MIT Technology Review

Recent highly publicized scandals have gotten the physics community worried about its reputation—and its future. Over the last five years, several claims of major breakthroughs in quantum computing and superconducting research, published in prestigious journals, have disintegrated as other researchers found they could not reproduce the blockbuster results. 

Last week, around 50 physicists, scientific journal editors, and emissaries from the National Science Foundation gathered at the University of Pittsburgh to discuss the best way forward."To be honest, we've let it go a little too long," says physicist Sergey Frolov of the University of Pittsburgh, one of the conference organizers. 

The attendees gathered in the wake of retractions from two prominent research teams. One team, led by physicist Ranga Dias of the University of Rochester, claimed that it had invented the world's first room temperature superconductor in a 2023 paper in Nature. After independent researchers reviewed the work, a subsequent investigation from Dias's university found that he had fabricated and falsified his data. Nature retracted the paper in November 2023. Last year, Physical Review Letters retracted a 2021 publication on unusual properties in manganese sulfide that Dias co-authored. 

The other high-profile research team consisted of researchers affiliated with Microsoft working to build a quantum computer. In 2021, Nature retracted the team's 2018 paper that claimed the creation of a pattern of electrons known as a Majorana particle, a long-sought breakthrough in quantum computing. Independent investigations of that research found that the researchers had cherry-picked their data, thus invalidating their findings. Another less-publicized research team pursuing Majorana particles fell to a similar fate, with Science retracting a 2017 article claiming indirect evidence of the particles in 2022.

In today's scientific enterprise, scientists perform research and submit the work to editors. The editors assign anonymous referees to review the work, and if the paper passes review, the work becomes part of the accepted scientific record. When researchers do publish bad results, it's not clear who should be held accountable—the referees who approved the work for publication, the journal editors who published it, or the researchers themselves. "Right now everyone's kind of throwing the hot potato around," says materials scientist Rachel Kurchin of Carnegie Mellon University, who attended the Pittsburgh meeting.

Much of the three-day meeting, named the International Conference on Reproducibility in Condensed Matter Physics (a field that encompasses research into various states of matter and why they exhibit certain properties), focused on the basic scientific principle that an experiment and its analysis must yield the same results when repeated. "If you think of research as a product that is paid for by the taxpayer, then reproducibility is the quality assurance department," Frolov told MIT Technology Review. Reproducibility offers scientists a check on their work, and without it, researchers might waste time and money on fruitless projects based on unreliable prior results, he says. 

In addition to presentations and panel discussions, there was a workshop during which participants split into groups and drafted ideas for guidelines that researchers, journals, and funding agencies could follow to prioritize reproducibility in science. The tone of the proceedings stayed civil and even lighthearted at times. Physicist Vincent Mourik of Forschungszentrum Jülich, a German research institution, showed a photo of a toddler eating spaghetti to illustrate his experience investigating another team's now-retracted experiment. ​​Occasionally the discussion almost sounded like a couples counseling session, with NSF program director Tomasz Durakiewicz asking a panel of journal editors and a researcher to reflect on their "intimate bond based on trust."

But researchers did not shy from directly criticizing Nature, Science, and the Physical Review family of journals, all of which sent editors to attend the conference. During a panel, physicist Henry Legg of the University of Basel in Switzerland called out the journal Physical Review B for publishing a paper on a quantum computing device by Microsoft researchers that, for intellectual-property reasons, omitted information required for reproducibility. "It does seem like a step backwards," Legg said. (Sitting in the audience, Physical Review B editor Victor Vakaryuk said that the paper's authors had agreed to release "the remaining device parameters" by the end of the year.) 

Journals also tend to "focus on story," said Legg, which can lead editors to be biased toward experimental results that match theoretical predictions. Jessica Thomas, the executive editor of the American Physical Society, which publishes the Physical Review journals, pushed back on Legg's assertion. "I don't think that when editors read papers, they're thinking about a press release or [telling] an amazing story," Thomas told MIT Technology Review. "I think they're looking for really good science." Describing science through narrative is a necessary part of communication, she says. "We feel a responsibility that science serves humanity, and if humanity can't understand what's in our journals, then we have a problem." 

Frolov, whose independent review with Mourik of the Microsoft work spurred its retraction, said he and Mourik have had to repeatedly e-mail the Microsoft researchers and other involved parties to insist on data. "You have to learn how to be an asshole," he told MIT Technology Review. "It shouldn't be this hard." 

At the meeting, editors pointed out that mistakes, misconduct, and retractions have always been a part of science in practice. "I don't think that things are worse now than they have been in the past," says Karl Ziemelis, an editor at Nature.

Ziemelis also emphasized that "retractions are not always bad." While some retractions occur because of research misconduct, "some retractions are of a much more innocent variety—the authors having made or being informed of an honest mistake, and upon reflection, feel they can no longer stand behind the claims of the paper," he said while speaking on a panel. Indeed, physicist James Hamlin of the University of Florida, one of the presenters and an independent reviewer of Dias's work, discussed how he had willingly retracted a 2009 experiment published in Physical Review Letters in 2021 after another researcher's skepticism prompted him to reanalyze the data. 

What's new is that "the ease of sharing data has enabled scrutiny to a larger extent than existed before," says Jelena Stajic, an editor at Science. Journals and researchers need a "more standardized approach to how papers should be written and what needs to be shared in peer review and publication," she says.

Focusing on the scandals "can be distracting" from systemic problems in reproducibility, says attendee Frank Marsiglio, a physicist at the University of Alberta in Canada. Researchers aren't required to make unprocessed data readily available for outside scrutiny. When Marsiglio has revisited his own published work from a few years ago, sometimes he's had trouble recalling how his former self drew those conclusions because he didn't leave enough documentation. "How is somebody who didn't write the paper going to be able to understand it?" he says.

Problems can arise when researchers get too excited about their own ideas. "What gets the most attention are cases of fraud or data manipulation, like someone copying and pasting data or editing it by hand," says conference organizer Brian Skinner, a physicist at Ohio State University. "But I think the much more subtle issue is there are cool ideas that the community wants to confirm, and then we find ways to confirm those things."

But some researchers may publish bad data for a more straightforward reason. The academic culture, popularly described as "publish or perish," creates an intense pressure on researchers to deliver results. "It's not a mystery or pathology why somebody who's under pressure in their work might misstate things to their supervisor," said Eugenie Reich, a lawyer who represents scientific whistleblowers, during her talk.

Notably, the conference lacked perspectives from researchers based outside the US, Canada, and Europe, and from researchers at companies. In recent years, academics have flocked to companies such as Google, Microsoft, and smaller startups to do quantum computing research, and they have published their work in Nature, Science, and the Physical Review journals. Frolov says he reached out to researchers from a couple of companies, but "that didn't work out just because of timing," he says. He aims to include researchers from that arena in future conversations.

After discussing the problems in the field, conference participants proposed feasible solutions for sharing data to improve reproducibility. They discussed how to persuade the community to view data sharing positively, rather than seeing the demand for it as a sign of distrust. They also brought up the practical challenges of asking graduate students to do even more work by preparing their data for outside scrutiny when it may already take them over five years to complete their degree. Meeting participants aim to publicly release a paper with their suggestions. "I think trust in science will ultimately go up if we establish a robust culture of shareable, reproducible, replicable results," says Frolov. 

Sophia Chen is a science writer based in Columbus, Ohio. She has written for the society that publishes the Physical Review journals, and for the news section of Nature. 

Fulgent Announces Second Drug In Development And New Prenatal Genetic Test

El Monte-based genetic testing and clinical lab analysis company Fulgent Genetics Inc., which rode the Covid testing wave to nearly $1 billion a year status, is moving ahead with its post-Covid strategy.

Fulgent announced in its recent quarterly earnings report that it had introduced a new genetic prenatal test and is laying the groundwork for clinical trials of its second drug candidate. These initiatives are the direct outgrowth of the sudden huge cash infusion brought about by the company's massive Covid testing contracts during the pandemic.

Then, last week, Fulgent announced a cancer drug development collaboration with the Moffitt Cancer Center in Tampa, Florida.

The prenatal test, called Knova, aims to greatly expand the genetic conditions and diseases that can be screened for through a single maternal blood sample. Fulgent began gradually rolling the test out this month as part of its laboratory diagnostics business.

The new drug candidate is a more powerful version of an existing chemotherapy drug used to treat tumors for several types of cancers. The hope is the increased potency can enable lower doses of the drug and reduce harmful side effects.

"We have a strong strategy with both laboratory service business and the therapeutic development business," Fulgent founder and chief executive Ming Hsieh told analysts on the company's earnings call.

The Knova prenatal test, which is to be administered by OB-GYN practitioners, marks the company's first move into this market. And Fulgent is thinking big.

"Historically, a blood draw during pregnancy is used to look for a small number of diseases and conditions, such as Down syndrome," said Brandon Perthuis, Fulgent's chief commercial officer. "It's all very limited. Our test allows from the same blood test to screen for dozens of other diseases and conditions that are not currently screened for."

These include Rett syndrome (a neurodevelopmental disorder that affects body motion, breathing, brain functions); Sotos syndrome (involving excessive physical body growth); and Tuberous syndrome (high rate of tumor formation in the brain and other organs).

Perthuis said the common feature of all of these diseases is that they originate in a single genetic "point mutation" that the Knova test can pinpoint.

"It represents a 60% improvement in detecting severe genetic conditions," he said.

Because of the advanced lab analysis the Knova test involves, it works through Fulgent's own clinical lab system only. It's not a generic test kit that can be taken to any lab.

As such, Perthuis said it takes some effort to convince OB-GYN practitioners to add this test to their prenatal test regimens. That's why he said the rollout of the test is gradual.

Ultimately, he said, the goal is much loftier: persuading OB-GYN practitioners to use Fulgent as the "one-stop shop" for all prenatal testing.

One analyst participating in the earnings call agreed with Fulgent's gradual approach.

"We think the team is taking reasonable actions to drive growth, and a paced entry into the OB-GYN setting with the newly disclosed Knova NIPT opens an additional door," Andrew Cooper, an analyst with St. Petersburg, Florida-based Raymond James and Associates, wrote in a research note.

More-potent chemotherapy drug

On the drug development front, Fulgent announced a second drug based on its nanoencapsulating technology that uses a microscopic coating to enhance the effectiveness of existing chemotherapy drugs.

The first drug enhanced in this way is paclitaxel, a chemotherapy drug brought to market originally by New York-based Bristol Myers Squibb Co. To treat a range of solid-tumor cancers. Fulgent's version of this drug is more potent and therefore can be administered in lower doses, reducing toxic side effects; it is now beginning Phase 2 clinical trials.

The second drug involves the chemotherapy drug irenotecan, brought to market by New York-based Pfizer and used to treat colorectal and other cancers. Fulgent actually applied its nanoencapsulating technology to the root drug behind irenotecan. With that enhancement of the root drug, Fulgent's version was made more potent than irenotecan.

According to Fulgent's May 3 announcement, the company intends to submit by the end of this year an application to the Food and Drug Administration for "investigational new drug" designation for its more powerful version of irinotecan that would then make it eligible to start clinical trials.

"It's more effective in fighting the tumor – at least 100 times more potent than the version that's on the market," Perthuis said.

Partnership with Moffitt Center

The deal involving the Moffitt Cancer Center is actually with Fulgent's subsidiary, Fulgent Pharma, the drug-development arm of Fulgent.

The Moffitt Center is one of 57 National Cancer Institute-designated comprehensive cancer centers.

The aim of the partnership is to speed up the development of personalized cancer therapies, using Fulgent nanoencapsulation and genetics expertise and Moffitt's clinical research experience.

Financial terms of the partnership were not disclosed, including the nature of any revenue-sharing arrangements, if any.

Under the partnership, the Moffitt Cancer Center will provide Fulgent with priority access to its clinical expertise and resources, with the aim of expediting the advancement of Fulgent's clinical pipeline. This includes prioritized clinical-trial activation, enhanced patient screening, and data sharing designed to get investigational therapies to patients in need more quickly and efficiently.

Additionally, the partnership will focus on co-developing next-generation personalized treatment options for cancer.

"Pooling our unique strengths, Moffitt and Fulgent will strive to create new precision oncology therapies customized to meet the specific needs of each patient, thereby improving future outcomes," Ray Yin, Fulgent Pharma's president and chief science officer, said in the announcement.

Substantial cash cushion

Both the new genetic test and the second drug development effort have been enabled by Fulgent's Covid testing bonanza. In 2019, prior to the pandemic, Fulgent was a small but growing genetic testing company that posted $33 million in revenue. Then, during the first summer of the Covid pandemic, Fulgent used its genetic testing capability to win huge government Covid testing contracts, including with the Los Angeles County Department of Health Services and the New York City public school system.

Fulgent initially had to scramble to boost its lab facilities – including opening a huge new lab in Houston. But by 2021, Fulgent's annual revenue had soared to $993 million, almost 30 times the 2019 total.

While the Covid testing revenue faded nearly as quickly as it arrived, Fulgent was able to bank enough of that revenue to emerge a much bigger and cash-rich company than before the pandemic.

"Covid-19 stress-tested our laboratories and our platform," Perthuis said. "We proved that this business is scalable and our technology is scalable. We went from zero Covid tests per day to 100,000 tests per day in less than a year's time."

Fulgent used some of this revenue to build up its non-Covid testing lines and to expand its small drug-development capabilities. So last year, while overall revenue of $289 million was less than one-third the 2021 peak, nearly 90% of that revenue was non-Covid related. Perthuis pointed out that this so-called "core revenue" of $262 million was still eight times the level of 2019.

What's more, Fulgent banked hundreds of millions of dollars in Covid-testing revenue for future growth and acquisitions. As of the end of the first quarter, Perthuis said the company had roughly $800 million in cash with virtually no debt.

"That can be deployed internally or towards additional mergers and acquisitions," he said.