“Homo Minutus” May Reduce the Need for Animal Testing

 Benchtop Humans  

Scientists are reporting significant progress toward creating "homo minutus" -- a benchtop human. Researchers have successfully developed and analyzed a liver human organ construct that responds to exposure to a toxic chemical much like a real liver.

Creating surrogate human organs, coupled with insights from highly sensitive mass spectrometry technologies, a new project is on the brink of revolutionizing the way we screen new drugs and toxic agents.

ATHENA, the Advanced Tissue-engineered Human Ectypal Network Analyzer project team, is developing four human organ constructs – liver, heart, lung and kidney – that are based on a significantly miniaturized platform. Each organ component will be about the size of a smartphone screen, and the whole ATHENA “body” of interconnected organs would fit neatly on a desk.

“By developing this ‘homo minutus,’ we are stepping beyond the need for animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs,” said Rashi Iyer, a senior scientist at Los Alamos National Laboratory, the lead laboratory on the five-year, $19 million multi-institutional effort. The project is supported by the Defense Threat Reduction Agency (DTRA).

"By developing this ‘homo minutus,’ we are stepping beyond the need for animal or Petri dish testing: There are huge benefits in developing drug and toxicity analysis systems that can mimic the response of actual human organs."

“By creating a holistic dynamic system that more realistically mimics the human physiological environment than static human cells in a dish, we can understand chemical effects on human organs as never before,” she said. “The ultimate goal is to build a lung that breathes, a heart that pumps, a liver that metabolizes and a kidney that excretes -– all connected by a tubing infrastructure much akin to the way blood vessels connect our organs. While some skeptics might believe that this is a utopian dream,” she said, “the team is confident that this is indeed achievable.”

Some 40 percent of pharmaceuticals fail their clinical trials, Iyer noted, and there are thousands of chemicals whose effects on humans are simply unknown. Providing a realistic, cost-effective and rapid screening system such as ATHENA with high-throughput capabilities could provide major benefits to the medical field, screening more accurately and offering a greater chance of clinical trial success.

The achievement is the first result from a five-year, $19 million multi­ institutional effort led by Iyer, and John Wikswo, the Gordon A. Cain University Professor and Director of the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) at Vanderbilt University.

The project is developing four interconnected human organ constructs -- liver, heart, lung and kidney -- that are based on a highly miniaturized platform nicknamed ATHENA (Advanced Tissue-engineered Human Ectypal Network Analyzer). The project is supported by the Defense Threat Reduction Agency. Similar programs to create smaller, so-called organs-on-chips are underway at the Defense Advanced Research Projects Agency and the National Institutes of Health.

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"The original impetus for this research comes from the problems we are having in developing new drugs," said Wikswo. "A number of promising new drugs that looked good in conventional cell culture and animal trials have failed when they were tested in humans, many due to toxic effects. That represents more than $1 billion in effort down the drain. Our current process of testing first in cell lines on plastic and then in mice, rats and other animals simply isn't working.''

In recent years, a cadre of scientists and clinicians around the world has begun to develop more relevant and advanced laboratory tests for drug efficacy and toxicity: small bioreactors that can form human organ structures and are equipped with sensors to monitor organ health.

Ultimately, the goal is to connect the individual organ modules chemically in a fashion that mimics the way the organs are connected in the body, via a blood surrogate. The ATHENA researchers hope that this ''homo minutus," with its ability to simulate the spatial and functional complexity of human organs, will prove to be a more accurate way of screening new drugs for potency and potential side-effects than current methods.

Devices of this type could also be extremely useful in the field of toxicology. Of the tens of thousands of chemical compounds being used routinely in commerce today, only a small fraction has been tested for toxicity. And even those have been examined only for acute toxicity, not for sub-lethal or chronic effects, because of the expense and time required by such tests. Human organ construct/organ-on-a-chip technology could make this process substantially cheaper and faster.

According to Iyer, this rich level of detail confirms that the ATHENA organ platform coupled with mass spectrometry technology can provide a more sensitive and effective method for screening both new drugs and toxic agents than is available today.

The team plans on hooking up their liver device to the Harvard heart this winter. They expect to add the lung construct being developed at Los Alamos next year and the UCSF/Vanderbilt kidney the year after.


SOURCE  Los Alamos National Laboratory

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