From cubes with menstrual cycles to a lung on a chip, this weird technique is picking up speed.
Courtesy of Northwestern Medicine
Of all the off-putting vaginal euphemisms, "box" might be the worst… unless, that is, you're talking about the Evatar—a palm-sized cube from Northwestern University researchers that has a menstrual cycle.
The first-of-its kind reproductive system—a portmanteau of "Eve" and "avatar"—made its debut last month. In the Evatar, cells from the uterus, ovaries, cervix, vagina, fallopian tubes, and liver are connected by a series of tiny passageways, which pumps fluid to the various organs. Every 28 days, the menstruating model releases an egg.
Evatar's inventors say the cube full of tubes addresses a pretty pressing need: Women have been historically and systematically underrepresented in drug trials.
"Until last year, scientists typically didn't use female mice in their research, because they thought the fluctuating levels of hormones would confound the results," explains biologist Kelly McKinnon, who helped develop the period-having chip. "Even at the clinical trial level—women are now required to be included—that didn't happen until 2001. Before that, women were banned in participating in clinical trials, and even now, drug and toxicology studies don't use women of reproductive age … to avoid those complications."
According to McKinnon, that means we still don't know how most drugs that come to market will impact fertility or other hormone-related processes in a woman's body. (Yes, in 2017.) The Evatar could help balance the gendered nature of drug testing by allowing researchers to take hormonal fluctuations into account. And that's just one of a number of benefits from this menstruating model; it'll also help scientists treat diseases like uterine and cervical cancer, for example, or endometriosis, for which there aren't good animal models simply because animals don't suffer from the same illnesses we do as humans.
Evatar also removes the problem of the petri dish, because as it turns out, two-dimensional dishes aren't a great physiological representation of a three-dimensional human.
"Most research that's done when you're developing a new drug ... it doesn't really capture what's happening in the human body, because those cells are static cultures," says Hunter Rogers, one of Evatar's bioengineers. The drug-testing process has remained largely the same for decades. It begins with cell cultures of a single cell type in a flat, plastic dish, which is already imperfect as there's no flow or removal of metabolic waste, something the human body does on a constant basis. From there, trials move to animals, and if those prove successful, you might get clinical trials with human candidates.
But even if a new drug makes it that far, that's often also where they meet their end.
"More often than not," Rogers says, "when you take a drug that was successful in treating a mouse and try to treat a human, it doesn't exactly work."
Because organs-on-chips can so closely mimic actual human physiology—they're more body-like than plastic petri dishes and more human than lab rats—these microfluidic models have taken off in recent years. Evatar isn't the first; scientists at Harvard University's Wyss Institute debuted a lung-on-a-chip in 2012 and have since developed micro-versions of the gut, liver, heart, and bone marrow. (The Design Museum of London gave the institute's organs its Design of the Year Award in 2015, and the chip lungs were later acquired by the MoMA, where they're part of the permanent collection.) UC Berkeley bioengineers have a heart-on-a-chip, too. Scientific American called organs-on-chips one of the Top 10 Emerging Technologies of 2016.
Donald Ingber, founding director of the Wyss Institute, explains that while the institute's clear, flexible, thumb-drive-sized organs-on-chips are different from the Evatar—"which is amazing, by the way," he interjects—they're trying to address many of the same concerns. Chief among them is the fact that most animal disease models are actually terrible, a problem that isn't limited to women's health. There's also the fact that companies spend billions of dollars and years of research on drugs that fail more often than not. Following each failure, Ingber says researchers sift through patient results to see if there's a subpopulation or genetic subgroup that responded a bit better than the rest, at which point they'll do smaller and smaller trials.
It's not the most efficient way to go about testing, which is where the chip-organ approach comes in, allowing researchers to take a genetically or clinically similar group—say, hispanic women who have asthma—and test and develop drugs specifically for them from the outset. "You can shortcut the whole process: Decrease the cost, shorten the time, and increase the likelihood of success," Ingber says.
This would mean better and potentially even less-expensive drugs would make their way to market, and it could also mean drugs that are safer overall. In the Healy Lab at UC Berkeley, Nathaniel Huebsch is one of the scientists working with the heart-on-a-chip, technology that he and his fellow researchers are using to learn if new medicines meant to target other areas of the body will have an unintended negative impact on the heart.
A drug like Cisapride, for example, which treats heartburn, is safe for most people. The liver metabolizes the medication, and heartburn improves. Unless, of course, you're one of a subset of people who have a liver defect or are taking another supplement that inhibits its effectiveness or have an arrhythmia—in that case, you might experience cardiac impairment or even cardiac death. By chaining together a heart-on-a-chip and liver-on-a-chip, Huebsch and the researchers at the Healy Lab are able to determine how inhibiting liver and heart function can make the drug toxic.
"Many drugs are going to be safe in 95 percent or more of patients," Huebsch says. "The problem that's causing drugs to fail in phase III—that's causing drugs that are on the market to have very bad effects in a very small number of people—is these rare adverse events."
And that's one of the truly incredible things about organs-on-chips: Scientists can use them to develop tailor-made, personalized treatment plans on a by-patient basis.
"We could take your blood cells or skin cells, treat them with a cocktail of genes or chemicals, and I could transform them into embryonic-like cells," explains Ingber. "Then, giving them the right signals, We can make them virtually any tissue type in your body—We can make your lung on a chip or your kidney on a chip or your liver on a chip. I can test drugs for you."
Update: A previous version of this story says scientists at Harvard University's Wyss Institute debuted the lung-on-a-chip in 2012. It debuted in 2010.
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