Author Archives: Editor

Guest Post: Obama’s Cancer Initiative and Animal Research

This is the one of the first posts of a new FBR blog which aims to provide people with relevant, timely and scientifically substantive information about how biomedical research is saving lives. This post was originally posted here, and is reprinted with permission from the Foundation for Biomedical Research. This blog was posted for yesterday’s World Cancer Day.

During his recent 2016 State of the Union Address, President Obama took aim at cancer. Promising to “make America the country that cures cancer once and for all,” the President tapped Vice-President Biden to lead the national effort that will focus on immunotherapy, genomics, and combination therapies to “make a decade worth of advances in five years.”

While animal research is an essential part of biomedical research, it plays an even bigger role in the fight against cancer. What follows are highlights of some of the most promising discoveries and therapies.

cancer-vaccine2

Immunotherapy Drug Development

Immunotherapy is a form of treatment that recruits a patient’s own immune system to fight cancer. Recently, genetically modified animal models have led to a host of effective new immunotherapy drugs.

Glioblastoma Multiforme (GBM) is the “most dangerous and aggressive” type of brain cancer. A diagnosis means a median survival time of 14.6 months. Current therapies, such as specialized chemotherapy, can add 2.5 months to survival, but they only work for less than half of GBM patients.

Immunotherapy offers much promise in treating GBM cancer by modifying the immune response in a way that slows or stops the spread of cancer cells. Current immunotherapies for brain cancer fall into ‘six broad categories’; cancer vaccines, checkpoint inhibitors, oncolytic virus therapy, adoptive cell therapy, adjuvant immunotherapies, and monoclonal antibodies.’

Several new immunotherapies targeting GBM promise to increase the survival rate. One, Rindopepimut, recruits the immune system to attack cells harboring a specific protein that only appears on the tumor. Once clinical trials are finished we will learn all of the animal models used to develop Rindopepimut – public data at present shows that researchers used mouse models in the early phases of creating the drug.

Mice are not the only animal helping to advance GBM research – dogs, zebrafish and fruit flies are also important models of the disease. Dogs have a long history as a valuable partner in cancer research. Dogs can develop spontaneous GBM in a manner similar to people. Researchers are currently giving dogs who have developed GBM cancer spontaneously cutting-edge immunological treatments with the hope of extending their lives and gleaning insights into fighting GBM that could also help people. The University of Minnesota operates a program that has treated over 150 dogs and advanced therapies for both dog and human cancer.

There are also impressive immunological approaches being used to treat other forms of cancer.  Nivolumab, commercially known as Opdivo, is a drug that helps the immune system’s T cells fight cancer in the body. Results have  improved on prior treatments; some patients with highly advanced melanoma have even had their cancer eliminated entirely.

Development and testing of Nivolumab used animal models extensively. Much of the research relied on genetically modified mice, known as PD-1 knockout models. Other animals used include rats, rabbits, and cynomolgus monkeys.

Cell-Based Therapy

Cell-based cancer therapy is a unique strategy wherein a patient’s own T cells are collected from his or her blood and genetically manipulated to be more effective cancer fighters. In CAR T-Cell Therapy, the T cells are modified to recognize certain proteins that appear on cancer cells, then loaded back into the bloodstream, where they go to work to kill cancerous tumors.

CAR T-Cell Therapy was created and refined by scientists using mice, dogs, and monkeys. The research with dogs led researchers at the MD Anderson Cancer Center to develop CAR therapy for dogs with leukemia. In September of 2015, scientists announced that they had developed and tested a cell therapy that cured glioblastoma in half of the mice treated.

Epigenetic Therapy

Epigenetics is the study of cell traits variations that are not caused by encoded DNA but rather by external and environmental factors that can switch genes on or off and affect how a cell reads genes. Epigenetics is what allows stem cells to become specialized types of cells, but may also lead to cancer. Recently, researchers have developed increasingly successful drugs by targeting epigenetic enzymes that regulate the cell. Most cancer treatments seek to kill the cancerous cells; epigenetic drugs make the cancerous cells return to their normal state.

One of the most successful epigenetic drugs, called AG-221, recently put 25 out of 45 patients with acute myeloid leukemia (AML) into remission with minimal side-effects. AG-221 is still in FDA testing, so all of the species of animals used are not yet publicized, but it is known that mouse models were essential to the drug’s development.

Research in Metastasis

Metastasis is the process that causes some cancer cells to break off from the original tumor and take root in a different tissue. Metastasis causes nine out of ten deaths from cancer and there have been few advances in survival rates.

Years of research have led scientists to a better understanding of metastasis. They have identified genes and pathways that drive the spread of cancer and discovered survival methods it uses – and which may be turned against it in future therapies.

Animal models have played a large role in advancing metastasis research. Scientists at Cold Springs Harbor Laboratory used new techniques to create an advanced mouse model of metastatic prostate cancer. By precisely mimicking aspects of the illness, the mouse model will allow scientists to investigate the causes of the disease while also testing new therapies to treat it.

Similar specially-bred mouse models are also used in studying metastatic breast cancer, bone metastasis, and colon cancer metastasis, to name just a few.

Foundation for Biomedical Research

Open Letter to the Australian Senate regarding a proposed bill to ban the import of primates

The following letter has been sent to the Committee Secretary of the Senate Standing Committees on Environment and Communications regarding the Environment Protection and Biodiversity Conservation Amendment (Prohibition of Live Imports of Primates for Research) Bill 2015. This proposed bill would ban the Australian research community from importing primates for use in biomedical research. The following is a segment of the proposed amendment:

Australian Bill

We encourage the scientific community to leave comments of support for our letter in the comment section below.

Dear Committee Secretary,

Nonhuman primate research has played an important role in many medical breakthroughs, from the polio vaccine to the development of life support systems for premature babies.

Studies with nonhuman primates are a small fraction of basic, behavioural, and biomedical research; however, they are critical to scientific research that seeks to address health issues of grave concern to the public. Nonhuman primate research includes studies relevant to understanding, preventing, and treating a range of diseases including, Alzheimer’s, Parkinson’s, stroke, HIV/AIDS, hepatitis, anaemia and a multitude of mental health conditions.

Thanks to research on primates:

  • Polio has been eradicated from Australia, saving tens of thousands of children from crippling disability
  • Thousands of Australians have had Deep Brain Stimulation to alleviate the symptoms of Parkinson’s
  • Over 20,000 HIV positive Australians can live a relatively normal life thanks to the development of antiretrovirals
  • Australian children can be vaccinated against Hepatitis B, diphtheria, measles, mumps and rubella

Measures to constrain nonhuman primate research in Australia puts future medical breakthroughs in jeopardy.

Australian law already bans the use of wild caught nonhuman primates for research (as does the EU). Such laws should continue to be actively enforced to uphold animal welfare standards, but importantly, should not be expanded to prevent important nonhuman primate research being conducted.

Preventing researchers from importing nonhuman primates could prevent scientists from responding to public health issues or new areas of biomedical research in Australia and beyond. The domestic supply of nonhuman primates may be able to provide for most of the needs of the scientific community, but also risks constraining it. Any future Australian research would be limited to species of monkeys currently bred in Australia’s three breeding colonies, effectively restricting the animal models available to the biomedical community.

Research conducted with nonhuman primates is strictly regulated. All research must be approved by Animal Ethics Committees, who apply the 3 Rs framework to ensure that animal studies are Replaced wherever there is a non-animal alternative, Refined to ensure animal suffering is minimised, and Reduced to ensure that as few animals are used as is necessary to produce scientifically viable results. Animal welfare remains a high priority for the scientific community – with animal care personnel and veterinary staff providing round-the-clock care for their wards.

Yours faithfully,

Speaking of Research

Inês Albuquerque
Jeremy Bailoo, Ph.D
Prof Mark G Baxter
Prof Allyson Bennett
Paul Browne, Ph.D
James Champion
Paula Clifford
Amanda M. Dettmer, Ph.D
Prof Doris Doudet
Jazzminn Hembree RLATG
Tom Holder
Prof J. David Jentsch
Juan Carlos Marvizon, Ph.D
Kimberley Phillips Ph.D
Prof Dario Ringach
Simon R Schultz, DPhil

Background Briefing on Animal Research in Germany

Speaking of Research have now added a fourth background briefing on animal research to our list. We now have a German background briefing – in both English and German – to add to our briefings on the US, UK and Canada. We hope this briefing will offer journalists, politicians and the public a short, handy overview of the key facts. Our two-page summary provides information including the number of animals used for research purposes, the laws and regulations surrounding animal research, and some key questions people have.

Download our background briefing on animal research in Germany [or in German]

As with our previous briefings, we encourage those working in universities, pharmaceuticals, and other research institutions, to help share this document when contacting or responding to journalists about research stories relating to their institution. By attaching this background briefing to proactive stories, or reactive statements, it can help ensure that your research is understood within the context of the wider research environment.

We would like to thank Pro-Test Deutschland – particularly Renee Hartig, Florian Dehmelt and Jennifer Smuda – for their help in gathering information on the German legislation, and for translating the German-language version of the document.

The latest version of all our briefings can be found on both the Multimedia resources page, and in the menu system under Facts->Animal Research Briefings.

See a sample of the briefing below:

Briefing note on animal research in Germany

We permit anyone to redistribute this briefing providing it remain unchanged, and in whole, with credit to Speaking of Research.

We would also like to thank the Science Media Centre (in the UK), who’s “Briefing Notes on the Use of Animals in Research” provided the inspiration for our own.

Speaking of Research

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Animal Research Statistics for Northern Ireland 2014

While England, Scotland and Wales (collectively “Great Britain”*) are regulated by the UK Home Office and produce one set of statistics together, Northern Ireland is regulated by the Department of Health, Social Services and Public Safety in Northern Ireland, which produces its own statistics.

According to the Department of Health, Social Services and Public Safety in Northern Ireland, in 2014, there were 19,857 procedures on 18,889 animals*. Most of these were on mice (12,946), but there were also a significant number of pigs (690), sheep (781), cattle (1,661), birds (1,376), and rats (605). In 2014 there were 72 cats (down 17%), and 156 dogs used in research (up 113%) – mainly for translational/applied studies (though 57 dogs were used for regulatory purposes). No primates were used in either 2013 or 2014.

*animals are only counted the first time they are involved in research, so an animal which is used in different projects in both 2013 and 2014 is only included in the 2013 “number of animals”, but will be included in the “number of procedures” for both 2013 and 2014.

CC-BY: www.speakingofresearch.com

Click to Enlarge

Compared with the previous year, there were 3 fewer animals used, a relatively insignificant drop from 2013. Rats and fish both fell as a proportion of the total, but the number of procedures on birds rose.  Also, given the change from reporting the number of procedures in started studies, to reporting the number of procedures in completed studies, comparisons to previous years should be taken with a pinch of salt.

CC-BY: www.speakingofresearch.com

Click to Enlarge

Other things to note from the statistical release:

  • Creation and breeding of genetically altered animals not used in experimental procedures accounted for 15% of all procedures, much lower than the 60%+ in the rest of the UK. Most procedures (49%) were for basic research, followed by Applied/Translational Studies (30%) and Regulatory (4%). [Table1]
  • 69% of research went on in Universities and medical schools, 25% was in non-profit-making organisations and 6% were in commercial organisations. [Table 11]
  • For the first time the Northern Ireland statistics include retrospective reporting of suffering. Rather than just submitting licence proposals to the DHSSPSNI that include estimated levels of suffering, the researchers now have to report on what was actually seen (using a variety of measures). Unfortunately the statistics put these in two separate tables (Table 3 and 8). So we have combined them to get severity for all procedures in 2014. We can see most experiments are sub threshold (4%; less than the introduction of a hypodermic needle) ormild (62%), with remainder as moderate (28%), severe (6%) or non-recovery (0.3%; the animal never awakes from anaesthesia). [Tables 3 and 8]

CC-BY: www.speakingofresearch.com

It should be noted that despite Northern Ireland using over 100 times fewer animals than the rest of the UK, is still holds itself to the same high quality of statistical reporting.

Lastly, by adding the statistics for Great Britain (3,867,439) to those of Northern Ireland (19,857), can see that 3,887,296 procedures on animals were conducted in the United Kingdom in 2014. Nonetheless, when referring to the UK stats throughout most of the website, we will actually be referring to Great Britain.

We are hoping to see 2014 reports for Denmark, the Netherlands, New Zealand and Poland soon.

Speaking of Research

*The statistics for Great Britain tend to be referred to as the “UK Stats”. While this is not technically correct, it is perhaps not too surprising, given that Great Britain accounts for over 99.5% of the UK’s animal experiments.

See the full Northern Ireland statistics here: https://www.dhsspsni.gov.uk/sites/default/files/publications/dhssps/asp-statistics-of-scientific-procedures-on-living-animals-ni-2014.pdf

Read last year’s release here:

http://speakingofresearch.com/2014/11/25/animal-research-statistics-for-northern-ireland-2013/

Why Testing on Prisoners is a Bad Idea

This post was originally written by Tom Holder and posted on the Understanding Animal Research blog. It has been reposted here (with permission). This is not the first time Speaking of Research has posted on this issue, with a previous post by Dario Ringach here. The original post was geared to UK audiences – we had added comparable US statistics where possible in red.

I recently wrote an article for Huffington Post UK on why we should support the new dog breeding facility to be built in Yorkshire. Like many articles dealing with animal research the comment section has a recurring theme – why not use convicts? This is usually (but not always) qualified by suggesting such testing be limited to the most violent offenders (usually murderers and paedophiles). Here is a selection of the comments found below the article:

Testing on prisonersPerhaps I should be unsurprised by the number of commenters supporting testing on convicts, given that support for capital punishment for those convicted of certain crimes has generally been over 50% in the UK (though dropping to 48% in 2014; in the US support was approximately 61% in 2015).

UK Death Penalty Support

UK Support for Death Penalty

Death Penalty Support in the US - Gallup

US Support for Death Penalty. Image not in original post.

But what about the scientific and practical issues relating to the use of prisoners in research?

We will, for the sake of time, ignore the legal arguments. But it should be noted that in order to allow the forced testing of prisoners in the UK we would have to withdraw from numerous UK and EU laws such as The Human Rights Act, 1998.

I am also putting aside the ethical arguments. Following World War II and the discovery of medical experiments on prisoners at Nazi concentration camps, the medical community came up with a set of 10 ethical principles called the Nuremberg code, which ruled out human experimentation without informed consent, and insisted that such research should only happen after prior knowledge gained from animal experiments. This was later built into the Declaration of Helsinki. The ethical debates are wide-ranging, but many of the arguments for and against align closely with those for and against the death penalty.

Medical Histories – do we have them for prisoners?

When scientists want to conduct an experiment to test a theory, they try and limit all other variables. So if researchers want to understand if a medical intervention is having a positive effect, they need to make sure that food, temperature, liquid intake, prior health etc, are as similar as possible. This can be done in animals, where such variables have been controlled and recorded; often since the animals’ birth. From this the researcher can see the benefits (if any) of the intervention, and begin to make conclusions knowing that the only thing that differed between the control group and the main group was the intervention.

This same is not possible with prisoners, whose medical history will be more limited. The individual could have picked up natural immunities to all manner of diseases, creating confounding variables in the research. Many of those in prison have past problems with drugs or alcohol, or other health related issues which may interfere with the experiments.

Genetics research – how could it be done?

There were almost 280,000 procedures done in 2013 to look at genetics. However, there were many more procedures where genetics were studies in relation to other diseases. For example, researchers may have been interested to know whether a certain gene was a risk-factor in cancer, or whether blocking a certain protein (coded for by a gene) would treat the symptoms of heart disease. In 2013, 52% of all procedures in the UK involved the breeding of a genetically modified animal – this is over 2 million procedures.

So, much research into genetics requires scientists to breed mice with certain genes turned on or off in order to understand what effects this has. This obviously has ethical problems with humans; surely the prison-born offspring of a guilty prisoner should be treated as innocent (and thus not eligible for testing). Even if we swept such ethical considerations aside, human reproduction takes 9 months to produce one baby, and then another 15-17 years for the offspring to reach sexual maturity. Mice can reproduce in 20 days, and the offspring are sexually mature within 6-8 weeks. A researcher can study the inheritance and effects of a gene over multiple generations of mice within a single year – the same research would take a lifetime to conduct in humans. The result is that many genetic studies would be almost impossible to conduct in prison populations.

Numbers – are there enough prisoners?

Currently, it is illegal to give a new medicine to a human volunteer until it has been safety tested in animals. This toxicology testing involves giving the new compound to animals and then carrying out a post-mortem examination in order to see if any harm has been done to any part of the animal. Thus toxicology testing using prisoners would necessarily mean the death of the individual. At the moment, around 109,000 animals are used each year in the safety testing of pharmaceutical compounds in the UK. How does this stack up with our prison populations?

Let’s have a look at the prison populations. In 2013 there were 83,842 prisoners – but our commentators want us to limit ourselves to the worst offenders. So limiting the population to those sentenced to more than 4 years (serious crimes) for either violence against a person (which includes murder, manslaughter as well as slightly less serious offences such as assault etc) or sexual offences (which include rape and paedophilia) leaves us with just 21,572.

UK Prison PopulationsAlternatively we could have looked at the annual sentencing. Most violent crimes that people have mentioned in the comments were either violent sexual offences (rape or paedophilia) or murder. Of the 3,687 custodial sentences for sexual offences in 2014, fewer than 2,800 were for serious crimes where the average sentences were over 2 years (which would certainly include rape and paedophilia). Of the 11,098 “violence against the person” custodial sentences, fewer than 700 were crimes involving death (murder, manslaughter, or a driving offence involving someone’s death). So overall we have up to 3,500 new serious violent criminals being added to the potential convict testing numbers every year. While comparable US statistics are difficult to get, consider that the US passes only around 100 death sentences per year to those whose crimes it consider heinous enough to justify the punishment.

In the UK we conduct around 4 million procedures on animals each year (4.1 million in 2013). Even if humans could be used more often, and even if fewer of them were needed for each experiment, it seems hard to square the 4 million procedures with either the 20,000 or so violent criminals in prison at any one time, or the 3,500 new ones coming into the system each year (as others complete their sentences and leave). Even if we just used prisoners for toxicology testing, this currently requires around 375,000 animals each year in the UK. In the US, around 12-25 million animals are used each year, though the number for toxicology is not collated.

Veterinary research

A final area where human research makes no sense (prisoner or otherwise) is veterinary science. While not all treatments are initially developed using the target species (a mouse may help develop a cancer treatment which is eventually given to dogs), the target species will need to be used at some point to test safety and efficacy. Such research could not be done on humans. Just as we use clinical trials on humans to determine the final safety of a new human treatment before it goes to market, so we use animals to test the safety of a new veterinary treatment for that animal before it can be used commercially.

In Conclusion, No

Overall, we see that it would not make scientific sense to replace many of the animal studies with human experiments. Prisoners do not come with lifetime medical histories, their genetics cannot be manipulated, and frankly, there just aren’t enough of them. It would not make scientific sense to use humans as a replacement for animals.

And while I said I would not ponder the ethics of testing on convicts, I will share a single ethical question that a colleague put to me. If it were morally acceptable to conduct medical testing on violent criminals, would it also be morally acceptable to eat them?

Tom Holder

A request to our multilingual readers

To our multilingual readers (or our monolingual readers’ multilingual friends), we need your help. We have been trying to build up a picture of animal research worldwide, however our efforts are limited due to language barriers in some countries. So far we have statistics for 13 countries and the EU, copied below. We are looking for people in other countries (or who speak the language) to help us get the animal research statistics for 2014 (or failing that, 2013).

Multilingual SpeakersDifferent countries have their own reporting requirements. All EU countries must now collate and report their animal research data in the same way (though some countries are slower than others at publishing these). On the other hand, countries like Australia do not collate them centrally, instead leaving this to individual territories – some of which collate these statistics, some of which do not.

In order to report on a country, we (at minimum) need the number of each species, or the number of procedures on each species, used in research in a given year. However, additional information on types of research, severity, previous years, etc., all help build up a picture of research in the country. It is also helpful if you can give us an English translation of the headings in any table that you send us. Information should be sent to contact@speakingofresearch.com

Some information may be easily found online – it is just a case of finding the correct webpage of the correct Government department (e.g. here or here or here). Other Governments have FOI laws which can be invoked by emailing the relevant department and requesting the figures. An example email might read:

To whom it may concern,

I would like to know how many animals were used in research in <country> in 2013 and 2014. Please could you provide these figures, or provide a webpage, with these statistics broken down by species.

Yours faithfully

Here is the list of countries where we currently have statistics. We are also interested in getting more recent statistics where they exist.

Country Year Number of animals (vertebrates)*
Number of mammals exc. mice and rats
More information
Canada 2013 3,023,184 307,109 Link
Denmark 2012 252,825 19,503 Link
European Union (EU) 2011 11,481,521 773,306 Link
Finland 2014 288,142 16,206 Link
Germany 2014 2,798,463 188,872 Link
Ireland 2014 224,249 9,841 Link
Israel 2014 340,330 ~6,800 Link
Netherlands 2013 526,593 38,487 Link
New Zealand 2013 224,048 111,471 Link
Northern Ireland † 2013 18,638 2,798 Link
Spain 2014 808,827 45,290 Link
Switzerland 2014 606,505 22,953 Link
United Kingdom (UK) † 2014 3,867,439 117,546 Link
United States (US) 2014 ~ 12-25 million‡ 834,453 Link

Full information, including explanations for certain elements of the table, can be found here

Thank you to all our readers for your support.

Speaking of Research

Investigating New Zealand animal research statistics

Speaking of Research has prided itself on being the most comprehensive source of information on animal research statistics. We recently got in touch with the National Animal Ethics Advisory Committee (NAEAC), who furnished us with their annual report for 2013.

The National Animal Ethics Advisory Committee (NAEAC) is a statutory body which provides advice to the Minister for Primary Industries and to Animal Ethics Committees (AECs) on the ethical and animal welfare issues arising from the use of live animals in research, testing and teaching (RTT).

In 2013, the number of animals used in research was 224,048.

Species of animals used in New Zealand research in 2013. Click to Enlarge

Species of animals used in New Zealand research in 2013. Click to Enlarge

While the total number of animals fell by 26% from 2012, it should be noted that the numbers of animals used each appears to fluctuate wildly between around 200,00 and 350,000, as we can see below. The main falls in 2013 were in cattle and mice, whereas there were large rises in birds and sheep.

Trends in New Zealand animal experiments 1999-2013. Note 2014 is in a different color to reflect the different reporting requirements. Click to Enlarge.

Trends in New Zealand animal experiments 1999-2013

Whereas in most countries mice, rats, fish and birds account for over 90% of animals in research, in New Zealand it is under 50%. Instead 44% of animals are cattle and sheep, reflecting the huge amount of agricultural research being done. Interesting only 2% (cattle) and 3% (sheep) of these species die or are euthanized (compared with 98% of the mice).

Animal Experiments in New Zealand in 2013. Click to Enlarge

Animal Experiments in New Zealand in 2013. Click to Enlarge

Other information provided by the annual statistics are:

  • Around half the research is done by universities (24%) and crown research institutes (23%) , the other half is done by commercial organisations (46%).
  • Only 36% of animals die or are euthanised. This tends to polarise between high rates for mice and rats, and a very low proportion for sheep and cattle.
  • 27.3% of animals were involved in research with no, or virtually no negative impact on the animal. 47.9% had little impact on the animal, 17.8% had moderate impact, and 2.0% were considered high impact.
  • The main purpose of research was basic biological research (23.4%), then veterinary research (19.5%), then animal testing (13.7%). The rest is illustrated below.

Use of animals in research in New Zealand 2013

The 2014 statistics should be coming out soon and we will report on them when they come out.