Science blog

3 posts from October 2016

27 October 2016

Replace, Reduce, Refine: Animals in Research.

PhD placement student Mandy Kleinsorge looks back on our most recent TalkScience@BL event.

TalkScience@BL - Replace, Reduce, Refine: Animals in Research

The use of animals in research is as controversial as ever. It is well-known that animal research has brought about some great discoveries in the past1, such as the development of Herceptin and Tamoxifen for the treatment of breast cancer or the discovery of bronchodilators to treat the symptoms of asthma. Today, the UK regulations for research involving animals are among the tightest in the world. In consequence, it is illegal in the UK (and in Europe) to use an animal in research if there is a viable non-animal alternative2. Despite this, the number of experimental procedures on animals in the UK has been steadily increasing over the last years3 and funding of non-animal research accounted for only 0.036 % of the UK national R&D science expenditure4 (2011). Apparently, three quarters of Britons agreed that there needs to be more research carried out into alternatives to animal experimentation5 (2012).

On 13th October, we invited experts in the field to the British Library to publicly discuss the current state of alternatives to animals, as well as the efforts that are made to improve the welfare of animals that are still needed in scientific research. The concept of reducing or even substituting animals in scientific experiments (or at least improving the conditions under which these experiments are conducted) is not new. In 1959, Russell and Burch established the principles of the Three Rs (Replacement, Reduction and Refinement)6 which came to be EU-wide guidelines for the more ethical use – or non-use – of animals in research. Today, a number of organisations campaign for openness and education as to why animals are needed in some areas of research, but also as to where we might not actually need them anymore. One of those is the National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs) who we collaborated with on our TalkScience event ‘Replace, Reduce, Refine: Animals in Research’. The event was chaired by Stephen Holgate, Professor of Medicine at the University of Southampton and Board Chair of the NC3Rs.

Taking a closer look at Robin's amoeba.
Taking a closer look at Robin's amoeba.

The first speaker of the evening was Robin Williams (Head of the Biomedical Sciences Centre at Royal Holloway, University of London). Robin uses Dictyostelium, a social amoeba and therefore non-animal model, to conduct research into neurological diseases like Alzheimer’s. He even brought some amoeba for the audience to look at! Besides bringing awareness to the fact that this organism can actually represent a viable alternative to animal experimentation, he also drew attention to two big problems that researchers using animal alternatives are facing. Acquiring funding and publishing scientific papers are the most important tasks of senior researchers and both of these are complicated by a limited acceptance of non-animal models. Although 3Rs practice is increasingly advocated in the UK, the peer review process regulating funding and publication of research projects is a global endeavour. Robin therefore called for a shift in attitude towards alternatives to animals on a world-wide level.

Our second speaker, Sally Robinson (Head of Laboratory Animal Science UK at AstraZeneca), shed some light into the use of animals in pharmaceutical research. Sally stressed the importance of using the most appropriate model – animal or non-animal – to answer the scientific question. This is not as trivial as it sounds, and is key to obtaining meaningful results and minimising use of animals where possible. The welfare of the animals used in drug development is equally important, as Sally illustrated with the refinement of dog housing. By optimising pen design7, the welfare of laboratory dogs can be drastically improved, and so can the quality of scientific research they’re involved in. Furthermore, Sally herself had a leading role in the challenging of the regulatory requirement for acute toxicity tests in drug development8, which ultimately changed international legislative guidance and reduced the number of animals needed in pharmaceutical research.

Our panel: Stephen Holgate, Robin Williams, Sally Robinson and Robin Lovell-Badge.
Our panel: Stephen Holgate, Robin Williams, Sally Robinson and Robin Lovell-Badge.

Our last speaker was Robin Lovell-Badge (Head of the Division of Stem Cell Biology and Developmental Genetics at the Francis Crick Institute). He opened his talk by endorsing openness in animal research. This is a welcome and necessary trend of the past few years – after animal research had been conducted behind closed doors in the UK for decades for fear of violent actions. The ‘Concordat on Openness on Animal Research’9 was initiated in 2012 and has been signed by 107 UK organisations to date. Robin explained which animals the newly built Francis Crick Institute will work with and why, and how Home Office guidelines on animal research have helped inform the design of their state-of-the-art facilities. He also mentioned some of their work that doesn’t involve animals, like research using induced pluripotent stem (iPS) cells. These iPS cells resemble embryonic stem cells and can be generated from any living cell of a human donor. They are able to differentiate into virtually every cell type of the body, presenting an alternative source of human tissue for drug screenings and the modelling of diseases10. This fairly new technology might even be useful as an alternative to animal experiments in the future.

In discussion with the audience it became clear that the UK is leading the world in the realisation of the 3Rs. However, there is still room for much improvement in furthering the 3Rs. While better experimental design using robust biostatistics and in-depth training of scientists handling animals is vital, increased acceptance of negative data would avoid unnecessary duplication of experiments using animals.

The discussion continued after the event.
The discussion continued after the event.

When asked whether an animal-free research in the immediate future was possible, the panel agreed that it wasn’t. A lot more research into alternatives as well as a change in people’s mindsets is needed beforehand. But how do we exert pressure for this change? Do we need animal activists to do this, one audience member asked. Good question. It is definitely necessary to bring different types of people together to have more balanced and open discussions about this emotive topic. So, thanks to the speakers and the audience of this TalkScience event for joining us to disuss this important issue.

Further reading:

1 Understanding Animal Research. Forty reasons why we need animals in research.
2 Animals in Science Committee. Consolidated version of the Animals Scientific Procedures Act 1986.
3 Home Office. Statistics of scientific procedures on living animals, Great Britain 2015.
4 Taylor, K. EU member state government contribution to alternative methods.
5 Ipsos MORI. Views on the use of animals in scientific research.
6 Russell, WMS and Burch, RL. The principles of humane experimental technique.
7 Refining Dog Care. Dog unit and home pen design.
8 Robinson, S et al. A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development.
9 Understanding Animal Research. Concordat on Openness on Animal Research.
10 Takahashi, K and Yamanaka, S. A decade of transcription factor-mediated reprogramming to pluripotency.


21 October 2016

Britain's first nose job

Science Content Expert Philip Eagle explores the first plastic surgery operation in Britain.

On 22nd October 1814, Joseph Constantine Carpue (1764-1846) performed the first plastic surgery operation in Britain, reconstructing the nose of an army officer whose nose had collapsed due to long-term mercury treatments for a liver complaint. The operation lasted fifteen minutes, with no anaesthetic. Three days later, the patient’s dressing was removed, and on observing the successful results a friend of the patient exclaimed: “My God, there is a nose!”

Illustration by Charles Turner from Carpue's book
Illustration by Charles Turner from Carpue’s book, digitised by the Wellcome Library and released under Creative Commons CC BY 4.0 licence.

Carpue was inspired to perform the operation after reading reports of successful nasal reconstructions in India, using skin flaps from the cheek or forehead. The most famous of these was a 1794 report in the Gentleman’s Magazine, describing the reconstruction of the nose of a man named Cowasjee. Cowasjee had been mutilated by the forces of Tipu Sultan during the Third Anglo-Mysore War for working for the British.

Broadside on Cowasjee's case published by James Wales
Cowasjee’s case published by James Wales, digitised by the Wellcome Library and released under CC BY 4.0 licence.

Nasal reconstructions had been practised as a relatively routine procedure in India for centuries. This was driven by the common use of nasal mutilation in India as a means of punishment or private vengeance for various forms of immorality. The procedures are described in two well-known early Indian medical works, the Suśruta Saṃhitā, thought to date to the middle of the first millennium BCE, and the Aṣṭāṅgahṛdayasaṃhitā, believed to date from the sixth century CE*.  By the nineteenth century the technique had been handed down through separate families in three different parts of India.

Rhinoplasty by transfer of skin flaps from other body parts had also been practiced in Italy in the sixteenth century, most famously by the Bolognese surgeon Gaspare Tagliacozzi (1545-1599). However, it had declined following Tagliacozzi’s death, due to a mixture of professional politics in Italy, misconceptions about the nature of the procedure, and moral disapproval of an operation that was often performed to repair damage done by syphilis. (Even in his own book, Carpue felt at pains to insist that the mercuric treatment that had damaged his first patient’s nose was not for syphilis.)

Carpue published a book in 1816 on the subject, discussing his predecessors and inspiration and then describing two cases of nasal reconstruction that he had performed. The second was on a named patient, a Captain Latham whose nose had been injured during the Battle of Almuera, in the Peninsular War. Carpue’s work inspired further practice by the German surgeon Carl Ferdinand von Gräfe, who is credited with coining the term “plastic surgery”.

Philip Eagle

With thanks to Pasquale Manzo (Curator, Sanskrit Collections) for information on British Library holdings of ancient Indian medical texts.

Further reading:


11 October 2016

Happy Ada Lovelace Day!

It’s Ada Lovelace Day today! Now in its 8th year, this special day aims to raise the profile of women working in science, technology, engineering and maths, but also to create role models to encourage girls to pursue scientific careers. The name giver herself was a prime example of a woman following her inclination for analytical thinking. Ada Lovelace made a name for herself as the first computer programmer at a time when women weren’t even allowed to vote.

But she was not the only woman who contributed to our understanding of science. The list of scientific heroines in history is surprisingly long, but mostly unheard-of. It comprises the well-known names of Marie Curie-Skłodowska, Rosalind Franklin and Florence Nightingale, but did you know the following female scientists?


Beatrix Potter's illustration
Beatrix Potter's illustrations of fungi in 'Wayside and woodland fungi' by W.P.K. Findlay (shelf mark X.329/15466)

Beatrix Potter (1866 – 1943)

The name of Beatrix Potter might be familiar to those who grew up with ‘The Tale of Peter Rabbit’. But besides being a famous author and illustrator of children’s books, she was also a natural scientist. Her love of flora, fauna and landscape, combined with her artistic talent and her ability to closely observe her surroundings, provided the ideal basis for this occupation. However, being a woman, she was rejected to study at the Royal Botanical Gardens. So Beatrix continued to study nature – fungi in particular – on her own and recorded her observations in beautiful drawings and watercolours, ultimately receiving the wide respect she deserved in the field of mycology. We hold a textbook on fungi at the British Library in which a collection of her brilliant illustrations has been used.


Agnes Mary Clerke (1842 – 1907)

Thanks to her parents, Agnes Mary Clerke was educated broadly in scientific subjects and languages, but it was the field of astronomy that became her passion. She started to write about the history of astronomy at the age of 15 and, after having her first important article published in the Edinburgh Review, she was repeatedly asked to contribute to scientific publications. She wrote the main article on astronomy as well as biographies of famous scientists for the Encyclopaedia Britannica. She also published books of her own, her best known work being ‘A Popular History of Astronomy during the Nineteenth Century’ (which, of course, we have at the British Library). Although Agnes Mary Clerke was not a practical astronomer herself, she gained the respect of the profession through her interpretation of astronomical research, and by doing so, also introduced astronomy to a wider public.


Sophie Germain's letter
A letter written by Sophie Germain under her pseudonym M. Le Blanc to C.F. Gauss (shelf mark 10902.h.5)

Sophie Germain (1776-1831)

Sophie Germain’s interest in mathematics was sparked at an early age, but in order to be able to study it, she had to overcome her parents’ opposition first and the society’s prejudice against her sex next. The latter she did by assuming the identity of M. Le Blanc, a former student of the Ecole Polytechnique near Paris, and sending the answers to his homework to his professor. She also corresponded with the famous mathematician Carl-Friedrich Gauss under her pseudonym. An impression of their discussions can be obtained through the letters in the British Library’s collection. In both instances, she was eventually unmasked, but was accepted immediately by the two men – and eventually by the whole scientific community – as an equal. Sophie Germain is best known for her progress on the proof of Fermat’s Last Theorem and her work on elasticity which to this day underpins the science of building construction.


Science Fiction by Margaret Cavendish
Margaret Cavendish's science fiction work 'The Blazing World' (shelf mark 8407.h.10) 

Margaret Cavendish (1623 – 1673)

Back when scientists were still called natural philosophers, Margaret Cavendish established herself as the first English female representative of this profession. She wrote treatises on a variety of subjects, including gender, power, scientific method and philosophy and by doing so helped popularise the scientific revolution. Although she was widely known (and often ridiculed) for her eccentricity, her innovative views added to the scientific discussion of her time. Not only was she one of the first to contest the validity of theological aspects in science, she also argued for the education of women and is claimed to be an early opponent of animal testing. On top of that, she managed to write one of the first examples of science fiction, ‘The Blazing World’, which has been digitised by the British Library and can be read online.


Hildegard von Bingen (1098 – 1179)

The German Benedictine abbess Hildegard von Bingen was what you call a polymath. She was a theologian, philosopher, author, linguist and composer, but also a physician and natural scientist. While most of her non-scientific work was heavily influenced by the visions she is said to have received from a young age onwards, her botanical and medicinal texts are based on observations and experience. You can find a translation of her first book on the treatment of diseases ‘Physica’ at the British Library. Some of the remedies she described in her works might seem far-fetched from a modern scientific point of view, but she also made many accurate observations and is with good reason considered to be the founder of scientific natural history in Germany.


These five women achieved extraordinary things through their dedication to further scientific knowledge, even though (or possibly because?) they were women. Let them inspire you to strive for the same. Happy Ada Lovelace Day everyone!

Mandy Kleinsorge, PhD placement student