In a lab at the UC San Diego School of Medicine a computer screen shows a video of a human lung with a form of fibrosis. Some parts of it have been dyed green and blue, with the deceased section in red. But this isn’t really a lung. It’s a very small model, made from human stem cells, and it’s called an organoid.
“We now have a way to screen the drugs on this, to reverse this exact condition,” Professor Pradipta Ghosh said as she pointed at the screen. “Because it has been determined that without these cells you cannot fibrose a lung. You cannot scar a lung.”
Ghosh is a professor of cellular medicine at UCSD and the founding director of the Humanoid Center for Research Excellence. The center is dedicated to improving and quickening the pace of drug discovery by testing with human tissue. Ghosh says the problem with animal trials and the current system is pretty clear.
“We have a report card that we can’t really ignore. Can we? The report card says we get it 9 out of 10 times wrong. That is a drug at least,” she said. “Most often it’s wrong because it is not efficacious enough once it hits the real world of patients. The second reason is because it wasn’t safe.”
Yes. About 90% of drugs under development fail in human clinical trials, the final stage of the approval process. Look closer and the news gets worse. Testing a drug from beginning to end usually takes a decade and can cost more than $1 billion, whether it’s eventually approved or not.
Now it seems like the federal government has taken notice.
Federal agencies that fund and regulate drug discoveries last month announced a broad plan to move away from testing animals for drug safety and efficacy. This was no surprise to San Diego scientists. In fact, they’ve already taken steps to use alternative ways to examine diseases and possible cures.
Ghosh said the shortcomings of animal testing is one problem with the current system. People, you see, are not mice.
“We have evolved differently. We know our immune systems are vastly different. A simple thing is; they are nocturnal, we are diurnal. And we now know that just that simple thing of when we sleep and when we wake up has an immense impact on the immune system, and immune systems impacts almost any disease we can think of that’s chronic,” Ghosh said.
The news of changing policies on drug trials was announced by the Food and Drug Administration (FDA) and the National Institutes of Health (NIH) last month.
The FDA said in its press release that their animal testing requirements will be “reduced, refined and potentially replaced” by computational models of toxicity and organoid toxicity testing.
The NIH announced it will create a new office to develop the use of non-animal approaches.
“This human based approach will accelerate innovation, improve health care outcomes and mark a critical step forward for science,” said NIH Director Jay Bhattacharya.
Lab testing of animals is not going away, and there are those who defend it. The National Association of Biomedical Research said in a statement that computational models and organoids are “not yet capable of fully replicating all the intricacies of living systems.”
Pradipta Ghosh said she favors a tiered approach to drug development that includes organoid testing and digital analysis. She said we should leave animal testing as a last resort.
With the right system, she said, 90% drug failure rate could be reduced to 10% or 20%. But adopting new, human-based forms of testing present some challenges.
“Barriers to entry. Cost is high. Skills. Knowledge. Limited to a few labs — still — in the world. So you need organized research units that can perhaps make multiple user access and drive these model systems into their fields,” Ghosh said.
And the push for more human-based drug and disease testing is happening at a time when the Trump administration is proposing dramatic cuts, perhaps more than 40%, to the budget of the National Institutes of Health. To Ghosh, that’s a problem.
“How do you invest in something that requires more skills, requires more resources, requires more infrastructure? Oh, and by the way, in the backdrop of less funding,” she said. “That could be a little difficult task.”
