On Internalizing the Ethical Standards of Scientific Research

There is an entry up on the Scientific American Blog Network’s Guest Blog by two of the principals of μBiome. In Crowdfunding and IRBs: The Case of uBiome Jessica Richman and Zachary Apte address prior criticism of their approach to the treatment of human subjects. In particular, the criticism over their failure to obtain approval from an Institutional Review Board (IRB) prior to enrolling subjects in their study.

In February, there were several posts about the ethics of this choice from a variety of bloggers. (See links from Boundary Layer Physiology (here, here, here) Comradde Physioprof (here, here, here), Drugmonkey (here), Janet Stemwedel (here), Peter Lipson (here).) We greatly appreciate the comments, suggestions and criticisms that were made. Some of the posts threw us off quite a bit as they seemed to be personal attacks rather than reasoned criticisms of our approach.

If you follow the linked blog posts, you will find that when Richman and/or Apte engaged with the arguments, they took a wounded tone. This is a stance they continue.

We thought it was a bit… much, shall we say, to compare us to the Nazis (yes, that happened, read the posts) or to the Tuskegee Experiment because we funded our project without first paying thousands of dollars for IRB approval for a project that had not (and might never have) happened.

I was one of the ones who brought up the Tuskegee Syphilis Experiment. Naturally, this was by way of making an illustrative example of why we have modern oversight of research experiments. I did not anticipate that any of the research planned by the uBiome folks would border on this sort of horrible mistreatment of research subjects. Not at all. And mentioning that older history does not so accuse them either.

PhysioProf made this point very well.

UPDATE 2: The need for IRB review has little to do with researchers’ intentions to behave ethically–nowadays it is rare that we are talking about genuinely evil exploitative abusive shitte–but rather that it is surprisingly complicated to actually implement processes, procedures, and protocls that thoroughly safeguard human subjects’ rights and safety, even with the best of intentions. This inquiry has absolutely nothing to so with whether the uBiome people are nice guys who just want to do cool science with the best of intentions. That is irrelevant.

IRBs are there exactly to ensure that earnest scientists with the best of intentions in their hearts are forced to think through all of the possible ramifications of their proposed human subjects research projects in a thorough and systematic manner before they embark on their research. The evidence we are in possession of as of now suggests strongly that uBiome has not done so.

This is a critical reason why scientists using human or animal subjects need to adhere to the oversight/protection mechanisms. The second critical reason is that the people doing the research are biased. Again, it is not the case that one thinks all scientists are setting out to do horrible Mengele type stuff in pursuit of their obsessions. No. It is that we all are subject to subtle influences on our thinking. And we, as humans, have a very well documented propensity to see things our own way, so to speak. Even when we think we are being totally objective and/or professional. By the very nature of this, we are unable to see for ourselves where we are going astray.

Thus, external oversight and review provides a needed check on our own inevitable bias.

We can all grumble about our battles with IRBs (and Institutional Animal Care and Use Committees for animal subject research). The process is far from perfect so a little bit of criticism is to be expected.

Nevertheless I argue that we should all embrace the oversight process unreservedly and enthusiastically. We should be proud, in fact, that we conduct our research under such professional rules. And we should not operate grudgingly, ever seeking to evade or bypass the IRB/IACUC process.

Richman and Apte of μBiome need to take this final step in understanding. They are not quite there yet:

Before we started our crowdfunding campaign, we consulted with our advisors at QB3, the startup incubator at UCSF, and the lawyers they provided us. We were informed (correctly) that IRBs are only required for federally funded projects, clinical trials, and those who seek publication in peer-reviewed journals. That’s right — projects that don’t want federal money, FDA approval, or to publish in traditional journals require no ethical review at all as far as we know.

Well, that is just plain wrong. Being a professional scientist is what “requires” us to seek oversight of our experiments. I believe I’ve used the example in the past of someone like me buying a few operant chambers out of University Surplus, setting them up in my garage and buying some rats from the local pet store. I could do this. I could do this without violating any laws. I could dose them* with all sorts of legally-obtainable substances, very likely. Sure, no legitimate journal would take my manuscript but heck, aren’t we in an era where the open access wackaloons are advocating self-publishing everything on blogs? I could do that. Or, more perniciously, this could be my little pilot study incubator. Once I figured I was on to something, then I could put the protocols through my local IACUC and do the “real” study and nobody would be the wiser.

Nobody except me, that is. And this is why such a thing is never going to happen. Because I know it is a violation of my professional obligations as I see them.

Back to Richman and Apte’s excuse making:

Although we are incubated in the UCSF QB3 Garage, we were told that we could not use UCSF’s IRB process and that we would have to pay thousands of dollars for an external IRB. We didn’t think it made sense (and in fact, we had no money) to pay thousands of dollars on the off chance that our crowdfunding campaign was a success.

and whining

We are happy to say that we have completed IRB review and that our protocol has been approved. The process was extremely time-consuming, and expensive. We went back and forth for months to finally receive approval, exchanging literally hundreds of pages of documents. We spent hundreds of hours on the project.

First, whatever the UCSF QB3 Garage is, it was screwing up if it never considered such issues. Second, crying poverty is no excuse. None whatsoever. Do we really have to examine how many evils could be covered under “we couldn’t afford it”? Admittedly, this is a problem for this whole idea of crowd-funded science but..so what? Solve it. Just like they** had to solve the mechanisms for soliciting the donations in the first place. Third….yeah. Doing things ethically does require some effort. Just like conducting experiments and raising the funds to support them requires effort. Stop with the whining already!

The authors then go on in a slightly defensive tone about the fact they had to resort to a commercial IRB. I understand this and have heard the criticisms of such Pay-for-IRB-oversight entities. From my perspective this is much, much lesser of a concern. The absolute key is to obtain some oversight that is independent of the research team. That is first-principles stuff to my view. They also attempt to launch a discussion of whether novel approaches to IRB oversight and approvals need to be created to deal with citizen-science and crowd-funded projects. I congratulate them on this and totally agree that it needs to be discussed amongst that community.

What I do not appreciate is their excuse making. Admitting their error and seeking to generate new structures which satisfy the goal of independent oversight for citizen-science in the future is great. But all the prior whinging and excuse making, combined with the hairsplitting over legal requirements, severely undercuts progress. That aspect of their argument is telling their community that the traditional institutional approaches do not apply to them.

This is wrong.

UPDATE: Read uBiome is determined to be a cautionary tale for citizen science over at thebrokenspoke blog.
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*orally. not sure civilians can get a legal syringe needle anywhere.

**(the global crowdfund ‘they’)

Additional Reading:

Animals in Research: The conversation begins
Animals in Research: IACUC Oversight

Animals in Research: Guide for the Care and Use of Laboratory Animals
Animals in Research: Mice and Rats and Pigeons…Oh My!
Virtual IACUC: Reduction vs. Refinement
Animals in Research: Unnecessary Duplication

Academic comfort levels

I have a question for you, Dear Reader.

During what fraction of the time you spent at each major career stage in academics – undergrad, grad school, postdoc, faculty level (TT or no, plz specify) – did you feel comfortable?

Not did you feel it was easy exactly, but did you feel as though you had it handled? As though there was little doubt you were doing a good job of what you were expected to do.

For me, undergrad all 4 yrs, grad school 3 yrs, postdoc maybe a scattered 2 yrs total time.

At the faculty level maybe my first three years and again for maybe 6 mo last year.

For faculty, make special note of the tenure decision- were you feeling comfortable in the few years leading up to that?

The antiK3rn approach to surviving to tenure

You no doubt remember the advice of Scott Kern and that of Mu-ming Poo with respect to what it takes to survive and thrive in an academic career.

It boils down to “work harder, no I don’t care how much you are already working, you need to work more. and baby’s are dying of cancer and something, something growth cones. so there”

One Radhika Nagpal has written a counter argument from her current position as Full Professor at Harvard.

Go read

The-Awesomest-7-Year-Postdoc or: How I Learned to Stop Worrying and Love the Tenure-track-faculty-life

So with some humor to balance my fear, here’s goes my confession:

Seven things I did during my first seven years at Harvard. Or, how I loved being a tenure-track faculty member, by deliberately trying not to be one.

• I decided that this is a 7-year postdoc.
• I stopped taking advice.
• I created a “feelgood” email folder.
• I work fixed hours and in fixed amounts.
• I try to be the best “whole” person I can.
• I found real friends.
• I have fun “now”.

right now. I can wait.

Here’s what I think about

Work Life balance

The paradox of the poles of the work-life balance discussion in Nature News is this.

Nobody who succeeds at work and then claims balance really knows if they just got very, very lucky in their career.

Nobody who works around the clock and drives their lab to similar performance knows that this was *required*.

The hidden side is that both balanced and St Kern/Poo’d types also fail in their careers.

UPDATE 09/06/11: Plus also, StKern/Poo’d types can also succeed in their careers really, really well….and still fail to cure cancer.

And about Protecting Your Time

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!!!!!

And one of my accidental mentors taught me this:

There were several areas in which I picked up either positive (“gee, that seems useful”) or negative (“not gonna go there”) PI patterns from this person. One of the former was this guy’s role as father and scientist. Whenever one had to find this PI, if he wasn’t around because of father duties his whole lab knew about it. “Oh, he’s at Opening Day.” or “He had a sick kid today, he’ll be back later”. or “He’s taking his kid to [SportingActivityX]”. This guy has a perfectly viable career with nice pubs, great NIH grant support, always seems to have at least 4-5 postdocs and a similar number of techs, serves study sections, organizes symposia, etc. In short, he’s well respected and does not appear to have paid any obvious sort of career price to date. This had a great impact on YHN as I was transitioning both as PI and father.
The power of this example for me was basically “Screw it, if he doesn’t worry about being known at work as a guy who takes his role as father seriously then I’m not going to worry about it either”.

The interesting thing, which is emerging on the Twitters, is that Professor Nagpal’s advice is really no different from a host of women who write “You can’t have it all” screeds and lament the fact “You have to be twice as good as a man to succeed”. The ones that describe not being their enough for their kids or the ones describing being their too much and failing. The men too, although their career advice is thinner. See Kern and Poo links at the top–they describe how “it has to be” because this is how it was for them.

And you know what? It is ALL true. All of it. Because these are personal anecdotes tied to the career history and success of the person giving the advice or reciting their life-story in academics (or other professional life).

My advice, scattered throughout this blog, is no different.

And just as the winners of global social politics write the histories of what happened and for what reason, likewise those who have succeeded in academic science tend to write the prescriptions for our careers.

I don’t think Professor Nagpal has written some amazing revelation here. It is not hugely different than arguments that I make myself on this very blog.

It is true that she has been very, very successful by appearance.

But there are also, I would wager, tons of people who made the choices she made and were denied tenure. Many who washed out of academic professordom entirely. And that is the point about this advice which runs from Nagpal’s 50 hrs max to the Kern/Poo maxim of “always more”.

It is no guarantee.

Repost: Musty Must-Read: "Mrs. Winslow's Soothing Syrup"

I originally posted this Jan 09, 2008 on the old blog and reposted it 12/12/2008 with small improvements over the prior version. It has been one of my more popular posts when it comes to Google hits. You might want to check out a personal recipe for opiate based cough remedy as well.

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The US Food and Drug Administration (FDA) began sending warning letters to sellers of so called “bio-identical hormone replacement therapy” today according to an AP report. Apparently the claims for alleviating menopausal symptoms are

not supported by medical evidence and are considered false and misleading.

Needless to say, these “compounded” products are being sold without FDA approval. It’s all a conspiracy man! Dang FDA is a tool of BigPharma trying to keep cheap and effective remedies from the public. Noted tool of TheMan_{(BigPharmaDivision)} Abel Pharmboy has a recent post in which he touches on “cosmeceutical” marketing of drugs and the FDA’s authority to regulate cosmetics under

their regulatory authority is in part ordered by the Federal Food, Drug, and Cosmetic Act of 1938 (and subsequent legislation).

source
This reminds me of the glory days of the quack remedy / patent medicine era and today, from the mouldering archives, we take up a Case Report published by A. B. Hirsch, M.D. [“Mrs. Winslow’s Soothing Syrup. American Medical Journal, 1884, 12(11):504-506] which is available from Google Books here. A footnote indicates that this Abstract was read before the Philadelphia County Medical Society on Sept 17, 1884. Ahh, Mrs. Winslow’s . Used for over 60 years by mothers for their teething children.

Something seems wrong with this tenure math

Prof-like Substance has written a post wondering if the grant-related criteria for tenure have been modified in the face of the current funding environment. One of the comments drew my eye. Elsa said:

We have monthly workshops for new faculty sponsored by the dean’s office and were recently told that “NIH funding rates are at 10-15% but we expect all of our faculty to be in the top 10-15%.” Large state school R1.

Deans who expect all of their faculty to be in the top 15% of all scientists funded by, for example, the NIH are delusional. That’s the first problem. Especially if you are in a large state school with a heavy research mission. There have to be at least 50 of these, by anyone’s criteria for “large state school R1”, in the US. The Rock Talking blog indicated there are something on the order of 85,000 applicant PIs to the NIH. Gating on R01 apps only, there are about 1,200 applicant institutions (1,900 counting all application types). Fifteen percent of 85,000 is 12,750 investigators. If these are evenly distributed between 1,200 or 1,900 institutions, we end up with 8-11 top-15%ile investigators at each institution.

Now, we don’t know the size of the skew in the distribution and my estimate of 50 large state schools is rough. It also overlooks the big private universities and medical schools as well as a couple of moneybag$$ research institutes. Luckily, there is the NIH RePORT. Ranking applicant institutions by aggregate funding in FY2013 I’m down to 200 places and still seeing Universities that might be seen as “large state schools, R1”. Especially by their own Deans of Research and/or Faculty. The Universities around a rank of 200 are landing about $8 million, each, from the NIH so far this Fiscal Year. Let’s suppose that the above 12,750 top-15%ile investigators were distributed only to these 200 applicant institutions- we end up with only 63 investigators per institution. From this analysis, the Dean would have to be overseeing only 63 faculty to make the expectation a valid one.

Soo…that leads to another question, how many awards per institution as we descend the ranks? Well ranking the FY2013 table by the number of awards, I make it to about 115 applicant institutions with more than 63 awards. Obviously, some subset of investigators are holding multiple awards so this is a very rough indicator. But still. The idea that only about 60 or so professors are seeking NIH funding from these rather large state Universities that slot in around the 116 total-NIH-funding rank is absurd. Clearly there are many, many more.

The abovementioned expectation was also, I remind you, directed at the first 6 years of a professor’s career since this is when the tenure decision comes. These poor suckers have a very narrow window to get their NIH grants funded. That’s a further absurdity in the expectation.

Finally, to undercut both my analysis and the expectation that triggered this post…. NIH grant success rates are per-application and do not reflect the per-PI success rate. We have not yet see, to my recollection, is a per-applicant success rate across a 2-3 year interval. It is likely higher than the NIH’s per-application success rate but I really don’t know that for sure. If it is substantially higher then succeeding in time where the NIH success rate is 15% is going to be available to more than 15% of all applicant PIs.

OTOH, the RockTalk analyses (here, here, here) argue that the massive increase in applications is being driven by more applicants, not by the same number of applicants submitting more grants. So it may be that the per-PI success rate really doesn’t differ much from the per-application success rate.

The science of privilege

an interesting segment from the PBS NewsHour:

Monteith Dead at 31. Drugs, one presumes?

Apparently this Cory Monteith was kind of a big deal, star of a hit television show and what not. Also a drug addict.

And now dead.

His latest stint in rehab, by reports, was this April.

Vancouver Chief Coroner Lisa Lapointe said the actor had been dead for several hours when his body was discovered.

“Mr. Monteith was found deceased in his room at approximately noon today,” Lapointe said at a news conference late Saturday.

2013 in Memoriam: ‘Glee’ Star Cory Monteith Dead at 31

Acting Vancouver Police Chief Doug LePard said the evidence shows Monteith was last seen returning to his room alone late Friday night.

Although the cause of death is not yet known, police have ruled out foul play. Police said they believe he was alone when he died.

In 2008 we discussed the death of Heath Ledger and upon wondering if he was a drug addict it emerged that we weren’t supposed to discuss his addiction. I have to admit my first thought on hearing this news was…weariness. I wasn’t going to blog it. Luckily, I don’t have to, see the end of the post.

I am, however, very interested to see how much our popular consciousness has changed. Particularly since this poor guy had been open about his struggles with drug use. Is it now okay to start right in with the discussion of how his addiction to drugs led to this? Or at least to speculate? Maybe we will be okay discussing his possible affective disturbances (depression? anxiety? other?) that led to his substance use? Can we discuss this without stigma just like we might discuss Tony Soprano’s bad ticker and Angelina Jolie’s breast cancer risk factors?

I am curious.

In the mean while, there is a fantastic post up at the unlikely activist blog. It talks a little bit about why those of us scientists who are interested in topics of substance use and abuse do what we do.

Over the forthcoming days, the facts and events that led to Mr. Monteith’s death will be splashed over the pages of every newspaper in the land.

His story, however, is played out every day in small communities around this country. He is only one example of a victim of a disease that knows no bounds. The anonymous die every single day in this country because of their disease, and their plight must not be ignored.

Wealth cannot protect someone from an addiction. Neither can talent or beauty. Neither can fame.

And in many cases, even the love of family, friends and a partner cannot stop it.

And in many cases, even the best treatments we have cannot stop it.

The hope for people suffering from this disease is scientific research into the mechanisms, causes and targets of treatment for addiction. It’s why we must put as many resources as we can onto research that aims to stop the needless suffering and deaths of the famous and anonymous alike. We must combine the use of sophisticated brain imaging methods and genetic analyses in human subjects, with molecular and cellular studies in animals. It’s why we must give the victims of this illness the compassion and help they need, just like we do so for people with other preventable illnesses like cancer, HIV/AIDS and diabetes.

Go read it.

UPDATE 07/16/13: The Coroner confirms Monteith’s death due to heroin and alcohol.

The Handmaid's Tale, Texas and Republican Dead Enders

BikeMonkey Guest-PostMost of you have been following, I presume, all of the anti-woman legislation being pursued by Republicans at the State level. It reached a bit of a fever pitch recently with the State Senate filibuster of an anti-abortion bill by Senator Wendy Davis. More recently the North Carolina legislature has been trying to enact draconian anti-abortion legislation as well. They did so, cravenly, by first shoehorning the policy into a bill launched (entirely un-ironically, apparently) to combat Sharia law and then putting it into a motorcycle safety bill! Resourceful these folks certainly are.

In this political conversation the occasional wag has been seen to refer to Margaret Atwood’s dystopian novel The Handmaid’s Tale. For those who are unfamiliar, the Wikipedia:

…a movement calling itself the “Sons of Jacob” launches a revolution and suspends the United States Constitution under the pretext of restoring order.

They were quickly able to take away all of the women’s rights, largely attributed to the financial records being stored electronically and labelled by gender. The new theocratic military dictatorship-styled “The Republic of Gilead”, moved quickly to consolidate its power and reorganize society along a new militarized, hierarchical, compulsorily cult-Christian regime of selectively skewed Old Testament-inspired social and religious ultra-conservatism among its newly created social classes. In this society, almost all women are forbidden to read.

The story is presented from the point of view of a woman called Offred (literally Of-Fred, however not a patronymic as some critics claim). The character is one of a class of individuals kept as concubines (“handmaids”) for reproductive purposes by the ruling class in an era of declining births. The book is told in the first person by Offred, who describes her life during her third assignment as a handmaid, in this case to Fred (referred to as “The Commander”). Interspersed in flashbacks are portions of her life from before and during the beginning of the revolution, when she finds she has lost all autonomy to her husband, through her failed attempt to escape with her husband and daughter to Canada, to her indoctrination into life as a handmaid. Through her eyes, the structure of Gilead’s society is described, including the several different categories of women and their circumscribed lives in the new theocracy.

Ahh, you hyperbolic feminists and liberals. Such a bunch of sensationalists! Surely the GOP wouldn’t try to cause any such thing. Totally different!

This country, the USA, reaching far back to it’s genesis as a European Colony, was not originally a slave country. In fact, it was formed under English common law which explicitly prohibited slavery at the time. It was formed by peoples who were at war with a country which did, at the time, have a legal slave tradition….that would be Spain.

The English common law did provide for indentured servitude. The indentured service arose from the 1562 Statute of Apprentices and subsequent English Poor Laws which allowed poor people to be indentured to work for a richer person for a period of time, 7 years and/or up to the age of 24 was in the original Statute. All considered perfectly reasonable so for discussion purposes, sure, let’s start with that assumption.

When Jamestown, Virginia was established (early 1600s) as a profit venture, it originally struggled. Mightily. Somewhere around 1616 the Virginia Company realized they should leverage indentured servitude and started shipping over poor individuals as cut-rate labor. It worked in various ways with first the plantation owners in Virginia pre-paying “passage” and then apparently devolved into captains loading up in England with passengers on spec, and then auctioning them off to the plantation owners upon arrival in Virginia. Auctioning of their indentured service interval. Let us be clear. These folks (some around these parts like to start spouting about the Scots and the Irish at this point in the story, we can roll with that) were eventually free colonists. Eventually. And maybe they were freed into a life of struggle and poverty too. Who cares? They were free.

The first recorded boatload of 20+ black people arrived at Jamestown in 1619 under the same deal. Sure, they’d been pirated off the Spanish who held them as slaves but originally they were treated under English common law. They were indentured for the “passage” costs between when the English pirates stole them from the Spanish and delivered them to Virginia. And as per this Wikipedia article:

After working out their contracts for passage money to Virginia, each was granted 50 acres (20 ha) of land (headrights) after completing the indenture. This enabled them to raise their own tobacco or other crops.

So far, so good, right? Just as the fake-equality defenders of the poverty stricken, Scots-Irish descendent Appalachian white folks of modern day would have it, the original black people arriving in the English colonies of America were treated as well or poorly as the in/voluntary poor indentured white folks.

The trouble is, shit happened.

What happened thereafter, from the early 1620s through about 1655, was that a gradual series of critical practices, laws and legal decisions were made that favored the interests of greedy individuals who were entirely callous to the rights of other people. This was against a backdrop in which rich English folks back home were making bank from high seas piracy of the Spanish slave trade. They did so for clear monetary gain, apparent personal convenience and, one must conclude, a considerable amount of ‘othering’ for people not like themselves. At first the clues that permanent lifetime indentured servitude existed in Virginia are scant. The William Wood essay reviews a 1643 case in which the valuation of white (700 pounds of tobacco) and black (3,000 pounds of tobacco) children as part of a decedent’s estate made it clear their indenture was of different durations. Also a 1649 case in which the two white runaway indentured servants had their indenture extended by several years whereas the black one, John Punch, was rendered to lifetime servitude. John Punch is thus often considered the first legally enslaved person of the American English colonies. Fascinatingly, a genetic and genealogical analysis suggests that John Punch is an ancestor of Barack Obama through his mother.

Slippery slopes, people, slippery slopes. What was the harm of a draconian punishment of just one criminal? (He’d run away from his indenture, after all, tch, tch, tch.)

Next up was the fascinating case, in 1654-1655, of one John Casor, indentured to Anthony Johnson, this latter was curiously enough one of the first 20+ black arrivals indentured in 1619. Mr. Johnson had worked free of his indenture, set up as a farmer and became prosperous enough to require indentured servants of his own. John Casor was one such and demanded his release after working 7 or 8 years for Johnson. Johnson refused, claiming he was actually indentured for life (remember those kids?) and Casor somehow ended up working for his neighbor. Johnson sued said neighbor for “detaining his Negro servant”. The court of Northampton County upheld Mr. Johnson’s claim to Mr. Casor which formalized the permanent enslavement of Casor as well as the right of a free black person to own a slave. From this perspective of property rights rather than punishment for a crime, some might claim that Casor was in fact the first formally, legally sanctioned slave of the Americas, rather than Mr. Punch.

Like it matters that much. I’m sure certain folks around here will be happy that the first slave was Obama’s relative through his white mother and others will be tickled to think the first slave was owned by a black farmer.

Oh, and we’re not done with the slippery slope. Not by a long shot. (Just like each abortion restriction isn’t the end of the modern GOP’s goals and attacks, people.)

In 1662 Virginia adopted partus sequitur ventrem which meant that children of black women slaves would be similarly enslaved. This ran counter to English common law which held that the status of a child was tied to the status of the father. Gee, I wonder what that was about….oh yes:

The change also gave cover to the power relationships by which white planters, their sons, overseers and other white men took sexual advantage of enslaved women. Their illegitimate mixed-race children were “confined” to slave quarters unless fathers took specific legal actions on their behalf. The new law in 1662 meant that white fathers were no longer required to legally acknowledge, support, or emancipate their illegitimate children by slave women. Men could sell their issue or put them to work.

Of course it was not just about keeping more black people as slaves, but also about maintaining the ability of rich white dudes to rape women who they quite literally owned. And you know, to force them to bear children for whom the father would take no responsibility whatsoever. (Sound familiar?) The span from 1662 to 1863 was two hundred friggin’ years of free rapin’ rights on the part of wealthy white Southron men in these here lands.

Initially the children of a free white mother and a black man would be free but they soon fixed that loophole. As of 1691 these kids were also indentured (for a mere 30 years!) and the mother had to pay a fine of 15 pounds sterling. If she couldn’t pay, she went into indenture for five years! Then, after having furiously imported lots of black slaves to work the plantations over a few decades, Virginia colony “deported” all free blacks in 1699. Thereafter, if you were black in Virginia, you were enslaved. And the oppression was complete.

A full conversion from the English common law, which banned enslavement, to full lifetime, permanent, cross-generational enslavement.

But naah. Couldn’t ever happen right? No way the current assaults from the GOP on women’s bodies, autonomy and rights could ever slide into the nightmare of The Handmaid’s Tale.

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I would recommend reading the Wikipedia entries on:
Anthony Johnson
John Casor
Nat Turner

and in particular the 1970 William J. Wood essay The Illegal Beginning of American Negro Slavery (HeinOnline, GoogleBooks).

Bias in Selection for NIH Study Sections

Interesting exchange on the twitts today with someone who is intimating that the process of selecting peers to serve as grant reviewers on NIH study sections requires some transparency and fixing.

As my longer term Readers are aware, my main objection along these lines is that I think Assistant Professors should not be excluded and that the purge urged on by Toni Scarpa back some years ago was misguided. I will also venture that I think it is ridiculous that the peer review pool is limited to those Professorial rank people who have already won funding from the NIH (for the most part). If really pressed, I’ve been know to suggest that it is even unfair that the more senior postdoc types who have not yet won a faculty-level appointment cannot review grants.

Other than that, I am generally down with the official mandates to seek ethnic/racial, gender and geographic representation on panels. My personal experience has been that the SROs do a pretty good job at this. Also, because of these factors, I have found that the types of institutions represented spans the range pretty well..small mostly teaching profs, big Research Uni profs, research insitutes of various sizes, public Unis, private Unis, Med Schools and academic departments.

So it is with some confusion that I read someone asserting that there is a problem with who is selected.

My query of the day, therefore, is to ask you if you know of people who seek to serve on study section but cannot seem to land an invite. Alternately, do you know of categories of investigators that are routinely overlooked?

It was the MDPV that killed him

New Case Report from the Maryland Office of the Chief Medical Examiner

Kesha K, Boggs CL, Ripple MG, Allan CH, Levine B, Jufer-Phipps R, Doyon S, Chi P, Fowler DR. Methylenedioxypyrovalerone (“Bath Salts”),Related Death: Case Report and Review of the Literature. J Forensic Sci. 2013 Jul 3. doi: 10.1111/1556-4029.12202. [Epub ahead of print][PubMed, Publisher]

The subject was a 39 year old man with a history of depression, back pain and drug/alcohol abuse. He was found in public talking to himself, delusional. Once admitted to the hospital, he became agitated, tachycardic and hyperthermic (107 degF noted). Although the decedent was positive for diphenhydramine, promethazine, diazepam and nordiazepam the conclusion was….

Based on the investigative, autopsy, and toxicology findings in this case, the cause of death was methylenedioxypyrovalerone intoxication and the manner of death was accident. It is also important to note that his bizarre behavior with life-threatening hyperthermia is consistent with an MDPV-induced excited delirium state in this individual.

Yep.

The peripheral blood level was 1.0 mg/L of MDPV. We’re just starting to see reports so we’ll just have to wait and collect various blood levels that are associated with medical emergency and death to try to get an idea of the danger zone. Of course, there will be no such thing as an absolute threshold, as individual susceptibility and the circumstances will vary.

Manuscript Review Musing

My initial mindset on reviewing a manuscript is driven by two things.

First, do I want to see it in print?. Mostly, this means is there even one Figure that is so cool and interesting that it needs to be published.

If there is a no on this issue, that manuscript will have an uphill battle. If it is a yes, I’m going to grapple with the paper more deeply. And if their ARE big problems, I’m going to try to point these out as clearly as I can in a way that preserves the importance of the good data.

Second, does this paper actively harm knowledge?. I’m not as amped up as some people about trivial advance, findings that are boring to me, purely descriptive studies, etc. So long as the experiments seem reasonable, properly conducted, analyzed appropriately and interpreted compactly, well I am not going to get too futzed. Especially if I think there are at least one or two key points that need to be published (see First criterion). If, OTOH, I think the studies have been done in such a way that the interpretation is wrong or clearly not supported…well, that paper is going to get a recommendation for rejection from me. I have to work up to Major Revision from there.

This means that my toughest review jobs are where these two criteria are in conflict. It takes more work when I have a good reason to want to see some subset of the data in print but I think the authors have really screwed up the design, analysis or interpretation of some major aspect of the study. I have to identify the major problems and also comment specifically in a way that reflects my thinking about all of the data.

There is a problem caused by walking the thin line required for a Major-Revision recommendation. That is, I suppose I may pull my punches in expressing just how bad the bad part of the study really is. Then, should the manuscript be rejected from that journal, the authors potentially have a poor understanding of just how big the problem with their data really is. Especially if the rejection has been based on differing comments between the three sets of reviewers. Sometimes the other reviewers will have latched on hard to a single structural flaw…which I am willing to accept if I think it is in the realm of ‘oh, you want another whole Specific Aim’s worth of experiments for this one paper, eh?’.

The trouble is that the authors may similarly decide that Reviewer 3 and Reviewer 1 are just being jerks and that the only strategy is to send it off, barely revised, to another journal and hope for three well-disposed reviewers next time.

The trouble is when the next journal sends the manuscript to at least one reviewer that has seen it before….such as YHN. And now I have another, even harder, job of sorting priorities. Are the minimal fixes an improvement? Enough of one? Should I be pissed that they just didn’t seem to grasp the fundamental problem? Am I just irritated that IMO if they were going to do this they should have jumped right down to a dump journal instead of trying to battle at a lateral-move journal?

Molly, Ecstasy and the alleged profession of journalism

Look people, this is really very exceptionally easy to understand. It is not rocket science.

New drug “Molly” produces lasting side effects

Recent social media posts have focused on the side effects of Molly, an MDMA (3,4-methylenedioxy-methamphetamine) drug similar to ecstasy that has become increasingly popular among college students over the past year.

No, it is not “an” MDMA drug and it is not “similar” to ecstasy.

Recreational drugs have all kinds of nicknames. Names that vary across time, place and subpopulation. A given user, however, means something specific.

“Ecstasy” was and is the drug 3,4-methylenedioxymethamphetamine, known as MDMA for short. You can read my musings in the archives.

It is also the case that illicit drug sellers, at times, provide the customers with a drug product which is something other than what the person intends to purchase. In the case of cocaine and heroin, most casual readers will be intimately familiar with teevee and movie plot lines which involve “cutting” pure cocaine or heroin with other substances. The goal, in fiction and in reality, is to make more money from a limited commodity.

“Ecstasy” supplies are notoriously variable in both active drug quantity per dose (i.e. traditional concepts of “cutting”) and in the psychoactive ingredients contained therein. In the case of the latter, there is reason to believe that the non-MDMA, psychoactive drugs might serve as a partial substitute. These alternatives include meth/amphetamine, MDA, MDE, mCPP and caffeine here, here, here, here and here. (Lots of caffeine, actually.) Head over to ecstasydata.org and you can search for pill constituents yourself.

Now, given this diversity and given that these are psychoactive drugs that have their own fan bases, it would not be surprising in the least to find people actually seeking out or preferring “Ecstasy” that was in fact not MDMA. There is a set of focus group comments here that I find illuminating. You can imagine for yourself why an Ecstasy consumer would prefer to think of methamphetamine as “speedy”-MDMA rather than good old methamphetamine. Also, people are very bad at blind identification of, say, methamphetamine vs MDMA. So there’s that. It is not impossible that some individual might have consistently been sold “Ecstasy” that is actually something else, like mCPP and caffeine, and prefer it and think that this is “Ecstasy”. But I doubt it. Hard to get clear estimates and it varies across time but something on the order of at least half of “Ecstasy” contains only MDMA.

Now, against this history of things marketed as “Ecstasy” that might or might not be pure MDMA, there arose a marketing trend (and user bragging right boast) for pure, genuine Ecstasy/MDMA. Reflecting, of course, that this particular compound/molecule is what substantial parts of the “Ecstasy” market were intending to purchase.

This marketed-as-pure MDMA became termed “Molly” in recent parlance.

Get it journalists? Molly = MDMA = Ecstasy.

And juuuuuusssst as with the prior episode, illicit drug suppliers are motivated to cut and substitute the product they move to people who are seeking to purchase MDMA. Once again, there is undoubtedly drug being sold as “Molly” that in fact contains other psychoactive substances and/or is cut with inert substances.

None of this makes “Molly” some new drug of uncertain identity, however.

Additional Reading:
Music Festival in Washington Leads to Dozens of Drug Overdoses, One Death
Molly: Pure, but Not So Simple
There’s something (potentially dangerous) about molly
Club drug ‘Molly’ on major upswing as Ultra Music Fest Miami approaches
These Rappers Hate Ecstasy

Some days, this is just about all you have to cling to

“The proposal is extremely well-written and clear.”

First Possible Funding Date July 1

Geez, are we here already? As you know, the 1st of July is the first possible funding date for NIH grants that were submitted in Oct-Nov and reviewed in Feb-Mar. I like to see what my favorite ICs are doing in terms of funding new grants. Everything is interesting. The total number, the ratio of R01 to R21 and/or R03, number of K99/R00s, BigMech grants, etc.

It may take a few days for RePORTER to update but in the mean time you can stalk SILK for the very latest of new NIH grant awards.

April 1 was an unmitigated disaster, coming within weeks of the sequester falling and the uncertainty of a continuing resolution (which passed mere days before April 1). Grants slated to start were delayed substantially although at least one of the ICs I follow seems to have caught up by now.

Another of the ICs of my closest interest has barely funded any new grants all Fiscal Year. It’s amazing and I have no idea what the hell is going on. Perhaps the floodgates will open in July? I’m sure their applicants are hoping so!

Anyway, happy browsing. Try not to notice how HUGE the NCI is and what a disproportional number of awards are made by that IC….

Note for PIs

If your lab requires a “weekly support group” meeting, there is no scenario wherein you are doing it right.