Animal rights ideologues like to refer to animal research as “animal testing”. This seems to be part of their new strategy of arguing that animal research is worthless because they claim that testing new medications on animals has no predictive value on their effects on humans. However, this is a gross misrepresentation of what animal research is all about. In reality, testing new medicaments on animals is just a minor aspect of animal research. After all, to test a new drug you have to have that drug in the first place. It is precisely that process of designing new medicaments that takes the bulk of the effort in biomedical research. It is an extremely difficult and time-consuming process, and it absolutely requires experiments on animals.
This is what is normally called “basic research”, as opposed to “clinical research”, which is research done on humans by directly studying our diseases and the efficacy of treatments to cure them. In between basic and clinical research there is “translational research”, whose goal is to take the knowledge acquired in basic research and to apply it to clinical practice.
Basic research is critically important. Without it we would get stuck with the medications and treatments that we currently have and would be unable to create anything new. That would mean that there would be no hope of addressing the large medical challenges that we face nowadays, like cancer, AIDS, cardiovascular disease, Alzheimer’s disease, chronic pain and drug abuse. Why is this? Because any new advance in medicine has to be rooted in knowledge about the basic functioning of living beings.
It is hard for a person without a scientific background to even begin to imagine the incredible complexity of the human body. Inside each of our cells there are many thousands of different compounds linked by a complex network of metabolic routes that transform them into each other. These metabolic routes are tightly controlled by signaling system that ultimately link them to genetic information stored in the DNA. The key machinery of this complicated factory are the proteins, which perform the great majority of the functions of the cell: they are the enzymes that mediate chemical reactions, transporters that move compounds across membranes, carriers of signals, and receptors that tell the cell what is happening in its environment. Beyond the cell there is the tissue, in which many different cells cooperate to perform a particular function like producing mechanical force (muscle), digesting (gut) or processing and storing information (brain). Finally, all the tissues in the body are linked by several information networks (the central nervous system, the endocrine system and the immune system) that keep it working as a whole.
What I want to emphasize here is that there is a staggering amount of information about how our body work, and most of it is not known yet. For example, although the phenomenon of neurotransmission has been known for almost a hundred years, new neurotransmitters and neurotransmitter receptors are still being discovered. There is no other way of acquiring this information other than going into a living organism to look for it. Computer models cannot do that, because we need to know quite a lot about something before we can put that information into a computer model. We cannot guess or deduce what goes on inside the body, because all those molecules and pathways have been created by evolution though a process that involves a lot of randomness. And we cannot conduct all basic research on the human body for many different reasons: some of it is too invasive and harmful, some requires experiments that need to happen in a time scale much shorter than the human life, and some involves genetic manipulation that would be unethical in a human being. Let’s take a closer look. Basic biomedical research is done at three levels:
- In vitro, which means in Latin “in the glass”. This is done to investigate the basic biochemical processes that occur inside the cell. A lot of it is not done in living systems at all, but on isolated proteins or DNA. However, a large part of in vitro research involves cell cultures. Some cell cultures are done with what is called “immortalized cells”: cells that are able to divide indefinitely while maintaining their basic properties (like the famous HeLa cells). The problem is that immortalized cells are basically cancerous cells and therefore not very similar to the healthy cells that we need to study. The other type of cell culture is called “primary culture” and involves normal cells harvested from an animal or a patient and kept alive for a limited time. Not all primary cultures can be started from a human patient, however. For a variety of reasons, most of them are started from an animal (typically, a mouse or a rat) that is sacrificed in the process of harvesting them.
- Ex vivo, which means “out of a living organism”. This is done to investigate the functioning of a tissue, for example, the brain, the gut, or the pancreas. The aim of these preparations in to preserve the integrity of the tissue while having access to manipulate it. Good examples are the brain slices that have been used to study many of the basic functions of the nervous tissue. On rare occasion the tissue can be extracted from a human, but by and large the source is an animal, because it would be impossible to extract the tissue that we want to study without killing its donor.
- In vivo, which means “in a living organism”. This is done to study the functioning of the body as a whole, looking at the interaction of all its different tissues. Some of these experiments may also study the behavior of the animal. They also include disease models; that is, the simulation of a human disease to learn more about it. Obviously, experiments in vivo are the ones that pose the biggest ethical problems in terms of animal welfare. Although experiments in vitro and ex vivo also require animals, the only thing that is usually done to them is to euthanize them to harvest tissue or cells.
As we can easily see, experiments in vitro, ex vivo and in vivo cannot replace each other, but form a hierarchical system that allows us to take information from the cellular level to the tissue level and finally to the level of the whole organism. In fact, most modern labs perform experiments at all three levels to address a particular scientific problem.
Then, how is basic research connected to the invention of a new medicine? Once we have understood a physiological process related to the disease we are studying, we can find key points in this process that can be manipulated to change it. These key points are normally a protein that performs a fundamental function. These proteins are called “targets”. By studying the structure of the target protein, we can find pockets in it where a small molecule can bind, changing its function. That small molecule is a candidate medicament. Then starts a long process of studying the function of that potential drug at the cellular, tissue, whole organism and finally human levels to determine its usefulness. Although many potential drugs never make it very far in this process, they are still useful, because they become new tools that can be used in labs around the world to further their research.
Hopefully, I have shown that animal research is very different from just testing a drug in an animal. I would also like to point out that we should be careful not to get hung up on thinking of only chemicals as the only possible cures. Basic science can also help discover entirely new ways to manipulate the body, like electrical and magnetical stimulation, revolutionary new surgeries and nanotechnology. We should also recognize that knowledge has value on itself. Not only can we not predict what piece of information can serve as a springboard for that revolutionary new invention or medical procedure, but we should consider also that what we learn about our bodies and our minds tells us something enormously valuable about who we are.
Biomedical research is one of the most difficult of human endeavors. It has been developed over two centuries by the join effort of thousands of our most brilliant scientists. No single person has decided that it should be done in this or that way; instead, it has been the critical interaction of those thousands of scientists what has made it the successful way that it is. Certainly, it can be improved and, in fact, it will be improved, given the self-correcting nature of science. But tampering with it by imposing over-zealous and ideological restrictions, like a prohibition of using animals for research, would have far-reaching consequences in our ability to cure human suffering.
Juan Carlos Marvizon