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PITTSBURGH (AP) — Lawrence Vernetti tested drugs on animals in a Chicago lab for four years before a friendly female beagle, scheduled to die in the tests, reset the course of his career. "I connected with it," Vernetti said of the unnamed dog. " . Here I was, the person that was literally scheduling to the day and to the hour when she would go into necropsy." He started researching alternatives to animal testing. Two decades later, Vernetti, the director of early drug safety at the University of Pittsburgh's Drug Discovery Institute, says "organ-on-a-chip" technologies could soon reduce animal deaths and predict more accurately how drugs will affect humans. The U.S. Food and Drug Administration has required animal testing since the 1960s to help prove drugs are safe and effective before they are tested in humans, but most drugs that prove safe and effective in animals fail in humans. An FDA analysis showed 92 percent of drugs that make it through animal testing fail in the first phase of human testing. "Animal models are becoming an outdated and kind of archaic model for predicting toxicity," said Jeremy Beckham, a research specialist at the California-based nonprofit Beagle Freedom Project. The group advocates for reducing and eventually eliminating animal testing, and is paying for some of Vernetti's research. About 768,000 animals were used in testing and research in the United States in fiscal year 2015, according to the most recent Department of Agriculture figures, with about 25,000 in Pennsylvania. About 61,000 were dogs, and, due to a quirk of history, most were probably beagles, Beckham said. The breed's small size and docile nature made beagles good candidates for Cold War-area researchers to test the toxicity of radioactive elements, he said, and an industry grew around raising the dogs and selling them to researchers. "Now it's just sort of become the breed that's on hand," he said. Researchers in 2015 also used about 20,000 cats, 62,000 nonhuman primates, and thousands of pigs, guinea pigs, hamsters, rabbits and sheep. The number doesn't include rats, mice or birds, the species Beckham said are used in 95 percent of animal research. The agency doesn't release numbers on how many of the animals are killed, but many are used for toxicity testing, which requires tissue analysis normally done after an animal is killed, Beckham said. Researchers often don't use the anesthetics a veterinarian would because the pain-relieving drugs would skew results, he added. Vernetti said that while animal testing is useful in developing treatments for some diseases, it is ill-suited to test complex human diseases such as cancer. Organ-on-a-chip models use human cells and incorporate some of the characteristics of a cell functioning in the human body, he said. His research focuses on the liver. He puts 225,000 liver cells — about a third of one-millionth the number in the human organ — into a device about half the size of a dime. Unlike petri-dish tests that use human cells, the device maintains a three-dimensional structure made from multiple cell types, he said. The device pumps a blood surrogate through the cells, mimicking fluid flow through living cells. Those two abilities, combined with advances in computing and in testing functions in living cells, are helping researchers replicate with the chips some common drug-human interactions. Once researchers can reliably replicate known drug-human interactions, they can start testing how new drugs will affect people, he said. He thinks that could start to happen in three to five years, reducing testing in animals. He estimates that if he can accurately replicate around 60 to 100 drug-human interactions he will be able to move into testing new drugs, although he acknowledged the threshold for proof varies widely among researchers. His lab so far has accurately replicated 20 to 25 interactions, he said. Other researchers around the country are using similar devices to test tissue from other organs, he said. The National Institutes of Health and the Defense Advanced Research Projects Agency are both funding research. DARPA seeks a platform that can test 10 or more physiological systems at once, according to the agency's website. "Human safety and drug performance is not always effectively predicted through animal testing," DARPA Biological Technologies Office Deputy Director Brad Ringeisen wrote on the site. "And the Department of Defense needs to rapidly develop and field safe and effective medical countermeasures against biological threats to warfighters." The Beagle Freedom Project funded Vernetti's research and three other projects. It is funding a Johns Hopkins University study to correlate data from dog testing with human data to improve understanding of how effective animal testing is, Beckham said. Another project at Miami University in Ohio aims to develop an artificial nose to test inhalation toxicity testing. The fourth project, based in the United Kingdom, aims to reduce use of dogs in the production of immune cells known as monoclonal antibodies. The group also promotes research organizations giving dogs up for adoption at the end of the research when possible, including pushing for state laws that require adoptions. Laws require adoptions in Minnesota, California, New York, Connecticut and Nevada, he said. No measures have been introduced in Pennsylvania, he said. "We know we're not going to end animal testing tomorrow, but until we get to that point, we at least owe a minimum of humane treatment for these animals, and that includes more normal life after the laboratory," he said. ___ Online: http://bit.ly/2n81D2Z ___ Information from: Tribune-Review, http://triblive.com

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