Author Archives: Blue Sky Science

Animal research openness in action – from Cambridge to Florida

Last week we published an article calling on all involved in animal research to speak up for science as animal rights activists held their annual World Week for Animals in Laboratories (WWAIL), writing:

This year, if your university or facility is among those that attract attention during WWAIL, we ask that you join in the conversation by providing protestors, public, and media your own voice.  Whether it is via banners, websites, or talking with reporters– speak up for science and for public interests in advancing scientific understanding and medical progress. Although it may not matter to those committed to an absolutist agenda, it can matter to those who are interested in building a dialogue based in fact and serious consideration of the complex issues that surround public interests in the future of science, health, and medicine.”

The past few days have seen several great examples of just the sort of engagement with the public that we had in mind, including videos form two top universities in the UK that take viewers inside their animal research facilities.

The first comes from the University of Cambridge, who have published a video entitled “Fighting cancer: Animal research at Cambridge”, which focuses on how animals used in research are cared for and how the University implements the principles of the 3Rs. It includes interviews with Professor Gerard Evans of the Department of Biochemistry, who uses mice in studies of lung and pancreatic cancers, and Dr Meritxell Hutch of the Gurdon Institute, who has developed 3D liver cell culture models that she uses to reduce the number of mice required for her studies of tissue repair and regeneration, as well as with members of staff as they care for the animals.

The second example is another video, this time from Imperial College London, which also show how research staff care for the animals used in research, and features an interview with Professor of Rheumatology Matthew Pickering, who studies the role of complement proteins in liver damage in mice.

For the third example we cross the Atlantic to South Florida, where animal rights activists are trying to close down several facilities in Hendry County  that are breeding monkeys for medical research, a service that is hugely important to biomedical research. One of the companies being targeted by the animal rights campaigns is Primate Products, so we were delighted to see Dr. Jeff Rowell, a veterinarian and President of Primate Products, speak up about the vital work they do in an interview with journalist Amy Williams of local news outlet News-Press.com.

Primate products

During the interview Dr. Rowell discusses how the work of Primate Products is misrepresented by dishonest animal rights campaigns, including the inaccurate and malicious allegations made by the group Stop Animal Exploitation Now (SAEN) in 2010. As we discussed in a post at the time, these allegations were based on the deliberate misrepresentation of photos taken during veterinary care of injuries several macaques received in fighting with other macaques when housed in social groups (a normal though infrequent behaviour in the species in the wild and in captivity).

The News-Press.com article also shows that there is still a lot of work to be done to improve openness in animal research, as the three other companies that are breeding monkeys for research in Hendry County refused to speak with the Amy Williams, a shame considering that it was their decision to base themselves in the county that triggered the current animal rights campaign. While they are justifiably nervous of speaking with the press (some journalists and publications are arguably beyond redemption) the truth is that the “No comment” approach works for no-one apart from those who oppose animal research. In speaking at length with Amy Williams, Jeff Rowell has provided an excellent example that his colleagues in Hendry County would do well to follow.

The initiatives we have seen from the University of Cambridge, Imperial College London, and Primate Products over the past few days are extremely welcome, and we applaud them for their efforts. Nonetheless, we acknowledge that the future of medical science will never really be secure until they are the norm rather than the exception.

Before we conclude, it’s worth noting that it’s not just in the US and UK that researchers are beginning to realise the importance of openness in animal research to counter misleading antivivisectionist propaganda. In Italy Prof. Roberto Caminiti, a leading neurophysiologist at the University La Sapienza in Rome whose work is currently being targeted by animal rights activists, was interviewed recently for an excellent video produced by Pro-Test Italia, in which he discusses his primate research and how it is regulated.

Speaking of Research

Animal Research and the 2015 UK General Election

On May 7th 2015 the British voters will flood to the polls to determine the next Government (which for the second time in a row is likely to be a coalition). The political landscape has changed a lot since the 2010 election resulted in a Conservative-Liberal Democrat Coalition, with the rise of several smaller parties including the United Kingdom Independence Party (UKIP) and the Scottish National Party (SNP). The negotiation process of forming a coalition will mean that smaller parties can make demands on the largest parties (Conservatives and Labour) to secure a coalition agreement.

In the last week the parties have released their manifestos, outlining what they promise to do over the next five years if they are elected into Government. Many of the manifestos have specific pledges relating to the use of animals in medical and scientific research (which is supported by around two-thirds of the British population).

Nature and the Guardian have analysis of what the parties and their  manifestos say about science in general, so this article will concentrate on policies specific to regulation of animal research.

UK General Election 2015

The Conservatives Conservative animal research

The Conservatives (or “Tories”) are the larger of the two parties in the 2010-15 ruling Coalition. Their manifesto’s only mention of animal research says:

“We will encourage other countries to follow the EU’s lead in banning animal testing for cosmetics and work to accelerate the global development and take-up of alternatives to animal testing where appropriate.”

This fits the business-focused Conservative messages. The Coalition Government’s 2014 Delivery Plan on “Working to reduce the use of animals in scientific research“, which called for the UK to “develop an international strategy towards the eventual eradication of unnecessary animal testing of cosmetics products, adopting a science-led approach” (2.2.3).

The Labour Party Labour animal testing

Labour is the second largest party in British politics, currently neck and neck with the Conservatives. Their manifesto mentions hunting, protecting dogs and cats, and defending the UK ban on hunting with dogs, but does not mention animal research explicitly anywhere. Separately, Labour released a manifesto called “Protecting Animals“, signed by the Labour leader which expands on the main manifesto, but similarly lacks any specifics on animal research.

During their previous term in government, which ended in 2010, Labour established the National Centre for the 3Rs, and implemented legislation to stop campaigns of harassment and intimidation against scientists by animal rights extremists.

The Liberal DemocratsLiberal Democrats animal experiments

Traditionally third party in British politics, the Liberal Democrats (or “Lib Dems”) were in Coalition with the Conservatives during 2010-15. The last two Home Office ministers in charge of animal research – Lynne Featherstone and Norman Baker, have both been from the party. Their manifesto states (p82):

“Liberal Democrats believe in the highest standards of animal welfare. We will review the rules surrounding the sale of pets to ensure they promote responsible breeding and sales and minimise the use of animals in scientific experimentation, including by funding research into alternatives. We remain committed to the three Rs of humane animal research: Replace, Reduce, Refine.”

Under the 2010-15 Coalition, funding for the National Centre for the 3Rs rose from £5.3 million to over £8 million. The manifesto also uses the word “minimise” rather than “reduce”, so as not to focus on baseline figures, but on the 3Rs – preventing a repeat of confusion over terminology surrounding early Coalition pledges.

The Scottish National PartySNP animal studies

Buoyed by the Scottish Independence Referendum, the Scottish National Party (SNP) look to be mopping up almost all the Scottish seats in (the Westminster) Parliament, and will likely become the third largest party. Their manifesto promises “further animal welfare measures” but does not specifically mention animal research. They separately promise to increase funding for Motor Neurone Disease, which would likely involve animal studies.

While no other party is likely to reach over 10 seats in parliament (of 650 seats), the following parties are still worth mentioning (of these, only the Democratic Unionist Party (in Northern Ireland) is likely to get over 5 seats).

United Kingdom Independence PartyUKIP animal testing cosmetics

UKIP are a relatively new party at the far right of the British political spectrum. While their polling suggests them getting around 10-15% of the vote, they are unlikely to get more than 3 seats in parliament. Their anti-EU platform means they believe that the UK “can only regain control of animal health and welfare by leaving the EU”. Their manifesto calls for:

  • “Keep the ban on animal testing for cosmetics;
  • Challenge companies using animals for testing drugs or other medical treatments on the necessity for this form of testing, as opposed to the use of alternative technology;
  • Tightly regulate animal testing.”

It would appear that UKIP are trying to put in place the existing UK regulatory system. As Chris Magee, from Understanding Animal Research, says:

“these aren’t bad policies – but we know this because they have been working effectively for at least the last 29 years.”

The Green PartyGreen party ban animal experiments

The Green Party have recently surged in British politics, but are unlikely to make gains beyond the single seat they currently hold.

Their manifesto reads like it was written by the animal rights group, the BUAV:

  • “Stop non-medical experiments, experiments using primates, cats and dogs. End the use of live animals in military training.
  • Stop the breeding and use of genetically altered animals.
  • End government funding of animal experimentation, including any that is outsourced to other countries.
  • Provide greater funding for non-animal research methods and link funding to a target for developing of humane alternatives to animal experiments.
  • Increase transparency and ensure publication of all findings of animal research, including negative findings.
  • Introduce a comprehensive system for reviewing animal experiments and initiate a comparison of currently required animal tests with a set of human-biology based tests.”

Four of these pledges have analogues among the BUAV pledges, and it would similarly result in the end of over 80% of animal experiments in the UK. Quite simply, this policy is a disaster for human and animal health. Interestingly, both the leader of the Green Party (Natalie Bennett), and their only MP (Caroline Lucas), have both signed the BUAV’s pledges.

Plaid Cymru 

This party will be contesting all forty parliamentary seats in Wales. They are likely to come out with up to five of them (they currently have three). Their manifesto pledges:

“[T]he introduction of a European-level Animal Welfare Commissioner and adoption at all government levels of the new and comprehensive Animal Welfare law to end animal cruelty.”

The Democratic Unionist Party

Contesting seats in Northern Ireland, and likely to win 5 – 10 seats (currently holding 8), their manifesto does not mention animal research but says:

“[We want] a UK wide charter for animal protection.”

Some predictions (from April 22nd) on the number of seats parties will win. 326 seats are needed for a majority

Some predictions (from April 22nd) on the number of seats parties will win. 326 seats are needed for a majority

Animal Rights Election Activism

There are also various animal activist groups which are working to convince parliamentary candidates (PPCs) to put in place new regulations for conducting animal studies. Those that have contacted candidates include:

The National Anti-Vivisection Society (NAVS) are focusing on household product animal tests (which will be banned from October 2015), and reforming Section 24 (which is already underway).

The British Union for the Abolition of Vivisection (BUAV) are running their “Vote Cruelty Free” campaign, which asks candidates to make six pledges which would effectively destroy British medical and veterinary research. These include bans on GM animals, on “non-medical research” and on the use of cats an dogs.

Animal Aid are calling for an end to all taxpayer money used to fund research involving animals – thereby denying the National Health Service of many future treatments.

Speaking of Research

Pioneering non-beating heart transplant success – thanks to animal research!

Yesterday a team led by Consultant Surgeon Stephen Large at Papworth Hospital near Cambridge in the UK announced the successful transplant of a non-beating donor heart to heart failure patient Huseyin Ulucan, the first time such an operation has been performed in Europe.

Current practice is for donor hearts are obtained when the donor has been declared brain dead, but their heart is still beating, and the heart is then cooled and transferred to the recipient.  The technique used in Mr Ulucan’s operation involves re-starting the heart in the donor five minutes after death and perfusing it and other vital organs with blood and nutrients at body temperature using the Transmedics Organ Care System (OCS). In this case the donor heart was kept nourished and beating for three hours before being transplanted into Mr Ulucan. The main importance of the technique it that it has the potential to substantially increase the  number of donor hearts available for transplant, though it also enables the surgical team to assess the health of the donor heart more thoroughly.

Transmedics_OCS

The Transmedics Organ Care System.

 

The technique they used was developed by Cardiothoracic Transplant Registrar Simon Messer, who developed it with Consultant Surgeon Ayyaz Ali, and commented:

Using techniques developed to recover the abdominal organs in non-heart beating donors, we wanted to apply similar techniques to hearts from these donors.

“Until this point we were only able to transplant organs from DBD (Donation After Brain-stem Death) donors. However, research conducted at Papworth allowed us to develop a new technique not used anywhere else in the world to ensure the best possible outcome for our patients using hearts from non-heart beating donors.”

This approach, known as normothermic donor heart perfusion, is an example of a technique that is showing great promise in surgery, in 2013 we discussed how the normothermic transplantation technique using the OrganOx system – developed through research in pigs – had been used successfully in a liver transplant operation, and large scale clinical trials are now underway.

In a review entitled “Normothermic donor heart perfusion: current clinical experience and the future” published in 2014 (1) Simon Messer and colleagues highlights the role of research in animals including dogs, pigs and monkeys in demonstrating that Donation After Cardiac Death (DCD) heart transplantation is possible, and that normothermic donor heart perfusion improves the success rate.

DCD heart transplantation has been shown to be possible in animal models [32-34] and in humans [35, 36] provided that the warm ischaemic time could be kept below 30 min. However, we suspect that the only safe way to adopt DCD heart transplantation into routine clinical practice is by ex vivo functional and metabolic assessment following appropriate reconditioning. Normothermic blood perfusion has been shown to be superior to cold storage in preserving DCD hearts in dogs [37]. In the pig, reconditioned DCD hearts were shown to have comparable function to BSD donor hearts [38]. In an asphyxiation pig model, DCD hearts exposed to 30 min of warm ischaemia were evaluated on the OCS using lactate assessment. Four of seven transplanted DCD hearts were subsequently weaned off cardiopulmonary bypass on low dose inotrope [39].”

In a key paper published in 2013 (2) – reference 38 above – an Australian team assessed whether the Transmedics OCS system could be used to successfully transplant non-beating hearts in pigs, concluding that:

The Transmedics OCS provides an excellent platform to assess DCD heart recovery following warm ischemia. Using a clinically applicable model, we have shown that DCD hearts with WIT ≤30 mins appear to be a viable source of additional organs in cardiac transplantation and warrant human studies.”

Pigs are a excellent species for many transplant research studies. Image courtesy of Understanding Animal Research.

Pigs are a excellent species for many transplant research studies. Image courtesy of Understanding Animal Research.

Results such as this led to Simon Messer and colleagues concluding in their 2014 review (1) that:

It is estimated that use of DCD hearts may increase the number of heart transplants by 11–15% [40]. We believe that functional assessment during ex situ normothermic donor heart perfusion must be made prior to transplantation in this setting. In Papworth Hospital, we are currently investigating whether DCD human hearts can be assessed on the OCS using pressure volume loop measurements.

In conclusion, cold ischaemic preservation for the donor heart has been universally adopted into clinical practice over the last 45 years. However, the diminishing pool of ideal donors coupled with the drive to further improve heart transplant outcomes mandate a rethink in this area. Normothermic donor heart perfusion is the logical next step and from the clinical experience to date, appears to hold promise.”

We congratulate Stephen Large, Simon Messer, Ayyaz Ali and colleagues at Papworth Hospital for taking this next important step successfully, and we wish Huseyin Ulucan a full recovery and long life.

Yesterday’s announcement was a reminder that more than 50 years after Norman Shumway’s pioneering heart transplants studies in dogs, animal research remains crucial to progress in this important field of medicine.

Paul Browne

1) Messer S1, Ardehali A, Tsui S.”Normothermic donor heart perfusion: current clinical experience and the future.” Transpl Int. 2014 May 23. doi: 10.1111/tri.12361. PubMed:24853906

2) Ali AA, White P, Xiang B, et al. “Hearts from DCD donors display acceptable biventricular function after heart transplantation in pigs.” Am J Transplant 2011; 11: 1621. Link

 

Animal research successes spur growth in science…but PeTA can only complain

What do multiple myeloma, influenza, advanced breast cancer, atrial fibrillation, thyroid cancer, ear infection, advanced ovarian cancer and obesity all have in common? One commonality is obvious – they cause suffering, sickness and sometimes death in people around the world. Another commonality is less obvious – these are each conditions that are now being treated with new drugs just approved by the U.S. Food and Drug Administration (FDA) in the past three months alone. That’s right… in the period from Thanksgiving 2014 until now, new drugs that treat each of these conditions have become available, and these agents will be used to treat the illnesses that may affect millions of Americans. Eventually, they will likely have enormous worldwide impacts on these diseases. That’s something to be thankful for.

While some are thankful that the scientific progress is successfully tackling human suffering and disease, others cast doubt on the way that progress is achieved. In a newly published analysis entitled “Trends in animal use at US research facilities” [1], employees of People for the Ethical Treatment of Animals (PeTA) – a self-avowed animal rights organization – report that, amongst the largest research universities in the United States, the number of animals involved in research has grown by over 70% during the past 15 years. In their publication, the authors express alarm over the growing use of animals not covered by the Animal Welfare Act (AWA), mostly mice and fish, in biomedical research, without making any mention of the impact of this research growth.

This growth in animal research in the US is directly linked to an accelerating pace of scientific study and its benefits. A brief visit to the FDA’s “New Drugs at FDA page” makes it quickly apparent that the rate of approval of new medications is astounding. Where is this progress coming from? At least in part, it’s coming from the scientific discoveries that are pouring out of the research laboratories located in colleges and universities, institutes and pharmaceutical and biotechnology companies around the globe. A good example is the innovative BiTE antibody Blincyto (blinatumomab) which was approved for use in treating B-cell acute lymphoblastic leukemia in December 2014 (clinical evaluation against other cancers is ongoing); as we discussed in a blog post in 2008, animal research – particularly studies in mice – played a key role in its development and early evaluation.

Thanks to the researchers that occupy laboratories around the world, scientific discoveries are coming faster than ever, and all of us benefit. It’s not just that there is more research being done – it’s that the impact of the science is better than ever thanks to more advanced technologies, accumulating knowledge of how the body works and more advanced animals models, including ones that mimic human disease processes in increasingly sophisticated ways that promote new discoveries and new opportunities to develop novel drugs.

Why is the scale of animal research growing in the US? The answer is clear: scientific progress is cumulative. One discovery often enables multiple other lines of work. The discovery of the structure of DNA, for example, enabled thousands of efforts to find the genetic causes of disease. Because of this, successes build on successes and research grows.

What is the consequence of the growth in animal research? The answer is: new treatments, new cures, less sickness and longer, healthier lives.

In their paper, the PeTA employees fail to mention any of the following accomplishments, allow of which resulted from the growing scientific research efforts around the world:

But this isn’t the end. To these existing accomplishments, add the work that was started in the past 15 years and will yet unfold in the forthcoming decade AND the overwhelming progress in basic/fundamental research that will lead to new treatments and cures throughout the first half of the 21st century, and you have the recipe for a growing animal research infrastructure in this country.

As recent statistics from the UK indicate, the increase in the use of mice and fish in research is driven almost entirely by the increasing number of studies that involve the use of genetically-modified (GM) animals. In other words, the increase is driven by scientific and technological advances that had a profound impact on biomedical research over the past 15 years, rather than any desire to avoid using species regulated by the AWA (while mice and fish studied in Universities are not covered by the AWA, research involving them is regulated in multiple ways, including through the federal Office of Laboratory Animal Welfare which issues the PHS Guide for the Care and Use of Laboratory Animals).

“Recent statistics from the UK indicate, the increase in the use of mice and fish in research is driven almost entirely by the increasing number of studies that involve the use of genetically-modified (GM) animals.”

Growing study of GM animals has occurred because these models are enormously useful. To take just one example, the National Institute of Child Health and Development recently published an online article entitled “It’s in the DNA: Animal Models Offer Clues to Human Development”, discussing the role of animal models in helping to understand human development and developmental disorders. But this is far from the only example, studies in GM mice are key to many of the state-of-the-art emerging fields in biomedical research. These range from the very new areas of optogenetics – which uses light to control activation of individual cells – and gene editing techniques such as CRISPR that have the potential to cure genetic disorders, to new therapies such as cancer immunotherapy and treatments for rare genetic disorders such as progeria and Pompe disease which are being used to successfully treat patients for whom effective therapies were previously unavailable.

The rise in the numbers of zebra fish is also driven by their value as research models. As vertebrates they share over 84% of the genes that cause disease when defective in humans, while their rapid reproduction and transparent eggs make them ideal subjects for genetic and developmental studies. It’s not surprising that they are both an increasingly popular species in basic biomedical research, and in the preclinical evaluation of potential new therapies and of the environmental safety of chemicals.

In recent years zebra fish have become an increasingly popular species in biomedical research.

What the statistics presented by PeTA in their article don’t tell you is that, while the number of experiments and studies have increased, animal research increasingly involves Refined techniques that produce minimized harm to the subjects and Reduced numbers of animals per study. And of course, animal research directly led to the ability to Replace animals in some types of studies, altogether. The efficacy and efficiency of animal research is advancing, and individual discoveries are, on average, being made with fewer animals. That is a fact missed entirely by the PeTA article.

Furthermore, within the concept of refinement is the idea that researchers should use animals that will suffer less in a laboratory setting wherever possible [2]. So replacing a small number of “higher” mammals with a high number of “lower” animals is consistent with the 3Rs principles of animal welfare. PeTA neglect to mention that USDA statistics show a 40% fall in the use of AWA-covered species over the last 15 years, and it is likely that a small proportion of the rise in use of non-AWA covered species is due to technological advances that have allowed non-AWA species (e.g. GM mice) to replace AWA species (e.g. monkeys) in some studies, for example to develop new treatments for HIV/AIDS, in line with the principle of Refinement we have outlined.

Number of animals used annually for research in the US

“PeTA neglect to mention that USDA statistics show a 40% fall in the use of AWA-covered species over the last 15 years”

Through the implementation of these 3Rs, scientists ensure that they engage in socially-responsible and ethical work. What the authors of the PeTA study should do is to explain how achieving their end goal of a virtual end to animal research, which will reverse the trend of accelerating discovery and medical progress upon which it depends, is ethical or defensible.

  1. Goodman, J., Chandna A., and Roe K. 2015. Trends in animal use at US research facilities in: J Med Ethics. 0:1-3
  2. Richmond, J., 2014. Refinement Alternatives: Minimizing Pain and Distress in Allen, D. and Waters M. ed. In Vivo Toxicity Testing” in: Reducing, Refining and Replacing the Use of Animals in Toxicity Testing. Cambridge: RSC. pp. 133

David Jentsch

Students in Rome to rally for Prof Caminiti and future of science in Italy

Tomorrow students at the Sapienza University of Rome – Italy’s largest University – will join their Professors and members of the campaign group Pro-Test Italia outside the Department of Physiology and Pharmacology to show solidarity with Professor Roberto Caminiti, a leading neurophysiologist whose work is being attacked by animal rights extremists.

Tomorrow Pro-Test Italia will return to the streets of Rome, joining students and scientists in support of crucial research.

Tomorrow Pro-Test Italia will return to the streets of Rome, joining students and scientists in support of crucial research.

As with many recent instances of anti-scientific populism in Italy, the campaign against Prof. Caminiti began in earnest with a dishonest broadcast on the Italian tabloid TV news programme Striscia la Notizia which misrepresented the work being done by Pr0f. Caminiti and his colleagues. Prof. Caminiti responded to these false allegations in a video which you can watch here (in Italian with English subtitles)

Following the broadcast the European Animal rights Party (PAE) announced that they would be holding a demonstration Sapienza University of Rome, on February 5 2015, with the declared will to “free” the monkeys that are used by Pr0f. Caminiti and his colleagues. This has sparked concerns that the PAE – and the more extreme animal rights groups who will no doubt accompany them – will attempt to repeat the events of 20th April 2013, when five animal rights activists forced entry into the Pharmacology Department of the University of Milan, stealing hundreds of mice and destroying years of research.

There is, however, a major difference between 2013 and today; today scientists and students are ready to stand up and  defend their research. A group of neurobiology students at the Sapienza University of Rome have organized a counter-demonstration (see this Facebook event for details) tomorrow morning – February 5 – to show support for Prof Caminiti, defend their department, and speak up for the future of scientific research in Italy.

On Monday their stand received a boost when Professor Vincenzo Vullo, Head of the Faculty of Pharmacy and Medicine at Sapienza University of Rome, circulated an email to all scientists, staff and students to express support for Prof. Caminiti, and called on them to join him in defense of the research being undertaken at the Department of Physiology and Pharmacology:

Dear colleagues, dear students,

I transmit an open letter by Prof. Roberto Caminiti in defense of the unacceptable smear campaign underway against the scientific activity of the Laboratory of Behavioral Neurophysiology, Department of Physiology and Pharmacology of our University.

In this regard, I wish to emphasize the scientific value of Prof. Caminiti, an internationally acclaimed researcher whose research has made a significant contribution to the knowledge of the central nervous mechanisms of motor control. I also want to remember especially his human qualities, demonstrated in the constant respect and care with which he always treated animals necessary for his studies.

In expressing my personal solidarity with Prof. Caminiti, I ask for the support of all members of the faculty in defense of the scientific research conducted at the Laboratory of Behavioral Neurophysiology of our university.

Vincenzo Vullo”

The email also included a letter addressed to all staff and students from Prof. Caminiti:

Dear Colleagues, dear Students,
On December 18 2014 the TV show “Striscia la Notizia”, using images illegally shot in our animal facilities, broadcast a report with the aim of stirring in the public opinion a campaign condemning the scientific activity of the Neurophysiology of Behaviour Laboratory, in the Department of Physiology and Pharmacology of our Atenaeum, where other professors and I carry out our scientific activity, which started in the year1985.
To reply to the accusation of animal cruelty, as an act of absolute transparency of research towards the public, I posted online a reasoned reply, in which it is showed and commented on everything that is performed in our laboratories, thanks to several projects financed by MIUR (Italian Government research funder- Speaking of Research) and the EU, and according to experimental protocols regularly authorized by the Ministry of Health.
On January 23 2015, once again “Striscia la Notizia” returned to the topic, using the images we put online, to claim, with the help of a “flora and fauna” specialist (!) that our studies were useless and cruel, where it is unanimously recognized in the scientific community that our research, together with other work carried out in a select group of international laboratories, lead to the development of brain-computer interface in humans and to the cerebral control of artificial prostetics in patients with paralysis due to neurodegenerative or neurovascular diseases, just like similar researches lead to the development of deep brain stimulation in the treatment of Parkinson’s disease.
Exploiting the footage broadcasted by “Striscia la Notizia”, the European Animal rights Party (PAE) launched a national demonstration, set to take place on February 5 2015, in front of our Department, with the declared will to “free” the animals that we are working with, and together with the Antivivisection League (LAV) stated that they have submitted a complaint to the Prosecutor’s Office in Rome, to open an investigation aimed to the confiscation of the animals, and to open a criminal case against me for animal cruelty.
I call on you, confident that you believe in a country guided by reason, commitment and study, and not driven by obscurantism, just like the “Stamina” case, that you all well know (for more on the Stamina scandal see this recent report -Speaking of Research) . And I ask yo to defend, with the appropriate instruments, the scientific activity and the dignity of a Department of our Atenaeum.
On the morning of February 5, wearing a white lab coat and flower in the buttonhole, I will be in front of my Department to defend and reaffirm that ideal that drove us all to become MDs and researchers.
With best regards,
Roberto Caminiti

We congratulate both faculty and students at Sapienza University of Rome for taking this action in support of science, and wish them, Pro-Test Italia, and all friends of medical progress every success as they stand together in this noble cause.

Speaking of Research

Peritoneal Carcinosis and HIPEC: A second chance for patients, thanks to animal research

When we hear the phrase ‘animal research’ we tend to think about the development of new drugs for the clinical practice, or studying molecular pathways involved in the progression of disease; but we must also remember that the techniques used in the operation room are a consequence of biomedical research, including the use of animals. It is not just the creation of these techniques but also for the prior steps necessary for us to consider a surgical technique as an option when faced with a disease. An example of this is research into a type of cancer known as Peritoneal Carcinosis (PC) and the development of a technique, known as HIPEC, that may dramatically improve the prognosis for patients with this type of cancer.

What is the definition of Peritoneal Carcinosis? We describe this medical condition as the presence of neoplastic nodules caused by the spreading of a primary or secondary tumor in the peritoneal cavity. The peritoneal cavity, also called the abdominal cavity, is the largest body cavity and contains many of the major organs – such as the liver, kidneys, stomach and intestines – surrounded by a protective membrane known as the peritoneum.

Although PC is sometimes seen in primary tumours, such as peritoneal mesothelioma or Pseudomyxoma peritoneii, it is more frequently observed as a metastatic diffusion of gastroenteric (stomach and colon, primary) or gynaecologic (ovarian) tumors. In the second situation, we could see it as an advanced manifestation present at the same time as the primary neoplastic disease or appearing in the years following treatment of the tumour. This condition is often associated with a poor prognosis (about 6 months), depending on the site to which it spreads, the involvement of abdominal organs (like colon or liver) and how aggressive is the tumor at the moment of diagnose.

Peritoneal Carcinosis viewed by laparoscopy. Image: www.cancersurgery.us

Peritoneal Carcinosis viewed by laparoscopy. Image: http://www.cancersurgery.us

In the past, physicians have had only two options when combating the disease: systemic chemotherapy or palliative surgical therapy to debulk the tumor masses- removing as much as possible of tumors which cannot be entirely removed –  and prevent severe conditions such as bowel obstruction. Recently, surgical research developed another therapeutic approach, known as Cytoreduction (CR) associated with Hyperthermic intraperitoneal Chemotherapy (HIPEC). This technique consists of a two-part operation: during the first part, the surgeon debulks as much of the neoplastic nodules in the peritoneal cavity as possible, and in the second stage the peritoneal cavity is washed with a hyperthermic chemotherapy solution, where a solution containing a high concentration of chemotherapy drugs is heated to above body temperature (usually 41.5°-42.5°C) which increases absorption of the drugs by the target tumor and therefor their effectiveness.

The role of the hyperthermic solution and the possibility of using a high-dose of chemotherapic agent was developed through research in rodents and dogs: these studies demostrated that the peritoneal barrier itself is not a barrier that prevents substances from pass through it. This is in agreement with observations made during surgery in human patients, when we remove the peritoneum (for example, when we debulk a neoplastic nodule on a peritoneal surface with a technique known as peritonectomy) the rate at which drugs are cleared from peritoneal cavity is not significantly affected. [1]

Studies in dogs and subsequently in human volunteers demonstrated that the high concentration of chemotherapeutic drugs in the peritoneal cavity is not related to a high concentration of these in the blood stream [2]. In particular a key study undertaken in dogs by Rubin et al. [3], consisted of studying the effects of removing portions of the perotineum such as the the omentum, the mesentery or the small bowel on the clearance of substances like glucose, urea and insulin from the peritoneal cavity. Surprisingly, this experiment indicated that these operations do not influence the clearance of these substances. On the base of these observation, clinical studies were started on clearance of drugs from the peritoneal compartment:. These clinical studies demonstrated that the process observed in dog with other substances occured also with drugs and that, in some cases, the concentration of a drug within the peritoneal cavity could be extremely high without having effects on the concentration in the bloodstream.

A natural consequence of this evidence is that we can use a high-dose chemotherapy drug against these nodules without having systemic adverse effects on the patient, a problem frequently observed in conventional systemic chemotherapy. These studies also led researchers to reconsider the spreading of a tumour in the peritoneal cavity not as a systemic dissemination but as a local disease, and that treatment might be able to cure it rather than just have a palliative impact. If the peritoneal barrier can selectively allow only some molecules to pass through, it could have also an active role on slowing the diffusion of metastatic cancer cells.

This evidence, together with the property of hyperthermia in helping drugs to penetrate cancer cells [4], and avoid the normal defences that a tumor cell has, led to development of this ambitious surgical technique.

The results of this combined technique is clear. Against primary tumors this technique shows a high survival-rate after 5 years (reaching 96% in some studies [5]). Against secondary spreading of gastroenteric or gynaecological tumours it shows a lower efficacy that may be related to the more diverse biological characteristics of the tumor cells, to the physiopathological features (diffusion, tumor already treated with chemotherapy etc.) and also to the characteristics of the patient (such as clinical status, age, concomitant diseases) [6],[7],[8],[9]. The 5-years survival rate for PC from colorectal cancer, for example, according to studies conducted by Dr. Paul Sugarbaker of the Washington Cancer Institute, one of the most important researcher on this field, is around 40%, when the cytoreduction is complete and the disease is not so diffuse in the peritoneal cavity. [7] Also, this surgical approach can be uses a second time, in case of a recurrence of PC, and, ultimately, as a palliative treatment to delay complications and reduce suffering of the cancer patients.

These numbers could seem low but we have to consider that we’re facing a disease that is often fatal within six months if left untreated. This technique gives patients another chance until very recently, they did not have. Why? Because of research that was built up, in part, thanks to animal research

These results are a direct effect of research in the fields of surgery and oncology, from the including the development of more effective chemotherapic agents, research that, as we have said many times, requires the study of animals for everything from the basic understanding of the processes involved to the preclinical testing a new therapy’s effectiveness and safety profile.

Marco Delli Zotti

[1] Michael F. Flessner “The transport barrier in intraperitoneal therapy” Am J Physiol Renal Physiol 288:F433-F442, 2005. http://www.ncbi.nlm.nih.gov/pubmed/15692055

[2] Pierre Jacquet, Andrew Averbach, Arvil D. Stephens, O. Anthony Stuart, David Chang, Paul H. Sugarbaker “Heated Intraoperative Intraperitoneal Mitomycin C and Early Postoperative Intraperitoneal 5-Fluorouracil: Pharmacokinetic Studies” Oncology 1998;55:130–138 http://www.ncbi.nlm.nih.gov/pubmed/9499187

[3] Rubin J, Jones Q, Planch A, Rushton F, Bower J. “The importance of the abdominal viscera to pertioneal transport during peritoneal dialysis in the dog.” Am J Med Sciences 1986;292:203– 208. http://www.ncbi.nlm.nih.gov/pubmed/3752166

[4] Elwood P. Armour, Donna McEachern, Zhenhua Wang, et al. “Sensitivity of Human Cells to Mild Hyperthermia” Cancer Res 1993;53:2740-2744. http://www.ncbi.nlm.nih.gov/pubmed/8504414

[5] Yan TD, Black D, Savady R et al. “Systematic review on the efficacy of cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei.” Ann Surg Oncol 2007;14:484-92 http://www.ncbi.nlm.nih.gov/pubmed/17054002

[6] Franco Roviello, Daniele Marrelli, Alessandro Neri, Daniela Cerretani, Giovanni de Manzoni, Corrado Pedrazzani, MD, Tommaso Cioppa, MD, Giacomo Nastri, MD, Giorgio Giorgi, Enrico Pinto
“Treatment of Peritoneal Carcinomatosis by Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemoperfusion (IHCP): Postoperative Outcome and Risk Factors for Morbidity” World J Surg (2006) 30: 2033–2040 http://www.ncbi.nlm.nih.gov/pubmed/17006608

[7] Paul H. Sugarbaker “Review of a personal experience in the Management of Carcinomatosis and Sarcomatosis” Jpn J Clin Oncol 2001; 31(12)573-583 http://www.ncbi.nlm.nih.gov/pubmed/11902487

[8] Zanon C, Bortolini M, Chiappino I et al. “Cytoreductive surgery combined with intraperitoneal chemohyperthermia for the treatment of advanced colon cancer.” World J Surg. 2006 Nov;30(11):2025-32. http://www.ncbi.nlm.nih.gov/pubmed/17058031

[9] Bijelic L, Jonson A, Sugarbaker PH “Systematic review of cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis in primary and recurrent ovarian cancer.” Ann Oncol 2007;18:1943-50 http://www.ncbi.nlm.nih.gov/pubmed/17496308

To learn more about the role of animal research in advancing human and veterinary medicine, and the threat posed to this progress by the animal rights lobby, follow us on Facebook or Twitter.

 

Thank You Doctor Salk! (and Drs Enders, Bodian, Landsteiner, Sabin…)

Today’s Google Doodle honours Dr Jonas Salk, who in 1954 created the world’s first effective polio vaccine, which was responsible for launching a campaign that has seen this terrible disease become an increasingly distant memory in most  – though sadly not all – parts of the world.

jonas-salks-100th-birthday-5130655667060736-hp

It’s an opportunity to reflect on the pioneering work of Dr Salk, who was born 100 years today, but we should also remember all the other great scientists whose work made crucial contributions to the development of the inactivated and live polio vaccines.

Salk’s 100yr anniversary: say thank you to those who helped develop the Salk vaccine against polio Tweet this!

Today, in honor of Jonas Salk and all the other polio vaccine pioneers, we are reposting this article, which we first published in 2011.

Albert Sabin and the monkeys who gave summer back to the children.

Albert Sabin has been called “the doctor who gave summer back to the children.”*

Because of his decades of research to develop the oral polio vaccine, children today know nothing of the fear that polio brought to the United States every summer well into the 20th century.  Swimming pools and movie theaters were closed and children were kept inside their homes by frightened parents.  Worldwide, the disease killed millions of people and left legions of others permanently disabled.

Albert Sabin administering the vaccine that saved millions from polio.

Albert Sabin administering the vaccine that saved millions from polio.

We’ve just celebrated the 50th anniversary of the introduction of Dr. Sabin’s vaccine. Estimates suggest that in just its first two years of worldwide use, the vaccine prevented nearly 500,000 deaths and five million cases of polio.  Today, the world is on the brink of realizing Dr. Sabin’s lifetime dream: the eradication of polio from the planet.

The development of the oral polio vaccine required years of extensive research with rabbits, monkeys and rodents.

Animal rights activists long ago seized on a single phrase by Dr. Albert Sabin, and have been using it ever since to try to support their outrageous claim that the developer of the oral polio vaccine(OPV) opposed the use of animals in research.

That phrase, “The work on prevention (of polio) was long delayed by an erroneous conception of the nature of the human disease based on misleading experimental models of disease in monkeys” spoken by Dr. Sabin during a congressional hearing in 1984, has been used in animal rights publications and comments for over two decades.

Dr. Sabin, a member of the Board of Directors of the pro-research Americans for Medical Progress until his death in 1993, spent years working to correct the record.  Here is a letter he wrote to the editor of the Winston Salem Journal, published in 1992.

Winston-Salem Journal

March 20, 1992

The Correct Conclusion

In a recent letter to the Journal (“Misrepresenting Research,” Feb. 20), Dr. Stephen R. Kaufman, the chairman of the Medical Research Modernization Committee, correctly quoted my 1984 testimony before Congress but he drew wrong conclusions from it.  Dr. Kaufman was also wrong when the said “the polio vaccine was based on a tissue culture preparation … not animal experimentation.”

On the contrary, my own experience of more than 60 years in biomedical research amply demonstrated that without the use of animals and of human beings, it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death not only among humans but also among animals.

In my 1956 paper in the Journal of the American Medical Association (Vol. 162, p. 1589), I stated that during the preceding four years “approximately 9,000 monkeys, 150 chimpanzees and 133 human volunteers were used thus far in studies of various characteristics of different poliovirus strains.”  These studies were necessary to solve many problems before an oral polio-virus vaccine could become a reality.

Albert B. Sabin, M.D.

Washington

It is true that in the early years of polio research some lines of inquiry eventually proved unsuccessful. An overreliance on a strain of the virus known as the MV strain that had become adapted to survive only in nervous tissue, and the fact that the Rhesus macaque, while a good model for many aspects of polio, cannot be infected through ingestion via the mouth, led to the incorrect assumption that polio could only infect nerve cells (despite evidence to the contrary from both clinical studies and laboratory studies with other polio strains and monkey species).   These mistakes were unfortunate, though understandable given the fact that virology as a science was in its infancy.

However, these failed attempts do not cancel out the fact that animal research, and research using monkeys in particular, was absolutely crucial to the development of vaccines for polio.  Without it the polio vaccine would certainly not have been developed by the end of the 1950’s, and we might even still be waiting for it.

These vital contributions made by animal research to the development of polio vaccines were not limited to the work of Albert Sabin, and include:

  • The discovery by Karl Landsteiner and Erwin Popper in 1908 that polio was caused by a virus, a discovery made by inoculating macaque monkeys with an extract of nervous tissue from polio victims that was shown to be free of other infectious agents.
  • The subsequent discovery by Simon Flexner  that blood serum from infected macaque monkeys could protect against polio infection.
  • The discovery by Carl Kling and colleagues in 1911, following an earlier discovery that polio virus could be isolated from the lymph nodes of the small intestine of monkeys, that polio virus was present in the throat and intestinal tissues of people who dies from polio. Soon afterwards they isolated virus from the intestines of patients suffering from acute polio, and importantly from family members who did not display the symptoms of polio, establishing that healthy carriers played an important role in spreading the disease. In these studies the presence of polio was demonstrated by injecting filtered fluid from the patients into monkeys, the only method then available to confirm the presence of polio (Introduction to Epidemiology, fifth edition, by Ray M, Merill, Jones and Bartlett Learning).
  • The discovery in the early 1930’s by the Australian scientists Macfarlane Burnet and Jean Macnamara that antibodies against one strain of polio did not always protect macaque monkeys against infection with another strain.
  • The discovery by John Enders, Thomas Weller and Frederick Robbins that the polio virus could be grown in a number of tissue types, not just nerve tissue as previously assumed, a discovery that required the use of mice and monkeys to prove that the cultured virus was indeed polio and still capable of causing paralysis.
  • The determination in 1949 by David Bodian and colleagues at Johns Hopkins University that there were three major families of polio virus, referred to as types 1, 2, and 3, and that a separate vaccine would be necessary for each to give broad protection against polio.
  • The discovery by David Bodian and colleagues in the late 1940’s and early 1950’s that the polio virus entered the body through the mouth, and then needed to pass into the blood stream before it could infect nervous tissue, and that if you could block the infection in the blood you could prevent the virus from entering nerve tissue and causing paralysis. The work of Enders and Bodian paved the way for the development of vaccines by Salk and Sabin.
  • The evaluation by Jonas Salk and his colleagues at the University of Pittsburgh  of vaccine candidates produced by inactivating the virus with formalin under a range of conditions, until a vaccine was identified that was effective and safe enough for human trials.
  • The evaluation by Albert Sabin of hundreds of polio virus strains in hundreds of monkeys and scores of chimps before identifying attenuated strains that were capable of efficiently entering the body through the digestive system and provoking an adequate immune response to protect against the different pathogenic strains of polio while not causing the disease themselves.

It is hardly surprising that those close to Albert Sabin are disgusted with the way in which his views are misrepresented by animal rights activists. Writing for the Wall Street Journal two years after his death Albert Sabin’s widow, Heloisa Sabin, discussed the value of animals to his research.

ANIMAL RESEARCH SAVES HUMAN LIVES

The Wall Street Journal, October 18, 1995

by Heloisa Sabin

Mrs. Sabin is honorary director of Americans for Medical Progress.

That scene in “Forrest Gump,” in which young Forrest runs from his schoolmate tormentors so fast that his leg braces fly apart and his strong legs carry him to safety may be the only image of the polio epidemic of the 1950s etched in the minds of those too young to remember the actual devastation the disease caused. Hollywood created a scene of triumph far removed from the reality of the disease.

Some who have benefited directly from polio research, including the work of my late husband, Albert Sabin, think winning the real war against polio was just as simple. They have embraced a movement that denounces the very process that enables them to look forward to continued good health and promising futures. This “animal rights” ideology — espoused by groups such as People for the Ethical Treatment of Animals, the Humane Society of the U.S. and the Fund for Animals — rejects the use of laboratory animals in medical research and denies the role such research played in the victory over polio.

The leaders of this movement seem to have forgotten that year after year in the early ’50s, the very words “infantile paralysis” and “poliomyelitis” struck great fear among young parents that the disease would snatch their children as they slept. Each summer public beaches, playgrounds and movie theaters were places to be avoided. Polio epidemics condemned millions of children and young adults to lives in which debilitated lungs could no longer breathe on their own and young limbs were left forever wilted and frail. The disease drafted tiny armies of children on crutches and in wheelchairs who were unable to walk, run or jump. In the U.S., polio struck down nearly 58,000 children in 1952 alone.

Unlike the braces on Forrest Gump’s legs, real ones would be replaced only as the children’s misshapened legs grew. Other children and young adults were entombed in iron lungs. The only view of the world these patients had was through mirrors over their heads. These, however, are no longer part of our collective cultural memory.

Albert was on the front line of polio research. In 1961, thirty years after he began studying polio, his oral vaccine was introduced in the U.S. and distributed widely. In the nearly 40 years since, polio has been eradicated in the Western hemisphere, the World Health Organization reports, adding that with a full-scale effort, polio could be eliminated from the rest of the world by the year 2000.

Without animal research, polio would still be claiming thousands of lives each year. “There could have been no oral polio vaccine without the use of innumerable animals, a very large number of animals,” Albert told a reporter shortly before his death in 1993. Animals are still needed to test every new batch of vaccine that is produced for today’s children.

Animal activists claim that vaccines really didn’t end the epidemics — that, with improvements in social hygiene, polio was dying out anyway, before the vaccines were developed. This is untrue. In fact, advanced sanitation was responsible in part for the dramatic rise in the number of paralytic polio cases in the ’50s. Improvements in sanitation practices reduced the rate of infection, so that the average age of those infected by the polio virus went up. Older children and young adults were more likely than infants to develop paralysis from their exposure to the polio virus.

Every child who has tasted the sweet sugar cube or received the drops containing the Sabin Vaccine over the past four decades knows polio only as a word, or an obscure reference in a popular film. Thank heavens it’s not part of their reality.

These polio-free generations have grown up to be doctors, teachers, business leaders, government officials, and parents. They have their own concerns and struggles. Cancer, heart disease, strokes and AIDS are far more lethal realities to them now than polio. Yet, those who support an “animal rights” agenda that would cripple research and halt medical science in its tracks are slamming the door on the possibilities of new treatments and cures.

My husband was a kind man, but he was impatient with those who refused to acknowledge reality or to seek reasoned answers to the questions of life.

The pioneers of polio research included not only the scientists but also the laboratory animals that played a critical role in bringing about the end of polio and a host of other diseases for which we now have vaccines and cures. Animals will continue to be as vital as the scientists who study them in the battle to eliminate pain, suffering and disease from our lives.

That is the reality of medical progress.

 

Animal rights activists are free to express their opposition to the use of animals in research, but they cannot do so by blatantly robbing society of scientific achievements.  This one fact is clear — if our critics had their way, today millions of children would be dead or disabled from polio and other infectious diseases.

* Of course Jonas Salk is equally, if not more, deserving of this accolade.