Look How Wrong You Can Be

Dear Chemistry Colleagues,

One of the most humbling and eye-opening events in my professional life happened about five years ago.  Our polyacrylamide gel images started getting blurry.  It happened to one student and then it stopped.  Then it happened to another and then it stopped.  And then it would come and go, happening to different people on different days.  Intermittent problems can drive a scientist nuts.  We had entire group meetings on this.  I held impromptu meetings in the hallway, in my office, and in the lab.  I would join the group for lunch and they would be debating the blurry gels.  Gel quality is critical to everything we do—assaying RNA kinetics, sequencing, and structure mapping.  There were tears and some of them were mine.  Theories abounded. The acrylamide was old, there wasn’t enough polymerizer, certain gel plates were better than others, we needed new spacers, the gel didn’t polymerize long enough, the gel wasn’t pre-run long enough, or the vacuum on the gel dryer was leaking.  We replaced every one of these things, borrowed reagents, and even dried gels in other labs.  Just when one of us thought we had it figured out, the problem would rear its ugly head again.  My group was literally in despair and I was too.  This problem plagued us for six months, and it is no exaggeration to say that our collective nerves were shattered.

Then, one day, my colleague Paul said that his lab, which was having a similar problem, fixed it by putting the same dried gel in a different cassette.  That was all the hint we needed.  Within ten minutes, we had the problem figured out: the spongy material in the bottom half of the cassette had worn down over the years, and the gel was no longer flush against the imaging plate on the top.  This was causing the radiation in the gel to spread out before hitting the imaging plate.  The problem of the blurry gel had been solved!  We were able to fix that problem by purchasing a new foam board at Michael’s, and we repaired all ten of our cassettes in a few hours for under twenty dollars.  This was such a cathartic experience that we wrote a short methods article on it in a single day—you can find it on my group website, “Eliminating blurry bands in gels with a simple cost-effective repair to the gel cassette”.  Five years later, the problem remains solved.  Later that weekend, the lyrics from a Rod Stewart song came to me, “Look how wrong you can be.”  So much time.  So many theories.  Every one of them, and every one of us, dead wrong.

Here we are in the time of Coronavirus and we have to remember how wrong each of us can be.  We can’t let our guard down or think we are in control of the situation.  Moreover, in the same way that the smallest of clues from another lab immediately allowed us to solve the blurry gel problem, teamwork can lead to breakthroughs on the COVID-19 problem.  In the last week, I’ve talked with Paul Cremer, Jean Paul Armache, and Howard Salis about COVID-19 research problems in their labs.  I don’t know if it will make a difference, but now is a time for all of us to help each other.  Who knows when the next hint might break the dam that is preventing a solution.

Walt Whitman wrote, “All truths wait in all things.  They neither hasten their own delivery, nor resist it.”  How true.  How simple.  How Zen.  Our blurry gels had truth waiting inside of them.  Although some days it seemed like the truth resisted its delivery, that’s neither true nor possible.  Likewise, the cure for coronavirus waits.  It cannot resist its delivery, especially if we approach it with humility and teamwork.

With Warm Wishes,

Phil