(Illustration)
(Illustration)Yossi Zamir/Flash 90

A partnership between scientists at Hebrew University of Jerusalem and a German research institute may have found the solution to make animal experiments a thing of the past.

Animal testing has been condemned for being cruel and morally dubious, but in recent years it also has been understood that such tests fail to predict human responses to drugs, and as regulations tighten massive investment has been turned to the field of alternative testing.

Hebrew University announced on Monday that its cooperation with the Fraunhofer Institute for Cell Therapy and Immunology (IZI-BB) in Germany has borne breakthrough results, and together the two have submitted a joint provisional patent application and are looking for industrial partners to implement their findings.

The Israeli and German researchers have developed a "liver-on-chip" device mimicking human physiology, so as to avoid animal experiments and get around the limitations of testing on human cells that survive just a few days outside the body.

"The liver organs we created were less than a millimeter in diameter and survive for more than a month," said Prof. Yaakov Nahmias, the study’s lead author and Director of the Alexander Grass Center for Bioengineering at the Hebrew University.

Other groups may have conducted similar research, but the unique breakthrough in the research was the addition of nanotechnology-based sensors.

"We realized that because we are building the organs ourselves, we are not limited to biology, and could introduce electronic and optical sensors to the tissue itself. Essentially we are building bionic organs on a chip,” said Nahmias.

Already the technology has borne fruits, with the researchers being able to identify a new mechanism of toxicity in acetaminophen (Tylenol) thanks to the addition of nanotechnology-based optoelectronic sensors.

“Because we placed sensors inside the tissue, we could detect small and fast changes in cellular respiration that nobody else could,” said Nahmias. “Suddenly nothing we saw made sense."

The researchers found that acetaminophen blocked respiration, much faster and at a much lower dose than previously believed. It had been thought that acetaminophen was broken down to a toxic compound, called NAPQI, before damaging the cells, and that the liver could naturally deactivate NAPQI meaning damage only occurred at high doses and in cases of liver malfunction.

However, the new research, which was published online in the leading Archives of Toxicology, disproves previous notions.

It found that acetaminophen can stop cellular respiration in minutes, even in the absence of NAPQI, explaining much of the off target effects of the drugs.

“This is a fascinating study," said Prof. Oren Shibolet, Head of the Liver Unit at the Tel-Aviv Sourasky Medical Center. Shibolet is one of the leading experts on drug-induced liver injury; he was not involved in the original study.

"We knew that acetaminophen can cause nephrotoxicity as well as rare but serious skin reactions, but up until now, we didn’t really understand the mechanism of such an effect. This new technology provides exceptional insight into drug toxicity, and could in fact transform current practice.”