Until the middle of the twentieth century, human beings had no defense against deadly microbial diseases. Bubonic plague, cholera, tuberculosis, and syphilis; waves of infectious diseases regularly swept across the globe killing millions of people. But then, suddenly, everything changed.
In 1935, the Bayer drug company in Germany was experimenting with the pharmaceutical properties of dyestuffs and found that one dye called Prontosil Red seemed to be effective in treating several common infectious diseases. Most dramatically, the new drug was given to President Roosevelt’s son who was dying in hospital from a mouth infection. His skin went red, but he was completely cured. The new drug, which became known as sulfanilamide was the first widely used antimicrobial agent. It seemed like a miracle. One minor drawback was that it tasted awful. To solve this problem, in 1937 the SE Massengill company in the United States began to sell a new preparation or “elixir” where the sulfanilamide was dissolved in polyethylene glycol (PEG) flavored with raspberry. Unfortunately, the PEG proved to be extremely toxic and over 100 people died. There was a huge public hue and cry and the US government reacted by passing the Food, Drug and Cosmetics Act, which required much more extensive testing of new drugs by pharmaceutical companies prior to their being approved for sale to the public. Similar laws were passed in other countries.
“The FDA has announced that it will no longer require animal testing if companies can prove effectiveness and safety using non-animal models.”
Over the years, these laws have been extended and refined. Pharmaceutical companies now have to present a large amount of evidence to the Food and Drug Administration (FDA) proving that their new drugs are both safe and effective. As it is not deemed reasonable to test numerous potentially poisonous substances on humans, most of the initial testing is done on animals, hundreds of millions of which are used every year for this purpose. Testing needs to be performed on at least two species—usually mice and another species such as dogs or monkeys. Multiple tests need to be run examining how drugs are metabolized and how they affect different physiological systems including reproduction, the gut, heart, kidney, and liver. Increasingly, however, much of this testing has come to be viewed as unnecessarily cruel and not particularly effective. Indeed, there have been several well publicized examples of drugs that were thought to be safe based on animal trials but produced extensive toxicity and fatalities in humans.
A revolutionary alternative to animal testing
Now, in a truly significant volte-face, the FDA has announced that it will no longer require animal testing if companies can prove effectiveness and safety using non-animal models. So, what changed? The first thing to realize is that animals aren’t humans. It’s true that in certain respects a mouse and a human resemble one another. For example, they both have bilateral symmetry and organs like the liver, heart, kidney, and lungs have a general resemblance from one species to another. However, recent advances in gene sequencing technologies have demonstrated that there are many significant differences between humans and other species in terms of their genetic structure and these differences can be of great importance when considering the potential effectiveness of a drug. Clearly therefore it would be much better to be able to screen drugs using human tissues. But, how?
In the 1877, the German scientist Ernst Haeckel, a dedicated follower of Charles Darwin, had an interesting idea. Just as different species evolved from one another he viewed the development of an individual animal in the same way. Each embryo would begin with a single cell that had the potential to develop into all the other cells of the body. He called this cell a “Stammzelle” or “stem cell.” Haeckel and his students began to investigate this concept and observed that cells obtained from early embryos could indeed generate complete animals. Over the next 150 years these studies continued leading to the realization that stem cells isolated from all creatures, including humans, could be used to generate all the different tissues of a mature animal. These cells could then be used for experimental or, potentially, therapeutic purposes.
“The use of animals is now behind the curve; it’s unnecessary and can be replaced by studies based on genuine human tissues.”
We now know that human stem cells can be used to generate complete organs in cell culture, structures known as organoids. Even eyes can be grown from stem cells and made to cry in a cell culture dish! Organoids can be linked to one another using what is known as “organ on a chip” technology, which mimics the communication usually mediated by blood and lymph between different tissues in intact animals. It is becoming clear that systems like these are much better for testing drugs and for many other purposes than using animals. Research in this field is advancing at a truly remarkable rate. It’s a revolution, that’s for sure! All this means that in an ever-increasing number of situations, including drug testing by the pharmaceutical industry, the use of animals is now behind the curve; it’s unnecessary and can be replaced by studies based on genuine human tissues. Moreover, because every person can provide their own stem cells, these procedures can represent the entire spectrum of human diversity. You just can’t do using mice.
Most people agree that performing experiments on animals, whatever their utility, is very cruel. Now, new laws reflecting the fact that we no longer need to do these things are being brought forward by members of the US government that represent both Democrats and Republicans working together (imagine that!).
Biomedical research using animal models is disappearing very quickly. It is already possible to imagine a future when we won’t do it at all. And you know what? We won’t miss it.