Can animal testing in the med-tech community really become a practice of the past in the U.S.?

Even with a recent five-year plan presented by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), a committee of National Institute of Environmental Health Sciences (NIEH), it is still up to individual med-tech companies to adopt recommendations from the plan and implement those recommendations.

Unlike Europe, there is no U.S. legislation to provide any backbone to the ICCVAM recommendations which recommend more humane ways of testing (Medical Device Daily, April 29, 2008).

In fact, the primary driver of less animal testing in medical research (and the development of cosmetics) is likely to come from advances in technology itself — often being developed by smaller firms. And for now, the reduction of animal testing appears to be a patchwork effort loosely linked among these small firms and research labs developing alternative strategies and showing that there are testing methods superior to the use of animals.

A small band of researchers at the University of Maryland (College Park) is demonstrating this with the development of a micro-fluidic chip, or a micro-factory, that allows the manipulation of cells using fluid, electrical and optical means.

"The biochips aren't that small — maybe an inch or two inches in size," said Gary Rubloff, a researcher with the project and a professor of materials science in the university's A. James Clark School of Engineering.

"What we can do inside the chip is interrogate the cell," he told Medical Device Daily. "The more techniques we use, the more we can understand how the cell responds to certain circumstances. I believe the impact of that is enormous — the true impact is just beyond belief."

Researchers place an enzyme on this tiny biochip that is created to mimic the environment within the human body, and the enzyme performs as it normally would.

The researchers then can proceed to the next step — testing new drugs to see, for instance, how effectively they can inhibit bacteria such as E. coli, rather than testing the drugs on animals.

One targeted application of the microfactory is to develop drugs that can interrupt a process called "quorum-sensing."

In quorum-sensing, bacteria cells, such as E. coli, communicate with each other to form a quorum, or group, capable of creating an infection. The team already has demonstrated that it is possible to interrupt this quorum-sensing ability or to introduce new communication to ultimately prevent such infections.

"Our drug therapy wouldn't kill the bacteria but [would] keep it from talking to each other," Rubloff said. "When you kill it you create a condition where later strains mutate and well ... we've all seen in the news what that leads to."

Such a discovery is almost impossible to test for in an animal, he said.

"Using biochip microfactories, we believe it will be possible to test potential drugs," Rubloff said. "We hope to enable scientists and physicians to create better, more effective drugs more rapidly and at reduced cost."

Part of those costs include the burden of animal testing. "Animal testing is unbelievably time-consuming and expensive," he said.

The high cost of animal testing is the hook that has allowed MatTek (Boston) to develop an alternative to the dermal toxicity test, known as the Draize skin test, using animals.

The company, founded in 1985 by two chemical engineering professors from the Massachusetts Institute of Technology (Cambridge, Massachusetts), produces a 3-D human skin equivalent for med-tech and cosmetic companies. The pieces of skin are fairly small — about the size of a dime or a quarter, depending on the experiment it is used for — and are grown inside a Petri dish. Cell viability and tissue toxicity can be observed from the reactions to the skin. Typically the cells that make the skin replica are donated and are grown in a dish.

"What we offer is a humane alternative and a qualitative look at analyzing the effects — at the end of the day a Draize skin irregularity was in the eye of the beholder," said Dave Ingalls, sales and marketing director of MatTek

"It was very arbitrary and very qualitative," he told MDD. "You could have 10 people observe the affected animal, and five would say its skin wasn't irritated and five more would say that it is irritated."

The Draize skin toxicity test is a test that measures the allergic reactions of rabbits to a chemical or application applied to their skin. Usually the backs of the rabbits are shaved and a chemical is placed on the skin. Then after a period of time, the skin is observed for any outbreaks or any rashes.

It's one of the oldest tests in animal experimentation and is the unfortunate "gold standard" that many companies such as MatTek seek to get past.

"This whole idea of in vitro testing has been around for at least a decade, but it's really just starting to catch on," Ingalls said. "We're seeing more companies gravitate toward it, but the process has been very slow."

He added that the recent movement to looking for animal testing alternatives has been "more scientifically driven."

ICCVAAM also has pushed for an alternative to the traditional tests for allergic contact dermatitis (ACD; a.k.a. skin sensitization). In this test a guinea pig is used and the researcher observes whether or not the animal's skin develops redness, swelling and itching over a four-week period.

For years ICCVAM has pushed the mouse local lymphnode assay, an alternative which has the substance applied to the animal's ear, a non-sensitive area.

The test ends after six days following injection of a radioactive marker to detect lymphocyte proliferation in the draining lymph nodes. If a substance is a sensitizer, it will induce a three-fold or greater increase in lymphocytes compared to controls.

Thus, the mouse test eliminates the need to see if redness and swelling result and essentially eliminates the pain and distress associated with the guinea pig test.

The recommendation for this test has been on the books for 10 years now, but it is still not widely adopted.

"To some extent we're always going to have some form of animal testing," Ingalls acknowledged, noting that human empathy for the suffering of animals is both easily rationalized and generally blind to our most superficial desires.