Tuesday, 29 November 2016

What if the animal tests fail – again?

You might have seen an interesting story in the news earlier this week - WWI antiseptic could fight common cold - and tackle superbugs. 

Okay, I know what you’re thinking! We’ve heard it all before - promises of medical breakthroughs that amount to nothing. We see these articles in the news constantly – taunting the ill and giving hope to those who have none – and then they quietly disappear into the nether.

This one was a bit different though.  The article started:
“A century-old antiseptic made from coal tar and used to treat wounds and sleeping sickness in World War I Australian soldiers has been found to help the body fight off viral infections, including the common cold.”

What I found exciting about this report was that the drug (Acriflavine) was used during World War I – on HUMANS – and found to be effective for the treatment of wounds, bladder infections, gonorrhoea and sleeping sickness.  It was used successfully until being largely replaced by penicillin 70 years ago. So we already know from decades of human use that it is safe and effective.

The drug has also been investigated in human cell cultures where it was discovered that it binds to the DNA of patients to activate the immune system when a viral infection was taking place. It was also tested in human lung tissue to investigate its effect on a common cold virus. It was found that “cells that had been treated with Acriflavine three days prior to the infection had a faster immune response to the virus, and the virus spread more slowly through them than in the control cells.”

Safety in humans established (from over 50 years of worldwide clinical use) – check. Promise of its success in in-vitro tests – check.  The Sydney Morning Herald reportsAs well as fighting the common cold and influenza, it could be useful in containing the spread of viral outbreaks including SARS, Zika and Ebola.

Why then am I still questioning this drug? Because it’s now being tested in animals.

Considering species differences between humans and other animals, what if this doesn't work the same way in mice or dogs or whatever other animal they use? Will it then be discarded despite its track record to date? The research paper already acknowledges some differences in other species: “The response to sub-toxic concentrations of flavine described here is likely to be cell-type dependent, and was, for instance, absent in mouse L929 cells”

Could this potential cure for a wide variety of ailments be discarded if the animal data does not stack up? Or if indeed the drug is marketed despite the differences in animals, well then why proceed with testing on a different species in the first place?

We already know that 92-95% of drugs successful in animal tests fail in human clinical trials. This drug already has a proven record through decades of clinical use in humans. It also shows great promise through in-vitro tests. Let’s not waste precious resources on unreliable and unpredictable animal tests and instead focus on human-specific test methods. Perhaps we will then see one of these reported medical breakthroughs finally come to fruition. 

Friday, 11 November 2016

The evidence is in. We’ve been doing it all wrong!

Last weekend a paper was published in Drug Discovery Today titled “Towards a 21st-century roadmap for biomedical research and drug discovery: consensus report and recommendations.”[1]

The paper, authored by internationally renowned experts in the field of non-animal research, analyses “decades of costly failures translating drug candidates from preclinical disease models to human therapeutic use.” It addresses “the failure of animal studies to predict drug efficacy and toxicity in humans”, examines Alzheimer’s disease, autism spectrum disorders, cholastic liver diseases, respiratory diseases and autoimmune diseases as case studies, and presents recommendations to help achieve a transition towards a human pathways-based paradigm shift.

The paper is not exclusive. A groundswell of literature now supports this view and provides compelling arguments favouring human-relevant (and non-animal) methods of research as being far more likely to accelerate translation to clinical practice and commercialisation.

Meanwhile in Australia, two important documents have recently been announced:
  • Healthier lives, stronger economy: Victoria’s Health and Medical Research Strategy 2016-2020
  • Medical Research Future Fund - Australian Medical Research and Innovation Strategy 2016-2021

The documents spell out the strategies to be employed to progress medical research in Australia.

Of much concern however, is that neither strategy includes any provision or incentives for the development of non-animal alternatives. In light of the new literature, this is rather disturbing.

Australia has made very little progress in replacing animals in research, as illustrated in the vast numbers of animals used each year (Australia is the fourth highest user), and with growing concern within the research community that animal models are not adequate human proxies for research, this is an area that requires urgent attention.

Both the Victorian Health and Medical Research Strategy and the Australian Medical Research and Innovation Strategy could have been opportunities to include a commitment by the Victorian and federal governments to fund research into seeking alternatives to animal use – as is already the case in other countries. In fact, Page 19 of the discussion paper for the Victorian strategy stated that “Australia punches far above its weight by producing 3 per cent of global research publications with only 0.3 per cent of the world’s population. However, compared with international standards, Australia has a poor record of commercial translation…”

Clearly something is amiss. Could it be our ongoing dependence on animal data in pre-clinical research?

Scientific literature raises questions about the reliability and predictive value of animal testing in research for humans. Systematic reviews continue to show that animal experiments are not predictive of human outcomes and can be dangerously misleading.

Humans differ from animals anatomically, genetically and metabolically and interspecies variations are a high cause of clinical trial failure of pharmaceutical products. Animals have different metabolic pathways, present broad ranges of physiological defences, and differ in the way their organ systems respond to toxic insults. Not only does this mean that results cannot be extrapolated to humans, but it also means that some possibly successful treatments are being ruled out preclinically due to adverse reactions or responses in animals. Animal use in research and safety studies is therefore misleading.

Research Translation
In spite of huge research effort and expense, development of new treatments has slowed, as preclinical success has not followed through into clinical trials. The U.S. Food and Drug Administration (FDA) recently reported a 92 percent failure rate of clinical trials following successful animal trials.

In a 2014 British Medical Journal article the author stated, “…if research conducted on animals continues to be unable to reasonably predict what can be expected in humans, the public’s continuing endorsement and funding of preclinical animal research seems misplaced.” (┼×entürk, 2015).

The use of animals in research is, according to the code, for cases where no alternative exists, but alternatives will never exist without support for the development of non-animal based scientific testing methods. There have been international moves towards supporting alternatives to animals in research. Techniques such as computer modelling, genomics, nanotechnology, microdosing, microfluidic chips and imaging techniques, just to name a few, have been developed with government funding and support to provide a human-relevant model. The process has been slow, as old habits persist and development of new techniques takes time. 

I do hope the aforementioned paper receives the attention it deserves.  It is remiss for both the Victorian Strategy and the MRFF strategy to exclude provision for research to replace animals and waste the opportunity to illustrate their commitment to the 3R’s Principle, which would in turn contribute to more innovative, high-quality and translatable research. 

Monday, 3 October 2016

October is Breast Cancer Awareness Month - but are we winning the battle?

October is Breast Cancer Awareness Month. It also marks the five year anniversary of my own diagnosis (making me officially a “cancer survivor”), and while I am of course happy and grateful to still be here, it’s bittersweet for me. You see, during this time I have lost two people extremely close to me, and as I continue to watch others battle the dreaded “C”, it breaks my heart.

I know I’m not alone. There would be very few people who have not witnessed the horrific demise of a loved one through this insidious disease, but it sucks. It really really sucks!

There are some terrific screening programs now to catch cancer in the early stages when it can still be treated. By definition, ‘treated’ means surgically removed, poisoned with chemotherapy and radiated. I can say with authority that all are far from being pleasant experiences, and despite the aggressive attack on the disease the current ‘treatments’ are far from being a true cure.

What irks me most though is the “research”. Cancer is such a frightening word to hear that many people willingly donate to cancer research with the best of intentions, but without much thought, and what they don’t consider is that much of the money is spent on animal experiments. Rats and mice are most often used – despite their anatomic, genetic and metabolic differences to humans. In fact many cancers have already been cured in mice, but they simply don’t work in humans, suggesting that perhaps we should move away from these inappropriate and misleading models of human disease and embrace other more relevant methods of research.

When I was first diagnosed it was of huge concern to me that I would be taking drugs that had been tested on animals. Looking into the drugs I was given though, I learned that the chemotherapy drugs I was to take were discovered around 50 years ago. The logical question then is what has become of all the cancer research since that time and where were all these ongoing promises of cures?

I am currently taking tamoxifen – a common treatment used in breast cancer as it acts as an “anti-oestrogen” drug by blocking the action of oestrogen in breast tissue. However the discovery that this drug could be used to treat cancer was quite serendipitous as it was originally tested as a potential contraceptive.  With regards to its current use in breast cancer it has a similar effect (in low doses) in rats and monkeys, but in mice, dogs and rats (in high doses) it actually has the opposite effect, behaving like oestrogen.  There are also many differences in the drug’s risk factors and side effects.  It is therefore surprising that with such conflicting animal data it ever became available – but I’m very lucky it did!

So I am acknowledging Breast Cancer Awareness Month and appreciate and support the need for greater awareness and early detection, but when it comes to research, please think carefully about where your donations are going. You can donate to health and medical research charities that do not use animals – including cancer groups (which can be found on the Humane Charities List) or you can ask specifically that your donation goes towards awareness, patient care, (human) clinical trials or other non-animal research.

I am hopeful that one day we will - through scientifically valid, non-animal methods of research - find the Holy Grail: a genuine cure for cancer, and no longer will we have to watch as our loved ones succumb to such a cruel and indiscriminate disease.

Monday, 26 September 2016

New guidelines for primate research will not protect our closest relatives

The Principles and guidelines for the care and use of non-human primates for scientific purposes was issued last week by the National Health and Medical Research Council (NHMRC), however it affords little protection for Australian primates used in cruel experiments.

The guidelines have been under review and public consultation for several years.  It is disappointing that the final outcome only serves to reinforce the perceived need to use these sentient and highly cognitive animals.

On both scientific and ethical grounds, HRA is opposed to the use of primates for research purposes and considers that instead of updating policies, more emphasis should be placed on a commitment to sourcing non animal alternatives and phasing out the use of these animals.  In the interim however, the revision of guidelines should have been an opportunity to introduce stricter requirements and policing of their use.

As part of their submission, HRA proposed the following actions:
   tighter regulation and monitoring of all primate research through creation of a national expert Animal Ethics Committee to ensure that there is no repetition and no alternatives to primate use
   a ban on the importation and exportation of primates for research purposes
   establishment of a retirement sanctuary for primates no longer required.

Unjustified cruelty:
The new document states: “The complex and highly social behavior and advanced cognitive capacity of many non-human primates make it difficult to adequately provide for their needs in a captive environment or research setting. In addition, many non-human primates have long lifespans and are often used in long-term research programs or re-used in multiple experiments over the course of their lives, presenting additional challenges for their care and welfare. Consequently, there is concern that the compromise to their life associated with their confinement and use in scientific research may cause greater psychological suffering than with other species.”

This, in itself, should be sufficient reason to end the use of primates in research, but when we also consider the growing evidence[1][2] showing that even chimpanzees (our closest genetic relatives - though not used in Australia) are poorly representative of human biology and diseases, then that makes their use in research even more unjustified.

The Australian breeding colonies were established to “provide a consistently high standard of care and management” yet earlier this year two marmosets, imported from France died unexpectedly and from unknown causes. The NHMRC argues that importation (and exportation) of primates is outside their jurisdiction:

Regulatory responsibility for the importation and exportation of non-human primates rests with relevant Commonwealth government departments
yet their new document also states:
NHMRC requires compliance with this document as part of its funding agreement”
And under “Use of Great Apes” (page 4):
Great apes must not be imported from overseas for use for scientific purposes.”

Why then, can’t the ban on importing great apes for research be extended to a ban on all primate importations? Subjecting these sentient and highly cognitive animals to long arduous journeys in the cargo of a plane is cruel and unnecessary.

Under Provisions at the conclusion of their use (page 6)
Retirement must be considered as an option if suitable in term of the health and temperament of the animal, and space and resources are available at a facility that can meet their species-specific physical, social and behavioural needs.”

Depending on the type of research conducted on the animals, it is acknowledged that some may be left in such a traumatised and/or dilapidated state that euthanasia may be the most humane option. However HRA recommends that the decision to kill the animals at the end of their use must be determined by an independent and qualified rehabilitator rather than the researcher or the animal ethics committee. Some animals may still have the ability to sustain a quality life and HRA strongly feels it should be up to the rehabilitator to make the judgement as to whether a quality life can be attained.

To merely dispose of these animals when they are no longer required is a total disregard of their individual worth.  If their use has been funded by the taxpayers then the NHMRC and/or research institution must take responsibility to ensure that the wellbeing of these animals is guaranteed for the remainder of their natural lives. The establishment of a retired primate sanctuary could be funded primarily by the NHMRC and supported (and overseen) by animal welfare groups.

These animals deserve a dignified retirement in return for their ‘contribution to mankind’.

After reading the new guidelines one can't help but get the feeling the NHMRC are planning on increasing the number of primates used in research rather than phasing them out.

[1] Monkey-based research on human disease: The implications of genetic differences. Bailey, J. (2014). Alternatives to Laboratory Animals, 42: 287-317
[2] It's time to end the use of non-human primates in research and testing - Antidote Europe's submission to the Scientific Committee on Health, Environmental and Emerging Risks.

Wednesday, 7 September 2016

We need more epiphanies

Last weekend a colleague sent me a link to the following article:

It’s a heartening account of a vivisector who saw the light and acknowledged that what he was doing to sentient beings went beyond his moral boundaries. It restored a little bit of my faith in humanity.

Another colleague then sent me another story – a bit older (from 2004) but of the same theme.  Don’t Fall in Love With Your Monkey

Each of the articles made me wonder – could those who willingly inflict suffering on animals “in the name of medical progress” actually have an epiphany?

Like many others, I honestly struggle to understand how anyone can inflict fear, pain or any harm on another – regardless of whether that other is human or non-human. Humane Research Australia generally focuses on the scientific arguments that oppose animal use (ie HRA supports alternatives to animals in research in order to expedite real medical advancement), but even if it was of human benefit, is it right to use animals? 

No doubt we could gain valuable knowledge if we used a human child in medical experiments, yet no one would dream of doing such an atrocious act. Regrettably, it seems this moral boundary does not extend past our own species, allowing other sentient and some highly cognitive animals to be used (or abused) in any manner of research, so long as the researcher convinces their institutional Animal Ethics Committee that the use is justified as it might lead to an increase in knowledge.

“The physiologist is no ordinary man. He is a learned man, a man possessed and absorbed by a scientific idea. He does not hear the animals' cries of pain. He is blind to the blood that flows. He sees nothing but his idea, and organisms which conceal from him the secrets he is resolved to discover”. ~ Claude Bernard

So who actually does this ‘work’ today?  If we look to the researchers we find that they often have no physical contact with the animals involved in their research. Their work is often administrative and tied up with securing grants. This might suggest cognitive or emotional dissonance on their part. Then there are the PhD students who often simply do as they are told in order to obtain their doctorate. And there are the technicians – often caring people who mightn’t even agree with animal experiments but are there to “do what they can” in order to provide those animals with the best life possible – short though it may be.

I was disturbed some years ago when I attended a seminar/workshop for animal technicians and there was a discussion on how best to deal with the guilt of causing harm to animals. Some of the tactics used were to allocate the animals a number rather than a name to avoid attachment, keeping a “spare” animal in the lab which was not used in experiments but instead petted and shown affection, and paying more attention to their own animals at home – to make up for what they were doing to the lab animals. If indeed these people required a coping mechanism to appease their guilt wouldn’t that suggest that their sub conscious was simply telling them that what they were doing was wrong?

Similarly when I was at university, a colleague (who was also an animal technician) was telling a group of us that when her daughter’s friends visited she lied about what she did at work because they “wouldn’t understand”.  Perhaps they did – and it was she who didn’t.

At Humane Research Australia we often hear from people who feel uncomfortable – sometimes outright enraged - about what they are expected to do in an animal laboratory or what they have witnessed. I suppose they see us as an outlet. However when we suggest a meeting, request evidence or further information we consistently see a wall go up – a retreat from previous statements or not wanting to go “on record” and it’s always out of fear of possible repercussions, whether simple negativity from their colleagues or the threat of their studies or careers being quashed.

Some months ago I provided evidence at a senate hearing about the use of primates in research. Also presenting was Assoc. Prof. James Bourne, Chair of the Gippsland primate breeding facility and himself a researcher who uses primates in invasive neurological experiments. He proudly proclaimed “I am about making cures to humanity. I want to know that, in my career, I have done something for the benefit and welfare of humans.” A noble endeavour perhaps, but I question humanity when it requires the inhumane treatment of others.

I can only hope that Bourne and others in his field will some day have an epiphany like those in the articles linked above and come to the realisation that just because you can doesn’t mean you should. Our morals should extend to all those that may suffer. Only then will humanity truly be worthy of his cures.

Sunday, 28 August 2016

You CAN support health and medical research charities without funding cruel animal experiments.

Several decades ago (at the risk of divulging my age) I, a rather shy and unassertive girl, sat at my desk, working diligently, in a large investment corporation. I enjoyed my career – assisting clients, the satisfaction of completing a hard day’s work - yet it was not my passion.  What I felt really passionate about was the injustice toward animals – animal experiments in particular.

It was for this reason that I felt my anxiety levels rising as I became aware of a work colleague walking from desk to desk soliciting donations in exchange for badges and tokens for Red Nose Day – a well-renowned annual fundraiser for SIDS (Sudden Infant Death Syndrome). 
As she edged closer to my desk I panicked. I knew that donations to Red Nose Day likely funded animal experiments and I was so vehemently opposed to that. But what was I to do?

I actually faced two dilemmas – speaking out to someone I felt intimated by (for no good reason other than my shyness) and being seen as someone who cared more about animals than dying babies. Of course the latter wasn’t true. As many readers will agree, spending valuable resources on research using a different species will not help dying babies at all - in fact it could delay the cure!  Should I speak up and state my disapproval, or should I just hand over a small donation which in the scheme of things was not going to contribute much either way?  

Sue finally reached my desk. She asked – rather nicely – whether I would like to make a donation to Red Nose Day.

I turned to her not knowing what would come out of my mouth, but said confidently, “I understand that you are collecting money for medical research and I wish all the best for those babies who are sick, however I am very much opposed to animal experiments, which I believe the money will contribute to and I’d therefore feel very uncomfortable making a donation.” Almost in disbelief at myself I waited on Sue’s response. She told me that she respected my view and thanked me for letting me know. Phew. Did I really just do that?

Being much older now, hopefully much wiser, and nowhere near as bashful as I was back then, this scenario seems almost cowardly. I mean, why wouldn’t  I be confident in speaking out against something I felt so strongly about? However the reality is that many people do indeed suffer from such anxiety and this is a concern. So I did something about it to help others in a similar situation. I initiated the Humane Charities List.

To be fair, it wasn’t my original idea. I’d heard of a similar scheme in the United States and contacted them to set up a similar thing in Australia and they were happy to assist.

The Humane Charities List is a list of health and medical research charities which have advised HRA that they do not fund animal-based research. This means that you can safely make a donation to these organisations knowing that you are not financially supporting cruel and unnecessary animal experiments. The list now stands at 96 and includes many well-known charities such as HeartKids, Beyond Blue and the Fred Hollows Foundation.

These days I’m not so shy and I do speak out against animal experiments at every opportunity, but I hope that the list provides some ease to others who, when solicited for donations can now ask “Are you on the Humane Charities List?” making it much easier to express their disapproval of animal experiments.

I would love you to support the Humane Charities List by joining its Facebook page, downloading the app and approaching your own favourite charities to ask if they fund animal experiments, and if they don’t, encouraging them to apply online to be on the list. The longer the list grows and the more people refuse to fund animal experiments the more charities will realise that they need to move toward more humane and scientifically valid methods of research which will bring more effective solutions to our urgent medical needs.

Tuesday, 7 June 2016

Guidelines for conducting unethical and dangerous research should NOT be sanctioned in Australia

The National Health and Medical Research Council (NHMRC) has been conducting a public consultation on its proposed guidelines for performing clinical trials in xenotransplantation – a dangerous and unethical method of research. Submissions close today.

Xenotransplantation involves the transplantation of cells, tissue or organs from one species (usually genetically-modified pigs) to another and carries the risk of inactive viruses jumping across the species barrier resulting in a ‘xeno-zoonotic’ disease.

In 2004, I served on the NHMRC’s Animal Issues Sub Committee which provided recommendations to the Xenotransplantation Working Party (XWP) as part of the NHMRC’s review on this subject.  I was therefore privy to the full set of submissions received which addressed grave concerns and illustrated huge public opposition to the practice. After a lengthy consultation process the NHMRC recommended that no clinical trials involving animal to human transplantation should be conducted in Australia for five years as the risk of animal to human viral transmission was not well understood.  

The moratorium was sanctioned for good reason:
  • Continuing risks to the community
  • Public opinion
  • Animal welfare and suffering

The NHMRC reviewed its decision in December 2009 and the ban was overturned pending release of ‘guidelines’ for conducting xenotransplantation.  Now that these so-called guidelines have been released, clinical trials of xenotransplantation can proceed once the expected commencement date has been agreed.

Importantly, it has recently been reiterated to Humane Research Australia by medical experts that the critical concerns, which resulted in the 2004 moratorium being announced, remain unchanged.

The uncertainty of risks of disease transmission, particularly across the species barrier, has been acknowledged by researchers.  Clearly, this is not just a theoretical possibility but a very possible outcome.  AIDS is already believed to have been contracted from chimpanzees. BSE and Ebola viruses originated from cross-species contamination.  Some of the major flu epidemics from the start of last century were believed to have originated from pigs.  Porcine Endogenous Retrovirus (PERV) has already been discovered in the animals intended to be used as source animals. With continued emergence of new zoonoses from unexpected sources, the inability to diagnose potential xenozoonotic viruses with current tests and their unknown pathogenic behaviour, the chances of cross-species infection seems to be exceedingly and unacceptably high.  Even more alarming is that, even if detected, the viruses are largely untreatable.

The global panic over Swine flu could perhaps serve as a (very modest) precursor of how the world might react should a new zoonotic disease emerge from xenotransplantation. While the outbreak of the H1N1 virus (Swine flu) was declared by the World Health Organisation to be a “public health emergency of international concern”, a more virulent strain might easily have a much higher level of transmissibility and far more serious health consequences.

Chapter 3.6 of the draft guidelines acknowledges this risk and states:
“Xenotransplantation differs from most other medical research where it is research participants who are predominantly exposed to risks. In xenotransplantation, not only the research participant but also their identifiable contacts and members of the wider community may be exposed to risk. Xenotransplantation research involves some known and, potentially, some currently unknown infection risks to those other than the research participant. The possible risk of xenotransplantation causing novel or latent infectious and potentially untreatable diseases raises an ethical issue that cannot be addressed by the consent of the research participant alone, since others may also be exposed to risk by the research. Further, because of the possible public health risk, research participants will need to participate in long-term monitoring programs.”

There remains serious concern about allowing this research to proceed. Aside from the individual patient’s risk of contracting a zoonotic disease, they are putting the health of the entire community at risk.  An individual has the right to expose themselves to any risks involved in scientific research but to further expose that risk to the wider community that has not given consent, is highly unethical.  The number of individuals that could suffer and die from a new epidemic  or without wishing to overstate the risk, even pandemic, could greatly exceed those potential lives which xenotransplantation was supposed to have saved in the first place.

Xenotransplantation research also inflicts great suffering on animals. HRA has uncovered disturbing cases including baboons rendered diabetic and set to receive pancreatic islet cells from genetically modified piglets; and a baboon known as Conan who received a renal transplant (a kidney from a transgenic pig) and was then killed  due to the development of disseminated intravascular coagulation. [Widespread activation of clotting in small blood vessels throughout the body leading to compromise of tissue blood flow and multiple organ damage.]

For such dangerous research to even be contemplated we would need:
  • A full public debate, making it a community decision rather than leaving it to the research community as it will be the general public that will pay the ultimate penalty of any fallout;
  • The Productivity Commission to report on the full economic impact of xenotransplantation should it be allowed to proceed – including the possibility of epidemics and emergency response plans in such events ;
  • A moratorium on all current pre-clinical xenotransplantation studies until further notice. 

Australia simply cannot allow research into xenotransplantation to proceed. Not only does it expose the recipient to further complications and disease, but it exposes entire communities to the risk of potential zoonotic epidemics, causes extreme and unnecessary cruelty to countless animals and holds little promise of resolving the problem of a shortage of suitable human organs and tissues. The added shame is that people with conditions awaiting transplants may believe that xenotransplantation is an effective cure – it is not - and may only lead to more misery, disappointment and complications.

A full copy of HRA’s submission can be found here.