Beyond the Use: The Paradox of Scientific Animal Utilization

Abstract

‘This is the last time I am doing this.’ Perfusion of an animal is a deeply dramatic task, an image that seems to be taken from an Alfred Hitchcock movie. I cleaned the room streaked with traces of blood, feeling some fear because the blood contained PFA, a carcinogenic substance. A cloud of doubts grew as I washed the equipment, but they all converged into one: Is this necessary? Is my soul being corrupted by so-called scientific curiosity? I filled out thousands of forms with abyssal haste: dosages, times, weights and so forth. I wrote down all the data as quickly as possible. I just wanted to leave. There was such meticulousness in ending a life, with each note serving as a grim reminder of what had just happened. I left the animal facility at a brisk pace. Leaving the Pasteur Institute felt like a breath of fresh air, even though it was raining outside. The rainwater fell over the city while a flood of doubts fell over me.

The anguish would not let me go. What hurts the most is that last moment when the anesthesia does its job and the animal falls asleep … a dream from which it will never wake. That and other thoughts attacked me without any compassion.

I would say the silver lining of having a ‘crisis of scientific vocation’ is that, at least in my case, it happens in Paris. During these intense moments, I have always been struck by how the beauty of the streets and buildings in Paris contrasts with my awful emotions. In any case, I lost myself in my thoughts, and at the same time, I lost myself in Paris.

I decided to take it step by step, tracing every glimmer of logic I could find in this situation. I began to remember, searching for the beginning, hunting fragments of memories in an attempt to reveal a response. Everything led me to the first Thesis Advisory Committee meeting. ‘I seek to study how the brain allows the storage of new memories while maintaining previous ones’, I said. My committee pressed me in the most determined and direct manner: ‘Why use animals? Cannot you study that with humans or using in vitro methods?’

I remember replying, ‘My experimental approach requires mice because one of my objectives is to determine if there is a change in the firing rate of the hippocampus when the animal has to create a new memory. Under these experimental conditions, I cannot use any other method to study the biological basis of this cognitive process.’ I recall a silence that I wanted to fill with more arguments: ‘We have used a mathematical model to predict the outcome of this experiment, and now we need to test it. We will evaluate this hypothesis using a limited number of animals, as well as previous results obtained in the laboratory.’

Now I understand why my committee was so insistent and somewhat inquisitive about my animal protocol. Did they foresee this crisis? I was a castaway in an ocean of doubts, but those arguments served as a lifeline, a lifebuoy. Those reasons helped me realize that there was a very compelling scientific rationale behind it all; however, I still felt confused. So much reflection made me lose track of time, and I did not even notice when I reached the end of Vaugirard Street.

Why had this last series of experiments affected me so much? Commitment. That is the reason. For a month, my weekends revolved around my mice. Throughout that time, I always gave the same answer: ‘No, no, no, I cannot make it. I have a training session with my mice tomorrow, maybe later’; ‘I would like to, but I have a recording session today; I might be free until 23 h.’ Family, friends, dates, colleagues, all displaced by a group of mice.

I believe I began to feel attached to those mice. Not too much, because it could influence the interpretation of the results; not too little, because I needed to detect if the animal experienced pain, discomfort, fear or any negative emotion. I think our relationship was characterized by great respect and cordiality.

Remembering those mornings of work with my mice brings a smile to my face. Arriving early, setting a very strict training schedule (always at the same time), preparing everything in advance. I even invented my own rules: never work with animals if I was in a bad mood or stressed, because that transfers to the animals and disrupts them.

‘Anesthesia, analgesia, future doctors. You have to follow these steps’, said Myriam Mattei, the manager of the Pasteur Animal Facility. ‘Changing each syringe for every injection? Isn't that an expense?’ Myriam, very serious, responded: ‘There is no unnecessary expense in animal care. Changing gloves frequently, checking water quality, food, or drugs to administer, and monitoring signs of emotional and physical well-being. You have to make sure that everything is perfect.’

At that moment, I thought, ‘Come on, Myriam! It feels like we are caring for these mice as if they belonged to the President of France, or worse, to my father-in-law.’ But truth be told, I appreciated having so many manuals. In Mexico, where I come from, we have similar practices, but the training is not as continuous, and having all this systematization makes learning and sharing easier. That is what I liked about Europe. And even though we all fear the animal-handling inspector, we all agree on the necessity of their work.

Inadvertently, I found myself at the Luxembourg Gardens. The scent of the fresh trees was instantly recognizable, and the dreaded phantoms of my memory still lingered. In fact, we had arrived together at the garden. Suddenly, a man walking his dog crossed my path, an exquisite old English shepherd. As I contemplated the majesty of that dog, I could not help but wonder if pet owners treat animals better than scientists do.

A memory hit me suddenly. I was having dinner with a friend when, out of nowhere, his dog ate an entire box of chocolates he had carelessly left on the sofa. My friend did not even seem concerned. ‘He will be fine’, he said, but I was worried and insisted we take the dog to the vet. Fortunately, nothing happened to the dog, but I was quite annoyed with him. Honestly, I have no idea what would happen to my scientific career if I ever made a mistake like that with my mice.

I stood up to continue walking along the path that wound around the central fountain of the garden. For a moment, I thought that this more emotional and personal approach to caring for animals was the key, but it was not really. Those who own animals and those who work with them have a great responsibility. In this case, scientific research is shielded by protocols so that it is not the turbulence of emotions and attachment that determines well-being, but rather those protocols and guidelines that will always strive to find a balance between animal care and research objectives.

A flood of ideas came to me, and I started looking around everywhere. I glanced back, and the owner gave the dog's leash a tug. The dog, naturally, almost bit him.

That reminded me of the statue commemorating the discovery of the rabies vaccine: a child fighting against a fierce and angry dog, which had his small arm between its jaws. ‘Animal research is necessary’, I thought. This and other vaccines, for example, were obtained thanks to studies involving animals, and many lives were saved.

In neuroscience, examples of major discoveries that have changed health and our understanding of the world are plentiful:

Cajal worked with bird brains to demonstrate that the brain is not a network and to establish the modern neuronal theory (Ehrlich 2016).

Hodgkin and Huxley, through their studies on squid axons, not only advanced our comprehension of the mechanisms behind propagating action potentials via voltage-gated ion channels but also established the foundational framework for investigating and analyzing ion channel kinetics (Catterall et al. 2012).

Rita Levi-Montalcini used goodness knows how many mice and chicken embryos to describe the process of cell generation, which would later be called growth factors and now allow us to understand senile dementia, tumours and nerve and tissue deformities (Chao and Calissano 2013).

However, the studies I like the most, because I am a devoted lover of memory, are that of John O’Keefe, May-Britt Moser, and Edvard Moser, with their discoveries on how neuronal cells form a positioning system in the brain and its implications in memory and cognition using rodents as an experimental model (Sugar and Moser 2019).

All these discoveries have changed our understanding of nature and human capabilities. They are not the only ones. An army of scientists has always fought against various diseases of the nervous system that cause pain to many people: autism, schizophrenia, Parkinson's disease, amyotrophic lateral sclerosis, and the one that terrifies me the most: Alzheimer's disease.

My first approach to science was with patients suffering from this illness. I saw how Alzheimer's progression consumed their identity and their memories. I experienced the suffering of their families and the helplessness of not having treatment. We take the life of a mouse in exchange for a grandfather, a mother, a sibling, a friend … a loved one.

Science is also a ritual for caring for and protecting life. How can we not strive to improve and discover better methods and results when someone somewhere is waiting for our answers? But what about the animals?

I was so lost in my thoughts that I did not realize I had arrived at the Pantheon: ‘Aux grands hommes la patrie reconnaissante’. A conclusion struck suddenly, abruptly, and with complete clarity: we cannot achieve any distinction without a firm ethical commitment.

Furthermore, the benefits we gain from our scientific work cannot come at the expense of important issues like animal suffering. In other words, the integrity of our research and its results depends on how well we minimize the suffering of the animals involved.

The 3Rs make more sense to me than ever: replacement, reduction and refinement (Fenwick, Griffin, and Gauthier 2009). Everything revolves around that. The mysteries surrounding life, the brain in our case, cannot be studied without that respect, without that care.

Once again, science surprises me. Behind every variable, instrument, participant, behind everything, there is always a reason that goes beyond mere preference or belief.

The view from the Pantheon was imposing. The rain stopped. The majesty of Paris is always indescribable, just like those the moments when calm arrives.

My mind replaced intrusive thoughts with more rational ones: Mice, and all species we work with, are held to high standards of care, feeding, stimulation, housing and continuous medical monitoring, where even the slightest issue or discomfort must be promptly addressed. We do this to achieve good results, but also out of respect for life.

We are still a long way from eliminating the use of animals in research. However, we have made remarkable progress. By integrating mathematical models, in vitro experiments, organ-on-chip devices and findings from other studies, we have managed to reduce the number of animals involved. I believe the scientific community must continue to prioritize efforts to replace and refine the use of animals in research.

There is no scientific cruelty, but rather a deep desire to understand life, a paradox that I hope the future will resolve as soon as possible.

The Eiffel Tower began to sparkle. ‘This moment is so beautiful’, I thought.

The author declares no conflicts of interest.