23andMe resumes sales: Ancestry only!

Well this is interesting. After being spanked by the FDA for selling their services without proper review and approval of their medical test (as the FDA interpreted it), the 23andme company is back.

I received an email spam suggesting I purchase one of their kits as a Mother’s Day present.

Intrigued, I see this in an alert banner across the linked page.

23andMe provides ancestry-related genetic reports and uninterpreted raw genetic data. We no longer offer our health-related genetic reports. If you are a current customer please go to the health page for more information.

When you go to purchase a new kit you are obliged to check a box indicating you’ve read an additional warning.

I understand I am purchasing ancestry reports and uninterpreted raw genetic data from 23andMe for $99. I understand I will not receive any reports about my health in the immediate future, and there is no timeline as to which health reports might be available or when they might be available.

Ok. Got it.

So what about existing customers who purchased their kit in the old, pre-ban era? Guess I’d better visit that “health page“.

Current 23andMe customers who received health-related results prior to November 22, 2013 will continue to have access to that information. However, no new health-related updates will be provided to your account.

Customers who purchased kits before November 22, 2013 will still receive
health-related results.

Customers who purchase or have purchased 23andMe’s Personal Genome Service (PGS) on or after November 22, 2013, (date of compliance letter issued by the FDA) will receive their ancestry information and uninterpreted raw genetic data. At this time, we do not know the timeline as to which health reports might be available in the future or when they might be available.

Customers who purchased kits on or after November 22, 2013 through December 5, 2013 are eligible for a refund. 23andMe has notified all eligible customers by email with refund instructions. If you are eligible and have not received an email, please click here.

Ok, so they are not turning off the results already provided to the older customers. If you fell into the cease-and-desist gap, you don’t get your info (boo FDA) but you can get a refund.

In the mean time, 23andme is an ancestry / genealogy company.

I suppose that is it until they pass regulatory approval for their health and trait information?

ASPET 2014: XLR-11 synthetic cannabinoid associated with nephrotoxicity

This is an overview of a presentation in Symposium 491. Scientists versus Street Chemists: The Toxicity of Designer Marijuana Wed, Apr 30, 9:30 AM – 12:00 PM at Experimental Biology 2014.

Wed, Apr 30, 10:45 – 11:10 AM Clinical and unexplained idiosyncratic toxicity of K2 exposure by G. Buser of the Oregon Health Authority.

One potential health consequence of the use of synthetic cannabinoids is acute kidney injury (AKI) or nephrotoxicity. There have been Case Reports published and there are more cases described in the MMWR report of the US CDC.

Buser indicated that in Oregon the index case for her agency’s attention was a 17 yo male who reported to the emergency department where he was found to have abnormal kidney function. He had been smoking a synthetic cannabis product. With such a finding, there are a number of questions: Is it a contaminant? Possibly a toxic solvent used to prepare the product? Toxic constituents of the plant material used for a given product? A hot spot in the product that resulted in an unusually high dose?

This thinking triggered an investigation around the state of OR, in which medical facilities, officers and other public health authorities were queried for cases of unexplained nephrotoxicity in young adults. Buser identified several additional cases in which it appeared from case histories that the smoking of synthetic cannabis products were involved. The author then attempted to secure the clinical course, case histories and any clinical samples collected.

She ended up with 9 cases collected between May-Oct 2012, all male with a median age of 18. Due to the variability in the cases, the onset from last smoking to symptoms was 2 weeks to 30 minutes although Buser cautioned that the case histories derived from friend or the user might not be that reliable.

Affected individuals (also see the above links) tend to suffer from nausea, vomiting and abdominal/flank/back pain. Buser said that in the OR cases, the individuals tended to wait anywhere from 12 hrs to a day after the start of their symptoms, thinking that it would resolve by itself.

The cases typically featured abnormal clinical chemistry (BUN, serum creatinine), proteinuria and kidney biopsies were found to confirm both acute tubular nephritis and interstitial nephritis.

The study interviewed 6 of 9 cases, all were habitual marijuana smokers, had obtained their synthetic cannabis over the counter from convenience stores or head shops and they reported 5 different product brand names. The team was able to secure 2 of the products for testing.

One of the more frustrating issues for a study like this is that the patients reported to Emergency services of some sort a long time after last exposure to synthetic cannabis. So there is a good deal of uncertainty about being able to detect any of the known agents. Nevertheless, one invidual was positive for (1-(5-fluoropentyl)-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl) methanone (XLR-11). No other known cannabimimetics were found. This individual happened to be one (of the two) for whom they were able to secure and analyze a sample of the product he had used. It was also positive for XLR-11.

XLR-11 was found in four of the five product samples and four of six patient’s specimens in the WY report as well.

It appears to be the case that no other cannabimimetic compounds have been reported in association with acute kidney injury. Obviously, the data are thin and in many cases of AKI, there are no analyses of the product and timing may be such that clinical sample would be negative anyway.

Still, there is enough of a smoking gun here to recommend some preclinical studies on the nephrotoxic effects of XLR-11, as mentioned by Buser.

Buser ended up by observing that in three of the cases there were other people smoking the same product with the affected individual. It was speculated that perhaps there was a hot spot, perhaps those individuals smoked more or perhaps they had an individul liability. With respect to the latter, she noted that two brother pairs were represented in the affected sample. This might point to shared genetic liability for these adverse effects of XLR-11 consumption.

One major takeaway from the presentation is that a specific synthetic cannabinoid might have specific risks for kidney injury. A second major takeaway is that we know far too little about this phenomenon, both from a mechanistic perspective and an epidemiological one. Efforts from public health officials such as Buser can enhance awareness and therefore detection of human cases.

Experimental Biology 2014: Transgenerational effects of stimulant drugs

This is a summary of a presentation in Symposium 222. Molecular Basis of Addiction: Neurocognitive Deficits and Memory Mon, Apr 28, 9:55 AM – 12:10 PM at the 2014 Experimental Biology meeting.

Mon, Apr 28, 10:25 – 10:40 AM Amphetamine exposure during development causes epigenetic trans-generational changes in drug sensitivity in Caenorhabditis elegant. Authors: Talus McCowan, Bryan Safratowich, Joyce Ohm, Lucia Carvelli

McCowen* presented a study which showed transgenerational effects of amphetamine in a C. elegans model.

Caenorhabditis elegans is a nematode about 1 mm long which has the dubious virtue of having 302 neurons of which a mere 8 are dopaminergic. This makes for a tractable model, particularly when you think you might want to model the entire nervous system.

The model involved Swimming Induced Paralysis (SWIP) which can be induced in a liquid medium by treating the worm with amphetamine. This is a time and dose dependent phenomenon which has been shown to depend on the dopamine transporter and D2/3-like dopamine receptors. Classic targets of the amphetamines.

The study exposed eggs to 500 uM amphetamine or control media for 15 hours. After maturation of the worms, they were subjected to the SWIP test in which it was found that the egg-exposed animals had an enhanced freezing response. In this case it was an increased percentage of the worms freezing in the context of a moderate dose, selected to give parametric range on either side. The authors then examined the F1 generation of worms, which had received no drug treatment up until the SWIP challenge. here it was found that the F1 offspring of the F0 worms exposed to amphetamine during development also had an enhanced response to amphetamine.

The lab is interested in methylation of histones as an epigenetic mechanism that might possibly convey this effect. They found decreases of histone H3 Lys4 trimethylation (H3K4me3) in the F1 offspring of amphetamine incubated worms compared with the offspring of control worms. This was selective as there was no difference in H3K27me3 expression.

Obviously this is just a start, one would think that the advantage of the worm is that you could go out for generations quite readily, in comparison with rodents (see below). So presumably this story will advance by the time we see it in publication. Nevertheless, this joins a growing appreciation of the transgenerational effects of drug. While there are many caveats in translating this to humans, it certainly puts a bright spotlight on familial abuse patterns and our potential targets for explaining them.
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Related: Heritability of Substance Abuse Meets Epigenetics?

*The speaker identified himself as a first year graduate student. I think he did a bang up job of the presentation and of handling the questions.

Experimental Biology 2014: Non-alcoholic fatty liver disease

I learned something at poster session 1116. Alcoholic and Nonalcoholic Fatty Liver Disease
Tue, Apr 29, 7:30 AM – 4:00 PM.

Tue, Apr 29, 12:45 – 3:00 PM 1116.11/A601 – Low copper and dietary sucrose drive fibrosis pathways in a rat model of non-alcoholic fatty-liver disease

Tallino and Burkhead presented a poster studying non-alcoholic fatty liver disease in a rodent model. I’m most used to considering similar damage in the context of alcohol exposure, given that abused drugs are my focus. So it was interesting to learn that some 20-25% of those on a Western diet may exhibit some signs of fatty liver disease that has nothing to do with alcohol.

The study Tallino and Burkhead conducted was based on evidence that steatosis may be related to copper (Cu) deficiency and that this may interact with sucrose in the diet.

The study consisted of four groups of Wistar rats, exposed to different dietary conditions for 12 weeks. The factors were a diet either sufficient or deficient in Cu and a 10% or 30% sucrose addition.

The authors show that low Cu diet works, serum Cu was significantly lowered in these groups. Interestingly there was an interaction whereby the group with low Cu and 30% sucrose diet was further depleted in serum Cu. As expected, serum glucose was elevated with 30% sucrose but this was only out of the normal range with the low Cu / 30% sucrose group.

Interestingly, these dietary conditions resulted in no change in free fatty acids and no change in body weight. Remember that now.

The low Cu diet increased liver steatosis significantly with an interaction with the sucrose treatment to increase this sign of non-alcoholic fatty-liver disease. So Cu deficiency can combine with high sucrose in the diet to produce liver damage in the absence of other indications of a fatty diet (weight gain, high circulating triglycerides).

The study then went on to find that the high sucrose, low Cu diet was associated with alterations in gene transcripts related to fibrosis progression, hepatic stellate cell activation and a few other things related to the hypothesized model of damage.

Will a dual sigma receptor antagonist / dopamine transporter inhibitor treat stimulant abuse?

This post covers a platform presentation in symposium 222. Molecular Basis of Addiction: Neurocognitive Deficits and Memory (Mon, Apr 28, 9:55 AM – 12:10 PM) at the 2014 Experimental Biology meeting.

803.3/D382 – Preclinical efficacy of the dual sigma receptor antagonist dopamine uptake inhibitor, CM699, as a medication for stimulant abuse

Johnathan Katz of the NIDA Intramural Research program presented an overview of the data and findings that led up to the creation of a new molecule (CM699) that functions a both a dopamine transporter (DAT) inhibitor and a sigma receptor antagonist. As a bit of background, NIDA has spent a tremendous amount of effort trying to use dopamine transporter inhibitors as agonist therapy for stimulant abuse. The theory of agonist therapy is familiar from the nicotine patch and methadone. The outline is that if you have a drug which mimics the abused drug in effect but has different time-course of effect, you may be able to blunt the acute high of the preferred drug and/or method of use. The nicotine patch supplies the identical drug but in a more sustained, slower and less-peaky manner. Methadone is relatively long acting at endogenous opioid receptors, apparently providing relief without the acute euphoric high. A similar strategy has governed attempts to identify compounds which would confer protection against stimulant abuse.

Since the acute reinforcing effect of stimulants such as cocaine and methamphetamine is mediated through the DAT, this was the target of considerable NIDA effort over decades. It has not been a successful effort.

First off, Katz pointed out that calling sigma a “receptor” is bit of a misnomer as it functions as an intracelluar chaperone protein. This molecule hangs out in association with the endoplasmic reticulum but under ligand activation can migrate to modulate the function of membrane bound proteins. One of those is apparently the dopamine transporter.

Another background consideration for the presentation is that cocaine, as Katz noted, blocks the DAT but also has some sigma affinity. The significance of this agonist activity was not made entirely clear in the talk and we should keep in mind that any antagonism of the sigma receptor will also likely remove the sigma-mediated effects of cocaine. This part was not well explicated in the talk.

At any rate, sigma antagonist compounds block the effects of cocaine. Katz described data indicating that the acute locomotor stimulant effect of cocaine can be prevented and that sigma antagonists can attenuate lethality from an otherwise toxic dose of cocaine.

An initial study from Remi Martin-Fardon, however, found that one sigma antagonist (BD1047) did not reduce cocaine self-administration. Katz then tested several additional sigma antagonists to rigorously determine that no, sigma antagonist compounds by themselves did not reduce cocaine self-administration, even cross a wide range of cocaine doses.

Katz next presented data to remind us that the DAT inhibitor methylphenidate (aka Ritalin) not only fails to reduce cocaine self-administration but that it can increase the self-administration of lower per-infusion doses of cocaine.

However, the combination of methylphenidate with any of several sigma antagonists produced an “insurmountable antagonism” of cocaine self-administration. Meaning that across a wide range of per-infusion doses of cocaine, the rats now failed to self-administer. Importantly, these combinations had no effect on food maintained operant responding, no effect on self administration of opioids or direct dopamine D1 or D2 like receptor agonists but did work to suppress methamphetamine self-administration. This indicates the effect is specific to DAT mediated reinforcing effects.

This all led up to the creation of a compound (CM699) that had the ability to both antagonize sigma receptors and to inhibit the DAT. It was found to blunt the dopamine response to acute cocaine, as measured with intracerebral microdialysis. Furthermore, this single compound produced the “insurmountable antagonism” of cocaine self-administration that had been found for the two-drug combinations.

The talk ended with a proposal that the mechanism of action is that sigma antagonism depletes cholesterol from the membrane which promotes an inward-facing conformation of the DAT.

Obviously, Katz is optimistic that this combined-action CM699 compound proves the concept for a stimulant abuse treatment medication. The half-life of this particular compound was only about 4 and a half hours, thus their immediate goal is to get a longer acting compound which both antagonizes sigma and blocks the dopamine transporter. Nevertheless, the chance that it can completely remove the rewarding properties of cocaine supports the idea that combined activity at DAT and sigma is the route to effective agonist therapy for stimulant abuse.

ASPET 2014: Vaccinating against the effects of nicotine

This platform presentation was in symposium 166. New Preclinical and Clinical Perspectives for Smoking Cessation on Sun, Apr 27, 3:00 – 5:30 PM at the 2014 Experimental Biology meeting.

R. I. Desai (University website, PubMed) presented new results from a study of a vaccine designed to attenuate the effects of nicotine.

I previously discussed the principles involved in anti-cocaine vaccination, and NIDA has generated this handy video explainer on the basic principle of vaccination against drugs of abuse

Desai noted at the outset that there have been four anti-nicotine vaccines developed by drug companies with some of them advancing to Phase II or even Phase III trials. As he remarked, they have all been viewed as failures. Nevertheless it is the case that some of the failures have been due to insufficient antibody titer having been produced in a relatively large proportion of the subjects. Thus, it may be that the principle is still sound but that the vaccines need to be improved in terms of generating more consistent, high antibody titers.

This study used the SEL-068 nano particle vaccine described here in abstract form. Although Desai did not hammer home the point in his presentation, one presumes that this new nanoparticle vaccine is hypothesized to generate higher antibody levels in animals.

This particular study used the drug discrimination procedure (see here for description) to evaluate the interoceptive stimulus or subjective properties of nicotine in squirrel monkeys. The animals were trained to discriminate nicotine from saline pretreatment with a stimulus-termination procedure; one lever was correct when nicotine had been administered and the other lever was correct when saline had been administered. Control animals learned the discrimination well within 30 sessions and some evidence of learning could be observed as early as 3-4 sessions of training.

The control animals received vaccination only after the nicotine/saline discrimination had been learned. The training drug was changed to epibatidine ( a nicotine acetylcholine receptor agonist, i.e., similar to nicotine in pharmacological action) during the vaccination to avoid complicating interpretation of the discrimination behavior. After a few weeks of the vaccination treatment, discrimination for epibatidine was high, however the animals were now unable to discriminate the original training dose of nicotine. A follow-up nicotine dose-substitution challenge showed that only a minor rightward shift of the dose-response function had been produced. A slightly higher dose of nicotine engendered over 80% responding on the lever associated with epibatidine (and previously nicotine).

The effect of vaccination could be overcome by slight increases in the dose, at least in animals previously experienced with nicotine.

Interestingly, the animals that were vaccinated prior to the start of any discrimination training did not learn the nicotine discrimination. Over about 30 training sessions, there was no selective responding on the nicotine paired lever when nicotine had been administered. This indicates that the subjective feeling of the training dose of nicotine had been attenuated to the point where it wasn’t reliably different from vehicle exposure.

The research team then went on to train the vaccinated group to discriminate epibatidine from saline. In this case, the discrimination was established with about the same time course as was seen for nicotine in the non-vaccinated group. It is structurally different, thus antibodies specific to nicotine that were generated by the vaccine would not be expected to recognize epibatidine. This part of the study shows that the vaccinated animals would still be able to form a discriminative set based on the activity of receptors through which a major part of nicotine’s action is conferred.

One of the most interesting outcomes of this study was that the learning of a discrimination based on nicotine could be blocked by vaccination. This tends to suggest that the most effective clinical target will be to vaccinate children before they have any experience with nicotine.

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also see Would you vaccinate against drug abuse?

Lost Labs and Implied Tragedy

Somebody I normally respect is on the Twitts naming and shaming scientists who have lost their NIH funding and are, allegedly*, shuttering their laboratories.

This makes me deeply uncomfortable for the naming and shaming part, one.

More important is the implication that it is somehow a greater tragedy** that people who have enjoyed something on the order of 20 years of NIH funding are now at the end of their careers.

This is nonsense. First of all, if you have the luxury to retire at 60 with a nice fat pension, maybe an Emeritus office to visit, with your kids through college (generationally more likely), house paid off (ditto), etc, etc then retiring “early” is what we used to think of as a huge win. So you stopped publishing science a little earlier than you might have liked. So what. Get a hobby.

More importantly, it necessarily diminishes the tragedy of others who never had funding.

I am not okay with this.

As you know, I’ve managed to keep my head above water as an NIH funded lab head……so far. And yeah, I feel the greatest affinity for my own continued survival in this career. Sure. Hard to avoid and I don’t fault anyone for feeling the same way. What I do fault people for is not realizing at some level how deeply selfish this tendency is. At least act like you understand everyone should have a fair shot?

And that is the point. It has been decades that I have watched the fate of people who might have become NIH-funded investigators of various levels of fame, fortune and pizzaz. Decades over which I have watched the career arcs of people who have enjoyed NIH grant support.

There are a lot of people who should have been PIs with generous amounts of grant support who never achieved this outcome. Lots. There are a lot of people who managed to maintain funding that are clearly no more, and often less, worthy than those who did not enjoy such success.

There has to be at least one unsuccessful young gun of your field that, were you the boss of science, you would put 5 senior investigators*** out to pasture to fund. If you don’t know of any people like that, you aren’t thinking very hard about it.

So sure, it is a tragedy when a luminary of your field closes shop. It is distressing even when a middle rank plodder has to pack it in. These people are salient to you, I realize. Because they are publishing. They have generated papers that are important to you.

The folks who never had a chance in the first place? All too easy to forget. All too easy to shrug off their failure to become a luminary as fault of their own (they “chose” alt career) or the system (life is hard).

But they are most assuredly a Lost Lab too.

Try not to forget that.
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*I say allegedly because we have heard a tremendous amount of rumoring about labs “about to close” because of the dismal NIH grant situation. See this 2009 report in Nature News. As it turned out, one of those researchers was just fine and one was picked up at the time but didn’t learn the proper lesson.

**I am also unimpressed by the recitation of these Lost Labs’ publication record by Journal or by the lab in which that PI was trained. As if that tells us anything about how tragic it is or is not to have lost their labs. Please.

***Naturally even within a subfield, not everyone agrees on who the most promising young gun(s) is/are and not everyone agrees on who are the 5 dispensable peers. I am not suggesting this Lost Lab situation is easy to fix.

Grant Review Site Visits

…need to be ended.

They represent a huge risk for bias dependent on the personal characteristics of the investigators to rule the day.

Are you an older, white-haired, heteronormative appearanced, able-bodied picture of “Scientist and Professor”? Great!

Are you overweight? Do you stutter? Express unexpected gender presentation? Nonwhite? Female? Are your language skills less than native to the reviewer’s ears? Too young? Too hot? Not hawt enough? …. Not so great.

Should your grant proposal be affected strongly by the direct face to face impression of these characteristics?

No.

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H/t: @jwoodgett

Update: See PDF for site visit procedures

A chance to support research on Parkinson's Disease

The scientist known as @parklifensci (Parklife blog) on the Internet will be walking in the Parkinson’s Unity Walk. The donation page says:

Why I’m walking:
Every walker and donor makes a difference by taking the Walk one step closer to finding the cause and cure for Parkinson’s. By joining together with thousands of others, we’ll be empowering those who are living with the disease, and honoring those who lived with Parkinson’s.

Who I’m walking for:
Over 1 million people in the United States have Parkinson’s. 60,000 people are newly diagnosed every year – one person, every nine minutes. Walking and raising funds and awareness for research is my chance to help.

Why I’m supporting the Parkinson’s Unity Walk:
100% of donations go to research. The Parkinson’s Unity Walk is the largest grassroots event in the U.S., raising funds and awareness for research.

Ways to support my fundraising efforts:
There’s strength in numbers so please join me. Donate, register to walk, and fundraise.

I encourage you to donate if you can or join the walk if you are nearby.

"These forces are real and I had to survive them"

Neil DeGrasse Tyson on “The Larry Summers question: What’s up with chicks in science?”:

From a panel discussion hosted by the Center for Inquiry. Starts at 1:02:30 of the video.

Your Grant in Review: The Biosketch Research Support Section

A question came up on the twitts about the Research Support section of the NIH Biosketch.
https://twitter.com/Dr24hours/status/458301809707483136

The answer is that no, you do not. I will note that I am not entirely sure if this changed over the years or if my understanding of this rule was incomplete at the start. However, the instructions on the Sample Biosketch [PDF] provided by the NIH are clear.

D. Research Support
List both selected ongoing and completed research projects for the past three years (Federal or non-Federally-supported). Begin with the projects that are most relevant to the research proposed in the application. Briefly indicate the overall goals of the projects and responsibilities of the key person identified on the Biographical Sketch. Do not include number of person months or direct costs.

The last bit is the key bit for Dr24Hour’s question but I include the full description for a reason.

dr24Hours also asked:
https://twitter.com/Dr24hours/status/458304459228340224

and there was a followup to my initial negative response

@MyTChondria @Dr24hours @drugmonkeyblog come on! The fact that he was awarded the grant does mean something concrete unlike noble price pie!

— Lax Iyer (@laxvid) April 21, 2014

Together, these questions seem to indicate a misunderstanding of what this section is for, and what it is trying to communicate.

Note the use of the term “selected” and “most relevant” in the above passage.

The Biosketch is, in total, devoted to convincing the reviewers that the PI and other Investigative staff have the chops to pull off the project under review. It is about bragging on how accomplished they all are. Technically, it is not even a full recitation of all the support one has secured in the past three years. This is similar to how the Peer-reviewed Publications section is limited to 15 items, regardless of how many total publications that you have.

Inclusion of items in the Research Support section is to show that the Investigators have run projects of similar scope with acceptable success. Yes, the definition of acceptable success is variable, but this concept is clear. The goal is to show off the Investigator’s accomplishments to the best possible advantage.

The Research Support is not about demonstrating that the PI is successful at winning grants. It is not about demonstrating how big and well-funded the lab has been (no direct costs). It is not even about the reviewers trying to decide if the PI is spread too thinly (no listing of effort). This is not the point*.

In theory, one would just put forward a subset of the best elements on one’s CV. The most relevant and most successful grant awards. If space is an issue (the Biosketch is limited to 4 pages) then the PI might have to make some selections. Obviously you’d want to start with NIH R01s (or equivalent) if the application is an R01. Presumably you would want to supply the reviewer with what you think are your most successful projects- in terms of papers, scientific advance, pizzaz of findings or whatever floats your boat.

You might also want to “selectively” omit any of your less-successful awards or even ones that seem like they have too much overlap with the present proposal.

Don’t do this.

If it is an NIH award, you can be assured at least one of the reviewers will have looked you up on RePORTER and will notice the omission. If it is a non-NIH award, perhaps the odds are lower but you just never know. If the reviewer thinks you are hiding something…this is not good. If your award has been active in the past three years and is listed somewhere Internet-accessible, particularly on your University or lab website, then list it on the Biosketch.

Obviously this latter advice only applies to people who have a lot of different sources of support. The more of them you have, the tighter the space. Clearly, you are going to have to make some choices if your lab operates on a lot of different sources of support. Prioritize by what makes sense to you, sure, but make sure you pay attention to the communication you are trying to accomplish when making your selections. And beware of being viewed with a suspicion that you are trying to conceal something.
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*Yes, in theory. I grasp that there will be reviewers using this information to argue that the PI is spread too thinly or has “too much” grant support.

Job ad for Assistant Professor position makes it explicit…

Drexel University College of Medicine is hiring! ….sortof.

The Department of Neurobiology and Anatomy at Drexel University College of Medicine invites applications for a tenure-track Assistant or Associate Professor. We seek a SYSTEMS/BEHAVIORAL NEUROSCIENTIST whose research utilizes contemporary molecular, physiological and/or imaging techniques to address fundamental questions related to monoamine networks, cognitive function and motivated behavior, or psychostimulant drug actions. Applicants should have a Ph.D. in Neuroscience or a related field, a record of excellence in neuroscience research and publication, and preferably extramural funding (e.g., K99/R00 grant).

emphasis added. Unnecessarily.

Very interesting to see this when the drumbeat against soft-money faculty hiring and Med schools lust for indirect costs is getting louder.

h/t: @markgbaxter

Thought of the Day: The NIH Can't Win

A comment over at Rock Talk made a fairly traditional complaint about the NIH funding system. Dan C stated that: “NIH is to be criticized that it funds “usual suspects.”

Today, I find this funny. Because after all, most of the people complaining about the NIH system want to become one of the usual suspects!

Right? They want to get a grant, one. They want to have some reasonable stability of that grant funding in a program-like sustained career. Most of them don’t want to have to struggle too hard to get that funding either….I doubt anyone would refuse the occasional Program pickup of their just-missed grant.

Once you cobble together a bit of success under the NIH extramural grant system, those who feel themselves to be on the outs call you a “usual suspect”. For any number of reasons it is just obvious to them that you are a total Insider (and couldn’t actually deserve what you’ve managed to accomplish, of course). This may be based on the mere fact that you’ve acquired a grant, because you work in a Department or University where a whole lot of other people are similarly successful. This may be because it appears that POs actually talk to the person in question. It may be because a FOA has appeared in a research domain that you work within.

Anyone sees the duck floating serenely on the water at a given point in time and it looks like this is one most usual suspect waterfowl indeed.

I used to be annoyed at my approximate lateral peers in science who appeared to be having an easier time of it than I did. I had my Insider attributes as a younger faculty member, make no mistake, but I also had considerable Outsider traits, considering where I was seeking funding and for what topics of research. Some of those folks, over there, well boy didn’t they get an easy ride because of being such Insiders to the subpart of the NIH system!

I still have those thoughts. Even though I’ve seen many of the people I thought had it made in the shade go through their dry spells and funding down-cycles. Despite the fact that as each year goes by and my lab remains funded, I become more and more one of the “usual suspects”.

I believe that if I ever feel like I am one of the usual suspects, if I feel like I deserve special treatment and stop fighting so hard to keep my lab going that this will be the end.

I advise you to try to retain the same feeling of “outsider” that you feel as a noob PI for as long as you can into your career.

Getting back to the point, however, the NIH simply cannot win with these criticisms. Those who are feeling unsuccessful will always carp about how the NIH just funds “their” people. And if the NIH does happen to fund one of these outsiders, this very act makes them a usual suspect to the next complainer.

The NIH can’t win.

Will You Be Attending Experimental Biology 2014?

The good folks at the American Society for Pharmacology and Experimental Therapeutics have seen fit to invite me to serve as an official blogger for the Experimental Biology 2014 meeting to be held in San Diego, CA, April 26-30. I will be joined in this effort by @katiesci who blogs at http://sicknessisfascinating.blogspot.com.

I would like to invite you, Dear Readers, to send me your presentation details, should you be attending this year. You can drop a note in the comments to this thread or send me an email (drugmnky at the google mail). I will try to stop by if it fits in my schedule and maybe blog it if I can understand what you do.

There may also be a meet up or two which revolves around either this community at the blog or my Twitter Tweeps. So stay in touch about that. If you are interested in such a thing and leave a comment, this may help to stimulate someone (say, me) to get off their behind and organize something.

Looking forward to seeing some of your science and to meeting some of you.

NIH backs down on resubmitting unfunded A1 grant applications

The rumors were true. NOT-OD-14-074says:

Effective immediately, for application due dates after April 16, 2014, following an unsuccessful resubmission (A1) application, applicants may submit the same idea as a new (A0) application for the next appropriate due date. The NIH and AHRQ will not assess the similarity of the science in the new (A0) application to any previously reviewed submission when accepting an application for review. Although a new (A0) application does not allow an introduction or responses to the previous reviews, the NIH and AHRQ encourage applicants to refine and strengthen all application submissions.

So, for all intents and purposes you can revise and resubmit your failed application endlessly. Maybe they will pick you up on the A6 or A7 attempt!

Sally Rockey has a blog entry up which gives a bit more background and rationale.

While the change in policy had the intended result of a greater number of applications being funded earlier,

I really wonder if she believes this or has to continue to parrot the company line for face saving reasons. There is no evidence this is true. Not until and unless she can show definitively that the supposed A0s being funded were not in fact re-workings of proposals that had been previously submitted. I continue to assert that a significant number of PIs were submitting “A0” applications that were directly and substantially benefited by having been previously reviewed in different guise.

As a result, we heard increasing concerns from the community about the impact of the policy on new investigators because finding new research directions can be quite difficult during this phase of their career.

If the true concern here was the ESI or NI, then they could have simply allowed them to pass the filter as a category.

The resubmission of an idea as new means the application will be considered without an association to a previous submission; the applicant will not provide an introduction to spell out how the application has changed or respond to previous reviews; and reviewers will be instructed to review it as a new idea even if they have seen it in prior cycles.

The only way this is remotely possible is to put it in a different study section and make sure there are no overlapping ad hocs. If they don’t do this, then this idea is nonsense. Surely Dr. Rockey is aware you cannot expect “instruction” to stick and force reviewers to behave themselves. Not with perfect fidelity.

However, we will monitor this new policy closely.

HA! If they’d decided to allow endless amendments (and required related apps to be submitted as such) then they would have been able to monitor the policy. The way they did this, there is no way to assess the impact. They will never know how many supposed “A0” apps are really A2, A4, A6, nor how many “A1” apps are really A3, A5, A7…etc. So what on earth could they possibly monitor? The number of established PIs who call up complaining about the unfundable score they just received on their A1?