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What Real Scientific Controversy Looks Like

What Real Scientific Controversy Looks Like

It is fun to be embroiled in an actual scientific controversy.

One of the great things about science is that it is not set in stone. We always say that scientists revise their thoughts based on new evidence, but there aren’t that many times when we actually see this happen. For example, while we can play around the edges of the Central Dogma (at least the dogmatic version of it, that DNA makes RNA makes protein), it is unlikely that anything is going to come along to dispel this foundation of modern biology.

This is why it has been fun to be embroiled in an actual scientific controversy. My colleagues in the Marcotte lab have been studying an interesting phenomenon for the last few years, the observation that when a variety of fluorescent protein fusions are expressed in yeast, they tend to aggregate into punctate bodies under starvation conditions. It was (and is) to some extent unclear what these punctate bodies are: functional or non-functional, happenstance or programmed, due to the fluorescent protein’s potential for aggregation or inherent to many different fusion partners. Over time, students have continued to piece apart the observation, and the current thinking is that it seems likely that at least some of the aggregation is unintentional, due at least in part to the propensity of the fluorescent protein itself to aggregate. This does not make the phenomenon less interesting, as there clearly are many aggregates that form in the absence of the fluorescent protein. But what has been interesting for me to observe is the sociology of science at work, as hypotheses are put forward and tested, and various arguments are crafted in narratives that do or don’t stand.

You see, that’s the very tricky part of this, the tricky part of most science. While we are dispassionate investigators going where the data may lead us, we are also storytellers who believe in our stories. Both can be true at once, we can hold both ideas in our heads, as long as we are honest with ourselves about both ideas. Data should not be twisted to fit a story, nor should a good story be overlooked because the data are incomplete. Narratives are to creative science what a modus operandi or profile is to someone in criminal justice; they tie the facts together and guide insights into how to look for more facts.
But beyond watching my peers down the hall work this puzzle, it has also been fascinating to see another story emerge, from half a continent away. Steve Benkovic and his lab have developed their own narrative about the purinosome, an aggregate of purine biosynthetic enzymes that may come together for functional reasons in cells, streamlining the passage of intermediates during purine nucleotide biosynthesis. It is a very compelling story, and is backed by a variety of data. But it also overlaps with the story that Marcotte and others have been trying to tell, as the punctates that we have observed overlap with the ‘some that Benkovic has been substantiating.

So, is it an aggregate or a functional body? A happenstance set of interactions or a finely crafted evolutionary machine where the parts come together to channel substrates? The dissection of such questions has taken up many pages in many journals, and it would be foolish of me to reiterate the arguments in miniature here. Rather, I want to point out how very cool it is that now you can see these arguments play out in real time, you can watch scientific culture at work, doing what it does best: search for truth.

The most recent fare from the Marcotte lab was published in PLoSOne (a journal that you can download and look at for free), and to a first approximation said that “Transiently Transfected Purine Biosynthetic Enzymes Form Stress Bodies,” to which Benkovic and company replied “Zhao et al. do not report on purinosomes.” Fun, fun! The Marcotte clan has responded to this, with many Figures and muchly logic, and the reader can decide for themselves what the status of the science is.

And that’s the point. That’s the wonderful, amazing, exciting point. There it is, right there. Give and take. Interplay. Thought and counterthought. All in public view. All with scientific precision. This is how science should be done. This is what we dedicate our lives to, this search for truth. Not glory, not money, not even necessarily impact, but the truth. I am humbled by my collaborators and even my adversaries, as the point and counterpoint continues.

And you can make fun of my sentimentality, but even as you do so, go and look, and see what the real world of science is like.

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Friday, 03 February 2023

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