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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