Search Results for "iacuc"

Feb 20 2013

A little reminder of why we have IRBs. Did I mention it is still Black History Month?

Reputable citizen-journalist Comradde PhysioProffe has been investigating the doings of a citizen science project, ubiome. Melissa of The Boundary Layer blog has nicely explicated the concerns about citizen science that uses human subjects.

And this brings me to what I believe to be the potentially dubious ethics of this citizen science project. One of the first questions I ask when I see any scientific project involving collecting data from humans is, “What institutional review board (IRB) is monitoring this project?” An IRB is a group that is specifically charged with protecting the rights of human research participants. The legal framework that dictates the necessary use of an IRB for any project receiving federal funding or affiliated with an investigational new drug application stems from the major abuses perpetrated by Nazi physicians during Word War II and scientists and physicians affiliated with the Tuskegee experiments. The work that I have conducted while affiliated with universities and with pharmaceutical companies has all been overseen by an IRB. I will certainly concede to all of you that the IRB process is not perfect, but I do believe that it is a necessary and largely beneficial process.

My immediate thought was about those citizen scientist, crowd-funded projects that might happen to want to work with vertebrate animals.

I wonder how this would be received:

“We’ve given extensive thought to our use of stray cats for invasive electrophysiology experiments in our crowd funded garage startup neuroscience lab. We even thought really hard about IACUC approvals and look forward to an open dialog as we move forward with our recordings. Luckily, the cats supply consent when they enter the garage in search of the can of tuna we open every morning at 6am.”

Anyway, in citizen-journalist PhysioProffe's investigations he has linked up with an amazing citizen-IRB-enthusiast. A sample from this latter's recent guest post on the former's blog blogge.

Then in 1972, a scandal erupted over the Tuskegee syphilis experiment. This study, started in 1932 by the US Public Health Service, recruited 600 poor African-American tenant farmers in Macon County, Alabama: 201 of them were healthy and 399 had syphilis, which at the time was incurable. The purpose of the study was to try out treatments on what even the US government admitted to be a powerless, desperate demographic. Neither the men nor their partners were told that they had a terminal STD; instead, the sick men were told they had “bad blood” — a folk term with no basis in science — and that they would get free medical care for themselves and their families, plus burial insurance (i.e., a grave plot, casket and funeral), for helping to find a cure.

When penicillin was discovered, and found in 1947 to be a total cure for syphilis, the focus of the study changed from trying to find a cure to documenting the progress of the disease from its early stages through termination. The men and their partners were not given penicillin, as that would interfere with the new purpose: instead, the government watched them die a slow, horrific death as they developed tumors and the spirochete destroyed their brains and central nervous system. Those who wanted out of the study, or who had heard of this new miracle drug and wanted it, were told that dropping out meant paying back the cost of decades of medical care, a sum that was far beyond anything a sharecropper could come up with.

CDC: U.S. Public Health Service Syphilis Study at Tuskegee
NPR: Remembering Tuskegee
PubMed: Syphilitic Gumma

31 responses so far

Feb 13 2013

Effects of MDPV ("Bath Salts") interact with the ambient temperature

A new paper from the Fantegrossi laboratory examines the behavioral and physiological effects of the substituted cathinone drug, and "bath salts" constituent, 3,4-methylenedioxypyrovalerone (MDPV) [ Search PubMed ] which is the compound which has dominated the US media reports of averse consequences of bath salts intoxication. To the extent that verification of the drug has been provided in such reports, of course. Additional confirmation can be found here, here.

ResearchBlogging.orgThe current issue of Neuropsychopharmacology has a bath salts image on the cover and contains an article from Baumann and colleagues on MDPV pharmacology (I discussed it here) and this paper from Fantegrossi and colleagues.

William E Fantegrossi, Brenda M Gannon, Sarah M Zimmerman and Kenner C Rice In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity. Neuropsychopharmacology (2013) 38, 563–573; doi:10.1038/npp.2012.233; published online 5 December 2012 [ ArticleLink(free); PDF ]

This is a behavioral pharmacology study in male NIH Swiss mice which first uses drug discrimination techniques to show that when mice are trained to discriminate 0.3 mg/kg i.p. MDPV from saline the subsequent dose response curves for 0.01 to 0.3 mg/kg of MDPV, METH and MDMA are nearly identical. This article has been made freely available so I won't belabor this part of the study.

Fantegrossi13-mdpvFig4What I wanted to focus on was the radiotelemetry studies of body temperature and locomotion. For reasons related to this classic paper on MDMA from Malberg and Seiden, most investigations of the effects of stimulant drugs in rodents should include some consideration of the role of ambient temperature. Fantegrossi and colleagues examined the effects of 0.3-30 mg/kg i.p. MDPV at both 20°C and 28°C. They showed, first of all, that MDPV produces no change in body temperature when administered at 20°C, but induces temperature elevations in a dose-dependent manner when animals are evaluated at 28°C. Even more interesting is what is shown in Figure 4 which I've included here. You can see that the locomotor stimulant effect (total activity counts over 6 hrs; left panel) of MDPV also is more pronounced at the higher ambient temperature with a peak differential observed after the 10 mg/kg i.p. dose (timecourse for this dose shown in right panel). There were also some other interesting phenomenological differences observed with the high ambient temperature condition.

At the highest tested dose of MDPV (30 mg/kg), significant focused stereotypy was observed at 28 1C, but not at 20 1C. Furthermore, four (of six) mice treated with 30 mg/kg MDPV at the high ambient temperature engaged in skin-picking and self-biting, which drew blood, and, in accordance with our IACUC approval, were removed from the study and euthanized. No signs of self-injurious behavior were observed at any dose of MDPV administered at 20 1C.

Repetitive, stereotyped behavior is common with locomotor stimulants and can be observed following high doses of amphetamine, methamphetamine and cocaine among other compounds. So this is probably an expected effect. What was interesting here was the dependency on ambient temperature. Off the top of my head, I can't remember either the stimulant drug sterotypy literature (which focuses on charcterizing the repetitive behaviors) or the locomotor studies (where the "inverted U" dose effect function often reflects the emergence of stereotyped behavior after high doses) focusing too heavily on the ambient temperature issue. No doubt I could stand to go back and review some papers with a closer eye on the ambient temperature.

This study, however, points a finger at environmental issues when trying to figure out the degree to which the drug MDPV might cause sensational media-friendly outcomes in some users. Studies such as the present one may indicate that factors as subtle as how hot it is the day a person takes a given drug can change the experience from relatively benign into something much more severe. Thus, a dose of a drug which has been taken before by the same user may have highly unpredictable effects just based on this one difference in the situation.

ADDITIONAL READING

Watterson et al 2012 demonstrated intravenous self-administration in rats.
Huang et al, 2012 showed locomotor effects of MDPV on activity wheels in rats.
Fuwa et al 2007 shows dopamine responses with microdialysis and locomotor effects [in Japanese, but the Abstract is in English and the figures are easily interpreted]
Meltzer et al 2006 present monoamine pharmacology on a series of pyrovalerone compounds

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Fantegrossi WE, Gannon BM, Zimmerman SM, & Rice KC (2012). In vivo Effects of Abused 'Bath Salt' Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology PMID: 23212455

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Aug 16 2010

Why Supposed Ethics Case Studies / Training Scenarios Are Idiotic

Dr. Isis has a post up responding to a Protocol Review question "Noncompliance in survival surgery technique" published in Lab Animal [2010; 39(8)] by Jerald Silverman, DVM. His column is supposed to be in the vein of practicum case studies that are a traditional part of the discussion of ethical issues. Given X scenario, how should person A act? What is the ethical course of action? Was there a violation? Should it be reported/evaluated/punished.

We see these sorts of examples all the time in the ethics training courses to which we subject our academic trainees, particularly graduate students and postdocs.

These exercises frequently annoy me and this IACUC / Animals-in-Research question is of the classic type. Continue Reading »

7 responses so far

Jul 27 2010

About

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About DrugMonkey

The US biomedical research industry is a huge enterprise which continues to drive our economy while improving public health and personal well being. Much of this industry is funded by the federal government through the National Institutes of Health. When it comes down to it, this industry is about people, hired by the taxpayer to do some good. These are the stories of a few of those people.

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*I take IACUC and IRB approval of research studies quite seriously and they are essential to the
protection of animal and human research subjects, respectively. The issue of dumb little unscientific
(read, not validated against various biases, screened for untoward harm to participants) internet polls
is very much a gray area. From what I can tell, there is a great deal of variance in the way local IRBs
deal with these sorts of things and there is always a question as to whether such polls should fall under "research" or not. I have actually gone so far as to get an initial read from my IRB in real life and have received the opinion that IRB consideration is not necessary for this sort of polling
activity (and for that matter blogging activity).

4 responses so far

Apr 16 2010

Don't t-a-a-a-a-a-a-aze me bro!

BlackSheepDM_234.jpg
source
A report in Popular Science (authored by Jeremy Hsu) points to a recent paper published in Academic Emergency Medicine. In this, Dawes and colleagues report on an investigation on the effects of TASER on sheep intoxicated with methamphetamine (MA). I was alerted to this by Damn Good Technician who wanted a little bit of context for what would seem to be a WTF? kind of study.
ResearchBlogging.orgThe study was conducted in Dorset sheep who were anesthetized, and administered 0, 0.5, 1.0 or 1.5 mg/kg of methamphetamine HCl (curiously from dissolved Desoxyn, the approved pharmaceutical product) in an IV infusion. The drug treatment was a between subjects factor (N=4 per group) and animals were monitored for "continuous blood pressure, heart rhythm (one-lead), pulse oximetry, and capnography... Arterial blood sampling was performed at baseline, 30 minutes after the administration of the methamphetamine, and after each exposure from a TASER X26".
To answer the question of why?, and for appropriate background on the science try a PubMed search for "cardiac TASER". I note a study in which 5 sec of TASER didn't cause cardiac damage or symptoms in law enforcement trainees and another showing minimal cardiac effects on law enforcement volunteers after vigorous exercise. Also of interest are the case studies of atrial fibrillation in a previously healthy adolescent and recovery of a teen in TASER induced asystole. These, a mini-review by the Dawes group and other searched papers should give you some context and support from the feeling you might have from half-remembered MSM reports over the years that TASER is suspected of being somewhat less than "safe".
What I'm not finding right away is very much about the drug intoxicated suspect who might be TASER'd by law enforcement. Remember this guy? My best estimate was that he was acutely intoxicated with 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") although that might be one of my blog interests talking. You might also wish to consider some papers found by searching PubMed for "methamphetamine cardiac toxicity", "methamphetamine vetricular fibrillation" and "methamphetamine heart attack".
Together this background would seem to identify a situation crying out for additional study.

Continue Reading »

8 responses so far

Dec 18 2009

Oklahoma Legislator Displeased by OSU Caving to ARA Demands

Published by under Animals in Research

For those of you that haven't been following along, Oklahoma State University President Burns Hargis unilaterally blocked a project on anthrax vaccine development from going forward. The project was IACUC approved and NIH funding had been allocated (OSU's end was a subcontract on the project). The reasons given by President Hargis were less than convincing. It boiled down to an assertion that the work was "controversial" and "not in the interests of OSU", combined with a rejection of the speculation that he had caved in to demands from one of OSU's biggest donor couples (the wife of the couple is a noted AR activist and well beloved by extremist organizations). Did I mention the project included baboons as research subjects?
[ A great summary is here at Speaking of Research. ]
In all the explaining coming from President Hargis and OSU spokespeople, we have a continued assertion that the University is not against all animal reseach and has not been swayed by AR activists. Well, one of the Oklahoma state legislators isn't buying this line of bullpockey anymore than I am.
Representative Phil Richardson:


"I bleed Orange as much as anyone, but I am deeply concerned by the actions of OSU officials, which appear designed to cater to animal-rights fanatics instead of providing a sound education in agricultural sciences," said Richardson, a Minco Republican who received his Doctor of Veterinary Medicine from OSU in 1967.

Continue Reading »

8 responses so far

Dec 02 2009

More on the OSU quashing of NIH-approved research

Following up my recent notes on the OSU situation (wherein the President decided to block a research project apparently at the behest of a wealthy donor) Speaking of Research has additional thoughts.

They also point out that the research is part of a much larger investment made by the state of Oklahoma and other funding sources that contributed over the past several years to construct state-of-the-art biosafety laboratory facilities at OSU. The facility was built with the express intent of supporting nonhuman primate research and under the condition that it would also be accessible to researchers at other Oklahoma institutions.

This makes this a much larger problem than the blocking of a single grant. The NIH frequently partners with the local University to build long-term infrastructure (yes, including major building renovations) with the intent of supporting a certain type of research. To accept this money and then refuse to subsequently conduct the intended research is a whole new level of bad on the part of the University.
If this is really the situation, that the baboon studies were a major part of the reason the original infrastructure award(s) were made...well, I think the NIH should be seeking cost recovery from OSU.
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Additional Reading:
ERV; ERV again

Continue Reading »

6 responses so far

Nov 30 2009

OSU President Blocks NIH Funded Science to Appease Philanthropist

Published by under Animals in Research

The web side of The Oklahoman reports that the president of Oklahoma State University has blocked some studies on anthrax from going forward:

Veterinary medicine researchers were told by e-mail last month that OSU President Burns Hargis wouldn't allow the National Institutes of Health-funded project, even though an internal faculty committee had spent more than a year setting out protocol for the care and use of the primates.
Veterinary scientists say the decision was sudden and arbitrary, and now they fear the president may call for ending other projects involving animal research.
OSU administrators declined to comment for this story, but released a statement through OSU spokesman Gary Shutt stating "this research was not in the best interest of the university. The testing of lethal pathogens on primates would be a new area for OSU that is controversial and is outside our current research programs."

ERV, in her inimitable style, called shenanigans.

Continue Reading »

54 responses so far

Sep 21 2009

SfN Committee on Animals in Research Issues Challenge to the NIH

A recent press release from the Society for Neuroscience informs us of the recent publication of two opinion pieces in the Journal of Neuroscience. One is by Professors Jentsch and Ringach and strikes a tone similar to their Letter to the Editor published Journal of Neurophysiology I mentioned previously. The J. Neurosci opinion by Ringach and Jentsch concludes:

We must now face the many threats to animal research in general and to neuroscience in particular. We must prove that "scientific community" means something more than the mere fact that we publish in the same journals and attend the same conferences. We must stand together to defend those colleagues under attack and defend the research we believe to be ethical and critical for our understanding of the brain in health and disease. The public is ready to listen.

Slightly more provocative is a call to NIH action from the current head of the SfN Committee for use of Animals in Research.

Continue Reading »

7 responses so far

Sep 15 2009

Polling my professorial rank readers

A pair of comments on my recent post on New Investigator data trends had me wondering if my PI / Professorial readership diverges from the overall distribution. ScienceWoman suggested a poll so here* goes.

Continue Reading »

23 responses so far

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