The Biology of Iron

Yes, sometimes the animals are like us and other times they are different than us. One of my early professors taught me that we can learn as much sometimes from how animals are different from us as they are the same. In many cases, as in the study iron deficiency, my topic area, the biology of iron is the same in a monkey, and a rat, and a human, and one can learn a lot from it. -- Chris Coe, Dane County Supervisors Executive Committee, July 8, 2010. (My emphasis.)

I mentioned in my last post that Dr. Coe's assertion concerning the biology of iron was worth looking at a little more closely.

Iron is a nutritional requirement for a number of species, perhaps even most, if not all. This isn't surprising given the fact that iron is a commonly occurring element and that life on earth has been exposed to iron throughout evolutionary time.

But needing and using iron has not led to a common fixed biology of iron, despite Coe's assertion.

His claim is far-reaching and inaccurate. Not only is monkey, rat, and human iron biology different, as would be generally assumed given these species' evolutionary separation, but, as it turns out, even within each "species" there is variability in the biology underpinning iron requirements and metabolism. ["Species" is inaccurate in this context. There are many species of rats and monkeys. Biomedical researchers using animals frequently and routinely interpret results from a small experimental group of animals of the same species with overly broad claims about the entire species or even multiple Families, as in claims about "monkeys" a generic term which encompasses somewhere around 500 species.]

Consider first the biology of iron in rats of the same species but from different strains.

The following passage is from Strain differences in inbred rats: influence of strain and diet on haematological traits. Hackbarth H, Burow K, Schimansky G. Lab Anim. 1983 Jan.

So what about the biology of iron in the approximate 500 monkey species? It is quite variable. But to be fair to Coe, I'm sure he doesn't have an inkling about the iron requirements or the biology of iron in all of these distinct species; he was probably referring to one of the three species most commonly used: rhesus monkeys, long-tailed macaques (aka crab-eating macaques or cynomolgus monkeys), and common marmosets, (or maybe even squirrel monkeys, species he once erroneously prophesied would "play an increasing important role in research." (See Rosenblum LA, Coe CL Handbook of squirrel monkey research. Plenum Press. 1985. vii.)

The standard text: Nutrient Requirements of Nonhuman Primates: Second Revised Edition 2003 (Committee on Animal Nutrition, National Research Council, Ad Hoc Committee on Nonhuman Primate Nutrition) notes that:

Marmosets (Callithrix jacchus), [like lemurs], develop hemosiderosis in captivity; it is also believed to be caused by high-Fe diets. When a diet lower in Fe (100 mg·kg-1) was fed, liver Fe was only one-tenth that of animals fed a high-Fe diet (500 mg·kg-1), demonstrating that lowering the Fe content of the monkey diet can reduce the risk of hemosiderosis. (p 100)

In Comparative haematological and plasma chemistry values in purpose-bred squirrel, cynomolgus and rhesus monkeys, Matsuzawa T, Nagai Y. Journal of Comparative Haematology International, 1994, the authors write (in regard to iron-related measures only):

The results indicated that squirrel, rhesus and cynomolgus monkeys have essentially biologically similar values for all of the parameters examined. However, haemoglobin level, ... in cynomolgus monkeys [was] statistically lower than those of rhesus monkeys. ... [H]aemoglobin level, haematocrit, ... in cynomolgus monkeys were statistically lower than those of squirrel monkeys.

In fact, iron biology even varies between human populations.

Correlates of anemia in American blacks and whites: the REGARDS Renal Ancillary Study. Zakai NA, McClure LA, Prineas R, Howard G, McClellan W, Holmes CE, Newsome BB, Warnock DG, Audhya P, Cushman M. American Journal of Epidemiology 2009 169(3)

ABSTRACT

For unclear reasons, anemia is more common in American blacks than whites. The authors evaluated anemia prevalence (using World Health Organization criteria) among 19,836 blacks and whites recruited in 2003–2007 for the REasons for Geographic And Racial Differences in Stroke Renal Ancillary study and characterized anemia by 3 anemia-associated conditions (chronic kidney disease, inflammation, and microcytosis). They used multivariable models to assess potential causes of race differences in anemia. Anemia was 3.3-fold more common in blacks than whites, with little attenuation after adjusting for demographic variables, socioeconomic factors, and comorbid conditions. Increasing age, residence in the US southeast, lower income, vascular disease, diabetes, hypertension, and never smoking were associated with anemia. Age, diabetes, and vascular disease were stronger correlates of anemia among whites than blacks (P < 0.05). Among those with anemia, chronic kidney disease was less common among blacks than whites (22% vs. 34%), whereas inflammation (18% vs. 14%) and microcytosis (22% vs. 11%) were more common. In this large, geographically diverse cohort, anemia was 3-fold more common in blacks than whites with different characteristics and correlates. Race differences in anemia prevalence were not explained by the factors studied. Future research into the causes and consequences of anemia in different racial groups is needed.

Apparently, Coe's claim that the biology of iron is the same in monkeys, rats, and humans is not accurate or at least requires much qualification. Stating simply that the biology of iron is the same was misleading and apparently something other than a science-based claim.

The Party Line

It’s part of the script. When the public questions a lab’s use and treatment of animals, lab spokespersons intone a litany of internal committees, federal and state agencies, and private accrediting bodies as evidence that any concern is based on ignorance, probably as a result of fabrications and brainwashing (by people like me.)

For instance, Chris Coe, director of the Harlow lab testified at the Dane County Executive committee in opposition to Resolution 35. This is a transcript, beginning at about 51:08. (I know it’s not all on point, but it’s interesting, and I can't resist the opportunity to comment, so I’ve included his entire statement here.)

My name is Chris Coe. I’ve been a resident of Madison for twenty-five years. I’m a professor at the university. I raised my family here. I consider myself to be a compassionate and ethical individual [as have many villains], and I am also a biomedical researcher who happens to study both animals and humans. So I can bring to the table the perspective of why one might study some questions, some problems in humans and find it advantageous to study other questions and issues in animals. I do both.

It was of interest to me that the first speaker tonight felt so kindly disposed to Sterling Johnson and the gerontology researchers, because I too know Sterling Johnson, and I work with him, and we collaborate on animal research using neuroimaging, studying the biology of aging, in ways that we can’t do the same type of research on autopsy tissue. As beneficial as that may be, when one is interested in mechanisms, in our case the benefits of certain types of diets for slowing down brain aging, delaying dementia and Alzheimer’s [Alzheimer's is a uniquely human disease], it can be better done in a study with animals than in a case example of a single person. [The "first speaker" is involved in a long-term epidemiological study of victims of Alzheimer's and their families backed-up by postmortem studies of their brains, research that actually has the potential to make a difference.]

I’m here to ask you to table and set aside this motion because there is more implicit, hidden in it than meets the eye. Just even the text, the words used, as you’ve heard tonight by half, from half the people in the audience, they see this not as an exploration, a winnowing and sifting of facts. They are advocates of a certain position. They see this as an opportunity not to just explore the issues but to advance their particular point of view. [Coe etal are arguing their very biased position. Supporters on the other hand are arguing that a panel of citizens should consider arguments and evidence from both sides.]

This is a thinly veiled attempt to have a propaganda coup. Let’s be realistic. You guys are being manipulated. [By Coe.]

As you’ve heard from many of the speakers tonight, today it is primates, but most of them are abolitionists, they do not endorse the study of any type of animal research. Will we be sitting here next year with a different sort of resolution advocating that we end research on farm animals? On dogs and cats? [This is classic misdirection. Resolution 35 would create a panel to consider the issue. Coe misleadingly or erroneously implies that the question before the committee was whether or not the research is ethical.] Lots of the research at the university is focused not solely on monkeys, but involves cows, horses, and the improvement of the health and well-being of our pet animals as well. [And if you question research on monkeys, what's next, questions about research on cows? Why wouldn't that be a reasonable question?]

I do animal research; I do human research; I do them simultaneously. I study the relationship between nutrition and health. I study iron deficiency, one of the leading nutritional deficits worldwide. It is true that there are one billion people worldwide who are anemic, but there are still questions that need to be understood better through animal studies. [Coe's funding would help more people if it was redirected into iron supplements for the poor.]

Since I do both animal and human research, I can tell you first hand that the regulation and oversight of my animal studies is greater than of my human research. [He really bore down on this.]

There are questions I can learn of the epidemiology research as one of the speakers here tonight suggested, but those are just associations. If I’m interested in mechanisms, pathways, that type of research is better done in an animal model. [Who gives a hoot what he is interested in? If the idea is to help people, then his interests come in a very distant fourth place.]

Yes, sometimes the animals are like us and other times they are different than us. One of my early professors taught [misled] me that we can learn as much sometimes from how animals are different from us as they are the same. In many cases, as in the study iron deficiency, my topic area, the biology of iron is the same in a monkey, and a rat, and a human, and one can learn a lot from it. [Hum... that will require some looking in to.]

I could attempt to wow you with all of the great findings from stem cells, from vaccines, and convince you that there have been major discoveries and advances from that type of work, but that’s not the issue tonight. [And he would have failed.]

The real issue tonight is what will the formation of this committee accomplish, and as several have suggested, I don’t think it will accomplish very much; it will not facilitate the dialog; instead it will put a line in the ground that further separates half of this room from the other half when in fact we need greater communication and dialog and discourse rather than a committee that in a sense codifies the difference between the two camps. [Over the years, Coe has repeatedly been asked to participate in public discussions and debates about the use of animals at the university and has consistently and flatly refused.]

Thank you for your attention.

Dr. Coe makes many misleading and confused statements above, but he is emphatic on a particular point: the regulation and oversight of animal studies is greater than of human research.

Now read this (you have to follow the link):

Regulation and Review of Animal Research
Eric Sandgren, VMD,Ph.D., Director, UW–Madison Animal Care and Use Program

Now consider what Sandgren says when he’s not writing to convince the public that all is well:

Academic Staff Ad Hoc Committee on the Research Enterprise White Paper January 21, 2010

Charge To assess whether the present UW-Madison Research Enterprise structure is capable of addressing current and future issues, or whether an alternative organizational structure such as that proposed by the Chancellor and the Provost is needed.

Members Sandra Austin-Phillips (Biotechnology Center)
Richard Brown (Research Animal Resources Center)
Jenny Dahlberg (Neuroscience Training Program)
Deborah Faupel (Genome Center of Wisconsin)
Sarah Mason (Wisconsin Center for Education Research)
Alice Pulvermacher (Center for Health Enhancement Systems Studies)
Noel Radomski (Chair, Wisconsin Center for the Advancement of Postsecondary Education)

APPENDIX K
UW-Madison Animal Care and Use Program Needs
Eric Sandgren, VMD, PhD
Associate Professor of Pathobiological Sciences
Acting Director, UW-Madison Animal Care and Use Program
The request for support of the UW-Madison Animal Program is outlined in detail in the document submitted by Dr. Bill Mellon. Key aspects of this request and my analysis of risk are summarized below....

..... Risk analysis...

Should we fail to correct deficiencies that have been identified at the campus level, and that also have been identified by USDA, OLAW, and AAALAC, we risk additional USDA fines, an OLAW investigation, loss of AAALAC accreditation, and loss of PHS research funding. The bad publicity that accompanies Program failures is intense and nation-wide. We also have an ethical responsibility to establish and maintain a strong program.

Examples of failures are available from other institutions. The University of Connecticut had 43 USDA citations over 3 years, paid a $129,500 fine, and had to commit $20 million to upgrade its animal Program. They also agreed to pay $25,000 for additional violations. Other institutions cited and fined from $2000 to $11,400 by the USDA include New York University, Columbia University, University of Nevada-Reno, Northwestern University, and UC-Davis. UCSF received a USDA warning in 1999, was fined $2000 in 2000, then legally challenged the USDA’s most recent citation and settled after much legal maneuvering by agreeing to pay a fine of $92,500. Each incident was accompanied by extensive press coverage.

UW-Madison received a USDA warning in 2004, was fined $6,875 for 24 violations of the Animal Welfare Act (AWA) in 2005. This reflected a discount of 75% applied to research institutions, currently allowed by USDA regulations. In September 2005, the Inspector general’s office audited the branch of USDA responsible for enforcement of the AWA. The auditors concluded that the USDA has not been aggressive enough in enforcing actions against violations of the AWA. One recommendation of the IG is to increase fines to $10,000 per violation for research institutions; another is to abolish the 75% discount. If the UW-Madison receives a similar fine in the future, it could total $240,000. The cost in bad publicity will be far higher.

We are under close scrutiny by USDA, OLAW, and AAALAC. We must finish implementing our Animal Program reorganization so that we establish the means to prevent additional violations. We do not want to find ourselves in a position of being forced to do so from the outside.

Clearly, even Sandgren, who usually cites the many agencies as evidence that all is well, knows that all isn’t well. He seems as worried, maybe more worried, by the potential negative publicity than he does about complying with the spirit of the very weak laws and regulations at play.

The claim that the public can be confidant that the animals are being well-cared for because of the regulations is false, apparently knowingly so, as Sandgren's (partial) recitation of problems around the country makes clear.

More undisclosed vested interests

If you haven't done so, be sure to read the lead story in the July 15, 2010 Isthmus: Man over monkey: UW researcher Dr. Paul Kaufman: Scientist believes humans have an ethical obligation to use animals to help their own species. Bill Lueders.

A short response letter appeared in this week's Isthmus:

Amazing advances

I'm glad you wrote about primate research at UW ("Man Over Monkey," 7/16/10), but I wish more emphasis had been given to the amazing medical advances it has generated instead of insinuating that UW just does it for the grant money.

Jess Otis

Whenever I read a letter like this, I wonder about the author. Why didn't Jess Otis mention any of these purported "amazing advances"? So I did a little on line sleuthing.

I can't say definitively of course that the Jess Otis who penned this little letter is the same Jess Otis in the UW-Madison vet school's Comparative Biomedical Sciences Graduate Program, but I'll wager she is. It appears that Jess (Jessica) experiments on thirteen-lined ground squirrels in Dr. Hannah Carey's lab.

Summaries of Recent Projects:

Gene expression and signaling pathways in cholesterol and lipoprotein metabolism in hibernation. Lab member: Jessica P. Otis, B.S.
Mammalian hibernators switch from a carbohydrate-based to a lipid-based metabolism during the long winter fast of hibernation. Plasma cholesterol levels increase about 2-fold during the winter months, but the mechanisms responsible for this change and its functional role in hibernator physiology are poorly understood. This project examines gene expression and signaling pathways related to cholesterol, lipoprotein and bile acid metabolism in ground squirrels during the seasonal cycle of feeding and fasting.

Here's a description of part of one of the the experiments this Jess worked on:

METHODS AND MATERIALS...

Animals. All procedures were approved by the University of Wisconsin School of Veterinary Medicine Institutional Animal Care and Use Committee. Thirteen-lined ground squirrels (Spermophilus tridecemlineatus) of both sexes were trapped in the vicinity of Madison, WI. Other squirrels were obtained as pups born in captivity from pregnant females trapped in spring. Squirrels were housed individually at 22°C with a 12:12 h light-dark cycle with free access to water and food (Purina rodent chow 7001, supplemented with sunflower seeds) except for pups born in captivity, which were food-restricted after weaning (12 g chow/day). Prior experience indicated this level of daily intake prevents excessive weight gain, which is common in ground squirrel pups born in captivity, yet allows them to gain weight at a rate similar to wild-caught animals. Squirrels were held in these conditions for at least 1 mo before use in experiments. Summer-active squirrel (SUM) squirrels were collected from the wild in early summer and, based on body mass, were judged to be at least 1 yr old (and therefore had hibernated in the wild for at least one winter). In August, other squirrels were implanted with temperature-sensitive radio telemeters (VitalView S3000; Minimitter, Bend, OR), and Tb was monitored every 2 min during the hibernation season. In September- October, squirrels were transferred to a room maintained at 4°C. The room was dark except for brief periods ... of low lighting once per day to check activity state. Water and food were removed after squirrels began regular bouts of torpor. SUM animals were killed in late July/early August ... after an overnight fast. Hibernating squirrels were killed in one of four states: entering torpor ...; late torpor, ... 7 d in torpor ...; arousing from torpor ... ; and interbout arousal .... Summer squirrels and hibernators ... were killed by decapitation after isoflurane anesthesia, and LT squirrels were decapitated without prior anesthetic. After laparotomy liver tissue was harvested and immediately frozen in liquid nitrogen. Nelson, C.J., Otis, J.P., Martin, S.L. and H.V. Carey. 2009. Analysis of the hibernation cycle using LC-MS based metabolomics in ground squirrel liver. Physiological Genomics 37:43-51 [Full Article(PDF)]

If this Jess Otis is the Jess Otis who wrote the letter, then she wasn't forthcoming about her vested interest and bias. I doubt that she actually could name many "amazing advances." And certainly she would be hard pressed to find many if any that have stemmed from Kaufman's research or the research taking place at the primate center.

Maybe an easier task for her, given her area of specialty, would be to name a few amazing advances that have resulted from capturing ground squirrels and killing them. I can't wait.

[If these are two different Jess Otises, then I apologize to the Carey lab Jess Otis for suggesting that she was less than honest for not identifying herself as a UW-Madison vivisector, and I say thank you to the honest other Jess Otis (assuming that he/she isn't involved in animal experimentation) for writing the letter that led me to notice the hideousnesses occurring in the Carey lab.]

Vested Interests, Double-Talk, Ethical Blindness

Two Dane County Committees have listened to testimony and deliberated on County Resolution 35. One modified the original version and eliminated consideration of Covance’s annual use of about 7000 monkeys from the proposed citizens’ advisory panel’s purview, requiring the panel to consider only the University of Wisconsin-Madison’s use of monkeys. The second committee took no action at all, leaving the resolution alive but in parliamentary limbo.

At the first meeting, supporters outnumbered those opposed by about five to one. At the second meeting, supporters still outnumbered those opposed, but not as overwhelmingly. In both cases, the opposition was almost uniformly made up of UW animal researchers and staff.

At the first meeting, an HIV-positive man spoke in opposition, but he said that he knew UW primate vivisector David O’Connor, who’s confusion I have discussed previously. Another person who spoke, Peter C. Christianson, identified himself as a Dane County resident, but did not add that he is on the Board of Directors of the Wisconsin Alumni Association or that he is a full time paid lobbyist, or that he is employed by a law firm representing the Wisconsin Alumni Research Foundation (WARF). A friend of mine sitting next to him told me that he was playing solitaire on his phone throughout the meeting. Everyone else who spoke in opposition seemed to have a direct financial interest in animal experimentation.

At the second meeting, everyone who spoke in opposition had a direct financial interest in animal experimentation, and most of them had a direct financial interest in primate experimentation.

In the case of O’Connor, he erroneously claimed that a British study of primate experimentation was particularly important because it was completely unbiased, made up of people who, he erroneously claimed, didn’t have a vested interest in primate experimentation (unlike him and most of his colleagues urging the committee to kill the resolution.)

Also at the second meeting, we heard a new line from the university, laid out first by Martin T. Cadwallader. I think most people in attendance felt that he was saying that the public would now be allowed to tour the primate center. You can listen to him here (he starts talking at about 22:50). This is a transcript of his statement:

I’m Martin Cadwallader, and I’m the vice chancellor for research and the dean of the graduate school at the University of Wisconsin-Madison.

The university is not in favor of Resolution 35 as currently written. However, the university proposes to increase opportunities for citizens of Dane County and beyond to learn about our animal research program, raise issues, and engage in dialog.

To this end, we propose a series of forums that would involve research scientists, ethicists, veterinarians, and others engaged in, or interested in, animal research both on and off campus. The purpose would be to provide periodic opportunities to exchange ideas, become aware of the changing federal landscape in research, and provide an open forum on a broad range of animal research topics.

The issues might include: Who funds research of this kind? Are experiments involving animals necessary? Are there alternatives to using animals for research? Who is looking out for the animals? What happens when animals are no longer needed for research projects? What’s the value of research with animals?

In addition, we are committed to offering tours of our primate center, and we encourage you to take a careful look at our website on animal research which provides a great deal of information about the research underway at UW-Madison. It also provides information about our animal care and use program.

Our aim is to make our animal research program more transparent to interested citizens, and to provide valuable information on the concerns and interests of our community.

Following up on this was Deb Hartley, animal technician training coordinator. (Her comments start at approx. 75:05. Below is an excerpt starting at about 75:40)

.... I give lectures, training sessions, and actually tours. We have at the local level, many people coming in for tours. [I] orchestrate that. People that come across the United States from other facilities will come to learn from us our expertise and techniques, and also learn a couple other things about the monkeys. And also that reaches globally, we do international tours or international people and things like that as well.

I do encourage you participate in the tour. It doesn’t take a resolution or a citizens’ act to get into the facility. It is secure, but it is closed, or not closed, but it is secure because we want to protect our animals as well and our staff. I do encourage you to come on the tour, learn what we do....

(78:27) Like I said, anybody can come in. You have to be 18 and older, get your TB test done, bring your paper work, because we want to keep you safe as well. Come on in, and we’ll show you what we have, we are as transparent as possible [unclear] can be, and we’re proud of that.

So, Dean Cadwallader and Deb Hartley appear to have said that the public would be able to tour the primate center.

Cadwallader: “[W]e are committed to offering tours of our primate center.... our aim is to make our animal research program more transparent to interested citizens.”

Hartley: “[A]nybody can come in.”

After Hartley spoke, she was asked in the hall whether she meant what she had seemed to say about a tour, and she said absolutely. She said to email her and she would set it up. So, she was emailed the next day, July 9, but as of July 22, has not responded.

Follow-up inquiries about possible tours were met with stonewalling. All the people who could make a decision seemed to have quickly gone out of town. In a response to a separate inquiry, she sent this:

From: Deborah Hartley
Date: July 14, 2010 10:22:43 AM CDT
Subject: Re: Lab tour

Good Morning,

Due to several staff members out of the office until next week, we will address your questions upon their return.

Thank you for your patience,
Deb

Multiple follow-up inquiries about possible tours finally led to a clear, if mealy-mouthed, NO!

Either Vice Chancellor for Research and Graduate School Dean Cadwallader was blowing smoke, or else he has much less say in or control over what happens at the primate center than he believed. [Insider gossip factoid: Insiders claim that the primate center is essentially opaque to RARC oversight.] Either Hartley was lying about the opportunity for tours, or else, and more likely, her perception of the university’s secrecy and aversion to public view and consideration is warped and unconnected to reality.

The primate center is right to be alarmed about the possibility of the public getting to see inside or to critically evaluate their work.

A notable example of primate vivisectors mistaking the public's likely reaction to the realities of the lab environment might be Jane Goodall's and Roger Fouts's tour of SEMA:

In 1986, an underground animal rights group called True Friends broke into SEMA, Inc. [now BIOQUAL], an NIH-funded laboratory in Rockville, Maryland. Scientists there did AIDS research. They had close to 500 apes and monkeys in the laboratory. When True Friends broke in – apparently tipped off by an unhappy employee – they brought video cameras with them. In the classic manner of such break-ins, they were interested in publicizing laboratory conditions. For their purposes, SEMA was perfect.

The AIDS-infected animals were boxed up alone. That meant each in a metal cube, with one small window. These “isolettes” were 40 inches high, 31 inches deep, 26 inches wide. Inside the boxes, animals were rocking back and forth in the blind, ceaseless motion of the mentally ill, of children who are emotionally starved. The resulting videotape was released through people for the Ethical Treatment of Animals, among the largest and most aggressive animal advocacy groups in the country. PETA sent the tape to television stations and newspapers. One copy was also sent to Jane Goodall in England.

Goodall’s specialty was chimpanzees. But her long relationship with them made her feel – as Fouts did – responsible. She felt, also, an obligation to speak out on their behalf. She was already in contact with Roger Fouts, and after seeing the tape, she asked him to visit SEMA with her. They were escorted by a top-level NIH administrator. Fouts, who knew caged chimpanzees better than Goodall, was still shocked. “It was a nightmare in there. They had these chimps in metal boxes. One wasn’t even rocking anymore. She was just lying on the floor of her cage. When we walked in, the chimp lifted her head and looked up. It was like those children you see in Somalia, that blank look. They’re not there. And the vet said, ‘See, she’s not screaming,’ and he told the tech to take her out. ‘See, she’s just fine.’ They were holding her like she was a typewriter, and she was just lying there.

Afterward, driving away, Fouts remembers, the government officials began cheerfully remarking that they must be reassured by what they had seen. Clearly, the facility met NIH standards. Fouts and Goodall sat silently in the back of the car. He looked over at her. She was crying, tears dripping off her chin. The experience convinced Fouts that NIH was indifferent to the animals. ... (The Monkey Wars. Deborah Blum. Oxford. 1994. 23-24.)

"Stay the course!"

I wrote recently about the seeming ethically-blind helmsmanship of the University of Wisconsin’s animal research program. The man at the tiller is Eric Sandgren, director of the university’s Animal Research Resource Center and responsible for compliance with federal regulations. Dr. Sandgren has said that ethical positions are arbitrary; one man’s right is another woman’s wrong, so to speak. It’s all so very confusing that one should simply throw up one's hands and get on with the important business of making money and growing the enterprise apparently. (Can you say: ka-$$$-ching!!?)

Lest I seem to be railing at a straw man, I acknowledge that he has argued that adherence to federal regulations is ethical behavior. But this puts him in a difficult corner. (And, if it requires mention: every violation at the university is an indication of Dr. Sandgren's performance as the director of the university's oversight program.)

The recent inspection of the university’s animal care and use by USDA/APHIS found that the university is still violating some of the same regulations they were cited for violating less than a year ago.

-------------------
Read the December 31, 2009Wisconsin State Journal story here. Read the July 17, 2010 Capital Times story here. View the inspection report here. Notice that the last item in the inspection report is labled: "REPEAT DIRECT NCI." REPEAT means that this is an on-going concern that the inspected facility has not corrected even after being cited for the violation. DIRECT NCI:
--------------------

Chump change

Dr. Sandgren’s argument leads to the inevitable conclusion that there are continuing ethical lapses at the university related to its use of animals, even if federal regulations are the part and parcel of ethics at the university. But he characterizes these lapses as “nickel and dime things,” and says he is “sick and tired of them.” He says they are “nickel and dime things” because nothing “major” was found.

I wonder how he defines “major”? Looking back through the local papers’ coverage of the past USDA/APHIS violations at the university that Dr. Sandgren has commented on, I can’t find an instance of him characterizing any problem as major, serious, important, etc.

The Animal Welfare Act has a couple purposes. It was passed into law in 1966 over concern that labs were knowingly buying and experimenting on dogs, likely people’s pets, who were being stolen off the street. (How times change. Rarely does one see dogs wandering neighborhoods as they once commonly did.)

Over time, the Act has been expanded in scope. A main thrust today is the requirement that institutions adhere (at least in writing) to the tenets of an idea called “The 3Rs” of animal research: reduction, refinement, and replacement. Refinement is the use of “techniques and procedures that reduce pain and distress.”

The university has been cited repeatedly for failing to assure that researchers demonstrate clearly that they have considered alternatives to procedures that “may cause more than momentary or slight pain or distress to the animals.” The ethical position encapsulated in this requirement is at the heart of the Animal Welfare Act and the Public Health Service Policy on Humane Care and Use of Laboratory Animals, the two documents Dr. Sandgren says are his ethical compass. Yet he calls the violation of this basic tenet a “nickel and dime thing.”

And speaking of a lack of an ethical or moral compass...

The members of the Dane County Board of Supervisors have been told that their opinions on the issue of experiments on monkeys don’t and won't amount to a hill of beans, but that it would be better if they just closed their eyes to the 9000 monkeys being used in the Primate Experimentation Capital of the World.

And here’s a big shocker: this is the opinion of the local trade group, BioForward, representing, among others, Covance (7000 monkeys) and the Wisconsin Alumni Research Foundation (WARF) – the UW shell organization that parleys scientific discoveries into dollars, mega-dollars.

The letter from BioForward prompted a note from a friend of mine that seems to capture the position of the vivisectors and their supporters pretty well:

I am getting sick and tired of all these misleading letters to Board members. The whole point of the advisory panel is to examine the ETHICS of primate testing. So why not send a letter with ethical reasoning and justification behind it? Nowhere in that letter is there a discussion of ethics or even treatment of animals, just whether it is already allowed and the economic benefits from it.

In my opinion, the litmus test for creating an advisory panel should be if anyone who is defending primate research can give a cogent ethical reason why it should continue then there is no need for the panel. So far, from everything I've read and heard, all the reasons for continuing such research deal with (1) existing laws already in place mandating such testing, (2) economic incentive to continue to do so, and (3) regulations already in place to make sure nobody does anything “bad.” Obviously none of these 3 even remotely comes close to an ethical defense of primate testing. We see how flimsy many of these ethical defenses are, or according to [Paul] Kaufman, because people can make films and listen to music, it's okay to use monkeys in experiments.

The issue is quite simple. But the people we are dealing with are so corrupted by money and blinded by cash that they can no longer disentangle sense from nonsense.

[Note: BioForwards's letter was sent before Covance (7000 monkeys) was unfortunately removed from the resolution. Thus, the false or erroneous claim that the experiments are required by law is no longer at issue because the university does not conduct regulatory preclinical safety and efficacy studies. FDA does require animal testing, which Covance contracts for pharmaceutical and chemical companies, on "new to the world" chemicals and compounds. FDA requires testing on two species; one must be a non-rodent. There is no mandated testing on monkeys.]

Dane County Supervisors: Greetings

It has come to my attention that David O'Connor has written to you and expressed his concern that I have "personally attacked" those with whom I disagree (him), on this blog.

To a degree that is true. Although, in the case of Dr. O'Connor, I have criticized his assetions rather than him personally.

He has made a number of claims recently which I believe are illogical and are often demonstrably erroneous. I hope you will peruse my arguments and the evidence:

Prophylaxis for occupational exposure to HIV. July 2, 2010.

O'Connor on HIV. July 8, 2010.

O'Connor's A-Mazing Claims. July 10, 2010.

See too: PRIMATES USED FOR BIOTERROR RESEARCH

Thanks in advance,

Rick Bogle

P.S. I hope you follow up on the university's invitation to tour selected parts of the primate center. If you do, I hope you will ask to see some specific things:

1. One of Ei Terasawa's microdialysis procedures, and the monkeys she uses.
2. The monkeys used for the longest time in Michele Basso's experiments.
3. Monkeys in SIV studies who are exhibiting the worse symptoms of SAIDS.
4. One of Paul Kaufman's procedures and the monkeys currently being used in his invasive glaucoma research.
5. Monkeys currently being used in Maria Emborg's Parkinson's research.
6. All the singly caged monkeys.

Thanks again.

R

O'Connor's A-Mazing Claims

At the July 8, 2010 meeting of the Dane County Board of Supervisor’s Executive Committee meeting (see: County panel's inaction puts monkey research plan in limbo. Cap Times), attendees were again entertained by the uninformed assertions of Dr. David O’Connor, a primate vivisector who studies Asian monkeys experimentally infected with an endemic disease of African monkeys, all the while claiming that he is studying a different disease (HIV) in an altogether different species (humans.)

This time he brought along a sidekick who was enamored with a certain claim made by O’Connor regarding a report that they both claimed to be slam-dunk proof that nothing positive or even different could possibly result from a county-sanctioned citizens’ committee looking into the ethics of experimenting on monkeys. (Resolution 35. See www.MonkeysInDane.info)

O’Connor went on at length about the absolute non-biased nature of the report. His sidekick (Thomas Friedrich, I believe), made the strange claim that he had never heard of the report, but then accused the resolution’s supporters in the audience of being uninformed. Apparently, this "proof" that primate experimentation is ethical had been unknown to either of them, but they felt everyone else should have known about it.

O’Connor and Friedrich should have done a little homework.

The report they referred to as the “Weatherall Report” is “The use of non-human primates in research: A working group report chaired by Sir David Weatherall FRS FmedSci.

You can read the report at your leisure here.

It is absolutely true that the report endorses experiments on monkeys. But it is far from true that the authors were not biased even if, as O’Connor repeated a couple of times, the authors do not themselves use monkeys.

One of the authors of the report is:

Professor Richard Morris FRS FRSE FMedSci
Professor of Neuroscience, University of Edinburgh
Neuroscience of learning and memory, neurodegenerative disease

I was shocked to discover that Richard Morris is the Morris of the infamous Morris Watermaze. You can visit his university webpage here.

Here’s his reminiscence about his famous invention: Long-term potentiation and memory. Morris RG. Philos Trans R Soc Lond B Biol Sci. 2003.

In my opinion, someone who has made his living and has achieved some fame by damaging rodents’ brains and watching them swim around trying desperately to find a way to avoid drowning, is not a reasonable choice if one hopes to get a non-biased opinion on the ethics of experiments on animals, any animal – monkey, dog, or rat.

The absolute fact that two UW-Madison primate vivisectors either didn’t know what they were talking about, or were too lazy to actually give the matter any real thought or even cursory investigation, or else were simply posturing and perhaps even lying (though I doubt that either one of them took even a moment to look at anything other than the report’s conclusions), is yet more evidence that university representatives should never be believed when they say anything in regard to the use of animals.

But that's not all. O'Connor also claimed that the report was reviewed by another group of also unbiased experts, a sort of jury who looked at the original report, and apparently gave it their blessing.

One of the members of that group (view them here) was Professor Torsten Wiesel. Torsten Wiesel! (OK, like O'Connor, you don't know who he is; but O'Connor claims to be an expert in animal experimentation. And remember, he was absolutely clear that a citizens' panel would have to come to the same conclusions as the so-called Weatherall report.)

Torsten Wiesel shared the 1981 Nobel Prize in Physiology or Medicine with David H. Hubel. Among other things, they blinded kittens in one eye and experimented on their brains.

Here are a few quotes from "Early exploration of the visual cortex." Hubel DH, Wiesel TN. Neuron. 1998.

Monkey Optic Nerve and Cat Geniculate

We had the feeling of being in a rich orchard, with lots of fruit ready to pluck. We recorded from the monkey optic nerve, because no one had yet looked at the behaviour of ganglion cells in a primate.

Monkey Lateral Geniculate

One of the most satisfying studies in the 60s was the work we did in the monkey lateral geniculate body.... Had we had the sense and will-power we would have gone back to 17 and checked there, and it was not till 1968 that we finally discovered hypercomplex cells in area 17 of macaque monkey. This motivated us to revisit cat cortex, where we did indeed find them, though they were less common than in macaques.

Macaque Monkey Striate Cortex

On first recording from monkey striate cortex, some time in the early 60s, what surprised us most were not the differences between monkey and cat, but the similarities. We saw all the receptive field varieties that we had found in the cat (simple, complex, etc.), and only when we looked more closely did any species differences appear. With smaller fields and more precisely defined orientation selectivity, we had the impression of dealing with a Rolls Royce rather than a Volkswagen. We were certainly pleased at this result, since it suggested that our work probably applied also to humans, given that we are far closer to monkeys than monkeys are to cats.

And on and on ....

Ethics at UW-Madison

Deciding whether something is or is not ethical is a personal decision...

-- Eric Sandgren. Director of the University of Wisconsin-Madison Research Animal Resource Center commenting on the proposed formation of a citizens' advisory panel to look at the questions of whether or not the monkeys at the university are treated humanely and whether the use of monkeys is ethical. (County committee pushes for citizen panel to examine monkey research. Capital Times. June 30, 2010.)

Eric Sandgren is entitled to his opinions, but the opinions of public employees in positions of influence should be looked at carefully by the public. This is why Congress interviews people nominated to serve in such roles at the federal level.

In Eric Sandgren's case, his opinions likely have a strong influence on the culture of the animal labs at the university. His publicly-stated position that right and wrong are mere personal opinion seems to give permission to the university vivisectors to do anything they want to the animals.

Sandgren would point out in his defense that the vivisectors are constrained in the things they do by the Animal Welfare Act and the Public Health Service regulations, so no, it isn't true that anything goes.

But someone who announces publicly that ethics is a personal matter probably feels that the law and regulations are arbitrary. Someone with this view might see the law and regulations as a nuisance. This would go a long way in explaining the repeated violations of the law and regulations by vivisectors at the university cited by federal inspectors.

Eric Sandgren's position does not seem to be unusual. His statement seems to be an expression of the institution's long-standing bedrock belief. On the one hand, they profess in public to have a strong concern for the animals and to treat them well -- better than most pet owners they claim. But they keep the animals in small cages that cause them great stress and routinely subject them to treatment that would be illegal if done in someone's home.

The idea that keeping an animal in a small cage, often for years, and infecting them with diseases, performing invasive experiments on them, modifying their diets in ways that harm them, frightening them, etc, is ethical if done in a lab, but would be unethical in done in one's basement, can only be explained by saying that "deciding whether something is or is not ethical is a personal decision...".

But Eric Sandgren et al don't really believe this. They preach a very self-interested version of moral relativism or situational ethics. If one listens to them or reads their arguments, you see that they aren't prepared to admit that the things they do could be immoral. They say they are offended by such a claim. A genuine belief in moral relativity would lead one to shrug off any opinion not in agreement with one's own.

A moral relativist, someone who genuinely believed that "deciding whether something is or is not ethical is a personal decision..." would have to argue that nothing is out of bounds. Torture, rape, molestation, who's to say what's right and wrong?

Putting a person professing to have such a faulty moral compass at the helm of the university's animal research oversight seems perverse. It should come as no surprise when details of great suffering emerge from the labs or to learn that compassion and even rudimentary compliance with the spirit of the few weak regulations governing the use of animals are routinely lacking.

O'Connor on HIV

Dane County Health & Human Needs on Research on Monkeys part 1 from luciano M on Vimeo.

[Breaking news: Breakthrough in HIV-fighting antibodies discovered. See bottom link.]

David O'Connor begins his comments to the Dane County Committee on Health and Human Needs at approximately 24:30 in the above video.

At about 25:19, he says:

However, the case of using nonhuman primates in AIDS research, which I do every day, is entirely different [than dissecting animals in anatomy classes] because its the cutting edge of science in the public interest.(1) Wanting to contribute to this effort is what motivated me to become an AIDS researcher 12 years ago and it continues to motivate me today. Simply put, the search for an AIDS vaccine relies on research with nonhuman primates.(2) Opposition to nonhuman primate research is therefore opposition to AIDS research, full stop.(3)

Don't just take my word for it. Here's what Dr. Anthony Fauci, who has directed the National Institutes of Health, the National Institute for Allergy and Infectious Diseases since 1984, wrote about HIV and nonhuman primates recently. Quote: The bar that a candidate HIV vaccine needs to pass will be raised on knowledge of prior clinical trials, nonhuman primate studies, and fundamental research.

Hum... OK, I won't take O'Connor's word for it.

Fauci didn't actually say this. The quote is from a report in Science with eleven authors, titled: HIV Vaccine Research: The Way Forward (Science 25 July 2008.) The report was published on the heals of yet another failed clinical trial of a vaccine that was developed using monkeys.

The MRKAd5 HIV-1 Gag/Pol/Nef candidate vaccine advanced to a phase 2b test-of-concept trial known as STEP, conducted by Merck & Co., Inc., and the HIV Vaccine Trials Network (HVTN). The vaccine neither prevented infection nor had an impact on early plasma virus levels in those who received the vaccine compared with the placebo recipients. In addition, a completely unexpected observation emerged in the STEP trial. Although a strict statistical analysis could not be performed because the data were analyzed in a post hoc manner, there was a trend toward a greater number of vaccine recipients infected, compared with the placebo recipients.

The report went on to say:

Although the vaccine in the STEP trial failed to show efficacy, the trial unequivocally demonstrated that the current simian-human immunodeficiency virus (SHIV) NHP challenge model is not appropriate for evaluating T cell vaccines; that the SIV NHP challenge model is more predictive ...

... After the disappointing results in the STEP study, the National Institute of Allergy and Infectious Diseases (NIAID) held a scientific summit in March 2008 (21, 22) to solicit input on how best to reinvigorate and advance the field of HIV vaccine discovery research.

...The summit provided no clear consensus on whether a vaccine should demonstrate efficacy in a NHP model of AIDS as a criterion for entering clinical trials (the "gatekeeper" role).

... Given the extraordinary genetic diversity of HIV, the many features of the envelope glycoprotein that shield the virus from antibody-mediated neutralization, and the speed at which viral replication occurs and latency is established, design of a vaccine that blocks HIV infection will require enormous intellectual leaps beyond present day knowledge.

It's far from clear that the primate researchers are capable of such mental feats.

In fairness to O'Connor, the report does champion the continued use of monkeys in the study of HIV. But, as noted a gazillion times by every critic of this model, the experimental disease isn't HIV, and it doesn't cause disease in humans; using the SIV model is probably a dead end and has been demonstrably misleading as was demonstrated in the STEP trial mentioned above.

And the authors seem to have a strong vested bias toward the continued use of monkeys:

Anthony S. Fauci

Margaret I. Johnston

Carl W. Dieffenbach

Dennis R. Burton: uses monkeys

Scott M. Hammer

James A. Hoxie: uses monkeys

Malcolm Martin: uses monkeys

Julie Overbaugh: uses monkeys

David I. Watkins: uses monkeys

Adel Mahmoud

Warner C. Greene


1. Ahem. "The cutting edge of science in the public interest?" If this means something like "the most important question in medicine," then he's just wrong. While HIV/AIDS is the leading cause of death in the developing countries, it doesn't make the top ten in the developed world. This means then, that access to treatment and condoms is very important, and relative to people dying, access to treatment and condoms is clearly more important than finding a vaccine. Finding a vaccine might be impossible but prevention and treatment clearly aren't. If the "cutting edge" means the most important medical question, then very many other questions stand in front of an AIDS vaccine.

2. "AIDS vaccine relies on research with nonhuman primates." Gibberish. Monkeys don't get AIDS as a result of HIV infection. Anthony Fauci came much closer to the target when he said: "Finally, understanding how some HIV infected individuals, the so-called “elite controllers” who are able to keep the virus in check for years to decades may provide a different sort of “proof of concept”. Perhaps the best that we can achieve is the best that nature has already done. Although developing a vaccine capable of preventing infection is the ultimate goal, development of a vaccine that enables the recipient to control infection for years to decades would delay the need to initiate antiretroviral therapy and potentially even reduce secondary transmission to others." [Fauci: Why there is no AIDS vaccine: Scientists need a better grasp of HIV's interaction with the immune system. MSNBC. 2009.] An AIDS vaccine, if possible, will likely come from an understanding of HIV infection in humans.

3. "Opposition to nonhuman primate research is therefore opposition to AIDS research, full stop." You're either with us or you're against us, by gawd! When I read silliness like this, I can't help notice the stark contrast between O'Connor's (and other vivisectors') mental fogginess and the "enormous intellectual leaps" that will be needed in order to develop an HIV vaccine.

In fact: see this: Antibody Kills 91% of HIV Strains. Wall Street Journal. July 8, 2010.

What's Bucky Afraid Of?

A few UW-Madison vivisectors spoke up on Tuesday, June 29, 2010, in opposition to the idea that citizens selected by the Dane County Board of Directors should look into the use of monkeys in Dane County.

An elderly man spoke to the committee and made an important point. He said something like: "Whenever an institution puts on a dog and pony show like we saw tonight urging us not to pay much attention to what they are doing, we can be sure that they think we would be alarmed it we learned the truth."

A dog and pony show.

My response? We ain't seen nothin' yet. In spite of Chancellor Biddy Martin's unprecedented efforts to assure the public and the non-vivisecting UW staff that all is under control and well managed (in spite of the NIH, USDA, and AAALAC saying otherwise), the UW's effort at the June 29 event paled in comparison to the university's efforts to convince the county not to look for a way to save the Vilas monkeys. In that dark affair, the conniving, the calculated lies, and the utter dismissal of ethics remain a low water mark in the university's history of animal experimentation propaganda.

The gentleman who spoke was squarely on target. Imagine public school teachers arguing that parents shouldn't be allowed to learn what goes on in their classrooms or to form an informed opinion about it.

Imagine nurses protesting the idea that a citizens panel should be allowed to look into local patient care practices, especially if there had been a long history of hospitals lying to the the public and deadly screw-ups.

The louder their protest, the more apparent it is that something is amiss.

Prophylaxis for occupational exposure to HIV.

I read an article about two months ago on Channel3000, the web companion to WISC-TV, the CBS affiliate in Madison. I posted a link to the on-line video; I was flabbergasted, agog, bewildered, and amused by the bizarre "proof" held up by so-called HIV researcher David O'Connor that experiments on monkeys have saved humans lives.

I say so-called, because, as far as I know, his research is focused on SIV, the simian immunodeficiency virus, rather than HIV, the human immunodeficiency virus. In spite of this, and like essentially every scientist studying monkeys dying of this experimental infection, he still calls himself an HIV researcher. Check out his website: http://www.pathology.wisc.edu/Faculty/bio.aspx?name=doconnor

Anyway, here's the passage, cut and pasted:

Yet O'Connor argues non-human primate AIDS research has already saved lives. It wasn't that long ago when researchers felt they were on to something because a vaccine they'd tested was working. It wasn't until a wider test of younger and immunocompromised Macaques was done that it was discovered the attenuated vaccine actually transmitted HIV.

“So it was the work that was done in non-human primates that prevented us from making a potentially catastrophic mistake in advancing these sorts of attenuated vaccines, which have been used against a wide variety of other diseases into people,” he said.

Did you get that? Let me put it in terms that might be a little easier to understand.

Experiments on monkeys misled scientists into believing that a vaccine they developed would protect monkeys from SIV. Further testing showed that the vaccine didn't work and actually caused the monkeys to get SAIDS (the monkey version of AIDS).

O'Connor claims that this line of research saved human lives because they discovered (in the nick of time?) that they had been wrong all along and then didn't test the vaccine in humans.

Let me put it in even simpler terms: I invent a bullet proof vest and announce it is absolute protection from bullets. Then I discover that it doesn't work. Then I announce that my research has saved lives because no one wore the faulty vest.

If this pretzel logic is typical of O'Connor's thinking, then he should be fired, because he is unlikely to be thinking clearly about the biology of retrovirus resistance.

O'Connor addressed the Dane County Board's Health and Human Needs Committee about Resolution 35: "Establishing an Advisory Panel to Study the Treatment of Monkeys Used in Experiments in Dane County and the Ethics of Experimenting on Monkeys." Unsurprisingly, he argued that the County should not sanction any critical look at the use of monkeys. (See: County committee pushes for citizen panel to examine monkey research. Capital Times. June 30, 2010.)

During that meeting, one of the committee members asked him if they had found a cure for SIV, the monkey virus. O'Connor beat around the bush, hemmed and hawed, and was then asked again. What he said is akin to his claim above, complete nonsense.

He said that experiments on monkeys had led directly to the use of antivirals as a treatment for accidental exposure to HIV in healthcare workers. He said that experiments with SIV in monkeys had shown that treatment with antivirals could stop the establishment of an infection if the medications were received within two or three hours of exposure.

My ears perked up when he said this, because the monkey vivisectors are embarrassed by the paucity of easily demonstrable benefits resulting from their use of monkeys, and whenever they make an overt claim, it gives one something concrete to investigate.

In this case, it took me about a minute to find what appears to be an authoritative refutation of his claim.

I looked at this paper because it is available in its entirety for free. I found it on PubMed. It's from 1996: "Prophylaxis for occupational exposure to HIV." Consider these passages:

Health care providers who are parenterally exposed to human immunodeficiency virus (HIV) are at risk for infection. The average risk attributed to needle punctures and similar percutaneous injuries involving HIV is approximately 0.32% (95% CI, 0.18% to 0.46%), or 21 infections after 6498 exposures. This risk estimate, which is based on data taken from 25 prospective studies of occupational exposure, does not account for factors that may change the probability of transmission during a specific exposure. The virus inoculum (the volume of material involved in an exposure and the titer of infectious virus in that material) is one important determinant of risk. New data suggest that antiretroviral treatment after exposure may also be an important factor affecting the outcome of occupational exposure to HIV.

In a case–control study, the Centers for Disease Control and Prevention (CDC) found that five factors were independently associated with the risk for HIV infection after percutaneous injury...

Use of zidovudine soon after exposure, the final factor that predicted infection in the CDC study, was associated with a 79% reduction in the odds of HIV transmission (odds ratio, 0.21 [CI, 0.10 to 0.60]). This observation is the first epidemiologic evidence for a benefit from antiretroviral treatment among health care providers exposed to HIV, and it has stimulated renewed interest in prophylaxis after exposure.

The efficacy of antiretroviral prophylaxis is biologically plausible. Local host defenses appear to be critical in deciding the outcome of transcutaneous exposure...The process of initial virus uptake, antigen processing, and presentation to immune effector cells is not instantaneous and may take several hours or even days. Thus, a window of opportunity for intervention before local virus propagation or dissemination almost certainly exists. Early antiviral treatment may favor the host by minimizing the effective viral inoculum...

The results of experiments done in animal models to evaluate the efficacy of antiretroviral treatment after exposure are inconclusive. Zidovudine treatment after exposure can prevent retroviral infection in mice and cats, but data from these models are difficult to generalize to humans. Most studies of prophylaxis with licensed antiretroviral drugs in primates have not shown efficacy, although treatment with zidovudine before exposure was effective in one study of infant macaques that were inoculated with a low titer of simian immunodeficiency virus. The titer of virus used in most experiments involving primates is substantially higher than the amount that would be encountered in occupational exposure. In addition, the animals used in these experiments are usually inoculated intravenously, a method that would bypass potentially important cutaneous host defenses. Hence, absence of efficacy of prophylaxis in a primate model cannot be generalized to predict the outcome of percutaneous occupational exposure. Adverse consequences of treatment on the natural history of infection and delays in seroconversion have not been seen in animal experiments.

So what was O'Connor talking about when he said that experiments on monkeys are responsible for the use of antivirals to treat accidental exposure to HIV? Not reality, apparently.