Ram Sasisekharan’s research on complex polysaccharides has led to more than 190 publications and 50 patents.Credit: Bryce Vickmark
In May 2019, a phone call to Ram Sasisekharan from a reporter at The Wall Street Journal triggered a chain of events that stalled the bioengineer’s research, decimated his laboratory group and, he says, left him unable to help find treatments for emerging infectious diseases during a global pandemic.
The journalist had rung Sasisekharan, who works at the Massachusetts Institute of Technology (MIT) in Cambridge, for his comment on an article in the journal mAbs that had been published a few days previously1. The article alleged that Sasisekharan and his co-authors had “an intent to mislead as to the level of originality and significance of the published work”.
At the time of the article’s publication, Sasisekharan, who joined MIT’s Koch Institute for Integrative Cancer Research in 1996, was running an 18-member lab and his research on complex polysaccharides had led to more than 190 publications and 50 patents. He had also founded six companies, one of which, an antibody-discovery company, Visterra, was acquired in 2018 by Japanese pharmaceutical firm Otsuka. The authors of the mAbs article were part of the leadership team at antibody-discovery firm Adimab in Lebanon, New Hampshire.
Max Planck’s cherished autonomy questioned following criticism of misconduct investigations
At first, Sasisekharan assumed this was a storm he could weather by providing scientific evidence to refute the allegation, which related to two papers he had published with collaborators, in the Proceedings of the National Academy of Sciences (PNAS)2 and Cell Host & Microbe3. But then, MIT received a formal complaint of research misconduct against Sasisekharan, triggering an internal investigation that took more than three years and only concluded this March, when he was exonerated.
Misconduct investigations and their outcomes usually remain confidential, but because of the media interest surrounding the publication of the mAbs article1, MIT took the unusual step of disclosing its findings. In an update, research vice-president Maria Zuber wrote that the aim of the statement was to “bring closure to this matter, quell any remaining rumors or speculation, and assist in fully restoring the reputations of Professor Sasisekharan and the members of his lab”.
Sasisekharan says he was completely “blindsided” by the call from The Wall Street Journal reporter. “He asked me to comment on this preprint and I had no idea what he was talking about.”
Research rebuttal
The mAbs article focused on Zika and influenza antibodies that had been computationally designed. Because there had been so few successes in this emerging area, the papers by Sasisekharan and his team had caught the authors’ attention, and they wanted to reproduce the findings. The paper1 said: “Strikingly, in both cases the extraordinary accomplishments were not supported by a detailed description of methods or intermediate results, nor were the end-products of these efforts, namely the amino acid sequences of the designed antibodies, disclosed, making it impossible to independently reproduce the reported functional characterization.”
In a rebuttal on his lab website — published once MIT had cleared his name — Sasisekharan noted that his original articles had never claimed that the antibodies he designed were based on completely new sequences. He also said that his methods were backed up by subsequent research (see, for example, ref. 4).
Furthermore, Sasisekharan points out, the article questioning his work was published in an entirely different journal and not in PNAS or Cell Host & Microbe. This, he says, goes against scientific convention, in which disagreements are usually conducted in the same journal that published the paper being discussed.
Sasisekharan’s name was mentioned in the reference list of the mAbs paper alongside his fellow authors, but the media interest that followed was all about him. “Why was I singled out?” he asks.
Swedish research misconduct agency swamped with cases in first year
Because the MIT investigation was confidential, Sasisekharan explains, he and his colleagues were effectively gagged for nearly four years, despite the public nature of the allegations against him. “This is the other absurdity,” he says. “I had to go through this confidential process. My close faculty colleagues knew what was going on but others didn’t know, and the fact that we didn’t respond to the accusations pretty much almost implied guilt.”
“It should have been handled differently when it was so public. We should have had the opportunity to defend ourselves publicly as well,” he adds.
Although the accusation had a huge impact on him in terms of his reputation, it was even harder for his staff, he says. “A lab is like a family — you have undergraduate and graduate students, as well as postdocs. The culture of a group and how we communicate is what makes it vibrant, and it was terrible to see how the lab suffered as a consequence of these very public allegations.” He adds: “You get really isolated, you stop being invited to things. There was this dark cloud hanging over us because we just couldn’t talk about it openly or defend ourselves.”
Drawn-out process
MIT had told his lab members not to talk about the case and to continue to work as usual. However, within two years, his team had shrunk from 18 members to just 3. In a letter to the MIT leadership in April 2021, the remaining lab members described how morale was at an “all-time low” and that their faith in the institution had been “shaken” as the investigation dragged on.
“One of the researchers said to me, ‘I just can’t live like this. I need to move on.’ Why should they put their life on hold for this?” says Sasisekharan.
He gave his laptop to the investigators and carried on teaching. “That’s what kept me at MIT — the vibrancy of the students and the positive interactions I had with them,” he says.
He also did small amounts of research. For example, he analysed the structure of the Omicron variant of the coronavirus SARS-CoV-2 to see which antibodies might work against it5, but feels that had his lab been at full capacity, he could have undertaken research that would have had a much greater impact on the pandemic. “The strength and expertise of the lab was severely diminished. I helped others and gave advice but it was not the same as driving the research,” he says.
When asked if he ever thought about quitting, he said he remained positive. “I’m somebody who always looks at what I can learn from a situation. That kept me focused, rather than being down and depressed because beyond a certain point, I knew there was not a lot I could do.” However, he adds, “the pandemic certainly compounded the isolation and dark created by the investigation”.
“It’s just not how science is done. You should have dialogue and discourse, you should be able to discuss scientific differences openly,” he says.
Nature asked MIT why the investigation took so long, what support was offered to the team during and after its investigation, and whether it would be reviewing its procedures in light of the decision. A spokesperson for MIT did not respond to the specific questions, instead referring Nature to the institute’s public statement.
Trust and transparency
Sasisekharan says he is talking to MIT about potential changes to the investigation process, particularly regarding confidentiality and commercial conflicts. He says his ideas have “resonated” with MIT’s leadership, but that discussions are in the early stages.
A source close to the MIT investigation, who did not want to be identified, said the process would usually take seven to nine months, but that the complex nature of this case slowed it down.
“The process designed to deal with ‘routine’ cases of research misconduct could not recognize the commercial motivations at play. Investigating how commercial interests affected the process is warranted,” they say.
What the Stanford president’s resignation can teach lab leaders
C. K. Gunsalus, a research-integrity specialist who had no involvement with Sasisekharan’s case, says that regulations typically recommend a 120-day timescale for misconduct investigations, but that this is rarely met. She adds that many investigations do not “have much urgency or sense of priority”.
“When, as in this case, the allegations were public and the lab is at a standstill, this lapse of time is very hard to understand and to find reasonable,” says Gunsalus, who is based at the University of Illinois Urbana-Champaign.
She also says that institutions need to be more transparent. “We live in a time when trust in institutions is at an all-time low. Saying ‘we’ve got this, trust us’ is simply not a sustainable situation.”
One of the problems for Sasisekharan was that there was no set procedure for dealing with non-routine cases, he says. “As one of my colleagues said, we have processes to deal with students who cheat in exams, but nothing for this,” he adds.
Bioengineer Tillman Gerngross at Dartmouth College in Hanover, New Hampshire, who co-authored the mAbs paper1, says he and his co-authors stand by their article, adding: “I strongly encourage you to carefully read the original paper published in mAbs.”
Commercial conflicts
Morteza Mahmoudi, a specialist in nanomedicine at Michigan State University in East Lansing, who also campaigns against academic bullying, says that when academia and commerce collide, the fall out is rarely positive.
“It’s good that academics have a role in industry, but when money gets involved, there are conflicts. In the past few years, we have been seeing a new pattern of unethical behaviours, where an academic with industrial conflicts gets accused of violating academic ethics and the accusation gets widely distributed by major news outlets,” he adds.
Even if an academic is later cleared, it is often hard for the person to rebuild their reputation, he notes. He thinks that those making the allegations should also be held accountable, to prevent abuse of reporting systems.
More than 30 scientists have signed an open letter calling for the mAbs article to be retracted in light of the MIT review decision. Janice Reichert, editor-in-chief of mAbs, told Nature she was unable to comment on the letter.
Sasisekharan says he is now mulling how to move forward, with MIT helping him to rebuild the lab. His former colleagues are settled elsewhere, but interest has started to grow: students have begun to contact him again and he can see the old magic building.
“In the past, students sought out our lab and getting a spot was competitive,” he says.
But, he notes, the rebuilding is “not going to happen overnight. It’s going to take months, as we will have to see what excites us and what problems we could work on,” he says.
He is also hoping to find a way to support people who are facing misconduct allegations. “I shudder to think how someone who was not as senior as me could weather a similar situation,” he says. “While I fully understand how difficult and isolating it is, it’s important to focus on the positive. The whole process just needs to be more open.”