|
|
A game-changer in toxicity testing
January 2013
SHARING OPTIONS:
RESEARCH TRIANGLE PARK, N.C.—The Hamner Institutes for
Health Sciences has established an Integrated Biology Initiative among multiple
organizations to facilitate bringing a 21st-century systems biology approach
and
modern computational biology to toxicity testing, with the goal of
revolutionizing the toxicity-testing paradigm that has been in place for the
past 80
years.
If successfully developed, human cell-based assays that
model and help to evaluate dose
responses should allow toxicity testing and
risk assessment of compounds to take place wholly via in-vitro tests, without the need for additional
testing using
intact animals, according to Hamner researchers.
The multi-organization,
precompetitive partnership consists
of several sponsoring providers, including Agilent Technologies Inc., Illumina,
Dow
Chemical, ExxonMobil, Unilever and others. The research will be conducted
by Hamner and Brown University.
The new approach to toxicity testing stems
from key
recommendations from a 2007 National Research
Council (NRC) report titled,
"Toxicity Testing in the 21st Century: Toxicity Pathways and Network Biology."
The report set forth a vision for the
modernization of toxicity testing using
systems biology approaches and computational biology to provide better, more
efficient tools for measuring
chemicals' toxicity risks.
For decades, the standard approach to testing a compound's
toxicity
has been to expose live animals—typically rats or mice—to high doses
of the compound, and then to wait and see what happens. If the compound proves
toxic to the animals at high doses, scientists must "work backward" to
ultimately calculate what level of dosage would be sufficient to create a
relevant toxic effect in humans. This approach calls for the extensive use of
animals, and the results from animal-based testing don't always
translate
particularly well to humans. Fundamentally, the NRC report's authors argue,
this approach fails to take advantage of the extraordinary
advances in the
understanding of human biology made during the past decade.
"There has
been extensive debate about the vision and how
best to implement it," says Dr. Melvin Andersen, associate director of the
Institute for Chemical
Safety Sciences at Hamner. "We determined the best way
to progress would be to develop case studies based on specific pathways and the
compounds that
affect them."
Participants in the Integrated Biology Initiative intend to
improve upon toxicity
testing methods by developing novel in-vitro assays in which human cells are exposed to low doses
of the chemicals in question. These standalone
in-vitro tools should be adequate for risk assessment without
the use of animals, and should be able to rapidly and inexpensively identify
which chemicals pose the greatest hazard to human health.
"We need to understand the dose response in
lower doses than
traditional toxicity testing considers," says Andersen. "There are other
parallel initiatives of this kind being conducted at the Environmental
Protection Agency, for example, but the lower-dose
screening is unique to our
programs."
The use of in-vitro-based
toxicity testing
holds significant ethical and financial advantages over the
traditional techniques that rely heavily on animal testing. The new approach
would reduce
the use of animals in testing overall, provide data that more
closely translates to human cell health and speed testing of new compounds and
those
already in commercial use.
The main beneficiaries of an improved toxicity testing
approach fall into
two main categories.
The first consists of what Andersen calls the "regulated
communities,"
which include the pharmaceutical and chemical sectors that must
ensure the safety of their products before taking them to market. One of the
major
failure modes of new compounds in the pharmaceutical industry is in
toxicology testing. The typical two-year mouse bioassay doesn't yield final
results on the toxicity of a novel compound until well after the pharmaceutical
company testing it has invested a great deal of time and money into its
product. Speeding the toxicity testing process will help pharmaceutical
companies to save money by allowing them to avoid wasting resources
developing
a product for two years that ultimately proves toxic and unmarketable.
The second
beneficiary of improved toxicology methods is the
consumer public at large, because in-vitro
schemes would allow for quick testing of existing
chemicals that have not been
well tested to date. Mary McBride, director of government relations, life
sciences and chemical analysis at Agilent—a
major technology partner in the
initiative—says there is currently a backlog of between 80,000 to 120,000
chemicals with no toxicology data on them at
all. Addressing this backlog with
the cumbersome methods of yesteryear may be an exercise in futility, but rapid
toxicology testing using in-
vitro
assays will allow researchers to screen and prioritize compounds that seem the
most problematic.
"We're in the early stages of demonstrating the feasibility
of an in-vitro approach to toxicity
testing, and we believe it is
important to be involved in work that promises to
make a big difference to many sectors and many people," says McBride.
Discussions are ongoing with as many as a half dozen other
technology providers, with an eye toward attracting still more companies
and
technology partners into the initiative. Several large companies, including GE
Healthcare and Kraft Industries, have expressed interest in joining the
partnership by providing funding or technology.
"We're getting close to having the funding base and critical
mass of technology partners to be able to begin to apply these appropriate,
contemporary tools," says Andersen.
"It's important to remember
that this is not a closed
consortium—we embrace others joining in this effort, especially if they are
able to bring genuine interest, relevant
technology or additional funding to
the table," says McBride.
Agilent, WiCell to offer microarray service
SANTA CLARA, Calif.—Agilent Technologies Inc. and WiCell, a
provider of cytogenetic testing of mouse and human embryonic stem cells and
induced pluripotent stem cells, announced
last month that WiCell will offer
comparative genomic hybridization plus single nucleotide polymorphism
microarray analysis using the Agilent SurePrint
G3 Human Genome CGH+SNP
Microarray.
Unlike previous assays that required performing CGH and SNP
separately, the CGH+SNP Microarray detects copy number changes by both SNP and
CGH, and simultaneously delivers copy-neutral change information such
as loss
or absence of heterozygosity. The assay maintains the high-resolution quality
achieved with CGH-only microarrays, using probes that have been
carefully
optimized and validated for maximal sensitivity and specificity.
"WiCell's
considerable experience and know-how in
cytogenetic analysis and their large CGH dataset for embryonic and induced
pluripotent stem cells, partners
well with Agilent's technology to enable
robust detection capabilities vital for research and commercial development,"
said Kathleen Shelton, senior
director of genomics marketing at Agilent.
Code: E0111316
Back
|
