Guidelines for US research called gain-of-function are set to be tightened

FDA Proposals for New Alternative Methods Program: How to Make Sense of New Methods, and How to Educate People about Drug Development

Drug development may be animal-free, or at least fewer animals than currently occur. Last June, the US Food and Drug Administration (FDA) set out proposals for the New Alternative Methods Program that will focus on replacing, reducing and refining the use of laboratory animals through the adoption of cutting-edge alternative methods. The aim is to produce findings that are more relevant to humans, streamline product development and reduce costs.

David Strauss is the director of the FDA’s Division of Applied Regulatory Science. Drug-development programmes around the world lead to a desire for companies to market their products in many countries.

“There’s a lot of moving pieces here,” he says. “The FDA has started the ball rolling, but we need more work to make sure we can use these new methodologies appropriately.”

Researchers are sweeping beaches and using satellites to gather data that will support a landmark anti-plastic pollution treaty. Antibiotics for sexually transmitted infections and animal-to-human transplants are included.

A health department in the United States has become one of the first to recommend that people who are at high risk of getting a sexually transmitted infection (STI) take a preventive dose of antibiotics after unprotected sex. There are clinical trials that show the strategy can reduce infections. Some researchers worry that it will contribute to antibiotic resistance. Researchers say guidelines about use are important for informing people about the safety of a strategy they might already be using. If it makes sense for them and their lifestyle, people should be able to use this tool.

Bacterial infections were associated with close to 8 million deaths in 2019, making them the second biggest killer globally after coronary heart disease. Death rates differed widely by region, from 230 deaths per 100,000 people in sub-Saharan Africa to 52 deaths per 100,000 across western Europe, North America and Australasia. The new data shows the full extent of the public health challenge posed by the infections.

Living on the Edge: How to Make Transplantation into Humans More Convenient and Possible Surgical Procedures After a Public COP27 Conference

In the wake of the 27th United Nations climate conference (COP27) in Egypt, diplomats, activists and scientists are pondering how to make such events more impactful. Some stakeholders suggest thatCOPs should focus less on targets and more on ways to incentivize drastic reductions in greenhouse-gas emissions, with rich countries leading the way.

The first trials of pig organs transplant into humans have raised expectations. In January, a man who was too ill to qualify for a human or artificial heart was granted emergency authorization to receive a pig heart. He lived for almost two months after the procedure. There have been other tests that show the transfer of genetically modified pig kidneys into legally dead people. It is possible that more clinical trials will help to make up for the thousands of people who need organ transplants. “I think we need to take that step forward and go to the clinic,” says transplant surgeon Wayne Hawthorne. But the mood is cautious. You could set the field back if there was a problem.

Source: https://www.nature.com/articles/d41586-022-04128-y

Are plastics fair? A warning warning to researchers and institutions around the world against a global plastics treaty after 75 years of campaigning in Uruguay

In March, 175 nations voted to create a legally binding international plastics treaty after nearly 30 years of warning about the problem. Negotiations start in earnest in Uruguay on 28 November. Yet the only way to ensure that a treaty — expected to be completed by the end of 2024 — is effective is to know where plastics come from, where they go and who’s responsible, every step of the way. Researchers are contributing by collecting tiny plastic particles from beaches, measuring light -reflecting off debris with satellites and dropping GPS-tagged bottles into India’s Ganges River.

Steve Woolgar wrote an influential 1979 book about laboratory life and Bruno Latour, a Gallic philosopher and anthropologist who brought a Gallic sensibility to his work. Woolgar wrote about how he wrote about profound issues with a disarming lightness. The junior researcher at the University of Oxford interrupted Bruno at a lecture to point out a logical discrepancy. Bruno paused, and exclaimed: ‘But I am French!’, to rapturous applause.” Latour was 75 years old.

In a brief, straightforward call for more equitable partnerships with collaborators, Dolors Armenteras Pascual said that he thinks there is a lot of ‘equity washing’. I mean that researchers and institutions add superficial in-name only equity efforts to their departments and nothing changes. Her suggestions for researchers were toavoid tokenism and build long-term collaborations.

Source: https://www.nature.com/articles/d41586-022-04128-y

Navigation System with Optical Frequency Multiplexing: Detection and Management of Diseases under FDA-Regulated Random Walks

A prototype navigation system overcomes obstacles. The system uses a telecommunications technique known as orthogonal frequency-division multiplexing (OFDM) to combine multiple mobile-phone signals. The transmitters are connected by optical cables to make sure they are synchronized.

The report suggests that the HHS should review the safety of research that is currently exempt from the regulations. “What got us out of the pandemic as quickly as it did was all the scientists who jumped in,” says Michael Imperiale, a microbiologist at the University of Michigan in Ann Arbor. I don’t want to see guidance going to the wrong direction because people don’t want to jump through hoops.

The report will go to the HHS when it is finished, so that they can make new policy guidelines. The HHS is “going to have to provide the ‘how’ level of details”, said NSABB chair Gerry Parker. But when that will happen is unclear.

The panel members at the meeting voted to modify the report after the acting policy chair from theNIH said a new gathering would be needed to reject the report. When or how those modifications would be made and which of the panel’s many concerns they would address were not clear.

In December of 2017, the agency lifted the moratorium after the HHS proposed a new framework for review of research involving certain pathogens. Since then, only three projects — all of which involved influenza virus research — have undergone the official review process put in place by the HHS.

That low number concerns Marc Lipsitch, an epidemiologist at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts. Most things never get to the stage of being reviewed at this stage and that’s the big loophole. Some recent research has attempted to modify a monkeypox vaccine to make it better at killing mice, as well as a study where researchers inserted the Omicron variant into an earlier strain of the virus. Neither underwent the lengthy review process by the HHS.

“Before COVID, we were thinking of [pandemics as] something in the future that may happen,” says Arturo Casadevall, a microbiologist at Johns Hopkins University in Baltimore, Maryland. The amount of damage to the world has been incredible.

Source: https://www.nature.com/articles/d41586-023-00257-0

Implications of a “Right-Beta” for Research Publication at the Strategic Planned Run II of the Advanced Research Projects Agency for Health

The new report’s recommendations include increased transparency in the review process, a role for research institutions in evaluating the risks and benefits of proposed experiments and improved regulation of NIH-funded research performed in other countries.

Although vague, Lipsitch says this is useful for scientists because they may never know where their research is going to lead. He says that they are talking about low-probability, but high-consequence events. He remains concerned, though, that the wording could also allow high-risk research to proceed without extended review, depending on how the phrase is interpreted.

Gronvall worried that “reasonably anticipated” could be interpreted so broadly that it would delay a lot of experiments, such as those involved in vaccine development during an outbreak or synthetic biology to engineerbacteria so that they produce biomaterials. “Almost all things are dual-use,” she says. “By not doing this research, we’re not making ourselves safer.”

Mark Denison, an infectious-disease expert at the University Medical Center in Nashville, Tennessee mentioned that it was difficult to determine what experiments could be risky. If identifying the function of a common protein might reveal that a mutation could make it more dangerous, for instance, would that identification constitute a risk? He said they need a better definition of gain-of-function.

A report from the GAO recommended that HHS create a clear, public standard for what “reasonably anticipated” means. The GAO said the US Centers for Disease Control and Prevention should evaluate whether the exemptions for public-health emergencies constitute a risk.

Launched one year ago by the administration of US President Joe Biden, the Advanced Research Projects Agency for Health (ARPA-H) has announced its first call for research proposals. The agency, armed with a US$ 2.5 billion budget, wants to change the way research is funded by using high-risk, high-reward projects.

ARPA-H will have an inaugural director who was picked by Biden to address these concerns. Renee Wegrzyn, a scientist and program manager for the defense Advanced Research Projects Agency, was chosen to head the agency. She said last week that the agency would have offices in three locations, one in the Washington DC area and two to be announced later this year.

Scalable Solutions and Resistive Systems: Where do we go from here? What are we going to do in the next 3+ years?

It’s a super exciting time for us. I am feeling really great about having what we like to think of as our business team in place. Now we’re bringing our technical team members [such as programme managers] on so that they can really hit the ground running. The critical mass allowed us to be open for business.

Scalable solutions is making sure that we can scale some of the therapies and diagnostics that we intend to pursue, And it is making sure that we reach the American people at scale. Many rural communities now face hospital closings because they are further away from a centre of care. How are we going to get technology and capability into people’s homes?

Proactive health is keeping people from getting sick in the first place. Think detection and diagnostics, and also behavioral and social science innovations that help people quit smoking or avoid certain things that are known to cause disease over the long term.

The final area, resilient systems, is thinking at a much broader level. What are the things that we can integrate to be more resilient against the next crisis? We haven’t seen the scale of those investments yet in other parts of government.

Source: https://www.nature.com/articles/d41586-023-00817-4

mRNA Vaccines for the Future: How will you be using an ARPA technology? Two Heilmeier Questions for the Programme Managers at ARPA

mRNA vaccines had initially been developed with research at and funding from the NIH. But DARPA was really able to drastically accelerate getting those to market and demonstrating their safety in humans [by funding vaccine makers Moderna and Pfizer]. It’s a really great example of how an ARPA might be a catalyst. It’s not meant to be the forever funder of these technologies, but that type of resourcing can really just quickly get a health advance to the public and into the hands of the people who need it most. I want to make clear, too, that under no circumstance does moving fast mean compromising on safety or efficacy — that is of utmost importance.

We won’t be a grant-based organization. These are cooperative agreements, contracts and other transactional authorities, so that ARPA-H has a seat at the table.

We are not just a copy and paste of the model. [Like DARPA,] we’re not going to have a conventional peer-review process. The programme manager is going to make the decisions. (Programme managers at ARPA-based agencies help to set priorities and see projects through from idea to implementation.) The Heilmeier questions have also been adopted by us. George Heilmeier was an early director of DARPA and he gave eight questions that the programme managers use to evaluate projects. We have adopted those, but we’ve adapted them to make them unique to us: we’ve added two more questions. In addition to cost and accessibility, One is focused on user experience, so we want to make sure that we don’t create the next device or the next diagnostic that sits on the shelf. The new question is: how will your new technology be used?

When a programme manager comes into ARPA-H, we already know a bit about their idea from their job talk. They come, and they refine that idea into a full programme with milestones and metrics that we’re going to pursue and announce to the public. The last step before they announce it to the world is to pitch it to me, in the director’s office, and to ask for a bank account. They have to answer a number of questions including, how are you going to address access and cost, are you helping patients that need it the most, and are there other services that they can offer? They don’t get a bank account if they can’t answer the questions well and have no plan for those issues.