Fingolimod (Gilenya; Novartis) for Multiple Sclerosis
May11

Fingolimod (Gilenya; Novartis) for Multiple Sclerosis

A very well-written review of an orally-active drug for multiple sclerosis has just appeared in the April 25th issue of the Journal of Natural Products, a publication of ACS in conjunction with the American Society of Pharmacognosy. The review, Fingolimod (FTY720): A Recently Approved Multiple Sclerosis Drug Based on a Fungal Secondary Metabolite, is co-authored by Cherilyn R. Strader, Cedric J. Pearce, and Nicholas H. Oberlies. In the interest of full disclosure, the latter two gentlemen are research collaborators of ours from Mycosynthetix, Inc. (Hillsborough, NC) and the University of North Carolina at Greensboro. My esteemed colleague and senior author, Dr. Oberlies, modestly deflected my request to post here on the publication of this review. So, I am instead writing this post to promote the excellent work of his student and first author, Cherilyn Strader. As of this morning, this review article is first on the list of most-read articles in the Journal. This status is noteworthy because the review has moved ahead of even the famed David Newman and Gordon Cragg review of natural product-sourced drugs of the last 25 years, the JNP equivalent of Pink Floyd's The Dark Side of the Moon (the album known for its record 14-year stay on the Billboard music charts.). The story of fingolimod is a fascinating journey from early 1970s work on fungal-derived immunosuppressants in Japan to synthetic organic synthesis by Tetsuro Fujita at Kyoto University in 1992 that has led to a non-injectable option for patients with multiple sclerosis. Some of these fungi are ones that infect insects and their fruiting bodies have been used in traditional Chinese medicine as elixirs. From a biology standpoint, Ms. Strader very nicely describes the in vitro and in vivo assays used to identify the natural product progenitor from Isaria sinclairii, myriocin (ISP-1), as an immunosuppressant agent. A clever mixed lymphocyte assay was used by Fujita and colleagues to detect inhibition of T-cell proliferation when splenocytes from two strains of mice were co-cultured in the presence of alloantigen. To confirm activity in vivo, the investigators then used rat skin transplant model where tissue would normally be rejected when transplanted from one rat strain to another. Active compounds were scored based on their ability to prolong the viability of the transplant. This work from the Journal of Antibiotics is available here as free full text. In both the in vitro and in vivo assays, ISP-1 exhibited activity superior to that of the immunosuppressant, cyclosporin A. But as with many natural products, the compound has some toxicity and solubility issues. Several groups went on to synthesize over 50 analogs of the ISP compounds and Ms. Strader...

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HeLa T-shirt and button design contest
Mar24

HeLa T-shirt and button design contest

Wanna put your mad Photoshop skillz to a good non-profit cause? Rebecca Skloot, author of The Immortal Life of Henrietta Lacks, (and I) need your help for scientist give-away items to support The Henrietta Lacks Foundation. Scroll down to the end of the post for information on the Foundation's mission or just click here. I'll be at the 102nd Annual Meeting of the American Association for Cancer Research in Orlando during first week of April and will be manning a booth to promote the Foundation to raise awareness about our mission and, hopefully, cultivate philanthropy among individuals and companies who may care to support the cause (Disclosure: I am a non-compensated member of the Foundation's Board of Directors). We want to offer two types of promotional items that are beyond my graphic design skills: 1. Two sets of buttons, both 1-inch diameter (2.54 cm), with the words: a. "Thank You #HeLa" or "I Love #HeLa" centered, and b. "I [heart] HeLa" centered both with the text of the URL, henriettalacksfoundation.org, around the bottom rim of the button The font can be of your choosing. 2. A black T-shirt using the following HeLa immunofluorescence image on the front with accompanying text, "Thank You HeLa" and the reverse with "henriettalacksfoundation.org" on the back. Once again, the font can be of your choosing. What would be lovely is to have the three cells in the center as the primary graphic with the other cells 'shopped out. However, we're totally open to whatever design wizardry strikes you. Update: some folks have asked about whether the image needs to be the exact photo of the cells or whether they can be an artistic rendering of the cells using the photo as a model.  Absolutely - use your artistic license and show us what you've got! If you wish to offer your assistance, you may send your graphics files to me via Gmail to abelpharmboy. The reward for the selected images will be a T-shirt with said design and a personally-inscribed (by Rebecca, not me) first-edition hardback version of The Immortal Life of Henrietta Lacks . Yes, I am so challenged as to not even be able to figure out how to make circular text around a button template. Hence, I simply want to be in a position to just hand off the image files to a printer and get our promotion items printed without me fumbling around with Photoshop and a billion different fonts. Thank you for considering helping out with this effort. If you have any questions, you can comment below, Gmail me at abelpharmboy, or tweet me @davidkroll. The Henrietta Lacks Foundation...

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Quinetta Shelby “exhibiting the utmost class” in finishing at DePaul
Mar10

Quinetta Shelby “exhibiting the utmost class” in finishing at DePaul

Academics who live on principle and persevere through adversity with dignity and pride may not always finish first, but their strength of character earns respect. We wrote last November about the case of Dr. Quinetta D. Shelby, a DePaul University chemistry professor denied tenure. Although a university appeals panel recommended to the DePaul president, Rev. Dennis Holtschneider, that the decision be overturned because of "numerous procedural violations" at the department level, the decision was left to stand. In the controversial aftermath, a group of faculty came out to support Dr. Shelby claiming that she and other minority faculty members were denied tenure because racism. During this past academic year, tenure was denied to six faculty: two African-Americans, two Asian-Americans, and two Latino professors. In contrast, no white faculty members were denied tenure this year. One can never know what occurs in promotion and tenure committees, especially at institutions with heavy teaching loads such as DePaul. Shelby held a prestigious NSF Career grant but even my commenters here were mixed as to whether her publication productivity was acceptable (here and at my crosspost). Since Christmas time or so, I hadn't heard much more about Dr. Shelby's case despite having some contact with her supporters and trying to get an interview with her. But I was pleased yesterday to receive the following comment at my Take As Directed blog from a person claiming to be a DePaul chemistry student taking class with Dr. Shelby this semester. I'm unable to verify that this student is indeed from DePaul but the comment did come from a Chicago IP address: I'm a student at DePaul and have taken General Chemistry and Organic Chemistry with Dr. Shelby. I've never met anyone so enthusiastic to teach. She is extremely approachable and more than willing to help students with the course material when they stop by, even if it's not her office hours. It was easy to tell how disappointed she was that she didn't get tenure. It's unfortunate that she won't be returning because of this, but very understandable. You wouldn't even know that she's not returning next year because she continues to teach as she always has, exhibiting the utmost class by not letting this [faze] her. I honestly think Dr. Shelby will continue to do wonderful things with her career, and that DePaul is really losing out on a great professor. She embodies a true example of a hard-working, caring, and FAIR teacher. Assuming the veracity of the commenter's identity, this account describes exactly how one should conduct themselves in the face of adversity. Of course, chemistry students were not responsible for Shelby's tenure...

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Open-access: ACS honors African American chemists for Black History Month
Feb07

Open-access: ACS honors African American chemists for Black History Month

In the United States, the month of February is known as Black History Month - a time to celebrate the contributions of African Americans to all facets of our lives. The ACS has done an absolutely wonderful job in offering an open-access feature on eleven of the most noteworthy Black chemists from across American history. The stories of these remarkable individuals span from New Orleans chemist Norbert Rilleaux and his industrial evaporation process for sugar refining to Marie Maynard Daly, the first African American woman Ph.D. in chemistry, then all the way up to our first two African American presidents of the American Chemical Society. The individual entries are accompanied by other ACS-associated resources such as the National Historic Chemical Landmark program - where the work of three of the featured chemists is honored - and biographies put together by the ACS-affiliated Chemical Heritage Foundation in Philadelphia who I spoke of last week. For science educators, whether at K-12 or university level, these biographies are fabulous for helping students appreciate just how rich the field of chemistry is with African American contributions. In all of these cases, these outstanding investigators had to overcome great obstacles to their success, societal and financial. However, we should all celebrate these remarkable individuals for their contributions to our rich history - regardless of their individual heritage. The eleven chemists represented in this feature are timeless giants in the field. In my field of natural products, the chemist Percy Julian is revered - and his story was elegantly portrayed in the PBS NOVA documentary, Forgotten Genius. Julian is perhaps best known for his original work on the synthesis of the cholinesterase inhibitor, physostigmine, for glaucoma and the search for cortisone precursors to treat the most debilitating forms of rheumatoid arthritis. My only criticism of this feature is that the lack of a twelfth block on the graphic above is rather glaring - as is the presence of only one woman. Does this mean that there was difficulty in identifying one more Black chemist of similar stature? If so, we - I mean all of us in chemistry and chemistry education - need to do a better job in providing equal opportunities to African American chemistry students and those of other traditionally marginalized groups. This is otherwise a tremendous resource - make sure you peruse it to see how you might best use this information in your own teaching or personal appreciation for the history of the...

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Post-publication peer review in public: poison or progress?
Dec08

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

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. Here's an excerpt of her conclusions: Bottom line: Lots of flim-flam, but very little reliable information. The mass spec measurements may be very well done (I lack expertise here), but their value is severely compromised by the poor quality of the inputs. If this data was presented by a PhD student at their committee meeting, I'd send them back to the bench to do more cleanup and controls. There's a difference between controls done to genuinely test your hypothesis and those done when you just want to show that your hypothesis is true. The authors have done some of the latter, but not the former. A CBC News article on Monday spoke further on Redfield's critique. As painful as her analysis might have been to read for the authors, NASA, and editors of Science, Redfield's critique represents the future of post-publication peer-review. Already the present at journals such as those from PLoS where readers can comment on papers at the journal website,...

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Women in chemistry blogging – lookin’ good, CENtral Science
Sep17

Women in chemistry blogging – lookin’ good, CENtral Science

Earlier this week, Jenny Rohn posted a graph on her Mind the Gap blog followed by: Celebrated science bloggers are male. Discuss. She specifically noted the male/female breakdown of the four newest blog networks - The Guardian, PLoS, Discover, and Wired - without considering ScienceBlogs, Science 2.0, Lab Spaces, Scientopia, or CENtral Science. I can tell you from my years at ScienceBlogs that a large contingent of bloggers were always pushing for more diversity - not just with regard to gender but in national origin and ethnicity, race, sexual preference, current geographical location, as well as diversity across the realm of what we call, "science." In response, Martin Robbins at The Lay Scientist, a Guardian Science Blog, launched a Twitter crowd-sourcing experiment this week with the hashtag #wsb to compile a list of women science bloggers regardless of indie or network status. But let's take a look here at CENtral Science: Melody Voith - Cleantech Chemistry Leigh Krietsch Boerner - Just Another Electron Pusher Lauren Wolf, Bethany Halford, Rachel Pepling - Newscripts Alex Tullo (with Melody Voith) - The Chemical Notebook Rudy M. Baum and A. Maureen Rouhi - The Editor's Blog Lisa Jarvis and Carmen Drahl - The Haystack Jyllian Kemsley and Jeff Johnson - The Safety Zone If you only count Melody once, CENtral Science was comprised of nine women and three men before this graying, bespectacled Y chromosome joined on August 24th. Nine-to-four would still look mighty good compared with other networks. Why might this be? Remember that CENtral Science is primarily written by editors and staff writers for C&EN (Leigh and I are the freelancers). A great many are trained scientists with Ph.D.s but who have sought careers away from the bench. All are superb writers, several of whom I read for a few years before joining CENtral Science (such as Rachel Pepling's treatise on phenobarbital in my all-time favorite C&EN issue (June 2005) on the world's top pharmaceuticals which sits beside my blogging desk. I find this leads to a very interesting second question: does the overrepresentation of women at CENtral Science reflect that women are more likely to choose "alternative" careers with their scientific...

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