Monthly Archives: October 2012

Air India supports medical research

In recent years a growing threat to medical progress in many countries has been the refusal of many airlines to carry animals that are destined for medical research. In August Eric Raemdonckdiscussed on this blog how important is for scientists to work together to safeguard medical progress by supporting laboratory animal transport.

 

Air India renews support for medical research by transporting laboratory animals. Image credit: MitRebuad

In September the prestigious scientific journal Nature highlighted this issue in a very strong editorial on the imminent threat posed to animal research posed by campaigns by animal–rights groups such as PeTA to stop air transport of animals by companies such as UPS and FedEx, noting that:

If individual scientists wait until they are personally affected — until the day when that mouse carefully bred in Shanghai or Singapore or Stockholm cannot be had for love nor money in San Francisco — it will be long past too late to mount the vigorous, public campaign in defence of animal research that is so sorely called for at this moment.

As researchers join this battle — and join it, they must — they should, as a first step, work through their institutions, academic societies and umbrella groups to make an urgent, articulate, unified case to UPS and FedEx that the shipping of animals, mammalian and other­wise, is essential for both biomedical research and scientific education”

The Nature Editorial made some excellent points, particularly in observing that it is not only research involving non-human primates that is threatened by transport bans, but potentially – if the situation is allowed to continue to deteriorate – also research involving fruit flies, nematode worms, and even some genetically modified mice, as being able to transport such research animals from breeders or strain archives plays a crucial role in facilitating 21st century medical research. Accompanying the Nature Editorial was a Nature News article that focused on the threat to research using Xenopus frog species if transport companies were to decide that they were no longer willing to carry them. Such research plays a particularly important role in helping science to understand developmental processes in vertebrates, some of you will no doubt recall that the 2012 Nobel Prize in Physiology or Medicine was awarded to Sir John Gurdon for his work on inducing pluripotency in adult Xenopus laevis cells, and this species continues to play a key role in new discoveries that he is making in this field.

This is work that needs to be safeguarded.

But can scientists really make a difference when facing well organized animal-rights campaigns?

The answer is: Yes!

The Nature editorial noted one particular PeTA campaign in particular, one that sought to end the transport of laboratory animals by Air India.

If this is not enough to make scientists sit up and take notice, they might consider the use of lab rodents, now under threat in India from a PETA campaign to halt the transport of all research animals by Air India.”

Last week we were concerned to learn that Air India had caved in to the demands of the animal rights campaigners and creased transporting laboratory animals, issuing an order in August telling managers and supervisors not to accept laboratory animals as cargo. Indian scientists who tried to contact the senior management of Air India were initially disappointed by the lack of response from the company, with Dr Satyajit Rath of the National Institute of Immunology asking:

Is the manager of cargo operations of an airline going to decide the scientific policies of this country?”

Fortunately it now appears that there were some people at Air India, and in the Indian government, who were listening to the scientists, and taking what they had to say very seriously indeed.  Last Friday it was announced that “AI’s chairman and managing director Rohit Nandan has now informed Civil Aviation Secretary K N Srivastava that the order [forbidding laboratory animal transport – SR] has been “subsequently withdrawn””.

This is very good news indeed, and shows that when scientists take the initiative and contact transport companies and government ministers they can make a difference to the policies those companies adopt. It also stresses the need for scientists and scientific organizations to take action to communicate to the public, politicians and the wider business world the importance of animal research, and to respond and debunk the misleading #ARnonsense spread by groups such as PeTA.

 

We congratulate Air India on their decision to safeguard the future of medical research in India, and urge all our readers to offer their support by leaving a comment on the Air India FaceBook page.

 

Speaking of Research

New gene therapy for mitochondrial diseases a step closer thanks to ONPRC

Mitochondria are fascinating. These tiny organelles that reside within almost all of the cells in our bodies (mature red blood cells being an exception) generate the supply of a molecule called adenosine triphosphate (ATP) which is the principle source of energy that cells, and ultimately ourselves, need to survive. They also have an intriguing evolutionary history, being descended from bacteria that over one and a half billion years ago formed a symbiotic relationship with primitive eukaryotic cells that are the ancestors of today’s plants and animals. A legacy of this ancestry is that animal mitochondria contain a tiny genome that encodes 37 genes that are crucial to the mitochondria’s function, and separate from the main genome which is found in the nucleus of the cell and contains just over 20,000 coding genes. Unlike nuclear genes, half of which are inherited from our mother and half from our father, mitochondrial genes are almost always inherited from the mother only, which means that if a mother has a mitochondrial genome mutation it will always be passed on to her children.  However, since a human egg cell contains many mitochondria, and only some of them may be defective, there is usually a threshold level of defective mitochondria which must be reached before the defects cause disease in children, and the severity of disease can be very variable. Nevertheless inherited mitochondrial disorders affect as many as 4,000 children born in the USA every year, and for almost all of them treatment options are limited.

One way in which the transmission of mitochondrial diseases can be prevented is by screening embryos during IVF, and earlier this year we reported on how a team at the Oregon National Primate Research Centre (ONPRC) led by Dr. Shoukhrat Mitalipov discovered through studies performed on Rhesus macaques how to improve the efficiency of this screening. However in cases where screening does not identify eggs that are free from mitochondrial genetic defects other ways of preventing transmission of the disorders are being examined, and one of these is the possibility of replacing the damaged mitochondria with healthy mitochondria from a donor.

Yesterday in a publication in Nature (1), Dr. Mitalipov’s team at ONPRC announced another major advance made possible through research on Rhesus monkeys, the first demonstration that it is possible to replace the faulty mitochondria of a human egg cell before fertilization and create healthy looking human embryos, from which embryonic stem cells could be derived that were identical to controls created through normal IVF.

Mitochondrial Gene Therapy. Source Mitalipov Lab/OSHU

Briefly, the procedure involved the removal of the nuclear genetic material from the egg of a patient whose mitochondrial DNA contains mutations, and its transplantation into an egg containing normal mitochondrial DNA from which the nuclear genetic material has been removed.  More detailed descriptions and discussion of the process used in this therapy and the team’s results can be found on the Oregon Health and Science University website, reports on the BBC and LA Times, and in Nature News, it’s clearly been a study that has caught the imagination of a lot of people!  It’s worth noting that a child born after fertilization with the partner’s sperm would be free of risk from maternal mtDNA mutations as well as being the biological child of the patients, since the mitochondrial genome accounts for only 37 of over 20,000 coding genes in the body it is inaccurate to refer to these as 3 parent embryos.

The news reports make it very clear that research on monkeys was crucial to this advance, indeed the potential of the technique used – which they term spindle–chromosomal complex transfer – was first demonstrated when they were able to produce 3 healthy monkey infants in 2009 (2).  They started by examining the distribution of Rhesus monkey mitochondria during the process of meiosis – the type of cell division through which gametes (sperm and egg cells) are produced – using confocal laser scanning microscopy, and observed that at a particular late stage in the process termed the  metaphase II stage the mitochondria were distributed relatively uniformly throughout the cytoplasm,  except immediately around the chromosomes and the spindle apparatus (a protein structure segregates chromosomes between daughter cells during cell division), which were devoid of mitochondria.  This suggested that it might be possible to isolate the spindle–chromosomal complex at this stage and transfer it to an egg cell from which the egg had been removed without transferring any mitochondria at the same time.

A significant challenge was how to avoid damaging the spindle-nuclear complex during this operation, but the team had recently developed new techniques to transfer the nuclei of adult skin cells from monkeys into egg cells and successfully derive embryonic stem cells from the resulting clones.  By modifying these techniques they were able to reconstructed eggs that were capable of being fertilized normally, undergoing embryo development and producing healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infant macaques originated from the spindle donors whereas mitochondrial DNA came from the cytoplast donors. This set the stage for the work announced yesterday.

In addition to reporting the production of human embryos through spindle–chromosomal complex transfer (ST) this week’s Nature paper (1) also reported the outcome of follow-up examination from birth to 3 years of four monkeys born through ST – the 3 reported in 2009 and one born subsequent to that publication – and found that they were developing normally and were in good health.

Because egg cells only remain viable for a short period of time after they are harvested from a donor, it is considered crucial that ST can be performed successfully using frozen egg cells for this technique to be clinically viable, so the team also examined if it was possible to do this using thawed Rhesus macaque cells. They were successful; the experiment resulted in the birth of a healthy monkey. More surprisingly they also found to their surprise that while the spindle–chromosomal complex could withstand prior cryopreservation the technique failed when the egg into which the spindle-chromosal complex is transferred had been frozen – indicating that most of the damage to the frozen egg is to its cytoplasm, rather than to the nucleus as had previously been thought, a discovery that may have wider implications for the future improvement of human egg cryopreservation and IVF techniques.

Impressive as this study is it is by no means the end of the road, this technique needs further refinement and optimization before anyone should attempt to use it in the clinic, but it does provide both scientists and ethicists with very valuable information.  This is particularly true in the UK, where the Human Fertilisation and Embryology Authority is reviewing this technique and another that is being developed by Professor Mary Herbert at the University of Newcastle. Speaking to the BBC yesterday, Peter Braude, Professor of Obstetrics and Gynaecology at King’s College London, said:

It is exactly the sort of science that the HFEA expert committee recommended needed doing, and demonstrates further the feasibility of this technique.”

We at Speaking of Research congratulate Dr. Mitalipov and his team at ONPRC on their groundbreaking work.

Paul Browne

1)      Masahito Tachibana, Paula Amato, Michelle Sparman, JoyWoodward, Dario Melguizo Sanchis, Hong Ma, Nuria Marti Gutierrez, Rebecca Tippner-Hedges, Eunju Kang, Hyo-Sang Lee, Cathy Ramsey, Keith Masterson, David Battaglia, David Lee, Diana Wu, Jeffrey Jensen, Phillip Patton, Sumita Gokhale, Richard Stouffer& Shoukhrat Mitalipov “Towards germline gene therapy of inherited mitochondrial diseases” Nature Published online 24 Oct 2012, doi:10.1038/nature11647

2)      Masahito Tachibana, Michelle Sparman, Hathaitip Sritanaudomchai, Hong Ma, Lisa Clepper, Joy Woodward, Ying Li, Cathy Ramsey, Olena Kolotushkina & Shoukhrat Mitalipov “Mitochondrial gene replacement in primate offspring and embryonic stem cells” Nature 461, 367-372 (2009) doi:10.1038/nature08368

Statistically Speaking the UK Counts Too

As Speaking of Research becomes increasingly active both sides of the pond we have had an increase in visitors wishing to find UK based statistics. They can now rest assured that such information is available on the UK Statistics page (subsection of Facts). As a result we have renamed our US Statistics page (although the link remains unchanged).

In the UK the Home Office (which issues project licenses) counts all invertebrates (so no numbers on fruit flies or nematode worms) including mice and rats. One can clearly see that mice, rats, fish and birds account for 97% of all animals used in research. Monkeys, cats and dogs together account for approximately 0.1%.

Wealso provide information on types of animals, numbers of animals (and how that has changed over time) and how other uses of animals (e.g. food) measure up to research in the UK. Please peruse the statistics page at your leisure.

Cheers

Tom

Prof. Steven Best gets a taste of his own medicine… and doesn’t like it

Every motherfucker who hurts animals is gonna feel the fear!”  The words come courtesy of Dr. Steven Best, from the Philosophy Department at the University of Texas, El Paso, in the YouTube video below.

Among the “motherfuckers” one will find a medical scientist searching for cures to terrible diseases such as Parkinson’s or Alzheimer’s, a farmer raising animals for food, and a gardener eating a ham and cheese sandwich for lunch. It is no secret, however, that the ultimate target of his moral philosophy is more ambitious — “May this upside down world be set right … and the human voice never again be heardhe declares.  Such expressions of deep, self-hatred for mankind as a whole are commonly shared among animal rights extremists.

For a number of years the UTEP Professor and co-founder of the North American Animal Liberation Press Office has been widely known for endorsing violence in his quest for “total animal liberation” under the concept of “extensional self-defense.”  Acting as a “proxy agent” for the animals, Best and his associates have concluded they (or preferentially someone else that can be solicited for the crime) are justified in using violence to impart their views of morality on the rest of society.  For these groups, “justifiable homicide” becomes an acceptable way to deal with moral disputes.

And what about the law?

In Dr. Best’s words: “Fuck the law. When the law is wrong, the right thing to do is break it”.

There are three points to clarify here.  First, he is not simply talking about civil disobedience or property damage.  “Let every motherfucker who shoots animals be shot; Let every motherfucker who poisons animals be injected with a barrel of battery acid; Let every motherfucking vivisector be vivisected and thrown away like the shit they are,” he wrote in 2011.  Second, it appears the premise is that Prof. Best is the one to decide if the law is wrong or not (society does not really have much of a say).  Third, Prof. Best thinks that event if the law is right, he is entitled to take it into his own hands. For example, it has been reported that:

In April 2010, he posted on NIO a video of himself attempting to confront a man rumored to trap and poison cats that wandered into his yard. The man wasn’t home, but his wife and small daughter were. “If I hear he’s hurting cats, I’m going to be all over his office,” Best told them. “You tell him I’ll have a thousand people all over this place. You tell him Steve Best dropped by. You remember that name.”

Best posted the man’s phone numbers and addresses, along with pictures of his wife and children, beneath the video. In an update the next day, he thanked “all who called and expressed concern” for letting the alleged cat-poisoner know “he is being watched.”

His hateful rhetoric has been duly noted by UK’s Home Office which barred him from ever entering the UK in the future, and by the Southern Poverty Law Center (SPLC), one of the largest nonprofits dedicated to fighting hate and bigotry. The SPLC recently ran an article highlighting Best’s connection and support of the animal right extremists group “Negotiation is Over”. The leader of this group, Ms. Camille Marino, follows her mentor’s teachings when she writes about a UCLA professor in the following terms:

If you spill blood, your blood should be spilled as well. [W]e’re no longer playing games. We will print your information. And we’ll be at your homes. We’ll be at your work. We’ll be at your country clubs and golf courses. We’ll see you at your manicurist and we’ll be kneeling next to you when you take that next holy communion wafer on Sunday. If I have my way, you’ll be praying to us for mercy.

Prof. Best not only provided the ideological basis for Marino’s hate campaign, but as we learned last year, he helped to fund her harassment of scientists and students.

Prof. Best clearly relishes a bit of harassment and intimidation.

Up to a point, that is.  When the same acts are directed his way then he prefers to have the law of the land enforced.

Camille Marino (left) and Steve Best (right)

In Steve Best – Animal Rights Activist vs Camille Marino he wrote that she “apparently has a fondness for blackmail, cyberstalking, harassment, threats, intimidation and slander for she has targeted a number of prominent people she considers her enemies in the US animal rights movement, me above all” (emphasis Best’s).  In the petition Dr. Best alleges verbal, mental and emotional abuse and wrote

She is crazy and she has done this to others so she will not stop with me.  She is suicidal but she told me she won’t go alone and she tastes my blood,  She is very dangerous and I fear for my life.

He adds:

I hope you see how little regard this woman has for the law, I want a full cease and desist order to stop her from ever again contacting me in any way, including ever mentioning my name in any public forum or context whatsoever, including her website and Facebook.

I hope you see how little regard this woman has for the law, for the rights and respect of others […]

I am a Dr. Professor at UTEP and I can’t have her slandering my name and the threats she is posting. Please help me.

So finally Dr. Best gets a taste of his own medicine… and doesn’t like it.

And now, he begs for help from the same organized society he hates and wants to see destroyed.

Really?

[Update: Nature is blogging on this ongoing developing story]

Public Opinion and the Importance of Transparency in the UK

The UK has a long history of animal rights activism and many might expect the public to be a difficult crowd to win over. However over the years the British public have expressed overwhelming support for the use of animal experiments for medical purposes. In 2010 90% were conditional acceptors (that is agreeing with medical research provided suffering is minimised and there are no alternative methods – all of which must be true if a project is to be licensed in the UK) and 60% were unconditional accepts.

So it was with some disappointment that the release of the latest Ipsos MORI polls which show a 5% drop in conditional accepts to 85%, and a 5% drop in unconditional accepts to 55%. To put in perspective, the British public still firmly support the humane, regulated use of animal research in concordance with the use of the 3Rs. It was notable that the survey found that support for animal research and enthusiasm for science was highest among those with higher levels of educational attainment, which should noth be surprising as the Ipsos MORI report notes that “Greater knowledge of science tends to garner more favourability towards it – so ABs [a higher socioeconomic group] are more positive about science’s role (84%), just as they claim to be best informed about scientific developments”.

Nonetheless, David Willetts, the Minister of State for Universities and Science, attended a press conference on the release of the statistics stating that animal research forms a small but vital component of bio-medical research. He also offered examples of some of the UK Medical Research Council funded work in dementia that involved animal work.

So how have research institutions and advocacy groups responded to the (albeit small) drop in support by the public? With action!

Understanding Animal Research have organised the “Declaration on Openness on Animal Research,” signed by 41 institutions including medical research charities (inc. Cancer Research UK and Alzheimer’s Research UK), Universities (inc. Oxford and Cambridge), Pharmaceuticals (inc. GSK and AstraZeneca) and other institutions. Those signatories have agreed:

The life sciences sector is at the forefront of developing ground breaking treatments and cures which transform the lives of humans and animals. To do this we need to increase understanding of normal biological functions and disease. Where possible, we use cells grown in a lab, computer models and human volunteers. When this isn’t possible, research may involve animals. When we need to use animals, we strive to reduce the number needed, and seek to develop viable alternatives.

Public acceptance of the use of animals in research has been strong over the last decade. Public scrutiny has also played an essential role in building the world-leading ethical framework that supports our research and ensures it meets the highest welfare standards, only using animals where no alternative exists.

Confidence in our research rests on the scientific community embracing an open approach and taking part in an ongoing conversation about why and how animals are used in research and the benefits of this. We need to continue to develop open dialogue between the research community and the public.

We, the undersigned, commit to work together to establish a Concordat that will develop principles of openness,

It is fantastic to see institutions agreeing to do more to explain to the public why and how animal research is carried out. We, at Speaking of Research, hope that many more institutions get on board with this Concordat. With almost two thirds of the general public claiming to be poorly informed about animal research, it is important that science institutions do more to fill these gaps in public understanding, let animal rights groups attempt to plug the gap themselves (leading to many of the common myths of research being propagated). After all, the Ipsos-MORI poll shows very clearly that the better informed people are about the role played by animal research in medical science, the more likely they are to support it.

In the meantime Speaking of Research continue to play their part in informing people around the world about animal research. A major campaign at the moment is the Science Action Network, which we urge you to get involved in.

ScienceWhiskers tells the story of the mighty mouse

ScienceWhiskers is a blog dedicated to the “scientific contributions of the mouse.” The blogger, highlights a wide range of topics. Recent examples include how the brain controls eating behavior to a study that may point the way to a male contraceptive pill.

It’s a relatively new blog. An entry dated August 10, 2012 welcomes readers to learn about “everything mouse related in the world of science.” The blogger’s aims are:

 . . . to keep you updated with new research using mice and its impact on science

And

. . . to try and educate you on the use of mice in scientific research and how much this wonderful small creature has helped contribute to science and what we know today.

The blogger also explores ethical implications of research, such as the study in which scientists created mouse eggs from stem cells. He/she also highlights resources such as Shared Ageing Research Models (ShARM), which keeps a database of current research on aging in mice in the U.K., as well as tissue bank of samples. This, as the writer points out, can help to reduce unnecessary duplication of the research.

The blogger is also to be commended for the tone of the essays, which is conversational and informative. This looks to be a helpful resource. Keep up the good work.

Alice

PeTA tries to save face… and fails.

During the past month the University of Wisconsin responded to an aggressive media campaign by PeTA suggesting photos of animal studies they obtained are “proof” of violations of the Animal Welfare Act.

PeTA filed complaints with the USDA and the National Institutes of Health demanding an investigation.  The university responded point-by-point to PeTA complaint stating that none of them were substantiated.

The USDA took PeTA’s complaint seriously, conducted a focused inspection of the study in question, and found the claims by PeTA to be groundless.  As reported by the Capitol Times, the Wisconsin State Journal and the Badger Herald, the USDA found no wrongdoing, no violations of the law.  Not one.

How did PeTA respond to the outcome?

Kathy Guillermo, Senior Vice President, Laboratory Investigations, went to Jane Velez-Mitchell (a PeTA supporter) and told her that “we report them [the alleged violations] to the federal authorities, to the USDA and the National Institutes of Health.” But, she added, “We [PeTA] don’t expect much about those agencies.”

What does Guillermo mean that they do not “expect much” when they file their claims with the authorities?

The USDA did take the claims seriously and took action as they requested.  They investigated the UW and found PeTA’s allegations to be untrue.  What Kathy Guillermo probably means is that when they file a claim PeTA does not expect that the findings will support their allegations. This would make perfect sense, as they probably know beforehand the allegations to be groundless. What PeTA truly expects from their claims is that their propaganda be picked up by the media before they are caught in their game and, unfortunately, they are rather successful in doing just that.

Sadly, it happened again.  In response to the USDA inspection PeTA found a former UW veterinarian that supposedly wrote a letter in support of PeTA’s claims which is being covered by the media.  But what did this veterinarian say exactly?

[…] Brown said the clear inspection report, which cited “no noncompliant items,” is not the fault of the USDA, or the veterinarian staff, but rather the fault of the administration.

According to Brown, who said he is familiar with the specific inspector who evaluated UW’s research facilities and is confident in her work, it is not in the nature of a USDA inspection to point out what is ethically “wrong,” but rather to cite noncompliance.

Hold on.  What is Brown saying?!  He is saying the inspector is known to him, that he has confidence in her work and, by inference, in the result of her inspections.  What is the problem then?  The problem is that in Brown’s eyes the work is unethical.  In other words, he acknowledges the work is legal, regulated, and that no violations of the law took place but, nevertheless, the work is unethical and he wanted the UW administration to take action.

His statement is hardly in support of PeTA’s claims.  To the contrary, it validates the position of the UW and puts confidence in the work by the USDA inspector.  You see, PeTA’s claimed a violation of the Animal Welfare Act — not that the work is unethical.

If PeTA believes the responsible and regulated use of animals to advance medical knowledge and human health is unethical, then they should try to convince the public and our legislators of such view. Instead, their preference to mislead the public and misrepresent the work of scientists are signs they simply cannot make a compelling case to the public.