Tag: bioethics

Going bananas over RotPotA…

ResearchBlogging.org
Caveat Lector: This post may contain what one might consider spoilers. Therefore, if you haven’t already watched the 2011 movie “”http://www.imdb.com/title/tt1318514/" style=“text-decoration:none;”>Rise of the Planet of the Apes" and are planning to do so, please cease and desist from reading any further. This post contains some of my thoughts and impressions on the said movie.

In no uncertain terms, I quite liked this movie, which has been imagined as a ‘prequel’ to the long running “Planet of the Apes” franchise (originally made in 1968 by Franklin Schaffner, featuring Charlton Heston; reimagined by Tim Burton in his 2001 multi-award-nominated feature). The 2011 Rise of the Planet of the Apes, under Rupert Wyatt’s competent direction, featured some spectacular CGI special effects, and a fabulous performance by Andy Serkis (of the LOTR Gollum fame) as Caesar, the chimp with genetically enhanced intelligence; I don’t know how Andy did it, but he has copied the simian movements almost in toto, making for a highly believable Caesar through a performance capture CGI technique (where the motion capture session includes face and fingers in order to capture and reproduce subtle expressions). The storyline was taut and exciting, without a dull moment, and contained some emotionally-charged sequences which were brilliantly executed. James Franco did a decent enough job as the geneticist Will Rodman, and the mandatory feel-good factor (of course!) was provided by India’s own Freida Pinto as the San Francisco primatologist, Caroline Alanha. All in all, an eminently watchable movie.

The Primates Meet
Image Credit: Weta Digital/20th Century Fox, via NY Times Movie Review Slide show

So what’s my beef with it?

Same as what gets my goat everytime, the piss-poor portrayal of scientific research in Hollywood movies. A part of me says, it’s all right, it’s fiction. But it’s also true that there’s no dearth of gullible people around who consider such portrayals the Gospel truth, and form a negative opinion of the work that scientists are engaged in, as well as of research ethics which is the cornerstone of good science. So, having enjoyed the Rise of the Apes, the average viewer possibly leaves with an egregious impression of science and scientific research – that scientists, in (the much-maligned) white coats/scrubs, are really a bunch of heartless brutes who go about mistreating the non-human animal test subjects for their fun studies, not the least of all when they involve primates.

Nothing could be farthest from the truth. First off, for anyone wishing to engage in research involving primates, there are definite and quite strict guidelines to adhere to and laws to abide by. In the US, the Animal Welfare Act, signed into law in 1966 and strengthened thereafter through several amendments, assures humane care and treatment of certain research animals; the US Department of Agriculture (USDA) is charged with the responsibility of administering the minimum care and treatment requirements under this law, including those for primates for research, testing, or experimentation. The Animal Welfare Information Center of the USDA has – on its webpage for Primate Research Animals – a wealth of information with links to documents that provide guidance on the husbandry, care and health of non-human primates used in research, in both US and the Europian Union. In the European Union, the Directorate General for Health and Consumer Protection (DG-HCP) has extensive information on the care and use of non-human primates in research and safety testing, including guidelines on the welfare of primate subjects and recommendations for the replacement of this model in future. Exhaustive information, guidelines and legal policies are also available from the Primate Info Net, an information service of the National Primate Research Center at the University of Wisconsin-Madison. All of these international bodies subscribe to the mandate of painstakingly avoiding any unnecessary and duplicated and/or redundant research using non-human primates, which, of course, hearkens to the rational principle of Three Rs of animal-based research – reduction, refinement and replacement, wherever possible.

Secondly, the primates to be used are not picked up randomly. Different types of primates are used in scientific experimentation, including prosimians, New World monkeys, Old World monkeys and Apes (tailless primates, such as Gorilla, Chimpanzee, Bonobo and Orang-utans), and it is very important to pay careful attention to their different original habitats in the wild, different physical and behavioural characteristics, patterns of social organization, as well as temperament styles – all factors that may affect their physiological responses. Therefore, experimental designs are created keeping all these considerations in mind, so as to maximize the information outcome with minimum use. According to the 2002 Report of the Scientific Committee on Animal Health and Animal Welfare to the EU DG-HCP, the maximum number of primates used in research in Europe belong to Old World and New World Monkeys, followed by prosimians, mainly in fundamental biological and toxicological studies. The use of apes is restricted to studies on human and veterinary medicine and dentistry, and accounts for <0.1% of all experiments.

In less enlightened times, primates were captured from the wild and sent up to be used in research – as shown at the beginning of the movie. This is largely no longer practised because of various concerns including physiological responses, adaption to laboratory environment, chances of introduction of unknown pathogens, as well as ethical issues. Currently, most non-human primates used in research are obtained from breeding colonies located in a diverse range of countries such as China, Indonesia, The Philippines, Mauritius, Israel and the US. Primates used within Europe are often sourced from either self-sustaining in-house colonies, other Europe-based breeding colonies or breeding and holding establishments outside Europe, according to the above-mentioned 2002 Scientific Committee Report to the EU DG-HCP.

This document also records specific guidelines for the reuse of the primate subject for multiple experiments, but never indiscriminately – certainly not in the manner shown in the movie. The goal of re-using a primate subject is to maximize the amount of informaiton obtained from one animal by engaging it in more than one experiment simultaneously, but only when this practise does not detract from the scientific objective or result in poor animal welfare. Maximization achieved thus would reduce the overall total number of animals required to be used; however, this objective is always judged against minimising any adverse affects on their welfare.

Unlike in the movie, one failed experiment usually doesn’t lead to en masse euthanasia of all primate subjects. Unless it is contra-indicated because of the procedures performed on them, or there is risk of harm, many laboratory primates are rehomed. Rehoming has been also found to benefit the morale of staff members involved with caring for the animals and can help further develop a culture of care. There are several reputable sanctuaries in Europe and the US where retired laboratory primates, including a number of New World and Old World monkey and ape species, have been successfully rehomed; this allows the animals to live out the remainder of their natural lives relatively free of human disturbance (Prescott, 2006; JWG Report, 2009). However, when it becomes necessary, non-human primates are humanely euthanized by trained personnel following guidelines, and tissue samples for in vitro studies are obtained and banked. Co-ordination, optimization and refinement of primate usage can be achieved by establishing tissue banks and data exchange networks. Such a system is already in place in the US – the Primate Info Net. The EU currently lacks a comprehensive pan-European databanks on the use of non-human primates and non-human primate derived tissues and cells.

None of this available information, of course, ever finds its way into any Hollywood production. I may be expecting too much, but… Honestly, would it kill Hollywood to maintain some semblence of truth in its portrayals of the work of scientists?

(N.B. This is why I was so surprised – pleasantly – to learn that the makers of the movie Contagion had a real-life virologist as a consultant, a welcome move.)

The controversy over using primates in research is far from over, with both sides providing heapin’ helpin’ of arguments. Meredith Wadman has written a nice summary with analysis of the current debates on Chimpanzee experimentation for a Nature News item; it’s well worth a read. Proponents of continued experimentation present some powerful arguments that resonate with me as an Infectious Disease researcher. Like others engaged in rational animal experimentation, I, too, advocate the considerations of the Three Rs of animal-based experiments. However, there are some areas where primate-based fundamental research is essential. For instance, as mentioned in Meredith’s report,

“… the research is necessary for continued progress towards a hepatitis-C vaccine; for developing more effective drugs against hepatitis B and C; for testing monoclonal antibody treatments for a variety of conditions; and for research to develop a vaccine against respiratory syncytial virus, a seasonal virus that kills more than more than 66,000 children under the age of 5 each year across the globe2. For many of these conditions, backers argue, the chimpanzee is either the only available model, or by far the best one.

As I mention above, the activities of all nonhuman primate research facilities – public or private – are affected directly by a plethora of international, federal, and state laws, regulations, rules, guidelines, and standards. All facilities where primates are procured, housed, maintained, bred and/or used in research are subject to Federal regulations, which encompass even the design, construction, maintenance, and operation of the said facilities, as well as the occupational and environmental protections afforded to not only the facility personnel, but also the general public.

Postscript:The opponents of animal experimentation, as a matter of course, endeavor to portray that this is not so. And I haven’t yet found their arguments to be convincing. Many of the reports authored by prominent opponents often provide unilateral screeds or opinions with misinformation or data cherry-picked from studies that appear to support their positions, not to mention the obvious conflicts of interest – since many of them are associated with organizations or institutions that promote a blanket abolition of animal experimentations. A lot of controversy also exists as to what construes ‘experimentation’ and what is ‘justifiable’ or not, and these issues often fracture the opponent community. This I hope to discuss in my next post. Stay tuned!

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Further Reading

Joint Working Group on Refinement. Refinements in husbandry, care and common procedures for non-human primates: Ninth report of the BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on Refinement (M Jennings and MJ Prescott, eds). Lab Anim 2009; 43(Suppl 1): S1:1-S1:47 (PDF)

Prescott, MJ. Finding New Homes for Ex-Laboratory and Surplus Zoo Primates. In: Schrier, JE (Ed) LABORATORY PRIMATE NEWSLETTER, Vol. 45, No. 3, July 2006, pp.5-8 (PDF).

Wadman, M. (2011). Animal rights: Chimpanzee research on trial Nature, 474 (7351), 268-271 DOI: 10.1038/474268a

In two minds… about BioEthics

I am really in two minds as I write this.

This post was prompted by a news item on Teh Grauniad this morning, brought to my attention by that esteemed daily’s twitterfeed. The title and the byline goes as:

Girl, nine, benefits from UK’s first IVF ‘saviour sibling’ therapy
Doctors treat girl with rare blood disorder by transfusing healthy bone marrow from baby brother created at IVF clinic

Intrigued, I read through the report.

The story, reporting a first-of-its-kind-in-UK procedure, is of a nine-year old girl with congenital Fanconi’s anemia, an autosomal recessive (or X-linked recessive in ~2% cases) disorder that can result in bone marrow failure; younger patients eventually develop acute myelogenous leukemia (AML), various other hematological abnormalities, kidney problems, and developmental issues, while older patients often develop carcinoma of head and neck, GI, or genito-urinary tract.

The 13 genes involved in Fanconi’s anemia (including 1 that is identical to the well-known breast-cancer-susceptibility gene, BRCA2) encode proteins that assist the recognition and repair of damaged DNA; one or more of these genes are inactivated in Fanconi’s anemia, a relatively rare disease, with a prevalence of 1-5 cases per 1 million persons (N Engl J Med 2010; 362:1909-1919). In this girl’s case, the poor parents were possibly unwitting hapless carriers (a copy each) of the inactivated gene(s), so that the girl received no active copy at all.

Therapy with androgens and hematopoietic growth factors may be effective for treating bone marrow failure in Fanconi’s anemia; however, the disease often becomes refractory to these treatments. For such patients, hematopoietic stem-cell (bone-marrow) transplantation is the only viable option, if a matched donor is available. Preimplantation genetic diagnosis is a new approach for identifying potential sibling donors for patients with Fanconi’s anemia (See the NEJM Paper above). However, the older brother of this girl was found to be an unsuitable donor, and a worldwide search also failed to find a suitable tissue donor match.

The young parents, in their 30s, chose to have an baby by in vitro fertilization (IVF), in which doctors implanted two out of 6 embryos created by IVF. Several tests showed that the implanted embryo was free of the genetic defect. One year after the boy was born and found to be a good tissue match for this sister, the doctors at the Bristol Royal Hospital treated the girl by transfusing healthy bone marrow from him. She has been monitored carefully for six-months, and is now well enough to consider returning to school.

This is a life-affirming story, as well as one of the wonders of modern medicine and applied biology. I am genuinely happy for the little girl, who got better, as well as a baby brother as a bonus out of it.

Yet, I am ashamed to admit, I cannot shake off a nagging feeling.

I have grown up on a staple of Bollywood (Hindi) movies, where sisters, brothers, parents, children were all ready to sacrifice themselves for the good of their [insert appropriate] family members. ‘Self-abnegation’ and ‘renunciation for the good of humanity’ and so forth are concepts that my parents, followers of Hindu philosophy and spiritual beliefs, drilled into me through endless mythological stories and parables and fables. So I should be comfortable with this situation where the younger brother saves the elder sister’s life, right?

And yet, I can come to no easy terms with the ideas that:

  • This child, the youngest son, was not borne out of love, but merely as a tool to be utilized, even if the cause was noble.
  • The bone-marrow was drawn from the child (a painful procedure per se) when he was just one-year old, much below an age where he was capable of giving consent. The boy was simply not in a position to agree or disagree to the procedure, a fact that is unaltered by the parents being empowered by law to provide proxy consent on his behalf. So, even though the son may have happily donated all his organs or even his life for his sister (à la my Hindi films), what if he refused, what if he could refuse? We will never know, will we?

Those who know me well know that I am not, I repeat, not, anti-abortion (those of you who are aware of the US scenario will appreciate the full force of that statement). I don’t consider a ball of cells (morula, gastrula, blastula) to be a living individual. I do draw a line at the fully-formed fetus, with neurological and cardiac activity, but to me, pre-partum, the mother’s health, well-being and wishes are paramount. But this is not one of those situations.

Here is a child who was created with the specific purpose of saving his sister’s life (hence the somewhat awful news-media moniker, ‘saviour sibling’). The fact that he had no say in being used thusly gives me a pause. How ethical was it to do that? Does the successful end (remission of his sister’s disease) justify the means? Will his life be just like anyone else’s? Will his parents love and cherish him like his elder siblings? Will his parents and sister be eternally grateful to him, thereby spoiling him silly and making a brat out of him? I don’t have any answer to these questions. Perhaps only time can tell.


How did you react to this news? Did any of you face the same ethical dilemma as I did? Or, am I just over-reacting or confused? Please let me know in the comments.