New ‘chip’ could streamline toxicity tests, save 90% of lab animals, researcher says
U of S professor part of team developing technology that’s attracting global interest
The rectangular, white plastic plate Markus Hecker holds in his hand serves as the matrix for a new way of screening chemicals for toxicity, one that could spare the majority of live animals now used for this purpose in labs.
“Especially in Europe, but now more and more in North America as well, animal testing is becoming a huge issue,” Hecker noted.
By early this summer Hecker and his research partners expect to begin testing the Ecotoxchips they have been developing.
“What we’re trying for the first time is packaging complex information to be (put) into a very simple format at the end that gives you a very clear yes or no answer,” Hecker said.
If the chips are proven to work, they could be an invaluable tool in the testing of thousands of chemicals already in use — chemicals that, in many cases, were launched on the market decades ago, before the advent of stricter safety rules.
“Ever since then we have been running after making sure that whatever we have produced, we have used for a long time, is actually safe to use,” Hecker said. “Plus there (are) 5,000 to 10,000 new chemicals on the market every year. So you have to assess all of those for their safety as well.”
It’s a massive task. Around the world, about 140,000 chemicals are in use, and the safety of more than 90 per cent of them still needs to be tested, he added.
The traditional lab method of exposing live animals to chemicals and checking for toxic effects will take decades, cost billions of dollars, and take millions of animals, he said.
“Can we come up with a faster, more efficient way to screen all those chemicals to avoid 30 years of testing to finally come up with an answer?”
That’s the mission of Hecker and his research colleagues.
Ecotoxchips could in most instances replace the live animals currently used in testing the toxicity of chemicals — reducing their use by 90 per cent, according to Genome Prairie, one of the project’s funders.
The chips could also deliver lab results seven times faster than live animal testing, and — according to Genome Quebec, one of the other project funders — save the Canadian government’s chemicals management plan $27.3 million per year. The plan is a multi-year initiative to assess the risk of 4,300 chemicals.
Hecker said the test could help pre-sort the list of chemicals requiring closer scrutiny, reducing the ones that still require live animal tests to a short list of a few hundred.
Originally from Germany, Hecker teaches aquatic toxicology at the University of Saskatchewan, and is also a Canada Research Chair in Predictive Aquatic Ecotoxicology.
He is one of a trio of principal investigators (along with Niladri Basu of Mcgill University in Montreal and Doug Crump at Environment and Climate Change Canada in Ottawa) leading a team to develop and commercialize the Ecotoxchip.
Assistant professors Natacha Hogan at the U of S and Jessica Head at Mcgill are the other two key players, lead investigators in the project.
Traditionally in screening for toxicity, scientists try to understand how the chemical under study interacts with an organism — perhaps disrupting its digestion, its nervous system or its reproductive system.
For example, Hecker mentioned ethinylestradiol, an estrogen used in birth control pills (and sometimes hormone therapy). Excreted in urine and carried in municipal waste water into natural waterways, it can transform a male fish into female, he says.
“It’s a pretty significant issue for a fish if (it) cannot reproduce anymore.”
Typically in testing chemicals, scientists would expose a live fish, for example, to a chemical and observe the toxic effect in action. Hecker and his research partners aim to use the Ecotoxchip to indicate how a chemical alters the expression (or activation) of the fish’s genes. Think of flipping a switch on or off — and the results lit up in colour.
This is where the chip’s frame comes in. About the size of a cigarette pack or large smartphone, it contains 384 tiny wells. Into each well, researchers can place material (rna) from a different gene, and mark it with a fluorescent tag. The genes that are “up-regulated or down-regulated” change colour when seen with a special machine. Scientists won’t have to wait to see the actual toxic effect in a live animal.
The genes are extracted from an egg or an embryo, instead of a live animal, which requires a much shorter exposure time — four to seven days rather than several weeks to months for a live animal, depending on the species. Perhaps a decade from now, Hecker said, scientists may just take a cell from an organism.
The trick is to identify the relevant genes to test, a task which has taken most of the two and a half years of work so far in developing the Ecotoxchips with the international company Qiagen.
By early June, Hecker expects to have the first plate ready for testing — genes from a Japanese quail. By fall, the team expects to be testing a fish species and by winter, a frog species — all of them species commonly used in testing for toxic impact on the environment.
The team will first compare results with live animal tests. If the results match, the plates will be tested in the labs of other project partner agencies — Environment and Climate Change Canada, the U.S. army and the EPA — to see if the results can be replicated. If so, commercialization could be the next stage.
The project is also attracting interest in the European Union, where chemical compounds are also coming under closer scrutiny through a regulation called REACH.
Hecker has preliminary meetings set with the European Chemicals Agency and the European Food Safety Authority for sometime this summer or fall.
He said the Ecotoxchip project originated with a call for proposals from a federally funded non-profit agency, Genome Canada, which serves as a catalyst for developing genomics-based technologies. The $9.6 million project cost is split roughly three ways between the national agency, its regional counterparts Genome Quebec and Genome Prairie (the latter through Innovation Saskatchewan), and private sector partners including Qiagen, Shell and the lab company SGS AXYS.
Can we come up with a faster, more efficient way to screen all those chemicals to avoid 30 years of testing to finally come up with an answer?