Uncovering alternatives to animal testing

Brown researchers are pursuing a promising new method that could transform toxicology testing, making it faster and more effective without the use of animals.

Image of two-compartment liver cells through microscope

Every day, we are exposed to approximately 75,000 artificial chemicals. They’re in the food we eat, the medicines we take, and many of the household products we use. But what do we know about how they affect our bodies?

Not much, it turns out. That’s because toxicology testing is a slow and painstaking process.

“This kind of research is conducted in mice and rats over a lifetime of the mouse and rat, which is two to three years,” says Kim Boekelheide, professor of pathology and laboratory medicine at Brown’s Warren Alpert School of Medicine. “And, it can take up to 10 years to actually get a report.”

Boekelheide says that each time this is done, it can cost approximately $3 million. But even then, scientists can’t be sure that the findings produced from rat and mice tissues are applicable to humans.

“If you expose mice and rats to the same chemical, the tumors you get in mice map to the tumors you get in rats less than half of the time,” he says. “So mice are not predictive of rats and yet we use both of them to predict the human response. I think we can do much better than that.”

Donna McGraw Weiss ’89, a Brown University Trustee, agrees.

“We're developing chemicals all the time and putting them out in the environment,” she says. “When we see some sign that there's a problem, then we go back and do the research once the chemical is already in use.”

McGraw Weiss and her husband Jason, who is involved with animal welfare organizations, thought that Brown would be the perfect place to investigate and promote new ways of performing this kind of science, without the use of animals.

“Our initial investment was actually in a piece of equipment—a high throughput microscope,” she says. “That initial foray into the equipment was like, ‘if we build capacity at Brown, they will come’. There were a number of researchers who said, ‘here's this shared facility at Brown; let me figure out how I can integrate that into my work.’”

And that’s how the idea for Center for Animal Alternatives in Testing (CAAT) at Brown was born.

25 million

animals used in research and safety testing of drugs and chemicals each year


of new drugs fail in human clinical trials

3 years

needed to test toxicity of one chemical in animals

The way of the future

green 3D Petri Dish
The 3D Petri Dish, patented by Brown, is a natural cell culture environment that accelerates the formation of 3D human microtissues.

The best way to eliminate the use of animals in toxicity testing is to develop strategies for testing living human tissues. The Center for Animal Alternatives in Testing brings together a collaborative team of bioengineers, pathologists, toxicologists, cell biologists, electrophysiologists, and mathematicians working with industry to develop new 3D microtissues that are more predictive of toxicity and drug efficacy.

The center’s current director Jeffrey Morgan, who had used 3D cell culture techniques to grow human skin cells earlier in his career, worked with graduate students in his lab to devise a faster way to grow microtissues. Their 3D Petri Dish, patented by Brown, maximizes cell-to-cell interactions and allows for examination of the resulting tissues through high-content microscopy.

“Our invention made it possible to make these tissue samples pretty quickly, and you could image them really nicely,” he says. “And, as Kim realized, it has applications in drug and toxicity testing. They’re made of actual human cells and comparable to living organs.”

If you source the cells from different individuals, Morgan says, you can begin building banks of cells that reflect the diversity of humans—the kind of diversity that is lacking in laboratory mice. This means testing will become more accurate based on characteristics of different groups of people.

“ If we look at what this past year has shown us, being able to do research quickly can be so important. And with animal research, you're limited by the time it takes. ”

Donna McGraw Weiss ’89 Brown University Trustee

Accelerating the pace of change

The methods and technology that faculty in the center are using allow for large numbers of microtissues to be tested in a short amount of time. With the help of automation and artificial intelligence, analysis of this data becomes more efficient, more accurate, and less expensive.

“This research can lead to a model where we can quickly test chemicals before we ever put them out there,” says McGraw Weiss. “If we look at what this past year has shown us, being able to do research quickly can be so important. And with animal research, you're limited by the time it takes.”

Boekelheide gives an example that puts the need for speed in perspective: The National Toxicology Program, a division of the National Institutes of Environmental Health Sciences, has spent 25 years testing for carcinogens using animal models. In their entire existence, they've managed to test just 600 chemicals out of the approximately 75,000 that exist.

The promise of Brown's research—both to eliminate animal testing and to improve the science of toxicity testing—has brought in additional external funding from the NIH and led to industry partnerships with Unilever and Corteva, a spin-off of Dow Chemical.

The Weiss family has also endowed the center director’s position, which ensures that this work can continue well into the future.

“Brown has a role to play in training people to think differently,” says McGraw Weiss. “Creating a center accelerates the research, but also the training of graduate students, undergrads, and postdocs who may take this out to other institutions, which really builds out a whole field.”

“I think you're going to see more and more of this work happening now that there is awareness of the limitations of animal testing,” says Morgan. “We’re attracting more people and more expertise. I see the whole thing beginning to snowball, and Brown is making it happen.”

Related Links