-interpret their work." scientists reluctant to take on projects that Albertini of the University of Kansas, referring Kutluk Oktay, a fertility expert at Weill Cornell confirm or counter Tilly's work, they note.
to Tilly's earlier work, which suggested that Medical Center in Tilly says it is "most revealing" that no one the stem cells reside in the outer covering of New York, says anec- has published data refuting his hypothesis in ovaries (Nature 428, 145–150; 2004). When the
dotal evidence from the 18 months following the Nature paper. He researchers could not isolate the stem cells from his patients suggests says some colleagues set the burden of proof ovaries, Tilly says, their data led them to the ovar- Tilly's observations incredibly high, suggesting that he should have ian blood supply, and then to the bone marrow.
might hold true in asked another lab to confirm his work in parallel. The team transplanted blood from normal people. But "people "If you are still critical," he says, "get into the lab female mice engineered to produce green fluo- expect duplication of this study, and that may and prove us wrong." rescent protein to mice that had been sterilized take someone else five years," Oktay says.
Kendall Powell, Denver
Maine company falls a-fowl for smuggling bird flu
As the virulent bird flu sweeping through Asia
Advantage Bio Consultants in South Dakota.
company's employees had changed vaccine
holds global attention, regulators in Maine are
The smuggled virus was an H9N2 subtype,
labels to minimize import costs for overseas
dealing with an avian virus closer to home.
less virulent than the H5N1 virus that has
clients and altered vaccine expiration dates.
A Maine biotechnology company that makes
claimed 57 lives in Asia since 2003. But
In July, four former executives were sentenced
vaccines for poultry diseases was in August
low-virulence strains can rapidly mutate to
to fines up to $30,000 and a year in jail. The
fined $500,000 for smuggling a chicken flu
become deadly. In 1983, the low-virulence
company is now under new management and
virus into the US.
H5N2 strain evolved into a highly pathogenic
says that it is in full compliance with the law.
Vaccine manufacturer Maine Biological
strain within six months in Pennsylvania,
To bring infectious agents into the country,
Labs in 1998 illegally imported the virus
forcing authorities to kill 17 million birds at a
companies are required to obtain permits
from Saudi Arabia so that it could develop a
cost of nearly $65 million.
from the US Department of Agriculture. The
vaccine for a disease-plagued poultry farm
These viruses can also occasionally be
agency may deny permits for dangerous bugs
in that country. According to court records,
transmitted to people. An H9 virus infected
not found in the US. In April 2005 it stipulated
the following year the company used falsified
two people in Hong Kong in 1999 and one in
that certain agents can only be sent to those
documents to send 8,000 bottles of the newly
2003, causing mild illness.
who are registered to receive them. But
created vaccine back to Saudi Arabia.
The Maine case came to light in 2002, when
stopping someone from illegally importing a
"If the virus got out, it could have decimated
a whistleblower sparked a federal investigation
virus, says Suzan Holl, a spokeswoman for the
poultry populations and cost billions of dol-
that found widespread illegal activity at
agency, is "almost impossible."
lars," says Keith Haffer, a vaccine consultant at
the lab. Investigators discovered that the
Emily Singer, Boston
NATURE MEDICINE VOLUME 11 NUMBER 9 SEPTEMBER 2005
Malaysian researchers bet big on home-grown Viagra
For the first few days you might have a light project is a collaboration with 230 researchers headache, a slight fever or even a rash. But the at the Massachusetts Institute of Technology results—increased sexual desire, enhanced (MIT), the Forest Research Institute of Malaysia performance and general well-being—should and 16 other Malaysian institutes.
be worth it. At least, that's what Malaysia's Critics say Malaysia is squandering its scarce researchers are banking on.
resources on research that is unlikely to pay off. Malaysians have long believed that consuming "Basic science should be equally emphasized, tongkat ali, a shrub that can grow to ten meters, but it isn't," says a biologist at Monash University has several benefits—most notably, aphrodisiac Malaysia in Selangor. powers for men. Scientists there now hope to hone The researchers have had some success in on the herb's active ingredients and market (Plant Physiol. 131, 1294–1301; 2003), but have
it to the world. If they succeed, the venture will mark not yet published reports on the herb's efficacy Malaysian biotechnology's first big triumph.
in high-impact journals. That is because the Most Malays ingest the herb, Eurycoma government is concerned about intellectual longifolia, as a tea prepared by boiling chunks of property, says Mohd. Ilham Adenan, the project's the root. More recently, a powder produced by coordinator. The researchers have already filed drying the boiled concoction is being put into patents in Malaysia, the US and Japan.
pills or added to food products. In Kuala Lumpur, The project suffered at least a temporary Hard sell: Nearly 200 products in Malaysia are
made with the tongkat ali root, thought to have billboards advertise canned beverages spiked with setback on 12 August, when the US rejected aphrodisiac properties.
the herb; tongkat ali chocolate and dried coffee an application for a patent on a 4.3-kilodalton are available at airport shops. There are nearly glycoprotein thought to increase testosterone The results have also borne out in early clinical 200 such products on the domestic market.
synthesis. But MIT plant biologist Anthony studies out on a small group of men, Azizol says. These products are ready to go abroad, says Sinskey remains bullish. "The findings are novel In one study, 40% reported feeling easily aroused, Azizol Abdul Kadir, president of Phytes Biotek, and important so we are confident," he says.
having longer erections and experiencing more a biotechnology company in Selangor. "I'll put The researchers decline to identify the protein, climaxes during intercourse. Many also reported tongkat ali on the world market." one of the herb's active components. Previous improved memory and better bowel movements. Malaysia's neighbor Singapore has won global studies have shown that in mice, gradually increas- But 12% noted constipation and 8% said their acclaim for its burgeoning biomedical research ing the herb's dose makes mice more sexually erectile problems persisted.
industry. In a bid to jumpstart its own ailing active (J. Herbs Species Med. Plants 9, 109–114;
Azizol says the herb might also become biotechnology industry (Nature 436, 620–621;
2002). Beyond a set dose, the males are overcome popular for combating malaria, cancer and aging. 2005), the Malaysian government has sunk with sexual desire, says Azizol, and "don't dis- "It's not just for sex—it's for the whole body." about $7 million into the herb. The central criminate between male and female anymore." David Cyranoski, Tokyo
Complaints of gender bias compel NIH to revise awards scheme
When the US National Institutes if Health
director's office—which had little experience
these things," he says.
(NIH) announced the winners of the first
with grants—to the National Institute of
The awards, worth up to $500,000 for
annual NIH Director's Pioneer Award last
General Medical Sciences. The agency also
five years, aim to support creative and novel
year, one fact stood out: all nine awardees were
named Jeremy Berg, the institute's director—
approaches to biomedical research. The 2005
men. This year, thanks to a flurry of protests
and one of several NIH researchers who
winners are set to be announced 29 September.
from scientists, the winners are likely to be a
complained—to redesign the program.
This year's applications have been
more diverse bunch.
Together with Nora Volkow, director of the
reworded to say that women and members
Shortly after the announcement of last
National Institute on Drug Abuse, and NIH
of underrepresented groups are "especially
year's winners in September 2004, individual
researcher Judith Greenberg, Berg redesigned
encouraged" to apply, and that the award is
scientists and groups such as the American
the award scheme to include more women and
available to early- and mid-career scientists.
Society for Cell Biology (ASCB) and the
minorities as both applicants and judges.
According to Berg, 26% of this year's
Association for Women in Science complained
"I was impressed with the changes they
applicants are female, and the breakdown
about the "striking lack of diversity."
made, this should be a model for other
for the 20 finalists reflects the applicant
"The selection of such a homogeneous
grant application processes," says Stanford
pool. In 2004, women made up only 21%
group of award winners sends an unavoidable
University neuroscientist Ben Barres (see page
of the 1,300 applicants and only 2 of the
message to women that they are not worthy of
916), who has served as a judge both years.
21 finalists. Because the award is given to
recognition as ‘pioneers' and indeed may be
The changes are significant: up to 40% of
researchers for novel biomedical research
considered less valued than men by the
this year's referees are women or minorities,
strategies, it attracts applicants with technical
highest levels of the NIH," wrote ASCB's
and applicants can nominate themselves. Last
and engineering backgrounds, fields that
then-president Harvey Lodish and Women in
year, by contrast, 60 of the 64 judges were men
have fewer women, says Berg. The NIH
Cell Biology chair Ursula Goodenough.
and "unconscious bias" probably affected the
does not have data on the status of minority
In response, the NIH transferred
outcome, notes Barres. "Applicants had to be
responsibility for the awards from the
nominated—people tend to nominate men for
Kris Novak, San Francisco
VOLUME 11 NUMBER 9 SEPTEMBER 2005 NATURE MEDICINE
EPA plans to set new
Lawsuit loss leaves
pesticide testing rules
links face scrutiny Merck with murky future
The US Environmental Protection Agency Many doctors involved in ongoing drug
Pharmaceutical giant Merck faces an uphill battle is expected to release in early September an trials have leaked confidential information
in future lawsuits after a resounding loss in the unprecedented regulation governing tests that to hedge funds and other investment firms,
first Vioxx trial. A Texas jury awarded $253.4 mil- intentionally dose people with pesticides.
according to a Seattle Times investigative
lion in damages to the family of Robert Ernst, A leaked copy of the regulation, which cir- report published in August. Early information
who died in 2001 after taking Vioxx for eight culated in Washington last month, lays out the on clinical trials can help investors decide
months. Merck plans to appeal.
ethical standards that human tests conducted whether to buy or sell a drug maker's stock
Jurors said they were swayed by documents by companies would have to meet. The agency before trial results are made public.
showing that Merck was concerned about Vioxx's plans to use the tests to help set safe levels for Hedge funds are private, unregulated
safety several years before pulling the drug from pesticide residues in foods.
investment funds for wealthy investors that
the market and downplayed the cardiovascular The Food Quality Protection Act of 1996 made specialize in short-term high-risk trading.
risk to doctors. The company pulled the pain- it difficult for companies to meet safety standards They pay researchers up to $500 an hour to
killer from the market in September 2004, after using animal tests alone. As a result, some pesti- talk about their ongoing work, sometimes
a clinical trial showed that individuals who took cides have been banned or severely restricted— getting an inside scoop that can garner
Vioxx for 18 months or more doubled their risk and companies have re-launched human testing, millions in stock trades.
of heart attack and stroke.
a practice they had largely abandoned in the early Hedge fund managers say they are doing
The coroner who conducted Ernst's autopsy 1980s. The new requirements would not be retro- nothing wrong and rely on the researchers to
testified that she thought Vioxx caused a blood active, allowing the industry to present data from honor their own confidentiality agreements.
clot that led to an irregular heartbeat and death. human tests dating back to the 1960s.
Some researchers in turn insist that they are
Merck officials contend the arrhythmia was Once the regulation is published in the Federal not sharing confidential information, only
caused by hardening of the arteries unrelated Register, a 90-day public comment period will giving details of their personal experience with
follow. Under a law passed by Congress this a drug. But seemingly small details, such as a
Analysts expect the win to prompt more summer, the regulation must be finalized by drug's side-effect profile in a few patients, can
lawsuits. More than 4,200 other Vioxx-related February 2006 (Nat. Med. 11, 811; 2005). As give investors insight into the drug's future
state and federal lawsuits have already been worded, the EPA document allows for some test- filed against Merck.—ES
ing on pregnant women and children, which has The finding follows on the heels of a June
report showing that nearly one in ten doctors
Clarification: A news article in Nature Medicine
in the US acts as a consultant to the investment
(Nat. Med. 11, 5; 2005) reported that the jour-
industry (JAMA 293, 2654–2657; 2005).
nalist Liam Scheff "does not believe that HIV Britain set to reassess Republican Senator Charles Grassley, head
causes AIDS." Mr. Scheff would like to clarify of the Senate Finance Committee, has urged
that rather, he is "not convinced that HIV is its fertility laws the Securities and Exchange Commission to
the sole cause of AIDS, based on evidence pre- The British government in August
investigate the practice.—ES
sented in the medical literature." announced plans to overhaul its fertility
laws for the first time in 15 years. Ministers
will consider whether to relax rules
China's mystery pig disease baffles experts
governing in vitro fertilization and other
A deadly strain of a pig-borne disease is sweeping through the Sichuan province of China, puzzling public health experts with Fertility treatments are regulated more
strictly in Britain than in the US and other
A group of international specialists convened by the World countries. Officials plan to update the 1990
Health Organization determined on 9 August that the outbreak Human Fertility Act, which many say is out
is consistent with infections caused by Streptococcus suis. The of step with current technologies.
bacterium is relatively common in pigs but, until now, has rarely Authorities will gather public opinion on
caused infections in people. The size of the current outbreak—at controversial issues such as sex selection
least 215 people are infected, and 39 have died—has led some for balancing families and the use of
experts to speculate that another pathogen may be involved.
preimplantation genetic diagnosis to screen
Most of those infected are male farmers involved in killing embryos for genes linked to diseases. The
pigs or processing their meat. Chinese authorities say there is no Philippe Lopez/AFP/Getty Images new rules could give parents more freedom
evidence of human-to-human transmission thus far.
to create ‘savior siblings,' babies that can
However, experts say more research is needed to determine the reasons for the outbreak's act as tissue donors for a seriously ill
unusual size and virulence.
sibling. The overhaul may also change rules
Chinese authorities knew of the first human cases by 24 June, but did not make the news governing storage of embryos.—ES
public until a month after. The government is enforcing strict measures to regulate the trade of live pigs and pig meat and says human cases have dwindled after a peak in late July. But reporters are banned from the affected areas, prompting international groups to criticize the News briefs written by Emily Singer and Chinese government's handling of the situation.—ES Meredith Wadman.
NATURE MEDICINE VOLUME 11 NUMBER 9 SEPTEMBER 2005
N E W S F E AT U R E
Revolt in Bethesda
you want to make the NIH intramural pro- Disheartened by restrictive new rules, researchers at the US gram a high-quality organization, you have to interact with industry," he says. "However, it National Institutes of Health are speaking out—and several are must be done in ways that don't interfere with choosing to jump ship. George S. Mack investigates.
the work people are doing for government." But beginning on 7 December 2003, a series of reports in the Los Angeles Times revealed that several NIH researchers had violated the Lynn Gerber was an idealist when she first distrust for the judgment of scientists," says 1995 guidelines by accepting large consulting arrived at the US National Institutes of Health Hynda Kleinman, chief of cell biology at the fees from biotechnology and pharmaceutical (NIH) as a college student in the summer of National Institute of Dental and Cranofacial companies. In one egregious example, Trey 1962. Gerber wanted to work in "the world's Research. "Everything from travel to meetings Sunderland, an Alzheimer disease researcher most exciting laboratory" where future to being on editorial boards was questioned." at the National Institute of Mental Health, had Nobel Laureate Marshall Nirenberg was Demoralized by the soured environment, received more than $500,000 from Pfizer over doing ground-breaking research on protein some senior researchers such as Kleinman are a five-year period, and had not disclosed the synthesis. Today Gerber is chief of deserting the NIH after long careers there.
arrangement to his ethics officer.
rehabilitation medicine at the NIH Clinical "The atmosphere is punitive, very restrictive It took only one day for Congress to ask Center, where researchers from the agency's now and a lot of our time has been spent Zerhouni to produce documents relating 27 institutes conduct trials.
talking about the changes instead of science," to the publicized cases. The first of three Gerber says that overall, her 32-year career says Derek LeRoith, who was chief of hearings was held on 12 May 2004. By July at the NIH has been exciting and rewarding, diabetes at the National Institute of Diabetes & of this year, Zerhouni acknowledged that of thanks to a supportive environment. But what Digestive & Kidney Diseases. After 26 years at 81 current and former NIH employees identi- was once a collegial atmosphere has been the institute, LeRoith in September begins work fied by the Congressional subcommittee, 44 tarnished by new policies that have left the at the New York–based Mount Sinai School had violated the 1995 rules. Of those, 9 were agency's staff, including Gerber, disheartened.
of Medicine. "The bureaucracy has become referred to the inspector general's office at "I've lived through every administration overwhelming," LeRoith says, "and the the US Department of Health and Human since [President] Carter," she says. "But atmosphere has just gone very negative." Services for possible criminal violations.
fundamentally, I have not experienced so Fighting to regain the agency's reputation, much change as now." Anguish on campus
Zerhouni promised Congress that he would From 1998 to 2003, the NIH adjusted to The biggest of the NIH's woes is the con- carry out "major reform" and lay down the growing pains that accompanied a massive troversy surrounding alleged violations of law to his 18,000-plus employees.
expansion, which effectively doubled its its conflict-of-interest guidelines. In 1995, He wasn't kidding.
annual budget. In May 2002 it also gained then-director Harold Varmus relaxed a set a new director, Elias Zerhouni, filling a post of anachronistic rules that had prohibited Not-quite-final rule
that had remained vacant for more than two virtually all outside arrangements, includ- On 1 February, Zerhouni's office released the years. Zerhouni had made a name for himself ing involvement with scientific societies, new "interim final rule" with broad prohibi- at Johns Hopkins University, where his work academic institutions, journals and compa- tions on outside employment and activities and on advanced imaging techniques led to 157 nies. The premise was that by loosening the stock holdings in healthcare-related firms— peer-reviewed publications and eight patents. rules, NIH institutes could more easily attract including companies such as General Electric But at the time of his appointment, few basic because it makes imaging systems. The rule also researchers knew of or trusted him (Nat. Med. "This was not just about money," says bans acceptance of awards with a value greater 8, 311; 2002).
Varmus, now president of than $200, with the exception of Nobel Prizes Zerhouni's tenure has, New York's Memorial Sloan- and the Lasker awards.
perhaps by chance, coincided Kettering Cancer Center. "It After an immediate groundswell of protest, with one of the most turbu- was at least as important that from formal letters to Zerhouni to corridor lent times in the agency's NIH scientists be able to par- coffee klatches, the administration promised history. The NIH has been ticipate in a range of outside to revise the rules—but it's anyone's guess under near-constant fire activities, so they wouldn't feel when that will happen.
from the media and the like second-class citizens." For 19-year NIH veteran Cynthia Dunbar, government, with allega- Varmus says the US Office of the ban has meant that even her husband must tions ranging from financial Government Ethics encouraged divest healthcare stocks in her stepchildren's improprieties to sexual mis- liberal policies to allow NIH trust accounts. "It's asking other people to conduct. Scientists there have the same privileges enjoyed by take huge financial hits for activities that also been under much tighter other agencies. But those guide- I'm carrying out," says Dunbar, a senior control of the administration.
lines must be accompanied by investigator at the National Heart, Lung National Institutes of Health "After the arrival of Dr. Troubled times: NIH director enough ethical guidance and and Blood Institute. "And what I'm doing
Zerhouni three years ago, Elias Zerhouni's tenure has formal consent, he notes.
actually has nothing to do with the stock price there was a lot more apparent "As I've said many times, if of General Electric." VOLUME 11 NUMBER 9 SEPTEMBER 2005 NATURE MEDICINE
N E W S F E AT U R E
For some researchers, the rules have had "There is no avalanche, unexpected consequences. Kleinman had but I think the obvious to resign from the boards of the Metastasis virtual halt in recruitment Research Society as well as the NIH's own and continued chronic Foundation for Advanced Education in the drain will decimate this Sciences. As a board member, the ethics offi- place over a few years," cers said, she would be making fiduciary deci- says Alan Schechter, chief sions—such as where a meeting would be held of molecular biology and and which speakers might be invited. "They genetics at the National saw it as a conflict," she says.
Institute of Diabetes & Kleinman also had to resign from her unpaid Digestive & Kidney Diseases.
adjunct professor position at Georgetown The rules also set a University in Washington, DC because the double standard, oth-university gets NIH grants—even though she ers say. About 10% of has "nothing to do with grants at NIH." For the NIH's $28.8 billion 15 years, she had also been a judge for the budget for 2005 goes to Derek LeRoith says the atmosphere at the NIH is "very negative." prestigious Westinghouse Science Talent Search, intramural programs car- After 26 years there, he has moved his lab to the Mount Sinai now called the Intel Science Talent Search. ried out by almost 6,000 School of Medicine.
"I had to resign from that too," she says.
researchers. Most of the Kleinman has been told she can reapply rest is awarded through competitive grants Varmus, who has firsthand experience of the for permission to do some activities, but no to more than 200,000 researchers elsewhere. pressure an NIH director can face, is also quick decision would be made until the revised set Extramural researchers in academia can use to defend Zerhouni. "I'm not going to place any of rules is published. "That was my tipping expertise developed through NIH grants to blame on Elias," Varmus says. "He's in a bind, point," she says. After 30 years at the NIH, she consult for companies, serve on boards and and putting him under pressure is a mistake. will leave in December to join the faculty of give lectures for compensation, note some You run the chance of having a different person George Washington University.
senior NIH researchers.
appointed, and that could be a huge issue." Other researchers say the regulations "This is a politically sensitive area," Varmus also expects the environment to are driving away their friends in Schechter says. "The medical schools and improve soon. "I have some reason to believe professional organizations. "People have universities would fight this, but I think it that the final rules will be less stringent—less worked cheek-to-jowl for years with should be out on the table," he says. "Conflict- draconian than the ones that are currently in colleagues in academia and in their of-interest issues must be solved for the effect," he says.
professional societies, and they are now entire biomedical research community if the In the meantime, scientists who want to being told they are not going to be invited solutions are to be meaningful." leave the NIH should think twice, says Ron to do so-and-so because there are so many Some researchers say they believe Zerhouni Crystal, chairman of genetic medicine at restrictions," she says. "They feel left out." buckled under pressure from Congress and Cornell University. Crystal, who spent 23 then came down too hard on researchers in years at the National Heart, Lung and Blood Institute before joining Cornell in 1993, says In April, Zerhouni acknowledged that some "I think that's patently not true," says he understands how challenging times are of the new rules might be loosened, but the NIH deputy director Raynard Kington. for friends at the NIH. But before leaving, sting of ham-fisted regulation hasn't subsided. "Dr. Zerhouni has vigorously defended the researchers should consider whether they Gerber says that as a federal employee, she the scientists of this agency, but we've also would be able to pursue certain projects— "truly understands" the importance of rules. recognized that a few—and we have such as trials of drugs that don't interest But requiring her to file a public disclosure of clearly said a few—scientists, have violated pharmaceutical companies—elsewhere, he all her mutual funds and stock holdings, she rules and regulations in a way that hurt says. "I think the answer, at least in some says, is going too far. "I feel it's draconian." instances, is that it would be very difficult Although there is not as yet an exodus from outside the NIH." the institute, the rules are making it difficult But for some researchers, it's already too to recruit good researchers to the NIH.
late. Gerber, for one, has made her decision. On 31 October, she joins George Mason University in Fairfax, Virginia, where she plans to develop a new center for the study of chronic illness and disability.
She says it pains her to speak critically of the agency she fell in love with as a wide-eyed college student. But "all these regulations coming down on us are seen as punitive, a rap on the knuckles," she says. "We are good Jan 2001 Jan 2002 Jan 2003 Jan 2004 Jan 2005 people, hard-working people and committed people—we don't deserve that." The NIH's population, which grew during the budget expansion, has seen a decline in the past George S. Mack writes for Nature Medicine
two years (left). At the same time, the proportion of young scientists has decreased (right).
from Columbia, South Carolina.
NATURE MEDICINE VOLUME 11 NUMBER 9 SEPTEMBER 2005
Neurobiologist Ben Barres may have a successful career, but he Barres says the disconnect between clinical and basic research is knows exactly what discrimination looks like. And over the years, a big obstacle in developing treatments for many diseases, and MD- he has learned to fight back.
PhD programs aren't successfully filling this need. "Unfortunately, many MD-PhDs do a short-track PhD and have less of a chance of doing well in research," he says. "It takes about ten years in the lab Ask Ben Barres whether women in science are treated fairly. But first to really become successful on your own." make sure you have plenty of time to hear his answer.
Barres is setting up a new Stanford program—which he will Barres is a successful and busy neuroscientist at Stanford University, direct—that would allow PhD students to sit in on the first two
but this is a topic close to his heart. Despite his many responsibilities, years of medical school coursework and begin thinking about he tirelessly champions women and minority scientists, speaking out how their research relates to disease. He has also helped against injustice wherever he sees it—and he sees plenty.
launch a nonprofit foundation that aims to develop drugs for Most recently, Barres wrote letters criticizing comments made multiple sclerosis.
by Harvard University President Larry Summers (Nature 434, 697;
As passionate as he can be, Barres also makes time to lead his lab 2005) and helped revise a US National Institutes of Health (NIH) members on hikes in the mountains, and to keep up with the Harry award scheme that unfairly favored male scientists. "I think as I have Potter books. Lab members say he ran out and bought the latest gotten older I have realized that I don't have to sit back passively book in the series the Saturday it went on sale and had read it by and take it any more, that people have a responsibility to speak out the following Monday. Much to his delight, his students last year against discrimination," he says.
modified a Harry Potter movie poster, replacing Harry's face with The most recent data say that most male scientists don't notice his own. "I think he somehow relates to Harry," says postdoctoral the hostility their female colleagues face (Science, 309, 1190–1191;
fellow Beth Stevens.
2004). But Barres has first-hand knowledge of what it means to be a member of an underserved group.
You see, until 1996, he used to be a woman.
"I think as I have Having experienced discrimination first as a woman, then as a gotten older I have transgendered individual, Barres says he is acutely aware of people's prejudices. In high school, Barbara, as he was called then, was the realized that I don't math team captain and planned to attend the Massachusetts Institute have to sit back of Technology (MIT). But the guidance counselor said Barres could never get in and should aim lower. "Fortunately I had sense enough passively and take it to ignore him and applied only to MIT, where I was accepted early decision," Barres recalls.
Things weren't much easier at MIT. Barres was one of few women in math classes and once again faced blatant bias. "I was once told by a mathematics professor that the reason I was the only one in the Barres also has a "mini-laboratory" in his house, where he experi- class to successfully complete an exceptionally complex homework ments with roasting coffee beans. "Ben is crazy about coffee," says problem was because my boyfriend probably helped me," he says.
Stevens. "He is always bringing us samples of his latest batch of Despite those obstacles, Barres completed an MD from Dartmouth beans. He's getting pretty good." University and a neurology residency at Cornell University. Driven But his mind never strays too long from neuroscience.
by his interest in research, he then went on to a PhD program at "Ben doesn't sleep, he works nonstop," Stevens says. "You'll come Harvard University, where he spent 15-hour days in the lab, moon- into work in the morning to find that he sent you ten emails at lighting weekends as a clinician to pay off his school loans. "I was 4 am, all with new ideas for your project." always tired," he says.
Still, he gives his students and postdoctoral fellow plenty of intel- At the end of nearly 14 years in training, Barres went to work lectual freedom. "Ben thinks about the big picture, but lets grad stu- as a postdoctoral fellow in Martin Raff 's lab at University College dents run with their own project," says fifth-year graduate student London. During his three years there, he developed a new technique Rick Daneman. Barres says researchers should even allow students to to isolate oligodendrocytes—central nervous system cells that sup- take reagents and mice with them when they start their own labs.
port the development of neurons—and made many contributions to He also wants the NIH to maintain a record of where trainees their study. "After he left, we routinely used his purification method from each lab end up. "That way, students and postdocs can look at and spent years following up his important findings," says Raff.
the labs and see which ones will let them best develop as an inde- Barres launched his own lab at Stanford in 1993, where he is pendent scientist," he says.
now vice-chair of neurobiology and co-director of the university's And there again, Barres is committed to creating an even playing Neuroscience Institute. "This is the greatest job—I feel so lucky to field. As one of the judges for the NIH Director's Pioneer Awards, have a lab," says Barres, whose research focuses on the degeneration Barres—along with several others—criticized the program for giving of nerve cells in injury and disease. "If I could do one thing before I out awards only to men, compelling the agency to revise the scheme die, I would like to discover something that could help patients," he (see page 912). "Half the people in my lab are women," he says, "and says. "Right now we don't have any drugs that can slow the progres- I just want to see them have a chance at getting these things." sion of any neurological disease." Kris Novak, San Francisco
VOLUME 11 NUMBER 9 SEPTEMBER 2005 NATURE MEDICINE
Biological activities of curcumin and its analogues(Congeners) made by man and Mother Nature Preetha Anand Sherin G. Thomas Ajaikumar B. Kunnumakkara Chitra Sundaram Kuzhuvelil B. Harikumar Bokyung Sung Sheeja T. Tharakan Krishna Misra Indira K. Priyadarsini , Kallikat N. Rajasekharan , Bharat B. Aggarwal a Cytokine Research Laboratory, Department of Experimental Therapeutics, Unit 143, The University of Texas M.D. Anderson Cancer Center,1515 Holcombe Boulevard, Houston, TX 77030, USAb Department of Chemistry, University of Kerala, Thiruvananthapuram, Indiac Bio-informatics division, Indian Institute of Information Technology, Allahabad, Indiad Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai-400085, India