JUNIORPROF returns to blogging with the #PainResearchMatters campaign

As I’ve noted elsewhere, practicing biomedical scientists often turn to blogging out of passion for their work and their desire to connect with the public to raise awareness about societal benefit of their research.

Exhibit A: Pain researcher, JuniorProf.  JP has come roaring back from a hiatus, joined Twitter, and has put forth a near-manifesto on his previous posts about pain research and why it is important:

1) The World Health Organization considers relief from pain to be a universal human right
2) Migraine headache is the most common neurological disorder in the world
3) More people seek medical attention for pain than for any other reason
4) Nearly 50% of people who seek medical treatment for pain report that they do not achieve pain relief with treatment
5) Chronic pain conditions disproportionately affect women

And like many of us, some critical personal and training experiences led him to this particular research area. You’ll learn about these if you go further in his post.

On a personal note, JuniorProf is a good online friend and has helped me out professionally as well. Our friendship began when he was a commenter at DrugMonkey and PhysioProf’s place. I told JP that his comments were so insightful and content-rich that he really needed to start his own blog.  So, he did (I wish I had that power of persuasion over others.).

Work issues pushed his nose to the grindstone at the university and on grant applications, but I knew he’d be back when he was ready.

He is now inspired.

Some of the most useful drugs in the management of pain come from natural products, such as morphine from Papaver somniferum. Unfortunately, some pain medications also have the potential to cause drug dependence. For this reason, chronic pain is largely undertreated. So, I’m really looking forward to learning more from JP about the advances in his field and his work that is designed to truly relieve human suffering.

I hope that you’ll follow his writing as well.

Update: Zuska now has a detailed post up on her migraines, allodynia, and the litany of drugs she has gone through to find some relief with botulinum toxin injections (Botox). That is why pain research matters.

And a hat-tip to DrugMonkey for making me aware of #PainResearchMatters

Dichloroacetate not yet an effective treatment for aggressive brain cancer

Dichloroacetate or DCA is a small molecule that has been in the press over the last four years due to its potential to inhibit aerobic glycolysis in cancer cells. The cells from each of us usually produce energy in the form of ATP from a variety of nutrient sources plus oxygen using a very efficient process called oxidative phosphorylation.

However, when oxygen is partly depleted, such as in skeletal muscle when exercising strenuously (“going anerobic”), energy is produced from glucose by a far less efficient process called glycolysis. Glycolysis is the most primitive form of cellular metabolism [Note added: This last sentence is not correct; see below for correction from Prof Larry Moran. – APB]

The glycolytic pathway has become of renewed interest in cancer. Why? Because some but not all cancer cells differ from normal cells by using the inefficient production of ATP by glycolysis regardless of the amount of oxygen that’s around. You’ll hear the term “Warburg effect” used to describe this phenomenon because biochemist Otto Warburg published a famous 1956 paper in the journal, Science, suggesting that the origin of cancer lies in the ability of cancer cells to shift metabolism to glycolysis.

In the intervening years, debate has ensued that accelerate glycolysis in cancer cells is just a by-product of the oncogenic process. But we now appreciate that in some cases, the accelerating of glycolysis encourages cancer. For example, the greater level of the enzyme lactate dehydrogenase (LDH) in some cancer cells is now known to be a direct effect of the oncogenic protein, c-Myc, which by itself can cause normal cells to become cancerous.

The unusual nature of some cancer cells to rely on glycolysis even in the presence of oxygen presents an opportunity to possibly target cancer more selectively while minimizing damage to normal cells as occurs with classical chemotherapy drugs or radiation therapy. Indeed, the promise of targeting the Warburg effect in cancer is intoxicating.

At present, there are a few chemicals known to inhibit glycolysis that resemble some of the intermediates in the process but require extremely high concentrations. One is called 3-bromopyruvate – as I wrote here in 2007, this chemical inhibits both glycolysis and oxidative phosphorylation so it would have to be injected directly into the artery that feeds the cancerous tumor. The other chemical is dichloroacetate (DCA).

DCA has been around for a long time and has been used in people with inherited diseases of mitochondrial metabolism. In 2007, a group at the University of Alberta led by cardiologist Evangelos Michelakis demonstrated that very high doses of DCA can slow the progression of human tumor cells grown in immunocompromised rats. The response to this story was unbelievable with internet marketers popping up to sell the simple chemical and conspiracy theorists saying that because DCA was cheap and not patentable, no drug company would ever develop it, it was being kept a secret, and so. In truth, the work was in very, very early stages.

This didn’t stop hopeful patients from seeking out DCA sellers even though DCA can be contaminated with other related substances that are far more toxic. And in the most egregious case among these DCA purveyors, an Edmonton man who purported to sell DCA online was recently arrested in Phoenix and pleaded guilty to five cases of wire fraud – not because he was selling DCA but rather a white powder comprised of some combination of sucrose, lactose, dextran, and starch.

Yes. Not even the unproven DCA. Fake DCA.

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Ah, the old days with Mom: baking, knitting, extracting DNA

I did not turn on the computer yesterday (yes, it was glorious) so I missed Mother’s Day coverage in our local newspaper. When we returned home, I was happy to see that on the front page of the print copy the dean of Duke School of Medicine, Nancy Andrews, MD, PhD, was featured with her daughter in the lab on their fun Saturdays together.
Also cited and pictured in the article was Duke vice dean for research and professor of pharmacology and cancer biology, Sally Kornbluth, PhD, and her daughter.
Written by News & Observer science editor Sarah Avery, the article describes how women are increasing in ranks in biomedical degrees earned while still lagging at the associate professor level and up. This trend was cited specifically for faculty and administrators in basic science departments of medical schools but is widespread in academic science and engineering.
In 2007, I wrote about Andrews becoming the first female dean of a top 10 US medical school and expressed my bewilderment that it took that long. In fact, local attitudes were such that Andrews recalled this recollection in a NEJM article about taking the dean’s position:

…it continues to be true that we do not expect women to hold certain positions in society or medicine. Recently, I witnessed firsthand the persistence of such expectations, when my husband, our children, and I went to visit a school in North Carolina where Duke staff members had made an appointment for the family of the new dean of the medical school. As we entered the school, its principal vigorously shook my husband’s hand and welcomed him, saying, “You must be the man of the moment.” Unfortunately, it is quite understandable that it wouldn’t have crossed his mind that I might be the “woman of the moment” instead…

It’s always a Good Thing to see science featured on the front page of a region’s major newspaper, especially the Sunday edition. And I recognize that it was a nice human interest piece for Mother’s Day and you don’t want to be a cynic on such a day. So, it’s no surprise that the article didn’t address the specific challenges that women face of achieving the academic heights of Andrews and Kornbluth.
And I see only one lab coat and no eye protection in the lead photograph.

UA Huntsville Dr. Amy Bishop holds active NIH R15 AREA award

First and foremost our condolences go to all our our colleagues at the University of Alabama at Huntsville and others in the Huntsville science community such as Twitter friend, @girlscientist, Dr. Chris Gunter.
As we are learning, yesterday’s shooting occurred after UAH Assistant Professor of Biology, Dr. Amy Bishop, learned that she would not be awarded tenure. My sentiment is very much that of my colleague, DrugMonkey. Originally appointed as a faculty member in 2003, she had previously been an Instructor at Harvard University after earning her PhD in Medical Sciences there in 1998.
We cannot assess her tenure dossier from a distance but we can tell from ratemyprofessor.com that she had the typical profile of positive and negative reviews and was considered a tough but helpful professor. But to my eye, the ratings grew more critical over the last two years.
She and her husband had also developed a proprietary cell culture incubator and software package called the InQ cell culture system that won a local $25,000 entrepreneurial prize in 2007 and launched a company called Prodigy Biosystems. Their webpage is only a shell but local reports indicate that Prodigy had raised $1.2 million in funding around the technology. However, the state economic development enterprise, Alabama Launchpad, reported that the product launch had been scheduled for the October Society of Neuroscience Annual Meeting. (scroll down at the link as it is the last story on the page).
Dr. Bishop’s publication record was modest for seven years at roughly a paper a year (although 3 in 2009), not uncommon for a school like UAH. UAH has disabled much of their website but this Google cache of Bishop’s faculty page provides the source of my information.
I mention this because not indicated in MSM press reports is that Dr. Bishop held an active R15 AREA award (1R15NS057803-01A2) from NINDS of NIH that began April 1, 2008 and ends March 31, 2011. The grant is entitled, “Elucidation of Nitric Oxide Resistance Mechanisms in Motor Neurons,” and the NIH RePORTER record can be accessed here. Clicking on the individual tabs at this page will reveal specific information about the various aspects of the award. For example, the grant has already led to one published manuscript in the Journal of Neurochemistry in April 2009.
The NIH AREA Mechanism, Area Research Enhancement Award (PAR-06-042, just reissued as PA-10-070), is a grant mechanism intended to support institutions that have not traditionally had a strong NIH funding base:

The purpose of the Academic Research Enhancement Award (AREA) program is to stimulate research in educational institutions that provide baccalaureate or advanced degrees for a significant number of the Nation’s research scientists, but that have not been major recipients of NIH support. These AREA grants create opportunities for scientists and institutions otherwise unlikely to participate extensively in NIH programs, to contribute to the Nation’s biomedical and behavioral research effort.

Previously restricted to $150,000 in total direct costs over three years, the recent release of the program announcement indicates the mechanism now support projects at up to $300,000 over three years. It appears that Bishop’s award was for $219,750 and that the fund were dispersed in total in 2008 although the project ran until 2011.
I present this information for our readers because this is the only aspect of Bishop’s teaching, research, and service that has not yet appeared in the mainstream media.
It is impossible at this point to know anything about the grounds for the denial of her application for promotion and tenure.
In fact, it is largely irrelevant in light of the suffering of the university community and the families of those killed and injured in the shooting.
Our thoughts and prayers are with all touched by this tragedy.

Florida Keys Shifting Baselines – Thoughts on World Oceans Day

KONK-1630AM 300px.jpgSince last December, we’ve been involved with a number of good friends in Key West, Florida, on a green initiative that includes the investigations of medicinal plants of the Florida Keys and northern Caribbean. Following from these interactions with students and colleagues at Duke University and in Key West itself, I had the good fortune of being interviewed last week together with conservation biologist Stuart Pimm on KONK-1630AM community radio by Erika Biddle for her biweekly Eco-Centric World program.

Raised in Germany, she participated in the formations of the first political Green Party after witnessing the destruction of the Black Forest (Schwarzwald) through acid rain and the River Rhein polluted through an eco disaster. In her extensive travels, she has experienced awe at the natural beauty of the earth and also outrage at the human disregard for its preservation. A Key West resident with her husband Joel for 16 years and a dedicated member of GLEE (Green Living and Energy Education) and the City’s Clean KW task force.

I first cut my teeth on AM talk radio and was reminded that even for this relatively new radio station, the continued reach of such a resource remains strong despite recent downturns in other forms of media. I spent a delightful hour with Erika and Dr Pimm discussing the unique terrestrial and marine resources of the Florida Keys and we had a fair number of callers coming in with questions. Despite a common view of Key West as a tropical party place (which it is, on top of the arts and culture, nature, history, incredible snorkeling and diving), I’m ecstatic that people who live in this island paradise take their natural resources and unique fragile habitat so very seriously.
While preparing for our radio show, I was reminded of my friend Jennifer Jacquet who recently reinvented herself at ScienceBlogs.com with her own solo blog, Guilty Planet.

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Pre-plated FDA-approved oncology drug collection now available to cancer researchers from US NCI DCTD

The US National Cancer Institute (NCI) has long had programs to make available to researchers any variety of compounds, natural and synthetic. These offerings are administered by the Developmental Therapeutics Program (DTP) of the Division of Cancer Treatment and Diagnosis (DCTD).
nci logo.gif
So, I was very happy to see this e-mail last evening:

Dear Colleague,
I am pleased to announce that the NCI Division of Cancer Treatment and Diagnosis can now bring a new, important resource to drug discovery efforts. Oncology drugs that have been approved by the Food and Drug Administration are being offered in plated sets. A collection of more than 50 oncology drugs is currently available and approximately 30 other drugs will become obtainable soon. The compounds are provided as 20 microliters at 10mM in 100% DMSO.
For more information about the sets and how to obtain them, please go to:
http://dctd.cancer.gov/ResearchResources/ResearchResources-oncologydrugs.htm.
Sincerely,
James H. Doroshow, M.D.
Director
Division of Cancer Treatment and Diagnosis
National Cancer Institute
Bethesda, MD 20892
301-496-4291
doroshoj@mail.nih.gov

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On the Nature bloggy hubbub

I’ve been scarce around these parts and hope to get a Friday Fermentable up before midnight. However, I just wanted to share the following on the last couple of days discussions about Nature Publishing Group’s various pronouncements on the importance of science blogging, especially their mention in Nature Methods of ScienceOnline’09, an unconference I co-organized this year with founders and online science visionaries, Bora Zivkovic and Anton Zuiker.
Bora has the main stories and DrugMonkey adds commentary and his own personal experiences.
But leave it to Anton Zuiker to capture the whole gestalt in the 140-character medium of Twitter:

Nature Methods editorial, “Lines of Communication,” mentions ScienceOnline’09. Would link to it, but it’s behind the paywall. #irony

Indeed.
Click here – if you don’t have a subscription, that’ll be $32, please.

Update (27 Feb 1743 GMT): Grace Baynes from Nature has kindly commented below that the aforementioned article is now free access here.
Snark is hereby withdrawn.

Chris Patil (ouroboros) on the Campisi lab’s new PLoS Biology paper: cellular senescence, protein secretion, and the aging/cancer paradox

ResearchBlogging.org[Point of clarification: I was delighted to use this post to congratulate my friend and blogging colleague, Dr Chris Patil, on his contributions to this paper from the laboratory of Dr Judith Campisi discussed below. As the formal press release notes, “[c]o-authoring the paper with Campisi were Jean-Philippe Coppé and Christopher Patil, members of Campisi’s research group in Berkeley Lab’s Life Sciences Division, Joshua Goldstein, now with the Novartis Research Foundation; Francis Rodier and Denise Muñoz of the Buck Institute; and Peter Nelson and Yu Sun from the Fred Hutchinson Cancer Research Center in Seattle.” I asked Chris for an interview since he is an e-colleague, was kind enough to pick one of my posts for his new blog carnival (Hourglass), and is a top-tier scientist with a substantial presence in the online science communications and open access communities. It’s great fun to learn the backstory on what I predict will become a Citation Classic/The Scientist Hot Paper. Thanks again, Chris, for being so generous with your time and sharing your thoughts with our readers.]
I’ve kept a passing interest in senescence (cellular, not personal) over the last 20 years or so because I’ve always felt that attempts to increase longevity in a multicellular organism would also increase the risk of cancer (more seasoned readers may recognize this as the Hayflick phenomenon of replicative cellular senescence first identified in 1965). As a newly-minted PhD looking for postdoc fellowship, including in a yeast lab focused on aging, I thought that harnessing the senescence pathway might be a valuable strategy for treating cancer.
Yesterday’s PLoS Biology paper from Coppé et al., builds on a newly-described cellular response that throws a wrench in that simplistic idea. Cells induced to undergo senescence with DNA-damaging agents exhibit a secretory phenotype, termed the senescence-associated secretory phenotype (SASP), whereby molecules involved in inflammation and metastasis are released into the local environment. In younger individuals, this mechanism could prevent the development of cancer but in older individuals could increase the risk of cancer. In cancer, for example, therapies that causes cellular growth arrest and senescence may be of limited utility unless those senescent cells are removed. My takehome message from this paper is that we may have to rethink the benefit of cancer therapies that are cytostatic.

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Perhaps if more of us were “that guy”

DrDrA at BlueLabCoats has returned with an outstanding post, entitled, “I want you to hear me, I don’t care what you see…,” that she wrote out longhand during her recent travels:

In my absence I picked up a whiff of a lot of chatter about what women scientists wear to work… or talk/write about wearing …. going on in the blogosphere. . .
You see- the struggle I’m in daily in my own life and career is not about appearances, and it is not about symbolism or femininity- and it is not about who I am as a person, my likes and dislikes etc. It is a struggle to be heard and taken seriously for my ideas, plain and simple. . .it is about training the students in my group – who right now happen to be all women- to be the best possible scientists, and teaching them how the system works. It is about not having to repeat the same reasonable idea 20 or 30 times and have it laughed off by a group of colleagues for two or three YEARS, and then having a man mention it once and have it roundly applauded and implemented.

Funny that she should write this outstanding post right now – since I’ve been reading her, Zuska, and many of my other women scientist friends (and witnessing my supremely accomplished wife get blown off by fellow academics), I’ve been trying my own experiments (not really experiments but rather real-life observations to which I’ve become attuned after reading my colleagues.).
The last one was at a meeting last week where I noticed at our opening reception a group of women academics next to the bar separate from the other groups of mostly men with one or maybe two women. I gently interrupted to introduce myself then spoke with a few about where they were, what they did, why they were here, etc., intentionally listening for 75-80% of the conversation rather than being the typical male ass who would descend upon such a group and hold forth on his greatness. Indeed, these women smoked me in terms of stature and experience and I did in fact have a great deal to learn from them (as I did for the rest of the workshop).
Well, wouldn’t you know if, but along comes a gentleman obviously hoping to rescue these highly accomplished female academics from a man who was actually listening to them. After a few minutes of his blustering and chest-puffing, I turned back to the person with whom I was already having an engaging conversation and the gentleman took leave shortly thereafter.
I present this anecdote not for any self-aggrandizment – after all, what is such a big deal about listening more than speaking to anyone, any colleague, regardless of their gender or geographical ancestry? Instead, DrDrA’s sentiments caused me to recall what DrugMonkey said in one of his more notable posts, gentlemen, it doesn’t hurt a bit to be “that guy.”

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Dr Douglas Prasher reprised on Inside Edition

We here at the Terra Sig World Headquarters have been inundated with traffic directed by search engines following our post the other day directing readers to the NPR story on Douglas Prasher. Prasher, as is now widely known, is the former Woods Hole science who cloned the cDNA for green fluorescent protein (GFP) that enabled the work leading to this year’s Nobel Prize in Chemistry to at least two of the three laureates. Prasher is currently driving a courtesy shuttle for Bill Penney Toyota in Huntsville, AL, for $10 (USD) per hour. Prasher had been working for NASA in Huntsville until his funding ended.
(A great many thanks to Jennifer C who apparently works with Prasher and says, “I really hope someone heard his story and will offer him an amazing job. He has never been anything but great to all of us that work with him.”)
An even greater uptick in search hits yesterday led us to believe that something else has happened – that something else was additional coverage of Prasher’s story on the celebrity news and gossip program, self-described as “America’s Newsmagazine,” Inside Edition, on their Tues 14 October broadcast. Currently, the video is not yet available but there is the text of the story and a few nice still photos.

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