Of Mice and Molecules...

Multifarious cogitations

Sabotaging My Own Career - Been There, Done That

9/28/2016

 
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This is one of the pics that pops up when you do a google image search for "career sabotage." It has nothing to do with the story, but was too good not to post.
As part of my ongoing blabbing about the peculiarities of science, I thought I'd share a fun story where it made good sense for me to try and derail my own career. 

Following my graduation from my PHD program, I joined a prestigious-ish lab at the University of Chicago as a postdoc (the now-mandatory period of career purgatory that now bridges one's schooling and - hopefully - future career). Initially, I was somewhat excited about the gig. The lab's PI (the professor, the boss) was a really smart guy who had changed research focuses several times (this is extremely rare for faculty-level people) and made interesting breakthroughs each time he'd done so. The lab had just crapped out a large number of extremely high-impact papers and I was eager to join the gravy train. ​
Unfortunately the party ended right about the time I stepped through the door*. Upon arrival, I learned that the boss was making yet another radical shift, this time to epigenetic regulation. This topic is actually less boring than it sounds: When we're conceived, sperm and egg fuse, and that one cell becomes virtually every cell in your body. This capacity, called totipotency, is maintained when one cell splits into two and when two cells split into four. However, at a certain point (gastrulation, for those who care), totipotency is replaced by multipotency; cells can only produce a subset of tissues, like certain organs. This limiting of differentiation potential continues as development progresses, until we're left with mostly progenitors (which are capable of producing only one type of cell - our continually regenerating skin is a good example), along with a few bona fide stem cells that can produce a narrow range of cells (neural stem cells, for example, can produce both neurons and their supportive cells in the brain). 

​Our PI wanted to know how this process was carried out. His hypothesis was that genes that would not be used in a certain lineage would be shuffled around and packed away in the back closet of the nucleus, left inaccessible and permanently dormant. This would prevent a cell in the brain from suddenly producing bone. That actually happens in a type of tumor called a teratoma and it's very, very bad news when it occurs. 
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Actual teratoma. This is pretty much the stuff of nightmares.
Anyway, to test his hypothesis, the boss had us run experiments where we would fuse skin cells and muscle cells together. When that occurred, transcription factors from the muscle cell would enter the skin cell's nucleus, turning on muscle-specific genes, genes that normally wouldn't turn on in a skin cell. Likewise, skin cell transcription factors would turn on skin genes in muscle cells. If the boss was right, not all the skin genes would turn on in the fused muscle cells (and vice versa), presumably because they were packed away in the junk closet (you don't really care about how or why, so I'm saving myself from describing the minutiae here).

As predicted, we did find that there were certain genes that failed to restart expression. Our boss used this as proof that the inexplicably silent genes were 'occluded', or physically prevented from activating. This would be a big deal, he argued; if we could identify the mechanism behind occlusis, it might be possible to 'de-differentiate' tissues in a damaged area and allow them to regenerate a damaged limb or organ the same way a starfish or salamander regenerates.

Although I've explained this rather succinctly, the work consisted of a long series of very, very complex experiments. To complete the work in a timely fashion, it was necessary for an entire team of postdocs to devote their full effort to the project. 

That's where the problems started for me. In academia, there are only two important people in any manuscript, the first author and the last. The last author was the senior author (our boss in this case), leaving only the highly-coveted first author spot. The first author would be the person who could lay claim to the bulk of the work, using it for themselves as the basis for a future faculty position. 

Everyone else in the paper would be regarded as a helper, even if it took years of work. Since I wasn't the first person to join the party, I would be relegated to somewhere in the middle. This effectively doomed my chances to make the postdoc a waypoint on the way to a faculty position. I was left with two choices - leave for greener pastures or stay as an indentured servant. 

I chose to stay. By that point, it had become abundantly clear that I was burned out on academic research and would not be continuing in academia anyway. My plan was to put in the standard 2-3 years and then find a job somewhere else. That left me with all the motivation you'd expect for someone who was underemployed in a dead-end job. I wish I could say my professionalism didn't allow my intensity to wane, but this is an honest blog. 

After a relatively painless year of mailing it in, my boss called me in. "Noah, it's time we talked about your career."

"Huh?" I asked, wondering how he'd learned of my still-nascent plans to leave.

"To be competitive for future jobs, you need to build a successful track record of receiving funding. You should start by applying for a T32 postdoc grant."

"Oh," I replied. "Yeah, I guess."

"Beauteous," my advisor replied (he actually said this made-up word with some regularity), before vigorously launching into the proposal that I should encapsulate in my application.

After I had time to review what I'd agreed to, it became very apparent that I'd created a serious problem for myself. It wasn't the extra work of making a competitive application, it was what would happen were I to succeed. At this point, I was working for a private foundation that was sugar-daddying my boss. While I was making only slightly more than postdoc scale pay (42K-ish, if you're curious), the appointment included a 5% retirement contribution and pretty decent health care. Initially, I thought that winning a grant would raise my pathetic salary and give me some more money. Nope. The "prestigious" government grant would actually cut my salary slightly.  

Fuck that noise. Money was literally my only motivation for this job. I'd be damned if I was going to cut my own salary for an award that would help me get a career I didn't want. 

The main problem was that I'd already agreed to apply for the grant, and telling my advisor the truth did not bode well for my temporary career here. When you crunch those numbers, what comes back is the need to sabotage your own grant application while making it appear as though you're trying.

This was not easy. My boss fought me like a tiger. But I fought like an enraged, methed-up baboon with hemorrhoids (five attempts on the spelling there). My application was shit. My goals were unrealistic and my timetables were overly ambitious. I purposely misspelled the word 'science' twice in the introduction. 

My boss, unaware I was trying my easiest, fought valiantly to fix these myriad errors. Every time he'd ask me to fix something, I'd do so while altering something else that was perfectly OK. Every strategy meeting we had was awful. I felt terrible that he was trying to clean up the shit that was oozing out of my computer. Not enough to, you know, come clean or anything, but I still felt remorse. 

My trump card were my references. For any grant application, you get the most powerful people you can to give you sterling recommendations. In the world of grant reviews, every candidate should be "in the top 5% of scientists I have ever met" (I'm paraphrasing the actual evaluation form), regardless of the impossibility of such a statistic. Anything less was to court certain failure. 

Instead of powerful faculty members, I asked the two friendly postdocs who sat near me to write me references. Not only did I get these relative nobodies to endorse me, I requested they make their letters, shall we say... less than sterling. As one of my friends put it, he "damned me with faint praise."

I submitted the grant on the deadline. Three months later, it came back triaged. This was the best possible result for me. It meant that the NIH staff reviewing it thought it had so little chance of getting funded, and it was essentially tossed aside before being evaluated by the full committee.

The boss was distraught at the poor reception my (his) application had received. He resolved that we (he) would re-submit it, this time better than ever. He was inexplicably motivated that I win the award. Upon reflection, the reasons for this are clear: by obtaining a grant, I would be effectively removed from his payroll, freeing up enough salary to bring in another smurf for the mines. 

The second application was much more difficult to torpedo. My boss knew that this was our (his) last chance at submitting the grant. There were twice as many meetings, twice as many tweaks. The review we'd received the first time around had called me out for using iffy references, and I was commanded to find better references. I grudgingly acceded, but only asked friendly junior faculty for their endorsement (all the while making clear my reticence to win).

Three months after the second iteration was submitted, the scores came back. My grant had done well. Dangerously well. My boss held out hope that I would squeak in, but in the end my score was just about one percent under the pre-established funding line. He called me in for a consolation meeting and I tried to look disappointed at my 'failure'.    

Postscript

So what, if any, effect did purposely failing have on me?

In the short term, it was great. My salary was unaffected, and I continued poking along at the University. However, my failure to secure funding would come back to bite me in the ass a year later during the financial downturn, ultimately resulting in me leaving the University in a hurry. That's a longer story best told later, but it ended with me landing in my current job. 

In hindsight, do I regret what I did?

This was pushing ten years ago. I've had a lot of time to ponder what I did and why, and I can honestly say that I would do the same thing again in that situation. Academia is a bizarre world, and the perverse flipping of motivations that occasionally occurs is something that cannot be fought against.  

If more proof was needed that I did the right thing, it came from anecdotally observing those who took the other path. There were two other postdocs in our lab, one slightly senior and one slightly junior. Both of them were real crackerjacks, and received the postdoc fellowship I didn't. Checking on them via Linkedin, I see that neither ever became faculty. However, secured in part by their fellowships, both of them lingered in their dead-end jobs for  very, very long time. From a money perspective, this was a terrible decision. Each of them spent between eight and nine years the a low-paying job that I escaped after two. After I joined a pharma company, there was a >100K difference in our compensation for the following SEVEN YEARS, which probably persists now to some degree (the positions at the companies they joined appear similar to the junior position I accepted eight years ago)**. While money certainly isn't everything, I'm very happy I moved on early, even if the road was rocky.  

Postscript

Remember that epigenetics project I worked on? The one that would change the world? It was eventually published in a decent-but-unspectacular journal and remains, as of time of writing, the least cited paper I have ever been involved with. I cared about as much as a fourth author could. 

*I am aware an alternate explanation exists - that anything I touch turns to shit. Har har. In my defense, the lab persisted for years after I left and never did anything that got traction. Perhaps you could argue I had the same effect as a lethal dose of radiation, but that's maybe too much truth for today.

**I am not bagging on these folks, both of whom are great people (and better/more professional scientists) than I. In case it's not been clear from my writing, luck plays a tremendous role in both science and life. 
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