Pharmaceutical companies face dense regulatory bureaucracy and
dozens of competitors seeking to fast-track their drugs to the market. Such
competition and red tape leaves little room for new methods and necessarily slows
the pace of drug development. Researchers have proposed a new device which they
hope will replace animal testing and reduce risks in phase I clinical trials. This
device is a 1/1000 scale human – small enough to fit on a desk. It will have a
beating layer of heart cells, breathing lung cells, and a blood-brain barrier
interconnected with other organs just as if they were in vivo – including the spleen, pancreas, and gut to name a few . This microfluidic human would be a
fully automated drug discovery platform – streamlining the drug testing
process, reducing risks in clinical trials, and cutting costs for
pharmaceutical research.
What we do now:
Drugs undergo extensive animal testing in the laboratory before
approval for human trials at sub-clinical doses. The details of stage I human
trials are heavily debated in bioethics, and animal testing is equally
controversial. This guess-and-check method of drug development has been the
model for decades, but presents dangerous problems while clogging the pipeline
for promising drug developments. Researchers like Don Ingber and John Wikswo argue
it is time for a change.
Why it fails:
Animal and human organ systems are simple not equivalent.
Predicting how organs in a human will interact and communicate based on a mouse
model leaves dangerous assumptions when entering phase I trials. In some cases, the health of the trial
subjects can be seriously endangered. In 2006, the trial antibody TGN1412 for
the treatment of autoimmune disorders went from animal testing to phase I
clinical trials on six volunteers in sub-clinical doses. Despite doses 500
times smaller than those found safe in animal trials, all volunteers faced life-threatening
conditions due to systemic organ failures. Failed trials like these increase
the regulations, time, and costs involved in approving drugs, inhibiting
promising developments.
Ingber, Wikswo, and others are involved in an effort to
build a micro-human composed of multiple organs-on-a-chip to reduce costs and
risks in drug trials. The micro-human is platform of interconnected microfluidic
chips, pumps, valves, and sensors which mimics the essential functions of the
body’s organ systems. From a beating layer of heart cells to active diffusion
across a simulated blood-brain barrier, the micro-human or homunculus is the
state of the art in biomedical engineering. Ingber began the work by building
an artificial lung-on-a chip at Harvard. Using vacuum and fluid channels and a thin
membrane of lung cells within a flexible polymer mold, Ingber’s chip replicates
the human lung alveolus, including blood flow and rhythmic pumping. An entire
human organ system can fit on a desk and contains all the inter-organ links needed
for a simple human analog. The active biological mass of the system is only
70mg, one millionth the mass of a human. Drugs tested on such a platform could
be carefully assessed on human cells without the ethical complications of phase
1 trials. For example, side effects of a heart treatment on the blood-brain
barrier could be noted, or dangerous chemical combinations identified. The
National Institutes of Health (NIH) and Defense Advanced Research Projects
Agency (DARPA) have issued over $137 million dollars to fund organ-on-a–chip research
since 2012. The micro-human may soon have macroscopic consequences at your
local Walgreens.
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