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From the LabLit short story series

João Ramalho-Santos 6 March 2015

Good science has a knack of seeming absolutely logical after the fact

Editor's note: Is your beaker half-full or half-empty? We are pleased to present a story by our regular contributor João Ramalho-Santos which exists in a state of quantum uncertainty. If you're a half-full kind of reader, choose the story below. If you're more of a half-empty kind of person, use the episode navigation links on the top right and select 'next' to read an alternative version of the same story. Which one is more likely? You decide!

As his group filed in slowly into the meeting room Jonas noticed a mixture of downtrodden and triumphant expressions. Identifying which of his collaborators sported which look immediately told him everything he was about to hear.

“It works!” Tiago beamed.

“Right,” Beth confirmed, despondent.

“The hypothesis seems to be supported by the data,” Yuki added, shrugging.

Well, at least it was unanimous. And Jonas knew exactly what would need to happen next.

Ten years ago he had left the relatively anonymous world of Planaria and Hydra in order to explore organ regeneration in organisms people (and funding agencies) actually cared about. Meaning mammals. As many of his colleagues anticipated it had gone spectacularly wrong at first. No grip on systems and techniques, little understanding of controls, contaminations galore in what were much more unforgiving settings, costs ballooning through the roof.

Then Maria came along. Having graduated from an excellent lab, but under the mentorship of a PI who had basically invented the field and micromanaged every experiment, the relative cluelessness of Jonas’ group (“experimental freedom”, she politely called it) made for an ideal setting to fully express her whirlwind dynamo persona as a postdoc. And express it she certainly had, whipping the lab techs into shape, providing all sorts of important practical tidbits, and offering pointed input (wanted or not) to all projects. Assays started to work, collaborations materialized, good papers were put together; suddenly Jonas’ midlife scientific crisis didn’t seem quite so crazy after all. By the time Maria left for a prestigious independent position the group was humming along, Beth, Tiago and Yuki well equipped to carry on.

The timing had been perfect; Maria was ready and, above all for Jonas, the same could be said for the others. Having arrived shortly before Maria, Beth was clearly unhinged by her success, would now have room to prove herself without constant suggestions and critical comments even Jonas felt were sometimes condescending. The same for Tiago, as soon as he let go of the orphaned puppy look, and stopped going reflexively by Maria’s now empty desk to ask for help on anything and everything. The hiring of quiet and deadly serious efficiency in human form that was Yuki had also proven a stroke of minor genius in terms of a change in pace.

They had all known what Maria’s master plan would be. It was no secret that, despite an excellent CV, she was miffed that the really Top Journals kept refusing her papers, especially because she had come so agonizingly close. When The Paper finally came out of her brand-new group no one was surprised, although Beth (and Jonas, though he would never admit to it) felt that that the work must have been at least initiated during her postdoc, and they might therefore have been cheated out of at least some partial credit on what seemed, as is the case with many great papers, a logical and clear result that many others should have been able to predict and prove. But hadn’t. Good science has a knack of seeming absolutely logical after the fact.

Actually, The Paper didn’t really reveal a groundbreaking effect; the basic starting and ending points were well known, and even Jonas’ lab had dabbled with them previously (before Maria suggested dropping it). What it described was rather an extraordinary increase in efficiency and yield that made all previous papers on the topic look like they were talking about rare epiphenomena. Maria’s paper meant industry people would take serious notice, that real applications might be developed much faster than originally anticipated by even the more optimistic in the field.

Well, Jonas thought philosophically, at least this showed the merit of his lab as a nurturer of talent. Besides, there were always other experiments he could do. He filed The Paper away, emailed sincere congratulations to Maria, and forgot about it.

Until the phone calls came in.

If Jonas were totally honest he’d have admitted to following the controversy as soon as it started. But it felt more proper, and even useful, having what was going on explained to him from the vantage point opposing the views raging through the electronic scientific communities he had browsed. These communities had concluded, with distinct degrees of certainty and levels of colorfully insulting language (correlated with levels of user anonymity), that The Paper did not stand up to close scrutiny, and was probably not valid, if not something much worse.

It was hardly surprising that many others had tried to repeat Maria’s results; increased efficiency was the whole point of The Paper. It was also not surprising that many of those researchers had written the original papers, and might have been miffed at being upstaged. And, finally, could Maria and the Journal Editors who contacted Jonas really be surprised at the detailed reactions posted online (and apparently sent to The Journal), if indeed none of those aforementioned researchers had actually managed to repeat the key findings?

Apparently yes. Both Maria and The Journal were taking it very personally, as discoverer and gatekeeper, respectively. The Paper had been vetted using the highest standards, and authors and publishers stood adamantly behind it, despite the jealous noise, as Maria put it. So much so that they were willing to have an independent lab replicate the findings and publish a detailed step-by-step protocol. Except this could not be any lab. Maria had steadfastly refused the many requests for reagents and protocols she had been flooded with, was not keen on having her precious cell lines, transgenic mice and drug cocktails “ransacked” by competitors – the openness of science be damned, they would have done they same to her if the roles were reversed.

And that, of course, is where Jonas came in.

Competent, independent, trustworthy, not a direct competitor. The ideal lab for a semi-sponsored validation, with Maria and the Journal’s blessing. There was the small matter of his also being Maria’s former lab, the Publisher's representative told Jonas in confidence, but he was reputable and completely outside the controversy, could not be seen as having much of an agenda, either way. Jonas would never be, although this was not explicitly stated, good enough for The Journal on his own; following Maria’s recipe was his shot at getting at least an online communication. Jonas couldn’t help but marvel at how much The Journal was praying for a repeat, but that was, he knew – besides the nature of the publishing business – the impression Maria made on most people. What The Publisher did not realize was that there was another reason Maria had suggested Jonas: she knew very well they had some expertise on the topic, but had “given up on it”, as she unabashedly put it.

Well, Jonas thought, at the very least it would be intriguing, perhaps even entertaining. And being a sort of understudy in an important play for once was better than a lifetime made solely of Off-Broadway efforts. Before saying yes he just wanted to ask his lab. Oh, and politely request that Maria not be involved at any stage of the experiments, besides providing detailed instructions. That was non-negotiable and would lead, Jonas knew, to many irate emails, tense phone calls and general unpleasantness from his former star pupil. But hey, it was still his lab, his shot; this time Maria was really just a mere pretext.

Of course his lab agreed; everyone had been actively following the controversy and were excited to be part of something that was potentially paradigm-shifting (or career crippling to someone else). In fact the project provided a rush, a frenzy; the lab cranked out experiments like never before. Probably similar to what drugs, alcohol, casual sex or organized sports did, Jonas (forever ignorant on any of these topics) thought. The reagents came in, the tasks were divided, Maria briefed everyone in detail before politely being asked to leave, just as she was about to unleash her micromanaging will. After that Jonas ran the show, Beth, Yuki and Tiago reporting directly to him.

And, following months of utter madness, it all came down to this meeting, three piles of data saying the exact same thing.

The Paper was right.

Beth and Tiago had identified minor issues, small mistakes in primers and a few bad antibodies that made some figures look “worse” than they should have, and might have fooled other researchers. But Yuki’s data uncovered the real issue: Maria’s cells had somehow changed in culture, and were primed to switch states faster than any other cell types they (and other researchers) had tested. It was as if Maria had been teaching a smart dog variations of a trick it already knew, while everybody else was working with clueless mutts. Jonas sat patiently through the obvious comments that followed: from Tiago, who was ecstatic about Maria’s complete exoneration, and from Beth, who scathingly noted that The Paper was useless if the high efficiency was valid only for very specific (and weird) cells. They were both right, but it was also tiring. Jonas thought about reminding Beth that she had been the most enthusiastic about being on the project (sensing a possible paper in The Journal), but thought better of it. He had to keep them in line, at least until they had everything organized.

Because all three would share authorship on a very carefully worded manuscript that would say that what was described in The Paper was mostly true, but that results described there depended on very specific conditions and were probably not as extraordinary as those initially presented, through no conscious fault of the authors. Eagerness perhaps, carelessness at the most. But if a way could be found to change other cells to behave like Maria’s, we could be cooking with gas; and that effort might certainly warrant another Paper. Jonas would put his best language skills on display, and was sure Reviewers and The Journal would edit the text to suppress any hint that anything but an honest, but somehow interesting, oddball effect had happened. Of course, when “translated” into practical terms, all this meant that The Paper currently could not be extrapolated to all cell types, and most people who read Jonas’ findings (and all of the people who “mattered”) would know. Thus saving face for the Journal, the Reviewers, Maria, her co-authors, and whoever else. Maria would be allowed to keep her position and grants and likely succeed in the long term with both, when one came up for tenure and the others for renewal.

But that, Jonas was sure she knew, was not going to be as easy as if The Paper had been as right as it was supposed to be; The System does not appreciate hiccups. Then again, Maria was the kind of scientist who could earnestly discuss these novel findings as if they were already part of the original Paper, just missed by careless peers. And she’d also note that this self-correcting nature was actually what made Science a great and worthy endeavor, which was, Jonas knew, actually a good point. In short, she’d be fine. After some blogger frenzy, either people would succeed in making all cells similar to Maria’s and produce a better version of The Paper, or they wouldn’t. Regardless, The Paper would ultimately fade into oblivion or the purgatory of citations left out for space reasons (even more likely, another one with similar issues would come up to distract vitriolic bloggers), and Jonas privately thanked for sort of saving the day, thus giving him more exposure and allowing Tiago, Beth and Yuki a good platform for new jobs. Which was great.

As soon as those three had secured new positions Jonas was going back to studying Hydra, Planaria, at the most zebrafish or axolotl, critters that did not grow hair or feel the need for warm blood and teat sucking (literally, or figuratively). And that would not lead to these tense and ultimately pointless discussions with The Journals. He would cut lab costs by 80%, and try to scrape by on minimal settings and a skeleton crew (undergraduates and the budget for lab classes, if it came to that) even if he had to use critters that had no skeleton to do it. There were always interesting and important things to be found in all systems; one just had to work harder in some of them, and most of that effort went into convincing others. Ironic, Jonas thought, that most of his colleagues who had greeted his previous move with derision would now probably comment on the return with equal disdain, if not utter shock. He was going back to slimy things now that he had “made it”? Was he mad? The Dean would be especially dismayed. But that was their problem.

At least this was what Jonas told himself as he exited the meeting room. Tomorrow would be another day; new things would be discovered as being right. And others, inevitably, wrong.

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© 2015 by the author.

For Sandra Varum and Rodrigo Santos, with thanks