Those experienced in self-citation will often sink to even murkier depths. For instance, self-citation is an excellent way of introducing something that seems implausible into your argument. Two common ways to disguise implausibility is the liberal use of such phrases as “paper forthcoming”, “manuscript submitted for publication”, “internal report” or “personal communication"

Such phrases as these have been heard to trip gaily off Bailey’s lips, entering my shell-like ear at a debate at the House of Commons last year.  Jarrod referred to a ‘forthcoming paper’ - authored by him, along with published papers also authored by him!  Unfortunately for Jarrod, the journal’s editor has since distanced himself from those published papers, stating in an email that they were reviewed by;

"an antivivisectionist, Claude Reiss, in the editorial board who did some of the editing,” Parvez said in the Email.  “After his 2 years stay in the editorial board, he did lots of harm to the journal and we all forced him to resign.”
... When contacted by The Scientist, Parvez said via Email that the journal wanted to provide a reasonable opening for discussion of alternative testing methods, but also to encourage science and not polemic. “The insertion of Claude Reiss in our journal remains a very painful event.”
The Scientist, Stephen Pincock, ‘Scientists call for retractions’, 2nd March 2006

Ouch.

In my view, animal studies play an essential role in the discovery and development of new medicines.  Without them new treatments for human disease would not be found; and the safety of patients would be very seriously compromised.  The notion that animal studies are “futile” is utterly wrong.

As a clinical investigator, there is no way I would be prepared to investigate new active substances in either volunteers or patients without essential information from studies in animals.

Now, a debate under the Chatham House rule means that although a transcript may be made of the debate, none of the comments are attributed to a speaker.  The idea is to use confidentiality to encourage a free exchange of ideas and views.  You might wonder then, how SPEAK (along with other antiviv/ animal rights groups) managed to attribute any comments to Sir Michael at all.  The path of the comment’s evolution has been traced by journalist Kieren McCarthy in his blog. 

When contacted by a journalist, SPEAK said that they had obtained the quote from a Daily Telegraph article.  Now, it’s not good research practice to base your conclusions on something as flimsy as a single newspaper article reporting on a debate – again SPEAK’s lack of scientific rationale is exposed – but if you must, then you really shouldn’t mess around with it and remove the context just so that it says what you want it to!

Here’s how the Telegraph actually quoted Sir Michael as he spoke on the spiralling costs of drug development:

Patients must be more involved in regulatory decisions, he said. “The population is going to have to realise there is a trade-off between absolute safety and the development of new drugs.”

The animal study regime, which could take up to six years, was “utterly futile”. The industry must do more research on how to conduct efficient clinical trials.
Daily Telegraph, 17th Sept 2006, Cost timebomb ‘may kill supply of new drugs’

Note SPEAK haven’t even managed to accurately lift the few chosen words: “the animal study regime” – a study being an individual project in a particular area of research – became “the animal testing regime” – just a teensy bit more of a sweeping generalisation!

SPEAK are claiming this is a conspiracy – why didn’t NICE complain about the Telegraph?!?!  I’ll spell out the two reasons for you Mel et al:
1.  The Telegraph left it in context – OK the reporting was maybe a bit confused, but not actionable.
2.  NICE has lots of important things to worry about, seeing that nasty drugs aren’t readily available etc… the Telegraph wrote about this once.  SPEAK have been using, and widely distributing, this for over two years – long enough for it to come to NICE’s attention.

SPEAK aren’t alone in their lack of research; other groups have jumped on the ‘futile’ bandwagon, most notably EMP in one of their newsletters (highlighting their complete lack of scientific credentials once again in glorious techicolour)… they at least retained the word ‘study’, but still failed to take into account the context of the comment:

"The animal testing regime is clearly not an effective safety net - indeed Professor Sir Michael Rawlins, chairman of the National Institute for Clinical Excellence, has publicly stated that the animal study regime is “utterly futile”.
EMP (formerly EFMA) Summer 2004 Newsletter

As these groups can’t be bothered to do serious sourcing and research, they should stop bitching that people don’t take them seriously.

No-one claims that animal experiments are perfect, and indeed it is well-known that at every stage of drug development – computer modelling, modern robotics, test tube studies, animal research, clinical trials – a large proportion of candidate drugs are discarded.  That’s why developing new treatments is such a long and difficult process and only two or three out of 10,000 potential treatments make it as far as clinical trials (see the ABPI’s web pages for more explanation of the process).

So it’s remarkable that in this study of six experimental treatments, chosen at random, as many as half of them worked well in both animals and humans. Two other treatments gave negative results in humans but positive results in animals. In the sixth example, the animal experiments gave insufficient data to draw conclusions.

In fact, the authors were critical of the design of the experiments they looked at, rather than the validity of animal research in general. They stressed that their aim was to find ways of improving experimental methodology, such as
• Prospective registration of animal experiments that might prevent publication bias.
• Research to identify the design features of animal experiments that introduce bias and that could improve validity.
• Reporting standards for animal experiments that might improve the quality of published reports.
• Promoting reviews of both animal and human studies that would encourage researchers to develop a shared language and better communication.

It was perhaps inevitable that antivivisectionists would draw their own, invalid conclusions. Rather than taking the trouble to analyse the results of the review, Animal Aid used it as a pretext to rehearse its usual unsubstantiated claims :

“animal experiments aren’t just cruel, they don’t appear to work”

and

“across a range of important human ailments, animal research provides misleading and conflicting information and is therefore dangerously unreliable”.

The observation by Animal Aid that “clinical trials with human patients get underway even before the animal research is completed” is plain silly as a critique of animal testing.

One wonders, though, whether the study authors were trying compare apples with oranges. Is it reasonable to expect that many scientists at many centres studying similar treatments in animals would adopt closely matched methodologies and protocols? Applied research can be used to answer many different questions, not just “does this drug work?” As a result, animal studies are not always conducted using the same standardised procedures as clinical trials. Should they be? Can they be? This is an area for more deliberation, and relates to work currently being carried out by the National Centre for the 3Rs. 

*Research Monograph from the NHS National Coordinating Centre for Research Methodology, RM04/JH18/IR: Testing treatments on animals: Relevance to humans, Pablo Perel, Ian Roberts, Emily Sena, Philipa Wheble, Peter Sandercock, Malcolm Macleod, Luciano E Mignini, Pradeep Jayaram and Khalid S Khan (2006).

Morphine:
cats and mice given (low) doses comparable with those given to humans are sedated ie ‘calmed’… conversely, humans who overdose on morphine become ‘excited’.

To make it even worse, NAVS was censured by the ASA way back in 1993 on the morphine claim (See RDS’ dossier on scientific validity complaints (p.20, complaint 3) showing ASA rulings against antiviv/ AR groups).

Penicillin:
in guinea pigs actually works very similarly to the way it does in humans. Again, the toxic effect is dose related and is apparent at high doses or in long-term treatment:

[Its] effect in the guinea-pig is due to an indirect effect. This is the conclusion of a study which showed that bacteria normally present in the guinea-pig intestine are sensitive to penicillin. Thus, after penicillin, all these bacteria disappear and are replaced by far greater numbers of other types of bacteria. Thus infection leads to absorption of toxins and death from blood poisoning. Thus it appears that the guinea pig, far from being strikingly different from humans, is in fact similar to the many patients who develop inflammation of the colon (colitis) when they take penicillin.
RDS website, The truth about penicillin

See these original sources of information if the RDS’ word isn’t good enough for you (Jarrod Bailey take note, sourcing info to someone other than yourself is a good move):
Med Microbiol Immunol (Berl). 1981;169(3):187-96 - giving penicillin to guinea pigs selectively kills bacteria in their gut, allowing Clostridium difficile to overgrow and produce a toxin that can kill.
Health Protection Agency - giving penicillin to people selectively kills bacteria in their gut, allowing Clostridium difficile to overgrow and produce a toxin that can kill (note the sense of déjà vu).
Clin Microbiol Infect. 2006 Feb;12(2):184-6 *bonus info on alternatives* - advanced alternative techniques mean guinea pigs don’t need to be used to test for C. difficile

If NAVS can’t be bothered to update these lies (pointed out to them – 13 years ago and counting – by independent bodies so no rigorous research required), it’s no surprise that the rest of their information is badly researched and scientifically inaccurate.

What good does it do you to test something in a monkey? You find five or six years from now that it works in the monkeys, and then you test it in humans and realise that humans behave totally differently from monkeys, so you’ve wasted five years.
- Dr Mark Feinberg, leading AIDS researcher

…the testing of vaccines and drugs in more animals will not be helpful if in the end these animals do not closely resemble humans. Even a vaccine that has 100% efficacy in [non-human primates]… might still be ineffective in humans. Conversely, a proficient vaccine developed in humans might never show benefit in the animal models.
- Nath BM et al at the University of Pennsylvania

That antiviv tactic that we know so well has struck again… both of these scientist’s words have been taken completely out of context.

Dr Mark Feinberg is indeed a “leading AIDS researcher” but far from being an opponent of the use of monkeys, he uses them in his own research.  Dr Feinberg’s personal website describes his research interests as:

investigations of the comparative outcomes of simian immunodeficiency virus (SIV) infection in non-human primate species that represent the natural hosts (such as sooty mangabey monkeys), and non-natural hosts (such as rhesus macaques and humans) for SIV infection.

And the purpose of this research is “to develop a safe, effective and affordable vaccine to prevent HIV infection” – something that the majority of people feel is a worthy cause.

Pro-Test recently contacted Dr Feinberg about this quote: he said that his words had been “taken completely out of context” and did not represent his views. He also stated that,

Important research efforts that will save millions of human lives depend on insights that can only be gained from studies involving non-human primates, and there is no alternative model in a number of important instances for the testing of the safety and effectiveness of new drugs and vaccines.

Time for one of my favourite Scottish colloquialisms: ‘get that up yer’, BUAV!

How about that second quote attributed to Nath BM et al?  It comes from an article titled The chimpanzee and other non-human-primate models in HIV-1 vaccine research, from the journal Trends in Microbiology Vol 8, Issue 9, pages 426-431, and is a review on the usefulness of chimpanzees and other primates into HIV research.  BUAV took their (mis)quote from the conclusion of the article:

This is the conclusion in full – the words quoted by BUAV are in bold; other sentences I feel are pertinent have been underlined:

In conclusion, primates have provided a great deal of information that has significantly advanced vaccine design. Chimpanzees have provided some benefits for researchers studying both HIV pathogenesis and some of the earlier proposed vaccine modalities. However, the minor advantages the chimpanzee model can provide to HIV research have resulted in scientists predominantly utilizing the rhesus primate models. Of even greater importance, the testing of vaccines and drugs in more animals will not be helpful if in the end these animals do not closely resemble humans. Even a vaccine that has 100% efficacy in all three challenge models discussed here might still be ineffective in humans. Conversely, a proficient vaccine developed in humans might never show benefit in the animal models. Earlier experiences in vaccine development have stressed the need for great caution when beginning human clinical trials. Immunization with a formalin-inactivated vaccine for respiratory syncytium virus infection induced immune responses in primates but exacerbated disease in children. Indeed, a great deal of study is still necessary before we can elucidate just how accurately either the chimpanzee or the rhesus macaque models will compare with humans and HIV-1 infection.
(p. 430) (1)

Hmm.  It seem obvious that BUAV lifted three sentences in isolation from the rest of the paragraph so as to falsely give the impression that the review concludes that primates are not useful to HIV/AIDS research… Even though the opening part of the para states exactly the opposite. (2)

Just to put the icing on the cake, here’s a few more quotes from the exact same article:

The use of animal models has been invaluable for studying the pathogenesis of numerous infectious diseases as well as for testing the efficacy of experimental prophylactic and therapeutic vaccine and/or drug regimens… (p. 426)

Although these animal models cannot flawlessly mimic human infection and disease pathogenesis, they are nonetheless important for research; for example, dogs are acceptable models for testing treatments for human hemophilia… (p. 426)

Non-human primates are excellent models for human disease because they exhibit remarkable similarities to humans in virtually every aspect of their anatomy, physiology and endocrinology… (p. 426)

These results, in conjunction with their close genetic relationship to humans, indicate that the chimpanzee is an important model for HIV research… (p. 427)

The SIV infection (Fig. 1b) of rhesus macaques has also demonstrated its usefulness as a model for HIV-1 owing to the similarities to HIV-1-mediated human disease… (p. 428)

With over 40 million people infected with HIV across the world and 8,000 people dying of AIDS every day, it is disgusting that BUAV would resort to such dishonest – and socially irresponsible – tactics in order to mislead the public about the nature of research into this devastating disease.

I hope that in future Alexei Sayle, Helen Chamberlain, Heather Small and Jenny Seagrove will check the accuracy of BUAV’s claims before agreeing to act as spokespersons.

-----------------------------------------------------------------------
(1) For an explanation of why the “formalin-inactivated vaccine for respiratory syncytium virus infection ... exacerbated disease in children” please see the RDS website, antibody therapy for bronchiolitis
(2) Sensibly, the authors have included a few words of caution about aspects of the research process, after all, uncritical reliance on any sort of research is foolhardy.

All of a sudden, microdosing seems to be the answer to every problem. If you were to listen to the antivivisectionists, microdosing can not only replace animal tests in toxicology, it will also pick up side-effects such as the alleged increase in heart attacks in patients taking Vioxx. Never mind that the antivivisectionists had nothing to do with the development of microdosing. According to their view, it’s the ultimate solution, but is resisted by old-fashioned vested interests wedded to animal testing.

It’s all very well the antivivisectionists trotting out this jargon. But what we are lacking from them is a single decent explanation of how microdosing is supposed to detect toxic effects of potential new medicines. It certainly wasn’t designed for that purpose. Microdosing uses a technology called accelerator mass spectrometry (AMS), which allows the accurate analysis of micro-doses of experimental drugs. It is typically carried out at doses one hundredth of what would be a therapeutic dose. This is intended to be so low that it does not cause toxicity, as explained in a simple and comprehensive briefing from the National Centre for the 3rs. Furthermore, it is widely recognised that animal studies are required before microdosing to ensure that the new drug is not severely toxic at very low doses. Imagine the disaster if we tried to microdose humans on a compound like ricin, which is toxic even at exceptionally low doses. This is exactly what animal tests are designed to avoid, although like any method of testing, they cannot guarantee safety.

Unfortunately for the antivivisectionists, microdosing simply doesn’t live up to their claims. If it were possible to devise a test that was guaranteed not to pick up side-effects of medicines like Vioxx, then microdosing would be a good attempt. Vioxx was subject to extensive clinical trials in human volunteers over long periods of time, at high doses and with large numbers of people. Instead, the antivivisectionists are proposing that microdosing carried out over short periods of time, at very low doses, with very small numbers of people, would do better.

The antivivisectionists point to a study carried out by the biotech company Xceleron which claims as a result of preliminary studies that microdosing is or can be predictive of drug behaviour. But that merely confirms that microdosing might work well at what it is supposed to do, namely trace the movement of drugs around the body. This does not mean that that it can pick up toxic effects, a point the antivivisectionists seem to have missed entirely.

Even respected journalists can fall into the trap of misunderstanding microdosing. Science writer Robert Matthews, whose work is much quoted on the website of Europeans for Medical Progress, recently wrote in the on-line journal The First Post: “the hope is that microdosing will weed out toxic drugs faster and more reliably than animal experiments.” To his credit, after further investigation Robert accepted that “the sentence should have avoided the word toxic”.

There is little doubt that microdosing is a technique with enormous potential for picking medicines which behave in a way we might want them to. The technique has not yet been fully validated, however, and doubts remain as to whether drugs in low doses behave in same way as drugs given at therapeutic doses within the body. There is good potential for replacing the use of some, but not all, animal tests in early-stage drug development.

But the idea that microdosing can replace whole scale animal toxicity testing is pie-in-the-sky. Not that the scientific facts have ever stopped the antivivisectionists from making their ill-informed claims. This is what Jan Creamer, Director of the National Anti Vivisection Society, said in a recent interview on the Today programme:

“everyone remembers recently the TGN1412 drug disaster which we had. Now those human volunteers were given the drug 500 times less than the animals. The monkeys had received a 500 times stronger dose and to no ill-effect - there were no adverse side-effects. It was then given to the human volunteers… And this is at a time when we already have available a system, microdosing, that would have avoided that… you go straight to using humans, but in ultra-low safe doses where you don’t get those sorts of horrific side-effects

Let’s go over that again - just to be clear. Jan Creamer is not happy about the results of giving a test drug to humans at very low doses. So instead, she wants to give test drugs to humans at very low doses. If ever there was muddled thinking on microdosing, this is it.

For example, Kathy’s organisation repeatedly claim that the arthritis drug Vioxx which was withdrawn in 2004, appeared safe and even beneficial in animal tests. Here she even contradicts the Physicians Committee for Responsible Medicine (PCRM), which is the sister organisation to EMP in the US - and another animal rights organisation in disguise. In a supposedly ‘scientific’ critique of animal testing for Vioxx, this organisation claims that “animal data have not been consistent… the possibility of a neutral, harmful, or even beneficial effect have all been raised...”.

So Europeans for Medical Progress are trying to argue that drugs like Vioxx are passed safe in animals, whilst simultaneously their partner organisation PCRM is trying to argue that animal tests give inconsistent results. These organisations will make pretty much any claim that they think they can get away with, so long as it serves their purpose of undermining animal research.

The true purpose of animal testing is persistently and deliberately misrepresented by these animal rights groups. For any new medicine such as Vioxx, the role of pre-clinical tests, including animal tests, are to answer the straightforward question: is this potential drug safe enough to go into initial human clinical trials with a reasonable chance that it will not prove to be severely toxic. In the case of Vioxx, the answer was a resounding yes. Vioxx was extensively studied in humans in randomized placebo- and active-controlled clinical trials both before and after it was approved by over 70 regulatory agencies around the world.  For example, before submitting VIOXX to the FDA for review in 1998, 58 studies were conducted in almost 10,000 patients.  More than 5,000 patients took VIOXX in these studies, many for more than a year. Severe toxicity was not reported - a good success for animal and other pre-clinical tests in protecting those early volunteers.

Kathy Archibald’s last gasp at credibility is to refer to a single decision by the Advertising Standards Authority to rule against a phrase used to describe the benefits of animal research by the Association of Medical Research Charities. Despite vehemently denouncing the ASA when they made five rulings against EMP, as well as appealing against the verdict, all of a sudden Kathy makes a bid to skew ASA rulings to her advantage. But crucially, she omits to link to the ASA ruling. We wonder why! Its findings provide no support whatsoever for the animal rights approach. Even on the one ruling which was upheld, the ASA suggested that the claim should be amended to read “some of the major advances in the last century relied on animal research ...” This is not something that Kathy Archibald would subscribe to at all! In the other two parallel adjudications, (which went against EMP), the ASA agreed that there was no alternative to use of animals at some stages of research, and supported a list of medical advances made possible with animal research, which included kidney transplants, heart bypass, polio vaccine and several others.

Like any other method of research, animal testing can never provide a guarantee that new medicines will be safe. But without animal tests, we would have to go from in vitro and computer tests straight into humans, without the ability to pick up drugs that are severely toxic to living animals. That would be a nightmare scenario. 

Indeed, the scientific magazine Science said a couple of weeks ago:

"Research is needed to define better animal models of the human response to CD28 agonists” and extra precautions need to be taken “when antibodies are used to stimulate rather than neutralize components of the immune system.”

Science, 24 March 2006

However, in a letter to The Independent today, Dr Gill Langley, Director of the Dr Hadwen Trust, a charity that funds alternatives research, said “The health of volunteers must be safeguarded, but so must the crucial role of volunteer trials”. So far so good. But she then repeated the tired old animal rights mantra suggesting the animal tests were at fault:

”... seven organisations supporting non-animal research techniques, have proposed more test-tube research and safer volunteer studies, using drug microdoses too low to cause side effects. In January, the US Food and Drug Administration said the same. This approach could improve human safety and relieve animal suffering.”

Gill Langley, Dr Hadwen Trust

Well, she would say that, wouldn’t she? Of course human tissue studies and animal studies and a whole lot more preceded the clinical trials. But Dr Langley can’t resist placing blame on the animal studies. What dose does she think was given to the human volunteers? One 500th that given to monkeys, ie a microdose. We need more human tissue studies AND animal studies, and less recourse to unthinking animal rights dogma.