Is it feasible to stop using animals in biomedical research?

Chen Bingliang, chief scientist of Innovent Biologics' new drug research department, told Intellectuals that the bill is to remove the "animal test mandate" for new drugs, with the goal of drastically reducing animal testing in the next few years, but does not say that animals cannot be used for testing
.

Since the birth of modern medical research, humans have been using animals as anatomical and physiological models, according to experimental needs, experimental animals include mice, monkeys, rabbits, dogs, ferrets, pigs, fruit flies and so on
.
Some animals are highly similar to humans in a biological sense, such as chimpanzees have 98% genetic similarity with humans, and mice and humans have a genetic similarity of more than
90%.
Therefore, their response to viruses and bacteria may be similar
to that of humans.

Stanford University School of Medicine pointed out that animals are prone to many of the same health problems as humans - cancer, diabetes, heart disease, etc.
, in addition, the animal life cycle commonly used in the laboratory is relatively short, taking mice as an example, they usually live 2-3 years in a better environment, so people can study their entire life cycle or even generations of mice, which is a key element
in understanding how disease develops and how it interacts with the entire living biological system.

The biological phenomena of some animals are well studied, and they are called model animals
.
For example, in a series of genetic experiments, fruit flies are a very important classic model animal
.
As early as the middle of the last century, some scholars won the Nobel Prize
for studying fruit flies.

In drug development, preclinical testing generally refers to animal testing
.
Animal tests generally select two species of animals, one is rodents, that is, rats or mice, and the other is large animals, including monkeys, dogs, small pigs, etc.
, by comparing metabolic profiles, targets and other pre-experiments, to determine which animal is more sensitive to drugs, and toxicity tests
on animals.

The founder of a pharmaceutical company said in an interview with the media in June this year that non-human primates have become the first choice for
preclinical trials.
It is estimated that about 70% to 80% of biological drugs will use experimental monkeys for preclinical trials
.
About 40 monkeys are needed for toxicology experiments, and about 20 monkeys are needed for drug metabolism tests, so at least 60 experimental monkeys
are needed for normal preclinical research of a new drug.

In 1938, U.
S.
President Franklin D.
Roosevelt signed the Federal Food, Drug, and Cosmetic Act, which requires all drugs to provide evidence
of safety before they can be marketed.
Testing safety in animals before using it in humans has become the only option
for decades.

In the 60s of the 20th century, doctors in at least 15 countries in Europe and the United States used "reaction arrest" (thalidomide) to treat women's pregnancy reactions, resulting in as many as 12,000 babies with short-limb deformities
.
The drug was tested in mice, but not in monkeys
.
Subsequent toxicological experiments found that the drug was less teratogenic to animal mice, but strong for primates, including humans
.
After a "reaction stop" event, new drug screening often requires the use of multiple species of animals
.

In addition, Wu Jun, assistant professor at the University of Texas Southwestern Medical Center, said in an interview with "Intellectual" that with the increase of disease models and the complexity of research, a consequent situation is that more and more animal experiments in scientific research, whether in terms of quantity or type, the dependence on experimental animals is increasing
.

Taking monkeys as an example, Niu Yuyu, deputy dean of the Institute of Primate Translational Medicine of Kunming University of Science and Technology, said in an interview with the media in 2021 that from 2016, in the field of biomedicine, whether it is the establishment of national scientific research projects or the research of each scientific research itself, primates will be involved, and everyone realizes that using monkeys to carry out research can answer more basic scientific questions
that have not been answered in rodents.
The development of cutting-edge research in biology such as stem cells and gene editing has also promoted the demand for
primate experiments.

Therefore, it is not difficult to understand that the United States, the most developed biomedical industry, is also a big country
for experimental animals.
According to the statista website, in 2020, the United States was the country with the largest number of research and test animals, with a total of about 20 million, followed by China, Japan and the European Union with 16 million, 11 million and 9.
4 million respectively
.

Tan Tao, a professor at the Institute of Primate Translational Medicine at Kunming University of Science and Technology, told Intellectuals that although the USDA has no longer updated its imported monkey numbers in recent years, it is known that the United States is the country with the largest number of monkeys in the
world.
According to statistics from the US Department of Agriculture in 2017, the use of monkeys in the country has reached a record high, with more than 74,000 monkeys used throughout the year, including drug safety evaluation and basic experiments
.

Before the pandemic, China became the world's largest supplier of non-human primate laboratory animals, and experimental monkey farms were mainly distributed in the Yangtze River Delta and provinces
such as Guangxi and Yunnan.

Rodents are the most
used.
The Foundation for Biomedical Research, a nonprofit organization based in Washington, D.
C.
, estimates that rodents such as mice and rats account for about 95 percent
of animals used for biomedical research in the United States.
At Pfizer, a multinational pharmaceutical company, 99% of the laboratory animals in its care are rats and mice
.
Other species include rabbits, hamsters, guinea pigs, ferrets, dogs, and non-human primates
.
The company states that its research animals come from approved vendors whose animal welfare practices and animal care programs are routinely audited
by Pfizer.

However, animal experiments are not perfect because drugs are absorbed, distributed and metabolized differently in different species, and animal models have been criticized
for their limitations in predicting the toxicity, safety and efficacy of new drugs.

In September 2021, a review article published in Expert Opinion on Drug Discovery noted that criticism of animal testing is not entirely unfounded
.
Animal models and associated preclinical data are not absolutely correct in terms of "predictability", with an estimated capacity of only 8% or less
for the successful translation of new anti-cancer drugs being studied, from animal model studies to clinical evaluation.
There are many reasons for these transformation failures, including ineffective molecular targets and targeting, insufficient drug dose-response relationships, and so on
.

Amez-Droz, program director for the Open Health Project at the Mercatus Center at George Mason University in Arlington, is a proponent of the latest bill, and she sees it as a regulatory advance.

Writing an October 5 opinion piece in the Wall Street Journal, she wrote that studies have shown that animal testing may not predict toxicity in humans (drugs, foods, etc
.
) very well.
The new bill will make such testing optional, allowing drugmakers to choose the most effective toxicity testing techniques
.
If the law changes, pharmaceutical companies can rely on more accurate testing before starting human trials, bringing safer, more effective drugs to commercialization
.

"This will reduce R&D costs, speed up drug development, and increase the number of
drugs on the market.
" Given that bringing a drug to market can cost $1 billion or more, removing these legal hurdles would also be welcome
.
Ultimately, this will mean more competitive drug prices
.
”

Although animal models are so important in research, in Europe and the United States, in recent years, there have been voices calling for less use of animals for research
.
Last October, Senators Paul and Booker introduced their original bill, S.
2952, and around the same time, the European Parliament passed a resolution in 2021 by a vote of 667 to 4 to phase out animal testing
.