Awards for former FRAME personnel Training school success
www.frame.org.uk
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Testing drugs on dogs
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Poached ivory an ethical question
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Promoting nonanimal laboratory methods through better science
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Issue 72, Easter 2014
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FRAME News
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Contents
From the Editor
3. GM monkeys: FRAME’s perspective 4. Support for FRAME 5. Should seized ivory be used for science? 6. Human studies 7. Friends of FRAME 8. Science news in brief 9. FRAME giftware 10. Order form 11. Drug testing on dogs: the FRAME annual lecture 12. FRAME successes 13. Patenting biotechnology 14. News from the FAL 15. Awards for FRAME personnel 16. Training schools
FRAME is often asked why it does not advocate an immediate end to animal experiments, unlike some organisations. FRAME takes a strictly scientific approach to the subject of laboratory animals.
FRAME News 72, Easter 2014 Published by: Fund for the Replacement of Animals in Medical Experiments Russell & Burch House 96-98 North Sherwood Street Nottingham NG1 4EE Registered charity number 259464 www.frame.org.uk Editor: Anne Jeffery E: anne@frame.org.uk Alternatives to Laboratory Animals (ATLA) www.atla.org.uk Perspectives in Laboratory Animal Science (PiLAS) www.pilas.org.uk 2 | FRAME News 72, Easter 2014
We are against their use because many results obtained from them do not accurately predict anything about human reactions to drugs or any other substances. This fact was vividly expressed in the latest FRAME Annual Lecture, which reported on the effectiveness of drug tests using dogs. We continue to campaign for the use of better science: to promote more relevant research using human-based methods; to educate researchers about ways to use fewer animals; to teach the next generation of scientists; and to spread information about alternatives to laboratory animals through the press and journals. For more than 40 years FRAME has been at the centre of work to reduce, refine and ultimately replace the use of animals in laboratories. Thank you for your continued support.
- Anne Jeffery (FRAME News Editor)
FRAME response to creation of GM monkeys FRAME has responded to a report of the creation of genetically modified monkeys that was being hailed as a potential breakthrough in the search for treatments for Alzheimer’s and Parkinson’s diseases. FRAME has always been concerned about the use of GM animals because their production can result in a huge number of animals that do not have the necessary genetic alteration required. A large proportion of the resulting animals are therefore bred and killed, without serving any other purpose. Use of non-human primates is also worrying because they have a level of sentience and social awareness that make the suffering from experimentation and captivity very severe. The original article was published at: Niu et al., Generation of Gene-Modified Cynomolgus Monkey via Cas9/RNA-Mediated Gene Targeting in One-Cell Embryos, Cell (2014).
The Statement Recent developments in genetic engineering techniques have led to the emergence of new experimental techniques to genetically modify animals. The increase in the use of genetically modified organisms is due at least in part to the introduction of these new techniques. These new methods make genetic modification of a wide range of species both much easier and crucially more affordable to create a transgenic mouse model can now cost as little as £5000 as compared to £50,000 a couple of years ago. The fact that technology is now accessible and cheap does not necessarily mean that the creation of greater numbers of transgenic animals is either good for science or human disease research. Animal models, in particular the widely used rat and mouse models are often very poor in terms of their similarity to humans. Human disease and responses to injury are often quite different to those seen in animals. The current paper describes the monkey as an important species in developing therapeutic strategies and that further research using monkeys has been hampered by the inability to genetically modify them. However, even though monkeys are more closely related to humans than many other laboratory animals they are still far from being an ideal model. For research to be relevant and useful for prediction of human adverse reactions, animals should not be stressed. Stress is known to cause hormonal changes that will affect responses to test drugs or behavioural studies. Monkeys are communal animals, like humans, and when held in isolation show the same behavioural differences. Thus to be of any value and to not make erroneous predictions it is vital that monkeys must not be isolated, because it would render the results potentially invalid. Drugs that have been tested on monkeys for toxicity and efficacy have been found to either be toxic or ineffective in patients. Whilst the technological advances in genetic engineering are to be both applauded and admired, their subsequent use to produce genetically modified monkeys is questionable at best. FRAME would call for more funding to be used to produce model systems based on human tissues and cells rather than try to develop more sophisticated laboratory animal species. If you’re working on human disease, then it is necessary to use human-derived material to predict human responses. FRAME News 72, Easter 2014 | 3
CORPORATE SUPPORT FRAME receives no money from local or central government and relies almost entirely on grants and donations from individuals and companies to carry out its vital work. Corporate support is particularly important because FRAME needs a reliable income to ensure the future of its high quality research. We are grateful to all our supporters and, in particular, to those who continue to help over many years.
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The Kennel Club has supported FRAME’s work for more than 10 years and provides the venue for our Annual Lecture each year. Here Public Affairs Officer Denisa Deli explains why the Club maintains its support. The Kennel Club is in principle against the use of animals for routine testing purposes, unless there is no alternative, and is keen to work towards improving animal welfare by increasing an awareness of human responsibility regarding animals and helping fund research into alternative testing methods. The Kennel Club strongly supports the principle of the Three Rs – replacement, reduction and refinement as they are the guiding principles underpinning the humane use of animals in scientific research. The use of animals in scientific research is a contentious issue and is the topic of much debate, frequently focused on whether or not it is ethical and necessary to use animals for research and how much suffering is associated with their use. Consequently, the public have genuine concerns, particularly over reports that might indicate a disregard for the animals’ welfare in the conditions under which animals are kept at research establishments and the methods used to kill them. The Kennel Club has a responsibility to do its best to ensure that the highest standards of animal welfare are maintained and that every effort is made to reduce the numbers of animals used to the absolute minimum. For this reason, the Kennel Club supports the work of FRAME through regular annual donations to support projects that aim to reduce the number of dogs being used in experiments. In addition, the Kennel Club Charitable Trust has funded FRAME to carry out a research project on the use of dogs in laboratories, with the aim of developing a scientific strategy to minimise, and eventually eliminate, the use of dogs in biomedical research and testing.
International consumer products group P Z Cussons recently increased its level of support for FRAME from one star to four star, with an associated increase in its donation towards research costs. FRAME now receives £10,000 a year from the company. Eileen Donnelly, Director of Sustainability and Communications, said: “PZ Cussons has supported FRAME for over 15 years and we fully endorse their campaign for better science through more relevant, and more valid, non-animal testing systems. Their advances in alternatives are to the benefit of the cosmetics and household products industry as a whole, promoting safety evaluations and future innovations in these sectors using human-based models.”
Destroying illegal ivory: is it a wasted resource? There has been an international ban on the trade in ivory since 1989, but hundreds of elephants are still killed by poachers. Last year saw record levels of ivory seizures around the world. Authorities are unsure whether the new levels imply an increase in poaching, or better law enforcement. Either way, a huge number of elephant tusks are being collected and most will be burned. A summit meeting in Botswana reported 18 seizures in 2013 that were classified as large: in excess of 500 kilos. The total was more than 41.5 tonnes. China recently crushed 6.2 tonnes of illegal ivory in a public demonstration of its stand against poached tusks. It is estimated that the figurines, sculptures and ornaments represented about 700 slaughtered elephants. There are ways in which ivory could be used in scientific and medical research, for example to replace bone or other animal tissues as a substrate when growing cells. So is it right that the seized tusks should be destroyed, or should they be recycled in the pursuit of science?
Destroy
The ivory market is associated with organised crime so it is important to do as much as possible to hinder the trade. Reusing ivory would potentially increase demand and, as a consequence, its value would also increase, providing a further incentive for poaching. Keeping ivory, even in a museum or a secure centre, risks its return to the illegal market and so there is a possibility that it would still eventually end up as ornaments or jewellery. Destroying it reinforces the message that poaching will not be tolerated. Ivory is a finite, non-renewable resource and nothing should be done to encourage even a legal trade in it. Elephant populations are under threat from more than just poaching. Increasing human populations and the demand for more land are destroying its habitat. Even though it makes a good substitute in bone models, its use would delay the search for a non-animal alternative. While there is a supply of any animal substance that works, researchers are less likely to look for other models.
Re-use
Ivory provides a good model for bone and is already used in some laboratories who are supplied from customs seizures. It has a relatively large cross section and so has some advantages over animal bones, because it provides a larger working area. As an alternative it could reduce the demand for bone. It is also possible to test ivory for the health of the animal it was taken from, and so provide a measure of the health of the population in general: information that could support conservation efforts. As well as seized contraband, it would be possible to source ivory ethically from zoos, or deaths in the wild. It could be dyed at source to make it useless for the ornament trade, but would still be helpful in scientific research. Crushing ivory does not actually answer the ethical question because there is still the problem of what to do with the remains. Even crushed, it might be possible to make use of the material. FRAME News 72, Easter 2014 | 5
Human studies FRAME has long advocated the use of human volunteers and tissues to obtain more relevant results in the field of human medical research. The FRAME Alternatives Laboratory (FAL) works closely with Nottingham University Hospitals NHS Trust to obtain samples, with full ethical approval and under licence from the Human Tissue Authority, in order to construct its in vitro models of human organs.
Sound treatments A report in Lancet Oncology (vol 13) has described the use of High Intensity Focused Ultrasound (HIFU) to treat prostate cancer. When high intensity ultrasound is focused onto tissue it generates heat that will burn away small areas at the point of focus. That means patients do not have to undergo surgery, because the sounds focus through the outer tissues. A trial at University College London Hospital involving 40 men has shown that using HIFU helps avoid the side-effects that scalpel-based treatments can cause, such as incontinence and loss of erectile function. A year after the trial 95 percent of the men showed no further sign of cancer.
Current models at the FAL include human liver, skeletal muscle, adipose tissue and skin. Here is a selection of projects from other research centres that have used human subjects. Does reading promote empathy?
Good health and dietary changes
It appears that reading a good book can help people empathise better with others. A study carried out at the New School for Social Research in New York, USA has found that, after reading literary fiction, test subjects were more able to identify emotions from facial expressions than those who read non-fiction. The effect was only temporary, and it worked best with books that had complex characters.
Good health might depend on dietary changes in more ways than previously thought. A study involving human volunteers has shown that switching from a meat-based diet to plant-based, and vice versa, can have a significant effect on gut flora. A team of researchers from Harvard University have monitored the bugs in the volunteers’ guts by sequencing microbial RNA. They discovered that changing from a vegetarian diet to one based on meat, eggs and cheese caused an increase in the bacterium Bilophila wadsworthia, which has been linked to inflammatory bowel disease in mice. Switching the other way caused an increase in bacteria associated with reduced inflammation.
Silk and the treatment of eczema Researchers at the University of Nottingham have recruited 300 children aged under 16 to take part in a clinical trial to establish whether silk clothing can help treat eczema. The youngsters will be split into two groups: one will receive conventional treatment and others will receive the same treatment, but be asked to wear silk underwear. Eczema is an extremely distressing skin condition that can be very painful for sufferers. It is believed that silk clothes have protective, possibly antimicrobial, properties that can reduce symptoms. The trial will continue for 18 months and aims to provide practical advice for patients once it is completed. 6 | FRAME News 72, Easter 2014
Friends of FRAME Friends of FRAME is the group for FRAME supporters who help us through regular donations and by spreading the word about FRAME’s work. They are individuals who believe in what we stand for and the way we go about promoting the end of animal experiments.
To join Friends of FRAME send £20 and your name and address to: 96-98 North Sherwood Street Nottingham NG1 4EE
We are always grateful to them for their belief and backing.
Kevin from Canada The newest member of the FRAME office team is Scientific Officer Kevin Coll. Here he introduces himself and explains why he wanted to work for FRAME. I was born and educated in Canada, near our largest City, Toronto. I graduated from the University of Guelph majoring in Biological Science, while minoring in Zoology and Business, in April 2013. I spent much time working within the Integrative Biology department, primarily at our Aqua-lab, while pioneering and governing the Biomimicry Collaboration organisation. Biomimicry, or biomimetics, is a real passion of mine. It’s a branch of science where natural processes and models are studied for inspiration to solve human problems. It promotes working with biological systems instead of against them. Although I was born in Canada, I do hold British citizenship and it has always been a goal of mine to explore working
Welcome baby Jack FRAME Scientific Programme Manager Michelle Hudson-Shore has become a mum for the first time. Baby Jack weighed in at 7lbs 12½ and looks like he is going to be tall, taking after his sporty dad Danny.
on this side of the Atlantic. FRAME has provided me with that opportunity and I could not be more excited and motivated to help FRAME in its mission. There are a number of reasons why FRAME intrigued me when I first began here, notably, its commitment to improving science in a time where things have become, relatively and regrettably, static. The path that lies ahead of FRAME and the rest of the scientific community is clear to me. This is one that progresses and advances contemporary techniques that rely heavily on historic practices towards ones that embrace new technologies and ways of thinking. My responsibilities at FRAME include, but are not limited to, the implementation of our Training Schools in experimental design and statistical analysis, researching alternatives to the use of laboratory animals, and preparing an interactive timeline to act as a tool for the public and researchers interested in learning about alternatives. I have also attended a number of meetings, and addressed students at a university biology department about the relevance of the Three Rs to their work. I am enthusiastic about this year and I’m looking forward to see what the remainder of it holds in store.
“Life is certainly very different now but we are really happy. Jack’s a lovely little man and charms everyone he meets.” Jack has already been for his first swim and is starting to have his first tastes of real food. FRAME News 72, Easter 2014 | 7
NEWS IN BRIEF A survey of pet owners in the UK, Australia and New Zealand has revealed that they are more likely to believe that animals can experience emotions, including guilt, shame, jealousy, boredom and grief. People without pets were three times less likely to think animals had feelings comparable with human emotions. Public attitudes play a key role in driving animal welfare measures and so have a greater influence than any scientific evidence for or against the idea of animal emotions. Authors of the study, published in the journal Animal Welfare, suggest that further work should be carried out to find what other variables affect public concern over welfare matters, including the use of animals in laboratories. Walker, J.K., et al. Does owning a companion animal influence the belief that animals experience emotions such as grief? Animal Welfare 2014, 23: 71-79.
3D printed livers An American company has developed a way to create artificial human livers using a 3D printer. The development is being hailed as an effective way to replace animal testing. It has been possible for some time to grow human hepatocytes (liver cells) in culture, but the company, Organovo of San Diego, California, says its printed version enables cells to be laid down in the same way as they are in the human organ. A statement on the company’s website reads: “Most liver functions are dependent, in part, on architecture. Hepatocytes inside the body are polarized along a border
8 | FRAME News 72, Easter 2014
of endothelial cells. Loss of polarization - as occurs when hepatocytes are cultured in simple monolayers on standard tissue culture-treated plastic - leads to loss of function.”
Biobanks access People who donate tissues and information to biobanks should have access to their own data, according to a new report. Writing in the journal Science, Jeantine Lunshof and George Church from Harvard Medical School and Barbara Prainsack from King’s College London, say that allowing donors access would be the most ethical approach. It would make the relationship between the database and the subjects more reciprocal and show respect for the donors. The authors say that current technological standards would make it easy to allow access, and that donors should be able to benefit from their own material. Currently only researchers are able to access data. Lunshof, Jeantine E. , Church, George M. , and Prainsack, Barbara. Raw Personal Data: Providing Access. Science 2014 Vol. 343 no. 6169 pp. 373-374
FRAME giftware Notelets
£2 or 3 for £5
Handy notelets in packs of 5, with envelopes, in a range of different designs. New for 2014 is the Spring Flowers collection. Also available: animals, birds, fairground, countryside scenes. To take advantage of the special offer simply write how many of each design you would like then put the cash total into the ‘offer’ line on the order form.
All prices for goods, postage & packing (but not donations) are inclusive of VAT
£2
Travel Wallet
Ideal for travel passes, tickets or even bank plastic. A useful two-pocket wallet in white with the FRAME logo in blue. Show people you care wherever you are.
Bubbles Notepad
£2
Notepaper
Natural cotton tote bag with stitched handles. Tough enough for groceries but small and lightweight when not in use.
£2.50 per pack
Dogs Pattern
A neat, A6 size notepad with a bubbly border.
Handy pack of 24 sheets of A5 paper, featuring two dog designs, with 20 envelopes.
There are 50 sheets to each pad.
Pens
£4.50
Tote Bag
Woodland Pattern
Our Woodland notepaper has an attractive animals and plants design along the lower border. There are 20 A4 sheets and 20 envelopes in each pack.
3 for £2
Three pens made from recycled plastic. Each carries the FRAME message “Researching alternatives to animal testing”.
Silk Tie
£13.50
The FRAME bunny wanders among lettuces on this 100% silk tie.
Keyring
£3 Perfect for shopping trips, this key ring has a detachable pound-sized coin for use in supermarket trolleys and lockers.
FRAME Stickers
Window Sticker
£1.75
Self-cling, but easy to re-position, the window sticker can be used in house or car. Shows the FRAME logo and message.
£1.50
Three sheets of useful stickers with 35 per sheet. Ideal for reusing envelopes, sealing small packs, or many other uses.
FRAME News 72, Easter 2014 | 9
ORDER FORM
Easter 2014
Item
Price £
No.
The Gift Aid scheme allows charities to reclaim tax paid by UK taxpayers without costing you anything extra. Total £ If you are a UK taxpayer, FRAME can reclaim the tax you have paid on money you give to us, and it doesn’t cost you a penny extra. The scheme is called Gift Aid. Basic rate income tax is currently 20 per cent, so that means for every £10 you give us we receive £12. Please sign the Gift Aid declaration below and let us make your money go further.
Notelets Spring flowers Animals Birds Fairground Countryside Notelets offer (3 packs) Dog notepaper Woodland notepaper Pens (set of 3) Bubbles pad FRAME stickers Window sticker Tote bag Key ring Travel wallet FRAME silk tie Postage and packing Donation (Enter amount) Total
2.00 2.00 2.00 2.00 2.00 5.00 2.50 2.50 2.00 2.00 1.50 1.75 4.50 3.00 2.00 13.50 3.50
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10 | FRAME News 72, Easter 2014
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Please notify the charity if you: 1. Want to cancel this declaration 2. Change your name or home address 3. N o longer pay sufficient tax on your income and/or capital gains
FRAME Annual Lecture FRAME’s Annual Lecture has always been an invitationonly event because of the size of the venue, but the latest was recorded and is available for anyone to view online...
Visit www.youtube.com and search for ‘FRAME annual lecture’
Drug tests using dogs The latest FRAME Annual Lecture revealed that testing drugs on dogs is about as accurate as flipping a coin. The talk was given by geneticist Dr Jarrod Bailey and featured his recent study reviewing the use of dogs in testing drugs intended for human use. He completed the project with Michelle Thew, of the BUAV, and Professor Michael Balls, FRAME’s Life President. They looked at data from 2,366 publiclyavailable toxicological studies that used dogs, and asked whether the use of dogs contributes significant weight to the evidence predicting the toxicity of potential new drugs in humans. The findings show that canine models are highly inconsistent predictors of toxic responses in humans. Dr Bailey is renowned for his body of work, which includes many research critiques of animal experimentation. He has authored and co-authored many reviews on a variety of topics, including the limitations and dangers of animal use in developmental toxicity and carcinogenicity testing, and of using chimpanzees and other nonhuman primates in medical research. He is a scientific adviser to the British Union for the Abolition of Vivisection (BUAV), and scientific director of the New England Anti-Vivisection Society (NEAVS).
Abstract Dogs remain the main non-rodent species in preclinical drug development. Despite the current dearth of new drug approvals and meagre pipelines, this continues, with little supportive evidence of its value or necessity. To estimate the evidential weight provided by canine data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive dataset of 2,366 drugs with both animal and human data, including tissue-level effects and ‘Medical Dictionary for Regulatory Activities’ (MedDRA) Level 1-4 biomedical observations. The resulting LRs show that the absence of toxicity in dogs provides virtually no evidence that adverse drug reactions (ADRs) will also be absent in humans. While the LRs suggest that the presence of toxic effects in dogs can provide considerable evidential weight for a risk of potential adverse drug reactions in humans, this is highly inconsistent, varying by over two orders of magnitude for different classes of compounds and their effects. Our results therefore have important implications for the value of the dog in predicting human toxicity. On this basis, combined with the high ethical cost of using dogs in research, we suggest that alternatives to using dogs in testing are urgently required.
FRAME News 72, Easter 2014 | 11
FRAME HAS... Attended an international, virtual, Laboratory Animal Science (LAS) BioConference to learn more on alternatives worldwide. Talked to bioscience students at the University of Cardiff about the Three R’s and non-animal methods. Responded to queries from researchers around the world. Taken part in the Big Animal Debate to discuss the rights and wrongs of animal experimentation. Planned new projects to promote reduction. Increased its social media share on Facebook, Twitter and LinkedIn.
ATLA gains its own website ATLA (Alternatives to Laboratory Animals), FRAME’s scientific journal, is being put onto its own website. The move is part of a rationalisation of FRAME’s online presence. After the changes, FRAME will have three websites, but all will be reachable through www.frame.org.uk Part of the reason for the change is to simplify access to papers published in ATLA. Last year it was decided to make all but the most recent two years available free to researchers. FRAME’s old website was unable to cope with the complexity and so the journal is being moved to www. atla.org.uk to make papers easier to obtain.
Featured in a number of UK national newspapers and magazines.
FRAME’s other site is Perspectives in Laboratory Animal Science (PiLAS), which is now hosted at www.pilas.org.uk. Its content has not changed and it is still an interactive site designed to promote discussion on the challenges facing researchers today.
Answered questions from members of the public about laboratory science and the welfare of animals used in research.
FRAME in Brazil
Published a special edition of ATLA featuring papers by winners of the Lush Prize awards for animal free research
Among recent coverage including FRAME was a programme by Brazilian company Globo TV. Two thirds of Brazilians support a ban on animal tests on cosmetic products and the country is currently reviewing its legislation covering cosmetics testing. The programme makers visited Europe to report on the latest changes in EU law. During the show the presenter visited the FRAME Alternatives Laboratory in Nottingham (UK) and spoke to Director Dr Andrew Bennett.
12 | FRAME News 72, Easter 2014
One of FRAME’s most important functions is to promote the principles of non-animal methods through better science to researchers and the public. As part of that aim, FRAME sends regular press releases to print and broadcast media in the UK and overseas. Journalists and producers also contact FRAME when relevant topics are in the news.
The value of patents By Rita Seabra
“If national patent laws did not exist, it would be difficult to make a conclusive case for introducing them; but the fact that they do exist shifts the burden of proof and it is equally difficult to make a really conclusive case for abolishing them.” Edith Penrose, 1951 The system of patents was introduced to encourage innovation that benefits society. When one is granted, the patent holder is granted short-term exclusive rights in exchange for the publication of a description of the invention. The reasoning is that a temporary monopoly rewards and encourages investment in innovation (inventions are generally difficult and expensive to conceive, while copying is easier and cheaper!) and publication of patented inventions ensures that innovations are not retained as trade secrets , and they cannot be exploited indefinitely by a single party. Monopoly rights to the invention are temporary and depend on the payment of yearly renewal fees. This is to ensure monopolies are only maintained for commercially viable products, which by implication are useful to society. However, monopoly rights granted by patents are not absolute - exceptions include, non-commercial research carried out for purely academic purposes, private use, and when there is a pressing societal need. To be protected by a patent, an innovation must be inventive, novel and industrially useful, but there are exemptions, for example, any that would be contrary to public policy or morality. In Europe, with regard to life sciences, there are several exemptions to patentability, under the EU Biotech Directive: processes for cloning humans, for modifying the genetic identity of animals (likely to cause suffering without substantial medical benefit), and the use of human embryos for industrial or human purposes. This last point can affect, for example, commercial research on embryonic stem cells. In terms of patentability, there is a distinction between a naturally occurring compound and its extracted and isolated
form for which a use has been identified. In an early test case in the USA, a patent was granted for isolated adrenalin for possible therapeutic use, but adrenalin in its natural state, in the human suprarenal gland would not have been patentable. It is also not possible to patent DNA sequences, or genes, or organs and tissues, as they exist in nature. But, once an industrially applicable use for a DNA sequence has been developed, and it is isolated from the organism, it might become a patentable product. This distinction is not always clear and is a matter of current discussions, such as whether an extracted or synthesised chemical compound can be considered ‘novel’ in terms of patentability if it is chemically identical to a compound that already exists in nature. Patents are valid only in the country where they are granted. A patent allowed in one country cannot be enforced in another. Public expectations, well-being and morals will influence patentability decisions. Overall the patenting process is often a lot more complex than it appears, and its worth to society may vary with the technology involved. No system is perfect and it has been argued whether patents actually foster innovation. Even a temporary monopoly prevents free use, and can disproportionately benefit the wealthy. Ultimately, the difficulty lies in ensuring there is balance between granting rights to the inventor and allowing the public to benefit from the technology. Since technological innovations have to be considered alongside societal and economic factors, patent law is a dynamic field.
~ Rita Seabra FRAME News 72, Easter 2014 | 13
Research at the FAL The FAL is FRAME’s Alternatives Laboratory, based at the University of Nottingham. FRAME was the first organisation to fund its own laboratory where new and innovative replacement methods are developed. The lab uses cells derived from human tissues to produce biologically relevant in vitro models of human organs, which behave and respond in the way they would in the body. The lab has a director and is staffed by post-doctoral fellows, PhD students and technicians. Louis Brailsford is a third year PhD student at the FAL. Here he discusses what his work has involved and how it will impact the Three R's.
What challenges have you faced with the project? During my PhD I have faced many hurdles along the way. I was the first PhD student in our research group to investigate the molecular mechanisms underpinning lipid transportation and signalling during pain reception. Coupled with the fact there is little published work examining the biological pathways we are interested in this made setting up cell-based experimental models difficult and time consuming. In many ways facing with these challenges and troubleshooting them has been immensely rewarding both intellectually and personally.
How will your work contribute to the Three R's? The different drugs and compounds of interest in my PhD are used exclusively on human cell lines expressing key proteins thought to be involved in nociception. Experiments such as these are firstly using cells from a relevant species (human!) and therefore reducing our dependency on animal testing. Additionally these experiments are easily replicable without the detriment of animal well-being. Pain research in general is often carried out using animals due to the complex nature of the signalling pathways involved and the fact that it is extremely difficult to assess pain and the potential effects of painrelieving drugs without using animals as surrogates for humans. The research I have been conducting over the past few years will allow the assessment of the potential usefulness of novel compounds and pathways at an early stage of development without the need for animal research.
What are you hoping to do after you finish? Background I studied for my BSc (Hons) degree in Biochemistry at the University of Nottingham. During my final year I worked under the supervision of Dr Andrew Bennett, Director of the FRAME Alternatives Laboratory, where I investigated the lipid signalling pathways that are activated in macrophage-like cells (part of the immune system). In 2011, I returned to the FAL to commence my 3-year BBSRC funded PhD, working under the supervision of Dr Andrew Bennett and Professor Victoria Chapman. My current research focusses on elucidating the key molecular mechanism by which fatty acid metabolites or lipids signal to ion channel proteins involved in pain detection in sensory neurons, that is, the chemical pathways by which the body feels pain. The overall aim of the project was to identify new targets for the generation of pain relief drugs using cell based models. 14 | FRAME News 72, Easter 2014
I hope to secure a Post-Doctoral position at another University. It’s a natural progression. I have learnt a great number of different techniques in molecular biology, biochemistry and cell biology, and would like to build on what I have learnt in my next post.
ALTERNATIVES TIMELINE PROJECT Use of animals in experiments is well documented. Its early history can be traced to the ancient Greeks and Romans, who first began exploratory surgery on animals to discover the inner workings of living things. The effectiveness of animal testing has also been questioned for hundreds of years but a clear record of that campaign is more difficult to find. Claims that modern advancement in drug development and medicine is only possible through animal experiments are strengthened by the amount of information available. An equivalent data store of non-animal methods is needed to counteract those arguments. Requests from researchers looking for a simple, direct and swift way to reach such information have led FRAME to create a new timeline, covering advances in nonanimal research. The project will be available online and will offer different levels of detail to suit everyone. It will be easy to access, visually appealing and content rich. It will also grow dynamically as reported successes from non-animal science increase. The timeline will: • act as a review of effective alternatives • provide a primary resource for researchers • raise the profile of alternatives research •p rovide a database of definitions and ongoing research cross-reference ineffective animal models and their alternatives •d efine when, where and by whom the alternative was formulated • define which of the Three Rs are in practice > Dr. Carol BarkerTreasure (centre) receives her Lush training prize
Professor David Morton, CBE Former FRAME Trustee Professor David Morton was awarded a CBE (Commander of the Order of the British Empire) in the New Year Honours List. The citation stated that the honour was “for services to the UK and International Veterinary Profession especially Animal Welfare and Ethics.” David said: “I cannot believe it. I would not have achieved it without the help and support of my friends and colleagues. I hope it is good for the field of animal welfare and ethics, as well as for the veterinary profession.” Professor Morton is Emeritus Professor at the University of Birmingham School of Biosciences. The Order of the British Empire was instituted by King George V on 4 June 1917 and is conferred for important services rendered to the Crown.
Top prize for Carol A contract laboratory founded by a former FRAME employee has won a prize for its training scheme. Dr Carol Barker-Treasure founded the XCellR8 lab in Cheshire to support, develop and implement the use of scientifically advanced and ethically sound alternatives to animal testing. She completed her PhD while working at the FRAME Alternatives Laboratory in Nottingham. Now her company has been awarded the Lush Training Prize for its work in educating young scientists in cell based testing techniques. Carol said: “It is crucial to educate the next generation of scientists about the ethical and scientific benefits of using human cell based alternatives to traditional animal tests. By enabling young scientists to take this knowledge forward into their careers, our goal is to help reduce the number of scientists resorting to unethical and outdated animal test methods in the future. I’m very grateful to FRAME, and to Dr. Richard Clothier in particular, for providing me with the training that has enabled me to pursue a fulfilling career in alternatives to animal testing. If I hadn’t gained this valuable experience, XCellR8 would not be here today to train future generations of scientists, enabling the continued development of human cell based alternatives.” FRAME News 72, Easter 2014 | 15
New FRAME training schools When scientists carry out experiments it is vitally important they are well designed, otherwise they may squander resources or give the wrong answers. This is especially serious if animals are used, because their lives can be wasted for no purpose
Review of animal research standards Results of an independent investigation into animal research at Imperial College London have been published by the UK’s National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). The report follows a complaint by the British Union for the Abolition of Vivisection (BUAV) in April 2013 about animal welfare standards at the college. An expert committee was invited by the college to assess its approaches to research on animals. Chaired by Professor Steve Brown of the MRC Mammalian Genetics Unit, the committee expressed concern about leadership, management, operational, training, supervisory and ethical review systems. Although it commended the college’s animal care staff and the standards of husbandry, it made a number of recommendations, including a complete reform of internal processes for the ethical and scientific review of animal studies. It also suggested increased staffing levels in the animal facilities, additional resources to support the training and competency assessment of those using animals and the creation of a new senior director role with overall responsibility for animal research and the Three R's.
Indian legal changes Animal welfare groups in India are calling on their government to tighten new regulations over cosmetics testing. The Indian Bureau of Standards recently introduced a ban on animal tests on cosmetic products manufactured in the country, but the law still allowed imports of products that had been tested on animals elsewhere. Now the Indian arm of Humane Society International has called for the ban to be extended. The change would require a further amendment to the Drugs and Cosmetics Rules 1945, which control product manufacturing standards.
FRAME has staged another of its highly successful schools in experimental design and statistics, and there are two more in the pipeline. It will be the first time that three schools have been held in the same year. The first was in Copenhagen in January, in association with the Danish National Research Centre for the Working Environment. A second school is planned within a few weeks in Portugal, and discussions are underway for a third school, in Dublin later this year. Around 50 delegates attend each school. The aim is to provide them with the tools they need to minimise the number of animals they use, while maximising the data they obtain from their work.
^ FRAME training school in progress