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TEDMED: Andrew Read’s Five Tips For Keeping Superbugs At Bay
Read (TEDMED)
Andrew Read thinks evolution is the best lens for staring down the superbugs. He took the stage Thursday at TEDMED, where he warned, “we’re picking a fight with natural selection.”
“Picking a fight without Darwin is like going to the moon without Newton,” Read added. “We are in the dark ages when it comes to evolutionary management.”
Read, director of Penn State University’s Center for Infectious Disease Dynamics, sat down with me on Thursday and shared a few principles he thinks the scientific community should keep in mind in order to keep antibiotic resistance in check. Here are his five tips for would-be superbug slayers. Continue reading →
TEDMED and Alzheimer’s: Gregory Petsko, Reisa Sperling, and the next Al Gore
Petsko (TEDMED)
Gregory Petsko knows why he came to TEDMED. “I’m looking for Al Gore,” he told me flat-out over lunch. Folks who know Petskoknow the former Brandeis University biochemistry department chair isn’t one to mince words. And he’s nailed the reason why an academic might want to look outside traditional conferences and soak up some of the TEDMED aura. He’s looking for a charismatic champion to take up a biomedical cause: in Petsko’s case, it’s support for research in Alzheimer’s disease.
Petsko and Reisa Sperling, director of the Center for Alzheimer’s Research and Treatment at Brigham and Women’s Hospital, talked about Alzheimer’s at TEDMED on Wednesday. Both talks were cast as calls to action. Just consider the introduction Petsko got from TEDMED chair and Priceline.com founder Jay S. Walker: “This is a man who hears a bomb ticking.”
Alzheimer’s statistics are sobering and Petsko used them to dramatic effect. People who will reach 80 by the year 2050 have a 1 in 3 chance of developing the disease if nothing is done, he told the audience. “And yet I hear no clamor,” he said. “I hear no sense of urgency.”
Petsko shared some not-yet-published work with TEDMED’s audience. Continue reading →
Francis Collins At TEDMED – Repurposing Drugs, Replacing Animal Models, Rocking Out
You know you’re at an interesting conference when the director of the NIH starts off his presentation with a guitar duet, and shares a session with Cookie Monster.
But the organizers of TEDMED made a very deliberate decision in opening this year’s conference with Francis Collins. This is the first year that the gathering of medical luminaries, artists, and design gurus (TED stands for Technology, Entertainment, Design) is taking place in Washington, DC, after moving from San Diego. It marks a philosophical shift for the organization, from TEDMED as idea incubator to TEDMED as inserting itself into the national conversation on health and medicine. What better way to do that then bringing in the head of the biggest biomedical funding agency?
Collins wants to compress the time it takes to get a drug development pipeline, and make the pipeline less leaky. This isn’t news to folks around the pharma blogosphere, including here at the Haystack, Ash at Curious Wavefunction and Derek Lowe, who’ve followed last year’s announcement of NIH’s venture for drug discovery, the National Center for Advancing Translational Sciences.
Folks have expressed some concerns about the concept, and its emphasis on the promise of gene-based drug discovery. But, as Derek noted, the fact of the matter is that everyone in drug discovery wants the things Collins wants, so there’s a measure of goodwill for the venture too.
Collins spent his time on the TEDMED stage emphasizing two things: drug repurposing and developing high-tech cellular solutions to supplement and replace often-imperfect animal models.
On the tech side, Collins showcased the Harvard-based Wyss Institute’s lung-on-a-chip, which combines tissue engineering and electronics to mimic the interface between the lung’s air sacs and capillaries (Science, DOI: 10.1126/science.1188302). He said that technologies like this suggest viable alternatives to animal testing are possible.
When New Scientist reported on the lung-on-a-chip in 2010, researchers praised it as a step in the right direction, but cautioned that immortalized cell lines, such as those on the chip, don’t neccesarily behave like primary cells from patients. Collins also noted that it might be possible to use such devices with patients’ own cells someday.
On the repurposing side, Collins cited an article on the topic in Nature Reviews Drug Discovery (DOI: 10.1038/nrd3473), and alluded to lonafarnib (SCH 66336), a farnesyltransferase inhibitor that was originally designed to be part of cancer-treatment cocktails. It didn’t pan out as a cancer drug, Collins said, but now clinical trials are underway to test whether the drug is effective at countering a rare mutation that causes Hutchinson-Guilford progeria, an ailment that leads to rapid aging in children. Collins shared the stage with 15-year-old Sam, a progeria patient.
Francis Collins (right) and Sam. (TEDMED)
To bridge the massive gap between ideas and applications in medicine “we need resources, we need new kinds of partnerships, and we need talent,” he told the audience.
In a conversation with reporters after his talk, Collins provided another repurposing story published last month– bexarotene, a retinoid X receptor agonist intended for lymphoma that was just shown to clear amyloid-beta and reverse cognitive deficits in a mouse model of Alzheimer’s (Science, DOI: 10.1126/science.1217697)
At that chat, I asked Collins how the repurposing effort and his call for talent squares with massive layoffs in industry and flat or declining funding.
“It would help if we had a strong foundation of support,” Collins said. He said his agency’s purchasing power has decreased 20% over the last 8 years.
Another reporter asked what was the main obstacle to getting repurposing become habit. “IP,” Collins said. He told reporters that a model intellectual property sharing agreement with pharmaceutical companies has been drafted. Asked if companies had signed on to it, Collins said “we’re working on it.”
UPDATED 3:30PM 4/12: Here’s the scoop on Cookie Monster, for Muppet devotee Robin:
he spoke later in the session with ultramarathoner Scott Jurek about nutrition.
Liveblogging First-Time Disclosures From #ACSSanDiego
Watch this space on Sunday as I cover the public unveiling of five drug candidates’ structures. I’ll be liveblogging the “First Disclosures of Clinical Candidates” symposium at the San Diego ACS National Meeting, which runs from 2PM to 5PM Pacific.
1:30PM It’s half an hour before the start of the session and the big ballroom is still pretty empty. Expect that to change in short order.
2:30PM
LX4211
Company: Lexicon Pharmaceuticals
Meant to treat: type 2 diabetes
Mode of action: dual inhibitor of sodium glucose transporters 1 and 2, which play key roles in glucose absorption in the gastrointestinal tract and kidney
Medicinal chemistry tidbits: this drug candidate had Lexicon’s chemists refamiliarizing themselves with carbohydrate chemistry. Most inhibitors of sodium glucose transporters incorporate D-glucose in some way. Lexicon’s chemists realized they could try something different– inhibitors based on the scaffold of L-xylose, a non-natural sugar. The team has already published a J. Med. Chem paper (2009, 52, 6201–6204) explaining that strategy. LX4211 is a methyl thioglycoside-the team went with a methyl thioglycoside because upping the size too far beyond a methyl lost activity at SGLT1.
Status in the pipeline: LX4211 is currently completing Phase IIb trials.
3:00PM
BMS-927711
Company: Bristol-Myers Squibb
Meant to treat: migraine
Mode of action: antagonist of the receptor for calcitonin gene-related peptide- increased levels of this peptide have been reported in cases of migraine
Medicinal chemistry tidbits: This team recently published an orally bioavailable CGRP inhibitor, BMS-846372 (ACS Med. Chem. Lett., DOI: 10.1021/ml300021s). However, BMS-846372 had limited aqueous solubility, something that might make its development challenging. To improve that solubility, the BMS team sought to add polar groups to their molecule, something that’s been tough to do with CGRP inhibitors historically. In the end, the team managed to add a primary amine to BMS-846372′s cycloheptane ring while maintaining CGRP activity, leading to BMS-927711.
Status in the pipeline: Phase II clinical trials
3:05 lots of questions from the audience for this talk! One questioner notes (as was noted in talk) that 4 CGRP inhibitors had gone before this drug in the clinic, and not made it through. Speaker notes that this candidate is more potent than others at CGRP (27 picomolar).
3:53 We’re a bit behind schedule but got plenty of good chemistry…
GSK2636771
Company: GlaxoSmithKline
Meant to treat: tumors with loss-of-function in the tumor suppressor protein PTEN (phosphatase and tensin homolog)- 2nd most inactivated tumor suppressor after p53- cancers where this is often the case include prostate and endometrial
Mode of action: inhibitor of phosphoinositide 3-kinase-beta (PI3K-beta). Several lines of evidence suggest that proliferation in certain PTEN-deficient tumor cell lines is driven primarily by PI3K-beta.
Medicinal chemistry tidbits: The GSK team seemed boxed in because in 3 out of 4 animals used in preclinical testing, promising drug candidates had high clearance. It turned out that a carbonyl group that they thought was critical for interacting with the back pocket of the PI3K-beta enzyme wasn’t so critical after all. When they realized they could replace the carbonyl with a variety of functional groups, GSK2636771 eventually emerged. GSK2636771B (shown) is the tris salt of GSK2636771.
Status in the pipeline: Phase I clinical trials
4:22
GS-9620
Company: Gilead Sciences
Meant to treat: chronic infection with hepatitis B and C viruses
Mode of action: agonist of Toll-like receptor 7, which recognizes RNA from viral sources
Medicinal chemistry tidbits: The team paid a lot of attention to particular sidechain in their drug candidates– they examined a range of pKa’s from the acidic side of the scale to the basic side, and learned that a basic amine was important for agonist activity.
Status in the pipeline: Phase Ib clinical trials
4:49
BMS-791325
Company: Bristol-Myers Squibb
Meant to treat: hepatitis C
Mode of action: inhibitor of viral NS5B replicase
Medicinal chemistry tidbits: This drug candidate is an allosteric inhibitor– early on in the program BMS researchers had evidence to suggest that allosteric inhibition of the replicase would be feasible, and would provide an alternative to the nucleoside analogs that constitute the vast majority of replicase inhibitors. The team started with fused indole lead structures which bound to the thumb site 1 allosteric site in the replicase (Bioorg. Med. Chem. Lett., DOI: 10.1016/j.bmcl.2011.03.067). Adding a morpholine amide enhanced potency, and adding substituents to it abrogated transactivation of the pregnane X receptor (PXR). Ultimately this group was replaced with a methylated piperazine, with substituents stitched together to give another ring. A cyclopropane adjusted the shape of the molecule to jibe with information gathered from an X-ray co-crystal structure.
Status in the pipeline: Phase II clinical trials
4:52 That’s it folks! Watch for additional coverage of these talks in an April issue of C&EN.
C&EN Picks For #ACSSanDiego
We almost can’t believe how quickly the San Diego ACS National Meeting is coming up. Enjoy the latest round of C&EN Picks to get a taste of which offerings our staff deemed newsworthy.
Chemistry Hashtags And Chemistry Communication-UPDATED
Last week, I sent out a request via Twitter–I asked chemists to send me popular hashtags that they use in their tweets. I don’t know that I need to introduce hashtags to the Newscripts audience, but just in case, hashtags are those words you see on Twitter preceded by the # sign, such as #ACSSanDiego. Folks use them to wade through the morass of tweets because they help classify tweets by topic, conference, location, etc.
I thought I’d share with you why I sent out said request. Part of the reason is to have a handy list of hashtags for chemists in one place. But it also has to do with my upcoming talk at the San Diego ACS national meeting. I’m part of ACS President Bassam Shakhashiri’s symposium, “Communicating Science to the Public”, which takes place Monday afternoon in the convention center. Click on the image to get the full lineup from the meeting program.
I’ll be talking about how C&EN reporters have our collective ears to ground of the chemistry world, and from time to time end up being sources of information for media outlets with a broader reach. For example, C&EN reporter and Fine Line blogger extraordinaire Rick Mullin was a guest on NPR’s Science Friday earlier this month, talking about unusual pharma partnerships. And in January I went on SiriusXM’s Doctor Radio channel to chat about how drugs get their generic names.
We reporters keep tabs on what chemists are talking about in many ways, but I’d like to emphasize Twitter in my talk (even though it is limited to a small group of chemists who are self-selecting to communicate with social media).
That’s where you and your hashtags come in. I could think of a few hashtags that have become symbolic of issues chemists care about.
#chemjobs – chemistry employment
#altchemicalfree – chemophobia in advertising and the mass media
#SheriSangji – everything related to the lab fire that killed UCLA lab assistant Sheri Sangji and the ongoing case, but I’ve also seen it referred to in general discussions of safety in chemistry labs
And so I decided to put out the call to see if any more such hashtags would pop out at me from the big list. Of course, many hashtags come and go, and some are more active than others. And still others are just for fun, like #chemvalentine, which was a collection of chemistry related love missives timed to Valentine’s Day. But I strongly believe that chemists are using social media to talk about issues that matter to them, and the number of issues is only going to go up the longer those channels are around. Anyone in the business of covering or communicating chemistry should be up on those conversations.
I’ll happily take more hashtag suggestions, or suggestions for meaningful conversations happening on Twitter, all the way up to Sunday March 25th. Email me
or send me a message on Twitter @carmendrahl.
In the meantime, here’s the collection of hashtags you sent so far. Please note: I haven’t checked all of these to see whether they are active.
#chemistry (which, as Adam Azman points out, has been co-opted for other purposes as well).
#chemicals
#openaccess
#icanhazpdf
#arseniclife
#clinicaltrials
#drugs
#pharma
#biotech
#STEM
#REACH
#climate
#chemhistory
#knuckledraggingorganicker
#lovehatechem
#inorgchem
#orgchem
#physchem
#compchem
#chem
#reachchem
#phneutral
#nonhazchem
#nontoxichem
#chemtag
#toxnetchem
UPDATED March 21:
Thanks to folks who emailed me or sent me a message on Twitter with a few more hashtags.
#chemsafety
#polymer or #polymers
#plastic
#rubber
Top Five Science Communication Tips From NASA’s FameLab
Horner (at right) speaks with astrobiologists at the FameLab workshop. (Drahl/C&EN)
Still prepping your video audition for that PBS chemistry show hosting gig? Then you might want to glean some tips from an ongoing NASA competition. It’s the NASA Astrobiology FameLab, and it’s essentially a search for the next Carl Sagan.
FameLab, founded in the U.K. in 2005, is all about the power of words to get the public and stakeholders excited about science. No slides, no graphs allowed in your short presentation.
That can be daunting for most scientists, especially the early-career folks FameLab seeks. So FameLab’s organizers include a mentoring and training component in the competition. For Friday’s preliminary FameLab round at National Geographic in D.C., that mentor was Beth Horner, an award-winning professional storyteller. Last Friday afternoon at NASA headquarters, Horner put 25 young astrobiologists through their storytelling paces. I journeyed to NASA to bring you the top five tips for science communication from her workshop. Here they are:
5) “Never do anything off the cuff. Always plan.”
It’s easy to think that you’ll be able to come up with a way to explain your work on the fly, but you’re less likely to forget a part of your message if you structure things in advance, Horner says. She showed workshop attendees how to storyboard and led several exercises in which she asked the scientists to write down three lines about something–themselves, a mentor in their field, or key aspects of their research. “That three-line thing is the start of a structure,” she said. Questions or issues might come up during your talk that may force you to improvise somewhat, she added, but you should let your structure be a guide so you don’t veer off course.
4) “It’s not about you. It’s about this information you’re trying to get across.”
Horner mentioned this mantra as a way of calming nerves onstage or on camera.
Early-career astrobiologists listen to Horner at the FameLab workshop. (Drahl/C&EN)
3) “Always try out your material on someone else.”
Horner always runs story ideas and analogies by colleagues to see what they think. “I ask them, ‘Do you care about this?’,” she says. “You get in your own head sometimes and it’s hard to get out,” but an outside perspective can give you clues about what might resonate with a listener and what won’t, she says.
2) “Tell a story.”
Every culture on Earth has a storytelling tradition, Horner says. “That means something,” she adds. Stories were a way for people to pass down lessons and traditions, and there’s something about their structure that sticks with you. It isn’t easy to structure science like a story, but the approach is likely to pay off, she says.
Continue reading →
Chemistry Romance Novel Drops Feb. 7
Courtesy of Heather Snow
Have too many long nights in the lab left you without a special someone this Valentine’s Day? Has grant writing drained all the spark from your relationship?
Well, debut author Heather Snow’s novel, “Sweet Enemy,” might be just the thing to push you over the activation barrier, if ya’ know what I mean. Snow’s book, available online and in bookstores February 7, is a historical romance novel with a chemist heroine.
Avid Newscripts readers may recall C&EN’s 2010 profile of Snow, when her then-manuscript Sweet Enemy was a finalist for a Golden Heart Award, essentially the Oscars of the romance novel world.
Since then, Snow, who majored in chemistry at the University of Missouri, Kansas City, has moved up in the romance novel world, selling her manuscript and launching a monthlong blog book tour to promote Sweet Enemy.
Snow sent Newscripts the book’s cover–a rendering of heroine Liliana Claremont, orphaned daughter of a well-known chemist. “No cool glassware,” she says. “But they did give her a quill and ink to make her look ‘smart.’ ”
Snow has also made the book’s prologue and first chapter available online, so you can find out how Liliana uses her scientific smarts to outwit an intruder.
From there, the drama kicks into high gear. But the heroine does get a happy ending. Snow let slip that Liliana’s hero proposes not with a diamond ring, but with a matrass–a round-bottomed flask with a long, slender neck, commonly used for distillations among Liliana’s 19th-century contemporaries. Clearly her lover knew the way to a chemist’s heart.
