Feng Zhang's CRISPR "Miami Moment"

I've spent a bit of time this week trying to grok the ever-expanding frontier where biology meets chemistry. RNA therapeutics, chemical probes, synthetic biology, protein engineering...I could go on and on. Of course, this list would be woefully incomplete without the new cool kid: CRISPR.

If you've read a few of the stories surrounding this field's origins, you'll recognize the names Doudna, Charpentier, and Zhang. An interesting story arc emerges in the countless biographies surrounding Feng Zhang, now at MIT / Broad. Here, it's retold through the lens of WIRED author Amy Maxmen:

"Soon after starting [at the Broad], he heard a speaker at a scientific advisory board meeting mention Crispr. 'I was bored,' Zhang says, 'so as the researcher spoke, I just Googled it.' Then he went to Miami for an epigenetics conference, but he hardly left his hotel room. Instead, Zhang spent his time reading papers on Crispr and filling his notebook with sketches on ways to get Crispr and Cas9 into the human genome. “That was an extremely exciting weekend,” he says, smiling."

Have you ever had a point in your life like this?  Perhaps Zhang truly found the conference boring, and researching CRISPR was his best escape. However, since this story crops up so often, I'd like to think it's an attempt to capture the "flow" state as it applies to crystallization of a new field of research or career direction. Hopefully you recognize the feeling - total immersion, loss of time, tuning out all external concerns while your brain opens up to the vast possibilities of something truly new.

Clearly, a computer algorithm with a scientific sense of humor printed this lotto ticket. 

From my own experience, I can remember a handful of flow moments that I sustained for longer than a few hours. In the first, I spent two or three days reading everything I could about a competitor's catalysis research - hoping not to get scooped - and encountering multiple exciting ideas about monodentate ligand binding left unexplored. In another, I tried to track the entire Vinca metabolism from Tryp to the few hundred polycyclic alkaloids like vincristine and ajmaline. Plant metabolism turns out to be much more complex than I'd ever imagined.

Readers, I'm certainly not alone...can you recall when you've experienced a version of Feng's Miami moment? What was it like?

Smells Like Chemistry Prose

From the April 2015 issue of Wired magazine, two wonderfully redolent paragraphs regarding the flavor chemistry of yeast metabolites, courtesy of writer William Bostwick:

"The best sourdoughs command the same sort of cultish reverence as the best sour beers and for years were thought to come only from a few places. San Francisco's loaves are so famous, a Lactobacillus species is named after the city: L. sanfranciscensis, known for molecules like fruity isobutanol, butter-sweet acetoin, and grassy 1-hexanol."

If you're more a fan of lambics, perhaps this flavor profile better suits you:

"Pediococcus produces lactic acid, lambic's dominant flavor note, but can also emit funkier flavors such as buttery diacetyl. . . Brettanomyces also makes stuff like caprylic acid (goat smell) and ethyl lactate (horse-blanket smell). They're what make a farmhouse beer taste like a farm."

--
*(Title: Apologies to Nirvana).

WWWTP - Lab Signs Edition

From the Sept 2014 issue of Wired magazine:

I understand that magazines require flashy, highly-posed photographs to move copy.
That said, did no one in the Editor's office notice all the warnings on that hood sash?
They read:

"Wear proper PPE (Goggles, Gloves, Protective Clothing)"

"Always properly label your chemicals, including your initials. Any unknowns will be disposed of as Hazardous Waste"

"NO STORAGE"

As far as I can tell, the researcher pictured is in violation of all three signs. Ye Gods.

Hey WIRED, Why No Chemistry Love?

101 Signals, WIRED Magazine's latest compilation of "...best reporters, writers, and thinkers on the Internet" just went live. They've broken down the list, which includes blogs, Twitter, and Tumblr feeds, into chunks: Business, Design, Consumer Tech, Gov't & Security, Culture, and Science.

Here's the Science group. A distinguished bunch, but guess what?
Not a chemist among them!!!

Sure, we've got great, well-known personalities like Ed Yong (Not Exactly Rocket Science) and Randall Munroe (xkcd), Phil Plait and Robert Krulwich. I see plenty of physicists, biologists, astronomers, geneticists, and science writers, but no chemists.
And yet, two Tumblr accounts with the word "f*ck" sprinkled in (Classy, WIRED, classy).

I suppose Maggie Koerth-Baker, who has written about chemistry several times, is the closest we get to full representation. But she's plugged as the BoingBoing science editor / NYT columnist, with nary a mention of chemistry to be found.

So, what gives? Folks on Twitter have suggested a few issues with the chemblogosphere, from "in-reach" in place of outreach, to a tendency to "punch-down," or even (gasp!) that our stuff just doesn't appeal to a mainstream audience.

All valid points. Well, allow me to retort: An aspect of chicken-and-the-egg surely works behind these listicles. Although we haven't fully ironed out all of chemistry bloggers' quirks yet, not featuring our blogs in mainstream offerings just exacerbates the problem!

How can we be part of the solution,* if we can't even get in the door?

In case a WIRED staffer happens upon this post, please consider the following widely-followed, high-quality chemistry blogs to include in your next collection:

In the Pipeline
ChemBark
Elemental
The Curious Wavefunction

*Please don't say, "If you're not part of the solution, you're part of the precipitate." We've all heard that one.

Naming Rights

(Thanks to the July issue of WIRED magazine for the tip-off)
(Check updates, below, for folks who've reminded me of more chemist-named facilities)

Andre Young and Jimmy Iovino:
Music Entrepreneurs / Academy Founders
(Wonder which guy gets to set the new dress code?)
Credit: Sam Jones | USC

Could you receive a doctorate from Dr. Dre?
Not yet, but maybe soon...

I somehow missed the announcement a few months ago:
Dr. Dre and Jimmy Iovino, two highly successful music entrepreneurs, donated a chunk of change to USC. The result? The USC Iovino Young Academy for Arts, Technology, and the Business of Innovation.
(Tagline: The Degree Is In Disruption.)

The program creates an L.A-based  incubator, with courses like "Marketing Radical Innovations," and "Managing New Enterprises." The students spend their fourth year working, quite literally, in a space dubbed "The Garage," filled with tools, gadgets, computers, and other budding entrepreneurs.

How much did this new Academy set Jimmy and Dre back? A cool $70 million. Not too shabby, for two guys who never went to college.

This got me thinking: Do chemists ever buy naming rights?

Most of us would be content to be known for a specific reaction or process - 'named reaction' books get reprinted almost annually. Sometimes well-known professors sponsor or are honored with named professorships, such as the Cram or Vedejs Chairs. One famous Nobelist even garnered his own Institute. Rarer still, chemists whose research translates into industry can name buildings (Silverman Hall), institutes (Warner-Babcock), or create charitable organizations (the Kenan Trust).

But, sponsoring entire academic programs? The only chemist* I can recall doing that is Jack Welch, with two programs: a "Management Institute" at Strayer, and the business school at Sacred Heart.

Too much money? Admittedly, most chemists only make a fraction of $70 mil over the course of a career. But, the top dogs at large chemical companies might come closer. So, how about it, guys? Who wants to see the Liveris Institute? The Svanberg Charitable Trust?

Better still? The Witty Professorship (that one just writes itself!)

*OK, OK, he's Chem-E. Close enough for this discussion.

1. Updates (7/7/13) - On the twitterz, James Banal points out that Ahmed Zewail (1999 Chem Nobel) has a Research Park ("city") named for him.
2. Learned that Jack Welch also named a business school at SHU. Text edited to reflect same.
3. On Twitter, Matt Hartings points to the Beckman Institute (Illinois and CA!), and Moore Centre (Cambridge) / Moore Labs (CalTech)
4. In the Comments, CE points out the (ironic) exclusion of one Alfred Nobel, he of the eponymous Prize, and Max Planck, he of the eponymous Institute.
5. Anon points to the Sanger Institute, the Curie Institute, and the Lawrence Livermore Nat'l Lab.

Making Time

Do you ever feel like you don't have enough time?

That seems to be a popular topic today, with two pieces in the popular press exploring that concept, albeit from very different viewpoints.

The first, from Wired writer (and Mythbusters host par excellence) Adam Savage relates the value of deadlines. He claims that he usually allows projects to languish on his workbench when given open-ended timelines, but while 'under the gun' performs at a high level and (in his words) finds solutions that are "innovative, elegant, and shockingly simple."

Of course, there's always that third option...
Credit: BBC | Wikipedia

The second, from the Times' Opinion Pages, tells a very different story: how to relax in order to increase one's productivity. Author Tony Schwartz, CEO of the consulting firm The Energy Project, argues that 'more is less' in the long run - we push to try and fill up work days with actual work, which results in tired, nonproductive employees. He recommends 90-minute 'sessions,' where one focuses solely on the task at hand, followed by breaks, exercise, or even - gasp! - naps.

Chemistry Angle: I like both approaches, but find they work best at different times in project cycles. While you're slogging through, trying to find those optimized conditions or exploring new leads, it's best to follow the '90-minute sessions' approach. Take a break! Nearly every scientific autobiography I've read suggests that problems get solved when the authors step away and do something completely unrelated for a while (Kekule, Feynman, Newton, Watson, Fleming, etc.)

Adam's approach (Hurry! Time running out!) fits best when you have a specific goal in mind - getting that paper out, presenting at the conference, filing that patent. Though I hate to admit it, the 48 hours leading up to submission often produce the bulk of such efforts. Sometimes it's worth the extra stress - and extra coffee - to get a superior final result.

Elemental Beer

It's October, which means falling leaves, football, cider, und Oktoberfest. Cracking open my copy of the latest WIRED Magazine last night, I came face-to-face with a full-page ad for Bud Light Platinum:

Source: Anheuser-Busch

Now, I understand the idea: an expensive noble metal speaks to the supposed quality of this latest beer offering. But it got me thinking - How often do you see element-themed noms de booze?

Let’s examine the obvious first. For the last few NFL seasons, Coors Light has run a promo with a speeding train called “The Silver Bullet.” Care for something else? Maybe some Molsen Golden, or anything from the Coors brewery in Golden, CO. With the help of Google and Beer Advocate, we’ll stray a little farther afield for a few more periodic pints…

Dieu du Ciel Helium, Montreal, Canada

Lithia Beer, West Bend, WI

Mount Carbon Beer, Pottsville, PA

(I know it’s cheating a bit, but how about the nitrogen Guinness rocket / widget?)

Gordon Finest Titanium, Scotland

Barney Gumble holds a
'Hassium Hefeweizen'

Fuji No Kina Vanadium Beer, Nigata Brewery, Japan

Carling Chrome, Molson Coors UK

Iron City Beer, Pittsburgh, PA

OMB Copper, Mecklenberg, NC

Arsenic, Belgium

Tsingtao Selenium-Riched 8, China

Krypton Rye PA, Victoria, BC, Canada

Tungsten Strong Lager, England

Tin Roof Beer, New Orleans, LA

There’s a brewery in Richland, WA called Atomic Ale, located just down the street from an historical plutonium reactor*. The ambience has apparently rubbed off; their beer roster includes Plutonium Porter, Seaborgium 106 Scottish Ale, Dysprosium DunkelWeisen, and Proton Pale Ale.

Surprisingly, several apt elements seem to have no brew to call their own. Quaff a Rubidium Red? A Lanthanum lambic, or maybe a Germanium Doppelböck? Americium Amber, Indium Pale Ale, Barium Brown…these things just write themselves!

Readers, have I missed any other elemental beers? Have any suggestions for ones you’d like to see?

Update (10/6/12) - How about elemental breweries? Telluride Brewing Co., Element Brewing Co.

*Several folks have commented that I might be grossly oversimplifying the importance of the Hanford site, akin to calling dinosaurs "those prehistoric dragons," or the Super Bowl "the last football game of the season." My apologies; I'll look deeper into it, and plan a follow-up post.

Chemistry "Hacks" (The Good Kind)

My hackathon drink of choice, coffee!
(And hey, ACS, why no more mugs?)

Last week, a fascinating article, "The 48-Hour Startup," appeared in Wired magazine. It explored the world of hackathons - events where pizza and Red Bull fuel two straight days of programming, hacking, and rebuilding code to create a functioning, marketable smartphone app. The upshot: some prize money, and sufficient street cred to attract more through angel investments. This article made me wonder . . .why don't more chemists have hackerspaces, like programmers and engineers do?


Let's go all the way back to the beginning of chemical research - who were we? Alchemists, who worked after hours, scribbling in secret languages; some hoped for profit, and some just loved the thrill (Sound familiar?). They didn't follow the implicit hegemony we do today: school student -> university trainee -> graduate study -> postdoc -> junior professor -> original ideas? By the time you're done jumping through hoops, you might have left your sense of curiosity and wonder behind.

Early Chemical "Hacker"
Alchemist with Scale, Johannes Weiland
Credit: Chemical Heritage Foundation

Well, how do we discover anything? If you believe much of the popular press, either by accident (saccharine, guncotton, Velcro), or by deep thought and monastic contemplation (relativity, total synthesis, calculus). I'd add a third avenue: cross-fertilization, the genius behind Bell Labs' design for their "idea factory."


Ever beat your head against a research problem, only to find the answer at a neighboring department's seminar? Borrowed something the next lab down the hall had on the shelf? Not to wax all Zen and the Art of Motorcycle Maintenance on you, but I subscribe to human quality precognition, a subtle mental undercurrent that guides you toward the right reaction or correct conditions. Others might call this gut instinct, and I've heard process chemists chat about initial optimization ("lucky on the first try!").


So why not speed this process along? Could we take a page from the video game designers, the hackers, and the dorm-room dot-com stars?


Here's my proposal (which, incidentally, might work pretty well at a large, national chemistry conference, just sayin'): What if visiting chemists had access to an open lab space, replete with all the latest catalysts, equipment, and reagents? One could imagine equipment dealers sponsoring this space, much like Cuisinart and KitchenAid sponsor cooking shows. 

Picture this, but with more fume hoods and Buchwald ligands

Access to a well-shimmed NMR and tuned LC-MS, along with a few high-speed internet connections and journal subscriptions, would complete the experience. Professors, hearing about a fantastic new reaction, wouldn't have to brief their lab groups. International scientists could mingle, and compare lab technique. Best of all? You could just play, try experiments for fun, on a whim, or because you were just curious about the result.


Who knows? Maybe, in time, the phrase "chemistry hack" might mean something good!

Rare Earths, Common Problem

Rare earth elements have made quite a stir lately: just last month, both Discover and National Geographic have written full articles about these 17 unique metals, which comprise the top part of the periodic table “f-block” (plus scandium and yttrium). Pundits and scientists alike are anxious that the US won’t be able to compete in the high-tech sector with scarce domestic rare earth supply.

Discover’s Hugh Aldersey-Williams (July / Aug 2011, p. 62) takes the historic view, starting from the elements’ first discovery in Ytterby, Sweden (1787, yttrium) and wending through the myriad of uses for the rare earths in modern-day electronics, hybrid cars, lighting, and materials.  The NatGeo article (June 2011, p. 136) takes a decidedly more polemically charged stance, peeking over the fence at China’s 97% share of the world rare earths market. Reporter Tim Folger argues that China’s unmatched mining infrastructure, coupled with lax environmental restrictions and cheap labor, make it tough for US miners to compete, despite the importance of a regular supply – the world demand for technology items such as iPods, wind turbines, flatscreens, and military equipment may drive lanthanide demand to a projected 185,000 tons by 2015, of which the US can only account for 5,000 tons of production. Worse, Folger bases this estimate on the production of a single mine (Molycorp) in California.

So what’s the impact for synthetic chemists?

Many of our favorite reactions use these metals. Lanthanum and scandium triflate promote aldols, acetylation, imine addition, cyclopropanation, and guest-star in new reagents like Leighton’s “EZ-crotyl” (JACS 2011, 6517). Samarium diiodide, a 1-electron reducing agent with a penchant for carbonyls and halides, underlies the Evans-Tischenko and Barbier couplings.  Cerium ammonium nitrate (CAN), a stable, off-the-shelf oxidizer, plucks off TBS and PMB groups, and promotes oxidative fragmentations. Perhaps even more worrisome is that the cerium and samarium reactions usually use the metal-containing reagent in large excess.

How can we fix the problem? New labs might find themselves conducting cost-benefit analyses simply to see if the improved reactivity or selectivity offered by these metals is worth their increased price (the Hoveyda-Grubbs 2^nd-gen catalyst, a highly active precious metal catalyst based on still-rarer ruthenium, runs $671 USD / 2g).  Perhaps the NSF will step in to issue challenge grants to develop catalytic processes intended to wean us from rare earth excesses. Either way, we’ve got to figure it out soon; as the US has shifted to a service-based economy, we’ve lost many skilled laborers (steel workers, miners, heavy industry) and may not be able to increase our rare earth capacity quickly enough.

Updates (July 28, 8:15PM) - Ever-helpful editor @carmendrahl informs me of a fantastic rare earth cover story from C&EN.  Others showed me the WIRED post about the US stealth fleet.

(July 30, 7:40AM) - Here's a July 2011 story in Scientific American debating the potential for harvesting rare earths from ocean floor sediment. Says Duke researcher Cindy Van Dover: "Four thousand meters in the deep ocean is a long way down"

(August 27, 10:36PM) - Commenter gippgig refers to Science News cover story, see here