Animals for antibiotic research: Is it necessary?
Sam is Research Fellow at the London School of Hygiene & Tropical Medicine (LSHTM) investigating novel antimicrobials and virulence factors. Sam is also the lead for biological and pharmacological sciences within LSHTM's AMR Centre.
Do we still need to use animals in scientific research? It’s 2017, do we not have reasonable alternatives by now that are just as informative? Well, yes and no.
The term “Animal Research” is laden with implications, and this is a big part of the problem. “Animals” is a vague term; “research” is a vague term. In the absence of information, our imagination fills the void. It is, quite rightly, an emotive topic, and the day we stop asking ourselves, “Is it still necessary?” is the day we abandon our ethical prerogative.
As a post-doctoral researcher with many years of experience working with some very nasty diseases, I am prepared to offer one perspective, to help demystify animal research. While “research” can provoke thoughts of anything from cosmetics to neurology to cancer therapeutics, my experience is with infectious diseases, particularly the field of antimicrobial resistance.
In order to have this debate, we need a safe space, and it must take place in wider society, not behind closed doors in the scientific community. The Concordat on Openness on Animal Research, launched in 2014, is a good start.
The answer to the question “is it necessary?” surely depends on the accompanying question “what happens if we don’t?”. One may justify animal experimentation that results in a protective new vaccine against Ebola, for example, but not for ensuring that Johnny does not develop itchy eyes from his new conditioner. The use of animals for cosmetics research is banned in the UK, and it has been illegal in the EU to sell products that have been tested on animals since 2013.
For context, I think it is worth pointing out at this stage the millions of large animals killed each year (2.6 million in December 2016 in the USA alone) for the grand purpose of feeling full until our next meal - but then Johnny does love a Big Mac… to comfort him from his bad conditioner experience.
Animal testing law in the UK
Let me provide an overview of what animal research looks like in the UK in 2017. We have, bar none, the toughest controls and regulation of any country in the world.
The Animals Scientific Procedures Act of 1986 strictly informs us what is and is not allowed. Not only do we individually require lengthy personal training and licencing by the governing body (within the UK, this is the Home Office), our institutes also require a license, and the project itself requires a license. You cannot make it up as you go, there is an agreed and approved experimental plan that cannot be deviated from. The Home Office has the right to inspect us at any time, without notice, 365 days a year to make sure we are abiding by our obligations.
The animals themselves are maintained in clean, climate-controlled conditions, and are inspected at least twice daily by specially trained staff for their physical and behavioural condition. There is a designated vet available at all times to ensure that animal welfare is the utmost priority of researchers and staff. If animals begin to look sick, they are euthanised by approved methods; they are not permitted by law to suffer from advanced disease symptoms. Often the humane end-point is a pre-determined and agreed indicator such as a weight-loss threshold, appearance or mobility.
What type of animals are we talking about?
The fastest growing group in terms of percentage is fish. Zebrafish, for example, are cheaper to maintain and breed than mice, and are genetically tractable. Within the EU, higher animals such as dogs, pigs and primates are also sometimes used, for example in clinical trials, although in much smaller numbers.
Is it necessary to use primates in animal research? They represent less than 0.1% of animals used in research, usually macaques or marmosets. Their use was instrumental in providing us with the Polio vaccine and life-support machines for premature babies. They are considered particularly valuable for the study neurological diseases such as Alzheimer’s and Parkinson’s due to their obvious physiological similarities with humans. Perhaps when the animal is as complex as a human it makes an excellent model, or perhaps at that point you could also gain informed consent from a human volunteer. If the work was predictable, there would be no need for research at all.
Adult zebrafish. Image credit: Tohru Murakami.
Animal testing for AMR
In my experience, research is incremental, and the same applies to the use of animals. We start simple and as we collect more data, we get more complex. Let’s look at antimicrobial resistance.
I think the argument is beginning to be won with the wider public and funding organisations that we need new antibiotics – the ones we have are running out due to increased resistance. Why would we need to use animals in this research? In order to address two queries that cannot be resolved without it: Does this new antibiotic work? Is it safe?
We start by doing our homework on the computer, using sophisticated modelling software to predict activity. Understandably, this then needs to be tested. We can begin by testing the new antibiotic in a plastic dish against free-living bacteria.
Okay great, that works, but can it kill bacteria that are living inside mammalian cells, as many pathogens do? This we can test using immortal cell-lines that we culture in the lab, and it will also provide some basic toxicity information.
But a cell line does not have organs, it does not have a circulatory system, it does not have multiple other cell types and proteins that may complicate the picture. We could next use a simple animal model such as a caterpillar to test our drug. Caterpillars do not experience pain in the same way that vertebrates do, they are not subject to the same legal framework, but they provide more information than a cell-line.
If we still have a drug candidate, and many promising leads fail at this stage, we can consider a rodent model. This will establish whether the drug is still active in a mammalian system, and if so it will inform us of the effective dose regimen, of how it is processed and cleared by the host, and whether there are unexpected side-effects.
These are questions that cannot be answered without animal research, but should only be asked once all the pre-requisite prep’ work has been conducted and the drug still looks promising.
The key question: Does a drug work and is it safe?
Sooner or later that leap needs to be taken and our drug needs to be tested in humans. After aggravating his IBS from his Big Mac, Johnny isn’t exactly raising his hand. The smaller the leap is from our lab research to human trials, the more relaxed Johnny – and drug consumers everywhere – can feel.
Animal research is always under scrutiny, and is always changing. The paradigm of the age is ‘Reduce, Replace, Refine’, and indeed the use of animals by UK academic institutes has been declining steadily since the 1970’s. We also see promising new techniques such as in vivo imaging that let us ‘see’ into living animals without causing stress or having to sacrifice them to look inside. The ‘organ-on-a-chip’ is a huge achievement of biomedical engineering that can replicate many of the conditions of a living system.
These methods were perfected as a direct result of our collective experience with and knowledge of animal research, and they will reduce the number of animals we need to use in the future.
Is animal research necessary? I ask myself the same question every time I pick up a pipette.
For more information, visit Understanding Animal Research.