The Cancer Letter reveals Rhodes Scholar falsification by Duke cancer researcher

This is not good. Not good at all.
On Friday, Paul Goldberg of The Cancer Letter reported on an investigation into Duke cancer researcher, Anil Potti, MD, and claims made that he was a Rhodes Scholar – in Australia. The misrepresentation was made on grant applications to NIH and the American Cancer Society.
The Cancer Letter, a $375/year go-to newsletter on cancer research, funding, and drug development, has made this issue free at this PDF link.
News & Observer higher education reporter, Eric Ferreri, has a nice overview of the situation. Potti has been placed on administrative leave by Duke and the American Cancer Society has suspended payments on his grant and initiated their own investigation.
This news follows on questions regarding Potti’s highly-promoted research conducted in the lab of Joe Nevins at Duke. From The Cancer Letter PDF on page 6:

The Nevins and Potti team emerged as pioneers of personalized medicine in 2006, when Nature Medicine published their paper claiming that microarray analysis of patient tumors could be used to predict response to chemotherapy.
However, two biostatisticians at the MD Anderson Cancer Center attempted to verify this work when oncologists asked whether microarray analysis could be used in the clinic. Keith Baggerly and Kevin Coombes, the statisticians, found a series of errors, including mislabeling and an “off-by-one” error, where gene probe identifiers were mismatched with the names of genes.
Baggerly and Coombes said they devoted about 1,500 hours to checking Potti’s and Nevins’s work. These efforts–dubbed “forensic bioinformatics”–resulted in a paper in the November 2009, issue of the Annals of Applied Statistics.

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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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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 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.

No, I’m not a millionaire either

This quick post is in response to one by DrugMonkey a few days ago entitled, “Nope, I just get my regular salary…” Drug speaks of the realities of federal research grant-supported scientists at US universities and research institutes and how the apparent large dollar figure grants do not line the pockets or supplement the salary of principal investigators.
Yes, there are some caveats here in that many institutions now offer professors a base salary that can be increased by some percentage if they receive X grant dollars or % effort. This was started at some institutions by taking one’s current salary, say $80,000, and telling faculty they were guaranteed $60K but could win back their full $80K if they got a grant that paid the other $20K. Happy day, eh?
Drug asked what others have found to be the perceptions of friends, neighbors, other university employees, etc. when they learn that one just received, say, a half million dollar grant.
Here’s one of my earliest experiences upon becoming an independent investigator:

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Moving advert from Cancer Research UK

Although I’m American, much of my training and early independent career was influenced by British cancer researchers. At the time, their laboratories were supported by ICRF, the Imperial Cancer Research Fund. In 2002, ICRF merged with the Cancer Research Campaign to create Cancer Research UK (CRUK).
I have several friends who work for Cancer Research UK, not the least of whom are blogger/author Ed Yong (Not Exactly Rocket Science) and writer/musician Dr Kat Arney, author of the aptly-named blog, You Do Too Much. Together with fellow professional science communicator Henry Scowcroft, they administer the Cancer Research UK blog, Science Update.
I note of all this to provide you with context for one of the most moving and persuasive cancer research ads I’ve seen in recent years. We’ve made great progress but we have a long ways to go.

It’s all moving but the words “brain tumour” from 9-year-old Eden Hubbard really got me.
In fact, you can learn the stories about all 36 cancer patients featured in the advert and the making of the piece on this page of the website devoted to this campaign,
Well done, mates. Well done.

Meet DOD/CDMRP Cancer Research Grants Officials at AACR Tomorrow

Never pass up an opportunity to get face-to-face time with grants officials from any research funding agency. This from the Department of Defense for those of you in Denver tomorrow:

To all individuals attending the 100th Annual Meeting of the AACR in Denver, Colorado:
The Department of Defense’s Congressionally Directed Medical Research Programs (CDMRP) will be presenting a series of short talks on CDMRP and its cancer research funding programs on Wednesday, April 22, from 8:30-10:30 a.m., in Room 607 of the Colorado Convention Center.
Scheduled to speak from the CDMRP are the Director, a Program Manager, and a Grants Manager. In addition, there will be presentations from an Integration Panel member, a CDMRP-funded investigator who has also participated in peer and programmatic review, and a Cancer Survivor involved with the program.
All individuals interested in successfully applying for cancer research funding are encouraged to attend!
Additional details can be found in the AACR Annual Meeting Program book.

Greybeards an endangered species

I was very late to the game on a DrugMonkey post last week examining the demographics of Early Career Award winners from the Howard Hughes Medical Institute (HHMI). Drug noted that only 9 of the 50 awardees are women:

So who got lucky? See the slideshow here.
huh. anything strike you? no? lemme get a pencil here….hmmm.
2 African-American looking guys, another maybe. Six Asian guys. Maybe another four or five men who look other than standard model white guy. Nine women.
Really? That’s the best you could do? Seriously? You couldn’t even that gender ratio up even a little bit better than that?

As one might suspect, the reasons for the predominance of mostly white guys drew a comment thread approaching 100.
But nowhere in the thread did anyone mention (until I did), another trend that struck me upon viewing the awardees’ photos.
The paucity of male facial hair.
I am deeply concerned that of the 41 men, a full 33 sport no facial hair. I’m being generous here in giving the dude with the soul patch a pass. Including him and the single-moustached guy among the eight bearded, only three were goatees. (Great facial hair style guide here).
How can a man do legitimate science without at least a goatee? From where will our future greybeards come? Have we gone mad?

Dr Geraldine Pittman Woods: Minority Scholar Pioneer

geraldine woods.gifDr Geraldine P Woods (1921-1999) was inarguably the most influential scientist in establishing and promoting NIH’s programs in research and research training for underrepresented groups. Therefore, I have chosen her story for my entry to this month’s Diversity in Science blog carnival recognizing Women’s History Month.
My interest in Dr Woods was inspired by a recent post by my friend and colleague, acmegirl, who writes the blog, Thesis – With Children. In her post recognizing the work of Duke University behavioral biologist, Dr Erich Jarvis, acmegirl noted that both she and Dr Jarvis are products of the MARC program – Minority Access to Research Careers – administered by NIH’s National Institute of General Medical Sciences (NIGMS). I have had a few friends who have been MARC scholars in their undergraduate and graduate years as well as several colleagues who have received research grants from the Minority-Based Research Support (MBRS) program.
NIGMS was established by an act of the US Congress in 1962. In 1964, Dr Frederick Woods was named as NIGMS director and Dr Geraldine Woods appointed to the National Advisory General Medical Sciences (NAGMS) Council. Among their other charges, the group began to evaluate NIH research support at traditionally minority-serving institutions. Keep in mind that it was the Higher Education Act of 1965 that also provided federal designation of 105 historically-Black colleges and universities (HBCUs; accredited by a national or nationally recognized regional accrediting agency, founded before 1964, and founded for the purpose of educating black students.). Of course, many more institutions today serve these and other underrepresented groups.
Woods and colleagues on the council determined that, at the time (late 1960s) NIH only provided about $2 million in funding to minority institutions with 80% of that going to Howard University in DC and Meharry Medical College in Nashville, Tennessee (these schools remain among the top research HBCUs). She later visited minority institutions around the US, encouraging investigators to submit research proposals to the NIH and presenting to upper academic administration the need to provide research infrastructure.
Believe it or not, it was President Richard M Nixon who, on 22 February 1971, issued to Congress in a directive on higher education a section entitled, “Special Help to Black Institutions.” According to Susan Athey, the NIGMS writer who prepared Dr Woods’ obituary:

This led to the 1972 launch of the Minority Schools Biomedical Support Program (now known as the Minority Biomedical Research Support Program; the administration of this program was transferred from NCRR to NIGMS in 1989). Also that year, NIGMS established visiting scientist and faculty fellowship awards through the Minority Access to Research Careers Program.
According to Dr. Clifton Poodry, director of the NIGMS Division of Minority Opportunities in Research (MORE), “Dr. Woods’ interest in our programs did not end with her retirement from active involvement. She was always grateful to hear some good news or success stories about MARC or MBRS participants, and she was also interested in knowing that the programs were continually striving to improve and in learning about new initiatives.”
“She fought hard for opportunities for others–we are greatly enriched for her efforts,” Poodry added.
In addition to her involvement with NIH’s minority initiatives, Woods was a prominent leader in other national educational, political, and scientific endeavors. Her activities included serving as the first woman chair of the Board of Trustees of Howard University and two terms as national president of the Delta Sigma Theta Sorority.

A more comprehensive history of these programs can be found at this NIGMS timeline.

“Dr. Woods was a person ahead of her time,” said Dr. Ruth Kirschstein, [then] acting NIH director and director of NIGMS from 1974-1993. “She received a Ph.D. in biology from Radcliffe long before any other African American scientist could so qualify. Yet she never forgot her roots and worked tirelessly to assist in establishing the MARC and MBRS Programs.”

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“Complementary and alternative medicine (CAM)” is not a single “thing”

I just had a chance to check in on a triad of posts by Prof Janet Stemwedel at Adventures in Ethics and Science (1, 2, 3) on the ethical issues of the conduct of studies, particularly clinical trials, supported by the US NIH’s National Center for Complementary and Alternative Medicine (NCCAM).
For background, NCCAM was originally established for political, not scientific reasons, as the NIH Office of Alternative Medicine in October 1991. It received a token budget of $2 million at the time. They still only get $120-ish million; modest by NIH standards as compared, say, with the 2007 NCI budget of about $4.8 billion. But that $120-125 million is pretty significant in that it could fund about 60 independent researchers and their laboratory groups for five full years.
How was alternative medicine defined then? Primarily as folk and cultural modalities not incorporated into conventional Western medicine but used and promoted for disease treatment or prevention without statistically-defined efficacy and safety. The net was cast very wide, from “energy therapies” that defy the basic tenets of physics to herbal medicines that have given rise to 25% of prescription medicines.
Hence, CAM is not one modality. It is a term used to describe a wide spectrum of health-promoting approaches that have not been evaluated previously under rigorous, controlled basic or clinical science standards.
CAM is a terrible term. It is NOT medicine. Modalities proven to work are medicine. Modalities that don’t work are not medicine. There is no complement to medicine. Medicine is medicine. There is no integrative medicine, either. Medicine already takes advantage of all modalities: surgical, pharmacological, radiological, physical, psychological, nutritional – if a clear benefit can be offered to a patient that outweighs the risk.
So-called integrative medicine gurus have adopted proven, preventive medicine techniques – diet, exercise, meditation, yoga – and have used them 1) to justify that “CAM” works and 2) that the efficacy of these approaches justifies study and implementation of approaches that have absolutely no scientific basis.
Oh yeah, often with substantive personal financial benefit.

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