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Archive → December, 2010

Who decides what’s an analog of a controlled substance?

“We’re like a naughty Holland & Barrett”: John Clarke, a pharmacology graduate, and Jo Hall have been selling legal drugs (in the UK) since 2006. Photograph: Suki Dhanda/UK Observer magazine

In this quiet week of reflection around the blogosphere, it makes sense that I should put up one last post on the topic that has brought us the most attention this year: synthetic cannabimimetics that have been sold in herbal incense blends such as K2 Spice. While marketed as “not for human consumption,” these products exemplify the growing legal highs industry (Coffeesh0p.com, a UK company run by John & Jo, pictured right, is a well-known example.).

Let’s take a moment to re-hash (I can’t help myself) these marijuana mimics before getting to the question posed in the title.

This series of compounds first synthesized by the laboratory of John W. Huffman at Clemson were originally investigated to establish structure-activity relationships for non-cannabinoid agonists at CB1 and CB2 endocannabinoid receptors. (See this post for more background from us and others about these compounds.) That is, Huffman and his collaborator, the late Billy Martin, were testing what structures similar to or different from the naturally-occurring compounds in marijuana could still allow high potency binding and modulation of these receptors.

Endocannabinoid inverse agonists have been explored by several pharmaceutical companies as anti-obesity drugs via appetite reduction (the opposite effect of marijuana). Unfortunately, many of these compounds have failed – rimonabant (Acomplia), most notably – due to increased risk of depression and suicide. Carmen Drahl had an extensive 2009 C&EN cover story on these compounds and other anti-obesity strategies.

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ScienceOnline 2011 Hotel Update

As we excitedly approach the ScienceOnline2011 unconference in currently-snowy Research Triangle Park, North Carolina, we now have to open a second hotel for those who have not yet made their arrangements. Much of the extensive demand appears to come from word among the paparazzi that C&EN’s Rachel Pepling, Carmen Drahl, and Lisa M. Jarvis will be in attendance.

The very kind folks at the Radisson RTP – Mr. Leon Bullard, I’m looking at you – are once again offering to us their US$72/night rate. While the Radisson is not the headquarters hotel (the Marriott will be the site of the Friday workshops), Mr. Bullard informs us that free Radisson shuttles will run between to the Sigma Xi Conference Center and the Marriott.

To book rooms at the Radisson, use this special URL:

http://www.radisson.com/scienceonline

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The Man Who Gave Us Epo

Professor Eugene Goldwasser (center) and future Nobel laureate Prof Harald zur Hausen (left) with King Bhumibol Adulyadej of Thailand (right) after receiving the 2005 Prince Mahidol Award. Source: Prince Mahidol Award Foundation.

I learned over the weekend via this tweet from Serena Stockwell at Oncology Times that Eugene Goldwasser passed away on Friday at age 88. The biochemist and renal physiologist who spent most of his career at the Argonne National Cancer Hospital and Department of Biochemistry and Molecular Biology at the University of Chicago (web page) demonstrated that a hormone made in the kidney could increase the number of new red blood cells, a major advance in physiology. His laboratory purified the protein hormone, erythropoietin (or Epo), from sheep in 1971 and from humans in 1977.

While a remarkable discovery of its own, Goldwasser’s partnership with then-Applied Molecular Genetics (Amgen today) led to the first- and second-generation recombinant biopharmaceuticals, erythropoietin and darbopoietin, and other versions such the the PEGylated EPO, Mircera. These drugs have transformed the lives of kidney dialysis and cancer patients, raised a furor in competitive sports – cycling in particular – and have been central to some of the most robust legal wrangling and medical costs discussions of our generation.

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The Future of Chemistry Jobs – Keep Reading and Commenting

Today marks the conclusion of a series of excellent blog discussions on the current state of the chemistry job market as led by Prof Matt Hartings at ScienceGeist (well, that’s who sent the press release), Chemjobber (opener and closer), Leigh Krietsch Boerner here at Just Another Electron Pusher, and Paul at ChemBark.

Here’s the quick list with descriptions from Matt:

• Monday, December 13: “We Are The Grist” at Chemjobber — an introduction to the topic and discussion of immediate ways to help clear the backlog of unemployed chemists

• Tuesday, December 14: “Too Many PhDs?” at Just Another Electron Pusher — an in-depth look at whether there are too many chemists on the job market

• Wednesday, December 15: “Time’s Up for Tenure” at Chembark — a critique of the current tenure system and how it influences academic competition

• Thursday, December 16: “How Do We Break This Cycle” at ScienceGeist — an overview of governmental policies related to science and technology and their impact on employment in these fields

• Friday, December 17: “The Future of Chemistry Jobs: Recap and Thanks” at Chemjobber — a summary of discussions initiated by each daily post.

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Five years of Terra Sigillata

No matter how old, she'll always be my little sister.

Today is my sister’s birthday – Happy Birthday, Sandi! (and keep an eye out for the FedEx truck today..wink, wink.)

Five years ago, I chose to start this blog on my sister’s birthday so that I’d always remember my blogging anniversary (I’m not fond of the portmanteau, “blogiversary.”). Mind you, I also got married in 2000 thereby making it painlessly simple to know how many years I’ve been married, a task I should be able to accomplish well into senility.

Five years ago, I was out of the academic environment and wanted a venue to both chronicle and share ideas I had about pharmaceuticals and alternative medicines. At the time, and still today, a great deal of information on the internet regarding herbal medicines is provided primarily by entities selling such products. With a background in natural products and degrees in pharmacology and toxicology, I felt that I could provide some truth and add perspective on those marketing claims and other sensationalized information on the web.

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Not Miley Cyrus: A small human trial of salvinorin A

Salvia divinorum. Source: Wikimedia Commons.

Some interesting news came out last week regarding Salvia divinorum, the hallucinogenic mint plant, whose primary active constituent, salvinorin A, is a highly selective kappa opioid receptor agonist that is remarkable as a nonnitrogenous psychoactive compound.

However, my interest had nothing to do with the widely-discussed video at TMZ.com showing actress and singer-songwriter Miley Cyrus doing a bong hit of the plant.

Instead, Dr. Matthew Johnson and colleagues at Johns Hopkins published a report in Drug and Alcohol Dependence on salvinorin A in four, hallucinogen-experienced human subjects that builds upon their investigations of similar compounds in a controlled and supportive clinical setting. Therein, a randomized dose-response study of volatilized salvinorin A revealed that subjects had qualitatively different experiences from other hallucinogens as determined by the use of two detailed measures: the 99-item Hallucinogen Rating Scale designed to show sensitivity to dimethyltryptamine and the 32-item Mysticism Scale used in a study described below to show sensitivity to psilocybin.

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Post-publication peer review in public: poison or progress?

Arsenic Warning Poster. Source: Archives of the USDA APHIS Pest Survey Detection and Exclusion Laboratory

What a difference a few days make. The much-ballyhooed story of arsenic-utilizing bacteria stemming from NASA’s embargoed press conference and paper in Science (somewhat ballyhooed here by yours truly), is accumulating criticism from microbiologists calling into question the degree of rigor applied to some of the paper’s experiments.

[Update: For an excellent, unexplored take on the analytical chemistry used in the paper, see this upcoming C&EN article by my colleague here, Dr. Carmen Drahl.]

On Sunday, I added to my post the first chink in the armor: a detailed technical critique by University of British Columbia microbial geneticist, Dr. Rosemary (Rosie) Redfield. Dr. Redfield has long found value in blogs and has encouraged her trainees to have their own blogs to openly discuss their science.

I’ve done some of the techniques (awhile ago) that Redfield discusses from the paper but it even took me some time to go through her critique. The central theme of her criticisms is that the experimental results leading to the conclusion that the Mono Lake GFAJ-1 bacterium can grow using arsenic instead of phosphorus may be an artifactual: the detection of arsenic in the bacterial DNA could have been due to insufficient clean-up of the DNA prior to ICP-MS analysis and that trace amounts of phosphate in the media and from dead cells could have provided the remaining cells with enough phosphate to survive in 40 mM arsenate. For example, the former artifact might result because the authors used phenol-chloroform to extract bacterial DNA from agarose gel slices which might have carried over some non-specifically bound arsenic that might not have occurred had a Gene-Clean type glass beads purification been done instead.

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Arsenic-permissive bacteria – implications for arsenical cancer chemotherapy

Like many of you, I waited this week for details on the NASA press conference and Science paper on a major discovery – painted as an “alien lifeform” by some news outlets. The truth did not live up to the hype but it was an impressive biological finding: a group led by Felisa Wolfe-Simon discovered a bacterium in California’s Mono Lake that could still grow when phosphorous was completely replaced with arsenic. The bacterium, strain GFAJ-1 of the Halomonadaceae family of Gammaproteobacteria, appears to use arsenic in place of phosphorus in molecules where phosphate is used – shown most conclusively here for DNA.

The story is perhaps best told by science writer extraordinaire, Ed Yong, at Not Exactly Rocket Science, and biologist PZ Myers is to be commended for representing us well to our chemistry colleagues by actually breaking out the periodic table in his excellent teaching post.

Addendum (4 Dec, 2:46 pm): An excellent chemistry-flavored post at The Curious Wavefunction also came to my attention – he/she cited this great 1987 Science paper, “Why Nature Chose Phosphates (PDF),” from the late Harvard chemist Frank Westheimer which discusses, among other things, the difficulties in overcoming the lability of arsenate esters in biomolecules.

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