The New Alternative Methods Program and the Challenge of Replacing, Reducing and Refining Laboratory Animals: Status and Perspectives in the United States
The future of drug development might be animal-free — or, at least, involve far fewer animals than is currently the norm. The New Alternative Methods Program will focus on replacing, reducing and refining the use of laboratory animals through the adoption of cutting-edge alternative methods. The goal is to produce findings that are relevant to humans, and to simplify product development.
The FDA’s Division of Applied Regulatory Science has a director who says it’s important to bring about change among the regulatory agencies. Drug-development programmes are global and companies want to sell products in many countries around the world.
A lot of pieces are moving here. The FDA has started the process but we need more time to make sure we can use the new methodologies correctly.
Allocating the funds through the annual appropriations process that is still in progress could become harder if Republicans gain control of the House, says Deborah Altenburg, who serves as associate vice-president for research policy and government affairs at the Association of Public and Land-Grant Universities in Washington DC. “We have to really push to get the science portion of the CHIPS and Science Act funded.”
Historically, it’s not unusual for the party that holds the White House to lose seats during the mid-term elections, two years after a president takes office. The country is dealing with a growing inflation and energy crisis worsened by the war in Ukraine as the stakes are especially high. There is a fear that democracy is at risk, as Donald Trump and many of the other candidates he endorsed continue to question the results of the 2020 election that put Biden in office. The Republicans are threatening to impeach Biden if they take power.
The White House Office of Science and Technology Policy, headed by Jane Lubchenco, is the subject of an investigative probe by House Republicans. She was sanctioned by the US National Academy of Sciences for violating scientificintegrity rules when she edited a paper authored by a family member. Observers who spoke to Nature say that this could be just the beginning if Republicans take charge.
One US agency that could be particularly hard hit is the historically bipartisan National Institutes of Health (NIH), says Allen Segal, who is the chief advocacy officer of the American Society for Microbiology in Washington DC. House Republicans have already signalled that they plan to investigate the NIH’s supervision of the Wuhan Institute of Virology in China, to which the biomedical agency had given funds before the pandemic for the study of coronaviruses. Some congressional Republicans have consistently speculated that the SARS-CoV-2 coronavirus might have been released by the virology lab, and they are sceptical that the NIH properly vetted and monitored any risky research that the lab was carrying out. Many biologists don’t agree with the theory because there is no direct evidence.
This could be a challenge for the CHIPS and Science Act, which authorized US$280 billion for science and technology programmes across multiple federal agencies, including what would be a historic boost in funds for the NSF. Republicans in the House urged opposition to the legislation that was passed in July.
Early this year, the Biden administration formally closed a Department of Justice programme known as the China Initiative, which launched in 2018 under the Trump administration to counter efforts by the Chinese government to steal secrets from US businesses and laboratories. On the other side of the political aisle, there are concerns about research security and the justice department discontinued the programme because they felt that the initiative discriminated against Chinese heritage scientists.
Some Republicans are looking to bring back the programme. If both chambers of Congress become Republican-controlled, such legislation could gain momentum — but it would be hard to fully bring back the initiative as long as Biden is in charge, observers say.
New space for bipartisanship has been created by the concerns about Chinese espionage, national security and economic competitiveness. 24 House Republicans supported the CHIPS and Science Act, which they claimed could reduce reliance on China by fostering the domestic production of Semiconductors.
Climate and energy are related to political forces. Although Republicans have steadfastly opposed legislation to curb greenhouse-gas emissions, many supported major investments in clean energy sought by the Biden administration and Democrats. The passage of two major bills over the past year has resulted in more than half a trillion dollars in clean-energy investments locked in.
David Hart tracks energy issues for the Information Technology and Innovation Foundation in Washington DC and he says that there is a strong front against both China and Russia. That was a strong unifying factor in this last Congress, Hart says, and is likely to continue in the next one, regardless of how the election plays out.
Making Peer Review Easy: The National Institute of Health’s proposal to cut Bias and Enhance Access to Research Expertise and Institutional Resources
The US National Institute of Health released a plan to change how it scores its research grant applications to reduce bias and to make it easier for reviewers. Under the new system, reviewers would no longer rate researchers’ access to resources or expertise, and there would be fewer scoring criteria.
In addition to considering the race and gender of reviewers, ensuring that panels have representation from under-represented institutions could have a big impact, says Enrique Neblett, a public-health researcher at the University of Michigan. He says that the National Institute of Health needs to take bolder action given the persistence of funding disparity.
Researchers who spoke to Nature say that changes to the peer-review system are long overdue, and that the proposals are a good start. Some think that the revisions aren’t enough to correct the problems.
The last category, which won’t be scored under the proposal, is frequently misinterpreted. Reviewers can score applicants and their institutions without considering them in the context of any research that might be done. This has led to higher scores for prestigious institutions and individuals. Under the proposal, reviewers would be able to choose whether or not the research expertise or institutional resources are adequate or not. They can give feedback in a text box on the review form if they choose the latter. It will stop reviewers from waxing poetic about a really famous investigator that tilts the evaluation of the science.
“For a big funder like NIH, these changes are quite bold,” says Sandra Bendiscioli, a research policy specialist at the European life-sciences organization EMBO in Heidelberg, Germany, who has published about bias in peer review.
Some advisers attending the 8 December meeting pushed back on the plan, suggesting that researchers and institutional resources are crucial factors in determining the merit of research projects. “I do think there’s some value in some objective score to assess the investigator,” said Shelley Berger, an epigeneticist at the University of Pennsylvania in Philadelphia. Without a score, Berger added, it could be difficult to understand the reviewer’s thinking and how they factored researcher expertise into their decision. Speaking at the meeting, Byrnes countered that reviewers would still have the option to leave comments about their concerns, which could be reflected in the overall impact score.
The CSR is accepting public feedback about the revisions until 10 March 2023. It will also release proposed changes to the criteria for scoring clinical-trial and training grants in the coming months.
In e-mail responses to questions from Nature Index, the NIH and NSF say they are drawing up plans for new processes in light of the GAO report. The June 2022, letter that lists the agency’s responses to the recommendations can be found in the report.
According to the report, the agencies “do not collect indicators of rigorous study design and transparency of research results such as study sample size, adherence to research plans, or the extent to which research data are findable, accessible, and usable”. This means they don’t have enough information to improve how grants are awarded or to prioritize funding areas.
Marcus Munaf believes that transparency and open research is a key component to driving quality. He leads the UK Reproducibility Network, a consortium that aims to investigate the factors that contribute to robust research. It also provides training and disseminates best practice in this area. “Funder mandates go some way to achieving this, but they need to be enforced to really drive change,” he says.
Wright wrote a report for the GAO saying peer review isn’t enough to weed out irreplicable science. She says the GAO will be engaging NASA about the benefits of the report’s recommendations.
The GAO plans to check in with the agencies at least once a year to assess progress, Wright says, and will give the funders up to four years to roll out any changes in full. The GAO will also keep an eye on related legislation being passed by the US Congress; for now, it will examine only whether the legislation is in line with the report’s recommendations.