We mightn't like it, but there are ethical reasons to use animals in medical research

The media regularly report impressive medical advances. However, in most cases, there is a reluctance by scientists, the universities, or research institutions they work for, and the media to mention animals used in that research, let alone non-human primates. Such omission misleads the public and works against long-term sustainability of a very important means of advancing knowledge about health and disease.

Consider the recent report by Ali Rezai and colleagues, in the journal Nature, of a patient with quadriplegia who was able to use his hands by just thinking about the action. The signals in the brain recorded by implanted electrodes were analysed and fed into the muscles of the arm to activate the hand directly.

When journalists report on such bionic devices, rarely is there mention of the decades of research using macaques that eventually made these early brain-machine interfaces a reality for human patients. The public is shielded from this fact, thereby lending false credence to claims by animal rights groups that medical breakthroughs come from human trials with animal experiments playing no part.

Development of such brain-machine interfaces requires detailed understanding of how the primate brain processes information and many experiments on macaques using different interfaces and computing algorithms. Human ethics committees will not let you try this on a patient until such animal research is done.

These devices are still not perfect and our understanding of brain function at a neuronal level needs more sophistication. In some cases, the macaque neural circuitry one discovers may not quite match the human’s, but usually it is as close as we can get to the human scenario, needing further fine-tuning in direct human trials. However, to eliminate all animal research and try everything out on humans without much inkling of their effects is dangerous and therefore highly unethical.

The technique Dr Rezai’s team used on human patients draws heavily upon work done on monkeys by many groups. This can be seen by looking at the paper and the references it cites.

Another case in point is the technique of deep brain stimulation using implanted electrodes, which is becoming an effective means of treating symptoms in many Parkinson’s patients. This is now possible largely due to the decades of work on macaques to understand in detail the complex circuitry involved in motor control. Macaques continue to be used to refine deep brain stimulation in humans.

Ethical choices

The number of monkeys used for such long-term neuroscience experiments is relatively small, with just two used in the study above. Many more are used for understanding disease processes and developing treatment methods or vaccines in the case of infectious diseases such as malaria, Ebola, HIV/AIDS, tuberculosis and Zika.

Approximately 60,000 monkeys are used for experiments for all purposes each year in the United States, Europe and Australia.

However, if one looks at what is at stake without these experiments on non-human primates, one must acknowledge a stark reality. In many cases, the situation is similar to that which once existed with polio. Nearly 100,000 monkeys were used in the 1950s to develop the polio vaccine. Before that, millions of people worldwide, mostly children, were infected with polio every year. Around 10% died and many were left crippled.

Now, thanks to the vaccine, polio is almost eradicated.

Similarly, about 200 million people contract malaria every year, of whom 600,000 (75% being children) die, despite all efforts to control the mosquitoes that transmit the disease. Development of a vaccine is our best chance, but again primates are necessary for this, as other species are not similarly susceptible to the parasitic infection.

Circumstances are similar with other devastating ailments such as Ebola, HIV and Zika. The ethical choice is often between using a few hundred monkeys or condemning thousands or more humans to suffer or die from each one of these diseases year after year.

In the popular press and in protests against primate research, there is sometimes no distinction made between great apes (chimpanzees, bonobos and gorillas) and monkeys such as macaques, leading to misplaced emotional reactions. To my knowledge, invasive experiments on great apes are not done anywhere, because of the recognition of their cognitive proximity to humans.

While the ape and human lineages separated six million years ago, there is an additional 20 to 35 million years of evolutionary distance from monkeys, which clearly lack the sophisticated cognitive capacities of the apes.

With urgent medical issues of today such as HIV, Ebola, malaria, Zika, diabetes and neurological conditions such as stroke and Parkinson’s disease, monkeys are adequate to study the basic physiology and pathology and to develop treatment methods. There is nothing extra to be gained from studying apes.

Alternatives have limitations

Opponents of animal research often cite the impressive developments of computer modelling, in-vitro techniques and non-invasive experiments in humans as alternatives to animal experiments. These have indeed given us great insights and are frequently used also by the very same scientists who use animals.

However, there are still critical areas where animal experimentation will be required for a long time to come.

Modelling can be done only on data already obtained and therefore can only build upon the hypotheses such data supported. The modelling also needs validation by going back to the lab to know whether the model’s predictions are correct.

Real science cannot work in a virtual world. It is the synergy between computation and real experiments that advances computational research.

In-vitro studies on isolated cells from a cell line cultured in the lab or directly taken from an animal are useful alternatives. This approach is widely used in medical research. However, these cells are not the same as the complex system provided by the whole animal. Unless one delves into the physiology and pathology of various body functions and tries to understand how they relate to each other and to the environment, any insights gained from studying single cells in in-vitro systems will be limited.

Though many studies can be done non-invasively on humans and we have indeed gained much knowledge on various questions, invasive experiments on animals are necessary. In many human experiments we can study the input to the system and the output, but we are fairly limited in understanding what goes on in between. For example, interactions between diet, the microbiome, the digestive system and disease are so complex that important relationships that have to be understood to advance therapy can only be worked out in animal models.

Of course, animals are not perfect models for the human body. They can never be. Species evolve and change.

However, many parts of our bodies have remained the same over millions of years of evolution. In fact, much of our basic knowledge about how impulses are transmitted along a nerve fibre has come from studying the squid, but our understanding also gets gradually modified by more recent experiments in mammals.

Higher cognitive functions and the complex operations of the motor system have to be studied in mammals. For a small number of these studies, nothing less than a non-human primate is adequate.

The choice of species for every experiment is usually carefully considered by investigators, funding bodies and ethics committees, from both ethical and scientific viewpoints. That is why the use of non-human primates is usually a small percentage of all animals used for research. In the state of Victoria, this constitutes only 0.02%.

Medical history can vouch for the fact that the benefits from undertaking animal experiments are worth the effort in the long run and that such experimentation is sometimes the only ethical choice. Taken overall, the principle of least harm should and does prevail. There may come a day when non-invasive experiments in humans may be able to tell us almost everything that animal experiments do today, but that is probably still a long way off.

Priorities in animal use

The ethical pressure put on research seems to be in stark contrast to that on the food industry. It is hypocritical for a society to contemplate seriously restricting the use of the relatively small number of animals for research that could save lives when far more animals are allowed to be slaughtered just to satisfy the palate. This is despite meat being a health and environmental concern.

To put this in perspective, for every animal used in research (mostly mice, fish and rats), approximately 2,000 animals are used for food, with actual numbers varying between countries and the organisations that collect the data.

The ratio becomes even more dramatic when you consider the use of non-human primates alone. In Victoria, for every monkey used in research, more than one million animals are used for meat production. However, the monitoring of the welfare of farm animals is not in any way comparable to that which experimental animals receive.

Reduced use of livestock can greatly reduce mankind’s ecological footprint and also improve our health. This is an ethical, health and environmental imperative. Animal experiments, including some on non-human primates, are also an ethical and medical imperative.

Trichur Vidyasagar receives/has received funding from the National Health and Medical Research Council (Australian Government) and Australian Research Council (Australian Government). He is employed by the University of Melbourne. He is also a member of the Board of Administration of the National Vision Research Institute.