Tag Archives: animal research

Herding Hemmingway’s Cats: Book review

What can cats with six toes, flies with wimpy testis, fish with hips, and mice with socks tell us about how our genes work? Turns out, they – together with a cast of characters ranging from bacteria to our own species – can tell us quite a lot.

In Herding Hemmingway’s Cats: Understanding how our genes work Dr Kat Arney takes the reader on a journey through the past and present of the science of genetics, exploring the key discoveries and concepts that are beginning to explain the complex processes through which the hereditary information in our genes constructs us “in all our wobbly, unique and mysterious glory”.

Can this cat be herded? Image: Marc Averette

Can this cat be herded? Image: Marc Averette

It’s a somewhat daunting challenge for a book that weighs in at just over 250 pages, but Dr Arney succeeds with a book that is accessible and entertaining without ever taking its subject for granted. This is in no small way due to the structure of the book, which unfolds in a series of interviews with pioneering scientists – some of whom have Nobel prizes, others who most surely will – whose work has uncovered many different ways in which our genes end up making stuff we need when and where we need it (mostly). Amid the details of their discoveries about phenomena such as junk DNA, gene splicing, imprinting, and RNA interference there are many fascinating glimpses into their personalities, motivations, and occasionally rivalries.

HerdingHemmingway'sCats

For all that Herding Hemmingway’s Cats provides an insight into the tremendous progress that science has made in understanding how genes are controlled, anyone looking for a triumphalist hagiography need look elsewhere.

In the 13 years since the publication of the draft human genome science has learned a lot about the protein coding regions of our genes – the 1.5 % of our  DNA whose sequence is translated into amino-acids that make up the proteins in our cells – our understanding of the function of the non-coding regions of our genes and the areas in between genes is still in its infancy. This is important because while many inherited diseases are due to errors in the protein coding regions, most of the differences we see between each of us individual human beings and between our species and others are due to differences found in this other 98.5% of our genome.

Dr Arney doesn’t shy away from these gaps in our knowledge and deficiencies in our understanding, she positively revels in them, so if you think we know nearly all there is to know about how are genes work than prepare to be surprised. With the help of her interviewees, she  throws buckets of cold water over some popular (and for some profitable) ideas about how the environment can influence the activity of genes, deftly skewers a few much quoted – but unwise – statements by leading geneticists, and shows how even many standard scientific textbooks are surprisingly inaccurate when it comes to explaining the ways in which genes are organized and regulated within cells.

The  interviewees – who are not all always in agreement with each other – are allowed to tell much of the story, and that’s OK, as it allows the author to show the often messy and imperfect reality of cutting-edge science. She approaches her interviews with a lot of humour and an open mind, but also a determination to get to the heart of the matter. Occasionally the author does allow her impatience with some current trends in genetic research to show, for example when discussing the work of scientists who trawl through the human genome looking for associations between small genetic variations called single nucleotide polymorphisms (a.k.a. SNPs, pronounced snips) and particular traits or diseases (in this case those linked to mental health problems) she writes:

But while this might yield a few more interesting links, I’m increasingly feeling that there are limited further gains to be made… To be fair to the snip-hunters, their discoveries do sometimes provide a useful chisel for researchers to start prising open the biological processes that underpin a disease. Not many people want to do that, though, because it’s hard. It involves doing tricky experiments, often using animal models, and taking years to unpick what’s going on. Much easier to apply for a million-pound grant and go fishing for yet more snips instead (I’ll get off my soap-box for now).

She needn’t apologize; her soap-box moment is most apt. This book is at heart a collection of stories of stories about scientists who spotted something odd in an experiment, and then, rather than shrugging their shoulders and moving on, did the tricky experiments, often using animal models, and put in the years to unpick what’s going on. In most cases they are still unpicking it, but through their failures and successes they have already transformed the way we understand how our genes work.

So who is this book for? It’s perfect for undergraduate biology students who are just starting to learn about genetics,and for those of us who have studied genetics in the past and wish to catch up with the current state of the art, but really it’s for anyone who is curious about how the information in our genes becomes us.

Herding Hemmingway’s Cats is a fascinating, funny, and at times provocative celebration of basic science, and an excellent debut by a new author whose enthusiasm for her subject we are sure will entertain and inform readers around the world.

Paul Browne

Herding Hemmingway’s Cats: Understanding how our genes work by Dr Kat Arney is published by bloomsbury Sigma, and is available in book stores nationwide, and online on Amazon as an audio book, hardback and e-book.

Interview: How our outreach experiences have changed!

In this Q&A post, we visit with Jordana Lenon, B.S., B.A., the outreach specialist for the Wisconsin National Primate Research Center and the Stem Cell & Regenerative Medicine Center, both at the University of Wisconsin-Madison. Jordana reaches her 20th anniversary working at the Primate Center this year. Here, she reveals how different her job is today from when she first began.

Speaking of Research (SR): How has your job changed in the past 20 years?

Jordana Lenon (JL): When I began in 1996, I was in charge of the newsletters and developing the center’s website. That was it. Today, face-to-face outreach events, mostly for K-12 groups, along with news media relations, is most of my job. I still edit the newsletters, but we are actually reaching more people we need to reach with our social efforts. And by that, I don’t mean social media, I mean in-person engagement. In the past five years alone, we’ve met with more than 35,000 students, teachers and community members through mostly school family science nights, science festivals, and visits both on campus and out to the schools and civic groups.

WNPRC outreachSR:  How have you advertised your outreach programs?

JL: First, the UW-Madison Campus Visit Program receives most of our on-campus requests. They promote all the science and other campus venues the public can visit on the university’s website. Second, the UW Madison Science Alliance outreach team has an awesome family science night Google docs sign-up sheet that teachers, parent volunteers and we campus presenters can access, which helps immensely with planning and logistics. Third, the power of good old word of mouth and referrals, from teacher to teacher, or from one civic organization chapter to another, cannot be underestimated.

SR: Are there any challenges to orchestrating so much outreach?

JL: Yes. This is the first year that I’ve had to postpone scheduling more than a few visits to the Primate Center Learning Lobby or Stem Cell Learning Lab. Demand is so high, with daily requests right now, that even with volunteers we just can’t meet it. I suppose that is a good problem to have! I would love it if more people would schedule visits in the Fall, because spring, especially April, fills up so fast.

SR: What is the most rewarding thing about your outreach efforts?

JL: Two things, actually. One is that more and more UW scientists and students have volunteered to help each year. This means a great deal to me, because I know how busy they are, how many different directions they are already being pulled in. When I see their faces, their looks of satisfaction, and hear from them how much fun it was afterwards, how great the students’ questions were, how smart the students were, and that they really “get” how important it is to share what they do and what the Primate Center or Stem Cell Center does, that is just an indescribable feeling. Another cool thing I’ve noticed over the past 20 years is that, when I began presenting, people didn’t know much about the Primate Center, where it was or what we did. They didn’t know about our research programs and how we take care of our animals, how dedicated our scientists, students, vets, animal caretakers and other employees are. There was always someone in just about every group who expressed strong feelings against research with animals. Today, it’s more like, “Yes, we’ve visited the Primate Center before and we wanted to come back again with another school group… what you do is so amazing… we support what you do… we know it’s not easy… my friend has Parkinson’s… my son has diabetes… I have MS… I just read you are working on Zika virus… I didn’t know stem cell research really took off here… I have a friend who worked at the Primate Center… I had no idea what you did before this visit… thank you…

Jordana Lenon takes a tour of the new Madison Science Museum with Ellen Bechtol, museum staff member. Behind them is one of the Why Files Cool Science Image Contest winners, of marmoset embryonic stem cells forming neurons, submitted by Primate Center scientists and students in 2015. http://whyfiles.org/category/cool-science-images/

Jordana Lenon takes a tour of the new Madison Science Museum with Ellen Bechtol, museum staff member. Behind them is one of the Why Files Cool Science Image Contest winners, of marmoset embryonic stem cells forming neurons, submitted by Primate Center scientists and students in 2015. http://whyfiles.org/category/cool-science-images/

SR: Are all the audiences so supportive?

JL: Most, but not all. And that’s okay. I want to know what people are thinking, what they know, what they don’t know. I want to answer questions, or find out the answers if I don’t know them. I learn a great deal from my audiences. Most of the complaints and concerns I get these days are from people expressing to me that it is taking too long for more stem cell research “breakthroughs” to get into the clinic. Rarely do I get someone in my groups anymore who tells me that they are an animal rights supporter (versus animal welfare). This may be because activists of all beliefs are using social media more to express their views. I am definitely seeing that our audiences have many more informed questions than when I first began. I think science education, blogs, shows, pro-science websites and social media are also helping, especially with the younger generation. More people are understanding the connections between the medicines and vaccines they take, and that it all began at some critical step along the way with biomedical research and humane animal care. Also, that the research benefits animals as well as people.

The hardest thing to tell people is why the research takes so much time. People are being wooed by these “miracle stem cell cures” on line, for example. So a large part of my job is explaining how research works, how to search clinicaltrials.gov, and what patients should be asking their doctors. But now that I’ve been here 20 years, myself, I can cite research that was ongoing when I began and that is now in clinical trials or even FDA-approved medical treatments and is saving millions of lives.

I am living proof, myself: UW-Madison scientists and physicians used several animal models, including our Primate Center monkeys, to develop new therapies for systemic lupus erythematosus in the 1980s through the early 2000’s. This research is why I am alive and healthy today. Twenty years ago, most patients with SLE were not expected to live a normal lifespan. Even surviving from year to year with this autoimmune disease usually meant forgetting about work or any real quality of life. People are still dying from lupus, but prognoses are getting better every year.

SR: Anything you’d like to add, plans for more outreach development?

JL: Well… I would like to do more social media… but I’m too busy being social to do it!

SR:  Thanks for your stories. Thanks for sharing the important work that you do!

JL: You’re welcome. We had 10 outreach events last week alone, so this week, I have a little more time to write and catch up on email… and get off my feet for a while!

Read more here:  https://www.primate.wisc.edu/wprc/outreach.html

Animal research and the University of Edinburgh: What does openness look like?

Speaking of Research have long urged research institutions to improve the information they provide online about their animal research. It helps the public understand how and why such research goes on, as well as reduces the number of questions an institution needs to answer by making such information readily available.

In 2015 we began collating and rating the information provided by institutions on their websites. Our list now contains over 200 websites in 10 countries, and it’s growing and being updated every day. Until recently we had 10 institutions’ websites which had full marks

The animal research information websites of Speaking of Research and Understanding Animal Research also received full marks. See the grading system here.

Recently the University of Edinburgh (UK) was awarded full marks for its new animal research section of its website. Edinburgh is one of the top ranked universities in the world (24th in THES), with a strong history in biomedical science. Unsurprisingly it is also one of the highest university users of animals in the UK (1st in 2013, 2nd in 2014).

The recent update of their animal research pages have fulfilled our criteria for “More information”, “Extensive Information”, “Case Studies” and “Images/Videos”. Let’s have a closer look at how it achieved this.

The first thing to say is the ease with which the website can be found. It is the second option on Google if you search for “Edinburgh University Animal Research”. It is the second option if you search for “animal research” through the University of Edinburgh website (in both cases the first link is the Roslin Institute – which is part of the University and focuses on animal health research). The website can also be found by clicking “Research” at the top of the page, then finding the “Animal Research” link on the following page.

The website begins with a strong statement in its Facts and Figures section.

Many of the medical breakthroughs we take for granted today – including vaccines, antibiotics, painkillers, asthma inhalers and cancer drugs – would not have been possible without research involving animals.

Animal research remains essential for developing new medicines and veterinary medicines, and for advancing our understanding of the body in health and disease.

It then goes on to explain how that relates to the University of Edinburgh, noting:

We are involved in a wide variety of medical and veterinary research investigating conditions that impact human and animal health across the world. These include diseases such as multiple sclerosis, Alzheimer’s disease, cancer and heart disease, as well as investigations in avian influenza and E. coli in farm animals.

The News page collates stories linked to animal studies – explaining how and why certain species of animal were used to learn more about certain conditions or physiological processes. These stories are illustrated with pictures of the animals’ in question. For example:

There are a number of pages explaining how and when animal research is conducted, including details on the regulation, welfare and the ethical review process. There is also a whole section on the 3Rs, including examples of how the University has implemented each of them.

Finally, as an institution which is often FOI’ed for its animal numbers, it has taken the decision to publish these numbers openly.

http://www.ed.ac.uk/research/animal-research - 16th March 2016

Such open information reinforces the view that the University of Edinburgh have nothing to hide. They signed the Concordat on Openness on animal research in the UK, which has helped drive many institutions into improving their web information – indeed one of the commitments signatories must abide by is to include a statement on their use of animals. Providing statistics online can also help take the momentum out of activist-driven stories about the number of animals used in research in a given institution – it’s generally not newsworthy when the information is freely available online.

So all that’s left to say is well done to the University of Edinburgh for its fantastic web resources. Speaking of Research will continue to celebrate good examples of openness and public outreach wherever we can find it.

Has your institution got a statement or set or web pages explaining its animal research for the public? Is it on our list (if not, tell us)? Could it be improved? Speaking of Research has written about what makes a good public-facing webpage on an institution’s animal research.

Speaking of Research

How zebrafish help advance cancer research

Do sharks get cancer?

Despite the widely touted myth that sharks do not develop cancer, fish of all species do occasionally develop spontaneous tumours. This is of course also true for the most common of laboratory fish, the zebrafish. In this article, I will give you a brief overview of how the unique properties of the zebrafish have been exploited by scientists to generate very useful models to study the molecular basis of various cancers.

The use of zebrafish in cancer biology goes right back to when scientists first started using them in the lab, at which point it was noticed that they spontaneously develop various kinds of tumours. However, using these naturally occurring malignancies to study cancer development is rather impractical – not only would you need a lot of fish due to the rarity of these cancers, but there would also be a lot of heterogeneity as to what kinds of tumours develop. This is clearly not ideal if you want to study the molecular basis and treatment options of one particular cancer.

From disease to model

Subsequently, carcinogenic chemicals were used to speed up the onset of cancer development. However, similar to using naturally occurring tumours, this strategy is not terribly useful for studying one particular kind of cancer, as the resulting tumours can still be very diverse(although some substances tend to always cause the same type). This approach is mostly used to identify cancer-causing chemicals during human and environmental safety testing.

To study one specific cancer type in detail, scientists started to create zebrafish carrying particular loss of function mutations (i.e. genes that lose activity due to a change), or overexpressing certain cancer-causing oncogenes (i.e. genes that cause cancer when they are overly active). Usually, this leads to the early development of only one – or at most a few – types of cancer. The first of these more specific models were acute lymphoblastic leukaemia (ALL) models, but nowadays there are models for cancers of various tissues, ranging from the brain to the pancreas.

Most of these mutant models were originally created using mutagenizing drugs followed by screening for a phenotype, but recently the research community has shifted to more targeted techniques. These make use of novel genome editing tools, such as the CRISPR-Cas9 system to switch off certain genes. The overexpression of specific genes on the other hand was usually achieved using proteins called transposases to integrate novel genetic information, but very recently the CRISPR-Cas9 system has also been tweaked to do the same.

Why study cancer in fish?

So why would anyone bother to go through this effort and do all this in fish, if we can just use the more closely related mice or rats? Apart from the lower expense and easier generation of large numbers of fish, the main reason why fish are used is that visualizing particular cells is much easier than in other organisms. This is mainly due to two factors: the existence of various transgenic fish lines in which a particular cell type is labelled, and the existence of transparent adult fish (the casper fish, as below).

Casper_fish

Transparent fish like these Casper fish shown here allow researchers to track cells inside the body of adult fish much more easily than ever before

The ease of labelling specific cell types has been exploited elegantly for studying the clonal expansion of cancer cells that drives tumor growth in vivo as it happens, as well for the study of cancer metastases. Now that adult transparent zebrafish have enabled even easier in vivo imaging, the approach has been used successfully to visualize the process by which metastases arise and cancer cells distribute throughout the body.

Understanding the origins of melanoma

A recent paper from Charles Kaufman of the Harvard Stem Cell Institute and colleagues nicely illustrates how these advantages can be very powerful indeed. In this paper published in Science magazine, the researchers used a zebrafish melanoma model that they had developed a few years earlier which expresses gene variants associated with the cancer in humans, and combined this with a newly developed transgenic zebrafish line, in which cells expressing a gene known as Crestin, which is involved in early neural development , are labelled in green. The Crestin gene is normally not expressed in adult humans, but is switched on again in melanomas. This is also why this combination is interesting; emerging melanoma cells will re-express the normally silent gene and be labelled fluorescently.

This method allowed the researchers to track melanoma development from the very first tumour cell to the macroscopically visible tumour comprised of millions of cells. The very early changes that have to occur for cancer to develop can now be studied at much greater detail than before, as these very early tumorigenic cells are extremely hard (or completely impossible) to distinguish from normal cells if they are not labelled. In this specific case the researchers identified the activation of several gene pathways that are usually involved in neural crest development in the embryo as key events in the initiation of melanoma, and believe that their findings could lead to a new genetic test for suspicious moles in patients. Their work suggests a model of cancer development where normal tissue becomes primed for cancer when oncogenes are activated and tumour suppressor genes are silenced or lost, but where cancer develops only when a cell in the tissue reverts to a more primitive, embryonic state and starts dividing.

This paper increased our understanding of the underlying biology of the very early stages of tumour development, and a detailed understanding of these early steps might be very important when developing preventative or therapeutic drugs.

Image: Kaufman, C.K., et al, 2016. A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation. Science, 351(6272), p.aad2197. DOI: 10.1126/science.aad2197

Image: Kaufman, C.K., et al, 2016. A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation. Science, 351(6272), p.aad2197. DOI: 10.1126/science.aad2197

In summary, the field of zebrafish cancer biology has made great advances in the last decade and will continue to do so with the increasing popularity of genome editing techniques. The easy visualization of particular cell types leads to distinct advantages of using zebrafish, particularly for the study of metastases and the very early stages of cancer development.

Jan Botthof

References
Kaufman, C.K., Mosimann, C., Fan, Z.P., Yang, S., Thomas, A.J., Ablain, J., Tan, J.L., Fogley, R.D., van Rooijen, E., Hagedorn, E.J. and Ciarlo, C., 2016. A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation. Science, 351(6272), p.aad2197. DOI: 10.1126/science.aad2197

Over 200 institutions publish online animal research position statements

It’s a good start but there’s plenty more still to be done, and it is being done. Yesterday the University of Edinburgh launched their excellent new animal research resource  http://www.ed.ac.uk/research/animal-research, too late to be included on our list this time around, but definitely worthy of full marks!

Over 200 research institutions now have clear policy statements or public facing web pages to explain the institution’s position on animal research according to Speaking of Research. In 2015, Speaking of Research began logging the policy statements of research institutions in Europe, North America and Australia.

Edinburgh_AnimalResearch

These web statements have been graded from 0 to 4, based on the level of information an institution provides about its animal studies. This information includes the level of detail of an institution’s research, its welfare procedures and the use of case studies, images and videos. To date, only 10 research institutions have received full marks, two in Germany, and four in each of the UK and US.

The list has been a joint effort by the research community, with scientists and members of the public submitting web statements they find – from their own institution or others – through a form on the Speaking of Research website.

Speaking of Research Director, Tom Holder, said:

There is a strong push worldwide towards openness in animal research. Speaking of Research encourage the scientific community to ensure their own institution has a clear and public statement on the importance of animals in medical and veterinary research, and to submit such statements to our website.”

The US has become increasingly open about its animal use in the past decade. Many more institutions are publicising details of the types of research going on, and the reason why on their website.

Paula Clifford, Executive Director of Americans for Medical Progress, said:

Openness about how medicine is advanced, especially information on the vital role of research animals and the care they receive, gives citizens truthful information and the knowledge necessary to make an informed decision to support of the scientists who work every day to improve the quality of life for both people and animals.”

Prof Dan Uhlrich, University of Wisconsin-Madison’s Associate Vice Chancellor for Research Policy, said:

Our work is important enough to merit public funding, so it’s important we make an effort to show people how and why animal research is conducted at the University of Wisconsin–Madison.  We’re gratified to be acknowledged for that effort and pleased to see partners and colleagues making the same commitment.”

While many institutions have received zero or one tick, they are still doing much better than those institutions which do not discuss their animal research in a statement on their website at all. We congratulate each and every institution that puts up any statement which clearly explains why they conduct animal studies.

Those institutions with full marks are:

 

HPV vaccines and cervical cancer – a success in animals is a success for humans

A recent article in the journal Pediatrics reported that vaccination against human papilloma virus (HPV) resulted in a 64% reduction in infections in girls aged 14-19 (1).

The vaccine, Gardasil, came onto market in June of 2006 and protects again four different HPV types: the two most prevalent high-risk viruses, HPV16 and HPV18, and the two most common causes of benign genital warts, HPV6 and HPV11. Protection against HPV16 and HPV18 is particularly important to human health given that these viruses are responsible for 70% of cervical cancers in women – a cancer which caused 270,000 deaths in 2012. The effectiveness of the HPV vaccine is excellent news in our quest to reduce the deadly toll of cervical cancer, and received widespread coverage in the mainstream media.

Vaccination against HPV prevents cervical cancer. Photo: Art Writ

Vaccination against HPV prevents cervical cancer. Photo: Art Writ

Where did the HPV vaccine come from?

As with most medical discoveries, animal research played a vital role in the development of the HPV vaccine, one that is discussed in depth in a recent issue of FASEB’s “Breakthrough in Bioscience” . From rabbits, to mice, to non-human primates, many species were involved in uncovering the link from HPV-cervical cancer and in developing the first effective vaccine.

Early observiations

In the early 1930s, Richard Shope isolated viral particles from wart-like tumors (papillomas) on the Eastern cottontail rabbit. These particles were then applied to non-infected rabbits, and within six to 12 days these rabbits, too, had developed warts. Shope also observed that the warts of the infected rabbits often progressed to cancer after about four months. This was the first animal model showing the progression from viral infection to cancer.

Papillomaviruses are highly species specific. That is, a rabbit papillomavirus will only replicate in rabbits, and a human papillomavirus will only infect humans. As such, an animal model that would effectively grow human papillomavirus was necessary to begin to understand the virus better. Immunocompromised mice (mice that lack a functional immune system) proved to be an effective model in which to grow human papillomaviruses. This breakthrough provided researchers the means understand the virus’s lifecycle as well as the host’s immune response paving the way towards the development of the HPV vaccine.

 Wild rabbit with tumors caused by papillomavirus infection


Wild rabbit with tumors caused by papillomavirus infection

While much was being learned about the biology of papillomaviruses through  animal studies, the demonstration by Harald zur Hausen and colleagues at the University of Freiburg that HPV was present in the majority of cases of cervical cancer suggested that vaccination may provide a means to prevent this deadly disease.

The path to a vaccine against cervical cancer

It wasn’t until the early 1990s that scientists were able to determine what the components of a vaccine should be. Because HPV is a DNA virus, it would have been unsafe to deliver the DNA since it alone is enough to cause cancer. Researchers needed an alternative, and they found that in the discovery of virus-like particles (VLPs), which are multiple copies of the main structural protein of HPV. Injection of bovine papillomavirus capsid protein L1, a protein that forms the outer shell of the virus, was found to induce a strong immune response in rabbits, and that the rabbits produced antibodies that bound strongly to bovine papillomavirus in vitro.  Researchers now needed to determine if delivering the VLPs were safe and effective protecting against HPV.

Because of the species-specificity of the papilloma viruses, animal efficacy trials had to be done with the animal equivalent of the vaccine. Investigators relied upon the biological effects of nonhuman papillomaviruses in nonhuman models to form the groundwork for HPV studies. The  bovine VLP based vaccine was found to  protect against the virus in cattle, and subsequent species-specific versions of the VLP vaccines were tested in rabbits and dogs. The vaccinated animals produced high levels of antibodies and the vaccines were at least 90 percent effective at preventing warts following exposure to papillomavirus. Next, VLPs of human papillomaviruses were tested in nonhuman primates to see if they could induce an immune response, and they did.

Clinical trials with human volunteers showed that the HPV VLP vaccines induced high levels of antibodies against HPV. Women vaccinated in the trials were also protected from persistent HPV infection and precancerous cervical changes. Because of the success in the human trials, Gardasil, the first vaccine against HPV, was approved by the FDA in 2006. In 2015, FDA approved a new version of the vaccine that is effective against nine types of HPV.

The value of vaccines…the need for animal research

The widespread coverage of the study showing the effectiveness of vaccination against HPV in preventing cervical cancer is a sign of how people appreciate  the importance of vaccination to protect against disease, despite ongoing misinformation campaigns  by misguided – and sometimes sadly high-profile – anti-vaccine activists.

Another sign of the importance people place on vaccines play protecting human health from disease comes from the UK, where a petition to the UK Parliament  asking the Government to “Give the Meningitis B vaccine to ALL children, not just newborn babies” has become the most popular UK Government e-petition to date. The UK was the first country to introduce a vaccination programme – with the Bexsero vaccine –  in babies against Meningitis B, and MPs and the government will need to weigh the benefits of increasing protection against the cost of the vaccine carefully.

Whatever their decision, it is good to note that the public recognize the critical role vaccines play in protecting health. They should also remember the critical role played by animal research in vaccine development, indeed, in an earlier post on this blog we discussed the innovative “reverse immunology” approach in mice that led to the development of Bexsero.

While we rightly celebrate the benefits of vaccination, and advocate for vaccines to be made available to all who need them, we should also remember where those vaccines come from, and ensure that the animal research that is so vital to their development continues.

Anne Deschamps

  1. Lauri E. Markowitz, Gui Liu, Susan Hariri, Martin Steinau, Eileen F. Dunne, Elizabeth R. Unger “Prevalence of HPV After Introduction of the Vaccination Program in the United States” Pediatrics, Published Online 19 February 2016. http://pediatrics.aappublications.org/content/early/2016/02/19/peds.2015-1968

PR, ethics, and the science of head transplants

There has been a lot of media coverage on the recent claims by Dr. Sergio Canavero that he has successfully transplanted the head of a monkey on to a donor body of another monkey. This story, originally posted by the New Scientist, has since gone viral with some touting miracle cures for paralysis, while others have publicly expressed outrage and disgust. As pointed out by the New Scientist, this is not science, or at the least, not yet. Until the veil of secrecy concerning the conduct of this study is made transparent – no formal conclusions can be made and one can only speculate in regards to the quality of the experiment that was performed. Moreover, as this work still has to pass through the peer-review process, it remains unclear whether this is simply an attempt at publicity. As Arthur Caplan, a New York University bioethicist told New Scientist:

It’s science through public relations. When it gets published in a peer reviewed journal I’ll be interested. I think the rest of it is BS”

So far, the only evidence that Dr Canavero has produced is a picture of a monkey which appears to have had a head/body transplant, as well as a short video of a mouse moving around (despite significant impairments), which also appears to have a transplant (but how long did they live for? When Dr Canavero’s colleague Dr Xiaoping Ren of China’s Harbin Medical University carried out similar head transplants in mice in 2015 they all died within a few minutes of being revived after surgery). While the monkey “fully survived the procedure without any neurological injury of whatever kind”, according to Canavero, it was euthanized after 20 hours for “ethical reasons”. The media storm surrounding this story appears to play up to the researcher’s aims – to find financial backing to continue his research and then move it into humans.

Canavero at TEDx

Two pieces of information in the article by the New Scientist bear scrutiny. The first is that Canavero is quoted as saying “this experiment, which repeats the work of Robert White in the US in 1970, demonstrates that if the head is cooled to 15°C, a monkey can survive the procedure without suffering brain injury.” Second, Sam Wong, author of the article in the New Scientists stated “they connected up the blood supply between the head and the new body, but did not attempt to connect the spinal cord.” Careful reading highlights a simple fact, this study is not novel in any regard – this is a replication of the work by Robert White and is quite simply a “head transplant”. Thus, the same criticisms that were levied in regards to the original experiment by Robert White apply here. As Stephen Rose, director of brain and behavioural research at Open University can be quoted as saying in 2001:

This is medical technology run completely mad and out of all proportion to what’s needed. It’s entirely misleading to suggest that a head transplant or a brain transplant is actually really still connected in anything except in terms of blood stream to the body to which it has been transplanted. It’s not controlling or relating to that body in any other sort of way. It’s scientifically misleading, technically irrelevant and scientifically irrelevant, and apart from anything else a grotesque breach of any ethical consideration. It’s a mystification to call it either a head transplant or a brain transplant. All you’re doing is keeping a severed head alive in terms of the circulation from another animal. It’s not connected in any nervous sense.”

And so, it is worth reflecting at this juncture on the moral and ethical issues surrounding this controversial procedure. Let us assume for a moment that this procedure is in fact feasible. In the original studies by Robert White and Vladimir Demikov, it was made clear that these experiments were lethal for the animal. Simply put, while the head of the animal was capable of “seeing, hearing, tasting, smelling”; none of the other regulatory processes were intact (e.g. breathing) as there was no control over the donor body. Furthermore, like many tissue transplants, rejection of the donor body from the immune system is a large possibility, immunorejection was after all the cause of death in the monkey whose head Dr White transplanted in 2001. Indeed, Canavero has yet to demonstrate any kind of proof of principle with regeneration of nervous tissue with any meaningful metric of control of the donor body.

Perhaps the most interesting insight into Canavero’s thinking comes from a quotation in the New Scientist article where he says:

Gene therapy has failed. Stem cells, we’re still waiting. Even if they come now, for these patients there is no hope. Tetraplegia can only be cured with this. Long term, the body decays, organs decay. You have to give them a new body because even if you take care of the cord, you’re going nowhere.”

These remarks by Canavero are somewhat naive as both gene therapy and stem cell therapy have made substantial advances in recent years, with many therapies now in clinical trials. Furthermore, the claim that “Tetraplegia can only be cured with this [head transplant]” flies in the face of evidence from recent successful animal and clinical trials on a variety of innovative therapies for paralysis, including epidural stimulation, intraspinal microstimulation, neuroprosthesis, and stem cell therapy.

There have recently been a series of major advances in treating paralysis, including epidural stimulation.

There have recently been a series of major advances in treating paralysis, including epidural stimulation.

While there is mounting evidence from studies in rodents that the polyethylene glycol (PEG) implantation approach favored by Canavero may be able to promote repair of injured spinal cord and recovery of motor function in paralyzed limbs, his casual dismissal of the work of other scientists – while often simultaneously citing their work in support of his own approach – exemplifies his arrogance. He would be better off lending his expertise to the work of others who are exploring the potential for PEG in spinal cord repair, work that has the potential to benefit millions of people, but instead appears set on a self-aggrandizing PR campaign in support of an approach that if successful – which seems highly unlikely even if the surgery is a technical success – can only benefit a tiny number of people…potentially at the cost of depriving many other transplant patients of much needed organs.

The reality, however, remains that the procedure exposes the patient (be it mouse, monkey or human) to far greater risks compared to the potential benefits. Indeed, these experiments would never be approved in countries which have strict review criteria, with a clear harm/benefit analysis needing to be performed before such a study is given approval. In these circumstances, the news that leading experts in animal research in China are currently undertaking a major revision to the country’s national regulation on the management of laboratory animals is timely.

But these issues are not unknown to Dr. Canavero. Indeed, as can be seen here (scroll to see response), and in what can only be described as derision and a willful skirting of the law, Dr. Canavero remains set to push forward with his ideas regardless of the consequences. For these reasons we have the gravest of reservations about the course being followed by Dr. Canavero and his colleagues, and call on them to halt this research until a full independent review of the scientific evidence and impact on potential patients can be undertaken.

Jeremy Bailoo and Justin Varholick

The opinions expressed here are our own and do not necessarily reflect the interests of the the University of Bern or the Division of Animal Welfare at the University of Bern.