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From the LabLit short story series

João Ramalho-Santos 11 February 2014

Pedro had no illusions about the role of his lab in this particular Grand Scheme of Things

As he randomly picked up one of fifteen theses on his desk there were several things going through Pedro’s mind, none particularly uplifting. He thought of how this was not a reflection on his lab’s productivity – one could hardly classify what he had in front of him as “research”. He thanked the strict confidentiality agreements to which the Company had made his University adhere, meaning that very few people were aware of the project, and that there would be no public thesis defenses. He marveled that all it took was a small scholarship to get fifteen reasonably talented students to actually sign up for something like this. He wondered if he’d ever get another grant that might get him back into the real game. Above all Pedro knew he should he happy to even be in this position, and felt somewhat guilty he didn’t. All he could muster at this stage was professionalism.

Pedro had no illusions about the role of his lab in this particular Grand Scheme of Things. The list of compounds that he had been given was daunting enough; this was merely the first batch. And he knew both that this was just a fragment of a much larger list, and that even that mega-list came about only after oodles of candidate compounds had been pre-selected in high throughput in silico screens. There were probably twenty or so labs around the world independently testing drugs for the Company. It was even likely that, unbeknownst to all involved, several anonymous students in different countries had theses with the exact same titles and (hopefully) results as the ones he was about to look through. It was what it was. And there was no point in complaining about the financial arrangements in place either: Pedro was being paid peanuts to carry out these preliminary in vivo studies because: a) peanuts were like caviar for him these days (and the Company knew this); b) peanuts were even more like caviar for the University itself (if anything his bosses had been enthusiastically on board before he was); c) he had the right experience and set-ups, and was well-respected (if currently probably also pitied) in the field; and d) he had access to good students who knew the training provided would serve them well in job interviews somewhere in industry, and for whom the data itself was actually not that relevant.

As he slowly plowed though, Pedro was relieved to find the theses competent enough, and with distinct and credible results; but there were fifteen of them, every single one organized the exact same way. In fact, the Introduction and Materials and Methods sections could have been copy-pasted fifteen times, not that it mattered. The problem was the Discussion; or, more to the point, the consistent lack thereof. But that wasn’t the students’ fault. Their job had been to inject one of compounds X1 to X15 into rats, and then see what happened. A little bit of everything had been involved: some pharmacodynamics, some biochemistry, some physiology, a dash of behavioral tests. Good overall training, if Pedro dared to say so himself. And the students had done exactly what had been requested, with the graphs, tables and statistics to prove it. In fact, accepting all fifteen students at once (and having them help train the incoming next fifteen midway through) had probably been Pedro’s best cost-effective effort as a supervisor; even the more hopeless in the group could manage decently with fourteen others who knew the exact same experiments.

Efficient it most certainly had been, assembly line-efficient. Which was also what made it excruciatingly boring. Pedro had always been unabashedly enthusiastic about Science, the unbelievable draw of deciphering the unknown, but even he couldn’t quite hype the projects he was mentoring, an issue he had tried to work around in lab meetings. Until he realized the students did not mind, and certainly did not share, his dismay.
At first Pedro thought they were mindless drones with no real interests or passion, in line with previous opinions on all generations that had followed his own. The fact that they were being paid for the privilege, a very rare occurrence, somehow further diminished them in their supervisor’s mind. But students couldn’t be faulted for making an obvious choice in the current economy, and Pedro soon realized that their gazes were distinct. For each one of his students it was a once-in-a-lifetime first laboratory experience, not the routine set of experiments multiplied by fifteen that he felt.

As the year progressed Pedro also started noticing that what to him was a severe handicap in the projects was not viewed as such by most of his trainees. While it was true that they could not really discuss their data, it was also true that, unlike their colleagues in the Masters Program, they did not need to awkwardly try to fit every single piece of that data into massive existing bodies of literature, and convince anyone of the role it might play in Explaining Everything. None of his students would ever co-author a paper with Pedro, but, then again, a letter of support stating the nature of their work might actually prove more efficient in opening that elusive first employment door. What kept Pedro awake at night looking for motivational tools was actually the main reason his students did not need any extra motivation, and slept like the baby scientists they were. One of them had been so bold as to state in her interview that she was grateful for the opportunity to be working in something that might be important in the “real world”, while everyone else was toiling away on far-fetched esoteric research. A statement that could be simultaneously viewed as somewhat true, and truly ironic. Because, although they knew very well what they were doing, no one in Pedro’s lab knew what they were doing.

They were all blind.

The Company had been very clear and detailed on what sort of experiments it wanted done with each of their compounds. Although they were clearly saving money by outsourcing this part of the project, that did not mean relinquishing total control. They were always incredibly straightforward, except when it came to one simple thing: the nature of whatever it was that Pedro’s team was putting in rats. No chemical formula, no structural information, no purported mechanism of action, no clue as to what the compound might actually be used for. The Company was big enough that they could be testing candidate antibiotics, cancer drugs, next-generation antidepressants...or products from rival Companies. Or placebos. Of course someone somewhere knew exactly what the compounds were, was probably salivating in anticipation to decode the very graphs Pedro had on his desk; and would make interesting conclusions based on the data he provided. Someone, somewhere. But not Pedro. And that drove him crazy. Not the all-out variety of craziness, unfortunately; but the subtle, insidious kind. The kind that made you see issues in everything, except in your own budding mania.

Pedro had always thought he understood the art of walking on the right side of weird to be able to do great science. Just enough obsession, just the right amount of paranoia, heaps of creative perfectionism. But he had never quite realized the importance of the main ingredient. Having all the information. Establishing context. Being able to see clearly. Not necessarily in the Results or in the Discussion sections. Those you could build up, tweak, interrogate, interpret. In fact, that was the whole point. But not knowing the nature of key Materials used in the experiments made everything else moot. It was like forgetting which wells in the Real-Time PCR or ELISA plates were which. Unthinkable, useless. And yet that was exactly how he was expected to oversee the experiments. Blind. It was not in his nature. Which was why his nature had fought back.

It had started with simple games played while doodling in seminars, like trying to guess the nature of a compound based on its molecular weight and solvent, its administration regime, or the exact tests the Company wanted run with it. It continued during the frustrating update visits by Company minions in charge of monitoring his progress, carefully manicured youths who cared only about deadlines or Good Laboratory Practice and ISO Certification, and who politely deflected Pedro’s attempts at extracting further information with wry smiles. Their well-paid and impermeable 9-to-5 bureaucracy-fuelled existence was probably the kind of job his students were gunning for, and that somehow made Pedro even more miserable. His misery was now reaching a climax of sorts, he realized, with endless interpretations of the more interesting data his students had produced.

What could the effects of the mystery substance X12 actually mean? Was one given result an actual effect, or a secondary effect? Could any of it be relevant for the “real world”, as the student had predicted? Would the Company be ecstatic of disappointed? Would Pedro ever know, either way? For a fleeting moment he even felt the urge to have one of his chemical analyst buddies go through some of the compounds, especially those that caused more obvious changes. However, not only was he required to account for every coded milligram provided in a detailed log, but the penalties listed in the contract were too steep to be challenged, especially by mere intellectual curiosity and professional quirks, powerful though they were. At the end of the day all he could do was call in the students with corrections to the way they presented their Results, the only thing the Company cared about. And compliment them on a job well done. It would not have been the job he had chosen for himself, but shouldn’t he feel grateful he was supervising others who were willing to do it?

Luckily, even while immersed in obsession, Pedro knew from experience that one could rationalize basically any setback, and feel content, if enough effort went into it. He also knew that his profession was, by definition, one of permanent unrest and search for all-elusive satisfaction. The trick was to walk the line in between. Perhaps that might even imply letting go of the Discussion once in a while. Forgetting the Materials, and dropping the Introduction. Could just Methods and Results provide at least a decent modicum of vindication, a modest blind buzz? Perhaps he should learn from his students, who seemed to have grasped this particular reality much more quickly than he had. Actually, that was what mentoring was supposed to be all about: enriching mutual exploitation.

Maybe, Pedro hoped, before the list of anonymous compounds and paired eager students had exhausted itself, he might be able to see again.

Other articles by João Ramalho-Santos