Postdoc Required? Check the Job Ads!

Both the New York Times and C&EN have written pithy pieces today referencing the recent Science survey about factors influencing postdoctoral study. 

The tone of all three comes across as confused, painting Ph.D. students as ill-informed, directionless lambs who take on postdoctoral appointments as, in the words of the Science authors, "default...holding patterns" because they "...don't know what they want to do with their lives." (NYT).

Well, for those of us, like me, who postdoc'd with the intention of going into industry, why did I "waste my time in a post-doc" (Science) for seemingly no reason? Here's some telling quotes, highlighting from me:

From Science: "...career goals are quite diverse even among these postdoc-planning students...[t]his may be surprising, given that the postdoc is not typically considered a stepping-stone toward nonacademic careers"

From C&EN: "Many students don’t have a sense of how many jobs are available or what background they require, Doyle says. Chemistry students think they need a postdoc for some high-level industry jobs in the pharmaceutical industry, for example."

From NYT: "[in 2013]...the most common reason students gave for doing a postdoc was that they thought it would increase the chances of getting the job they wanted."

These sound bites sound aloof at best, slightly pandering at worst. Here's my question: Did anyone quoted for this story, or the authors of the Science study themselves, actually read the job ads for the industrial positions in question? Maybe students' fears are well-justified, because the ads I'm seeing from multiple companies read like this:

GSK, API Chemistry Automation Team Member

Pfizer, Sr. Scientist - Obesity + Eating Disorders

Amgen, Scientist, Immuno-Oncology

Genentech, Sr Scientific Researcher, Discovery Ophthamology

In case you missed it, all recommend postdoctoral research. I didn't have to go digging for these, either - simply typing "chemistry" along with "postdoctoral" or "post-doc" into the Career search engine on any corporate site will reveal roles like these. I find it rather ironic that the last quote from the Science lead author reads: "We don’t know enough about the industry labor market” (C&EN write-up). That seems to be the only part of this whole situation I completely agree with. 

OK, grumpiness aside, how can this situation be fixed? I actually appreciate the incentive strategy advanced in the paper, which neither news outlet captured well. Here's most of the penultimate paragraph from Science, highlighting again mine:

"Whereas the recent National Academies report recommends that students make career plans early in the Ph.D. program, we argue that they should consider labor market conditions and career options before starting a Ph.D. program. Doing so may avoid escalating commitment to a research career and may prevent individuals from entering a postdoc holding pattern. Graduate schools could encourage career planning by requiring that applicants analyze different career options and justify why a Ph.D. is the most promising path forward. Funding agencies could implement similar requirements, especially in conjunction with moving a larger share of funding from research grants to training grants and individual fellowships."

Amen. One thing I believe saved me from five years of postdoc purgatory was walking in "eyes open," understanding exactly what jobs I'd qualify for and where I needed to end up to pay back all my student loans. I also realized it would be no cakewalk: I began applying for jobs in my second year of study, and never looked back. 

Grad students: If you're confused about your options, feel free to drop me an email at seearroh_AT_gmail. Confidentiality guaranteed.

Invisibly Important

Who does more important work: The scene-stealing front man, or the patient show-runner backstage?

Sumac in Fall, 2014

Writing at the New York Times "Motherlode" blog, author David Zweig posits that, in an era of attention-grabbing occupations - Internet whiz-kids, Wall Street financiers, American Idols - the real winners may be those who select the quiet, thoughtful "enabler" roles behind the scenes. He claims that, though they may not get the glory, such "Invisibles" end up better paid and more highly satisfied with their chosen stations.

Though Zweig volunteers occupations like structural engineers or quantitative analysts, I'd offer that most important roles in scientific research belong equally on his list: Spectroscopists. Molecular modelers. Patent examiners. Grant writers. Purification staff. Procurement. Health and Safety. Administrative assistants. Graduate students.

If you get a chance today, think about the Invisibles that help your science to succeed.
And buy that mass-spec guy a beer, already!

"Cantrill-ing" Hits the NY Times

Apparently, U.S. Senator John Walsh has been accused of plagiarising a final assignment for his Master's degree. And how did the New York Times cover this story? Why, by literally "cantrilling" the paper!

Source: NY Times

Remember us all when you're famous, Stu.

Smells Like Satiety

The NYT Well Blog recently covered a fascinating study out of TUM* in Munich, Germany: olive oil may cause you to feel satiated faster and eat less food. Apparently, study volunteers fed yogurt with olive oil mixed in showed a spike in serotonin levels, and ate about 175 calories less each day than experimental groups given different fats (rapeseed, butterfat, or lard).

But was it the fat, or was it the flavor? The researchers isolated aroma compounds from the olive oil, specifically hexanal and 2E-hexenal, and mixed them in with yogurt. Same effects! In the press release, Prof. Peter Schieberle comments "Our findings show that aroma is capable of regulating satiety."

Smells rule neurochemistry. It wasn't that long ago, really, that Axel and Buck won the 
Nobel Prize for their research into olfactory organization. Two years later, another unsolved mystery, that of "blood smell," came to light in ACIEE. Turns out, both blood smell and the new research on olive oil aroma depend partially on medium-chain aldehydes (hexanal-decanal) and unsaturated ketones. You can even smell ketosis, an alternative metabolism found in diabetic crises and Atkins dieters, by the tangy, astringent odor on the breath. 

Amazing how sensitive the human nose is for volatile carbonyls! Perhaps this harks back to a rather strange notion of odotopes, or "weak-shape" theory. This suggests that, rather than the "lock-and-key" model observed for enzymatic binding, smell may result from a collection of weak interactions with multiple receptors, based predominantly on molecular shape. 

*Bonus note: I knew I recognized the TUM group from somewhere! Remember this abstract, from J. Agric. Food Chem. last year? Based on my (single, not to be repeated) experience with durian fruit candy, I do wonder how they convinced this poor scientist to be the GC smell-port 'volunteer.'

You couldn't pay me enough.
Source: Steinhaus, TUM | J. Agric. Food Chem 2012

Chicken Chemophobia

A recent New York Times Op-Ed spot made the rounds late last night on Twitter. Full of inflammatory language, it seemed wholly bent on scaring the heck out of anyone reading it. The title - "Arsenic in Our Chicken?" - didn't exactly calm me down.

Is this in my chicken? Only very, very little
Credit: slashfood.org

Well, I'm a scientist, so let's look at this rationally. First things first: here are links to the two papers referenced in the study, one from Environmental Science and Technology (ACS), and one from Science of the Total Environment (Elsevier). (Editor's Note - Whenever a columnist feels pressed to validate his opinion with the words 'published in a peer-reviewed scientific journal,' I turn on the skepticism). 


In both papers, analytical chemists take a peek at feather meal, a poultry industry byproduct, for compounds you might expect from factory farms: antibiotics, stimulants, and antihistamines. A surprise dark horse was encountered in arsenic, which apparently caught everyone so off guard that they required a full second paper to adequately discuss it. 


Glancing quickly at both journals' major tables, it's clear we're talking small amounts here: parts per billion (ppb), which for EST means ng / g, and for STE ug / kg. To put this in perspective, let's imagine we had a swimming pool, which we filled with 1000 L (~270 gallons) of water, which will weigh 1000 kg (density of water = 1 g / mL @ room temp). Now, what's a ppb for this scale? One milligram of material, or about what you'd add if a snowflake fell into your pool.

Better start eating....
Source: Home of Science Wonders

Overall, the article smacks of rampant chemophobia and fear-mongering. While the individual compounds, in acute (high) doses might be cause for concern, the detected values aren't near that much. The LD50 (oral, mouse) for arsenic, the value at which half of tested lab animals die, is 145 mg / kg; the maximum arsenic detected in feather meal = 4 mg / kg! This leap of logic contains an even more far-fetched premise: you'd have to eat two pounds of feathers just to take in that much!


Remember: infinitesimally tiny amounts of several "bad" substances float by you every day, but you don't often see people dropping dead.


Maybe that's the reason that this NYT reporter buries his lede - a quote from his source, Dr. K. Nachmann, an author on both papers: "We haven't found anything that is an immediate health concern." 


And look, now I've gone and buried it, too.


(Update, 12:09 4/5 - Commenters on Twitter point out that a topic I did not address - detection of banned antibiotics - could be cause for concern. I agree with that point)

Illegal Drugs Spur Chemists to Create Cures

White powders marketed on grocery shelves as “bath salts” are quickly becoming problematic for politicians and police, as reported in the July 17^th New York Times.  These “salts,” derivatives of a compound called methylenedioxypyrovalerone (MDPV) cause many of the same symptoms as methamphetamine intoxication. The wide availability of these new mixtures, compounded by their ease of synthesis and seemingly no lack of supply, has led to an explosion in their abuse (Note: I won’t cover the chemistry behind MDPV, the active ingredient, because my in silico mentor David Kroll’s posts on Terra Sigilata have mostly covered it).

That’s the gist of the article, in which illicit chemical synthesis fuels a new drug craze, and the public perception of chemists is dragged down again by sound bites such as “state bans thwarted by chemists who have to change only one molecule… to make [the salts] legal.” What happened to fair and balanced coverage?

For every illegal manufacturer of psychoactive compounds hoping for addiction to promote sales, there are many more chemists working on analogs of bioactive substances to treat disease.  Compounds that show high potential for abuse tend to interact with three neurotransmitters: serotonin, dopamine, and norepinephrine. In the case of bath salts, the main ingredient is a norepinephrine-dopamine reuptake inhibitor (NDRI), which allows these neurotransmitters to stay longer in the synapse, creating feelings of pleasure and wakefulness. Phenethylamines, such as MDPV, meth, or Ecstasy, the popular club drug, are one major class of compounds which activates these receptors, and are easily tweaked synthetically to prepare drug leads for Parkinson’s disease, schizophrenia, and ADHD.

Prof. David E. Nichols, of Purdue University, has devoted much of his career to understanding the mechanisms by which addictive drugs can interact with brain receptors, and designing novel compounds to take advantage of these traits (See this October 30, 2010 Wall Street Journal piece for Nichols’ comments regarding black market applications of his academic work). Prof. Nichols has synthesized variants of psilocybin, mescaline, and notably for this particular story, MMAI, a “cyclized” version of a typical methamphetamine scaffold.  On the day the NYT article went to press, Prof. Nichols had a J. Med. Chem. ASAP publication (DOI: 10.1021/jm200334c) appear online, in which his group prepared four new methylated analogs of their lead compound dihydrexidine. This analog, developed off the phenethylamine scaffold, has been shown to bind to the D₁ dopamine receptor, and both improve blood flow to the brain and to reverse Parkinson's-like symptoms.



Photo Credit: obrag.org

 Two other medicinal chemists are using methamphetamine derivatives as “Trojan horses” to trick the body into immunizing itself against the drugs. Their end goal is a vaccine that could be administered to control meth addiction. Kim Janda, of the Scripps Research Institute, and F. Ivy Carroll of the Research Triangle Institute (just down the block from David Kroll!) have both recently reported their groups’ respective efforts towards methamphetamine vaccines. Each group strategically introduces a hapten, an immunological “stamp” that latches onto a human protein, which the body can use to recruit white blood cells to the foreign substance.

Janda (JACS 2011, 6587) attaches a six-carbon chain ending in a thiol (SH) group to the amino group of (+)-methamphetamine, the more potent enantiomer, and observes high antibody titres in mouse models. Carroll (J Med Chem, 2011, ASAP) also uses a sulfur antigen, but attaches his via an amide linker connected to the aromatic core. After connecting this linker to a suitable immune-responsive protein, Carroll generates a monoclonal antibody with a 6.8 nm K_D for (+)-meth.

Update (July 30, 6:50PM) - Changed "bloodstream" to "synapse," since commenter gippgig is (again) correct that the compounds influence synaptic function, not bloodstream chemistry. Thanks!