What Are Your Favorite Non-U.S. Drug Discovery Stories?
Jun18

What Are Your Favorite Non-U.S. Drug Discovery Stories?

Over at my other gig at the Pharma & Healthcare section of Forbes.com, I’ve been covering a few stories of new drugs and improvements on old drugs. Although I’m focusing on natural products like vancomycin and semi-synthetics like lurbinectedin, I’ve been thinking a bit about the stories behind the discoveries of all drugs. Part of my thinking has been driven by my current reading of Happy Accidents: Serendipity in Modern Medical Breakthroughs by Morton A. Meyers, MD, professor emeritus of radiology and internal medicine at SUNY–Stony Brook. Therein, I’m reading stories like that of Gerhard Domagk, who first showed that prontosil was an effective antibiotic in vivo but not in vitro because it liberates sulfanilamide when metabolized. The story was told in even greater detail in the superb Thomas Hager book, The Demon Under the Microscope. This got me to thinking: I hear quite a bit about drug discovery stories in the U.S. but rarely about modern drugs that have been discovered elsewhere. The brain tumor drug, temozolomide, for example, was developed in the laboratory of Malcolm Stevens at Aston University building upon work of the late Tom Connors (expertly told by Kat Arney at Cancer Research UK last summer). But one rarely hears stories like these, even in pharmacology courses at pharmacy schools where the teaching is more likely to be chemistry-oriented. So, chemistry world hivemind: What are your favorite stories of drug discovery and development that didn’t occur in the United States? Bonus points for natural products or...

Read More
Does Ada Yonath’s Gender Really Matter?
Jul31

Does Ada Yonath’s Gender Really Matter?

  My apologies to regular readers and my colleagues at C&EN for my month-long silence at the blog. I saw cobwebs on my laptop screen when I opened the back end this morning. Part of my hiatus came from complications of an infected molar extraction and my inability to concentrate. I’ve also been trying to take short Internet holidays over the last two months because all of the political nonsense in my state is negatively affecting my mental health. But the tooth canyon is about 50% healed and our state legislature has finished, for now, shifting progressive North Carolina toward its pre-Research Triangle Park level of ignorance, racism, and poverty. During this month, I came across an excellent post on the Scientific American Guest Blog by Atlanta-based science journalist, Kathleen Raven. In “Ada Yonath and the Female Question,” Raven discusses her experience at this year’s Lindau Nobel Laureate meeting — dedicated to chemistry — and her reflections on hearing and attempting to interview the 2009 Nobelist in chemistry, Dr. Ada Yonath. Yonath, a structural chemist recognized for her extensive work in showing how the ribosome catalyzes protein synthesis, has generally not made much of the fact that she’s only the fourth woman to receive the Nobel Prize in Chemistry, and the first since Dorothy Hodgkin in 1964. As I did back in 2009 when interviewing Yonath at the North Carolina Biotechnology Center, Raven debates whether focusing on Yonath as a female scientist is a good thing for the cause of women scientists. Should we focus only on the accomplishments? Or should we focus on her accomplishments in the context of the distinct barriers often facing women scientists? I’m equally torn, particularly since my 20-year laboratory career was advanced by a group that consistently ranged from 75% to 100% women. I never specifically recruited women to my laboratory but it seems that they might have self-selected for reasons not known to me. My activism in diversity in science extends back to my pharmacy faculty days at the University of Colorado where I assisted in selecting minority scholarship recipients for a generous program we had from the Skaggs Family Foundation. The goings-on in North Carolina politics is not germane to this scientific discussion. We can speak all we want about our modern society being post-racial and having more women leaders than ever. But voter laws that disproportionately disenfranchise African-Americans and legislation that severely compromises women’s reproductive health tells me that we still need to pay attention to the influence of racial and gender attitudes. Heck, even our Governor Pat McCrory showed his true colors yesterday while protestors, primarily women, were holding a...

Read More
The Cinnamon Challenge: On Being Charged with #Chemophobia
Apr23

The Cinnamon Challenge: On Being Charged with #Chemophobia

As many of you are likely to have heard yesterday, a paper from Steven Lipshultz, MD, at the University of Miami appeared in the journal Pediatrics detailing poison control center reports on an adolescent misadventure called The Cinnamon Challenge. The challenge: to swallow a teaspoon of cinnamon powder in 60 seconds without any liquids. The practice has been rummaging about the internet since 2001 but really took off on YouTube over the last three years. Lipshultz’s report discusses the risks of such tomfoolery, particularly due to the inhalation of cinnamon powder while one is choking. I planned to write about this practice both here and at my Forbes.com blog since I thought both chemists and the general public would be interested in the topic. I wrote the Forbes post earlier this morning and drew a series of comments from a kindly San Diego-area chemist who took issue with my facetious comparison of cinnamaldehyde (cinnamic aldehyde) to formaldehyde. While Lipshultz states that much of the acute pulmonary toxicity of cinnamon powder is likely due to the cellulose content, I submit that some damage could be due to protein adducts formed by cinnamaldehyde. Yes, yes, it’s not as dangerous as formaldehyde. But even at roughly 1% (w/w) in the powder, I hypothesize that the cinnamaldehyde could cause epithelial damage. Also note that cinnamaldehyde is not just any aldehyde but rather an unsaturated aldehyde. That makes me think of acrolein. The experiments have not been done. But one animal study has been published showing that intratracheal administration of cinnamon powder — not pure cinnamaldehyde — can cause acute lung injury in rats and trigger pulmonary fibrosis within a month. Alas, my concerns about cinnamaldehyde rubbed two commenters the wrong way and one, well, sought to chemsplain me. I was originally trained in toxicology so I know the whole Paracelsan story that the dose makes the poison (to which I’d also add “route of administration”). But do you chemists, especially those in chemical toxicology, think that I’m overreacting (as it were) to the potentially reactive nature of cinnamaldehyde in inhaled cinnamon powder? I’m willing to be corrected if I appear to suffer from #chemophobia. But I hypothesize that 1% (w/w) cinnamaldehyde can be...

Read More
Saturday Morning Natural Products PharmChem Radio!
Mar23

Saturday Morning Natural Products PharmChem Radio!

If you’re up on this lovely Saturday morning and looking for something fun and educational to pass the time, dial up wknc.org for the “Mystery Roach” radio show from 8 am until 10 am Eastern time. There, I’ll be discussing the discovery of drugs from nature and the differences between herbal remedies and medicines. The show, hosted by forestry and natural resources doctoral student Damian Maddalena, will be interspersed with psychedelic music from the 60s and 70s. I’ll be monitoring my Twitter account @davidkroll for questions and comments and you can also post at the Mystery Roach Facebook page. Maddalena is an experienced scientist-communicator whose show, named after a Frank Zappa song, celebrated five years last November. The Research Triangle’s independent weekly, INDY Week, recognized Maddalena last year as runner-up for both top radio show and radio host, a tremendous accomplishment for a science and music show in a highly-competitive media market.   Livestream at this wknc.org...

Read More
Why Isn’t Caffeine Called “Theoanaleptine”?
Feb13

Why Isn’t Caffeine Called “Theoanaleptine”?

This question came to me as I read last week’s C&EN cover story by Dr. Lauren K. Wolf on caffeine toxicity entitled, “Caffeine Jitters.” By the way, read it if you haven’t — it’s open-access on C&EN right now and remains the most-read (last 7 days), most-commented (last 30 days), and most-shared (last 30 days) article since it appeared. Lauren did a terrific job of sifting through decades of information on the physiological effects of caffeine to make sense out of the true health hazards of caffeine consumption at “normal” and excessive doses. Caffeine, a natural alkaloid found predominantly in coffee beans, is 1,3,7-trimethylxanthine (not IUPAC, but you get it). In the body, the hepatic cytochrome P450 CYP1A2 catalyzes the N-demethylation of caffeine to theophylline, theobromine, and paraxanthine.   Divine chemicals Of note, theobromine and theophylline also occur in nature. Theobromine is found in cacao beans. Because chocolate is heavenly, it was given the Greek name for “food of the gods”: theos – god; broma – food. Correct, theobromine contains no bromine. Had it contained bromine, the name might have been the same but would have been derived from the Greek bromos, or “stench” – “stench of the gods,” which, clearly, it is not. Theophylline also occurs naturally and had been extensively used as a bronchodilator for folks with asthma. Primatene tablets used to contain theophylline but today are ephedrine. Again, theophylline has the godly theo- prefix while the -phylline suffix indicated that it comes from leaves. And apologies to paraxanthine. It’s known historically for having first been isolated from urine in 1883. Not until the 1980s was it shown to occur in some plants. In any case, the biosynthesis of the di- and tri-methylxanthines originate with xanthosine from purine metabolism. So to my question. . . Because caffeine is so widely worshiped, why is it not known as theoanaleptine? The Greek analeptikos means stimulant and the English term analeptic is defined as a stimulant drug. So, why not? My best guess is because caffeine was described in the literature prior to theophylline and theobromine. From M.J. Arnaud’s chapter in Caffeine (Springer, 1984): The isolation of caffeine from green coffee beans was described in Germany in 1820 by Runge and confirmed the same year by von Giese. In France, Robiquet in 1823 and then Pelletier in 1826 independently discovered a white and volatile crystalline substance. The name “cofeina” appeared in 1823 in the “Dictionaire des termes de medécine” and the word “caffein” or “coffein” was used by Fechner in 1826. Arnaud goes on to say that theobromine was discovered in cocoa beans in 1842 and theophylline in tea leaves...

Read More
Okay, Who’s Huffing Vicks VapoRub?
Nov14

Okay, Who’s Huffing Vicks VapoRub?

One of the fun things about having a blog is the traffic analytics feature on the dashboard of WordPress (although I really miss the features of SiteMeter that don’t run on WordPress because it doesn’t accept JavaScript. But I digress.) Besides the addictive nature of looking at one’s traffic numbers, I always find it interesting to look at the search terms that bring people to our humble little corner of CENtral Science. I became hooked on this way back when I started the original version of Terra Sig on Blogger: in February 2006, I had an unusual spike in traffic originating from the UK via the search term “terra sigillata.” So, I posted this and learned this. Usually, search term hits tell me that something has come up in the news. But, alas, I cannot find anything recent that would account for Vicks VapoRub to elicit much searching. Perhaps telling is that all 27 searches came via a misspelled search for “vicks vapor rub.” (By the way, the search term brought folks here to read this post I wrote on Vicks VapoRub after a 2011 PR snafu with journalists like Ivan Oransky at Reuters Health. I ended up writing a bit more about the North Carolina pharmacy history that brought the world this lovely concoction.) I do know that misguided youth will huff volatile chemicals for the acute high one might get. Vicks is most commonly used to enhance the experience of MDMA (ecstasy) – I’ve seen kids at raves wearing N95 facemasks inside which they have smeared the VapoRub. So, what’s with you people wanting to know about Vicks...

Read More