Monthly Archives: March 2014

A liver in a test tube to predict the effects of drugs in humans without animal testing

IMG_2107Promising research into chemosynthetic livers that mimic metabolic processes could soon replace the use of rats, mice, rabbits and other animals currently being used to test drugs. The use of chemosynthetic livers could also speed up drug testing.

This technology has been developed by Empiriko, a clinical intelligence technology company using algorithms, advanced analytics, predictive modeling and scientific and clinical interpretation of research data. Empiriko has designed biomimetic systems that emulate biological structure, function, mechanism and reactivity. Biomimicry or biomimetics is the imitation of the models, systems, and elements of nature for the purpose of solving complex human problems.

The chemosynthetic liver technology called Biomimiks™ was presented at a recent meeting of the American Chemical Society (ACS). Dr Mukund Chorghade, chief scientific officer of Empiriko Corporation and president of THINQ Pharma. said:

Researchers in drug discovery make small quantities of new potential drug compounds and then test them in animals. … It is a very painstaking, laborious and costly process. Frequently, scientists have to sacrifice many animals, and even after all that, the results are not optimal.

The media release of the ACS explains how this new technology works:

Typically, when researchers are onto a new compound that could address an unmet human health need, they test it on animals to see if it’s toxic before taking it into clinical trials with human subjects. They figure this out by doing something called metabolic profiling. That is, after giving an animal a test drug, the experimental compound does its designated job in the body until the liver breaks it down. Then researchers try to detect the resulting, minute amounts of molecular byproducts, or metabolites. It’s these metabolites that are often responsible for causing nasty side effects that can derail an otherwise promising therapeutic candidate. …  [R]ather than using lab animals, researchers could figure out metabolic profiles of drugs by mixing them in test tubes with chemosynthetic livers.

Chorghade and his team at Empiriko have already demonstrated how Biomimiks™ works with several pharmaceutical compounds. “These chemosynthetic livers not only produce the same metabolites as live animals in a fraction of the time,” Chorghade said, “but they also provide a more comprehensive metabolic profile, in far larger quantities for further testing and analysis.”

Is this technology superior to animal testing? Dr Chorghade thinks so:

Animal models are based on a variety of animal species, which produce different metabolic pathways and don’t necessarily correlate with human pharmacology, leading to variations in efficacy and toxicity of drugs,” Chorghade said. “It is difficult to extrapolate [from animals to humans] the maximum tolerated drug dosing and minimum observed biological effects.

The chemosynthetic livers have not yet been approved to replace animal tests. But Dr Chorghade’s team has tested more than 50 drugs so far to show that the catalysts accurately mimic how the human body processes them. He said that they are working to test 100 drugs, which is the number required by the U.S. Food and Drug Administration for regulatory approval.

References:

American Chemical Society. (2014). An end to animal testing for drug discovery? Washington DC: ACS.

Empiriko Corporation. (2013). Metabolism profiling: Changing the game with biomimetic oxidation technology. White paper.

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Update: Companies’ use of animals

To date, I have contacted 30 companies. Eight responded to my questions. Of these, three companies advised that they do not – directly or indirectly – use animals as part of their research. The others pointed to regulatory requirements for animal research. While, to my knowledge there is no regulatory requirement for animal testing in Australia, companies operate in a global environment. For example, the U.S. FDA requires animal testing for medical products.

The three companies that do not use animals in their research and/or testing of products are:

  • Australian Pharmaceutical Industries Limited
  • OncoSil Medical Limited
  • Resmed Inc

The company Fisher & Paykel Healthcare Corporation Limited noted that they allocate funding toward the development and validation of non-animal research methods.

You can find more detail, such as a list of companies contacted and a link to an Excel file, on the Companies and animal use page.

Animal experiments are not good science

Humane Research Australia has just released a 6-part presentation by Dr Andrew Knight who explains why animal use in research is not good science.

Image

Source: Wikimedia Commons/Linda Bartlett

Andrew Knight is a European Veterinary Specialist in Welfare Science, Ethics and Law, a Fellow of the Oxford Centre for Animal Ethics, UK, and an Associate Professor of Welfare and Ethics at Ross University School of Veterinary Medicine in the Caribbean.

Animal Experiments – a failing science

Efficacy –  accessing the utility of animal experiments

Statistics and regulation

Non-animal methods of research – a more humane and scientifically valid option

Humane education – caring, not killing

Working together for change

Other links:

Dr Andrew Knight’s website 

Dr Andrew Knight talks about his book The costs and benefits of animal experiments

The slow road to change

AHU TONGARIKI o los 15 moais.

Source: Wikimedia Commons/Gallardoval

As Rob Buttrose and I have argued on the ABC Drum, last year’s update of the Australian code for the care and use of animals for scientific purposes (the Code) has brought no improvement for the animals used in research and teaching. The new Code does not address the lack of transparency and secrecy around the use of animals in research. Many procedures and protocols that are cruel and unnecessary are still allowed, and the new Code provides as little protection to animals as the previous 2004 version.

While the Code encourages the 3Rs: replacement (not using animals where possible), reduction (reducing the number of animals used) and refinement (minimising impact), the number of animals used in research here in Australia and overseas is increasing.

Earlier this year, the UK government launched its delivery plan to replace, refine and reduce the use of animals in research. But, as the BBC reports, there is no commitment to reduce the total number of animal experiments, which has been on the rise.

Change is slow, argue Hartung and Corsini:

Over the last two decades, little has changed in the practice of immunotoxicity testing for regulatory purposes, especially for immunosuppression, and autoimmunity is still a challenge. Current guidelines still rely on animal tests, which include some immune endpoints in repeated dose tests and trigger dedicated tests only when certain alerts indicate a problem. At the same time, however, a wealth of in vitro approaches has been developed, but few have been adopted for routine testing.  (p. 411)

So, what are some of the stumbling blocks for change?

Jean Harrington has undertaken research in stem cell laboratories, exploring attitudes toward the use of alternatives, in particular human tissue. She argues that:

The production and maintenance of animal models is a serious commercial concern, deeply woven into the fabric of medical research. Indeed, this leads one to ask whether the artifact—the animal model—has become such an integral part of experimentation that other materials, such as human tissue, are viewed as inappropriate within the scientific framework.  (p.188)

For a small lab, the procurement of human tissue is often more difficult and inconvenient than using animals: it requires collaboration with hospitals who supply the tissue (which they consider a waste product). The tissue may arrive at an unsuitable time and require the scientists to work at an inconvenient time, such as over night. The supply of tissue

… is sporadic and the key concepts of control and purity—represented in the manufactured artifact of the manipulated, standardized animal model—are challenged because its heterogeneous nature threatens the replication of the experiments. Thus the use of human tissue places at risk the timely production of publications. These tensions produce an ethical and practical predicament: on one side of the argument, animal models are seen to be the best material to produce what is required— experimentation, results and output; and on the other is the logic of using human tissue to explore human disease.  (p. 190)

In the environmental hazard and risk assessment area, Scholz and colleagues have argued that perceptions rather than facts can be stumbling blocks:

Finally, a serious problem in the implementation of alternatives approaches in environmental risk assessments arises from the fact that discussions about alternatives are frequently based upon ‘perceptions’ and not exclusively based on scientific arguments. The problem is that such perceptions may interfere with an objective discussion of pros and cons of various alternative approaches.  (p.525)

They conclude that:

Even without available alternative methods, there would be scope for a reduction of animal tests via modification of risk assessment schemes or experimental test designs. (p. 513)

And yet, there have been positive developments.

The cosmetics industry

From June this year, China plans to remove its mandatory animal test requirements for domestically manufactured cosmetic products. This may be expanded to include imported products and certain “special use” cosmetics as well. Europe has already phased out animal tests on cosmetic products and ingredients. Israel and Norway have had bans on animal testing in place for several years and, in 2013, India became the first country in Asia to announce a ban animal testing for cosmetics. Korea, Brazil and ASEAN are also making strides toward ending cosmetics testing on animals.

In the U.S., Congressman Jim Moran has just introduced a Federal Bill to End Cosmetics Testing on Animals in Congress.

The pharmaceutical industry

There are also changes ahead in the pharmaceutical industry. A recent article in the Genetic Engineering & Biotechnology News proclaimed: Alternatives to Animal Testing Drive Market”. The author, Robert G Hunter, commented that in vitro (using tissue and cell cultures) and in silico (performed on a computer) technology

products and services are now about the same size as the in vivo services (contract research organization) industry … In addition to almost doubling the market to $10 billion by 2017, we expect to see increased diffusion of these so-called alternative methods and technologies across clinical applications like biomarkers and systems biology over the next 5–10 years. And mice will play!

More than 20 companies have now adopted policies to not conduct or financially support invasive research on great apes. For example, the drug company Merck will end tests on chimps.

Further, the National Institutes of Health in the U.S. announced last year an end to most testing on chimps and support for research that uses chimps.

Chimpanzee head

Source: Wikimedia Commons/Antony Stanley

***

The world as we have created it is a process of our thinking. It cannot be changed without changing our thinking. ― Albert Einstein

References – some alternatives to animal testing

Doke, S. K., & Dhawale, S. C. (2013). Alternatives to animal testing: A review. Saudi Pharmaceutical Journal

Alt.Tox.org. Non-animal Methods for Toxicity Testing. AltTox.org is a website dedicated to advancing non-animal methods of toxicity testing through online discussion and information exchange.

AltTox.org. Table of Validated and Accepted Alternative Methods

@ltWeb, the global clearinghouse for information on alternatives to animal testing. Johns Hopkins Bloomberg School of Public Health

ALTES Food For Thought Columns

Humane Research Australia. Replacing animals

Pincock, S (2013) Miniature kidney grown in a dish. ABC Science

Interview with Alan Faulkner-Jones from Heriot Watt University in Edinburgh (2013). 3D-printed human cells could “replace animal testing”

New England Anti-Vivisection Society (NEAVS). Alternatives In Testing

European Union Reference Laboratory for alternatives to animal testing (EURL ECVAM)

European Union Reference Laboratory for Alternatives to Animal Testing. Advancing safety assessment without animals: EURL ECVAM. video

Summary of ICCVAM Test Method Evaluations. National Toxicology Program, U.S. Department of Health and Human Services

Antidote Europe. Antidote Europe is a not for profit NGO that promotes sound scientific methods of research and campaigns on issues of consumer safety.