HUMAN skin, eyes, the lining of the throat — snippets of these and other tissues are now routinely grown in test
tubes from donated human cells. The goal is not to patch up ailing people but to use the human tissues in place of mice, dogs
or other lab animals for testing new drugs, cosmetics and other products.
The methods for engineering tissue samples are among the most complex of an expanding portfolio of technologies intended
to eliminate or reduce animal testing. In other cases, testing is being conducted virtually, using computers and simulation
software. And for some tests, people have replaced animals: volunteers get microdoses of potential drugs that can be analyzed
but cause no ill effects.
The development of such alternatives is a tale of creeping technical innovation, exemplifying what happens when slowly
accumulating pressure for change encounters a major scientific challenge.
“Nothing has gone faster than we expected,” said Alan M. Goldberg, a toxicology professor and director of
the Center for Alternatives to Animal Testing at Johns Hopkins University, a nonprofit research group founded in 1981. “That’s our big disappointment.”
By conservative estimates, tens of millions of animals are killed or maimed each year in research on the safety and effectiveness
of new drugs, agricultural chemicals and consumer products. For companies, animal testing can be a public relations nightmare,
involving confrontations with animal-rights activists, or less intense but still negative reactions from consumers.
The high costs and concerns about reliability, however, have been the biggest forces behind the shift away from tests
on animals. Industry executives say that as much as 25 percent of the drugs tested on animals failed to show side effects
that later proved serious enough to prevent the drugs from being marketed. To avoid such mistakes, companies often test products
on multiple species and large numbers of animals.
Concern about the costs and questionable benefits of animal testing has been growing since the 1970s, and the number
of lab animals sacrificed in the United States has fallen since then by nearly 50 percent among the species tracked by the
Department of Agriculture; the total was 1.18 million in 2005, the last year for which numbers have been reported. The government’s
statistics are limited to cats, dogs, primates and a few other species and do not cover birds or fish, or the most common
lab animals, mice and rats.
“It’s hard to say whether the overall numbers are down or up,” said Martin Stephens, vice president
of animal research issues at the Humane Society of the United States.
Developing the alternative methods has turned out to be daunting partly because it takes years of testing to satisfy
users and regulators that the results are as accurate or better than animal trials. Many researchers believe the caution is
justified.
David B. Warheit, who oversees research at DuPont on the potential hazards of new nanoscale materials, cited his own experience as an example. Nanoscale particles, so-named
because they are measured in nanometers, or billionths of a meter, are so tiny they can slip easily inside cells. That might
pose novel hazards, and some reported tests of carbon nanoparticles, called fullerenes, had shown alarmingly that they killed
various human cell samples in test tubes.
But when DuPont researchers injected the fullerenes into the lungs of rats, the animals’ immune systems apparently
removed them before any lasting damage was done. For various reasons, Mr. Warheit said, he believes the live-rat studies produced
a more accurate reading on the risks than the test-tube experiments did.
Still, in-vitro tests using human cells have been making headway. Analysts estimate that businesses spent $716 million
last year for contract research at labs that specialize in such alternative techniques.
The field is crowded with start-up companies like MatTek, Admet and Xceleron. MatTek, a small company in Ashland, Mass.,
grows human tissues for testing from donor cells. The tissues take up to four weeks to grow in the test kits in which they
are shipped, said John Sheasgreen, the company’s president. Up to three types of cells might be combined in a single
tissue to produce realistic behavior, he said.
Admet owns In Vitro Laboratories, which charges up to $20,000 to screen a drug against liver cells and other human tissues
for toxic effects. To get the same information from animals, a drug company would have to use much more of the drug, wait
a lot longer and pay for the upkeep and eventual autopsies of the animals it used, said Albert P. Li, chairman of Admet. “We’re
not making a huge profit,” he added, “but we’re making a living.”
Charles River Laboratories, the world’s largest supplier of genetically engineered rodents for labs, also has a
subsidiary called Endosafe, which provides an alternative to the testing of solutions in rabbits’ eyes for contamination
with fever-producing bacteria. The test, which can be as cheap as $5, has not only replaced most rabbit testing in quality-control
rooms at drug company factories but is also finding a market at dialysis centers as a check on water quality, the company
said.
“We are the fastest-growing division in Charles River with the highest margins,” said Foster Jordan, head
of Endosafe. “There’s a business incentive to push this.”
Other small companies, like Entelos, in Foster City, Calif., supply computer simulation programs for virtual testing.
Such software incorporates hundreds of variables to simulate how humans who suffer from conditions like asthma, obesity or
Type 1 or 2 diabetes will react to a new drug.
But in many ways the alternatives are driven by a few giants eager to move from animal testing for scientific, business
and image reasons. Procter & Gamble has spent $225 million developing and deploying alternative testing methods for a wide range of personal-care and pet food
products over the last 20 years, said Len Sauers, the executive who oversees the work.
And L’Oréal, the French cosmetics giant, says it has spent more than $800 million over the same period. That includes
deals to buy Episkin and SkinEthic, two companies that make alternative tests.
“This is not an area of competition for us,” said Patricia Pineau, L’Oréal Research’s spokeswoman,
who said that its tissue testing products and services were sold at cost to other companies, including rivals like P.&G.
and Unilever.
Those cooperative impulses are being driven by European regulators, who have set 2009 as a deadline for all animal testing
on cosmetics. Another push has come from European legislation, which requires companies to provide safety data for about 30,000
chemicals over the next 11 years. Estimates found that the program could require killing an additional 3.9 million animals,
but regulators have responded by putting heavy pressure on industry to develop and validate alternatives.
As a result, Mr. Stephens said, European regulators and industries have a 10-year lead in adopting alternatives in the
United States, where there have been no similar government mandates to reduce animal testing. But American advocates who want
to move from animal testing have been heartened by a recent study from the National Academy of Sciences, which was sponsored by the Environmental Protection Agency.
“The report says we now have the tools to look much more closely on how toxicity occurs, and that we have to do
it on human cells,” said Rodger D. Curren, president of the Institute for In-Vitro Sciences, a nonprofit testing center
in Gaithersburg, Md. The study concluded that over time, the use of animals for testing could be greatly reduced and possibly
eliminated.
