The Surreal Killer

The Surreal Killer
Machu Picchu. Peru

Wednesday, June 13, 2012

My Strangest Patent---Just Add Water

            A long time ago, right after I finished my postdoctoral training, I took a job with a large pharmaceutical company to see what earning a decent salary felt like.  One day after I'd been there for several months we had our first crash program where we all were supposed to drop whatever we had been working on and turn our efforts to solving a big problem related to developing a new product.  Not to be technical, our organic chemists had developed 25 steps of a complex synthesis of a new antibiotic.  They were stuck on the 26th step, so they turfed the problem to someone else, the group of biochemists and bacteriologists I was in.  My job was buying a bunch of enzymes from Enzymes R-Us (to be honest, the company was named Sigma, but doesn't Enzymes R-Us have a certain ring to it?), and testing all of the enzymes at random to see if any of them could make that elusive 26th step happen.

             A week or so later the enzymes arrived and it was time for me to do something to earn my paycheck. The day before I ran my first experiment in this crash program, I stuck my head into my older and wiser colleague's office.  He had been helping me adjust to life in the real world, rather than the ivory towers of academia, by giving me advice on what was expected of scientists in this setting.  I asked something that translated into: "Should I just go through the motions, or should I do things very carefully, like I was doing a real experiment?"

            "Do it carefully and do it right," he advised.  "Later on when nothing has worked for anybody and they still can't do that 26th step they'll be looking for someone else to blame.  You don't want it to end up being you."

            In this particular case, doing it right meant that each experiment had several controls run with it.  For each enzyme tested there would be a tube with everything added including the enzyme and the stuff that had to be changed in the 26th step, everything added except the enzyme, and two more tubes just like them that were boiled in water to inactivate the enzyme before running the reaction.  After the reaction was over all of the tubes were put on ice to stop any reactions occurring, and a sample was analyzed overnight so we'd have an answer the next morning.

            The net morning I got in at my usual time, a bit earlier than the rest, and casually checked the analytical results.  Wait a minute!  Something had to be wrong!  I had a 20-25% yield of the desired product in all of the tubes.  It didn't matter if I boiled the enzyme first; it didn't even matter if I left the enzyme out altogether.  Just mixing the stuff together in a tube and leaving it overnight seemed to be enough.  All of a sudden, doing it carefully and doing it right was going to pay some unexpected dividends.  As people trickled in the word spread, and I got my nickname that would remain attached for the rest of the year I spent at the drug company, "Lucky".

            For the techies who read this, the 26th step that eluded the organic chemist's expertise was a simple reaction called hydrolysis, adding the parts of water to the larger molecule. The magic ingredient I added to all of the tubes was plain water, which was easy to show the next day.  The chemists had never tried water for this reaction, it turned out, because theoretically it would prefer to cause an undesirable side reaction and they believed too much in the theory to test it.  I ended up with a US patent and several international patents, now expired, and a paper published in a prestigious chemistry journal to make the new antibiotic using water as a reagent to cause a hydrolysis reaction.  Weird!

            What's the point?  The old cliche that says "If it's worth doing, it's worth doing right" is indeed still alive and well.  Keep saying it over and over when you try to decide whether the manuscript you've worked on over and over until you're sick of it deserves one more round of editing.  It usually does.

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