Commercial airlines now refusing to transport lab mice

Via ScienceMag:

Twenty-nine transgenic mice that two Spanish airlines had refused to transport hitched a ride to the Canary Islands on a military plane Friday and are now at their final destination

Y’all looked away when they stopped shipping purpose bred non-human primate laboratory subjects. “Oh please”, you thought, “there is no way anyone gives a care about genetic mouse models”.

Guess what? You were wrong and Niemöller’s principle rules the day.

Santa Cruz Biotech fined, banned from animal use

The big news of the day is that Santa Cruz Biotech has been punished for their malfeasance.

Buzzfeed News reports:

After years of allegations of mistreated research goats and rabbits, a settlement agreement (pdf) announced late on Friday will put Santa Cruz Biotechnology out of the scientific antibody business. The company will also pay a $3.5 million fine, the largest ever issued for this type of violation.

The settlement is only three pages so go ahead and read it. It is pretty much to the point.

Santa Cruz Biotech neither admits nor denies the allegations, blah, blah, but it is settling. They are to be penalized $3.5 million dollars, payable by the end of May, 2016. Their animal welfare act registration is revoked effective Dec 31, 2016. They will not use any inventory of the blood or serum they have on hand collected prior to Aug 21, 2015 to make, sell, transport, etc anything from May 20, 2016 to Dec 31, 2016 (after which they still cannot, I assume, since the license will be revoked). They agree to cease all activity as a research facility and will request cancellation of their registration with APHIS as such as of May 31, 2016.

I don’t know how easy it will be for the overall company to get around this by starting up some other entity, possibly off shore, but it sure as heck looks like Santa Cruz Biotech is out of business.

Hoo-ray!!

There are several specific allegations of animal use violations under the Animal Welfare Act at play. But for me there was one really big deal issue, I assume this was why the hammer came down so hard and why Santa Cruz Biotech decided they had no choice but to settle in this manner.

As Nature reported in early 2013, Santa Cruz Biotech hid an animal facility from Federal inspectors.

A herd of 841 goats has kicked up a stir for one of the world’s largest antibody suppliers after US agricultural officials found the animals — including 12 in poor health — in an unreported antibody production facility owned by California-based Santa Cruz Biotechnology.

“The existence of the site was denied even when directly asked” of employees during previous inspections, according to a US Department of Agriculture (USDA) report finalised on 7 December, 2012. But evidence gathered on a 31 October inspection suggested that an additional barn roughly 14 kilometres south of the company’s main animal facility had been in use for at least two and a half years, officials said.

This is mind bogglingly bad, in my view. Obviously criminal behavior. The Nature bit described this as “another setback”. To me this should have been game over right here. Obviously trying to cover up misuse of animals so my thought is that even if it worked, and you can’t actually observe the misuse, well, “get Capone on taxes even if you can’t prove the crime” theory.

But then there was more. In the midst of all the inspecting and reporting and what not….

In July 2015, the major antibody provider Santa Cruz Biotechnology owned 2,471 rabbits and 3,202 goats. Now the animals have vanished, according to the US Department of Agriculture (USDA).
…
the company seems to have done away with its entire animal inventory. When the USDA inspected the firm’s California facility on 12 January, it found no animal-welfare violations, and listed “no animals present or none inspected”. USDA spokesman Ed Curlett says that no animals were present during the inspection.

The fate of the goats and rabbits is unclear. The company did not respond to questions about the matter, and David Schaefer, director of public relations for the law firm Covington & Burling in Washington DC, which is representing Santa Cruz Biotechnology, declined to comment on the animals’ fate.

This sounds like an outrage, I know. But the bottom line is that a company in good standing with animal use regulatory authorities could in fact decide to euthanize all of its animals. It could decide to transfer or sell them to someone else under the appropriate regulations and procedures. This is really suspicious that the company won’t say what it did with the animals, but still.

It’s the concealment of the animal facility mentioned in the Dec 7, 2012 report that is the major violation in my view. They deserve to be put out of business for that.

Dissection of sleazy, dishonest AR shillery posing as journalism

Notice what I did there? Setting a bias right from the start with click-bait headlining?

Well, that is just how a buzzfeed piece entitled “The Silent Monkey Victims Of The War On Terror” starts.

“Victims”.

I called this piece out for being sleazy and dishonest in a tweet and the author, one Peter Aldhous, Buzzfeed News Reporter, took exception. He emailed me asking how I could possibly accuse him of being a shill for the AR agenda, asserting he has no allegiance whatsoever to animal rights and complaining about how someone as allegedly influential as me could damage his professional reputation.

So I felt I owed him an explanation.

First, I make no apology for my distaste for AR adherents. They are terrorists, yes, terrorists, and they inhabit a nihilist, anti-social ideology. Of terrorism.

Second, I’ve written a few posts about the use of animals in research (see below for Additional Reading). There is a pretty good dose of information at Speaking of Research as well. I mention this not so much to draw specifics as to show that there is information available on the web, readily searchable, for a journalist to quickly find for an alternative viewpoint to the AR nonsense. That is, if they are interested in researching a story. I’ll also point out that the Science Editor at Buzzfeed is someone who spent years pounding the floors at the annual meeting of the Society for Neuroscience and has even written on the use of nonhuman primates in autism models. Again, the point is that this journalist has a route to further education and balance, if he had only chosen to use it. The piece does not reflect any such background, in my reading of it.

What I want to dissect today, however, is the way this piece by Aldhous is carefully crafted to attack nonhuman primate research, as opposed to providing a reasonable discussion of the use of animals in specific research.

The article starts with “victims” and has chosen to describe this as resulting from “The War on Terror”. Right away, we see a sleazy link between something that many Americans oppose, i.e., the description of the Bush agenda as a war on terror and the Bush agenda itself, and the use of animals in research. It is a typical tactic of the AR position. If you can establish that one area of research is unneeded in the eyes of your audience then you are three quarters of the way home.

And this is AR thinking, make no bones about it. Why? Follow the logic. There are sizable swaths of Americans who disagree that we should spend public money investigating any number of health conditions. From infectious disease like HIV (although see this) to obesity to diabetes to depression to substance abuse. Simply because they do not agree that these are topics that are worth of investigation. Anthrax, botulism and nerve gas are no different in this respect. Some people feel that the war on terror is overblown, the risks of a bio or chemo weapon attack are small and we should not put any public money into this topic whatsoever- from research to law enforcement.

So if you argue that your particular agenda should rule the day when it comes to research, you are saying that everyone’s agenda in a pluralistic democratic society should rule the day. This leaves us with very little science conducted and certainly no animal science. This is why I call this a bit of AR shillery. The logic leads to no animal research on any health topic.

Note, it is fine to hold that belief in pluralistic democratic society but let us be honest about what you are about, eh? And sure, I can see that there would be some agenda so narrowly focused, so out of the mainstream that we cannot reasonable credit as being a legitimate concern of the American people. It should be self-evident from the support for the Bush administration’s war on terror (and our public discussion over bioterror) that this is not the case here.

Ok. But what about the converse? Is just any use of animals in research okay then? No, no it is not. Certainly, we have a cascade of federal law, federal regulation and widely adopted guidelines of behavior. We have rules against unnecessary duplication. We wrangle, sometimes at long length, over reduction and refinement of the research that uses animals. Even an apparent exemption from the full weight of the Animal Welfare Act for certain experimental species doesn’t really exempt them from oversight.

Getting back to the article, it next pursues two themes including the idea that there are a “lot” of monkeys being used and that they are all “suffering” and in pain. The article includes this pull quote:

“Wow, that’s a lot of monkeys,” said Joanne Zurlo of the Johns Hopkins Bloomberg School of Public Health, who studies alternatives to animal experimentation. “It’s quite disturbing.”

It is? How do we know this? How are we to evaluate this with any sort of context? How is it “disturbing” unless we have already decided we are against the use of monkeys in this, or for that matter any, research?

The piece brags about some exclusive review Buzzfeed has conducted to examine the publicly-available documents showing about 800 nonhuman primates used in “Column E” (the most painful/distressful category) US research in the 1999-2006 interval and a jump to about 1400 in the 2009-2014 interval.

Speaking of Research maintains an animal-use statistics page. The US page shows that of the species not exempted from tracking by the Helms Amendment, non-human primates account for 7% of the total (all categories of research use) in 2014. This is 57,735 individuals- note that given that non-human primates can be used for years if not decades in some kinds of research, this does not equate to a per-year number the way it would for a species that only lives 2 years like a rat. But at any rate, the 600 extra [ETA: “E” category monkeys] that the Buzzfeed piece seems to be charging to the war on terror is only a 1% increase in the annual “E” use of non-human primates.

This is “disturbing”? Again, I think this alone shows how disingenuous the piece really was. A “one percent increase in the use of monkeys for bioweapon research” doesn’t really have the same punch, does it?

What about other frames of reference? From the Speaking of Research page:

Scientists in the US use approximately 12-25 million animals in research, of which only less than 1 million are not rats, mice, birds or fish. We use fewer animals in research than the number of ducks eaten per year in this country. We consume over 1800 times the number of pigs than the number used in research. We eat over 340 chickens for each animal used in a research facility, and almost 9,000 chickens for every animal used in research covered by the Animal Welfare Act. For every animal used in research, it is estimated that 14 more are killed on our roads.

Or what about the fact that Malaysia culled 97,119 macaque monkeys (long-tailed, i.e. M. fascicularis and pig-tailed, i.e. M. nemestrina; common research lab species) in 2013. Culled. That means killed, by rough means (by the reporting) without any humane control of pain or suffering. No use for them, no scientific advances, no increase in knowledge…probably not even used for food. Just…..killed. 167 times the number scored as used in bioweapons research were just eliminated in a single year in a single country.

Failing to provide these contexts, and writing a piece that is majorly focused on the number of research monkeys used for bioweapons studies is dishonest, in my view.

Okay, so what about the pain and suffering part of the piece? Well, Aldhous writes:

BuzzFeed News has calculated the number of primates used each year for what the USDA calls “Column E” experiments, in which animals experience pain or distress that is not fully alleviated with painkillers, tranquilizers, or other drugs. Because monkeys are emotionally complex creatures that are thought to experience suffering similarly to how we do, such experiments are especially controversial.

The number of primates used in these ethically fraught experiments

Notice the slant? First of all, human introspection about the “pain and suffering” of nonhumans is suspect, to say the least. Yes, including monkeys, dolphins or whathaveyou. The statement about monkeys being “emotionally complex creatures” is pure AR theology. The idea that nonhuman suffering is identical to human suffering is entirely unproven and there are large numbers of people who disagree with this characterization (see the Malaysian culling, above, for an example). If you try to get people to define terms and provide evidence you devolve into really bad eye-of-the-beholder anecdata on the one hand up against a profound lack of evidence on the other. Humans are demonstrably different from all other species we know to date. And efforts to view nonhumans as “like us” invariably involve some very convenient definitions, goal post moving, blindness to the quality or universality or ease of the human trait, etc.

Calling it “especially controversial” and “ethically fraught” is hardly even handed journalism. Where is the balance here? The people who shout loudest about the use of monkeys being “controversial” don’t believe in any animal research. Seriously, probe them. What use of animals isn’t ethically fraught? Hammering this idea over and over throughout the piece is poisoning the well. It is acting like this is established fact that everyone agrees with. Not so. And the slant of these terms is certainly on the side of “this research is bad”. You use other terms when you want to describe a neutral disagreement of sides.

One very important point is the lie of the truncated distribution. We know perfectly well that there is a big part of the American distribution that is essentially unconcerned about animal use and animal suffering. If you know anyone who uses sticky traps to deal with unwanted household rodents…they are doing Category E research. Catch and release fishing? Ditto. People who own large dogs in city apartments and walk them just twice a day….well it isn’t Category E but it sure doesn’t sound humane to me. The point is that research and researchers do not operate in this part of the distribution. They operate in the well-regulated part of the distribution that is explicitly concerned with the welfare of animal subjects in research. Notice all the pull quotes he included from researchers seem to express caution? Obviously I can’t know how selected and cherry picked those comments were (I suspect very) but they do testify to the type of caution expressed by most, if not all, animal researchers. We are always looking to reduce and refine. And look, individual scientists may view different research priorities differently…but it is hardly fair to only present the skeptics. Where are the full throated defenders of the bioweapons research in this article? Well, they wouldn’t talk on record* due in very large part, I assert, to a well-informed skepticism that journalists ever care to be balanced on these topics.

The Aldhous piece goes on to a very sleazy sleight of hand by mentioning a violation report in which an animal research facility was cited for failing to follow care protocols. He picks out three institutions:

three institutes have dominated the most ethically contentious primate experiments: the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick, Maryland, the Lovelace Respiratory Research Institute in Albuquerque, New Mexico, and the Battelle Memorial Institute in Columbus, Ohio.

Since 2002, these three institutions have collectively used more than 6,400 Column E primates. In 2014, they accounted for almost two-thirds of the monkeys used in these experiments.

Again with the “most ethically contentious” charge. Nice. But the point of this is…what? Many bioweapons pathogens can only be studied at very high cost isolation facilities. It is good and right that there are not many of them and that they account for the majority of the animal use. It is also good and right that they are subject to regulatory oversight in case any slip ups need to be corrected, yes?

After a routine inspection in March, Lovelace was cited for failing to provide monkeys with the care that was supposed to be delivered — including intravenous fluids, Tylenol for fever, and antidiarrheal drugs.

The report shows that three animals did not receive Tylenol when they should have, and three did not receive anti-diarrheals when they should have, for 2-4 days of symptoms. There were 57 animals in a Cohort that did not receive injections of fluids but there is no indication that this resulted in any additional pain or distress and we can’t even tell from this brief protocol language whether this was supposed to be as-need-per-veterinarian-recommendation or not. There are two additional Cohorts mentioned for which it is noted the animals were treated according to protocol and the table in the Aldhous piece lists 431 animals used at Lovelace in 2014, probably the year for which the above citation refers. Naturally, Aldhous fails to mention these citation numbers leaving the reader free to assume the worst. This is classic misdirection and smearing at work. Which is why I call it dishonest. “Loose stools or fever for 2 to 4 days in less than 1% of individuals” sounds more like an over the counter medication warning or a threshold for when to finally call the doctor to the average ear.

Aldhous next diverts into a fairly decent discussion of how animal models may or may not fully predict human outcome but I think that in the context, and with his shading, it falls short of the mark. I’m not going to step through all of his examples because there are certain fundamental truths about research.

1) If we knew the result in advance, the experiments wouldn’t be necessary. So if we sometimes find out that animal models are limited, we only come to this conclusion in the doing. There is no way to short circuit this process.

2) We use animals, even monkeys, as proxies and models. Sometimes, they are going to come up short of full prediction for human health. This does not mean they are not valuable to use as models. Again, see 1. We only find this out in the doing and most research is novel territory.

3) The overlap between animal testing and research is fuzzy in this discussion. If you want to evaluate medications, your research may not be dedicated to, or idealized for, novel discovery about the disease process itself. This doesn’t make it less valuable. Both have purposes.

4) It is dishonest to point to places where animal research failed to predict some adverse outcome of a medication in humans without discussing the many-X more potential medications that were screened out with animal models. Protection from harm is just as important, maybe more so, than identification of a helpful medication, is it not?

So as you can see, I think this piece in Buzzfeed is written from start to finish to advance the AR agenda. It is not by any means fair or balanced. This is relatively common with journalism but that is no excuse. It is sleazy. It is dishonest. There is every reason to expect that balanced information and opinion is readily available to a journalist, even one who has no scientific background whatever.

I do not know the heart and mind of the author and as I mentioned at the outset, he protested vehemently that my take was not his intent. Which is why I have tried to focus on the piece and what was included and written. I will suggest that if Aldhous is sincere, he will read what I have written here, follow the links and take a very hard editor’s look at what he has written and the impact it has on the average reader.

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*I don’t know the solution to this problem. A piece like this one Aldhous wrote is the type of thing that hardens attitudes. Which makes it harder for the balanced story to get out. It’s a vicious cycle and I have no idea how to break it until and unless science journalists stop with this sleazy and biased AR shillery on their own.

Additional Reading

Logothetis driven out of monkey research

UCLA scientists have been under attack for over a decade

Repost: Insightful Animal Behavior: A “Sufficiently Advanced Technology”

Dolphins ain’t all that either

Logothetis driven out of monkey research

Neuroscientist Nikos Logothetis (PubMed) has informed his colleagues that he is stopping his long running nonhuman primate research program. An article in ScienceInsider by Gretchen Vogel details the issues:

Nikos Logothetis, a director at the Max Planck Institute for Biological Cybernetics in Tübingen, Germany, says he will conclude his current experiments on macaques “as quickly as possible” and then shift his research to rodent neural networks. In a letter last week to fellow primate researchers, Logothetis cites a lack of support from colleagues and the wider scientific community as key factors in his decision.

This is not the “start” as was alleged by a Twitter person today. This is a long running trend that has been going on for decades. Productive laboratories that use nonhuman primates have been closing one by one. The decision by Harvard to shutter the New England National Primate Research Center was shocking in the way it violated the trend for picking off research labs one by one, but it was otherwise simply part of a larger trend.

And why are Universities and Research Institutes like Max Planck divesting themselves of monkey labs as quickly as possible? The Vogel article suggests an answer.

Logothetis’s research on the neural mechanisms of perception and object recognition has used rhesus macaques with electrode probes implanted in their brains. The work was the subject of a broadcast on German national television in September that showed footage filmed by an undercover animal rights activist working at the institute. The video purported to show animals being mistreated.

Logothetis has said the footage is inaccurate, presenting a rare emergency situation following surgery as typical and showing stress behaviors deliberately prompted by the undercover caregiver. … The broadcast triggered protests, however, and it prompted several investigations of animal care practices at the institute. Investigations by the Max Planck Society and animal protection authorities in the state of Baden-Württemberg found no serious violations of animal care rules.

Emphasis added. This is a typical scenario. In essence, animal rights terrorist fanatics are able to get Universities and Research Institutions to turn their backs on productive researchers simply because they don’t want to deal with the headaches any longer. Or because they fear bad press. The accusations are almost always falsified. Baseless. But it doesn’t matter. The Universities are running in absolute terror of the fanatics.

Of course it goes beyond that, which is why Logothetis called out his fellow scientists.

The [Max Planck] society is “one of the best scientific organizations worldwide,” Logothetis wrote, but it has failed to take concrete steps against the activists. “I am no longer willing or able to accept the never-ending stream of abuse from animal activists toward myself and my co-workers while seeing them encouraged to increase their aggressive activities by the tolerance and very slow reactions of scientific organizations. There is a clear lack of consequences for illegal actions such as infiltration, violation of privacy, theft of documents, and even intentionally caused distress to animals in order to film supposed animal torture or abnormal behavior,” the letter states.

Logothetis’s letter also faults his scientific colleagues in Tübingen for distancing themselves from the controversy. The neighboring Max Planck Institute for Developmental Biology posted a disclaimer on its website emphasizing that there are no monkeys at the institute, he notes, and colleagues at the nearby Hertie Institute for Clinical Brain Research refused to issue a declaration of support.

Pastor Niemöller once observed:

First they came for the Socialists, and I did not speak out—
Because I was not a Socialist.

Then they came for the Trade Unionists, and I did not speak out—
Because I was not a Trade Unionist.

Then they came for the Jews, and I did not speak out—
Because I was not a Jew.

Then they came for me—and there was no one left to speak for me.

There are certainly parallels. Biological scientists express a range of attitudes about many things and the use of animals in research is one of them. From fears of coming under assault themselves if they speak up, to discomfort with making an informed decision about the allegations against Professor Logothetis to frank antipathy to research in monkeys, we span the same range as many lay people.

We are easily able to delude ourselves that if we just let the most-detested targets of the terrorists get thrown under the bus, we can live our own lives in relative safety for another few years. Maybe run out the clock on our career before things get too bad.

Money is tight, after all, and gee, well lets not do anything to rile up the nice little old ladies who are poised to donate a few million to the University, eh? Let’s not do anything to draw the attention of animal right’s Congress Critters. That might make things awkward for the NIH.

Normally this is the point of my post where I exhort you to fight. To stand up and oppose this assault on scientific research. Where I point out to you that after the monkeys (and cats and dogs) comes the goats and the rabbits from which you get your antibodies. Where I tell you that all this pressure is doing is to move certain kinds of research to non-Western countries in which the animal research protections are, at best, at the lever of the US in 1950.

This is the point where I am supposed to be telling you to call your Congress Critter.

But I can’t.

Logothetis is not the first and he will not be the last.

We have had ample opportunity for biological scientists to see and be motivated to do something about this situation.

They have not done so.

So I would be wasting my breath.

UCLA scientists have been under attack for over a decade

A new post at Speaking for Research details the history:

Back in 2003, Neurobiology Professors John and Madeleine Schlag saw their property vandalized at a home demonstration. “The way it proceeded … we felt that the door was going to be kicked in,” they commented in an interview.

In 2006, Professor Lynn Fairbanks was targeted with an incendiary device. It turned out animal extremists got the wrong address and planted the firebomb at the doorstep of an elderly neighbor.

In June 2007 another firebomb was placed under the vehicle of Professor Arthur Rosenbaum, who dedicated his life to pediatric ophthalmology by helping children with strabismus. His wife later received a threatening note which told her to persuade her husband to stop his research or “…we will do exactly what he does to monkeys to you.”

In 2007, Professor Edythe London finds her home flooded by animal rights extremists, and received the threat, “water was our second choice, fire was our first.”  She decided to reply by explaining, in a thoughtful OpEd in the LA Times, the reasons for her work.

In 2008, the UCLA community saw once again an incendiary device char the front door of a home owned by a Professor, the vandalism of three vehicles parked outside the home of a postdoctoral student, and the firebombing of a university commuter van.

Then, in 2009, the car of Professor David Jentsch, parked in his driveway, is set on fire while he was sleeping at home.  He subsequently received a letter containing razor blades and a threatening note that fantasized about sneaking up behind him and cutting his throat

The harassment of UCLA scientists in their homes has continued on a monthly basis every since. This year, the scientists have decided to organize counter protests.

The next counterdemonstration will be February 15, 2014. If you are local these scientists would appreciate your support.

 

Please join us to defend UCLA, our science, and the hope for medical advances and new cures.

When: February 15, 10:15am sharp!
Where: NE Corner of Westwood and LeConte

Join us to end the decade-long age of terror at UCLA!

Repost: Insightful Animal Behavior: A "Sufficiently Advanced Technology"

The news is chattering over a new paper by Smet and Byrne entitled “African Elephants Can Use Human Pointing Cues to Find Hidden Food” [link]. The lede is frequently the typical one for comparative cognition studies. Take this example from VOA:

Elephants are able to recognize human gestures without any sort of training, new research shows. Scientists believe the finding indicates that elephants are able to understand humans in a way most other animals do not.

They might be excused for this since the authors themselves write, in the Results and Discussion section “Here we found elephants capable of responding spontaneously to pointing gestures that require attention to subtle differences in the position of the forearm and hand.“. This is, however, a tired and old problem with this type of study.

Even Carl Zimmer, writing in the NYT, makes most of his post about this wonderous “spontaneous” property of all elephants. Still, to his credit he does include the critical caveat.

Diana Reiss, an expert on elephant cognition at Hunter College, wondered if the elephants had already learned about pointing by observing their handlers pointing to each other.
“In these elephant camps such opportunities can easily go unnoticed by their human caretakers,” said Dr. Reiss.

The authors themselves point this out, although they try to handwave it away:

All of these elephants have lived in captivity since infancy: they have had the opportunity to witness pointing used between humans. However, observation of human interactions does not automatically translate into aptitude at interpretation of these interactions.

Whoa dude. Whoa. Hold up. Extraordinary claims require extraordinary evidence. Except, apparently, in comparative cognition when we are just sooooo keen to believe findings that show species X is “just like humans” in some cognitive or behavioral property.

I have at least one observation in the archive that points out where not thinking hard about the study design can lead to unsupported conclusions being widely disseminated. This post was originally published Feb 25, 2008.

---

In the midst of World War I, Wolfgang Köhler conducted a famous series of experiments to investigate problem solving ability in chimpanzees. The lasting impression of these experiments, reinforced by just about every introductory Psychology text, was Köhler’s assertion that the chimps demonstrated “insightful” learning.
Did they now?

Dolphins ain't all that either.

There’s a great review of a new book (Are Dolphins Really Smart?,  by Justin Gregg) penned by Jessa Gamble at LWON. Go read because it is incredibly important to realize:

A disproportionate amount of dolphin research time has been devoted to teasing out any potential for language – the science-fictional myth of dolphinese – from their vocalizations. If dolphins had language, we would almost certainly have found it by now. When their vocalizations turned out to be rote and inflexible, “I’m scared!” “I’m mating!” “I see food!” pretty much covers it, the research turned to echolocation clicks. Perhaps dolphins were sending each other 3D holographic messages encoded in their clicks. Nope.

and

[waccaloon terrorist AR org]’s lawsuit against SeaWorld challenges dolphin captivity under anti-slavery legislation, citing exceptional intelligence as evidence of their “non-human personhood.” When advocacy for the ethical treatment of animals is based on exaggerated claims of their intelligence, it fails to recognize the inherent worth of animals regardless of their similarity to humans. And in dolphins, that similarity is easily refuted. It’s time relieve the dolphins of all our human baggage and realize that evolution has produced all kinds of intelligence, and it’s all around us.

Gamble notes that the book by Gregg systematically dismantles many popular myths about dolphins and, of course, points out that dolphins are total dicks

Adult male dolphins routinely kill porpoises, not for food — or even out of competition for food – but because the porpoise is similar in size to a dolphin calf. The killings serve as practice for their regular infanticidal behaviour, a sure way to ready mothers for mating.

Sounds like a good read.

 

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Additional:

Repost: Insightful Animal Behavior: A “Sufficiently Advanced Technology”

Jane Goodall, Plagiarist

 

The naked chutzpah and hypocrisy of an AR wackaloon

There’s a new post up over at Speaking of Research that documents The Double Life of Dr. Lawrence A. Hansen. The most astonishing thing is that this AR wackanut has the gall to hold research funding as PI and publish papers that, you guessed it, involve animal research. Including a study in “mongrel dogs” [cited 21 times including twice in 2012] which he first authored some ten years before hitting the scene in outrage over med school physiology labs which used canine models.

Go Read.

Perspective on the use of animals in research

We were just discussing the closure of the New England National Primate Research Center. One of the uncertainties about that decision of Harvard Medical School was where the approximately 2,000 animals of various species were to be placed. 2,000. Remember that now. Some of the news reporting also referred to the deaths of some of the NENPRC nonhuman primate subjects as a triggering cause for a two year attempt to improve their procedures. These deaths comprised a series of ones and twos going by the available news reporting…perhaps amounting to a dozen or score of animals[ETA 4, see first comment]? We have no information over what timeframe those deaths occurred.

According to the LA Times, Malaysia has culled 97,000 cynomolgous macaques. Last year. The article claims they culled 88,000 of them in the previous year.

The cynomolgous macaque, btw, is a very commonly used species in research laboratories in the US. From Speaking of Research we learn that in 2010 there were about 73,317 nonhuman primates used in 2010. Of all species. This is out of an estimated 25 million vertebrate animals used in research for that year. And remember, for the longer-lived species such as dogs or nonhuman primates, the vast majority of studies use them across multi-year and even multi-decade intervals. So across time the comparison of the yearly use of, say dogs versus mice, tends to overestimate the dogs on a per-individual basis.

We are incredibly parsimonious with the approximately 1% of animals used in research that are cats, dogs or monkeys, the ones usually of greatest concern to the average person. Parsimonious with all of them, in reality. As the Speaking of Research page puts it.

Let us put the number of animals used in perspective. Scientists in the US use approximately 26 million animals in research, of which only around 1 million are not rats/mice/birds/fish. We use fewer animals in research than the number of ducks eaten per year in this country. We consume over 1800 times the number of pigs than the number used in research. We eat over 340 chickens for each animal used in a research facility, and almost 9,000 chickens for every animal used in research covered by the Animal Welfare Act. For every animal used in research, it is estimated that 14 more are killed on our roads.

Malaysia just euthanized (how we don’t know but I’m pretty sure IACUC oversight wasn’t involved) 185,000 monkeys in the past two years. Why?

Tourists and many Malaysians gather near jungle edges to watch the monkeys, snap photos of them and feed them peanuts and bananas. But the wildlife department, also known as Perhilitan, says the extensive culling was necessary to curb a “pest species” that breeds prolifically, adapts with ease, and ransacks homes for food.

“It is a hard decision, but in order to safeguard the well-being of people and to maintain a stable macaques population … it might be the best option in a short run,” the department said in an email to The Times.

185,000 culled as annoying pests over two years. A problem that may or may not have been increased by tourists. Even if the above stats reflected different individuals in each year, this is about equivalent to the total number of nonhuman primates used in US research laboratories. In fact, the number is likely to be much closer to the annual 73,317 count, given the longevity of the species. And we have no idea when Malaysia will stop culling.

In a related vein the ASPCA says that about 3-4 million companion animals (dogs and cats) are euthanized in shelters in the US annually. Annually. Why? Because nobody wants them. 64,930 dogs and 21,578 cats used in research in 2010. Versus 3-4 million. That’s 3,000,000 vs 86,508. Mere inconvenience and irresponsibility versus the advance of knowledge and creation of new medical treatment for humans and animals as well.

The inadvertent deaths of a handful to perhaps a score of monkeys[ETA 4, see first comment] at the NENPRC led to massive shut down of research, a two year reorganization process and ultimately the demise of the Center. The center which made demonstrable advances in AIDS, drug abuse and Parkinson’s disease amongst other accomplishments.

At the very least this should give some perspective on how seriously the research enterprise and oversight system takes the humane treatment of research animals. It compares very favorably indeed with how the rest of the world (including the US) treats animals (yes, including companion species).

Harvard to close their New England National Primate Research Center

Harvard has decided not to seek to renew NIH support for their New England National Primate Research Center, established by Congress in 1962. The Center has operated with a so-called “base grant” from the National Institutes of Health underpinning the not-inconsiderable costs of housing thousands of nonhuman primates and the usual grab bag of investigators’ independent sources of funding. The NENPRC site lists an impressive series of accomplishments.

First unambiguous evidence that AIDS is caused by a virus.
Discovery of Simian Immunodeficiency Virus (SIV) and development of first animal model of AIDS.
Original demonstration that vaccine protection against AIDS is theoretically possible.
Discovery that a gene product of the AIDS virus activates lymphocytes necessary for disease progression.
Identification of therapeutic genes that can prevent infection of cells by the AIDS virus.
First demonstration that protective genes introduced into blood stem cells can block HIV or SIV infection.
Discovery of primitive blood stem cells lacking CD34 and their implications for bone marrow transplantation
Isolation of type-D retroviruses as major causes of illness and death in macaques.
Discovery of the oncogenic herpesvirus, Herpesvirus saimiri.
Discovery of a nonhuman primate virus closely related to the human Kaposi’s sarcoma-associated herpesvirus.
First nonhuman primate models of colon cancer and inflammatory bowel disease.
Evidence leading to the use of hydroxyurea to treat sickle cell anemia.
Discovery of stunned myocardium and its role in myocardial ischemia.
Discovery of cellular organization and critical period for development of the visual cortex.
First unambiguous evidence for the addictive properties of nicotine.
Identification of major risk factors in self-injurious behavior.
First animal model for progressive neurodegeneration in Parkinson’s disease.
Development of improved brain imaging techniques for early diagnosis of Parkinson’s disease.
Development of novel cellular and pharmacological strategies for treatment of Parkinson’s disease.
First survey of distribution of cocaine binding sites in primate brain.
Identification of the dopamine transporter as a principal target for cocaine in the brain.
First nonhuman primate model of drug relapse.
Development of novel drug classes to treat cocaine addiction and other brain dopamine disorders.

Most of the news reporting has focused on a series of lapses in the care of nonhuman primate subjects, leading to several deaths. I cannot comment on the degree to which this situation reflected lapses in the system, but clearly Harvard was undergoing major corrective measures. The news accounts describe situations which seem to me to be procedural lapses that have relatively straightforward fixes. Nothing appears to be systematically unfixable…again, going by the news accounts.

The Harvard Medical School press release is slightly more instructive, however.

The decision to conclude NEPRC operations follows a two-year period during which the Center leadership successfully addressed operating issues with input from the NIH and other governing agencies. The process resulted in new procedures that have significantly strengthened the Center’s day-to-day activities and that can serve as a model for other institutions throughout the country. Many of those changes carried additional costs, and HMS will continue to make investments in the Center to ensure ongoing compliance with all federal regulations.

Right? So the problems were fixable and they’d been investing in fixing them for two years. “Additional costs”, eh? Well, no biggie if the investment is good.

But what has happened in the past several months, hmm? The sequester. The Continuing Resolution for FY2013. Obama’s budget request for FY2014. None of this is good news. If you look at the NENPRC as effectively a small, soft-money research institute funded in large extent by federal grants (and let’s face it, partnering with for-profits isn’t going that well for academia right now either) then its prospects are pretty dim. Look at the situation through the lens of Return on Investment and everything becomes clear.

As they weighed whether to renew the base grant from the NIH, HMS leaders made a strategic decision based on a review of the long-term academic benefits and the financial cost of continuing to operate the NEPRC.

“Deciding how to best assign our limited resources is not unique to HMS,” said Jeffrey S. Flier, Dean of the Faculty of Medicine of Harvard University,

also…

Driving the decision was the fact that the external funding environment for scientific research has become increasingly challenging over the past decade. Recent funding pressures have added uncertainty to this already-challenging fiscal context. As Harvard Medical School leadership evaluated the long-term need to use its resources in the most effective manner across all of its missions, they came to the conclusion that winding down the operations of the NEPRC was more beneficial to the School than investing further resources in maintaining and renewing the NEPRC grant.

So yeah, this looks from the outside like a small, specialized research institute closing down due to the NIH funding situation to me.

Maybe I have NIH grant myopia but this is the way it looks.

I am reviewing some of the claims made about their listed accomplishments and going back to the original papers, where I can deduce them. In a few areas that I am familiar with….man. Straight up. These are valid claims, even if we recognize that no science breakthrough arrives entirely by itself. And more importantly, particularly when it came to the early days of AIDS, I am having trouble imagining how progress could have been made so rapidly without one of the National Primate Research Centers. They really do seem to serve a unique function in the NIH / US Federal extramural research enterprise and it would be a shame if this was merely the lead indicator in shuttering the whole program.
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Disclaimer: I have professional acquaintances that work at NENPRC. I am disturbed that they are losing their jobs and I do hope that they get snapped up by some other University.

Blogrolling: unlikely activist

I invite you to put the new blog of Professor J. David Jentsch on your list. At the unlikely activist you will find fare such as:

The mystery of addictions, Part 1: Why spend money on addiction research at all?

If they are remarkably lucky and have proper medical and psychological support, they may return to a healthy life and never use again. But for most, their freedom is only temporary, and they will relapse again days, weeks, months or even years later, returning them to their suffering and to their fateful spiral. You see, drugs kill. They are powerful toxins that can stop breathing or a heart. If they are injected, they can bring infectious diseases like hepatitis and HIV along with them. And because they intoxicate the mind, they lead to reckless driving and other behaviors that risk the lives of the addict and those around them.

Ignoring science, from the bench

Put differently, juveniles and teens have a brain fully capable of feeling powerful emotions (like anger), but their ability to resist those emotions and to behave in a socially appropriate manner (like to inhibit aggressive reactions) is not at adult levels. The 5 justices who struck down harsh penalties for child offenders recognized this; it was a crucial part of their logic in this, and the earlier death penalty, case.

But like a frightening number of people in our society, the other 4 justices viewed the science as either being wrong or irrelevant. Their own ethical or philosophical views about crime and punishment appeared to trump their interest in scientific principles and facts. In this regard, they are not unlike strident animal rights activists opposed to biomedical and behavioral research involving animals.

A solemn voice in support of medical researchers

In the fall of 2010, an animal rights extremist sent me razor blades and heinous threats to cut my throat in the mail. It became a national news story, again highlighting the abject cruelty of some in the anti-vivisection movement. During this time, I turned on my phone one evening to see that I had received a voice mail. Anticipating the worst – yet another cruel, rabid and profane threat from my opponents – I found something quite different. I have kept this communication private for long enough. Now, at the wishes of the caller, I am sharing it with the broader community to demonstrate that support for humane animal research is everywhere…. It comes not from greed or ignorance, but from love and a hope that no one should ever suffer the same loss as the caller.

VoiceofSupport (click on this link to listen to this .wav file)

On discovering new medicines

A link from writedit pointed me to a review of drugs that were approved in the US with an eye to how they were identified. Swinney and Anthony (2011) identified 259 agents that were approved by the US FDA between 1999 and 2008. They then identified 75 which were “first in class”, i.e., not just me-too drugs or new formulations of existing drugs or whatnot. There were 20 imaging agents, not further discussed, and 164 “follower” drugs.

The review also focused mostly on small molecule drugs instead of “biologics” because of an assumption that the latter are all exclusively “target based” discoveries. The main interest was in determining if the remaining small molecule drugs were discovered the smart way or the dumb way. That’s my formulation of what the authors term “target based screening” (which may include “molecular mechanism of action”) discovery and “phenotypic screening” type of discovery. As they put it:

The strengths of the target-based approach include the ability to apply molecular and chemical knowledge to investigate specific molecular hypotheses, and the ability to apply both small-molecule screening strategies (which can often be achieved using high-throughput formats) and biologic-based approaches, such as identifying monoclonal antibodies. A disadvantage of the target-based approach is that the solution to the specific molecular hypotheses may not be relevant to the disease pathogenesis or provide a sufficient therapeutic index.

A strength of the phenotypic approach is that the assays do not require prior understanding of the molecular mechanism of action (MMOA), and activity in such assays might be translated into therapeutic impact in a given disease state more effectively than in target-based assays, which are often more artificial. A disadvantage of phenotypic screening approaches is the challenge of optimizing the molecular properties of candidate drugs without the design parameters provided by prior knowledge of the MMOA.

You will note that this is related to some comments I made previously about mouse models of depression.

The authors found that 28 of the first-in-class new molecular entities (NMEs) were discovered via phenotypic screening, 17 via target based approaches and 5 via making synthetic mimics of existing natural compounds. To give you a flavor of what phenotypic screening means:

For example, the oxazolidinone antibiotics (such as linezolid) were initially discovered as inhibitors of Gram-positive bacteria but were subsequently shown to be protein synthesis inhibitors that target an early step in the binding of N-formylmethionyl-tRNA to the ribosome

and for target based approaches:

A computer-assisted drug design strategy that was based on the crystal structure of the influenza viral neuraminidase led to the identification of zanamivir

The authors even ventured to distinguish discovery approaches by disease area:

Evaluation of the discovery strategy by disease area showed that a phenotypic approach was the most successful for central nervous system disorders and infectious diseases, whereas target-based approaches were most successful in cancer, infectious diseases and metabolic diseases

Unsurprising of course, given that our state of understanding of nervous system disorders is, to most viewers, considerably less complete in comparison with some other health conditions. You would expect that if there are multiple targets or targets are essentially unknown, all you are left with are the predictive phenotypic models.

Of the follower drugs 51% were identified by target based discovery and 18% by phenotypic screening. This is perhaps slightly surprising given that in the cases of the me-too drugs, you would think target-based would be more heavily dominant. Perhaps we can think of a drug which initially looked to have property X that dominated but then in the phenotypic screening, it looked more like a property Y type of drug.

The authors take on this is that it is slightly surprising how poorly target-based discovery performed within a context of what they describe as a period in which there was a lot of effort and faith placed behind the target-based approaches. I suspect this is going to be in the eye of the beholder but I certainly agree. I can’t really go into the details but there are areas where my professional career is…affected, let us say…by the smart/dumb axis of drug discovery. It should be obvious to my longer term readers that I align most closely with animal models of various things related to health and neurobiology and so therefore you may safely conclude that I have a bias for phenotypic screening. And even in the case of the target-based discovery:

at least three hypotheses that must be correct to result in a new drug. The first hypothesis, which also applies to other discovery approaches, is that activity in the preclinical screens that are used to select a drug candidate will translate effectively into clinically meaningful activity in patients. The other two hypotheses are that the target that is selected is important in human disease and that the MMOA of drug candidates at the target in question is one that is capable of achieving the desired biological response.

Right. You still need good phenotypic models and ultimately you are going to have to pass human clinical trials. The authors further worry that this higher burden, especially knowing the MMoA is going to lead to some misses.

in the case of phenotypic-based screening approaches, assuming that a screening assay that translates effectively to human disease is available or can be identified, a potential key advantage of this approach over target-based approaches is that there is no preconceived idea of the MMOA and target hypothesis.

Ultimately I think this review argues quite effectively for an “all hands on deck” approach to drug discovery but it can’t help but come off as a strong caution to the folks that think that “smarter” (aka, “rational drug design”) is the only solution. Yes, this points the finger at Francis Collins’ big thrust for a new translational IC at the NIH but also at the BigPharma companies that seem to be shedding their traditional models-based, phenotypic discover research units as fast as they can. No matter which side you come down on, this is a great read with lots to think about for those of us who are interested in the discovery of new medicines.
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Swinney, D., & Anthony, J. (2011). How were new medicines discovered? Nature Reviews Drug Discovery, 10 (7), 507-519 DOI: 10.1038/nrd3480

A refreshing change in MSM framing of the animals-in-research issue

The Seattle PI’s Big Blog (Covering Seattle news, weather, arts and conversation, along with a grab bag of stuff that’s just plain interesting) has an article up covering an animal rights extremist group’s billboard campaign in their fair city. What is interesting about this is the rather fair handed set of options they have chosen.

• Eye opening. Glad they’re spreading the message.
• Unfair and sensationalistic.
• Disturbing, but it’s a message we all need to hear.
• Just plain incorrect.
• Boring. I wish [AR extremist group] would go back to naked demonstrations.

Naturally I encourage you to visit the poll and cast your vote.
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My point about this being a refreshing change can be best understood by reading this post.

IOM Committee on Chimpanzee Research

The Nature News Blog has a bit on the recent meeting of the Committee on the Use of Chimpanzees in Biomedical and Behavioral Research. The NIH commissioned the Institute of Medicine to:

Explore contemporary and anticipated biomedical research questions to determine if chimpanzees are or will be necessary for research discoveries and to determine the safety and efficacy of new prevention or treatment strategies. If biomedical research questions are identified:

Describe the unique biological/immunological characteristics of the chimpanzee that make it the necessary animal model for use in the types of research.
Provide recommendations for any new or revised scientific parameters to guide how and when to use these animals for research.

Explore contemporary and anticipated behavioral research questions to determine if chimpanzees are necessary for progress in understanding social, neurological and behavioral factors that influence the development, prevention, or treatment of disease.

I was struck by a comment reported by the Nature News blog from a participant who objected to the scope of the study.

Animals in Research: Groupthink?

My email box overfloweth with references to an article in the Chronicle for Higher Education penned by Lawrence Hansen, M.D., a pathologist at the UCSD Medical School.
Dr. Hansen is an animal rights extremist who came to national attention with a fight to eliminate dog physiology lab classes from the UCSD medical education program. Since that era, he has penned a number of editorials and opinion bits that make it clear he has a more general interest in stopping the use of animals in research.
or…some animals, anyway.