Progress - Biochip

Biochip technology can eliminate animal testing in the chemicals and
cosmetics...now if we can just pry the hands of vivisection industry
lobbyists off FDA rulemaking...


Source: Rensselaer Polytechnic Institute

http://www.physorg.com/news117133544.html

Human liver cells are dotted across the new DataChip to quickly
determine if various chemicals, drugs, and drug candidates are
toxic. When coupled with the MetaChip, the two biochips could
provide a highly predictive alternative to animal testing. Credit:
Moo-Yeal Lee/Rensselaer Polytechnic Institute

A new biochip technology could eliminate animal testing in the
chemicals and cosmetics industries, and drastically curtail its use
in the development of new pharmaceuticals, according to new findings
from a team of researchers at Rensselaer Polytechnic Institute, the
University of California at Berkeley, and Solidus Biosciences Inc.
The team's most recent discovery will be featured in the online
Early Edition of the Proceedings of the National Academy of Sciences
(PNAS) on Dec. 17.

The researchers have developed two biochips, the DataChip and the
MetaChip, that combine to reveal the potential toxicity of chemicals
and drug candidates on various organs in the human body, and whether
those compounds will become toxic when metabolized in the body, all
in one experiment without the use of live animals.

Traditional toxicity testing involves the use of animals to predict
whether a chemical or drug candidate is toxic. However, with the
large number of compounds being generated in the pharmaceutical
industry, and new legislation stipulating that chemicals undergo
toxicity analysis, there is a rapidly emerging need for high-
throughput toxicity testing.

"We looked at the issues facing companies and realized that we
needed to develop something that was low-cost, high-throughput,
easily automatable, and did not involve animals," said co-lead
author Jonathan S. Dordick, the Howard P. Isermann '42 Professor of
Chemical and Biological Engineering at Rensselaer and co-founder of
Solidus Biosciences Inc., the company that is working to
commercialize the chips. "We developed the MetaChip and DataChip to
deal with the two most important issues that need to be assessed
when examining the toxicity of a compound -- the effect on different
cells in our body and how toxicity is altered when the compound is
metabolized in our bodies."

When the biochips are used together the result is a promising and
affordable alternative to animal-based toxicology screening and a
direct route to developing safe, effective drugs, according to
Dordick, who is also a member of the Rensselaer Center for
Biotechnology and Interdisciplinary Studies.

Currently, detailed toxicity screening does not come into the drug
discovery process until later in the development, when significant
time and money have been invested in a compound by a company. And
animal testing does not always provide information that translates
to predicting the toxicity of a compound or its metabolites in a
human, Dordick said.

The collaborative team sees the combined chips as an efficient, more
accurate way to test drug compounds for toxicity earlier in the
discovery process. But, co-lead author and Solidus Biosciences co-
founder Douglas S. Clark, professor of chemical engineering at the
University of California at Berkeley, views pharmaceutical companies
as only one potential user, and not necessarily the first.

"The initial market will not necessarily be pharmaceuticals," Clark
said. He further explains that the initial market will likely be
chemical and cosmetic companies that are being pushed to eliminate
animal testing or cannot afford such testing. In fact, by 2009
cosmetics companies in Europe will be restricted from using animals
in testing for chemical toxicity. "Obviously cosmetics need to be
safe, and ensuring the safety of new compounds without testing them
on animals presents a new challenge to the industry, especially as
the number of compounds increases. These chips can meet this
challenge by providing comprehensive toxicity data very quickly and
cheaply."

The team's most recent achievement outlined in PNAS is the DataChip,
a biochip comprising up to 1,080 three-dimensional human cell
cultures. The three-dimensional structure is more closely in line
with how the cells would be arranged in organs of the human body.
The DataChip can provide companies or academic labs with an
extremely fast screen of potential toxicity of chemicals and drug
candidates on different types of human cells.

In an earlier paper published in a Jan. 25, 2005, edition of PNAS,
the team introduced the MetaChip. The biochip mimics the metabolic
reactions of the human liver, where chemicals and drugs are
processed in the body. Depending on the compound, a seemingly benign
chemical like acetaminophen can become highly toxic when metabolized
by the liver. Because of differences in the type and amount of their
drug-metabolizing enzymes, most of which are in the liver,
individuals can metabolize a drug or other chemical compound
differently. What is harmless to one person may be toxic to another.
By arranging the ratio of enzymes on the MetaChip, scientists could
develop a personalized chip to determine how toxic a drug might be
to different people.

"We are still a ways off from personalized medicine, but the
MetaChip offers that future possibility," Dordick said. When coupled
with the new DataChip, the two chips could someday be used to
determine the levels and combinations of drugs that are safe and
effective for each individual patient, Clark explains.