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FEATURE
Grave New World - Emerging technologies with the power to harm or help pose tough ethical choices – and a challenge for educators. + By Art Pine

Among pet and wildlife lovers, few topics incite more fury than the use of animals in laboratories. But federal regulators and many scientists agree that mice, along with rabbits, dogs, and even horses, are preferable to human guinea pigs for risky experiments. And just as medical researchers resort to animal tests before trying out new drugs or vaccines on patients, biomedical engineers conduct similar trials to help perfect medical devices, tissue regeneration techniques, and even plastic surgery tools like TissuGlu®. An adhesive that reduces the need for drainage after tummy tucks, TissuGlu is the product of a start-up, Cohera Medical Inc., cofounded by University of Pittsburgh chemical engineering professor Eric Beckman. The material began trials involving 150 patients only after it was tested on dogs. Beckman is on the faculty of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, one of hundreds of academic settings in the United States where animal use is commonplace.

“Currently, [animal testing is] a necessity if you want to get through the FDA and get your product to market,” says Kristen O’Halloran Cardinal, an associate professor of biomedical engineering at California Polytechnic State University, referring to the U.S. Food and Drug Administration approval process. Though not engaged in animal testing herself, Cardinal says, “There’s just a lot of information you can get from animal models that you can’t get anywhere else.”

Soon, however, there may be an alternative—and one developed by engineers. At the University of Maryland’s Clark School of Engineering, Cal Poly, and elsewhere, researchers are developing human tissue in a lab, opening up a new pathway for testing medical therapies without involving patients—or subjecting animals to what some consider inhumane treatment. To Andrew Rowan, chief scientific officer of the Humane Society-U.S. and CEO of HS International, this kind of research is the wave of the future. He predicts that together with other changes in practice brought about by regulation, the new technological advances will result in an abolition of invasive testing by 2025 and all testing by 2050.

Life on a Chip

For the best data, human cells trump animal ones, says William Bentley, founding chair of Maryland’s Bioengineering Department. So, he and his team are helping develop a way to mimic our organs and bodily systems without any danger to humans. Real cells are grown in a lab and placed, in a specific order, on computer chips. “If you can get human cells and human tissues to function on a chip, then that’s what you want. That’s the goal,” he says, since it eliminates a lot of the variables with an animal model. Pioneered by Michael Shuler, biomedical engineering chair at Cornell, the “human on a chip” concept is being pursued by researchers at the Massachusetts Institute of Technology and other universities. But much of the essential ground-level research is being accomplished by Bentley’s research team, which is part of a Biochip Collaborative. His group studies how bacteria communicate with each other through molecules, a process called quorum sensing. It is discovering how to disrupt this communication when the bacteria are near human cells on a chip.

The result? Bentley’s work might eventually replace the use of antibiotics and stop drug-resistant bacteria in their tracks. While there are limitations, such as testing metabolism, immune system response, and behavioral changes, he says, “the promise [of the research] is so large” that “we gotta go there.” He doesn’t necessarily think the end result of his work will replace animal testing, but he contends that it will be cheaper, which would be enticing for pharmaceutical companies and institutions. And reducing animal-based research is “clearly a big motivation.”

What Schools Are Doing... Here are some of the varied approaches to engineering ethics:A different approach is being taken at Cal Poly, where Cardinal is building blood vessels from scratch. The many uses of her bioreactor-produced blood vessels include direct grafting into the human body and testing whether coronary stents are tolerated by the endothelial cells that make up the vessel walls. Stents are used to keep an artery passage open following a heart attack. Now cell response to the device can be measured in a laboratory setting without the need of a living subject.

Typically, stents would be tested inside the artery of a rabbit’s leg, since it is fairly similar in size to a human coronary artery, but this invention could eliminate that need. “We don’t think these will totally replace the need for animal models,” Cardinal says. “We’re not there yet.” But she thinks “it definitely has potential.”
Cardinal has her students wrestle with the pros and cons of animal testing in a 10-week graduate-level class on the FDA process for approving medical devices. “The ethical concern with taking animals’ lives is what frames the argument.” Is the final product worth hurting animals if it has the potential to save human lives? What are the arguments against it? But she doesn’t tell her students if the practice is right or wrong. Instead, she lets them decide. “It’s important for the students to come to their own opinion on that,” she says.

In the here and now, even researchers who would prefer to abandon animal tests find their hands tied. While those in the biomedical fields “feel guilty,” according to Rowan, and “tend to get defensive,” since their work does result in the deaths of animals, the FDA requires that all chemical entities, in order to be approved for human trials in the United States, must be tested on animals first. This includes tests on drugs, vaccines, and surgical adhesives.

At Maryland, Bentley is part of an effort to modernize the regulatory process for medical research. He is a leading investigator at one of two Centers of Excellence in Regulatory Science and Innovation. The other is at Georgetown University. As part of a collaborative effort among the universities, corporations, and the FDA, the centers aim to improve rules for evaluating drugs and medical devices and help the process keep up with new areas of science like cell therapy and nanotechnology.

Gaps in Regulation

Mice and rats account for an overwhelming proportion of laboratory animals. Scientists at the Jackson Laboratory, the Bar Harbor, Maine-headquartered institution that breeds mice for researchers worldwide, say the rodents are ideal for drug efficacy testing and modeling complex human diseases ranging from atherosclerosis to glaucoma, neuromuscular disorders, and cancer. Among other purposes, mice are used in the early phases of testing to determine whether or not a substance is toxic. These animals are never given pain medication, and Rowan says they “always suffer.” They’re not covered by the Animal Welfare Act of 1966—neither are birds, horses, farm animals, or invertebrates—and thus procedures performed on them are not necessarily regulated, especially when no federal funding is involved. When labs break the few laws and regulations currently on the books, those responsible are rarely brought into courtrooms, and almost never see jail time, Rowan says. But treatment of animals, he adds, is “far better in corporations than in academia,” thanks to tighter controls.

Rowan also insists that “animal data is not a gold standard,” and it is an unreliable indicator of what a substance will do inside humans. In order to meet 21st-century needs for understanding and testing the more than 30,000 chemicals in existence and their interactions with the human body, using animals would take too long, as well. “[The tests are] not good. They’re mediocre at best.” Each chemical requires multiple trials to determine if it’s safe and each test uses up hundreds of animals. A test for carcinogens alone requires 400 mice and rats across three years to complete, according to Rowan. Such a cumbersome process is one reason for a steady decline in animal-based research, he says.

Hoping to see a complete end to animal testing, Rowan is a staunch champion of the “human on a chip” and similar ventures. Meanwhile, Humane Society lobbyists are seeking stronger regulations against mistreatment of lab animals, and they’re working to restrict or eliminate the use of some animals—such as primates—altogether. In 2012 alone, the group helped persuade Air Canada and United Continental to refuse shipments of primates meant for lab experiments, and it was instrumental in getting Europe to drop many of its animal test requirements in pesticide regulations, the largest ever reduction of its kind. In the United States, after lobbying from the organization, Minnesota stopped all pound seizures, where lab animals are taken from shelters instead of bred, and NIH released hundreds of chimps to a special sanctuary, with more to be “retired” soon.
But at least when it comes to rodents, science is pushing in the opposite direction.

The Jackson Laboratory has created a “humanized” laboratory mouse through planting human blood cells into animals with suppressed immune systems. And a January 2013 study published in the Proceedings of the National Academy of Sciences describes a new genetically engineered breed of mice with humanlike immune system responses. The value of data derived from drugs tested in mice is greatly improved by these and similar breakthroughs. As a result, there has been a recent uptick in the laboratory use of mice with altered genes, which allow researchers to better mimic human bodies without actually using them.

 

Jaimie Schock is assistant editor of Prism.

 

photo collage by Nicola Nittoli



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