As coronavirus cases continue to climb, researchers are beginning to realize that while testing COVID-19 vaccines on animals is required by the Food and Drug Administration (FDA), it isn’t the only option or the most effective one.
More than 150 COVID-19 vaccines are currently in development around the world. In the process, thousands of mice, monkeys, and other species are being used in research experiments.
During COVID-19 vaccine tests, researchers may inject animals with a vaccine and then purposely infect the animals with the virus to challenge the vaccine. In early trials, the Centers for Disease Control and Prevention (CDC) report that monkeys have shown signs of sickness when infected and that ferrets, cats, and hamsters have spread the infection to other animals in laboratories. But after nearly 60 years of research, experts are not certain that drugs and vaccines tested on animals can be effectively translatable to humans.
According to a 2004 study by the FDA, over 90 percent of drugs that move past animal trials fail in human clinical trials. Despite less-than-promising results, the FDA typically requires that new drugs and vaccines be tested on animals prior to being used in clinical trials with human volunteers.
“The problem is that our governmental agencies, like the National Institutes of Health—which is the largest funder of medical research and testing—still prioritize the use of animals in testing over the development of new human-based methods,” says neurologist and public health specialist Dr. Aysha Akhtar, President and CEO of the Center for Contemporary Sciences (CCS).
Funding for animal research often comes from governmental agencies. According to estimates, the National Institutes of Health (NIH) alone spends as much as $14.5 billion in taxpayer money on animal research each year. But that’s just a guess. The way that the agency breaks down its spending reports is fuzzy, at best. NIH spending is broken down by disease, condition, and other broad areas of research, making it unclear how much of the money spent on each project went to animal tests. This means that a substantial portion of $41.7 billion spent the agency spends on medical research every year could be dedicated to animal experiments.
The figure also does not account for other federal bodies funding animal research, including the FDA, which, in 2019, dedicated about $1.9 billion to drug development.
Proponents of animal research argue that animal testing has been essential in the progress of medicine to this point and that it must be continued. The Foundation for Biomedical Research writes, “It’s one of the first steps in medical discovery. To understand how a disease works in the body, scientists study the disease in animals.”
The price paid by animals used in research is steep. Faunalytics estimates that 25 million animals are used in testing in the United States each year. The organization points out that researchers are not required to report the number of rats, mice, and birds used, despite them accounting for 95 percent of all animals used in experiments.
In March, as labs closed due to COVID-19, researchers were forced to kill thousands of animals. But much like the culling of animals on factory farms, the killing of animals used in research is not new to the pandemic. The coronavirus pandemic has only made the reality of animal suffering more visible.
According to a report by the National Research Council and the Institute of Medicine Committee on the Use of Laboratory Animals in Biomedical and Behavioral Research, “Some research animals are subjected to toxic substances and painful procedures until they are disabled or die, as when determining the lethal dose of radiation used in cancer therapy. Some are killed to obtain an essential organ, such as the liver, to be used in further studies. Others are anesthetized, subjected to an experimental procedure, and killed without regaining consciousness.”
The ‘Right Animal Models’
In the urgency of the pandemic, researchers fast-tracked the Moderna vaccine, testing the drug in human trials before animal trials concluded. Later, they touted the results of animal testing, claiming that monkeys given a vaccine and intentionally infected with coronavirus remained infected but were able to fight off the virus to a certain extent, according to The New York Times.
Some medical experts caution against skipping animal testing, even in crisis scenarios. “Outbreaks and national emergencies often create pressure to suspend rights, standards, and/or normal rules of ethical conduct. Often our decision to do so seems unwise in retrospect,” Jonathan Kimmelman, director of McGill University’s biomedical ethics unit, told Stat.
Normally, labs conduct animal trials to show that a drug is safe before it moves on to trials in humans. But Dr. Jarrod Bailey of CCS says this argument does not always hold true. First, animal trials are not always reliable, he says, meaning that their findings will not necessarily be replicated in human trials. Second, they are sometimes conducted at the same time as human trials, as has been the case primarily in the development of a COVID-19 vaccine, rather than being done beforehand in order to show safety in animals before being tested in humans. This begs the question: why do the animal tests in the first place?
AstraZeneca, Johnson & Johnson, Merck, and Pfizer are all currently working on a COVID-19 vaccine. In July, Pfizer entered a contract with the U.S. government to provide 100 million doses of the vaccine once it is developed and approved. The company declined Sentient Media’s request for an interview, but the company’s Director of Global Media Relations, Jerica Pitts stated that Pfizer has conducted both “traditional animal and clinical model studies” for its BNT162 vaccine program and expects to publish results for two candidate vaccines within weeks. Pfizer is one of the world’s largest pharmaceutical companies, bringing in around $51.8 billion of revenue in 2019. Johnson & Johnson, which is also working on a COVID-19 vaccine, did not reply for comment prior to publication.
There are more than five million confirmed coronavirus cases in the U.S., as the world surpasses 820,000 deaths. The pandemic has created an immediate need to produce a safe vaccine—a process that researchers say typically takes as many as 20 years in some cases. From securing funding, to animal and human trials, and conducting analysis, each stage may require up to five years to complete.
According to Dr. Akhtar, who has served as a Medical Officer at the FDA and a Commander in the U.S. Public Health Service Commissioned Corps, assisting in national public health emergencies, animal testing could be taking up precious time.
“Animals in labs are either not naturally contracting the virus or not showing the symptoms in the way that humans do. So researchers have been trying to create what they call the ‘right animal models’ for this. There is no such thing as the right animal model because they are not based in human biology, so that’s led to a lot of delay,” says Dr. Akhtar. She calls animal testing a significant cause, though not the only cause, of failure to produce effective vaccines, treatments, and cures for humans.
On March 18, the International Coalition of Medicines Regulatory Authority stated that researchers are not required to use “animal challenge” models, where they inject animals with the vaccine and then infect with the disease to demonstrate COVID-19 vaccine efficacy before human trials.
What’s the Alternative?
Given the industry’s poor record, some researchers doubt that testing the coronavirus vaccine on animals will yield better results.
“I don’t see any reason at all why any animal models, any animal tests are going to be sufficiently predictive of the human efficacy and safety of COVID vaccines,” says Dr. Bailey. “There’s just no sign that’s the case.”
The failures of animal testing to produce useful human vaccines against many diseases are becoming common knowledge in academic circles, says Dr. Ahktar. So what’s the alternative?
While no testing method is perfect, Dr. Akhtar says there are techniques that “offer the potential to really understand how a vaccine or drug is going to work in humans, without the problems that we face when we’re trying to look at completely different biological species.”
New techniques include what are known as “human on a chip” models, “a mechanism in which researchers distill a human organ to its micro-components on a chip. For example, the human lung on a chip is a living three-dimensional cross-section of the lung, and it breathes and functions like a regular human lung,” Dr. Akhtar explains.
The “human on a chip” technique has already been deployed in work on a potential treatment for COVID-19. The Times reported on the efforts of the Wake Forest Institute for Regenerative Medicine, creating miniature human lungs and colons for this purpose and sending them to George Mason University for use in testing.
“No one single method here is going to give us all the answers,” Dr. Akhtar adds, emphasizing the need for a wide variety of tools—from imaging, pathology, and autopsy studies to “human on a chip” models and big data analysis—to “give us the best answers about human biology and human diseases.”
For Dr. Akhtar, the bottom line is simple. “Medical research needs to start and end with human biology.”
When Animal Testing Fails Us
Matthew Bailey, president of the Foundation for Biomedical Research, believes animal trials were essential in the development of drugs that now treat HIV. In an op-ed for Detroit News, he writes that a COVID-19 vaccine is “poised to be the product of animal research. It’s a case study in just how crucial animal research is to improving public health.”
Work to produce an effective HIV vaccine has spanned decades. But Dr. Akhtar notes that while about 80 HIV vaccines have been found to be effective and safe in various animal species, including chimpanzees and other non-human primates, “not one has proven safe and effective in humans.”
In his 2008 study, Dr. Jarrod Bailey wrote that “claims of the importance of chimpanzees in AIDS vaccine development are without foundation,” calling any potential return to the use of chimpanzees in this research “scientifically unjustifiable.” He points out that in the case of some other vaccine development too, such as for Hepatitis C and malaria, vaccines have not worked for humans “despite decades of animal testing, despite dozens of vaccines that have appeared to work in animal models.”
Countries and regulatory agencies around the world are leaving animal testing behind. Two years ago, the European Pharmacopoeia Commission dropped abnormal toxicity tests—a method in which batches of human vaccines are injected into animals, typically mice and guinea pigs—from its vaccine safety requirements. This July, India banned these tests, in a move that Humane Society International (HSI)/India applauded as “the first vital step towards consigning animal testing for vaccines to history books.”
“The future of scientific research lies in state-of-the-art, non-animal approaches like human organoids, organs-on-chips, and next-generation computing and AI, not in poisoning, dissecting or genetically modifying mice, monkeys, and other animals,” states Borami Seo of HSI/Korea.
The organization recently conducted a nationwide poll in South Korea, where 3.7 million animals were used in testing in 2019 according to the Ministry of Agriculture, Food and Rural Affairs. The public showed overwhelming support for non-animal testing in general, with 83.4 percent agreeing that the Korean government should increase funding to develop alternatives and 66 percent agreeing that research inflicting pain on animals must improve.
“With the new techniques, the human-specific, human-relevant techniques that are available to us, they can be constantly fine-tuned and honed and improved, and made even better, even more predictive. You can’t really do that with animal tests,” says Dr. Bailey. “If they’re poor and they’re not really predictive of human biology, then that’s it.”
In the U.S., signs of a shift away from animal testing are beginning to emerge. As part of the NIH’s 2021 budget, a working group was formed “in response to growing concern about the rigor and replicability of animal research for improving health outcomes.” The group has not stated whether or not its efforts will impact companies developing COVID-19 vaccines.
According to a timeline published on June 12, the group is due to report to the NIH at the end of this year with its findings regarding both animal testing and its possible alternatives.
“Animals and humans will benefit if we do the right science,” says Dr. Bailey.