According to a summary of a recent presentation from Francis Collins (NIH Director) to the SMRB on May 29 provided by the Research Society on Alcoholism. Key points:


“We are hearing from some of the lobbying organizations that are involved in the use and sale of alcoholic beverages – the wine, beer and liquor industry.
They are not particularly happy about this. We are going to have to see what response comes forward from them. They are very well connected from the political side of this. We are proceeding forward, but I want to give you a heads up that there could be some noise.”

Sol Snyder asked why and Collins had this to say:

“Their view is that alcoholic beverages are an acceptable, social, desirable thing. Consider it to be a food. Noted that it has health benefits. Notion that it will be lumped with drugs of abuse, many of which are illegal, rubs them the wrong way.”

Exactly what I’ve maintained all along. This proposal to merge the NIAAA with NIDA is, scientifically speaking, a no-brainer. It makes a lot of sense and if any ICs are to be merged, this is the first thing on the table. If this can’t be done…there doesn’t seem any point to discussing any other mergers.

However. I’ve also noted that the beverage industry has a HUGE amount of pull in Congress and and HUGE interest in not seeing alcohol defined as a drug like any other. They don’t want to be mentioned in the same sentence with drug cartels! They sure as hell don’t want people discussing, matter-of-factly, that their beloved product is really not substantially different* from cocaine, methamphetamine and heroin, save by historical accident.

So this whole proposal could come crashing down if the beverage interests can buy up enough support in Congress to quash this. Personally I think all this comes down to is the extent to which they care. I believe if they throw around enough cash in Washington DC they can halt this.

Question is, will they?

Will they be bought off by some careful wording** and policy statements that preserve the special status of alcohol within the new IC?
*by some ways of looking at things. First and foremost, addiction.
**Perhaps by keeping the word “Alcohol” in the title of the IC to distinguish it from “Drugs” and even “Substances”?

ps: as always, see Disclaimer. I’m an interested party in this process.

A brief dialog

May 30, 2012

“It seems like just about every time I manage to get up from the mat, the system punches me back down again”

“Yeah, doing science on the NIH extramural dime is like that. deal, dude”

DrKlapperich asked for input on the Twitts:

NIH grantees: Weigh in on the phenomenon of senior co-I’s piling onto an R01 with a PI who still has “new investigator” status.


I’ve noticed this with some jr colleagues in a couple of cases. Wondering if it was wide spread.

It would take some data mining from the NIH extramural office to determine whether there are any changes going on, of course. Hard to determine from the handful of colleagues that you happen to know and who happen to share their grant strategies with you.

There are at least three possibilities that spring to mind.

Number one, grant strategy from the more-junior investigator.
It has been a thing, since forever approximately, for junior investigators that they should involve a more-senior colleague to hold their hand. This was infuriating for me, certainly, when I started writing grants. The supposedly substantive reasons for this were vague and seemed to me to be very thin cover for an ill-considered StockCritique. A StockCritique of grants that, like so many others, appeared to me to be transmitted culturally down study sections without much examination. You can file it in the general category of “riskiness” that continually irritates me. It sounds good, right? “let’s not risk all this tax payer money on an untried investigator”. Sounds like due diligence. But when you think about the maturity of these people who have finally managed to land a faculty level job, start up their own program and (otherwise) put together a competitive grant application….risk?

No more so than for any applicant. That’s my view. However, there has always been an undercurrent of supposition that if a brand new Assistant Professor (or equivalent) has a senior colleague on their proposal for 5% somehow this make everything better.

So this may be one answer to the question in these much, much more competitive days for youngsters. They are larding their proposals up with senior collaborators to stave off the criticisms of “risk” associated with a junior PI.

Number two, more grant strategy from the more-junior investigator.
Science is becoming increasingly more collaborative and the most competitive applications are simply more likely to involve collaborative projects. Maybe….

Number three, grant strategy from the more-senior investigator.
The way the original Twitt phrased the question makes it sound like the impetus is coming from the more-senior person. The implication is that s/he is trying to take advantage of the ESI/ New Investigator policies at place in the NIH right about now. Policies that fund New or Early Stage Investigators applications preferentially. From the perspective of the senior investigator, it may not matter how the money comes into the lab, the major factor is that the money DOES arrive. Who cares who the PI is? Maybe this is good for everyone (see above) and maybe it is exploitative. That will come down to specifics.

The factor that more concerns me is the drive at the NIH to kill the rich. We’ve been discussing this set of proposals that are targeted at making sure those who are successful at present don’t become too successful. or something. One clear response of the senior investigator is to hide the amount of NIH money that is supporting his/her lab by getting it through collaborations. Anything that keeps the senior investigator name off of the “PI” list would help. Sure, the NIH can always get down to the specifics of collaborative relationships but it is going to be hard to account for. Modular grants list percent effort for co-Investigators (as long as they are Key Personnel) but not specific dollar amounts. Who is to parse every grant application to try to figure out how many modules are going to be spent in the PI’s lab versus her close collaborator’s lab? How much percent to assign to the postdoc who is bridging the two labs?

So you are damn right that at present the smart senior PI will be looking to get onto as many other people’s grants as possible. A module here, a percent effort there….anything to keep the overall funding as hidden as possible. Driven 100% by all this discussion of capping the rich.

Sure, the current limits are unlikely to affect that many people and it is an unknown how many of those who trigger the special consideration will actually get denied. But why risk it? Who knows what the future holds? They may decide to get even stricter. So the smart money says to pile on to as many junior investigator grants as possible.

Sadly, this reverses a prior trend in which the more successful senior investigators in the departments went out of their way to try to bring the brand new people along under their coattails by writing them into the senior investigator’s proposals.


Just like I was sayin’

it is more reasonable for the NIH to stop wasting money on Profs who are all distracted with teaching and service and nonsense and just pay straight up for services rendered. If they want to leverage, put more research into the hands of soft money faculty since their salary doesn’t scale with projects. Full time attention on NIH’s biz is more verifiable and efficient.

The latest post at Rock Talk shows the data.

Read the rest of this entry »

In NIH land (and apparently at NSF) the annual Progress Report functions as the application for the next non-competing interval of support. The NIH ones are short, 2 pages, and you have to squeeze in comments about progress on the project goals and the significance of the findings. So there isn’t a lot of room for all the data you have generated.

Science Professor indicates that she involves trainees in the preparation of progress reports.

I was asked to do this when I was a postdoc and I have continued the tradition with my postdocs. As you will surmise, I always think it a good idea to train postdocs in the grant-game. How much were/are you involved with progress reporting as a postdoc, DearReader?

Prof-like Substance’s post was asking how seriously to take the NSF progress report. I have always taken my NIH ones pretty seriously and tried to summarize the grant progress as best I can. (Yes, I rewrite the drafts provided by the postdocs – thus is training after all.) One benefit is that when it comes time to write the competing renewal application you have a starting point all ready to go.

For the noob PIs… Don’t sweat it. I’ve only once had a PO so much as comment on the Progress Report. In that case this person was, IMO, clearly out of line since we were right on target with the grant plan. More so than usual for me. And the PO also was misunderstanding the science in a way that was a little concerning for that little subarea of the IC…but whatevs. I made a response, the PO backed down and the project went on without further kvetching from this person.

So how about it? Do you involve your trainees in writing Progress Reports? Have you had any responses from POs on these? How seriously do you take them?

case in point, michael b eisen, who we know as @mbeisen. He’s HHMI, UCB prof, of a certain age and publishing stature….basically your science 1%er.

He has no fucking clue about normal people.

still think people mostly use it as excuse; page charges for most nonOA society Js are higher

What is under discussion is the publication fee of some $1,350 required at PLoS ONE.

This came about because I have been idly speculating of late about the Impact Factor of PLoS’s about 4.4. This compares favorably with many run of the mill journals (tied to a society or otherwise) that publish huge amounts of general neuroscience stuff. Take initial modifier [American, European, Canuckian, International….etc], add “Journal of”, insert [Neuroscience, Pharmacology, Toxicology, Drug, Alcohol, Neurophysiology, Behavior, Cognition….blahdeblah] and you’ll get the corpus. Some variants such as “Neuroscience” or “Psychopharmacology” or “Neuropharmacology” or …. You get the point. Published by the usual suspects: Springer, Wiley-Blackwell, Elsevier.

Most of these come in with IFs under 4.4…or at least as close as make no practical difference.

They also publish a LOT of the papers in the fields that I follow and participate in.

I happen to think this is where the real science exists. If you’ve ever cited a paper in one of these journals…..yeah.

I also protest, when people are talking about the level of peer review at the Glamour Mags and attempting to sidestep the outsized retraction rate at those journals (hi PP!), that oftentimes the review is harshest at these journals. The reviews are by more directly focused experts and the scope of the paper is lesser. So the review comments can be brutal.

They can also, at times, be pretty demanding. I, myself, have in recent memory been asked for essentially an Aims worth of data be added to an already not-insubstantial manuscript at one of these sub-PONE-IF journals. AYFK? If I added that, I’d be submitting UPWARD you dumbasses!!!

As you know, PLoS ONE promises to accept manuscripts that are SOUND. Not on the basis of all the extra stuff some reviewer “would like to see”. Not satisfying the nutty subjective “disappointment” of the reviewer that you didn’t do the study he would (in theory) have conducted. Most emphatically not on the prediction of “impact” and “influence”. Supposedly, not on the basis of even having a positive finding!

So with a higher IF and this promise….I’m all of a sudden having a hard time figuring out why people aren’t just putting all their stuff in PLoS ONE? What is keeping them back?

It appears to me from doing some harder thinking about what is IN this journal that subfields are either in or out. There are some cultural forces going on here which I touched on previously. People want to make assumptions that they are going to get “their” editors and “their” reviewers….not just whatever random fringe OpenAccess Wackaloon who signed on to the PLoS ONE train sort-of/kinda overlaps with their work.

The other huge problem is the cost. $1,350 to be exact. There’s a waiver….but it isn’t really clear how likely one is to GET that fee waived. They don’t make any promises before you submit the paper. And that’s where it counts! Why go through the hassle of review just to find out several weeks later that you have to pull it for the $$? Might as well not even try.

Part of the problem here is the 1%ers like mbeisen and @namnezia think “society journal” means: PNAS is $70/page, JNsci is about $950 total.

yeah, SOME journals that technically qualify as “society” journals have page charges or publication fees. But the ones I’m talking about, for the most part, do not. Not. ONE. dime. Not a $75 “submission fee”. Not a page charge.

They are FREE from start to finish.

JNeuro and PNAS are not normal, run of the mill society journals. This is not what we are discussing. It strikes me that this frame of reference is why mbeisen can’t grasp the problem I’m trying to explore. It makes me fear that PLoS ONE is falling short of what it could be because it was founded by Science 1%ers who are clueless and out of touch.

It’s like I’m blogging in the wind here.

Dario Maestripieri pointed to an Opinion by Fred Southwick in The Scientist over at The Creativity Post. Southwick’s point, in part:

The maladaptive insistence that research scientists obtain their financial support by continually writing federal, state, and private grants often prevents scientists from stepping outside the boundaries established by this grant process. Because the success rate is now down to 10 percent, academic scientists are forced to spend much of their time writing proposals, rather than performing creative research.

The balance of his remarks seem mostly directed at what University changes are needed.

Maestripieri adds a bit more finger-pointing at the NIH (and other major granting agencies):

Obtaining research grants has become an increasingly competitive business. Many more people apply for grants now than in the past while the amount of funds available has remained the same or decreased. Federal funding agencies fund only about 10% of the applications and grant review panels have become highly risk-averse. They tend to fund proposals by well established investigators, which often represent replications or minor extensions of previous work, while creative, original, and riskier proposals by young researchers are penalized. The funding issue has its origin outside of academia and its solution must also come from outside of academia: a political decision to allocate more funding to research.

More money, yes. But let us not take our eye off the ball.

Those of you* who have been with me for all these years should remember from whence this blog voice came.

One of the problems that I have always had in my head, driving my comments about fairness to young investigators, is that of the inherent conservatism of the NIH granting system. This comes from two major sources. First, the peer review by those who are already well-ensconced in the system. That means people who were selected by that system for success. You have to have been awarded an R01 to serve on a review panel, mostly speaking. This means you have to be able to at least fake writing the grants the way the established folks “expect” to see them. If you can’t….you are going to fail. It means that you have to propose science that those who are already on the inside “get” in some way. Sorry, but even in the 25 page days, that wasn’t necessarily long enough to get three people totally on board with your ideas. It helps a lot if the reviewers are already predisposed to see things your way.

The second major driver is the review culture often expressed in words such as “risky”, “feasibility”, “fishing expedition”, “insufficient supporting preliminary data”, “untried investigator”….and “highly productive scientist can solve any problems that may arise”

It can sometimes** be appallingly conservative on panels.

Being something of a student of the past few decades of research supported in my areas of interest, mainly by NIDA, I’ve been bothered by all of this and the Street Lamp Problem***. The SLP is common in science, far too common. And before you get all huffy, yes we all suffer from this on occasion. It may not be such a bad thing for labs but it is death for a broad-based funding agency such as the individual ICs of the NIH.

To give you a flavor, that has trickled through my posts now and again, the preclinical drug abuse world has two theoretical poles that have driven much of the research modelling. One is the “feel good” or reinforcement side. The notion being that if we understand why drugs make us feel good and why they may stop making us feel quite as good (for a given dose) then we’re on to something. The other pole says, nonsense, this is about feeling bad. Everyone feels good on drugs but not all become addicted****. What really matters is that some people start to feel so crappy when they are not intoxicated that it drives them to take more just to feel normal.

For a very long period of time the reinforcement types ruled the day. They had the tools, the simplest models, the biological targets were obvious. Cocaine, meet dopamine transporter. easy peasy.Ditto heroin. Methamphetamine? No problem. And the current midcareer “reinforcement” butt kickers sucking up all the NIDA money are at least three scientific generations removed from the start of this.

umm, “feeling crappy”? where’s the target? how do you even define that in a mouse?.

Anything rats won’t readily self-administer intravenously (THC, nicotine) or where the targets weren’t known (THC, Alcohol)….well, shrug. The light isn’t very good over there. So they received short shrift. At NIDA. Luckily in the case of alcohol there was a whole ‘nother IC devoted to it. It is no coincidence that one of the the main drivers of the “feel bad” pole is dug in much more deeply at NIAAA than ever at NIDA.

Things eventually opened up. The CB1 receptor was cloned and the streetlight flickered into life above THC research. Some folks finally worked out what was UP with nicotine self-admin and that started rolling. People flogged the hell out of “reinstatement” and “escalation” models to try to get past a couple of problems with the straight-up acute “feel good” models.

Funding-wise, it took some heroic efforts, if you ask me. Remember, all the while the scientists were working through this, the Program staff was getting their best intel from those scientists. People made discoveries and published papers and kept getting high grant scores. So Program thought they must know what they are talking about. The fringe complainers? Bitching about their biased grant reviews? Failing to publish their ideas convincingly (because they can’t get the awards, of course)? Chalk them up to lunatic fringe, right? “Come back when you convince us all”, they are told.

But we haven’t learned our lesson, I have little doubt. In fact, we (as a whole enterprise- scientists and Program staff are doubling down. Kill the R21! Circle the wagons on feasible projects where the “significance” and “likely impact” is obvious to all. Demand more Preliminary Data. Save the Small Town Grocer and the Noonans. Just keep plodding along with your models, the same as half a dozen others, and you deserve “your piece of the pie”.

“Innovation” can only come from within a defined space of the “feasible”.

I could cry for wholesale changes. Dismantle everything. Break down the large, established groups, radically restructure grant review panels and turnover your entire Program Staff with their “established relationships”. But that’s not going to happen.

What we can push for is the restoration of the R21. The expansion of it, perhaps. With the very, very firm goal of making sure the ones getting high scores are “Exploratory”, “Developmental” or both. It can be done. The simplest way would be to give extra bennies on an R01 application that arose from a prior interval of R21 support. But you could get the right reviewers and instruct them properly as well. Some of us get R21s. Some of us can’t help but talk about supporting data and whether it is going to “work”. SROs know who is who.

*PP and maybe one or two others.

**often. Not always, often.

***Policeman comes across obviously drunk guy searching through gutter at night under a street lamp and inquires as to the problem.
“Lost m’ keys” slurs the drunkard.
“And where did you lose them”, queries our intrepid flatfoot.
“Up the block on my way home from the bar.” is the reply.
“So why on earth are you looking here, my friend?”, puzzles the copper.
“The light is better”, comes the response.

****Ok, in fairness while that is my take, it is only recently that people are coming around to this extent.

Oh yes. Via pharmalot and Science Insider:

RePORTER tells us that the NIMH has funded:
from 17 May 2012 to April of 2017. With Charles Nemeroff as the Principal Investigator.
To the tune of $401,675 total costs for FY 2012. His institution seems to come in at 53% overhead which would make it $263K in direct. Hmm. Maybe that IDC rate is outdated because why would you bother with a traditional budget just to request another $13K?

if you are wondering, as I was, “2 of 2” appears to be this project. This junior partner in the deal gets only $290K in total costs.

YHN on:
Nemeroff’s third strike
Inselgate linkage

Nothing to say, really. It was a COI case where nobody really laid gloves on the guy for fraud. All he’s really guilty of is underreporting his earnings from Big (and small) Pharma interests to his prior employer Emory U. That should have triggered a stink with his NIH awards but again the rules are about managing conflict…nothing to prove that he actually defrauded the NIH with faked research to benefit his corporate paymasters. Nothing like that ever confirmed. Plus a failure to disclose his conflicts on some review articles or whatnot. Again, if he had disclosed properly it is very likely nothing would have been done differently.

Still, the whole thing smells and I’m sad that it happened in fields which vaguely intersect with my interests. I’m sadder still that the NIH fails to recognize the effect it has on all the scientists who are busting their behinds to secure a grant and do good work that isn’t tainted by conflict and extra-job income to the tune of hundreds of K per year in “consulting” gigs.

Dude. Fuck. Sigh.

UPDATE 052912: Grassley Investigates. Of course. Great move NIMH, great move.

Thoughts on NOT-OD-12-110:

The threshold of $1.5 million total costs. How’s that break down? Well if you are in a consensus ~50% overhead state university, let’s see…Thats FOUR full-modular awards. But let’s be clear, odds are you got cut by at least a module per award so that’s only $900K get to be in a University with about 70% overhead and you are still clear. What bout the much-rumored 100% overhead small institutions? well, you get three R01s before you go under strict scrutiny.

I do wonder if this will satisfy all the “kill the rich” voices? Will they see this as the NIH taking them seriously or as a meaningless sop?

Next question, this is just identifying special Council level review…No guarantee that any grant will ever be blocked because the PI has too much $$. No guarantee that negotiations wouldn’t be made either. “Say, PI Jones, would you please put some more junior colleague on as titular head to one of your other awards so we can give you this one”?

new MultiPI awards won’t trigger the scrutiny unless all PIs trigger the threshold. Hello courtesy “multi”PIship!!!

It may possibly change some people’s strategy so that they work harder to distribute effort around to other people’s awards in small percentages. Like junior PI is going to screw BigCheeze over on the agreed upon part of the direct costs? No worries there.

How are study sections going to respond to this. Will they take this as the NIH saying “This is our threshold for being worried about too much money. Now shut up about this for anything below this amount.”? Or will they take this as encouragement to think about lab size even more when they are reviewing the grant in front of them?

The AAAS has a summary up which deals with NIH’s head of the Office of Extramural Research Sally Rockey’s comments on the FY13 budget for the NIH.

Sally J. Rockey, deputy director for extramural research at NIH, said that some changes in grants management already have been proposed as part of the president’s budget submission for the 2013 fiscal year.

and those solutions will be familiar to those following along at the RockTalk blog. It boils down to “kill the rich!!!”. If you already have it, or have too much of it, they are gunning for you.

These include an across-the-board funding cut of 1% for continuing grants; negotiating the budgets for new competitive grants to avoid growth in the average size of award; eliminating increases for inflation in multi-year grants; giving additional scrutiny to researchers who already receive in excess of $1.5 million a year; and continuing to fund early-stage investigators at the same rate as established investigators for new grant applications.

The alternative posed by Rockey is “Darwinian”.

“Many people thought we should keep the current system,” Rockey said. “Just keep the Darwinian approach. Don’t try to go in there and socially engineer anything.” Others weighed in on the merits of the various options for change, including some approaches beyond those discussed by Rockey. These could include limiting payment for indirect costs associated with grants, limiting large project grants, and providing more support to small labs and individuals by limiting grants to large labs.

Well it sure looks like this depiction to me.
Just about the only person who is not under potential attack under this scenario is the small town grocer. Otherwise known as Noonan. I have been reluctant*, I will admit, to even think very much about something that has been raised (identified?) by PhysioProf on numerous blog posts. It boils down to the suggestion that it is the Small Town Grocer scientists that are precisely who the NIH should be dropping from the system. Actually, PP tends to phrase this as a suspicion that this is just what the NIH is up to, rather than a suggestion that they should do so.

Since he’s been making this comment I’ve gradually noticed that this option is never raised. Rockey maybe touched on it a teensy bit in the AAAS piece.

Institutions also could help manage the demand for grant money by reducing the number of applications submitted by their faculty, Rockey said. And NIH can examine its research priorities, seeking to reduce support for less innovative ideas and eliminating some of the duplication of effort.

Oh yeah. You do it for us, University of State. Right. Like that is in their interest. Sorry but we’re in tragedy of the commons territory Dr. Rockey and you are going to have to do this yourself if you want it to happen. Take a hard run at the smaller, lesser and slower producing laboratories. Stop saving them with bridge funding, stop taking pity on your “long term funded investigators” and the like.

It is indubitably the case that we have too many investigators seeking too few grant dollars. All of the main solutions on the table are going to squeeze the most productive, best funded laboratories (not to mention the noobs who finally managed to land their first grant to find a cut that oblates a warm body). Just so that more awards can be made. To, presumably, the small timers.

And those more productive labs are going to fight back as best they can. Submit even MORE grant to make up for the cut funds. Work deals with their friends and junior colleagues to be collaborating investigators so to hide the amount of direct funds going into the laboratory. Pursue training grants, beg for supplements….whatever it takes. They are not going to go “hum, well, I’m just going to be happy with less”.

And, sad but true, these are likely going to be the people on study section stepping down hard on, guess who? Investigators who are not like them.

You want Darwinian, Deputy Director Rockey?

If a better-funded, more-active reviewer is really thinking, s/he is best off bashing the crap out of one-trick-pony PI’s grants. Why? Because you might just put them out of the game permanently! If you can do that, you’ve reduced the competition in a real way. Conversely if you stamp on a reasonably well funded and reasonably active PI, you haven’t put them out of business at all. Just ensured they will put in yet more grants.

Look, I’m still not sure I know the best path. I love the democratic nature of the ideal of the NIH pure Investigator Initiated system. Anyone with a good idea should be able to get funding.

But I also believe that little gets done on one full modular, cut to $200/yr, maybe reduced to 4 yr grant anymore**. Research programs may not be efficient after 5 grants but they sure as heck aren’t in the sweet spot with one either.

And I know for damn sure the insecurity and grant churning of the past 5-8 years has been hugely detrimental to the conduct of science.

Sadly, I don’t see that any of the proposals of the NIH do anything to decrease churning.

UPDATE: see NOT-OD-12-110, just published today:

This Notice announces NIH’s intent to pilot procedures for investigator-initiated grants and cooperative agreements in consideration of managing resources during austere times. During May 2012 NIH Institute and Center (IC) Advisory Council meetings, Councils will discuss and pilot-test procedures for the additional review of grant and cooperative agreement applications from Program Director(s)/Principal Investigator(s) [PD(s)/PI(s)] who already receive in excess of $1.5 million per year in total costs to determine if additional funds should be provided to already well-supported investigators. The feedback from this pilot will help NIH further refine policies for managing limited grant resources.

The cartoon, btw, is stolen with apologies from Dent. I, uh, altered it.

*anyone who thinks their relative position in the NIH world is predictable or static needs their head examined. I could be calling for an option that will end my lab’s viability here.

**Read this. It is short.

A recent HuffPo piece on that rather flagrant bit of cover trolling from TIME magazine irritates me.
Read the rest of this entry »

In yesterday’s discussion, I finally got a partial glimpse of the issue when NatC observed:

Discussions about how to manage and plan protected pockets of time OUTSIDE work to do whatever – walk the bulldog, play music, train for a triathlon, watch baseball, play with your kids or nieces/nephews ir travel – would be extremely valuable work/life balance discussions to have early in this sometimes crazy career.

In full disclosure this has rarely been a problem for me. I’ve managed to get to where I am today (such as it is) with what I think is a healthy balance of work-to-life. Obviously some, including my spouse, might disagree but the important thing is that I think this is the case. We’re talking personal, subjective “balance” here and nobody can define it for you. If you have reached it, you are going to be relatively happier and if you feel imbalanced you are going to feel sad* about it.

Yes, I for damn sure wish for more hours in the day. Yes. Of course. And at each and every major stage there were things being neglected so that I could pursue some other thing. Either in the proximal, days to weeks, or in the long-haul, years to decades(!), perspective. But I have never been an obsessive and any fair read would fail to find any major imbalance.

How did I do it?

I think the most useful and general approach is that you have to be willing to fail.

Let me say it again: YOU HAVE TO BE WILLING TO FAIL!!!!!

I was not, I think, willing to fail at getting the PhD. This was a defined, obtainable target for which the steps were mostly clear to me. Do the research, write that shit up into a dissertation and bob’s your uncle.

After that? Well, yes, of course I wanted to succeed career-wise. In one of the professorial paths preferably. But I was willing to…not. To fail.

There have been several defined choice points at which I did the considerably sub-optimal career move for the sake of issues that we shall encompass under “life”. (Also career moves which might have in the long run been suboptimal but looked great** at the time. Some of this initial appearance was influenced by “life”.) Sometimes I did this out of unthinking ignorance, I will admit. I didn’t perhaps realize the magnitude of the risk I was running. But I for damn sure knew there was risk. Risk of not making it in some way. Of not getting on the independent research track. Of not getting funding…or not keeping it. Of letting the lab and research program crash down to nonviability.

This hasn’t stopped and it continues to this day.

Is my virtue untested? Some might observe that. From the perspective of some it looks like I have a pretty schweet gig***. From above the waterline it looks okay. Something a disgruntled postdoc or Year 3 faculty member might think is pretty much IT. As in “career accomplished”…all it takes now is running it out like you always wanted to. No risk.

I don’t see it that way. I still risk failures of various sorts. Mostly the big axe is the grant funding….and it is a big one, hanging over my head more often than it is not.

So much like the disgruntled postdoc and the terrified junior faculty member…I could always work harder. More. Put in more grants. Squeeze out more papers. Refine my lab efficiency to maximize the data. Chase small project funds. Woo more trainees. Hit the seminar circuit harder. Go to more meetings.

All of this would probably benefit my career. It would make things go better professionally. We’d be more productive, no doubt.

I choose not to. That’s it. There’s no secret. There’s no special case of insulation from the risks of choosing not to work harder than the next person. You risk paying a price.

Balance implies tradeoffs. I’ve certainly found it to be so. There are costs to go with every benefit. Costs that may be “just” stress, may be health issues (mental or otherwise), may be definable career failures. Having “life” balance makes this inevitable. There will be tradeoffs****, people.

This is my answer to NatC’s question. Choose. Choose to take the time. Make room for what is important to you. Realize that by doing so you might fail. You might.

But you know what? These St Kern and Poo types?

I know for damn sure they’ve failed at life.

And that I was never willing to risk.

*don’t get a puppy to cheer yourself up.
**so we won’t count these, at the time they seemed really pro-career.
***and I do, I do.
****of course it goes both ways. you may be choosing a career path that really isn’t compatible with your desire to tour Europe with an opera group every summer. You may have to give up some of the “life” stuff

If you’ve been following along my posts on the substituted cathinones you will recall that cathinone is beta-keto-amphetamine. And much like amphetamine, chemists can hang little bits off the core structure to create new and interesting drugs which may offer different subjective experiences. For people who are into that sort of thing. The compound termed “Methylone” is the cathinone cousin of 3,4-methylenedioxymethamphetamine or MDMA. Which we’ve discussed a time or two on this blog. As we’ve also discussed, MDMA can result in significant medical emergency and death. Yes, really, it is the MDMA.

ResearchBlogging.orgA Case Report has just popped up on the preprint queue of the Journal of Analytical Toxicology. In it, Pearson and colleagues detail three cases of fatality involving the methylone compound. For me the interest is the way this slots neatly into the Case Reports on MDMA fatalities, especially given the drug-discrimination paper that was our first introduction to the cathinones on this blog. Although there is great diversity, MDMA cases frequently involve an individual who was “found collapsed” by friends. Emergency medical services are invoked, whereupon the individuals are frequently found with high body temperature, rhabdomyolysis, hyponatremia (dilute blood) and may have seizure-like symptoms. Cardiac arrest is not uncommon during the course of care, as is cascading organ failure. Diversity rules the day. Some individuals have been rave dancing, some have not. Some were exposed to a broad array of other psychoactives. Alcohol, nicotine and cannabis are very common but you also see methamphetamine, caffeine and a list of other stimulant/entactogen/hallucinogen class drugs. The denialists like to point to the other factors as causal, insisting that “pure MDMA” is as safe as sea salt. My position is that the great similarity of clinical courses across the diversity of “other factors” makes it even more convincing that the single shared factor, i.e., MDMA, is the causal factor. ….plus there’s this little thing called the preclinical literature.

As always with Case Reports, the work by Pearson et al. will be less than satisfying. It is only through the gradual building of the Case Reports and the addition of preclinical investigations that we will really know what is going on. But every journey starts with a single step….

The second case is the most canonical, to my eye. A 19 year old woman at a rave was observed to collapse, briefly recover, claim to “not feel well” and then exhibit seizure-like symptoms. She went into asystole en route to the Emergency Department and had a body temperature of 103.9 F. She was found negative for cocaine metabolite, cannabinoids,
opiates, benzodiazepines, phencyclidine, amphetamines, barbiturates, methadone and propoxyphene on immunoassay and positive for methylone and lamotrigine. Wait, what? This anticonvulsant sodium channel blocker is a most interesting finding. Was it being used intentionally (by the user or the tablet manufacturer) to modulate the methylone effect on monoamines? Perhaps. Or was she an epileptic prescribed an anticonvulsant? That would be interesting given this prior MDMA-related Case and the Giorgi et al. 2005 preclinical study.

Case 1 is a little more unusual, if we’re assuming methylone acts much like MDMA. In this case a 23 year old male was acting erratically in public and was detained by the police and transported to the ED. This one sounds a bit more like a classical amphetamine case, with reports of forced restraint, combativeness and, sigh, the strength-of-five*-men thing. Initial symptoms included rhabdomyolysis, a body temperature of 105.9F, seizure and renal failure. After about 3.5 hrs of care a series of cardiac arrest/recovery events culminated in a fatal arrest about 24 hrs after admission. The blood workup detected detected methylone, dextromethorphan, cotinine, caffeine and lidocaine and the Medical Examiner ruled it due to methylone. As we’ve occasionally seen from the outside of the deaths of the rich and famous, the MEs are seemingly going on an assessment of drug levels to reach their decision. One might assume that the levels of the other drugs were considered to be below the threshold for causing a death. Naturally, we are in the purest speculation territory to start dreaming up drug interaction stories. For me, the strength will eventually lie in matching up the constellation of clinical symptoms with all the cases of fatality and medical emergency that involve methylone. I’d like to know a bit more about the dextromethorphan, however, given that it is degraded by the same CYP2D6 hepatic enzyme which degrades MDMA and, presumably, methylone. Dextromethorphan is also capable of causing serotonin syndrome, thus might have the same direction of effect as methylone in this context, i.e., this may support a relatively simple additive-effects conclusion.

The final case is just plain disturbing. A 23 year old male was acting erratically in an after-hours club when management had him secured to a chair in a van outside with plastic wrap. He was left there for 3-4 hours before being discovered. Paramedics found low blood pressure, weak (but rapid) heart rate and convulsions. Upon arrival at the ED, he had body temperature of 107 F and died after about 45 minutes of attempted life support. He had 0.03 g/dL blood alcohol concentration and methylone, in addition to several therapeutics administered in the ER (but might possibly have obscured recreational use of benzodiazepines and synthetic opiates). A positive immunoassay for cannabinoids was not confirmed on followup analysis.

I think you can see that being wrapped in a chair with plastic wrap for 3-4 hours in a van might have possible had effects. I’m most concerned about the physical exertion that might have been going on, much like in Case 1 in which the guy was struggling against police. The body heat has to come from somewhere and muscular exertion (due to intentional activity) could be that somewhere. Note that in Malignant Hyperthermia, seizure-like muscular contraction can provide that same input to the system. This would be relevant to all three cases.

As I mentioned above, this is the beginning of the story. By no means can three Cases nail down a connection with high confidence. But this is all strikingly familiar and dovetails with the aforementioned drug-discrimination finding and a recent report of neuropharmacological similarity of methylone and MDMA. So I’m betting we’ll see more of these Case Reports of medical emergency and death that involve methylone.

And the profiles are going to look just like the ones involving MDMA.
*well, at least it was five, not ten.

Julia M. Pearson, Tiffanie L. Hargraves, Laura S. Hair, Charles J. Massucci, C. Clinton Frazee III, Uttam Garg, & B. Robert Pietak (2012). Case Report: Three Fatal Intoxications Due to Methylone Journal of Analytical Toxicology

There are differences in importance within the scientific career arcs, for different work/life balance issues. And yes, the reason most presentations sponsored by your local post-doc association and/or academic society focus on child-bearing and child-rearing issues is because they are deemed most important.

So while you are feeling miffed at “yet another one focused on the family” try to keep your shit together.

Is it that you are genuinely unable to get the info you need from these or another source? Or is it that you are sitting there fuming about your *perception* that the world finds your issues unimportant or is “telling you” to reproduce? Because some of that is on you and you need to deal.

Can you really not generalize the points being made for your own situation? Elder care, spouse with disability, self with disability… sure, there are differences but there are also a lot of parallels. So take the baby-focused stuff and adjust it for your situation. Interpret!

Or is it that the world does not accept your issue of “balance” as being important?

“I can’t go to that meeting, I have my first Ironman that weekend!”

or perhaps,

“My pitbull needs walkies three times a day so I’ll be missing for two hours at lunchtime”

yeah, good luck with that.

UPDATE: posts from microdro and BabyAttachMode. The latter reminded me that I failed to link to this trigger for the day’s discussion. In it one Clara B. Jones (@cbjones1943) opines:

It is my personal opinion that the major disadvantage for females in
research science careers concerns how to arrange UNDIVIDED, UNINTERRUPTED,
FOCUSED TIME…sometimes, for protracted &/or unpredictable periods.
10. My own “solution” was to surrender custody of my children; however, I
am not recommending this choice to anyone else and know, from personal
experience, that this decision is one that most females are averse to
thinking about.

you know, in case you think *I* make outrageous statements or anything…..

@Neuropolarbear opined:

Now that my lab is collecting data, I think my students would be more productive if I leave and stop pestering them for 2 months.

Stop pestering and stop helping them. And maybe I really mean postdocs rather than students. But I often think this.

Trainees would in many cases be better served if the PI said “Hey guys, I’m taking off on sabbatical, see you in six months or so.”

I’ve never had the nerve to try that one out though. I can’t see my way to risking my precious projects that way. Either that or I can’t bear the thought of having a trainee really bollocks up their training stint with me to the point that it is an abject failure…and think I could have been more involved in oversight.

I worry, however, that this hovering weakens them.

So how about it, PI-tariat? How long would you let your trainees go without having any decent idea what they were up to? More than two weeks? More than a month?

….Six months????