One of the several I found, titled “Common Student Difficulties in Organic Chemistry,” caught my attention more than the others.  The document, which appears to have been assembled using a typewriter (for the unfamiliar, you can find information about typewriters here), lists problems students encounter while navigating through the dreaded “O Chem”.  In any case, at the bottom of the page, in bold, is the following message:

If you start to get into trouble in this course review this sheet.  Knowing what has gone wrong allows you to fix it.

This closing interested me from a historical perspective.  Did enough students bomb the course to warrant this document’s assembly?  Did the professor discover this or a similar list at an ACS meeting and felt it was prudent to include it in his/her course?  Did the document actually help students better understand the course material?

Although I can speculate until the cows come home, I’m throwing it out to you, the blogosphere.  Do you agree with this list?  Would you change anything on it?  I’m curious to see what the blogger generation thinks (FYI, I believe this list was developed in the 1980’s).

1. Lack of organization
2. Difficulty in keeping up with lecture while taking notes
3. Failure to finish exams
4. Inability to manipulate three-dimensional structures on paper
5. Too little drill – lack of repetitive practice
6. Falling behind
7. Poor problem analysis
8. Inability to see and mentally manipulate three-dimensional objects
9. Insufficient energy and/or motivation for the challenges of this course

After discussing the finer points of Moore’s Law, and how he agonized over purchasing a 20 MB hard drive in the 1980’s for $400, the substance of the conversation switched.  “Have you ever researched your Ph.D. lineage,” he asked.

“I’ve gone as far back as Breslow,” I replied, completely forgetting that he probably didn’t know this “Breslow” character.

It turns out that several of his doctoral computer buddies had recently taken on this task, many of them somehow descending (academically) from Charles Babbage.

Our discussion prompted me to further examine my background.  I soon discovered that there are several University websites that provide chemistry academic lineage for their faculty members.  Being an organic chemist, I was interested to learn that E.J. Corey worked for John Sheehan (I admit it…I’m nerdly).  In any case, here are some websites I found interesting:

• UT Austin is a really good site to start exploring.  Here, I was able to learn that my roots (through Eric Anslyn) purportedly go through Breslow and Ira Remsen (1870), all the way back to Torbern Bergman (1758).
• My personal favorite website is the lineage posted by North Dakota State University.  Apart from deriving academic lineage all the way back to Nicolo da Lonigo (1453), they’ve complied all of the data/information into a colorful map that would no doubt look good on a faculty member’s wall.
• Some other sites: UMass Amherst, Illinois, UConn, Kentucky, and Michigan State.

It seems the term “junk science” has been in use in the legal profession since the 1980’s.  Yet, despite its existence, “junk science” is actually an ambiguous concept.  In 1998, legal experts Edmond and Mercer attempted to conquer this beast by identifying “good science,” then considering outlying cases “bad.”  Here’s what they considered “the good”:

“’Good science’ is usually described as dependent upon qualities such as falsifiable hypotheses, replication, verification, peer-review and publication, general acceptance, consensus, communalism, universalism, organized skepticism, neutrality, experiment/empiricism, objectivity, dispassionate observation, naturalistic explanation, and use of the scientific method.”

Does this list really mean that everything else is considered “junk”?  I can think of a few brilliant studies that used trial and error methods in lieu of the scientific method.  Conversely, I’m aware of peer-reviewers who simply check the “publish” box without actually reading the manuscript.  As is argued on several other blogs, identifying “junk science” is a very gray area.

Perhaps one way to define junk science is to take the Jacobellis v. Ohio approach.  In a 1964 US Supreme Court case involving obscenity, Justice Stewart Potter wrote in his opinion, “I shall not today attempt to define the kinds of material I understand to be [pornography]…but I know it when I see it.”  Clearly the same frame of thought can be applied to junk science.  I am less inclined to accept the Jacobellis approach because it offers nothing tangble.

There must be some empirical qualities that set the good from the bad.  Despite all the skills I’ve learned with a mere decade of lab experience, I am disheartened to admit that I honestly never perfected the skill of detecting bad science.  So, like a responsible, up-and-coming assistant professor of chemistry, I went crawling through the literature to determine what separates the good from the bad.  Below is a list of a few things I learned.

In the spirit of Jeff Foxworthy, science might be “junk” if…

Researchers are more concerned with holding press conferences than publishing results in reputable, peer-reviewed journals. One might assume that “breakthroughs” ought to be showcased in the most prestigious journals after being subjected to a rigorous peer review process.  Fast tracking all the way to the press conference phase certainly raises some flags about credibility.  I’ve seen this phenomenon happen first-hand, and when the science is questionable, the ensuing public announcement can get really ugly (and entertaining, for that matter).

Something about the research seems off kilter. If you think something doesn’t feel right, you might be correct.  Although going with your gut will only get you so far, analysis guides such as “Tipsheet: For Reporting on Drugs, Devices and Medical Technologies” help identify specific areas for journalists to consider when examining the veracity of medical therapies.  Cook and co-workers suggested that similar checklists might likewise serve the general scientific community when evaluating the credibility of reported work.

Conflicts of interest are not explicitly disclosed. In these cases, scientific integrity might be compromised for financial, political, or other external motivations.  In developing this article, I encountered journals, funding agencies, and governing bodies that require authors to declare any potential conflicts of interest while publishing or applying for grants.  Although editors and referees try to uphold strict transparency policies, authors can still fail to report external influences and biasing.  These cases essentially touch every facet of research–cancer, testing pesticides (Berkley Scientif. J. 2009, 13, 32-34), and even drug development.  The onus is put on the audience to look into the author’s sources of funding.

The flow of logic doesn’t make any sense. Junk science may have gaping holes in experimental descriptions or proposed models.  Fortunately, overly simplistic and inaccurate scientific explanations usually evoke sharp criticism from the scientific experts.  Credible “debunkers” often attack the logic of an issue by (for example) discrediting cited authoritative opinions, identifying assumptions, and/or offering overlooked hypotheses.

Colleagues in the field are widely skeptical of the work. Mix it up with your cohorts.  A simple, “Hey, what did you think about the most recent (insert name of researcher here) article in JOC,” can shed some light on the context of published or presented findings.  “[He] hasn’t published anything reproducible in the past 20 years,” my PI once said.  “I sincerely doubt that this latest paper is anything new.”

I recently bought a 2009 re-issued copy of Pearl Jam’s first album “Ten,” originally released back in 1991.  Those who know me well are also aware of my interest in Pearl Jam; I enjoy collecting demos or live versions of their music.  Anyhow, their officially released re-issue contains a remixed version of their 1991 album and (in my opinion) parts of it sound distinctly different than the original mix.  For you music buffs out there in internet land, Brendan O’Brien—the original producer—dumped the supplemental reverb applied to the original tracks in this newer version.  As a result, the guitars and drums sound much cleaner and less wet (I recommend listening to both versions of “Why Go” or “Oceans” for a good example of the remixing).

Thinking about the whole concept of “re-issue” got me thinking about organic chemistry (big surprise).  How often do scientists report fantastically optimized results, table the idea, and then revisit it at a later date (to make vast improvements)?  Or better yet, how much “new” chemistry has derived from “re-issuing” processed developed in the late 19^th or early 20^th century?  My PI calls refers to this particular phenomenon as, “teaching an old dog new tricks.”  In writing my dissertation (an ongoing process) I had the pleasure of reading Lipshutz’s recent review about cuprate chemistry (Synlett 2009, 509-524; DOI: 10.1055/s-0028-1087923).  This personalized narrative discusses the Lipshutz group efforts and contributions to the field of copper(I) hydride chemistry. 

This article is of particular interest apart from discussing it at length in the ‘ol thesis.  A few months back, I had a conversation with a colleague of mine who claimed that since Stryker’s contributions, “conjugate reduction chemistry has (basically) fallen to the wayside.”  I recall laughing out loud at his remark.  “What about Lipshutz or Riant or even Buchwald,” I asked.  He claimed, with a sense of arrogance, that their work was “just a new twist on Stryker’s original work.”  Based off of this logic, if someone successfully synthesized Taxol from table sugar in three steps, would it be considered a new twist on Nicolau or Holton’s contributions?  Arrogance aside, this idea of “re-issuing” is a common phenomenon in research chemistry.  It’s done frequently, often to the tune of 10-20 additional printed publications (apart from the seminal contribution).  Perhaps, it’s these instances that call into question the process of “re-issuing” chemistry. 

That said, re-issued chemistry can result in significantly new discoveries and improvements on original methods.  Taking the conjugate reduction example, Stryker’s catalytic reactions, performed under a high pressure of H₂, were plagued with over-reduced products.  In switching the stoichiometric hydride source from hydrogen gas to PMHS, Lipshutz reported a vast improvement in reaction times and overall yields (Tetrahedron 2000, 56, 2779-2788; doi: 10.1016/S0040-4020(00)00132-0).  This change has spawned a whole new area of carbon-carbon bond formation, particularly in the field of reductive alkylation reactions. 

While I’m genuinely interested in the idea of inventing new and exciting reactions, the thought of tweaked processes resulting in “re-issued” chemistry is largely appealing (when done responsibly).  A prominent neutron chemist once told me that real chemistry lies in unexplored places.  “We want to be doing things that others aren’t,” he said.  I agree.  But on occasion, it’s necessary to explore the landscapes previously claimed by others for the betterment of the (scientific) community as a whole.

Generally Speaking.  On Monday, we were greeted with some light snowfall, and I don’t think it’s going to get much warmer while I’m here.  Aaron from Wired Blog made the comment that attendance looks low at ACS in Salt Lake City.  I agree, and I wonder if it’s a function of the economy.  On the humorous side of science, there was a vendor in front of the Salt Palace this morning selling “Obamium” t-shirts.  I didn’t get one (we live in a McCain/Palin household).  Also, I’ve noticed that there isn’t a lot of ground-breaking synthetic organic chemistry being presented. 

LENR = Cold Fusion?  Not quite a tabletop source of energy, but interesting nevertheless.  Pamela Mosier-Boss, Steve Krivit, Antonella De Ninno and a few other experts took questions from a packed house about the interpretation of recent results surrounding advancements in low energy nuclear reactions (LENR).  Those in attendance included Scott Chubb (of Infinite Energy fame), KSL-TV Channel 5 and the legendary Mitch Andre Garcia.  I’m not even going to try and explain the crux of the talk (being a synthetic organic chemist, and all).  However, the video of the press conference is available here, and I encourage you to check it out if you’re interested.  Perhaps if you ask Mitch really nice, he’ll write a post on the ins and outs of the debate.  While there are several critics of the research (for example, click here), the crux of the talk appeared to focus on recruiting young chemists to explore this “new” area of science. 

Feel the Burn.  The U.S. Geological Survey (USGS) announced their discovery of gas hydrates—“a frozen form of natural gas that bursts into flames at the touch of a match.”  Tim Collett (project co-leader) claims that this work may bridge the gap between relatively dirty fossil fuels and clean energy because gas hydrates purportedly leave a small carbon footprint. 

Just Scan it.  I took a few moments to speak with Dr. Jeffrey Silk, president of Silk Scientific, about his digitizing software.  I haven’t seen this sort of program before, so I’ll make the assumption that others haven’t either.  The product (called “UN-SCAN-IT”) takes a chart, graph, HPLC trace, etc. and converts the image into data points, which can be dropped into a program such as Excel.  With the “raw” datapoints, UN-SCAN-IT allows you to integrate, take derivatives, and perform curve fitting.  If this sort of thing tickles your fancy, you can download a demo of the software here.  For all of you bio-type peeps, Silk Scientific also sells a second program called “UN-SCAN-IT gel,” which acts as a densitometer for gel images.  As for future generations of products for Silk Scientific, I suggested he make a program that will automatically solve ¹H-NMR spectra.

On my flight into Salt Lake City, I was greeted to nasty turbulence, an overcast sky but a comfortable mid-50 degree temperature, which eventually turned to rain (there’s a chance of snow tonight). 

So, what happened today?

The Inorganic/Medicinal Version of Brown.  M. Frederick Hawthorne is slated to win the highly coveted ACS Priestley medal for his contributions to boron chemistry in SLC this week (March 24, 2009).  In addition to synthesizing polyhedral borane clusters such as B₁₂H₁₂^2- in the 1950’s, he is noted for his boron neutron capture therapy (BNCT)—a promising technique in the war on cancer (see: J. Am. Chem. Soc. 2007, 129, 6507-6512).  I realize this isn’t really news per se since C&EN covered it last June, but some of you might have missed it.

Smith’s Dithiane Chemistry.  I caught most of Amos Smith’s talk about his lab’s recent efforts in the realm of dithiane transformations (you should be thinking “umpolong”).  He did a nice presentation on multicomponent anion relay chemistry (“ARC”; for example see: J. Am. Chem. Soc. 2006, 128, 12368-12369 and Angew. Chem. Int. Ed.  2008, 47, 7082-7086) while making a cute comment that the resultant “protected” alcohols are easily removed with Philadelphia tap water.  For those not familiar, the Smith lab has been applying hybrid umpolong/Brook rearrangement chemistry to synthesize cool “proof-of-concept” natural product-like molecules.  Smith mentioned that this type of work has caught Jeff Johnson’s attention (hence the umpolong connection) evidenced by a fairly recent publication about the synthesis of zaragozic acid C (J. Am. Chem. Soc. 2008, 130, 17281-17283).  I had to leave the talk a bit early, but from my vantage point I noticed a lot of male chemists slowly starting to assemble for M. Christina White’s talk.  I was truly sorry that I missed it.  Oh, in case you were wondering, I did not notice her trademark ostentatious belt buckle.

CAS and Nanotechnology.  In the few hours I’ve been at the ACS conference, I’ve noticed that there’s an awful lot of material (no pun intended) on nanotechnology.  While nanotechnology touches areas of pharma, materials and even the molecular automotive industry, the issue of classification is making its way through the chemical community.  Roger Schenck (of CAS) did a fine presentation on the issue from Chemical Abstracts Service’s vantage point.  CAS currently catalogs 80 sections of chemistry (#1 is pharmacology), and, according to Schenck, CAS is not planning on adding #81 (which would be nanotechnology) anytime soon. It seems that the issue will be tabled for a bit longer while the field continues to grow/evolve.  For you history buffs out there, Schenck contends that nanotechnology probably began with Kroto’s C₆₀ discovery (Nature 1985, 318, 162-163). Interesting tidbit: Kroto even mentioned that he’d “prefer to let this issue of nomenclature be settled by the consensus.” 

Alright, I’m off to the expo social event.  See you tomorrow. 

Cheryl Hogue’s recent piece entitled “Naming What’s in Cleaning Products” caught my attention earlier this past weekend (C&EN, February 23, 2009).  Cheryl does a great job covering the interface of chemistry and the environment—hitting the high points while remaining concise—and the brief article in question is no exception.  However, the issue at hand was rather concerning.

In a nutshell, activists from an Oakland-based firm called EarthJustice recently filed a lawsuit in New York State demanding that several manufacturers/distributors disclose ingredients on the label of their household chemical products (detergents, cleaning agents, etc.).  Companies named in the lawsuit include Church & Dwight, Colgate-Palmolive, Procter & Gamble and Reckitt Benckiser.  The suit accuses manufacturers of failing to comply with a New York law that was enacted over 30 years ago.  The legislation at issue was passed in 1976 and makes two specific requirements.  First, the law essentially bans the presence of phosphates and nitrilotriacetic acid in household chemicals sold within New York State.  Second, the law requires household chemical manufacturers to stamp a list of ingredients onto the labels of their products.  From what I understand, this act was implemented to protect the overall environment of New York State (from urban areas to surrounding watersheds).  Ultimately, EarthJustice claims that forcing companies to comply with the law purportedly will increase public awareness, which, in turn, will help the environment

The lead attorney for EarthJustice, Keri Powell, made this argument to C&EN:

“People deserve to know whether the products they use to wash their dishes, launder their clothes, and clean their homes could be harmful.” 

I’m skeptical of this argument/lawsuit for a couple of reasons.  First, if this law has been dormant for the past 30 years, why is EarthJustice now pushing the issue?  Was New York State asleep at the wheel?  Isn’t this something that should’ve been handled by the EPA?  I realize environmental awareness is a hot topic and a popular vehicle for political action.  While the act of suing over labels to protect the environment is (in my mind) illogical, I am troubled over whether the issue is truly legitimate or a way for an unbiased organization to grind a political act (yes, I’m being cynical and possibly paranoid). 

Second, and more concerning, Ms. Powell (and her colleagues at EarthJustice) assumes that proper labeling will, in fact, increase public knowledge.  Her assumption is entirely conditional (certainly not sufficient) on whether or not a reasonable consumer would understand what they read.  Example: my mother is obsessed with the product Goof Off and has two cans of it on hand at any given time.  However, if Goof Off was labeled with its ingredients, she couldn’t tell you the first thing about xylene (the main chemical in Goof Off).  It took her strapping, young (and most definitely handsome) son to explain the potential risks of using such a product.

Don’t get me wrong.  My diverse background in hard science has taught me two very important lessons: learn as much as you possibly can and label everything.  Consumer chemical awareness requires the same conditions, and simply forcing a company to slap a label on something doesn’t solve the problem.  In my mind, the issue of chemical awareness is similar to the “ban dihyrogen monoxide” prank conducted a few years back.  Without education (i.e. learning what the chemicals names actually mean), this proposed labeling crusade is largely irrelevant. 

Furthermore, chemical information is readily available (assuming you or your public library has access to the internet).  While there are a few exceptions, every chemical product (including those used at home) must have an MSDS, which can be found online.  Every MSDS identifies the chief ingredients in said product.  Granted, MSDS’s were created for the purposes of right-to-know information in industrial/commercial settings.  But, in my opinion, if John Q. Consumer can read a label, he can certainly read an MSDS.

I salute EarthJustice for all the work they’ve done to protect America’s environment.  Their commitment to public interest is genuine and deserves applause.  However, I think they are barking up the wrong tree with this lawsuit—dragging a whole bunch of companies through expensive court process to get something to happen that’s relevance is moot (at best).  My solution?  Shift the focus.  For example, serve the public’s interest by teaching them how to access/read/interpret chemical information.  Or educate the public on how phosphates are detrimental to the environment.  Lobby politicians to entirely ban certain household chemicals in the state (beyond the ppm limits currently set). 

Let’s assume EarthJustice wins the lawsuit.  What happens next?  Maybe it’s me, but I don’t see an end game in sight.  

P.S. In addition to C&ENews, this story has been picked up by Scientific American, the New York Times and the Los Angeles Times.

Good news (nerds alike)!  In an attempt to combat early-morning insomnia, I was flipping through the channels and saw a commercial for the new season of Breaking Bad.  Having fallen victim to last years writer strike, the show was cut at 7 episodes with no indication whether it would get picked up.  Fortunately, the second season of Breaking Bad premieres March 8 (10 EST/9 CST) on AMC.  For what it’s worth, Comcast is running the whole first season in its On-Demand package. 

For those not familiar with the show, Walt White (portrayed by Bryan Cranston) is a high school chemistry teacher in his 50’s recently diagnosed with inoperable lung cancer.  In what appears to be a mid-life crisis, White partners up with a former student to launch a fairly lucrative methamphetamine business.  The show twists and turns through a maze of fundamentally accurate synthetic chemistry (chem-geeks no doubt rejoiced in terms such as “chirality,” “reductive amination” and “titration”) and the street drug business.  While most pilots are pretty rough around the edges, Breaking Bad’s was reasonably tolerable and starts the show off fairly well. 

I’ll caution you (should you need it) that the show is quite graphic in some scenes and largely presents an overall sense of dread.  

On December 18, 2008, the Food and Drug Administration ruled the natural sweetener Truvia “generally safe” for use in foods and beverages. Truvia (trade name Rebiana) is comprised of a diterpene called steviol glycoside, which is isolated from the extracts of the leaves of the plant Stevia rebaudiana bertoni.  The herb Stevia—basically the leaves of the plant—has been available for years, so steviol glycoside is nothing new, per se.  Cargill Food and Ingredient Systems now markets Truvia as a singular, “fully-characterized product” (Stevia, by comparison is a witch’s brew of anywhere from 40 to 200 compounds).  More interesting data about Truvia can be found here.  As a result of the FDA’s ruling, Coca-Cola Company will soon launch a new line of reduced-calorie drinks with the most prominent being a new version of Sprite called Sprite Green (comes in a nifty aluminum can).

Stevia was purportedly discovered by Moises Santiago Bertoni in 1887 while exploring the forests of Paraguay—Stevia rebaudiana’s natural habitat (see: Econ. Bot. 1983, 37, 74-82).  Additionally, the plant had been identified in Korea, China and Japan (J. Med. Chem. 1981, 24, 1269–1271).  Word spread about the plant and eventually Stevia made its way to the US (courtesy of the Department of Agriculture) in 1918 due to the growing interest in its strong sweetness.  A wide array of physiological studies determined that the sweet sensation of Stevia derives from the presence the compound steviol glycoside.  Since then, several studies have been reported on its structure and function of steviol glycoside including stereochemical analysis (J. Am. Chem. Soc. 1963, 85, 2305–2309) and metabolic analyses (J. Agric. Food Chem. 2006, 54, 2794–2798).

In the spirit the Truvia saga, I figured that I’d cover its first total synthesis of steviol methyl ester, which Mori and co-workers first reported (Tetrahedron Lett. 1970, 11, 2411-2414).  Starting from the tricyclic methyl ester, Mori protected the aldehyde then installed ketone by way of a hydroboration-oxidation and ensuing Jones oxidation.  Deprotection of the dioxolane was accomplished using aqueous acid in acetone followed by tandem acid-catalyzed aldol addition to furnish the 1,3-ketol, which was converted to the 1,3-dione via second Jones oxidation.  Clemmenson reduction afforded the 1,2-ketol (I encourage you to push the arrows for that transformation), which was converted to the allylic alcohol by methylenation. 

As is the case with most “new” sweeteners, Stevia has been the subject of criticism over toxicological effects.  One study, conducted by John Pezzuto and co-workers at the University of Chicago, concluded that steviol is actually metagenic (PNAS 1985, 82, 2478-2482).  However, the asterisk to this scientific study—“steviol is mutagenic toward S. typhimurium strain TM677” and not human cells—should clearly be taken into consideration when weighing the toxicity of the supplement as a whole.  Just so we’re all on the same page, the “S” in “S. typhimurium” stands for salmonella—a bacterium. 

All in all, I think it’ll pretty interesting to watch more information about Truvia find its way into the public eye.