Are the lab rat's days numbered?

Are the lab rat's days numbered?

More accuracy seen in living cell stand-ins for human organs
By Colin Nickerson, Globe Correspondent | March 30, 2009

Bioengineers are striving to topple a scientific icon: the lowly lab mouse. And to replace bunnies, beagles, and other warm-blooded animals with insentient but biologically sophisticated substitutes.

At Brown University, the Massachusetts Institute of Technology, and other research centers, new efforts to build complex living "microtissues" from cultured cells represent some of the most promising progress toward reducing the need for laboratory creatures.

Numbers have been reduced in recent decades, but hundreds of thousands of mice, rats, chickens, and other creatures are still employed for medical experiments. More controversially, but also in greater numbers and with less oversight, millions of animals worldwide are sacrificed for testing of products whose only aim is to impart a sexier sheen on lips or more sparkle in toilet bowls.

The feud between animal rights activists and researchers is among the bitterest in science. But many researchers - although adamant that animal research remains critical to finding cures and expanding medical knowledge - have come to concede that using creatures as human stand-ins is unnecessary for many procedures. Indeed, it often isn't even the best science: New drugs that show great promise in mice, for example, often confer zero benefit to humans, or even prove harmful. Plus, animals are messy, require feeding and constant care, draw protests, and, yes, can be a bit smelly.

"There's a serious effort afoot to find ways to phase out animal testing in research," said Jeffrey R. Morgan, professor of medical science and engineering at Brown University in Providence.

Morgan leads a team that is building three-dimensional assemblages of living cells as a step toward fashioning functional simulations of human organs.

For Morgan and other bioengineers, the big dream is that their labs might someday yield crops of transplant-ready livers, kidneys, and other vital parts. In the shorter term, however, the ambitious experiments ongoing at scores of major universities worldwide could produce complex tissues better suited for testing new medicines and procedures.

"There is a need for tissue models that more closely mimic natural tissue inside the body in terms of function and architecture," Morgan said. Unlike the thin, single-layer tissue cultures in common use today, more complicated 3-D structures will consist of cells taking form from each other - not just the petri dish or some other human-made lattice - and containing blood vessels and other features of true organs.

Morgan's team recently scored an advance, detailed in this month's issue of the journal Biotechnology and Bioengineering, by forging three-dimensional freestanding cellular structures from "building blocks" of living cells. The microtissue was cultured from human surgical waste - neonatal foreskins, circumcised from newborns - and from rats' livers.

"From small spheres of cells, we were able to build a more complex, honey-comb pattern," said Adam P. Rago, one of the researchers. "Cells that build themselves on other cells alone . . . work more like cells in the body."

The Brown work is partly funded by the International Foundation for Ethical Research, an animal rights group that believes supporting scientific effort - as opposed to mounting protests or issuing angry proclamations - is the most effective way to reduce scientific and commercial dependence on lab animals.

"We want to end needless suffering by sentient creatures, yes" said Peggy Cunniff, president of the Chicago-based foundation. "We also want to advance science. We don't think saving mice is more important than saving humans. But there is obvious over-reliance on animals. Animals are often poor [test] predictors for humans."

Other scientists are making different assaults on the same Everest.

Linda G. Griffith, professor of biological engineering at the Massachusetts Institute of Technology and a recipient of the MacArthur Foundation's famous "genius" grant, is developing a "liver chip," a computer chip embedded in lab-cultured liver tissue.

The cells should behave like normal human liver tissue, reacting to medicines or potential toxins as in a real liver - but with the chip conveying to scientists with high precision how, physiologically, the cells react to new drugs or other experiments.

Griffith's eventual aim is to build a "body on the bench," a full set of chip-containing human organs - from bladder to lungs - that could be used to study body functions by simply plugging the appropriate part into a computer.

The MIT research is meant to advance human medicine. "But my work is also squarely in the realm of finding alternatives to animals," Griffith said. "Beyond any moral issues with the use of animals in research and development, alternatives made with human cells might be scientifically better choices - and more economically feasible."

Replacing animals with human tissue has already proven to be good business bet.

MatTek Corp., of Ashland, makes kits of cultured "skin tissue equivalent" for use in testing of commercial products and in medical labs where researchers need to know how human skin will respond to chemicals or treatments.

In a milestone for the company, a European regulatory body recently "validated" MatTek's Modified Epiderm Skin Irritation Test as an accurate and reliable replacement for animal testing. That's perfect timing: This month, the European Union - which, according to nearly all observers, has much more aggressively sought to reduce use of lab animals than the United States - launches a full ban on use of animals in testing cosmetics.

Culturing skin equivalents in a petri dish is not as scientifically complicated as orchestrating cells into functioning 3-D organs. But MatTek's skin points to the future for product testing and some areas of medical research.

"It started out not wanting to hurt bunnies," said Dave Ingalls, spokesman for MatTek. "But we've found that using [human equivalent] tissue is better science, more cost effective, and much more accurate than doing the same tests on animals."