Medical Writing, Editing & Grantsmanship

Blogged everywhere in cyberspace by now, I’m sure, but just too cool. But of course my immediate thought was the pandora’s box of ethical issues (& potential for scientific-research misconduct) …

Genome Transplantation in Bacteria: Changing One Species to Another
Carole Lartigue, John I. Glass , Nina Alperovich, Rembert Pieper, Prashanth P. Parmar, Clyde A. Hutchison III, Hamilton O. Smith, J. Craig Venter. The J. Craig Venter Institute, Rockville, MD 20850, USA.

As a step toward propagation of synthetic genomes, we completely replaced the genome of a bacterial cell with one from another species by transplanting a whole genome as naked DNA. Intact genomic DNA from Mycoplasma mycoides large colony (LC), virtually free of protein, was transplanted into Mycoplasma capricolum cells by polyethylene glycol-mediated transformation. Cells selected for tetracycline resistance, carried by the M. mycoides LC chromosome, contain the complete donor genome and are free of detectable recipient genomic sequences. These cells that result from genome transplantation are phenotypically identical to the M. mycoides LC donor strain as judged by several criteria.

Genome transplant makes species switch
One type of bacterium has been reprogrammed into another.
Philip Ball

By transplanting their genomes, US scientists have converted one species into another. Read the rest of this entry »

For whatever reason, I’ve never interacted much with the hard-core cancer crowd, perhaps because NCI-designated cancer centers seem to be their own fiefdoms at academic health centers. Hardly an excuse, but I’ve just come across this incredibly sweet NCI portal while introducing a new (junior) faculty researcher to the land of milk & honey.

The Cancer Research Portfolio allows you to quickly and easily search for NIH funded research, funding opportunities, and research resources on all topics, types, and stages of cancer research. Skip CRISP and the NIH Guide if you want info on cancer-related extramural research awards, contracts, intramural studies, clinical trials, and funding opportunities. And who knew there was a Common Scientific Outline for cancer research? Or that this Common Scientific Outline provides structure for a comprehensive International Cancer Research Portfolio that includes ACS, ONS, Komen Foundation, Congressionally Directed Medical Research Programs, the Prostate Cancer Foundation, and the Calif Breast Cancer Foundation.

Two from Oklahoma … note the use of the term “scientific” rather than “research” misconduct (see the helpful comment below for explanation).

Notice is hereby given that the Office of Research Integrity and the Assistant Secretary for Health have taken final action in the following case:

Joy Bryant, University of Oklahoma Health Sciences Center: Based on the report of an investigation conducted by the University of Oklahoma Health Sciences Center (OUHSC) and additional analysis conducted by the Office of Research Integrity during its oversight review, the U.S. Public Health Service found that Ms. Joy Bryant, Tribal Efforts Against Lead (TEAL) phlebotomist, OUHSC, engaged in scientific misconduct in research supported by grant R01 ES008755. Specifically, Ms. Bryant falsified research in the TEAL study by substituting or conspiring with another phlebotomist to substitute her blood or blood of another phlebotomist for blood samples of 10-15 child participants in the TEAL study.

Notice is hereby given that the Office of Research Integrity and the Assistant Secretary for Health have taken final action in the following case:

Diana Layman, University of Oklahoma Health Sciences Center: Based on the report of an investigation conducted by the University of Oklahoma Health Sciences Center and additional analysis conducted by the Office of Research Integrity during its oversight review, the U.S. Public Health Service found that Ms. Diana Layman, TEAL phlebotomist, OUHSC, engaged in scientific misconduct in research supported by grant R01 ES008755. Specifically, Ms. Layman falsified research in the TEAL study by substituting or conspiring with another phlebotomist to substitute her blood or blood of another phlebotomist for blood samples of 10-15 child participants in the TEAL study.

The first National Science Foundation Regional Grants Conference of fiscal year 2008 will be hosted by Portland State University on October 22-23, 2007, with an optional FastLane and Grants.gov workshop on October 21.

The conference is considered a must, particularly for new faculty, researchers, educators, and administrators who want to gain key insight into a wide range of important and timely issues at NSF: the state of current Grants; the proposal and award process; and current and recently updated policies and procedures.

Conference Highlights (view agenda):

-New programs and initiatives
-Future directions and strategies for national science policy
-Proposal preparation
-NSF’s merit review process
-Cross-disciplinary and special interest programs
-Conflict of interest policies
-Breakout sessions by discipline

(in the meantime, you can download presentations from prior Regional Seminars - keep scrolling down)

In the course of collecting evidence to justify why my current employer hauled my ass up here & paid my salary for the last 6 months, I came across a file I prepared shortly after arriving and before getting this blog off the ground. Last Nov, an NCI program officer who was previously a faculty member here came back to address a packed audience of young investigators on strategies for succeeding in the NIH shell game. Her advice works just dandy for seasoned PIs as well.

She spent a bit of time on what remains a controversial issue at the NIH, but her stance was clear: new PIs should concentrate on crafting and submitting a very competitive R01 rather than divert their effort to R21 or R03 proposals. Neither of the latter are renewable, and neither are appropriate “starter” grants on the road to independence. The R21 is appropriate if the work is truly exploratory - but not if the work is just a 2-year R01. The R03 is appropriate if the new investigator has no internal sources of pilot data collection funding … but she indicated that study sections & program officers prefer to see the home department/school picking up the tab for pilot data collection if the new PI is truly promising. That is, the NIH wants to see some institutional commitment & co-investment in this process. [I will add that responding to a specific RFA or PA with an appropriate proposal for the mechanism is another matter as well ... just be sure the proposed research is responsive to the stated objectives and the mechanism.]

In the category of putting out a strong new PI R01, she also recommended that you include letters of support from your mentor, division/dept chair, outside collaborators, etc. who could vouch that you are ready to launch your independent career. These are not like the formal K award letters but short, specific, clearly sincere recommendations to the IC and study section that awarding the grant would be a good investment. A senior study section member in the audience confirmed this - but added that the letters must clearly demonstrate that the mentor (or whoever) has read the R01 and helped refine the narrative … a glowing letter of support appended to an unfundable narrative backfires for both the new investigator and the mentor. [As a reviewer of internal pilot funding applications, I can attest to the frustration of a ridiculously immature proposal paired with a bubbling mentor letter - makes everyone look bad.]

When resubmitting (A1 or A2), she reminded the audience they could certainly ask the SRA to not reassign a specific reviewer (by number on the last summary statement). Those cover letters I keep telling you to write are confidential documents only read by the referral officer and the SRA (scientific review administrator - the NIH staff person assigned to each study section). She said usually one-two of the original reviewers re-reviews amended applications, with one-two new reviewers. The SRA can look at your last summary statement and concur (or not) with your request that Critique #2 (e.g.) was way off base. In fact, SRAs will ask an outlier study section member to leave the room during your review since the SRA now considers that reviewer to have a conflict of interest (based on the tone-content of the initial review in comparison with the other reviews & the application itself).

And she emphasized there is life after an unfunded A2 submission - not to get discouraged, not to give up, not to let your career/life be defined by this … especially with the budget in the toilet and submissions at an all-time high. She immediately explained why you cannot submit a disguised A3 (fourth attempt) submission … that the referral officers check the recent submission history of every application coming in, and if they see a recently unfunded A2, they search your current application for matching word strings and other tell-tale signs of illegal fourth submissions. She said at least 50% of the aims must be new and that often the mechanism can be changed (apply for piece of a failed R01 as an R21 if exploratory or R03 if pilot data are needed). Alternatively, given that 3 cycles have passed, use data accumulated over the years to expand an R21 into an R01 or develop a truly new R01, again taking the time needed to prepare a really polished and readable application.

Okay, Drugmonkey, let the commentary begin …

From Science as well … get your thinking caps on:

Two hot biological research areas–epigenetics and the microbes our bodies host–will lead Roadmap 1.5, the second round of research initiatives that cut across all 27 institutes and centers at the NIH. Alan Krensky, incoming director of NIH’s new planning office, says solicitations for these two 5-year programs will go out this fall. Epigenetics will catalog genetic changes that affect gene expression but don’t involve a change in DNA sequence. The Human Microbiome Project will examine the body’s microbial communities and their relation to disease. Two more projects to start as pilots include work on human phenotyping and protein probes. NIH projects spending $30 million next year and $80 million for each of the next 4 years.

In this week’s issue of Science … a dissertation unto itself:

“Because of “numerous questions,” Osaka University’s Graduate School of Medicine has told one of its research groups to retract a 2004 Science paper on an insulin-mimicking protein secreted by fat tissue. The school’s dean, Masaya Tohyama, last week held a press conference to issue the unusual demand, which came after a year-long investigation.

The school has not alleged scientific misconduct, and the paper’s corresponding author, Iichiro Shimomura, says the issues raised by the investigation, such as ignoring data that complicated the paper’s conclusions, do not warrant retraction. The metabolism researcher says he and the other authors are considering legal action against the university for how it handled the case.

… Harvey Lodish, a biologist at the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology, both in Cambridge, says that the decision to drop the female heterozygotes “seems all right to me.” But Lodish, who co-authored a commentary in Science on the research, says that because of other questions about the work, “we reserved judgment as to the reality of visfatin as a secreted insulin-mimetic hormone.”

… Shimomura says the group responded to other issues raised by the investigating committee in a rebuttal and stands by its original results. In a statement issued by Science, its editor-in-chief, Donald Kennedy, said the journal was taking the matter “very seriously.”

… This is the second time Shimomura has been a corresponding author on a problematic paper. In November 2005, he retracted a paper published by Nature Medicine a year earlier when it was found that the first author, Nobuyasu Komazawa, had fabricated data. Komazawa was not a contributor to the visfatin paper. “

Based on the report of an inquiry conducted by the University of Texas Medical Branch at Galveston (UTMB) and additional analysis and information obtained by the Office of Research Integrity during its oversight review, the U.S. Public Health Service found that Carlos A. Murillo, M.D., former Surgical Resident, Department of Surgery, UTMB, engaged in research misconduct in research supported by grants R01 DK48498 and T32 DK07639. Specifically, Dr. Murillo falsified research on the amelioration by antisense RNA (siRNA) of dextran-induced colonic toxicity in mice. He altered the concentrations of dextran solution fed to mice to induce colonic inflammation, by intentionally including little or no dextran in the drinking water of siRNA treated mice, so that the animals that received siRNA would have few or no colonic lesions.

Thank heavens the X02s for the Molecular Libraries Program are due next week. I think.

The PA innocuously states: “This announcement utilizes the X02 mechanism for submission and consideration of pre-applications. The X02 application is relatively brief and is subjected to peer review that will identify applicants who will be invited, in the second step, to submit full applications for U54 centers for the anticipated January 4, 2008 submission date. No formal awards will be made under the X02 announcement.”

Those of you who enjoy preparing U54 center applications, raise your hands. Just as I thought … not a lot of enthusiasm, especially after grinding out these damn “relatively brief” (but not relatively easy or simple or painless by any means) pre-application essays. However, very nice to be spared the U54 agony if your submission was going to be trashed anyway. Conversely, very nice (& highly motivating) to be invited to submit a proposal for a comprehensive screening center award worth $13M per year for 5 years.

I am wondering how many more big NIH funding mechanisms will move to the X-men model of 2-stage peer-review followed by Advisory Council discussion & funding decisions. It would almost be a blessing if it meant avoiding the unnecessary spewing of dozens of 600-page CTSA proposals or other similarly long and involved U54, P50, and P60 applications. Particularly if everyone and his brother is now applying, and someone has to read the damn things.

And for those of you with tuberculosis on the brain, please visit the very comprehensive TB Website maintained by NIAID, including a nicely organized Resources for Researchers section.