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FRAME News 

Fund for the Replacement of Animals in Medical Experiments Editor: Susan Trigwell No. 62 October 2007 

OFFICIAL OPENING OF THE 

NEW FRAME ALTERNATIVES 

LABORATORY 

The FRAME Office has been located in Nottingham since Novem ber 

1981, and the FRAME Research Programme, established in October 

1982, has involved an uninterrupted partnership with the University 

of Nottingham Medical School. On 6 July 2007, about 50 invited 

guests met in the School of Biomedical Sciences at the University of 

Nottingham Medical School for the opening of the extended and fully 

refurbished FRAME Alternatives Laboratory (FAL). 

Dr Andrew Bennett, Director of the 

FAL following the retirement of Dr 

Richard Clothier, welcomed those 

present, from the Medical School, clinical 

departments at the QMC, FRAME, 

the NC3Rs and Alliance Boots, and, 

especially, members of the Girling family, 

Dr Nick Palmer MP and the Rt Hon. Ed 

Balls MP. He said that this was a particu- 

larly significant occasion, since it marked 

not only the reopening of the FAL, but 

also a further expansion of the collaboration 

between FRAME and the 

University. 

Professor Don Grierson, Pro-Vice- 

Chancellor, extended his welcome on 

behalf of the Vice-Chancellor and the 

Ed Balls MP unveiling a plaque dedicated to Julia Girling, during the opening of the 

new FAL 

FRAME News http://www.frame.org.uk 

INSIDE... 

Official opening of the FAL 

Minister at Nottingham 

University 

The last moral frontier 

Sixth World Congress 

on Alternatives and 

Animal Use in the Life 

Sciences 

FRAME Reduction 

Committee presentation 

Phasing out primate 

experimentation discussion 

Dorothy Hegarty Award 

winners 2006 

AstraZeneca R & D 

Generic 

biopharmaceuticals and 

the rising demand for 

animal tests 

New Minister at Home 

Office 

Meg Hillier 

Animal experiments 

reach a 15-year high 

Home Office statistics 

New FRAME Website 

goes live 

FRAME “Putting 

Replacement First” 

initiative 

Reception at House of Lords 

FULL CONTENTS ON 

BACK COVER

University. He congratulated Ed Balls on 

his recent appointment as Secretary of 

State for Schools, Children and Families, 

adding that he himself had been one of 

Ed’s Father’s first class of honours 

students, at the University of East Anglia 

(UEA) in 1966. He said that the FAL 

had earned an international reputation 

for its contributions to the application 

of the Three Rs concept, and that, on 

Richard Clothier’s retirement, the 

University and FRAME had no hesitation 

in deciding that the FAL should continue 

its work under a new Director. He added 

that the focus of the FAL on human 

tissue culture systems and the applications 

of modern molecular and cell 

biology, in collaboration with scientists 

and clinicians in the Medical School and 

the QMC, was entirely consistent with 

the University’s ethos of doing firstclass 

research whilst being mindful of its 

ethical context. He concluded by saying 

that the University thanked FRAME for 

its financial support over the last 25 

years and looks forward to continuing 

the fruitful collaboration. 

Professor Michael Balls, Chairman of 

the FRAME Trustees, reviewed the 

history of the FAL and the collaboration. 

He said that, in the early 1970s, his 

research group at UEA worked on 

comparative physiology, pharmacology 

and toxicology, by using organotypic 

cultures of all kinds of amphibian 

tissues, since they had found that they 

would survive and function in vitro for 

weeks, whereas mammalian tissues could 

only survive for a few hours. Then, 

whilst on holiday in the summer of 

1974, he had seen an advertisement for 

a senior lectureship in the Department of 

Human Morphology in the new Medical 

School at the University of Nottingham. 

On discovering that its Head of Depart - 

ment, Rex Coupland, was also interested 

in organ culture, he had decided to 

apply for the job, and, as a result, he 

and Richard Clothier, then a postdoctoral 

fellow on a Cancer Research 

Campaign grant, moved to Nottingham 

in January 1975. 

In April that year, they organised a 

British Society for Cell Biology symposium 

on organ culture, at UEA, which 

led to a Festschrift for Dame Honor Fell, 

the doyenne of organ culture. Shortly 

afterwards, they were visited by Pro fes - 

sor David Smyth FRS, the retired Head 

of the Department of Physiology at 

Sheffield University, who had heard of 

the symposium, and who was conducting 

a survey on alternatives to animal experiments 

for the Research Defence Society, 

of which he was then Chairman. Profes - 

sor Smyth asked if they knew that they 

were working on alternatives, and 

suggested that they should apply to 

animal welfare societies for research 

support. This led to a very good relationship 

with the Humane Research 

Trust, and the receipt of some invaluable 

support for their research. 

As a result of this, Michael was invited 

to speak at a conference on The Use of 

Alternatives in Drug Research, organised 

by FRAME and held at the Royal Society 

in 1978. This led to an invitation to 

become a FRAME Trustee, in 1979. At 

that time, FRAME was based in a former 

draper’s shop in Wimbledon, where its 

founder-Chairman, Dorothy Hegarty 

lived. In March 1981, having been 

elected to succeed her as Chairman, he 

persuaded his fellow Trustees to move 

FRAME’s headquarters to Nottingham, 

principally so that a research collaboration 

could be established with the 

University’s Medical School. 

This turned out to be a master stroke. 

Initially located at 5B The Poultry, 

FRAME subsequently moved to the 

Eastgate House in the Lace Market, and 

then to a new building near what was 

then Trent Polytechnic, which FRAME 

was able to buy as a result of a success - 

ful £1 million 20th Anniversary Appeal. 

When FRAME moved to Nottingham, 

the Charity’s income for 1981–1982 

FRAME News http://www.frame.org.uk 2

Dr Andrew Bennett, the new Director of 

the FAL 

was £55,000 — in 2006–2007, it was 

almost £775,000. 

The first stage of the multi-centre research 

project, which included the University, 

had been fully funded within a few weeks 

of its launch in 1982. In 1983, FRAME 

received the first Gov ern ment grant dedicated 

to alternatives research, and played 

a crucial role, with the British Veterinary 

Association and the Committee for the 

Reform of Animal Experimentation, in 

advising the Govern ment on what was to 

become the Animals (Scientific Proced - 

ures) Act 1986. 

Up to now, the FRAME-supported 

research in the FAL has focused principally 

on in vitro toxicology — that is, on 

ways of using cell and tissue culture 

systems to investigate the mechanistic 

basis of the adverse effects of chemicals 

and chemical products, and on ways of 

identifying hazardous chemicals, without 

the traditional reliance on the use of 

laboratory animal models. During the 25 

years from 1982, FRAME has been able 

to donate almost £4,400,000 to the 

University for alternatives research, 

thanks to the support FRAME itself has 

received from the general public, 

industry, government, other charities 

and the European Commission. 

Part of FRAME’s work here has been 

conducted under the supervision of Jeff 

Fry, whose quiet patience and academic 

excellence has served the collaboration 

very well. Then there has been the 

FRAME Alternatives Laboratory. Michael 

Balls described its development in the 

following words. 

When we came to Nottingham, no provision 

had been made for laboratories for 

our research group, but we were permit - 

ted to use a corner of Professor 

Coupl and’s tissue culture suite, part of 

the laboratory used by honours 

students, and some rooms in the animal 

unit, where we once had 10,000 

Xenopus toads. We progressively took 

over the whole tissue culture suite, then 

had it remodelled in 1992, with 

FRAME’s support, and it became the 

FRAME Alternatives Laboratory. That 

remodelling was very significant at the 

time, but was not on the scale of the 

dramatic redevelopment and extension 

we see before us today. 

Ed Balls MP and Professor Michael Balls at the opening of the FAL 

Professor Don Grierson, Pro-Vice- 

Chancellor, extends his welcome on 

behalf of the University of Nottingham 

While I spent a lot of time at the FRAME 

Office from 1982 onwards, Richard ran 

the FAL. We specialised in the development 

of replacement alternative test 

methods, and, in particular, in their 

validation, i.e. on the independent 

assessment of the reliability and relevance 

for particular purposes. In fact, the 

FRAME International Alternatives Vali - 

dation Scheme, established in 1983 with 

support from the Home Office, was the 

first such scheme in toxicology, outside 

genotoxicology. For this, the FAL has 

earned an excellent international reputation, 

and in 1993, I was invited to set up 

a European Centre for the Validation of 

Alternative Methods (ECVAM), at the 

European Commission’s Joint Research 

Centre, at Ispra in Italy. Richard took over 

sole responsibility for the FAL. 

In its early days, under Mrs Hegarty’s 

leadership, FRAME gradually built up 

support from the general public, but that 

kind of support was progressively lost as 

the Charity’s scientific base was streng - 

thened, and the new Trustees replaced 

leaflets headed What Price Vanity? 

(about cosmetics testing) and How Safe 

are Your Medicines? (about the testing 

of pharmaceuticals and vaccines) with 

more complex messages which did not 

lend themselves to catchy slogans. 

Researching Alternatives to Animal 

Testing was about as far as we felt we 

could go. Some of our supporters 

appreciated our commitment to the 

progressive replacement rather than to 

outright opposition to all forms of 

animal experimentation. One of them 

was Julia Girling, who raised money for 

FRAME in all kinds of ways, from 1984 


Gerard Duvé admires the FRAME tie, presented to Brough Girling at the reception 

until 2005. Our most loyal supporter, 

Julia also represented the other 

supporters at a number of social and 

fundraising events. Sadly, she died in 

2006, and we were deeply moved and 

encouraged when we learned that she had 

given FRAME a legacy of £100,000. At 

about the same time, the University said 

that it would like to refurbish and extend 

the FAL at a cost of about £240,000, 

and wondered if FRAME could make a 

contribution. The Trustees decided that 

this would be a most fitting way of recognising 

Julia’s support, and we are very 

pleased that her husband, Brough, and 

her daughter, Sarah, approved of the 

idea, and also that they are able to be 

with us here today. 

Richard Clothier retired as Head of the 

FAL at the end of 2005, and, as 

Professor Grierson has told us, FRAME 

and the University agreed that Andrew 

Bennett should be invited to succeed him. 

We have high hopes that the FAL will 

thrive under his leadership, and that it will 

move forward in new directions, ever 

Jack Ferguson, with Brough Girling and 

Sarah Milligan in the FAL 

toward new heights. Andy certainly has a 

facility which should make this possible. 

Finally, he pointed out that the Minister, 

who was about to speak, had once been 

a research assistant at FRAME, and that 

his first publication, The Last Moral 

Frontier — An Alternative View, had 

been published in FRAME News 25, in 

March 1990. 

Ed Balls said that it was a privilege to 

have been invited to take part in this 

important occasion, but that he also felt 

strange on returning to territory in 

which he had spent so much time in the 

past, but which had now been remodelled 

beyond recognition. He said that, 

while his new position required him to 

promote the Three Rs in the classroom, 

his upbringing had inevitably given the 

term another meaning. He spoke of his 

long association with Nottingham, 

recalling that, when he had met the 

Queen a few days earlier, to become a 

Privy Councillor, he remembered how, at 

the age of 8, he had been one of those 

waving flags when the Her Majesty came 

to open the QMC in 1976. Later, as a 

student, he had been able to use the 

University’s library, and he was very 

proud to have been awarded an 

honorary degree by the University, a 

year or two earlier. 

Referring to the article published in 

FRAME News, he said that it had 

resulted from a visit he had made to the 

Financial Times in December 1989, at 

the invitation of its Editor, at which he 

had been given a copy of Michael 

Prowse’s article on The Last Moral 

Frontier, published in the paper that day, 

and told that, if he could write a good 

enough reply in 800 words, he would be 

offered a job. He did so, and was given a 

job as an editorial writer. 

He said that FRAME had two outstand - 

ing and parallel characteristics. One was 

to always be rigorous in trying to understand 

the world, to consider the 

evidence and seek answers to difficult 

questions, while the other was a desire 

to make changes by being practical in 

applying the understanding gained. As a 

result, FRAME had greatly influenced 

the thinking behind the Animals (Scient - 

ific Procedures) Act 1986, as well as the 

establishment of ECVAM, by focusing, 

not merely on whether we can have alternatives, 

but on how to validate them, so 

that they can be relied on and used 

throughout the world. He concluded by 

saying that FRAME and the University 

were leading the country and the world, 

and that all concerned should be very 

proud of the opening of the remodelled 

FAL, which would lead to the next phase 

of the partnership. He then unveiled a 

plaque to record FRAME’s appreciation 

of the support given over many years by 

Julia Girling. 

The ceremony was followed by a reception 

and a lunch in the University, which 

was kindly sponsored by Alliance Boots. 

Anthony Holmes (NC3Rs), Vicky 

Robinson (NC3Rs) and Robert Combes 

(FRAME Director) in the FAL 


THE LAST MORAL FRONTIER — AN ALTERNATIVE VIEW 

“The abuse of animals presents mankind with its last 

great moral challenge.” 

So wrote Michael Prowse, a Financial Times journalist in a recent article in the 

paper’s LOMBARD column (‘The Last Moral Frontier’, Financial Times, 

22.12.89). Prowse argued that by recognising our moral “blindspot” as 

regards animals, by accepting that “our maltreatment of them betrays an unjustifiable 

bias towards our own species”, humankind will reject not only blood 

sports and unnecessary cruelty, but all animal experimentation and meat-eating 

as immoral and unacceptable. The following opinion was written as a reply to 

Prowse’s argument. 

Man’s relationship with animals appears 

riddled with contradictions. Animals are 

adored as domestic pets, but hunted for 

sport, eaten, and used in painful scientific 

research. Some argue that such exploitation 

is immoral, others that morality only 

embraces man’s relations with other 

humans. Neither view captures the 

complexity of our relations with animals. 

We have never fully faced up to our 

responsibilities, perhaps because we have 

never properly understood their source. 

The moral complexity of our relationship 

with animals arises from the existence of 

both key similarities and differences 

between most humans and non-humans. 

Like us, many animals can suffer, and 

suffering necessarily undermines the 

quality of any life. Thus, the central 

innovation of the Animals (Scientific 

Proced ures) Act 1986 is the requirement 

that pain inflicted in research be out - 

weighed by likely reduction in future 

human, or animal, suffering. While 

research for idle curiosity is unacceptable, 

we allow many animals, though not 

humans, to suffer each year in the search 

for new, safe vaccines and treatments that 

will prevent future suffering. Many of us 

feel this trade-off is morally justified. 

It can be argued that such use of animals, 

regardless of the prevention of future 

suffering, violates their “rights”. Moral 

or political debate is often conducted in 

terms of conflicting “rights”, used as 

rhetorical devices to emphasise the rightness 

of each side’s claim. This devalues a 

valuable commodity. Rights must mark a 

special domain of morality. 

While a life merely free from suffering 

does not constitute a “good life” for 

either humans or non-humans, animals 

do not possess the capacities which rights 

exist to protect. To talk of “animals” in 

this context is a gross simplification — an 

amoeba merely lives and reproduces, 

whereas, to flourish, a higher nonprimate 

needs companionship and a 

stimulating, non-restrictive environment. 

But the distinguishing feature of a human 

existence is a consciousness of the 

potential value of our lives. We additionally 

cherish our ability to plan for 

tomorrow, the liberty to choose our own 

life-structuring interests and relationships, 

and the autonomy to live according 

to our chosen life-plan. It is these central 

capacities that generate basic human 

rights to freedom of speech, freedom of 

worship, and access to a basic level of 

education and resources. To experiment 

using humans would cause immediate 

suffering, but would also undermine the 

security of the process by which humans 

plan their lives, free from the threat of 

drastic interference, which rights exist to 

protect. 

Animal lives undoubtedly have value — a 

value which, perhaps, increases with 

complexity of needs and behaviour, but 

their inability to make their lives of 

greater value, to have rational aspirations 

for themselves and others, deprives them 

of the capacities which moral rights exist 

to protect. To be free of a charge of 

speciesism, we must accept that not all 

humans possess these moral rights. The 

unborn fetus and the newborn baby, as 

with the brain-dead accident victim, do 

not possess the capacities moral rights 

protect. But this in no way removes them 

from the sphere of moral concern. There 

are clearly compelling reasons for out - 

lawing infanticide, and controlling the 

availability of abortion — reasons which 

do not depend on rights. So it is with 

animals. 

Human responsibilities, not animal rights, 

should be the focus of the moral debate. 

But the fact that animals do not have 

rights does not imply, as is argued by the 

Research Defence Society, that animals will 

always take second place to human interests. 

Because we have the power to use 

animals, we cannot escape the responsibility 

that requires us to use them with 

respect for their value as well as for 

human needs. Organisations such as 

FRAME argue that our responsibility lies 

in reducing, refining and, ultimately, 

replacing all animal experiments with nonanimal 

alternatives. Herein lies the real 

challenge. 

A clearer view of the way in which animals 

fit into our moral thinking allows us to 

reassess our treatment of animals more 

generally — in farms, in zoos, for sport. 

Clearly, in many areas we do not face up 

to our responsibilities seriously enough, 

if at all. 

While the painless killing of animals for 

food is not immoral, the case for vegetarianism 

is on stronger ground when 

highlighting our current disregard for the 

quality of lives of both animals and 

humans that our meat-eating implies. A 

recognisably good life for a chicken must 

include the ability to flap its wings, peck 

the ground and see the sky — and not to 

be imprisoned in a battery cage. How ever, 

it is not only our responsibilities to 

animals that we neglect. The gross inefficiency 

of our meat-eating behaviour, while 

resources are scarce and malnutrition 

afflicts large areas of the world, is absurd. 

It is not only our disregard for the feelings 

of other species, but our blatant disregard 

for the needs of large sections of our 

own, that makes overcoming our greed 

and myopia the next moral frontier. 

Edward Balls 

This paper was first published in 

FRAME News 25, in 1990. Ed Balls 

had read Philosophy, Politics and 

Economics at Oxford University 

from 1985 to 1988, and was a 

research assistant at FRAME in 

1988. The article came about as the 

result of a visit he made to the 

Financial Times in 1989, while he 

was reading for a Master’s degree 

in Public Administration at Harvard 

University. 


DOROTHY HEGARTY AWARD WINNERS 2006 

The 2006 Dorothy Hegarty Award has 

been won by Rachael Jupp, Palminder 

Dusanjh, Andrew Walding, Mark 

McHale, Graham Belfield and Stephen 

Delaney (all Department of Molecular 

Biology, AstraZeneca R & D Charnwood, 

Loughborough, UK) for their paper, 

Rapid Simultaneous Cloning of Drug 

Targets from Multiple Mammalian 

Species (ATLA 34, 295–303). 

One of the co-authors, Stephen Delaney, 

who is a Principal Scientist at 

AstraZeneca R & D Charnwood, told 

FRAME, “The whole team were 

delighted to receive the 2006 Dorothy 

Hegarty Award. In recent years, it has 

become more routine to generate in 

vitro assays by involving synthetic 

(recombinant) human and rodent drug 

targets, but we wanted to improve the 

speed and success of setting up such 

assays for other species used in drug 

discovery. In this way, we hoped to be 

able to refine or replace some in vivo 

tests. The methods described in the 

paper have indeed improved our ability 

to generate the in vitro assays, at least 

fifteen of which are currently being used 

in several drug discovery projects in 

AstraZeneca”. 

The Award is presented annually to the 

author(s) of the paper published in the 

previous year’s volume of FRAME’s 

scientific journal, ATLA, which, in the 

opinion of the members of the Editorial 

Board, is likely to make the most significant 

contribution to the reduction, 

refinement and/or replacement of animal 

experimentation. To determine the 

Award winner, each member of the 

ATLA Editorial Board is entitled to make 

up to five nominations for the Award, in 

rank order. As in previous years, a large 

variety of papers were nominated, 

reflecting the diversity of the work 

published in ATLA, and the wide range 

of interests of the members of the 

Editorial Board. 

The 2006 Dorothy Hegarty Award winners. From left to right: Graham Belfield; 

Stephen Delaney; Rachael Jupp; Andy Walding; and Mark McHale. (Palminder 

Dusanjh was unfortunately unavailable). 

DEVELOPING AND USING TISSUE CULTURE 

MODELS OF HUMAN TOXICITY 

The October 2007 issue of ATLA 

contains articles based on presentations 

made at a one-day symposium, held at 

the University of Nottingham Medical 

School, Queen’s Medical Centre (QMC), 

on 30 November 2005, in recognition of 

the retirement of Dr Richard Clothier 

from the School of Biomedical Sciences. 

The articles include a review by Professor 

Larry Ruben (Reed College, Portland, 

Oregon, USA) on research on the imm - 

unology of Xenopus laevis (the South 

African clawed toad), undertaken during a 

long collaboration with Richard and 

Michael Balls. This is followed by a series 

of research reports on the subject of 

models of barrier functions in the skin, 

eye and tracheobronchial tract, by Richard 

Richard Clothier 

and some his Nottingham colleagues and 

former PhD students, namely, Alison Gray 

and Julie McLeod, Helena Hurst and 

Margaret Pratten, Nancy Khammo, Linzi 

Reid and Jane Ogilvie, in which they 

describe studies on the development and 

use of different types of in vitro tissue 

epithelial mono-culture and co-culture 

organotypic systems to investigate the 

mechanisms of differentiation and development 

of barrier functions. 

After an appreciation of Richard’s 

contributions by a former industrial 

customer, Petrina Fridd, the articles 

conclude with an analysis of the 

published papers which represented his 

contribution to the FRAME Research 

Programme, by Robert Combes, and a 

tribute to Richard’s unfailing enthusiasm 

and scientific integrity, by Michael Balls. 


GENERIC BIOPHARMACEUTICALS AND THE 

RISING DEMAND FOR ANIMAL TESTS 

As the US Congress considers laws that would give the US 

Food and Drug Administration (FDA) the authority to approve 

generic versions of biological medicines (biopharmaceuticals), 

the FDA is considering whether more-extensive safety testing of 

generic biopharmaceuticals will be required than is the case for 

generic chemical drugs. This would almost certainly include 

additional animal tests. 

The issue arises, because it is unclear 

whether generic biopharmaceuticals 

should be classed as similar to, or interchangeable 

with, the more expensive, 

patented parent products they are 

designed to replace. This is a relatively 

new situation, since the first generation 

of biopharmaceuticals, marketed back in 

the 1980s, are now beginning to lose 

their patent protection. 

At a hearing of the US House of Rep - 

resentatives Committee on Oversight 

and Government Reform, the FDA 

Deputy Commissioner for Operations 

and Chief Medical Officer, Dr Janet 

Woodcock, remarked: 

“The amount of assurance and the 

amount of data that would be needed is 

really based on how complex something 

is and how well it can be characterised”, 

and that: 

“Although this may be currently possible 

for some relatively simple protein products, 

technology is not yet sufficiently 

advanced to allow this type of comparison 

for complex protein products.” 

Insurers and patient groups argue that 

generic versions of biopharmaceuticals 

would be cheaper, since generic drug 

manufacturers would have to compete 

for sales, whereas brand-name drug 

makers monopolise the market for a 

particular type of drug. 

Brand-name drug makers, predictably, 

claim that biopharmaceuticals are too 

complicated to duplicate, and that small 

differences will affect their action and 

Human erythropoietin 1 — one of the 

first biopharmaceuticals developed, 

which is central to the concerns about 

the manufacture and testing of followon 

biologics. 

safety. Indeed, it is often impossible to 

create true generic versions of biopharmaceuticals, 

because small changes in 

the manufacturing process, the cell types 

used and the conditions under which 

they are grown, all contribute to variations 

in the way a protein might fold or 

the extent and nature of post-synthesis 

events, such as the addition of sugars or 

phosphate groups, or the cross-linking 

of protein chains. These small differences 

can, in turn, affect the proportion 

of active molecules, the stability of the 

biopharmaceutical, and how the body 

transports and eliminates it. Hence, a 

more accurate term for a generic 

biopharmaceutical is a follow-on 

biologic. 

In a country where approximately 60% 

of prescriptions are made up of generic 

drugs, this debate promises to be a 

heated one. FRAME’s concern is that, in 

the worst case, if it is decided that a 

follow-on biologic is sufficiently 

different from the parent biopharmaceutical, 

almost all the animal tests that were 

conducted for the parent drug might 

have to be repeated for the follow-on 

biologic. Bearing in mind that nonhuman 

primates are used far more 

extensively to test biopharmaceuticals 

than traditional medicines, and because 

of difficulties in establishing the relevance 

of tests on other laboratory 

species for human-specific drugs, this 

could result in a dramatic increase in 

testing on non-human primates over the 

next few years. 

Further information is available at: 

http://uk.reuters.com/article/scienceNews/ 

idUKTON68451520070326. 

REFERENCE: 

1 Cheetham, J.C., Smith, D.M., Aoki, K.H., 

Stevenson, J.L., Hoeffel, T.J., Syed, R.S., 

Egrie, J. & Harvey, T.S. (1998). NMR 

structure of human erythropoietin and a 

comparison with its receptor bound 

conformation. Nature Structural Biology 

5, 861–866. 

UFAW Animal 

Welfare Science 

Conference 2008 

Recent Advances in 

Animal Welfare Science 

3 July 

2008 

Council House 

Birmingham, UK 

See: www.ufaw.org.uk 


FLAWED ANIMAL TESTING 

Attention was drawn to the poor quality of animal testing at the British 

Association Festival of Science, organised by the British Association for the 

Advancement of Science, on 9–15 September 2007 at the University of 

York. 1 This can contribute to the failure of drugs to live up to their 

promise, and even cause serious harm, as in the case of TGN1412. 

Michael Bracken (Yale University, New 

Haven, CT, USA) said that there is an 

urgent need for improvements in how 

animal experiments are performed, so 

that the health and safety of patients and 

research volunteers are not put at risk. 

Malcolm Macleod (Stirling Royal Infirm - 

ary, Scotland) agreed that there was 

substantial room for improving animal 

studies. He said that 800 drugs for the 

treatment of stroke had been tested in 

animals, of which 500 seemed to work. 

However, when 100 of them were tested 

in patients, only one worked. The main 

problem lies in the design of the animal 

tests, which introduces biases. 

Derek Fry (Home Office, London) said 

that the animal research community has 

lagged behind when it comes to appreciating 

the importance of double-blind 

randomised trials. 

According to a report by Steve Connor 

in The Independent, 2 a survey of 300 

animal studies involving six different 

experimental drugs “suggested that such 

flawed methodology is rampant in the 

A recent study of US FDA statistics 1 

suggests that both adverse and fatal drug 

events more than doubled between 

1998 and 2005 in the USA, even 

though the percentage of drug withdrawal 

had almost halved in the same 

period. A disproportionate number of 

the drugs that caused adverse events 

such as deaths, birth defects or other 

debilitating or life-threatening incidents, 

are pain killers (e.g. the COX-2 inhib - 

itors, Vioxx and Bextra), drugs that 

target immune function (e.g. Seldane) 

and narcotics (e.g. Fentanyl and 

morphine). However, the sharpest rise in 

pharmaceutical industry”. He referred to 

the example of NXY-059, a stroke drug 

made by AstraZeneca. Animal studies 

indicated that it improved outcomes by 

more than 50%, but when the studies 

were properly randomised and blinded, 

the actual improvement was 25–30%. 

The concern about flawed science was 

reflected in an editorial in The Independ - 

ent, 3 which said: “The drug industry 

cannot claim animal tests are essential 

when it funds flawed science. It must be 

a precondition of funding, and of scientific 

publication, that studies are 

properly carried out.” 

This was echoed at the Festival, by 

Michael Bracken, who said: “The general 

public takes the view that it will only 

tolerate animal experiments if the results 

improve human health, but how much 

adverse drug events involved a number 

of biotechnologically-derived drugs, 

such as Neutrospec, an antibody that 

was used briefly for the imaging of 

appendicitis. 

animal experiments improve human health 

is a scientific question. The key question 

is whether animal studies translate to 

human medicine.” 

Virginia Barbour, who took part in a 

session at the Festival organised by 

CAMARADES, an organisation that pro - 

vides a supporting framework for groups 

involved in the systematic review and 

meta-analysis of data from animal studies 

in experimental stroke, has commented 

that the basic premise of the session was 

that animal experiments, in stroke research 

at least, are not being done to the level of 

rigour that we have come to expect of 

human studies. 4 She spoke about what 

journals can do, and summarised it in two 

points: 1) Make sure that what’s reported 

is the truth, the whole truth and nothing 

but the truth; and 2) Make all the studies 

available for all to read. 

REFERENCES: 

1 Highfield, R. & Fleming, N. (2007). Drug 

trials put at risk by flawed animal testing. 

Available at: www.telegraph.co.uk/earth, 14/09/2007 

(Accessed 17.09.07). 

2 Connor, S. (2007). Effectiveness of 

drugs ‘overstated because of biased 

testing’. The Independent, 15 September 

2007. 

3 Anon. (2007). Leading article: Flawed 

science. The Independent, 15 September 

2007. 

4 Barbour, V. (2007). Setting better standards 

in reporting — and doing — 

animal research. Available at: http://www. 

plos.org/cms/node/258 (Accessed 18.09.07). 

ANIMAL TESTS FAIL TO DETECT THE 

RISKS POSED BY SOME MEDICINES 

Whilst the aforementioned drugs are 

among the 30 or so that have been 

completely withdrawn from the US market 

for safety reasons, around 20% of drugs 

that continue to be marketed will, at some 

point, be subject to restricted use or 

labelling changes. The labelling changes 

may reflect the post-market observation 

that some drugs pose higher risks to 

women, their unborn children (e.g. 

thalidomide), young children (e.g. 

Seroxat) or the elderly (often because 

they are likely to be taking several medicines 

and therefore are at greater risk 

from adverse drug interactions). 


The question is, why were these adverse 

drug events not anticipated from 

preclinical studies in animals or during 

clinical trials in healthy volunteers or 

patients? Perhaps the answer lies in the 

types of drugs that have been withdrawn. 

Take, for instance, the COX-2 inhibitors 

Vioxx and Bextra. The FDA, despite 

recognising that these non-steroidal 

anti-inflammatory drugs, once used for 

the treatment of inflammatory disorders 

such as arthritis and for pain relief, pose 

unacceptable risks, has authorised the 

use of Celebrex, another COX-2 

inhibitor. Yet, evidence submitted to the 

FDA suggests that subtle and ill-defined 

differences between the distribution and 

role of COX-2 in humans and animals, 

make the interpretation of preclinical 

information extremely difficult, so that 

animal tests can be of little value for 

predicting human outcomes. The same is 

true of drugs like thalidomide, given its 

varied effects on the in utero development 

of offspring in several laboratory 

species, and of Seroxat and other 

centrally active mood-altering drugs, 

which are extremely difficult to assess 

with animal models. 

Worse still, there are cases where, not 

only does a drug pose an unanticipated 

risk to patients, but it also has little therapeutic 

value. A good example of this is 

the diabetes drug, Avandia, which has 

caused heart problems without actually 

providing a better therapy for type 2 

diabetes than other drugs on the market. 

Finally, there are diagnostic aids, such as 

Neutrospec, that, despite their known 

potential to trigger immune responses, 

were not subject to appropriate testing, 

prior to going to market. 

In December 2006, the FDA announced 

that it was considering allowing experimental 

drugs to be given to terminally ill 

patients, after phase I trials in healthy 

volunteers and prior to market approval. 

The problem with this proposal is that 

some 90% of drugs fail to demonstrate 

any notable benefit to patients at this 

stage. Several possible solutions to the 

problems of adverse drug effects and lack 

of efficacy exist, but these focus on using 

new technologies, such as pharmacogenomics, 

to guide patient and volunteer 

selection, and on human cell-based and in 

vivo studies using low doses, rather than 

the traditional and rather out-dated core 

set of animal tests. 

REFERENCE: 

CRITICISM OF EMEA PROPOSALS 

Proposals by the European Med - 

icines Evaluation Agency (EMEA) for 

improving the safety of initial human 

clinical trials of new biologicals have 

been criticised as being too timid. 1 

The proposals are a result of last 

year’s disastrous incident, when 

TGN1412, a mono clonal antibody 

designed to specifically affect cells of 

the human immune system, had very 

severe effects on the six healthy 

human volunteers used in the trial. 

The EMEA proposals are based on 

the findings of an investigation for 

the UK Medical and Healthcare pro - 

ducts Regulatory Agency (MHRA), 

which was chaired by Sir Gordon 

Duff. 

Fifty-nine different experts submitted 

comments in response to a public 

consultation on the draft guidelines. 

One of the main criticisms levied at the 

guideline was the rather vague definition 

of what exactly would constitute a high 

risk medicinal product. On a related 

point, several respondents pointed to 

the notable absence of any guidance on 

how, in these circumstances, risk information 

would be conveyed to volunteers 

for first-in-man studies, regardless of the 

country in which the trial took place. 

The issue of what compulsory insurance 

cover is needed also varies between 

countries, hence the tendency to elect to 

conduct such studies in countries, such 

as the UK, where the insurance requirements 

are less stringent. The call by 

several respondents for an international 

standard for first-in-man studies, would 

certainly address this concern. 

On a separate issue, in the response 

submitted by FRAME, it was highlighted 

that very often (as in the case of 

TGN1412), the information from studies 

in different species can give rise to uncertainties 

that stem from lack of 

concordance between data from different 

studies conducted in vitro or in vivo or in 

different animal models, and, potentially, 

with different, but related, species homologues 

of an investigational medicinal 

product. The respondents acknowledged 

the potential advantage of setting starting 

doses for first-in-man clinical trials on the 

minimum active dose of any homologue in 

any such study. The starting dose may, 

1 Moore, T.J., Cohen, M.R. & Furberg, 

C.D. (2007). Serious adverse drug 

events reported to the Food and Drug 

Administration, 1998–2005. Archives of 

International Medicine 167, 1752– 

1759. 

2 Pippin, J.J. (2005). The Need for 

Revision of Pre-Market Testing: The 

Failure of Animal Tests of COX-2 

Inhibitors. (FDA Open Public Hearing. 

Arthritis Advisory Committee, Drug 

Safety and Risk Management Advisory 

Committee), 23pp. Washington, D.C., 

USA: Physicians Committee for 

Responsible Medicine. 

however, be different if the first-in-man 

study is conducted in patients where efficacy 

is expected. 2 

The EMEA guidelines are non-binding, 

partly because the 2001 Clinical Trial 

Directive, which is intended to 

harmonise practice within the EU, is 

interpreted differently in the various 

Member States. An EU-wide regulation, 

which is rigorously enforced, is the only 

way forward. Meanwhile, there seems to 

be a reluctance to conduct first-inhuman 

trials of immune system-targeted 

biologicals in human volunteers. 

One of the key lessons to be learned 

from the TGN1412 affair is that the 

value of animal testing for humanspecific 

biological drugs must be 

seriously questioned. 

REFERENCES: 

1 Mitchell, P. (2007). Critics pan European 

response to TeGenero as too timid. 

Nature Biotechnology 25, 485–486. 

2 Bhogal, N. (2007). After TGN1412: 

The CHMP draft guidelines. Hospital 

Pharmacy Europe 33, 45–46. 


ANIMAL EXPERIMENTS REACH A 

15-YEAR HIGH 

Figure 1: Number of scientific procedures started by species or genre of animal in Great Britain, 

1988–2006. Total column height equals total number of procedures. 

thousands of procedures 

The latest version of the Home Office Statistics of Scientific Procedures on Living Animals: Great Britain 2006 1 

showed that, once again, the levels of animal experimentation conducted in Great Britain are increasing. The number 

of procedures rose by 4% in 2006 to 3,012,032, and the number of new animals used increased by 4.8% to 

2,946,624. These figures are the highest for 15 years, and there are no indications that this trend will be reversed 

in the near future (Figure 1). Indeed, the impending REACH legislation and the increasing movement toward the 

development of specific human-based medicines, will inevitably increase the demand for animal experiments. 

Meanwhile, the numbers of procedures involving the creation and use of genetically modified animal models will 

inevitably increase. 

3500 

3000 

2500 

2000 

1500 

1000 

500 

0 

’88 ’89 ’90 ’91 ’92 

Fewer procedures were performed on 

rats, rabbits, dogs, primates, reptiles and 

amphibians, and ferrets (down 4%, 11%, 

1%, 10%, 5% and 14%, respectively) 

than in 2005. However, the number of 

procedures that involved the use of mice 

’93 ’94 ’95 ’96 ’97 

year 

’98 ’99 ’00 ’01 ’02 ’03 ’04 ’05 ’06 

(up 5%), fish (up 18%), cats (up 5%), 

pigs (up 31%), birds (up 1%) and sheep 

(up 24%) increased last year, as comp - 

ared to 2005. As in previous years, the 

majority of animals were used for breed - 

ing followed by fundamental research 

(Figure 2), but, in stark contrast to recent 

years, the numbers of applied procedures 

also increased in 2006. This is reflected 

in an increase in the number of toxicology-based 

safety tests, which account 

for the majority of the applied studies. 

FRAME News http://www.frame.org.uk 10 

fish 

reptile/ 

amphibian 

bird 

other 

mammal 

primate 

mouse 

rabbit 

other 

rodent 

rat

Figure 2: Primary purpose of animal procedures in Great Britain 1995–2006 

100% 

90% 

80% 

70% 

60% 

50% 

40% 

30% 

20% 

10% 

0% 

1995 

= Fundamental biological research; = Applied research; = Other research; = Breeding. 

Once again, the production of genetically 

modified animal models was the main 

reason for the increase in animal experiments. 

Procedures on genetically modified 

animals accounted for over a third (34%) 

of all the animal procedures, 67.5% of 

which were for breeding purposes. Over 

90% of the genetically modified 

(including harmful genetic defect) animal 

procedures involved mice. In comparison, 

the use of rats was low and accounted for 

only 3% of all procedures of this type. 

However, recent studies at FRAME have 

questioned whether the mouse really is 

the most suitable model of human 

Box 1: Recent trends in the use of genetically modified (including those with harmful defects) 

rodents — a comparison of mice and rats as models of human disease and toxicity 

The use of genetically modified (GM) 

mice has steadily risen since the mid 

1990s. The GM mouse is greatly 

favoured over the GM rat, with over 

1.2 million procedures being 

performed in 2006 on them, as 

compared with only 37,000 procedures 

on rats. 

Overall, the use of rats has fallen over 

the past decade, from almost 700,000 

in 1995 to just over 400,000 in 

2006. However, whilst the use of rats 

declined generally in 

2006, 53% more of 

the procedures 

involved generating 

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 

disease, and suggested that the rat might 

by a better model in many cases (Box 1), 

such that we may soon see a slow down in 

the development and use of new genetically 

modified mouse strains and an 

upturn in the genetic modification of rats. 

The continued rise in the levels of animal 

experimentation is an ongoing concern 

for FRAME. There is an urgent need for a 

review of why certain types of experiments 

are permitted, which takes into account 

the availability of alternatives and the 

scope for using existing information to 

enrich our understanding of human and 

or using GM rats than in the previous 

year. This may be a consequence of the 

recent release of the rat genome 

sequence. 

To date, the laboratory mouse remains 

the primary target for genetic modification 

due to its ease of manipulation, 

extensive knowledge of its physiology, 

and its cost-effective housing and 

husbandry. However, there is also a 

growing body of evidence to suggest 

that, in some circumstances, the rat may 

be more relevant for studying human 

diseases, for some forms of toxicity 

testing, and for the evaluation of 

specific pharmaceuticals. For example, 

the use of the popular NOD (non- 

animal physiology and to improve animal 

welfare. There needs to be greater 

dialogue between all interested parties, 

including industry, academia and the 

Government, and better application of the 

Three Rs by all scientists, if this worrying 

trend is to be prevented from escalating 

out of control. 

REFERENCE: 

1 Home Office (2007). Statistics of 

Scientific Procedures on Living Animals: 

Great Britain 2006, Cm 7153, 44pp. 

London, UK: HMSO. 

obese diabetic) mouse model has been 

unsuccessful in deciphering how 

diabetes is triggered in humans, 

because of important species differences 

in how insulin levels are 

regulated in mice and humans. 

However, the use of rat models, such 

as the LEW rat, have helped to overcome 

these limitations. 

Thus, while no single model can mimic 

all of the aspects of a human disease, it 

is important to highlight the significance 

of using the most relevant rodent 

species. FRAME has conducted 

research in this area, and is currently 

preparing an article detailing its findings. 


FRAME AT THE SIXTH WORLD CONGRESS 

ON ALTERNATIVES AND ANIMAL USE IN 

THE LIFE SCIENCES 

WC6 took place in Tokyo, Japan, on 

21–25 August 2007, with the 

support of the Japanese Society for 

Alternatives to Animal Experiments 

(JSAAE), the Alternative Congress 

Trust (ACT), and the Science Coun - 

cil of Japan (SCJ). The previous 

World Congresses had been held in 

Baltimore (1993), Utrecht (1996), 

Bologna (1999), New Orleans 

(2002), and Berlin (2005), so 

WC6 represented a significant move 

toward implementing the Three Rs 

in Eastern Asia. 

The Congress was attended by more than 

900 scientists, regulators and government 

administrators from all over the world. 

FRAME was strongly represented, as 

Michael Balls, Nirmala Bhogal, Christina 

Grindon, Michelle Hudson and Michelle 

Scrivens were all in attendance. The 

FRAME scientists made a number of oral 

and poster presentations, and chaired 

scientific sessions as well as a discussion 

group on primate research (Box 1). Two of 

these presentations were made in oral 

sessions for young scientists (Box 1, items 

7 and 9). 

The following reports can only focus on 

some of the many issues discussed at 

what was, scientifically and socially, a 

very successful Congress. 

An elegant ceremony in honour of animals used in research 

THE PAST, PRESENT AND 

FUTURE OF THREE RS 

RESEARCH 

During the opening ceremony, Michael 

Balls gave a special lecture to commemorate 

the life and work of William Russell, 

one of the founders of the Three Rs 

principles, who died in July 2006 (Box 

1, item 1). This was followed by an 

elegant ceremony in honour of the 

animals that had been used in Japan for 

research purposes. 

A number of plenary lectures were given 

by experts in a number of fields, includ - 

ing Baroness Perry of Southwark, who 

Martin Stephens (HSUS), introducing the HSUS Russell and Burch Award prior to its 

presentation to Rodger Curren (IIVS) 

described consultations by scientists, 

including Robert Combes of FRAME, 

that led to the publication in 2005 of 

the Nuffield Council on Bioethics report 

on the scientific and ethical issues that 

surround animal experimentation. 

Julia Fentem (Unilever, UK) gave a 

plenary lecture entitled Exploring New 

Approaches to Assess Safety Without 

Animal Testing, which gave encouraging 

news on the application of new technologies 

and risk-based approaches 

instead of animal-based procedures. She 

explained how the EU REACH legislation 

on chemicals and the 7th Amendment to 

the EU Cosmetics Directive, had stimulated 

Unilever to undertake a substantial 

research programme on the feasibility of 

using new in vitro and computer-based 

models, and new technologies such as 

the ‘omics’ and bioinformatics, to gather 

data for risk-based safety assessment for 

endpoints such as skin allergy. 

HUMANE 

EXPERIMENTATION 

A session on assessment of the severity of 

animal procedures involved experts on the 

documentation of severity from the UK 

(Jon Richmond, Home Office), the USA 

(Andrew Rowan, Humane Society of the 


United States), Canada (Gilly Griffin, 

Canadian Council for Animal Care), New 

Zealand (David Bayvel, Ministry of Agri - 

culture and Forestry), and Japan 

(Takatoshi Kuthara, Juntendo University, 

Japan). These countries have different 

ways of reporting animal suffering and of 

classifying severity. It became clear that an 

internationally agreed system for classifying 

animal suffering is needed, to permit 

direct comparisons of practices in 

different countries, and to ensure that the 

suffering of laboratory animals is 

minimised. 

Differences in severity reporting related to 

procedures involving genetically modified 

(GM) animals are a particular cause for 

concern. Gilly Griffin highlighted work 

being undertaken at the CCAC toward 

harmonisation. New guidelines are being 

prepared, which will mean that protocols 

in which GM animals are generated will be 

classed as Level D (moderate–severe). 

However, the breeding of GM animals and 

their use in experiments will be no longer 

be categorised in Canada at this level, as 

at present, but will depend on the specific 

case. 

Paul Flecknell (Newcastle University, UK) 

opened a session entitled Alleviation of 

Pain and Distress in Laboratory Animals, 

by examining how changes in sensory 

discrimination, cognitive dimension and 

complex central processing can alert 

researchers to whether an animal is in 

pain. He argued that we need to be able 

to measure pain markers quantitatively, to 

ensure accordance with the Three Rs. 

Martin Stephens (HSUS) called for a 

holistic approach to taking research 

animal suffering seriously — one with all 

the stakeholders sharing the responsibility 

for minimising animal suffering. Tsutomu 

Miki Kurosawa (Osaka University Medical 

School, Japan) then described how pain 

and distress in laboratory animals are 

classified in Japan, based on US categorisations, 

thus supporting a move toward 

the international standardisation of pain 

and distress classifications and protocol 

review processes. 

In a session entitled 3Rs for Primates in 

Research, Paul Honess (University of 

Oxford Veterinary Services, UK) showcased 

the Oxford University Rhesus 

Mon k ey Colony: Refinements in 

Husbandry DVD, which aims to promote 

better understanding of the application of 

refinement to improve the welfare of laboratory 

primates. Janet Kelly (Covance 

Laboratories Ltd, UK) described how 

their laboratory primate facilities have 

improved over the past 20 years, during 

which measures toward refinement, such 

as encouraging natural behaviours, 

providing play rooms and group housing, 

and staff training, were considered. The 

history of chimpanzee experimentation in 

the US was described by Kathleen Conlee 

(HSUS) in her presentation about the 

HSUS campaign to end chimpanzee 

research. Michelle Thew (BUAV) gave a 

presentation on Chimpanzee Research: An 

Examination of its Efficacy in Combatting 

Human Disease, outlining the results of a 

literature survey of biomedical research 

that suggests that chimpanzee research 

has led to very few, if any, medical benefits. 

The session ended with a description 

of laboratory primate use in Japan by 

Tsutomu Miki Kurosawa. This included 

Members of the Alternatives Congress Trust, taking part in a traditional sake barrel 

opening ceremony at the WC6 farewell banquet 

information on the fields of research in 

which Japanese scientists feel that 

primates are indispensable. Ethical opinions 

about primate use are different in 

Japan, as the Japanese macaque is seen as 

a pest and its eradication is considered to 

be desirable. 

POLICY AND REGULATION 

In a session on Globalisation, Validation 

and International Cooperation, a series 

of presentations gave updates of validation 

studies from three alternatives 

centres around the world — ECVAM, 

ICCVAM/NICEATM and JaCVAM — 

and of OECD activities. 

Hajime Kojima (JaCVAM) described 

studies on in vitro dermal toxicity, in vitro 

and revised in vivo methods for skin 

sensitisation, and an in vitro test for 

endocrine disruption being developed in 

Japan. Thomas Hartung (ECVAM) 

described the recent successful validation 

of in vitro methods for mutagenicity, skin 

irritation and eye irritation, and of two 

revised in vivo methods which reduce the 

number of animals required for acute 

ecotoxicity and skin sensitisation testing. 

He went on to relay the role of alternative 

methods in halving the number of 

animal tests that would be required to 

fulfill the testing requirements of the EU 

REACH legislation on chemicals. William 

Stokes (NICEATM) discussed validation 

studies being performed in collaboration 

with JaCVAM and ECVAM, on in vitro 


assays for cytotoxicity and on oestrogen 

receptors, and the in vivo rodent Comet 

assay. 

Also in this session, Patric Amcoff 

(OECD) discussed how the OECD has 

focused on validation issues and test 

method development with regard to the 

implementation of the Three Rs. Two 

guidance documents (GDs) have recently 

been produced (GD1 and GD34), which 

outline the views of the OECD on issues 

such as test guidelines for commercial 

tests, and how to undertake the validation 

of test batteries and testing strategies. 

RISK ASSESSMENT AND 

MANAGEMENT STRATEGIES 

THAT MINIMISE ANIMAL 

EXPERIMENTS 

A session on Risk Assessment Strategies 

focused on European organisations, such 

as the European Food Safety Authority 

(EFSA) and the European Partnership of 

Alternative Approaches to Animal 

Testing (EPAA), and a new EU integrated 

project to develop testing 

strategies for REACH. Herman Koeter 

and Pierre Le Neindre (EFSA) discussed 

the role of the EFSA in providing scientific 

advice and technical assistance on 

food and feed safety matters to the EC 

and to MEPs. EFSA was set up recently, 

in the aftermath of the BSE crisis, and 

covers a wide range of animal welfare 

issues for food producing animals. It 

also has a policy for the welfare of 

experimental animals, which includes 

active cooperation at the technical level 

with organisations such as the OECD, 

ECVAM and the WHO, as well as the 

development of in-house expertise on 

alternatives to animal testing. Similarly, 

the EPAA was set up in 2005, and 

already has a large number of partners 

from industry, the EC, governmental 

bodies and animal welfare organisations 

on board. The aim is to encourage the 

development and validation of alternative 

methods, and to expedite their use in 

regulatory testing. 

Manfred Liebsch (ZEBET, Germany) 

discussed the new EU integrated project, 

OSIRIS (Optimised Strategies for Risk 

Assessment of Industrial Chemicals 

Through Integration of Non-test and Test 

Information), set up earlier this year. 

OSIRIS has 31 partners from 14 countries, 

working together toward the 

development of Integrated Testing 

Strategies (ITS) which will enable the 

increased use of non-test and non-animal 

testing within REACH. The approach will 

take into account the chemistry, biology 

and exposure of the substance, with an 

ITS likely to include the following steps: 

exposure-informed waiving; 

chemical/biological read across; chemical 

categories; QSAR testing; thresholds of 

toxicological concern; genomics analysis; 

in vitro testing; and, finally, optimised in 

vivo tests, if required. 

The OECD guidelines on one-generation 

and two-generation reproductive toxicity 

guidelines were discussed in a session on 

risk assessment approaches, where Horst 

Spielmann (ZEBET) described the reasons 

why a second generation study adds little 

of value to the information needed for 

REACH testing. He pointed out that the 

abandonment of two-generation studies 

would result in a massive reduction in the 

number of animals used. 

Marilyn Wind (US Consumer Product 

Safety Commission) introduced a new 

aspect to the World Congress — one 

which looks at nanomaterials and how 

difficult it may be to get the information 

needed to assess their safety. Nirmala 

Bhogal presented the outcomes of a 

FRAME Risk Assessment Workshop 

within this session (Box 1, item 6). 

Another area which presents new challenges 

is the testing of biotechnologically 

engineered proteins as replacement therapies 

or new therapeutic agents. In a 

session entitled The Three Rs in the 

Development, Production and Quality 

Control of Biologicals, Toru Kawanishi 

(NIHS, Japan) made a case for 

promoting activity within the research 

community to develop methods capable 

of predicting, with greater certainty, how 

immunogenic a protein-based therapeutic 

may be in different people. This is 

important, since immunogenicity can 

result in very different levels of activity 

of a protein drug in individual patients. 

Richard McFarland (US Food and Drug 

Adminstration) reiterated some of the 

key regulatory practices with regard to 

testing of biological products in the 

USA, and outlined the types of alternatives 

that are being developed within 

their research centre. Yoji Sato (NIHS, 

Japan) described how a holistic approach 

that uses gene expression profiling, 

produces data which might help to identify 

the likely biological responses to a 

new protein drug, and proposed ways in 

which this data can be used toward the 

planning of further experiments. Nirmala 

Bhogal gave a presentation on the problems 

highlighted by the failed clinical trial 

on TGN1412 last year, describing how 

alternatives should be used to address 

these issues in the case of proteins 

which have enhanced or novel activities 

within the body (Box 1, item 5). 

CURRENT AND FUTURE 

REPLACEMENT 

ALTERNATIVES 

Two separate sessions were devoted to 

the consideration of genotoxicity testing 

and the Comet assay. In the first of these 


Box 1: FRAME presentations at the Sixth World Congress 

1 Animal Welfare Memorial Lecture: Professor William Russell (1925–2006): Doyen of the Three Rs Opening 

Michael Balls Lecture 

2 The Validation Process is Under Attack — An Inconvenient Truth 

Michael Balls and Robert Combes 

3 The Potential Role of in silico Methods as Part of an Integrated Testing Strategy for Predicting 

Aquatic Toxicity 

Michael Balls, Robert Combes, Christina Grindon, Mark TD Cronin, David W Roberts and John Garrod 

4 Hazard Data from Non-animal Toxicity Testing Methods are Currently Insufficiently Used for Risk 

Assessment 

Michael Balls and Robert Combes 

5 The Quality and Safety Assessment of Bioactive Proteins: Lessons from TGN1412 

Nirmala Bhogal 

6 Possibilities for a New Approach to Chemicals Risk Assessment — The Outcome of a FRAME 

Workshop 

Nirmala Bhogal and Robert Combes 

7 The Continued Use of Primates is Essential: Fact or Fiction? Reflections on the 2006 Weatherall 

Report 

Michelle Hudson 

8 Comparison of Mice and Rats as Models of Human Diseases and Toxicity 

Michelle Scrivens and Nirmala Bhogal 

9 The Use of in vitro Reporter Gene-based Systems in Toxicity Assessment 

Michelle Scrivens and Nirmala Bhogal 

10 Update on Efforts to Apply the Three Rs to the Mouse LD50 Assay for Assessing the Potency of 

Botulinum Neurotoxin-based Products 

Martin L Stephens, Michael Balls and Sherry Ward 

11 Working Toward the Phasing Out of Primate Experimentation 

Michelle Hudson and Martin L Stephens 

12 The Relevance of Genetically Altered Mice to Human Medicine 

Nirmala Bhogal 

13 Reducing Animal Use through Raw Data Availability 

Michelle Hudson, Robert Combes, Rose Gaines Das, Bryan Howard, Graham Moore, Derek Fry and Laura 

Playle 

14 Development of an in vitro Inhalation Model to Identify Irritants and Carcinogens 

Alison Gray, Nadine Gobert, Robert Combes and Julia McLeod 

15 Integrated Testing Strategies for REACH 

Christina Grindon and Robert Combes 

16 Novel Strategies for Developing Human Hepatic Cell Lines for in vitro Testing 

Robert Combes, Yan Sun, Elke Gottschalg, Monica Owen, Tyson V Sharp and Andrew Bennett 

FRAME News http://www.frame.org.uk 15 

Oral 

Presentations 

Poster 

Presentations

sessions, David Kirkland (Covance 

Laboratories, UK) described some of 

the problems with in vitro assays as a 

means of predicting in vivo genotoxicity. 

A variety of possible ways in which to 

use batteries of in vitro tests to improve 

the detection of true genotoxins were 

considered. Specific models of in vitro 

genotoxicity models were subsequently 

described by Takehiko Nohmi (NIHS, 

Japan). A brief overview of the COLIPA 

strategy was also given by Stefan Pfuhler 

(Procter and Gamble Prestige and 

Professional, Switzerland), highlighting 

the move toward animal-free genotoxicity 

testing and the reduction of 

false-negative data in in vitro experimentation. 

This was consistent with the 

activities at ECVAM with regard to 

genotoxicity and carcinogenicity, as 

described by Raffaella Corvi. The validation 

of the in vitro micronucleus test was 

given as an example, which demonstrated 

the ready transferability and 

reduced variability of the model. The 

method has already been accepted for 

use in the REACH system, has draft 

OECD guidelines in place, and ICH 

guidelines will shortly be available. 

The session on the Comet assay opened 

with a useful overview of the assay by 

Raymond Tice (NIEHS, USA). This assay 

detects DNA damage by changes in 

DNA motility during gel electrophor esis. 

Brian Burlinson (Hunting don Life 

Sciences, UK) showed how the Comet 

assay is superior to other assays that 

monitor DNA damage. Other speakers 

in this session considered standardisa- 

tion, protocol design, and the use of the 

Comet assay to measure multiple experimental 

endpoints. 

GM ANIMALS AND NEW 

TECHNOLOGIES 

In a session entitled Genetically 

Engineered Animals and the 3Rs: Moral 

Responsibility in the Generation of New 

Animals, the trend toward using GM 

animals to meet rapidly changing scientific 

needs was considered by Margaret 

Rose (University of New South Wales, 

Australia). Michelle Scrivens also 

presented in this session (Box 1, item 

8). Renee Gardner then presented the 

results of a general questionnaire, which 

gathered the responses of scientists and 

non-scientists to give an overview of 

opinion concerning pain as an acceptable 

endpoint. The welfare of the 

transgenic mouse was highlighted, and 

was illustrated with interesting videos of 

transgenic mouse behaviour. Housing 

and cages were discussed, and it was 

emphasised that specific modifications 

to cages were needed, and “mouse passports” 

should be more carefully 

considered in relation to each mouse 

strain. 

A session on new technologies and 

approaches included presentations that 

described the epigenetic engineering of 

histones to maintain the characteristics 

of human liver cells for cell-based 

metabolism studies (Vera Rogiers, 

Belgium). Andreas Hess (Germany) 

Michael Balls, presenting the Opening Lecture, commemorating the life and work of 

Professor William Russell 

Michael Balls, Andrew Rowan and Alan 

Goldberg 

described the results of a recent survey, 

which lists MRI, CT scanning and ultrasound 

imaging among the 30 most 

highly-rated recent medical inventions, 

and outlined how small animal imaging 

has equivalent advantages for animalbased 

research, not least because it 

permits non-invasive and repeated 

measurements in a small number of 

animals. Another presentation in this 

session described a microfluidic system, 

recently developed in Japan, which can 

be used to examine effects of 

substances on different cell types in a 

single miniaturised system (Hidenari 

Nakayama, Institute of Industrial 

Science, Japan). 

THREE RS IN EDUCATION 

AND TRAINING 

In a session on the Three Rs in education, 

David Dewhurst (University of 

Edinburgh, UK) raised the question of 

whether undergraduate pharmacology 

classes can be performed without using 

animals. A strong case was put forward 

to eliminate the need for animals, with 

the use of new technology to fulfill the 

learning objectives of pharmacological 

undergraduates. This viewpoint was 

supported by Garry Scroop (Royal 

Adelaide Hospital, Australia), who 

commented that “the teaching of life 

science is in the dark ages” and 

proposed that the way forward is the 

elimination of animal use. Alternative 

methods for veterinary teaching and 

medical training were also discussed in 

this session, by Andrew Knight (London, 

UK). 


DISCUSSING PHASING OUT OF PRIMATE 

EXPERIMENTATION 

The 6th World Congress on Alternatives and Animal Use in 

the Life Sciences, held in Tokyo, Japan, in August 2007, 

provided the ideal opportunity for FRAME and the Humane 

Society of the United States (HSUS) to hold a group 

discussion about Working Toward the Phasing Out of 

Primate Experimentation. 

The discussion group, which was 

attended by representatives from several 

animal welfare and alternatives organisations, 

the Home Office and biomedical 

science, was opened by the moderator, 

Dr Martin Stephens (HSUS). 

Michelle Hudson (FRAME) began 

proceedings by explaining that the zero 

option is a plan which could be used to 

phase out the need for primates in 

research and testing over a fixed period 

of time, until no primates are used at all. 

She discussed why it is needed, how it 

might be implemented, and highlighted 

what the benefits will be. Kathleen Conlee 

(HSUS) then elaborated further on these 

aspects, including discussing what the 

obstacles might be and how the first steps 

toward phasing out could be made. She 

was followed by Dr Paul Honess (Univer - 

sity of Oxford Veterinary Services), who 

described some of the areas where the 

phasing out of primates might be problematic 

due to the important medical 

benefits that have resulted from their use, 

including research in the neurosciences 

and on degenerative disorders and 

immunological diseases. He also identified 

some of the problems associated 

with primate research. The introductory 

presentations were rounded off by a 

description by Andrew Knight (Animal 

Consultants International) of a review of 

published literature that suggests that 

very few, if any, medical benefits have 

arisen from chimpanzee-based research 

and concludes that their remaining use 

should be phased out. The topic was then 

opened up to the floor for discussion. 

The aim of the discussion was to explore 

if, how and when the laboratory use of 

primates in biomedical research could be 

phased out. There was caution at first, 

but then, once ideas began to be 

expressed, the discussion continued in a 

constructive manner, with some interesting 

points being raised. The main 

topics and important points that arose 

from the discussion were as follows: 

ACCEPTANCE OF THE 

PHASING-OUT CONCEPT 

The biomedical community are reluctant 

to accept that phasing out laboratory 

primates entirely will ever be possible. 

They argue that primate experiments 

are always the last resort, and that they 

are stringently reviewed before they are 

allowed to proceed. A minority of 

scientists believe that they have a right 

to perform such research, and that 

there will only need to be one significant 

breakthrough in terms of curing 

human disease to justify the majority of 

the primate experiments. Other scientists 

insist that they do not want to use 

primates in their work, but that the 

expectations of regulators demand it. 

An attendee commented that alternatives 

to the primate are usually 

discovered incidentally, because the 

major funding agencies are all 

medically-based and will not directly 

fund studies aimed at finding alternative 

methods for performing research 

related to human diseases. It was 

suggested that something should be put 

in place, such as a new European Union 

Directive, in order to drive a change in 

attitude toward the need for primate 

use, in much the same way that amendments 

to the European Union 

Cosmetics Directive, aimed at banning 

animal testing on cosmetic products 

and their ingredients, has forced 

companies and scientists to devise and 

develop alternative methods. 

Poster presented at the 6th World Congress, advertising the discussion group and 

promoting the zero option 


PROSPECTS FOR PHASING 

OUT 

Despite the obvious reluctance from 

biomedical scientists to accept the 

phasing out of primates, there was positive 

dialogue regarding the possibility in 

some fields of research. In particular, 

one attendee felt that the first area in 

which it would be relatively easy to 

replace primate experiments, would be 

fundamental neuroscience. As non-invasive 

imaging technologies continue to 

improve over the next 10–15 years, it 

will be possible to get increasingly accurate 

and precise information from 

studies on human volunteers, which will 

mean that invasive experiments on 

primates will become more and more 

irrelevant. Therefore, scientists should 

be encouraged to move toward these 

non-invasive studies, to drive the technological 

developments required. 

POSSIBLE MECHANISMS TO 

START THE PHASING OUT 

PROCESS 

The group discussed several possibilities 

for making the first steps toward the 

zero option. To drive change, it would 

be important for alternatives organisations 

and scientists that wish to stop the 

use of primates to lobby the regulatory 

agencies, such as the Food and Drugs 

Administration (FDA) in the USA, to 

encourage them to change their expectations 

and regulations regarding the need 

for primate data. In addition, the 

harmonisation of regulatory toxicology 

practices could be a target for gaining 

international collaboration on phasing 

out primate use. It was also suggested 

that increasing the critical scrutiny of 

primate experiments would have a direct 

effect on reducing them. This might be 

achieved via the education of ethics 

committees about failures to meet promised 

clinical outcomes, so that the real 

benefits of primate research are often 

much less than predicted, or through 

systematic reviews of each field of 

research, highlighting why primates are 

used, what alternatives would be needed 

to replace them, and what a sensible 

timeline for developing the alternatives 

would be. 

Continuing to increase the quality of 

best practice with regard to the care 

and maintenance of laboratory primates 

may indirectly reduce the demand for 

primate research. As requirements 

become more stringent for both 

housing conditions and animal health, it 

may not be economically viable for 

scientists to conduct some forms of 

primate research. During the discussion, 

it emerged that the USA does not 

regulate the use of wild-caught 

primates, and scientists will more than 

likely go for the cheapest primates available. 

As 80–90% of primate imports 

are by the USA, pushing for tighter 

regulations regarding the use of 

purpose bred, disease-free animals 

from designated centres may again limit 

some forms of primate use. Educating 

the American public and scientists 

about the problems associated with the 

capture, transportation and use of wild- 

caught animals should be a priority. It 

was also suggested that there should 

always be an under-supply of laboratory 

primates, to ensure that only high 

priority work could be pursued. 

CONCLUSIONS 

This small, but well-informed, discussion 

group highlighted some important 

barriers to the phasing out strategy, and 

gave some insights into how to make 

the first steps toward achieving, either 

directly or indirectly, this important 

goal. It also illustrated that a constructive 

and engaging dialogue can exist 

between those who conduct primate 

research and those who strongly 

oppose it — something which will be 

essential, if an end to experiments on 

non-human primates is to be accomplished. 

FRAME REDUCTION 

STEERING COMMITTEE 

UPDATE 

A FRAME Reduction Steering 

Committee (FRSC) poster entitled 

Reducing Animal Use Through Raw 

Data Availability was presented by 

Michelle Hudson at the 6th World 

Congress on Alternatives and Animal 

Use in the Life Sciences, held in Tokyo, 

Japan, in August 2007. 

The poster described the Committee’s 

proposal that all scientific journals 

should require authors to make available 

the raw data from the 

investigations presented in the papers 

submitted for publication. It included a 

set of guidelines for editors and 

authors, outlined by the Committee, 

to facilitate making the availability of 

data possible, and the advantages of 

such a scheme were highlighted. 

The Committee’s Working Party on 

Implementing Reduction in Practice is 

continuing its work on this proposal, 

with the aim of publishing the guidelines 

alongside a commentary 

highlighting how the availability of 

raw data may lead to a reduction in 

the numbers of animals needed for 

scientific experiments and an 

improvement in the analysis and 

quality of the scientific outcomes. 


US FUNDING AGENCY TO PERMANENTLY STOP 

BREEDING CHIMPANZEES FOR RESEARCH 

The world’s largest funder of 

chimpanzee biomedical research, 

the US National Institutes of 

Health (NIH), has announced 

that it will no longer provide 

funding for breeding laboratory 

chimpanzees. 1 

The NIH’s National Center for Research 

Resources (NCRR) implemented a 

breeding moratorium in 1995, largely as 

a result of the failure of chimpanzee 

models of AIDS to produce any clinically 

useful outcomes. Barbara Alving, 

Director of the NCRR, revealed that they 

are now making this long-standing moratorium 

permanent. This move has been 

hailed as a success by the Humane 

Society of the United States (HSUS), 

whose campaign against the use of chimpanzees 

in biomedical research included 

nearly 22,000 letters to the NCRR. 

However, the NCRR denies that this had 

any effect, stating that the decision was 

purely financial, as each of the 650 

animals supported cost $500,000 over 

a lifetime. Without NIH support, the 

current population will steadily be 

retired or will die within the next 30 

years. 

Researchers who do studies with the 

chimpanzees have denounced the move 

as short-sighted, claiming that maintaining 

a large, genetically diverse 

population of chimpanzees could help 

answer fundamental biomedical questions 

about diseases such as Alzheimer’s 

disease (AD) and hepatitis B and C. This 

is despite the fact that chimpanzees have 

never been used in AD research in the 

past, and there is no indication that they 

will be needed in the future. The chimpanzee 

is also not the only means by 

which to study hepatitis, as both transgenic 

mice 2 and human immune 

response measurements 3 are now being 

used in the search for an effective 

vaccine. As well as the scientific arguments 

against the moratorium, the critics 

have also claimed that the breeding 

programme serves as an insurance 

policy, should the chimpanzee become 

extinct. This is indeed clutching at 

straws, since investment in dedicated 

breeding and release programmes and 

habitat conservation would certainly be 

more ethical and more successful in 

preventing the threat of extinction in the 

first place. 

However, the existing NIH chimpanzees 

can still be used for research until they are 

retired, and 600–650 other chimpanzees 

are still owned by privately-funded 

researchers not affected by NIH policies 

and decisions. The HSUS therefore 

continues, through its Chimps Deserve 

Better campaign, to seek an end to the 

use of any chimpanzees in invasive 

biomedical research and testing, and to 

retire the chimpanzees currently in laboratories 

to permanent and appropriate 

sanctuaries, by: influencing policymakers; 

gaining support from the public and 

members of the scientific community; 

scientifically challenging the arguments 

advocating harmful chimpanzee research; 

and preventing the breeding of additional 

chimpanzees and their introduction into 

the research system. Further information 

on the campaign can be found at http://www. 

hsus.org/animals_in_research/chimps_deserve_better/ 

Whether primarily financial or not, this 

decision by the NIH should be 

welcomed, and it is hoped it will set a 

precedent to encourage other funding 

agencies around the world to follow suit, 

and even to consider expanding such a 

moratorium to other non-human 

primate species, where the scientific 

justification for their continued use is 

weak or outdated. 

REFERENCES: 

1 Cohen, J. (2007). NIH to end chimp 

breeding for research. Science, New York 

316, 1265. 

2 Engler, O.B., Schwendener, R.A., Dai, W- 

J., Wölk, B., Pichler, W., Moradpour, D., 

Brunner, T. & Cerny, A. (2004). A liposomal 

peptide vaccine inducing CD8 + T 

cells in HLA-A2.1 transgenic mice, which 

recognise human cells encoding hepatitis 

C virus (HCV) proteins. Vaccine 23, 58– 

68. 

3 Houghton, M. & Abrignani, S. (2005). 

Prospects for a vaccine against the hepatitis 

C virus. Nature, London 436, 

961–966. 

ETHICAL STEM CELLS AVAILABLE 

IN THE NEAR FUTURE? 

According to Shinya Yamanaka, Japan’s leading genetics researcher, skin cells from laboratory 

mice have been manipulated back to their embryonic state. In an interview with 

The Times, he said that, if the research progresses as he hopes, the ethical problems 

of using embryonic stem cell research would disappear. Professor Yamanaka, who 

dislikes the use of human embryos as a source of stem cells, said, “It is hard to predict 

how the science will develop, but I think we could produce a basic prototype-induced 

stem cell made from a human adult cell within six months to a year”. He added that 

“Within two to three years, we may be able to create a stem cell that is indistinguishable 

from one taken from an embryo”. Professor Yamanaka explained that his technique 

for inducing stem cells does raise some safety problems that need to be eradicated 

before the “ethical stem cell” could be considered fit for use in humans, as one of the 

four genes he manipulates to create the transformation is a “cancer switch” for healthy 

cells. 

Further information is available at: http://www. timesonline.co.uk/tol/news/uk/science/article2080314.ece 


NEW MINISTER AT THE HOME OFFICE 

Meg Hillier, MP for Hackney South and 

Shoreditch since May 2005, has been 

appointed Parliamentary Under- 

Secretary of State at the Home Office, 

where her duties will include responsibility 

for the Animal (Scientific 

Pro cedures) Act 1986. A journalist 

with wide experience in London local 

politics, she read PPE at Oxford. One 

of her first public statements with 

respect to animal experimentation was 

to say, in the face of a 4% increase in 

animal procedures in the UK in 2006, 1 

that “Where animal research is the 

only option, we will continue to ensure 

that the balance between animal 

welfare and scientific advancement is 

maintained”. 

An immediate challenge to Meg Hillier’s 

sincerity will be dealing with the criticism 

that, despite having been involved in 

revising the appendix to the Council of 

Europe Convention ETS 123 which deals 

with the housing of laboratory animals, 

the Home Office has not announced a 

revision of its own Code of Practice to 

meet these new standards, nor taken 

measures to ensure that British laboratories 

will be expected to comply with 

them. These shortcomings were recently 

highlighted by the Dr Hadwen Trust, a 

charity which funds non-animal research 

(for further information, go to: http://www. 

drhadwentrust.org/news/exposed-britains-animal-labs-fail-tomeet-new-eu-standards). 

Of particular concern is 

the likelihood that non-human primates in 

British laboratories will be housed in cages 

up to eight times smaller than the new 

Council of Europe recommendations. 

Substantial improvements to the housing 

of cats, gerbils, guinea-pigs and rabbits 

are also recommended. 

The revised appendix says that “If existing 

facilities or equipment do not conform to 

the present guidelines, these should be 

altered or replaced within a reasonable 

period of time, having regard to animal 

welfare priorities and financial and practical 

concerns”. It is to be hoped that, 

before Ms Hillier allows herself to be 

persuaded by her civil servants to say, yet 

again, on behalf of the Government, that 

Britain has the highest standards in the 

world with regard to the management of 

Meg Hillier MP 

laboratory animal experimentation, she 

will insist that they set up an acceptable 

time-table for making all the laboratories 

under her jurisdiction comply with the 

new European standards. 

The new Minister was presented with yet 

another challenge on 27 July 2007, when 

Mr Justice Mitting ruled in the High Court 

that the Home Office had acted unlawfully 

according to the Animals (Scientific 

Procedures) Act 1986, by licensing 

experiments on marmoset brains at the 

University of Cambridge as likely to cause 

moderate, rather than substantial, 

suffering. 2,3 He said that the work had 

been licensed on the basis of expert 

advice that understated the extent of 

“pain, suffering, distress or lasting harm” 

that could be caused to the animals. 

The judicial review had been granted to 

the British Union for the Abolition of 

Vivisection in an earlier judgement, after 

the organisation had obtained video and 

documentary evidence during an undercover 

investigation at the university during 

2000–2001. In the earlier judgement, the 

BUAV were given a Costs Protection 

Order, so that the case could be brought 

in the public interest, without the risk of 

having to pay the Home Office’s defence 

costs, estimated at £150,000, if the 

action proved unsuccessful. 

Concern has been expressed repeatedly, 

and over many years, about how nonhuman 

primates (NHPs) are treated in 

British neuroscience laboratories. For 

example, attention was drawn to the 

problem in the RSPCA/FRAME survey on 

the use of NHPs before the 1986 Act 

came into force, and more recently in the 

FRAME submission to the Weatherall 

NHP study. 4,5 We had hoped that the new 

law would improve the situation. However, 

perhaps because there is now a requirement 

that procedures in NHPs involving 

substantial severity must be referred to 

the Animal Procedures Committee, it was 

administratively convenient for the Home 

Office, and very good news for the 

researchers involved, when it was decided 

that most of this kind of work would be 

classified as of moderate severity. That 

this has been allowed to apply to rhesus 

monkeys strapped in primate chairs with 

head restraint and electrodes in their 

brains, for many hours per day for several 

weeks over many months, defies belief, in 

a country which claims to have the 

strictest regulation of animal experimentation 

in the world. 

Mr Justice Mitting granted the Govern - 

ment lawyers leave to appeal against the 

verdict. However, even if any subsequent 

appeal is successful, the BUAV have 

undoubtedly won a huge moral victory. 

Let us all hope that the Minister will 

recognise this truth, and will instruct her 

officials to take the appropriate action. 

A more-detailed review of this affair will 

appear in a forthcoming issue of ATLA. 

REFERENCES: 

1 Anon. (2007). Statistics of Scientific 

Procedures on Living Animals: Great 

Britain 2006. Cm7153, 49pp. (plus 

supplements). London, UK: The 

Stationery Office. Available at: 

http://www.homeoffice.gov.uk/rds/scientific1.html 

2 Anon. (2007). Review ordered on animal 

test labels. BBC News, 27.07.07. Avail - 

able at: http://news.bbc.co.uk/1/hi/sci/tech/6919505.stm 

3 Henderson, M. (2007). Ministers must 

review severity of animals tests. 

Timesonline, 27.07.07. Available at: http:// 

www.timesonline.co.uk/tol/news/uk/science/article2154728.ece 

4 Hampson, J., Southee, J., Howell, D. & 

Balls, M. (1990). An RSPCA/FRAME 

survey of the use of non-human primates 

as laboratory animals in Great Britain, 

1984–1988. ATLA 17, 335–400. 

5 Bhogal, N., Hudson, M., Balls, M. & 

Combes, R.D. (2005). The use of nonhuman 

primates in biological and medical 

research: Evidence submitted by FRAME 

to the Academy of Medical Sciences/ 

Medical Research Council/Royal Society/ 

Wellcome Trust Working Group. ATLA 

33, 519–527. 


PUTTING REPLACEMENT FIRST 

FRAME’s Patron, Lord Soulsby of Swaffham Prior, hosted a reception in 

the Cholmondeley Room of the House of Lords on 14 June 2007, at 

which FRAME’s new initiative, Putting Replacement First, was launched. 

The reception, attended by about 60 invited guests, was generously sponsored 

by Marks & Spencer and Waitrose. 

The aim of the Putting Replacement First 

initiative (outlined in detail in FRAME 

News 61) is to encourage greater investment 

in a vigorous and concerted effort 

to facilitate the development and use of 

modern and advanced methods in cell 

and molecular biology, cell and tissue 

Michael Balls with Lord Soulsby 

culture, computational modelling, ethical 

clinical studies and epidemiology. It is an 

urgent necessity that the use of animals 

in medical research and safety testing is 

progressively replaced by scientifically 

sound, better focused and more-relevant 

strategies for curing many human 

diseases and reducing the risk of others. 

This is the only way of avoiding the 

inescapable problems which stem from 

the fact that, since humans and animals 

are different, so their diseases are 

different, as are their responses to 

chemicals, medicines and products of 

many kinds. 

A FRAME Replacement Committee is 

being formed in the light of the new initiative, 

to strengthen the Charity’s 

commitment to achieving the most difficult 

of the Three Rs. The new Com mittee 

will work alongside other FRAME scientific 

committees, the FRAME Reduction 

Committee and the FRAME Toxicity 

Committee, and FRAME will continue its 

active involvement in the Focus on 

Alternatives group, and will also cooperate, 

wherever possible, with other 

organisations, such as the National 

Centre for the Three Rs and the European 

Centre for the Validation of Alternative 

Methods (ECVAM), in promoting the 

Three Rs concept as a whole. 

Research in the FRAME office at Russell 

& Burch House, led by Professor Robert 

Combes and Dr Nirmala Bhogal, will 

focus on the development of strategies 

for integrating the emerging non-animal 

technologies into intelligent approaches 

to efficacy and safety/toxicity testing for 

chemicals and drugs and other products. 

Meanwhile, the remodelled and 

expanded FRAME Alternatives Labora - 

tory in the University of Nottingham 

Medical School, will move into new 

research areas, under the direction Dr 

Andrew Bennett. 

On behalf of FRAME at the launch 

reception, Michael Balls, Chairman of 

the FRAME Trustees, said that, since the 

introduction of the Animals (Scientific 

Procedures) Act 1986, there had been 

insufficient investment in the targeted 

development and application of replacement 

alternative methods. He explained 

that the legislation requires that, when 

such methods exist, they must be used, 

but it does not stipulate that effort 

Ed Balls MP 

David Amess MP 

should be put into developing them in 

the first place. Meanwhile, he added, the 

testing continues to rely on the use of 

traditional animal procedures, often of 

limited value and doubtful reliability, and 

it is increasingly claimed that the use of 

genetically altered animals will provide 

opportunities for the effective treatment 

and eventual elimination of all the 

diseases which continue to compromise 

the length and quality of human life. 

Professor Balls stated that, in the 

opinion of William Russell and Rex 

Burch, who initially spelled out the Three 

Rs principles, Refinement is never 

enough, and we should always seek 

further Reduction and, if possible, 

Replacement — Replacement is always a 

satisfactory answer. In conclusion, and 

based on this fundamental statement by 

Russell and Burch, he invited all those 

who seek reliable ways forward that take 

full account of the interests and welfare 

of both humans and animals, to work 

with FRAME to seize the exciting opportunities 

available, for reaping benefits of 

every kind — scientific, economic and 

humanitarian. 

This announcement of the purpose of 

the FRAME initiative was welcomed in 

speeches by David Amess MP, Chairman 

of the All-Party Parliamentary FRAME 

Group, Ed Balls MP, at that time 

Economic Secretary to the Treasury, and 

Yvette Cooper MP, Minister of State in 

the Department of Communities and 

Local Government. 


RECENT FRAME PUBLICATIONS 

Balls, M. (2007). Alternatives to animal 

experiments: Time to focus on 

Replacement. AATEX 12, 145–154. 

Balls, M. (2007). Time for real action 

on chimpanzees and other Hominids. 

ATLA 35, 191–195. 

Balls, M. & Combes, R. (2007). Putting 

Replacement first. ATLA 35, 297–298. 

Bhogal, N. (2007). Testing new pharmaceuticals 

after the 2006 UK drug trial 

tragedy. European Journal of Hospital 

Pharmacy Practice 13, 22–24. 

Bhogal, N. (2007). After TGN1412: 

the CHMP draft guidelines. Hospital 

Pharmacy Europe 33, 43–44. 

Combes, R. (2007). Why ‘suitable’ in 

vitro methods, as defined in the final EU 

REACH legislation, are an inappropriate 

basis for risk assessment. ATLA 35, 

289–293. 

Combes, R. (2007). Developing, validating 

and using test batteries and tiered 

(hierarchical) testing schemes. ATLA 35, 

375–378. 

Combes, R. & Balls, M. (2007). 

Comments on the sub-group reports of 

the EU Technical Expert Working Group 

on the revision of Directive 

86/609/EEC on the Protection of 

Animals Used for Experimental and 

Other Scientific Purposes. ATLA 35, 

155–175. 

Combes, R., Grindon, C., Cronin, 

M.T.D., Roberts, D.W. & Garrod, J. 

(2007). Proposed integrated decisiontree 

testing strategies for mutagenicity 

and carcinogenicity in relation to the EU 

REACH legislation. ATLA 35, 267– 

287. 

Grindon, C. (2007). The new EU 

REACH Regulation has finally been 

adopted: Is this the end of the campaign 

trail… or just the beginning? ATLA 35, 

239–242. 

Also since the last FRAME News, a new addition to the Focus on FRAME 

educational leaflet range has been produced. Entitled Risk Assessment in the 

Safety Testing of 

Chemicals and 

Products, this latest 

leaflet describes what 

is meant by risk, how 

it can be measured, 

and the procedures 

involved in undertaking 

a risk 

assessment to assess 

the safety of a new 

chemical or product 

(e.g. a cosmetic, food 

additive, household 

product). 

The leaflet is available 

from the FRAME 

Office, and is also 

accessible online via 

the E-learning pages 

of the FRAME website 

(www.frame.org.uk). 

NEW FRAME WEBSITE GOES LIVE 

The new, improved version of the 

FRAME website is now available at 

www.frame.org.uk, allowing users to: 

— find information on FRAME’s 

research activities 

— download issues of FRAME News 

from the archive 

— access a wide range of educational 

material relating to the Three Rs and 

alternatives to animals 

— make donations 

— download FRAME Annual Reports 

and FRAME Position Statements 

— search the ATLA journal for papers 

by subject of interest 

Subscribers to the ATLA journal may 

also, by using their given password, gain 

online access to current and archive 

issues of the journal. 


© Crown 2007 

PRESUMED 

CONSENT 

Organ donation has hit the headlines 

again, as England’s chief medical officer, 

Sir Liam Donaldson, has suggested that it 

should be assumed that everyone is a 

potential organ donor on their death, 

unless they expressly request not to be. 

This idea of ‘presumed consent’ is not 

new, as many countries, including Austria, 

Belgium, Denmark, Finland, France, Italy, 

Norway, Singapore, Spain and Sweden, 

already have versions of such a scheme in 

force. 

Sir Liam Donaldson 

Although a system of presumed consent 

was rejected by Parliament when the 

Human Tissue Act 2004 was passed, 

Liberal Democrat MP, Dr Evan Harris — 

who chairs Parliament’s All-Party Kidney 

Group — says that it was time for the 

Government to back a change in the law 

to introduce presumed consent. However, 

this would be opposed by the Con - 

servatives, and the Shadow Health 

Secretary, Andrew Lansley MP, has said 

that “The state does not own our bodies 

or have a right to take organs after death”. 

Presumed consent would almost inevitably 

result in a more organs becoming available 

for scientific research, due to their 

unsuitability for transplantation. However, 

it does raise questions about who owns, 

or has the right to take, our organs after 

death. 


http://news.bbc.co.uk/1/hi/health/6902519.stm 

THREE-DIMENSIONAL MODEL 

OF HUMAN BREAST CANCER 

An in vitro model, which replicates the 

early stages of a specific type of breast 

cancer — ductal carcinoma in situ, has 

been developed by researchers at the 

Institute of Cancer at Queen Mary, 

University of London, London, UK. The 

research project was funded by the Dr 

Hadwen Trust, a charity that funds nonanimal 

medical research. By using a 

collagen gel to form three-dimensional 

structures, they were able to permit cells 

from normal and cancerous breast tissue 

to create structures similar to those 

According to a report in The Financial 

Times, 1 Brian Cass, Managing Director of 

Huntingdon Life Sciences (HLS), has 

urged the financial services industry to 

shrug off fear of animal rights extremists 

and support his company in the development 

of new medicines. He also said that 

he regretted the reluctance of many pharmaceutical 

companies to say publicly that 

what is done for them by HLS is essential. 

The background to these comments is 

that 10 people accused of conspiracy to 

blackmail are shortly due to be appear in 

Birmingham Crown Court, as a result of a 

long-running police investigation, 

Operation Achilles, into threats against 

HLS’ suppliers. 2 The court actions will be 

under the Serious and Organised Crime 

and Police Act 2005, introduced when 

Charles Clarke was Home Secretary, and 

probably result from the activities of the 

National Extremism Tactical Coordination 

Unit. 

What is seen as progress against 

extremism has been welcomed by Aisling 

Burnand, Head of the BioIndustry 

Association, which represents British 

biotechnology companies. However, 

figures from the Association of the British 

Pharmaceutical Industry (ABPI) show that, 

since 2004, there have been 113 capitulations 

of suppliers and other companies 

to intimidation by extremists, but there 

has been a recent decline, with 39 capitu- 

found in vivo. It is hoped that fundamental 

knowledge of direct relevance to the development 

of human cancer will be 

forthcoming, leading to treatments which 

have not depended on the use of animal 

models of doubtful relevance. 


http://news.bbc.co.uk/go/pr/fr/-/1/hi/health/6636373.stm 

CONFRONTING ANIMAL 

RIGHTS ACTIVISTS 

lations in 2006, and only two in the first 

half of 2007. 

In an editorial, 3 The Financial Times has 

called for more effort against bullying by 

extremists, including strengthened international 

cooperation. It also called on 

drug companies to be more courageous 

in openly stating that contract laboratories 

play a vital role in the development of 

their new products. 

The animal-use institutions and industries 

have invested heavily in recent years, in 

trying to persuade the general public that 

all they do is essential and unavoidable. 

However, the greater threat to HLS may be 

the increasing evidence that animal testing 

is not a sufficiently reliable way of evaluating 

the efficacy and safety of medicines 

intended for human use. This particularly 

applies to the products of the companies 

which employ Aisling Burnand as their 

representative. 

REFERENCES: 

1 Jack, A. (2007). Shrug off fear of animal 

activists, says drugs research chief. The 

Financial Times, 17 September 2007. 

2 Jack, A. (2007). Tactics to combat 

animal rights extremism. The Financial 

Times, 16 September 2007. 

3 Anon. (2007). Confront animal rights 

fanatics. The Financial Times, 17 

September 2007. 


VETTING FOR 

RESEARCHERS 

The European Commission has 

released a widely-anticipated 

Green Paper on countering 

bioterrorism in universities and 

research facilities. The counterterrorism 

plans put forward by 

Brussels include: an EU system 

of security clearance for 

researchers to combat infiltration 

by bio-terrorists; 

institutions where research takes 

place being vetted according to 

strict EU standards, before being 

allowed to carry out sensitive 

experiments; compulsory ethics 

lessons for science undergraduates, 

to raise awareness of the 

ways in which their work could 

be exploited by terrorists; and, 

most controversially, restricting 

the publication of sensitive 

research findings. The last 

suggestion is likely to provoke 

most controversy, as it raises 

fears of censorship, but Franco 

Frattini, the Justice 

Commissioner, said that, “If we 

leave it too late, it is absolutely 

useless”. He pointed out that, 

“We are aware that terrorists 

are exploiting all the potentials 

to attack democratic countries”. 

Contents 

Official opening of the new FRAME Alternatives Laboratory 1 

The Last Moral Frontier — An Alternative View 5 

Dorothy Hegarty Award Winners 2006 6 

Developing and Using Tissue Culture Models of Human Toxicity 6 

Generic Biopharmaceuticals and the Rising Demand for 

Animal Tests 7 

Flawed Animal Testing 8 

Animal Tests Fail to Detect the Risks Posed by Some 

Medicines 8 

Criticism of EMEA Proposals 9 

Animal Experiments Reach a 15-year High 10 

FRAME at the Sixth World Congress on Alternatives and 

Animal Use in the Life Sciences 12 

Discussing Phasing out of Primate Experimentation 17 

FRAME Reduction Steering Committee Update 18 

US Funding Agency to Permanently Stop Breeding 

Chimpanzees for Research 19 

Ethical Stem Cells Available in the Near Future? 19 

New Minister at the Home Office 20 

Putting Replacement First 21 

Recent FRAME Publications 22 

New FRAME Website Goes Live 22 

Presumed Consent 23 

Three-dimensional Model of Human Breast Cancer 23 

Confronting Animal Rights Activists 23 

Vetting for Researchers 24 

Meanwhile, in the UK, a three-year review 

of voluntary arrangements for vetting 

students is in the process of being 

completed by the Foreign Office and the 

Cabinet Office. All non-EU postgraduate 

research students in certain sensitive areas 

will be covered by these arrangements. “It 

will require students who fall into the 

category above to seek and obtain ‘clearance’ 

before they can apply for a visa or 

entry clearance to come to the UK, or to 

renew a visa if they are already in the 

UK,” said a spokesman. 

Further information is available at: http://www. 

timesonline.co.uk/tol/news/world/europe/article2056570.ece 

Published by FRAME, Russell & Burch House, 96–98 North Sherwood Street, Nottingham NG1 4EE, UK 

Tel: +44 0115 958 4740 Fax: +44 0115 950 3570 e-mail: frame@frame.org.uk Website: http://www.frame.org.uk 

Opinions expressed in FRAME News do not necessarily reflect the views of the FRAME Trustees, Staff or Editor. ISSN 0268-4306 

©FRAME. Registered Charity Number 259464 Design by 4 Sheets Design & Print Ltd. Tel: +44 0115 910 1140.

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