Enhance Your Productivity by Ignoring Biophysics

Usually when I write about biophysics, it’s with the uplifting message that understanding physics helps us make sense of biology, bringing varied phenomena together under umbrellas of general principles. This is true, and there are countless examples. Brownian motion explains the meandering of neurotransmitters and the patterning of embryonic body segments. Electrical interactions influence the packaging of DNA and the expansion of mucus. The list is long.

Now, however, I’ll write a dismal post. Our microbial systems journal club at the University of Oregon includes a wonderful collection of students, postdocs, and faculty who meet every week to discuss a paper. A recurring motif is that the paper seems good at first glance, from the title and abstract for example, but turns out to be bad upon deeper reading.

Sometimes the papers are unclear. Sometimes, depressingly often, the authors make claims unwarranted by the data. Sometimes, also often, the conclusions are based on sparse data, wishful thinking, and meaningless p-values.

The paper two weeks ago was particularly bad, in part for the reasons above but also for a less common reason: ignorance of very basic biophysics, I decided not to cite the article here — I’m not sure doing so would help anyone — but you can probably find the paper with a little searching.

The authors studied biofilms, aggregates of bacteria (blue in the illustration above) encased in a dense polymer matrix (black) of their own making. Bacteria secrete chemical signals (pink) by which they communicate with other bacteria. If you remove the polymer matrix, will the secreted chemicals spread farther, compared to having an intact matrix?

The authors show that the answer is “yes.” Isn’t this obvious, you ask? Chemicals diffusing through “stuff,” like a dense polymer gel, should spread more slowly than if the gel were absent. Yes, that’s true, but that doesn’t stop the authors from treating the finding as a major revelation. Perhaps, you wonder, the authors showed that the secreted chemicals spread more slowly than other similarly sized molecules, implying that they’re specifically trapped by the matrix? No, they didn’t. Perhaps the finding, though not surprising, were particularly well-measured, a rigorous test of diffusion in a complex environment? (After all, diffusion in gels is complicated.) No. Here, for example, are the concentrations of two chemicals versus distance from the source. More striking than the shortage of datapoints is the bizarre linear fit.

Since the mid-1800s, even before we knew that molecules exist, we’ve known how diffusing particles spread. A good picture to have in mind is a Gaussian function, a bell curve, which describes diffusion from a point; the more general case is simple to model. Describing it as linear is like imagining that the force of gravity decreases linearly with distance from an object, and also imagining that no one ever studied this and figured out the truth.

The authors spin a tale that the bacterial biofilm “cloaks” its members’ chemical cues, hiding them from predators, implying some sort of elegant and specific mechanism rather than “stuff slows down diffusion.” There are biological problems with the paper as well, especially the poorly justified claim that mutant bacteria that don’t make biofilm polymers secrete the same amount of chemical signals as those that do make biofilms, but I’d like to focus here on the physical problem that the finding is trivial. I would think that anyone who has any familiarity with biophysics wouldn’t have bothered to pursue it. The authors, however, got a paper out of it — a paper in a good journal that has been cited 22 times in less than two years.

More generally, I don’t think anyone would argue that ignorance is good for science, but it occurs to me that ignorance can help individuals’ scientific output. Without the advances of the past or the unifying umbrellas of biophysical concepts, the variety of ways signaling molecules can spread may be breathtakingly vast! Every molecule can lead to a paper. This lesson applies not just to biophysics, of course. I recently attended a fascinating conference, one recurring message of which was that cells are systems of many interacting parts; it’s generally silly to ask if one gene has an effect, or “is significant” — of course it is. This has not, however, stopped the production of single-gene papers.

What can we do about this dismal conclusion? Education, I suppose, to make sure that well known things really are well known! That isn’t an easy task, of course, especially as it calls for education across fields, but it’s a good goal to aim for.

Today’s illustration

I made a few attempts at a self-portrait recently. This, the last, turned out fairly well, though a bit over-shadowed and stern.

— Raghuveer Parthasarathy. February 29, 2024