Author Archives: Sara Reardon

White House suspends enhanced pathogen research

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Past research made the H5N1 virus transmissible in ferrets.

Past research has made the H5N1 virus transmissible in ferrets.{credit}Sara Reardon{/credit}

As the US public frets about the recent transmission of Ebola to two Texas health-care workers, the US government has turned an eye on dangerous viruses that could become much more widespread if they were to escape from the lab. On 17 October, the White House Office of Science and Technology Policy (OSTP) announced a mandatory moratorium on research aimed at making pathogens more deadly, known as gain-of-function research.

Under the moratorium, government agencies will not fund research that attempts to make natural pathogens more transmissible through the air or more deadly in the body. Researchers who have already been funded to do such projects are asked to voluntarily pause work while two non-regulatory bodies, the National Science Advisory Board for Biosecurity (NSABB) and the National Research Council, assess its risks. The ban specifically mentions research that would enhance influenza, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Other types of research on naturally occurring strains of these viruses would still be funded.

This is the second time that gain-of-function research has been suspended. In 2012, 39 scientists working on influenza agreed to a voluntary moratorium after the publication of two papers demonstrating that an enhanced H5N1 influenza virus could be transmitted between mammals through respiratory droplets. The publications drew a storm of controversy centred around the danger that they might give terrorists the ability to create highly effective bioweapons, or that the viruses might accidentally escape the lab. Research resumed after regulatory agencies and entities such as the World Health Organization laid out guidelines for ensuring the safety and security of flu research.

The OSTP’s moratorium, by contrast, is mandatory and affects a much broader array of viruses. “I think it’s really excellent news,” says Marc Lipsitch of Harvard University in Cambridge, Massachusetts, who has long called for more oversight of risky research. “I think it’s common sense to deliberate before you act.”

Virologist Yoshihiro Kawaoka of the University of Wisconsin–Madison, who conducted one of the controversial H5N1 gain-of-function studies in an effort to determine how the flu virus could evolve to become more transmissible in mammals, says that he plans to “comply with the government’s directives” on those experiments that are considered to be gain-of-function under OSTP’s order. “I hope that the issues can be discussed openly and constructively so that important research will not be delayed indefinitely,” he says.

The NSABB, which has not met since 2012, was called back into action in July, apparently in response to a set of lab accidents at the US Centers for Disease Control and Prevention in which lab workers were exposed to anthrax and inadvertently shipped H5N1 virus without proper safety precautions. The NSABB will spend most of its next meeting on 22 October discussing gain-of-function research, and the National Research Council plans to hold a workshop on a date that has not yet been set. Lipsitch, who will speak at the NSABB meeting, says that he plans to advocate for the use of an objective risk-assessment tool to weigh the potential benefits of each research project against the probability of a lab accident and the pathogen’s contagiousness, and to consider whether the knowledge gained by studying a risky pathogen could be gained in a safer way.

Correction: This post has been changed to specify that Yoshihiro Kawaoka’s 2012 gain-of-function research increased the transmissibility of H5N1.

NIH awards $46 million for brain-research tools

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Just 18 months after the White House announced the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, the US National Institutes of Health has awarded its first US$46 million in grants for the programme.

“We have referred to this as a moonshot,” said NIH director Francis Collins at a 30 September press conference. “To me, as someone who had the privilege of leading the Human Genome Project, this sort of has the same feel as October 1990, when the first genome centres were announced.”

The 58 NIH grants, which range in size from about $300,000 to $1.9 million, will support more than 100 researchers. According to Story Landis, director of the National Institute of Neurological Disorders and Stroke, the NIH received more than 300 grant applications, and ended up spending $6 million more than it had anticipated in order to fund as many of these grants as possible.

The awards address research priorities included in the NIH’s 10-year plan for the BRAIN Initiative; most will support the development of new tools to monitor the brain, such as a wearable positron emission tomography (PET) scanner that could monitor a person’s brain activity as she goes about her day. Some of these tools could eventually be used for studying and treating human disorders, including grants for imaging neurotransmitters such as dopamine in real time in a living brain, which Thomas Insel, director of the National Institute of Mental Health, says will be extremely useful for studying disorders such as depression. Other tools will be useful primarily for basic research, including many potential improvements on optogenetics – using light to control neuronal firing in animals.

“It’s a new era of exploration, an exploration of inner space instead of outer space,” says Cornelia Bargmann, a neurobiologist at Rockefeller University in New York . “We feel a little like Galileo looking at the sky through his telescope for the first time.”

The NIH’s master plan calls for $4.5 billion for BRAIN Initiative research over the next 10 years, a goal that will require support from Congress to increase the agency’s overall budget. To allay concerns that BRAIN initiative will detract from other NIH-funded research, Collins noted that the BRAIN funding request is dwarfed by the $5.5 billion the agency spends on neuroscience research annually.

The NIH is the last of the three agencies involved in BRAIN to announce its awards. The Defense Advanced Projects Research Agency, which received $50 million this year, has announced several multimillion dollar grants for therapeutic applications such as brain stimulation to improve memory and prosthetic limbs controlled by brain activity. The National Science Foundation received $30 million and, in August, announced 36 small awards for basic research in topics such as brain evolution and ways to store data collected from brains.

Meanwhile, two additional federal agencies — the US Food and Drug Administration (FDA) and the Intelligence Advanced Research Projects Activity (IARPA) — are set to join the effort, the White House announced on 30 September.

The FDA will be working with the other agencies to enable the development of medical and research devices that could be used in humans. IARPA will be joining BRAIN with several of its own ongoing research programmes, including an effort to develop new artificial intelligence systems based on the brain’s network patterns and a study on the use of brain stimulation to increase human problem-solving ability. According to the White House, the total investment in BRAIN Initiative research this year by government and private funding sources, such as the Kavli Foundation, totals more than $300 million.

US announces rules for potential bioterror agents

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A long-awaited US government policy on biological research that could be used for terrorism or other nefarious purposes is little changed from a draft released 19 months ago, despite receiving 38 comments from institutions and researchers concerned that it goes either too far or not far enough. The centrepiece of the policy, released on 24 September, is a set of guidelines for researchers working on 15 specific pathogens or toxins. But the rules do not regulate experiments that engineer pathogens not on the list to make them more deadly – so-called gain-of-function research.  Officials from the White House and US National Institutes of Health (NIH) say the government will be addressing these concerns in coming weeks.

The White House released its first draft policy on dual-use research of concern, or DURC, in February 2013. The policy requires researchers at institutions that receive funding from the US government and are working with one of 15 specific pathogens or toxins to notify their institutions if there is potential that their work could be misused. The institutions will then assess whether or not the research qualifies as DURC. In parallel, the federal government will assess whether such research should receive funding. It will work with the institutions to plan how to manage concerns such as containment of listed pathogens and the public release of information that could allow them to be misused. Amy Patterson, director of the NIH Office of Science Policy, says that it is “incumbent upon investigators”  to report projects that have become potentially dangerous since they were funded, such as the discovery of a new pathogen, at which point the institutions and government would review the project again. Institutions that do not comply will have their government funding withdrawn.

The rules apply only to labs that receive government funding. All institutions are required to register with the US Centers for Disease Control and Prevention (CDC) if they are using one of a longer list of “select agents” defined by the government. But experiments that would, for instance, make a pathogen not on the list more dangerous “would be outside the scope of the current framework,” Patterson says.

Such experiments would include the controversial creation of a mutant flu virus that is deadlier and more transmissible between animals.

Marc Lipsitch, an epidemiologist at the Harvard School of Public Health in Boston, thinks the policy may be of limited use for biosecurity. “I think any list of agents is a temptation, if you’re trying to get around it, to find another agent to do mischief with,” he says.

Patterson says the National Science Advisory Board for Biosecurity (NSABB), which monitors and advises on biological threats to the NIH and federal government, will discuss regulating gain-of-function research at an upcoming meeting on 22 October — its first meeting in two years.  Possible dangers include not just misuse but unintentional releases of pathogens. In two recent incidents at the CDC, H5N1 virus was accidentally shipped to a lab instead of a harmless virus, and dozens of workers were potentially exposed to anthrax.

The 15 pathogens and toxins on the list include:

  • Avian influenza virus (highly pathogenic)
  • Bacillus anthracis
  • Botulinum neurotoxin6
  • Burkholderia mallei
  • Burkholderia pseudomallei
  • Ebola virus
  • Foot-and-mouth disease virus
  • Francisella tularensis
  • Marburg virus
  • Reconstructed 1918 influenza virus
  • Rinderpest virus
  • Toxin-producing strains of Clostridium botulinum
  • Variola major virus
  • Variola minor virus
  • Yersinia pestis

 

Clarification: The original version of this post failed to identify the source of the quote in the third paragraph. The post has been amended to add the source.

Ebola economic impacts to hit US$359 million in 2014

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The Ebola outbreak in West Africa is not only devastating the lives of thousands of people in Liberia, Guinea and Sierra Leone, but it is devastating the economies in those countries as well.

The outbreak is expected to halve economic growth this year in Guinea and Liberia, and reduce growth by 30% in Sierra Leone, according to a 17 September report from the World Bank. It estimates total economic damages from the three countries will total US$359 million in 2014. If the world does not respond quickly with money and resources to halt Ebola’s spread, this impact could grow eight-fold next year, warns the report — the first quantitative estimate of the outbreak’s economic impact.

The United Nations’ 16 September Ebola response plan estimates that the cost of immediate response to the crisis will be close to $1 billion, double the $495 million called for by the World Health Organization on 28 August. This estimate will only continue to increase if other countries do not contribute to the response soon, World Bank Group President Jim Yong Kim said in a phone conference with reporters.

In the long term, the World Bank imagines two scenarios for Ebola’s economic impact: a ‘low Ebola’ scenario in which the outbreak is rapidly contained within the three affected countries, and a ‘high Ebola’ scenario in which it goes unchecked until well into 2015. Under the latter scenario, the economies of Guinea, Liberia and Sierra Leone would suffer significantly; Liberia could lose as much as 12% of its gross domestic product in 2015, the analysis says, thus reducing the country’s growth rate from 6.8% to –4.9%.

Agriculture and mining are the sectors worst hit, along with manufacturing and construction.

“There are two kinds of contagion,” Kim said. “One is related to the virus itself and the other is related to the spread of fear about the virus.” Health-care costs and illness from the virus itself contribute little to the economic impact, the report found. Rather, 80–90% of the economic effects are due to the “fear factor” that shuts down transportation systems, including ports and airports, and keeps people away from their jobs.

The exact number of Ebola cases, for which estimates are constantly changing, is not relevant to the economic model that the World Bank developed, Kim said. “What really matters is how quickly we scale up the response so that we can address the entire number of cases. If we get an effective response on the ground in the next few months, we can blunt the vast majority, 80–90%, of the economic impact,” he added. If this does not happen and the epidemic spreads to other countries such as Nigeria, Ghana and Senegal, Kim cautioned, the ultimate economic hit from this outbreak could reach “many billions”.

Kim also announced a new effort to develop a “universal protocol” for Ebola treatment. Paul Farmer, a physician and global-health expert at Harvard University in Cambridge, Massachusetts; Anthony Fauci, director of the US National Institute for Allergy and Infectious Disease in Bethesda, Maryland; and several non-governmental organizations such as Médecins Sans Frontières will work on the protocol for the World Health Organization to adopt to ensure that all health-care workers will be trained to treat Ebola in the same way.

Such protocols have been crucial in improving management of diseases such as tuberculosis, Kim said. For Ebola, measures that are likely to be part of the protocol include simple steps such as isolation of patients and hydration, which can greatly improve survival.

US government labs plan biohazard-safety sweep

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The discovery of smallpox in a refrigerator at the US National Institutes of Health (NIH) in Bethesda, Maryland, on 9 July has apparently sparked some soul searching in the US government. On 27 August, the NIH designated September as National Biosafety Stewardship Month, encouraging researchers to take inventory of their freezers for potentially dangerous agents such as pathogens and toxins, and review their biosafety protocols. The White House Office of Science and Technology Policy (OSTP) did the same in a memo released to the public on 28 August, suggesting “a government-wide ‘safety stand-down,’” and “strongly urging” both federal agencies and independent labs to complete these steps within the month.

Although the OSTP does not have the regulatory power to enforce inspections, documents obtained exclusively by Nature show that some government agencies are already starting strict surveillance of their labs. In July, the NIH began scouring its own facilities for any misplaced hazards. Its rigorous strategy, obtained through public-records request, requires laboratories at all of its campuses — whether they work with infectious diseases or not — to survey their vials and boxes for potentially dangerous pathogens, venoms, toxins and other agents.  The scientific directors of each NIH institute have until 30 September to submit affidavits confirming that this has been completed by the laboratories in their institutes.

The protocols for this comprehensive sweep describe steps that the laboratory directors must take “including, but not limited to: a) randomly choosing several containers in the inventoried repository and confirming that their contents are as expected; b) if feasible, visually inspecting the contents of a substantial number of containers in the repository to be sure they hold vials of the expected type.” Anything unlabelled must be thrown away, and labs are instructed to pay specific attention not only to pathogens, but also to other hazardous materials such as poisons, venoms and explosive materials.

For extremely large collections with more than 10 million vials, such as the tissue sample repositories managed by the National Cancer Institute (NCI), researchers will not need to evaluate every single sample. Instead, they can apply a  statistical algorithm to determine how many are likely to be misidentified. The NCI’s algorithm, for instance, would require examining 10,000 out of 10 million samples and matching them to existing electronic records of the inventory, and then extrapolating the rate of mismatches to the entire sample collection.

Other government agencies that work with infectious diseases are also beginning laboratory sweeps. In testimony to Congress on 16 July, Thomas Frieden, director of the US Centers of Disease Control and Prevention (CDC) promised a sweeping inventory of all CDC labs at the wake of a pair of incidents in which scientists were exposed to anthrax, and accidentally shipped flu virus to another lab.

On 25 August, the US Department of Veterans Affairs (VA) sent out a memo to its staff announcing that it would be complying with a “government-wide safety stand-down” while the agency makes sure that none of its labs have unregistered dangerous biological agents or toxins and reviews its security practices. VA scientists have until 24 September to submit affidavits that they have complied with this order.

Carrie Wolinetz, the associate vice-president for federal relations at the Association of American Universities in Washington DC, says that a number of scientists were initially concerned about that the vaguely worded VA requirement meant that research would be suspended for an unspecified amount of time. She sent out a memo to universities on 26 August, clarifying that the OSTP would not be enforcing any mandates.  “It’s saying just take a day to take a look through your freezer,” she says. “It’s a good opportunity to do some reflection on what’s in your lab without it being burdensome or regulatory.”

But the lack of regulatory power is what worries epidemiologist Marc Lipsitch of the Harvard School of Public Health in Boston, Massachusetts. “Overall the White House memo is encouraging as the first, small step in a comprehensive approach to biosafety and biosecurity, but it will have little effect unless many other changes are put in place, which remain unspecified at this time,” he wrote in an e-mail to Nature.

Lipsitch is particularly concerned about regulation of experiments that make pathogens such as influenza virus more dangerous, and incidents such as those at the CDC. “The three incidents with [dangerous pathogens] in federal labs that spurred this action are among hundreds that happen each year in US laboratories,” Lipsitch writes. “Given the magnitude of the response that these three incidents have provoked, it is unsupportable to keep secret the details of [these] incidents in general. The poorly justified ‘security’ reason for keeping such incidents secret cannot outweigh the need to understand and learn from them.”

NIH advocates gear up for budget fight

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The US National Institutes of Health (NIH) would see its budget worries eased if a long-time political champion gets his way.

Senator Tom Harkin, the Iowa Democrat who leads the Senate panel that oversees the NIH, introduced legislation on 24 July that would ensure that the NIH’s budget never drops below its current US$29.9 billion. The bill also proposes that Congress increase the NIH’s budget by up to 10% for the next two years, and 5% each year for the next five years. By 2021, the agency’s budget would rise to $46.2 billion.

The legislation is unusual in that it sets a minimum level for NIH funding regardless of the government’s total budget for a given year. That approach could pit the NIH against other agencies when money is scarce, a scenario that some agency supporters worry is not so hypothetical. A 2011 law known as the Budget Control Act caps total government spending to 2021 (although the caps have since been relaxed for 2014 and 2015).

The Harkin bill would allow increases for NIH beyond this cap. Some advocacy groups say that NIH is not the only biomedical agency that is in need of a boost. “The painful effects of austerity span beyond NIH across the entire health continuum,”  Emily Holubowich, senior vice-president of the Coalition for Health Funding wrote to Nature. “We support a balanced, comprehensive, permanent solution to end this era of austerity for all public health and core government functions.”

The legislation’s future is uncertain, however. Harkin is retiring at the end of this year, and Congress is working on a schedule shortened by the federal election in November. Lawmakers are not expected to finish work on a funding plan for the 2015 budget year — which begins on 1 October — until after the election.

Researcher reassigned in wake of disease centre’s anthrax scare

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The US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, has taken its first disciplinary steps in response to a laboratory mix-up that potentially exposed dozens of employees to anthrax earlier this month.

The agency reassigned the head of the Bioterror Rapid Response and Advanced Technology Laboratory, which was involved with the incident, pending completion of the investigation. An agency spokesperson would not confirm the employee’s name.

The agency says that it still does not know why the lab failed to follow a simple protocol that would have killed the bacteria. According to CDC statements, between 6 June and 13 June, workers at the lab inadvertently shipped live Bacillus anthracis to another CDC lab that was not equipped to handle live bacteria.

According to CDC spokesman Thomas Skinner, the researchers were using a new protocol for the first time. Rather than irradiating the bacteria, which is the more common way of killing them, the researchers were treating them with a series of chemicals and then incubating them for 48 hours to ensure the bacteria were no longer alive. But the workers waited only 24 hours before sending the bacteria off, and the lab that received them did not verify that the bacteria were dead before starting to work with them. Researchers discovered the oversight a week later when they found bacteria growing on a dish.

Skinner says that the CDC is still investigating questions such as why researchers followed the protocol improperly and why the staff did not wait the full 48 hours. On 20 June, the US Department of Agriculture took over the investigation to avoid conflicts of interest.

Although initial reports said that 75 people were potentially exposed, Skinner says that the agency is no longer attempting to estimate an exact number. But he says that more than 70 people have been treated with antibiotics, and some of those have also been vaccinated. The CDC believes that only about seven people had direct contact with the bacteria and are hence at high risk of exposure.

Because the workers were treated quickly, the chances of a worker actually contracting the disease are slim, says Amesh Adalja, a biosecurity expert at the University of Pittsburgh Medical Center’s Center for Health Security in Baltimore, Maryland.

The greater concern, he says, is the failure to follow proper biosafety procedures.  “The work they do on anthrax is important, and you don’t want to set back public confidence so people question whether this research needs to be done,” he says.

Richard Ebright, a molecular biologist and biosecurity expert at Rutgers University in Piscataway, New Jersey, says that the incident is the latest in a series of biosecurity failures at CDC labs and the labs the CDC certifies, including a nearly identical event at a California lab in 2004 in which 12 people may have been exposed to anthrax. “The fact that CDC is reprising this ten years later shows they’ve learned nothing,” he says. “Changing one person doesn’t solve problems there.” The agency, he says, needs to undertake a close reassessment of safety training and management.

US Supreme Court strikes IQ cutoff for death penalty cases

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When deciding whether a defendant is too intellectually disabled to receive the death penalty, courts must take into account inherent variability in intelligence quotient (IQ) scores, the US Supreme Court ruled today.

In its 5-to-4 decision, the court said that it is unconstitutional for states such as Florida to use an IQ score of 70 as a cutoff above which a defendant is considered to be intelligent enough to understand the consequences of his or her actions.

The plaintiff in the case, Freddie Lee Hall, has been on death row in Florida for 35 years after being convicted of murdering two people in 1978. He has taken multiple IQ tests, yielding scores ranging between 60 and 80, and testimony from people who knew him suggest that he has been intellectually disabled his entire life. But under Florida law, an IQ score above 70 disqualifies a defendant from being spared execution on the basis of intellectual disability, and Florida’s Supreme Court ruled in 2012 that Hall’s scores were too high to qualify for this reprieve.

But the American Psychological Association (APA) and the American Association on Intellectual and Developmental Disabilities hold that IQ tests have an error margin of about ten points. Consequently, Hall’s lawyers argued that IQ tests are too imprecise to determine whether his score falls on one side or the other of this cut-off.

“Florida’s rule disregards established medical practice in two interrelated ways,” Justice Anthony Kennedy writes in the court’s majority opinion. “It takes an IQ score as final and conclusive evidence of a defendant’s intellectual capacity, when experts in the field would consider other evidence. It also relies on a purportedly scientific measurement of the defendant’s abilities, his IQ score, while refusing to recognize that the score is, on its own terms, imprecise.”

The Supreme Court sent Hall’s case back to Florida’s court for a reassessment. It is not yet clear what Florida, and as many as eight other states with similar laws, will adopt in lieu of the IQ threshold. But the court’s decision compels states to incorporate other evidence if a defendant’s scores fall within the range of error.

James Harris, a psychiatrist at Johns Hopkins University in Baltimore, Maryland, and an expert on intellectual disability, is pleased with the decision. “The Supreme Court validates professional practice in measurement,” he says. “They confirm the dignity of the process and the dignity of the people with intellectual disability who are being served by the process.”

But Harris would have liked to see the ruling go further in emphasizing the importance of testing for adaptive functioning — a person’s ability to function in society — which is another factor that the APA uses to diagnose intellectual disability. This factor, he contends, is often more relevant to a case than an IQ score, which mainly tests academic ability.

Although the APA has held for decades that IQ scores have a margin of error, Justice Samuel Alito worries that the ruling opens a can of worms, as the guidelines of professional societies change over time. Tying the law to these views will “lead to instability and continue to fuel protracted litigation,” he writes in the minority opinion.  Alito adds that the court’s decision “adopts a uniform national rule that is both conceptually unsound and likely to result in confusion”.

NIH alternative-medicine centre proposes name change

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The US National Institutes of Health’s Center for Complementary and Alternative Medicine (NCCAM), a perennial punching bag, no longer wants to be ‘alternative’. Director Josephine Briggs announced today that NCCAM is accepting public comments on a proposal to rename itself the “National Center for Research on Complementary and Integrative Health”.

The decision, Briggs says, is a reflection of NCCAM’s changing mission. When the centre was founded in 1998, it funded studies of questionable therapies such as homeopathy and remote healing. Over the years, such trials have become less common; NCCAM’s current research focuses more on holistic health — such as the role of yoga in pain management, as a complement to medication. “We’re seeing a progression in our research agenda and an increased integration of the types of practices we study into conventional care,” Briggs says.

She emphasizes a distinction between this complementary approach, which she says is increasingly used by institutions such as veterans’ hospitals, and alternative medicine that patients may choose over evidence-based medicine. “I worry a lot about people who choose something that’s completely unproven when good medical care involves something we know will help,” Briggs adds.

But NCCAM’s name change may not be enough to convince some critics that the centre has integrated itself into the National Institutes of Health’s research mission. Donald Marcus, an immunologist at Baylor College of Medicine in Houston, Texas, says that  the centre’s research programmes and attempts to include complementary medicine in medical education continue to be a “waste of time”. While he agrees that NCCAM’s research portfolio has improved — it has discontinued funding clinical trials of herbal therapies, for instance — Marcus see the change as cosmetic. So-called integrative care, which includes therapies such as acupuncture, includes “therapies not supported by scientific evidence,” he says.

Arthur Grollman, a pharmacologist at the State University of New York in Stony Brook, questions the motives of the name change. “I think they do understand these names are extremely important,” he says, now that criticism of alternative medicine “is beginning to register and hurt”. He adds that integrative health  has a fuzzy definition. 

Briggs says she does not know whether the new name will eventually alleviate the criticism. “We are trying to make the very strong case that we are about research,” she says. “It has research in the name.”

NIH to require sex-reporting in preclinical studies

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The US National Institutes of Health (NIH) will require grant applicants to report the sex of animals and cells used in preclinical studies, officials said today.

The shift could help to reveal differences in the ways that diseases affect males and females. Depression, for instance, more often causes anger in males and hopelessness in females; failing to account for this type of variation can skew research results. It can also be dangerous — last January, the US Food and Drug Administration halved the recommended dose of the sleep aid Ambien for women. Although the drug has been available for 22 years, researchers only recently discovered that women who take Ambien are at increased risk of accident. 

The NIH has long recognized animal sex bias as a problem, says Janine Clayton, director of the agency’s Office of Research on Women’s Health (ORWH), who announced the agency’s new policy in a Nature commentary with NIH director Francis Collins.

A 1993 law requires that NIH-funded clinical trials include women, with few exceptions, and the numbers of participants recruited to such trials appear to have evened out over time. “If you look at NIH clinical research last year, over 50% of participants were women,” says Clayton. “It’s in the preclinical space where we haven’t seen a corresponding revolution.”

Much of this, she says, is due to a belief that the oestrus cycle affects the female animals’ physiology and throws off results; as a result, researchers tend to prefer male animals, though recent meta-analysis studies of literature have shown that this is not the case. (Some studies use female animals because they can be housed in groups, whereas male animals tend to fight unless given their own cages.)

Under the new NIH policy, which will begin to take effect in October of this year, grant applicants will have to describe how they plan to balance the sexes for cells and animals used in their studies. Clayton says that the NIH rules will not be so prescriptive as to require equal numbers of males and females, but both sexes must be represented. “This is more than a numbers game,” she says.

The NIH will monitor whether its grantees are complying with these plans “so we get pinged if there’s a problem,” says Clayton. There will be exceptions — research on reproductive organs, for example — but they will be few and far between.

In recent years, researchers have come to recognize the importance of sex differences in animal work, and many are actively including both sexes and reporting them in the methods of their papers, says Sherril Green, a comparative pathologist at Stanford University in California. She adds that pharmaceutical companies are also separating animals by sex early in the drug development process so as to avoid costly missteps such as the case with Ambien, which may have been avoided with more testing in women.

Yet the problem is bigger than just sex bias: factors such as age and genetic background can all greatly influence how an animal responds to a treatment. Brad Bolon, a veterinary pathologist at Ohio State University in Columbus, thinks the new NIH rules ignore the real problem. “By drawing so much attention to matter of sex, it avoids the whole crux of the issue,” which is too little transparency on the details of experimental design as a whole, he says.

Bolon also worries about added costs that may result from the new rules. To get enough statistical power to draw conclusions about each sex, researchers may need to double the number of animals used in the study. “Arbitrarily saying that research must be done in both sexes, especially early on, is going to take money out of testing truly novel hypotheses,” he says.

In recognition of such concerns, in 2013 the ORWH began offering funding supplements to grantees to allow them to add the appropriate number of animals to their studies. But Clayton says that this programme will probably be eliminated because investigators must now begin accounting for sex difference in their experiments from the very beginning.

Bolon says that a more direct way to persuade scientists to use both sexes in their research would be for journals to require reporting of certain variables in their methods sections. Many journals already have such guidelines, and Clayton says that NIH plans to work with journals so that sex reporting becomes the norm.

Editor’s note: a previous version of this story incorrectly referred to the “gender” of lab animals and cells rather than their “sex”.