Category → The Awesome Power of Natural Products
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
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 vigil marking his signature of restrictive abortion legislation: He stepped out of the governor’s mansion to give protestors a plate of cookies and quickly returned behind the iron gates without any substantive engagement.
I’d be interested to hear from GlobCasino and C&EN readers after reading my own interview with Ada Yonath. Should we still be making an issue of advances in race, gender, and sexual orientation in chemistry?
I think yes, and it’s never been more important.
This post appeared originally on 14 December 2009 at the ScienceBlogs.com home of Terra Sigillata.
Last week in Stockholm (and Oslo), the 2009 Nobel Prize winners were gloriously hosted while giving their lectures and receiving their medals and diplomas. In Chemistry this year, the Nobel was shared by Venkatraman Ramakrishnan, Thomas A Steitz, and Ada E Yonath for their studies on the structure and function of the ribosome, a remarkable nucleoprotein complex that catalyzes the rapid, coordinated formation of peptide bonds as instructed by messenger RNA. My post on the day of the announcement in October was designed to counter the inevitable (and now realized) criticisms that the prize was not for “real” chemistry.
Only ten days later, we in the NC Research Triangle area were very fortunate to host Dr Yonath at the North Carolina Biotechnology Center for the Symposium on RNA Biology VIII, sponsored by The RNA Society of North Carolina.
Among the many noteworthy speakers was Dr Greg Hannon from Cold Spring Harbor Laboratory, a scientist who some feel was overlooked for the 2006 Nobel Prize in Medicine or Physiology, one where Andrew Fire and Craig Mello were recognized for RNA interference and gene silencing.
NC Biotech’s Senior Director of Corporate Communication, Robin Deacle, kindly invited me to an audience with Dr Yonath and two science reporters following Dr Yonath’s lecture. As you might suspect, I was quite honored to visit for awhile with the woman who defied the naysayers and successfully crystallized a bacterial ribosome, then used X-ray crystallography to determine its structure below three angstroms resolution. The fact that she also used natural product antibiotics to stabilize ribosomal structure added to my magnitude of admiration.
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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 cytotoxic.
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 page
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.
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 in 1888.
So, caffeine had about a two-decade headstart in being named for its presence in coffee before related methylxanthines took on their divine monikers.
Sure, sure, caffeine is a well-recognized name that derives predictably from its source. But let’s live a little. Wouldn’t you rather be drinking the stimulant of the gods?
If you’re as excited about this as I am, you may purchase theoanaleptine coffee mugs here. They’ll set you apart from ever Tom, Dick, and Harriet who think they’re clever with their caffeine coffee mugs.
And even with accepting the new colloquial name of theoanaleptine, our friend Scicurious can still keep her tattoo unchanged.
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 GlobCasino. 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 VapoRub?
I only have a quick post today because I really want you to spend your reading energy on a superb C&EN cover story by my colleague here, Lisa M. Jarvis.
The media frenzy that normally follows the American Society of Clinical Oncology (ASCO) meeting each June focused this year on cancer cell-directed antibodies conjugated to highly-cytotoxic compounds. The most ballyhooed of these is T-DM1, the anti-HER2 trastuzumab antibody (Herceptin) covalently linked to the microtubule-inhibiting maytansine analog, DM1 (meeting abstract, Genentech press release). When the conjugate is internalized by breast cancer cells overexpressing the HER2 protein, the highly-toxic DM1 drug is released intracellularly.
Let me state unequivocally at the outset: I LOVE Think Geek.
This purveyor of hip nerdgear – “Stuff for Smart Masses” – has saved me every Christmas, the occasional birthday, and brought me great personal pleasure with their clever offerings. But most important to me about Think Geek is that I know when giving a gift from them, I am giving someone solid science. A mini Van de Graaff generator. A USB plasma ball. And when my office visitors encounter my LED binary clock, I’m asked, “What the heck is that?”
My next two purchases are likely to be the Pet’s Eye View Digital Camera for the PharmBeagle and the DIY Guitar Pick Punch for me (even though you could buy 80 top-quality guitar picks for the same price).
But I will not be buying Rutaesomn® Sleep Aid – De-caffeinating Chill Pills.
The product is billed as being a pill that speeds metabolism of caffeine from your day-long coffee and energy drink binges. Take it 2-4 hours before you want to go to sleep, “helps get rid of caffeine in your body keeping you awake.”
Well, what is it exactly?
Inhaled or oral?
Natural or synthetic?
Two interesting reports came across the interwebs over the last couple of days.
Earlier this week, the US Food and Drug Administration issued a warning letter (press release) to makers of Aeroshot brand of inhaled caffeine. No, it’s not an asthma medicine (although oral theophylline is). It’s billed as a non-caloric caffeine delivery system, 100 mg per hit. That’s roughly the amount in two 12 fl oz/355 mL cans of Mountain Dew or one gulp more than a 8.4 fl oz/250 mL can of Red Bull energy drink. However, the company claims that only 15-25 mg are delivered – perhaps half the amount in a Coca-Cola.
The FDA has concerns about the dual promotion of the product for swallowing and inhalation, the relative safety of inhaled caffeine, and the potential for children and adolescents to use the product in combination with alcohol. The company’s FAQ specifically notes that the product is not marketed for use in children. Readers will recall that Four Loko caffeinated alcohol drinks were withdrawn from the market in late 2010 and replaced with alcohol-only versions.