What does science get us? That’s always the question from those who fund it, but not from those who do it. This tension is in full swing in the US right now, as the Trump administration takes a hacksaw to the scientific ecosystem. But it isn’t new.

In 1969, as Robert Wilson was testifying before the US Congress to get funding for a new particle collider at Fermilab, he spoke on the topic. The senators were grilling him on how this scientific endeavour would contribute to national defence or help compete with Russia during the cold war. He answered: “It has nothing to do with the military… it has to do with: Are we good painters, good sculptors, great poets?… It has nothing to do directly with defending our country except to help make it worth defending.”

The utilitarian view always misses that so many of the biggest and most important discoveries come from the unobstructed pursuit of knowledge. And the line from discovery to application to return on investment is rarely a straight one. Without Albert Einstein musing in the early 20th century on the weightlessness felt by a person in freefall inside an elevator, we wouldn’t have his theories of relativity and we wouldn’t have GPS – a technology that has revolutionised life around the world.

Many of the biggest discoveries come from the unobstructed pursuit of knowledge

It is impossible to predict what purely scientific inquiry will lead to, which is why the destruction being done to science in the US is so short-sighted. But it is much easier to foretell what damage slashed funding will cause. Losing programmes to treat and prevent tuberculosis, malaria and AIDS will lead to preventable disease and death. Cuts at NASA, including vital climate studies on extreme heat and air pollution, will be felt for decades if not longer (see “Are Trump’s cuts to science the end of the endless frontier?”).

After physicist J. J. Thomson discovered the electron in 1897, he famously said it was useful for nothing. What followed was the electric age, a century of unimaginable global progress built on this humble particle. What revolutionary age to come is being impeded now?

An eight-year-long investigation into the reliability of preclinical cancer biology research has found that fewer than half of the results published in 23 highly cited papers could be successfully reproduced.

, director of research at the  in Virginia – which conducted the investigation – says the original plan was to reproduce 193 experiments from 53 papers. But, as explained in one of two studies the team publishes today, this was reduced to 50 experiments from 23 papers.

“Just trying to understand what was done and reported in the papers in order to do it again was really hard. We couldn’t get access to the information,” he says.

In total, the 50 experiments included 112 potentially replicable binary “success or failure” outcomes. However, as detailed in the second study published today, Errington and his colleagues could replicate the effects of only 51 of these – or 46 per cent.

The experiments were all in-vitro or animal-based preclinical cancer biology studies, and didn’t include genomic or proteomic experiments. They were from papers published between 2010 and 2012 and were .

The results are “a bit eye-opening”, says Errington.

The investigation’s findings do, however, align with those of earlier reports published by the big pharmaceutical companies Bayer and Amgen. , who recently co-founded US biotech Parthenon Therapeutics, was a senior cancer biologist at Amgen and an .

“We looked back at the papers that we had relied upon at Amgen and found that we could only reproduce 11 per cent of the studies,” says Begley.

The Amgen report was applauded by some in the research community for shining a light on an important problem. But Begley says the report was also criticised for a lack of openness about exactly which studies it tried and failed to replicate.

This criticism can’t be levelled at the new investigation. Errington and his colleagues have published all the data about the studies they included on the , a website and data repository run by the Center for Open Science, to help facilitate data sharing. They also invited peer review of their methods for replication before the study was completed.

Although the investigation focused on preclinical studies, the replicability problems it uncovered might help explain problems with later-stage studies in people too. For instance, a showed that less than 30 per cent of phase II and less than 50 per cent of phase III cancer drug trials succeed.

Even if there isn’t a direct link between the problems at the preclinical and clinical trial stages of scientific investigation, Errington says the high rate of failure of later clinical trials in this area is very concerning.

“At that point, you’ve already invested in the very expensive clinical trial pipeline,” he says. “This is people’s lives, hopes and livelihood on the line here.”

He adds that the Center for Open Science is now advocating for a scientific culture change that places more focus on data sharing and good quality early-stage studies, which could help highlight any issues with replicability employed in this sort of research.

at the University of Edinburgh, UK, agrees this is important, but says more needs to be done to persuade scientists to get on board. “It requires institutions and their appointment panels and promotion panels to value the fact that you have done this, but the incentive structure just isn’t there at the moment,” she says.

There are promising signs of change on the horizon. The US National Institutes of Health, one of the largest funders of health-related research, is instituting a new policy in early 2023 that will make data sharing the default for the projects it funds. Several journals have also changed their publishing systems in recent years to encourage open science and data sharing.

Begley says he has seen a real change in the decade since he co-authored the Amgen report. “When I first started talking about this issue, people would get very angry and say, ‘Well, this just proves that Amgen scientists are incompetent’,” he says. “Now, when I give a talk, the focus is on what should we be doing about this.”

Journal references: eLife, �����Ի�

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