Precision medicine will be available to everyone because of Tissue Chips. Hear the fascinating story of the most important technology you have never heard of before. In this episode of the Amazing Things Podcast, brought to you by United For Medical Research, we take you inside the Tissue Chip program - an NCATS collaboration with the Defense Advanced Research Projects Agency and FDA to support the development of bioengineered devices to improve the process of predicting whether drugs will be safe or toxic in humans.
Precision medicine will be available to everyone because of Tissue Chips. Hear the fascinating story of the most important technology you have never heard of before. In this episode of the Amazing Things Podcast, brought to you by United For Medical Research, we take you inside the Tissue Chip program - an NCATS collaboration with the Defense Advanced Research Projects Agency and FDA to support the development of bioengineered devices to improve the process of predicting whether drugs will be safe or toxic in humans.
Adam Belmar:
This is Amazing Things. I'm Adam Belmar. In the age of coronavirus and COVID-19, Americans are suddenly more aware than ever before that translating what could be promising in the research laboratory into what will actually be therapeutically helpful for patients takes time and hard work.
President Trump:
Another essential pillar of our strategy to keep America open is the development of effective treatments in vaccines as quickly as possible.
Adam Belmar:
The struggle is real and these days happening in real-time. Join us for a look inside the NIH research program that Dr. Francis Collins hopes ...
Dr. Francis Collins:
Might be the best way to figure out whether a drug intervention is going to work for you or whether you're going to be one of those people that has a bad consequence.
Adam Belmar:
Inside the amazing story of tissue chips after this.
Speaker 4:
The Amazing Things Podcast is presented by United for Medical Research, because America's investment in medical research through the National Institutes of Health is making amazing things possible. Learn more at unitedformedicalresearch.com.
Adam Belmar:
On the top floor of a nondescript office building in Bethesda, Maryland is the home of NCATS, the National Center for Advancing Translational Sciences. It is one of 27 institutes and centers at the NIH. NCATS is off campus and nestled in a tree-lined office park. We're here to talk with Lucie Low, PhD. Dr. Low is the scientific program manager of the trans-NIH Tissue Chip program.
Dr. Lucie Low:
That's correct. There's actually now two of us, scientific program managers, because the program's grown so huge that we split it into two pieces. So I am now one of two.
Adam Belmar:
For her part, Dr. Lucie Low wears many hats at NCATS. You might even say that she is the connective tissue in the Tissue Chip program. She is the liaison between all the funded investigators. The FDA, DARPA, NASA, and the pharmaceutical industry. She also manages more than 20 research teams involved in the Tissue Chip program.
Dr. Lucie Low:
One of the reasons that NCATS is really special here at NIH is because we are designed to be nimble. We are mandated to try and do things differently. But we also are disease agnostic. We work across the entire translational spectrum. We exist solely to try and have an impact faster than the currently used ways of doing things. Our whole point of being here is to try and speed up the process of helping people.
Adam Belmar:
Speeding up the process is most certainly the order of the day now in 2020. Understanding of course, that it really does take a long time and a great deal of money for drugs and therapeutics and vaccines to be developed.
Dr. Lucie Low:
That's where tissue chips come in. Tissue chips are essentially bioengineered micro devices that contain human cells in a three dimensional cellular construct, and they're designed to mimic your human tissues in a home away from home. They're designed to mimic the structure and function and responses of your tissues in this bioengineered device, in a way that you just can't do right now with two dimensional cell models, or even with animals, and in a way that really mimics the human condition much more closely. They can be designed to mimic the biomechanical forces that your cells are subject to. Every time you take a breath, your lung tissues, they inflate, and then they deflate. You inhale, then you exhale. So you can create tissue chips that actually recreate that biomechanical force.
Dr. Lucie Low:
If you look at your blood vessels, if you look at your kidneys, if you look at your liver, they all have different biomechanical forces and different chemical gradients that they're subject to. Whether it's hormones, whether it's blood or cytokines or cell stress responses, whether it's drugs that you put in, they'll have different gradients across your tissues. You can mimic those on a tissue chip in a way that's just not possible anywhere else. So it really offers whole new opportunities to do lots of exciting things, ask different questions, and really see how human relevant models can fit into the existing pipeline. And it helps speed the process of the development of these therapeutics.
Adam Belmar:
Once again, in the age of coronavirus, news of anything that can help speed the development of therapeutics is not only welcome, but exciting. Thankfully, NIH and Congress, and multiple administrations, have been funding tissue chips since their infancy.
Dr. Lucie Low:
They're often called microphysiological systems, but they're easy to create in labs. They're created by the same process the silicon chips in computers are created, which is why they're called tissue chips. It's a process called soft lithography. It enabled a whole new way of experimenting with these different kinds of designs. Putting channels in different places, putting the cells in different architectures, and seeing what best we created how your lung, liver, kidney would actually respond within your body.
Dr. Lucie Low:
Around the same time, DARPA was very keen on getting involved as well, so they funded their own program. They funded two big projects to create 10 linked organ systems, so 10 organs in a linked body on a chip. Which was tremendously ambitious and extremely difficult. So instead of using them for toxicity testing, essentially, so safety and efficacy testing, we're really using them now. We're using a lot of iPS derived sources to create disease models on a chip. Because it's all very well to recreate a lung, but what's really helpful is if you can recreate a lung with emphysema, or COPD, or cystic fibrosis. And so the ability to then start modeling disease on a chip is pushing the whole field forward because it's opening up the areas that tissue chips can be used.
Adam Belmar:
One critical way the NIH is opening up the areas that tissue chips can be used is by making sure the technology is widely available.
Dr. Lucie Low:
We realized that the development of tissue chips is great, but if they only exist within one person's laboratory, they're essentially existing in a vacuum and they're not going to be helpful. Everything NCATS does is to develop, demonstrate, and disseminate. So we needed this technology to be translational and translatable. What that meant is that we established two independent testing centers called Tissue Chip Testing Centers, where we got the teams. We charged them with onboarding the technology from a number of different developers, and testing them in their labs. Basically, recreating what the developers have been able to do. Seeding them with the same kinds of cells, checking that they gave the same kinds of responses, checking that the drugs that they put into the systems gave the same kind of readouts. We also realized that we needed a central repository for all of that data to go. It should be publicly accessible because we are a publicly funded institution.
Dr. Lucie Low:
We wanted to make this technology accessible and available to everyone, so we created what we call the MPS Database System. That's based at the University of Pittsburgh. They onboard all of the data from the testing centers. Those centers are still going strong. They're on the verge of becoming financially independent. That was one thing that we wanted was to build a sustainable economy in this area for the testing of the chips and the validation. But we're still very much focused on keeping the data in the database open access. The idea is that everyone from the pharmaceutical industry could see what kind of chip gives what kinds of assays and outcomes, and how variable is that. Is it very robust? Does it depend if it's a Tuesday or there's been a thunderstorm the night before or someone's brought cat hair into the lab? How reliable, how valid is that result that it's giving? How useful is that result for the context of use in which it's being specified to be used?
Dr. Lucie Low:
So, there's a lot of information that our database is absorbing. They're doing some wonderful work in making the analysis to ask those kinds of questions very easy, so that people who are not necessarily skilled users or who don't necessarily understand tissue chips are able to go and look at what kind of assay and what kind of responses they might expect from a specific chip.
Adam Belmar:
Innovations on innovation. That is why platforms like tissue chips have myriad potential applications. So much so, that as I noted at the beginning of this episode, the NIH director himself speaks of the promise of precision medicine through tissue chips like this.
Dr. Francis Collins:
Basically, if you started with your own skin cell, made it an iPS cell, and then put it on a chip, you've got you-on-a-chip.
Adam Belmar:
You-on-a-chip.
Dr. Lucie Low:
A human body-on-a-chip or you-on-a-chip. If you think about that in the context of clinical trials. You're talking about first in-human trials or you're talking about later phases, then what's to say that we wouldn't be able to recruit patients as they're enrolled in clinical trials. Especially if it's rare disease patients and patients that currently are not well treated with the existing therapies, the ability to then create tissue chips that actually model their responses, before they are given a particular drug or treatment, means that we can start actually changing or altering or adapting the treatments or the dosages they might get that would make it more effective. Or if we knew, for example, that a particular chemotherapeutic cocktail would be much more toxic for one subsection of patients, then we would know not to do that particular chemotherapeutic cocktail, but we could try something else instead. We could try it on a tissue chip first.
Adam Belmar:
That is most definitely the goal. To get to a point where you can try it on a tissue chip first. But science is, as ever, a process of iterative failure. You learn, you try the next thing, and you adapt. And so, it is quite fortuitous that one of the earliest projects funded in the tissue chip realm belong to the all star team of Don Ingber and Kit Parker at the Wyss Institute for Biologically Inspired Engineering at Harvard University.
Dr. Lucie Low:
This heart-lung micro machine was designed to model aspects of the heart and the lung cardiovascular system. This lung-on-a-chip came out of it. Where you had lung cells on one side, and epithelial cells, which line the airways of your lung, on the other side. And then it had vacuum channels down the side. That when you apply this vacuum, it stretches and relaxes a membrane that the cells sit on. So it's really mimicking that inhalation and exhalation that your lungs go through every single breath you take. This was a tremendously exciting idea. As with all tremendously exciting ideas in science, it was one of those ones that would have come around at some point, but those guys did a really great job and they got there first.
Adam Belmar:
Since Ingber and Parker published that work in 2010, advances in bioengineering have really taken off. No, seriously, taken off. Like, outer space.
Dr. Lucie Low:
Tissue Chips in Space is, without a doubt, my favorite program. Partly because I'm a space nerd anyway, but also because it is a really exciting opportunity. NCATS's partnered with the International Space Station National Lab about three or four years ago, and we decided to send our tissue chips to space. Now, on the outside, that looks like a crazy thing to do. Taxpayers tend to look at that and go, "Why on earth are NIH sending their research to space? We don't do space research." But when you look at the changes that happen to astronauts bodies, they lose bone mass, they lose muscle density. Their cardiovascular system changes. Their eyesight changes. Their kidneys change because they're losing bone mass. There's a lot of changes that occur in astronauts. Scott Kelly's book Endurance, he talks about some of those changes and how they're kind of hard to deal with.
Dr. Lucie Low:
But some of those changes look very similar to various different types of aging or disease down here on earth. Loss of muscle mass is sarcopenia, which is seen in older adults, muscle wasting. Osteoporosis, well known disease down here on earth. Kidney stones. Everyone's heard of kidney stones. All of these effects that can occur as a result of microgravity are seen down here on earth too. We saw the opportunity to actually use microgravity as a way to model disease and aging, but on a really short timeline. Astronauts start seeing changes after days or weeks when they got up to microgravity. But a kidney stone could take decades down here to form. The loss of bone mass is seen after just two weeks in microgravity. You don't tend to monitor that on earth. But also osteoporosis, again, takes decades.
Dr. Lucie Low:
We see tissue chips as a way to really model exactly what's going on at a molecular and a cellular genetic level, on a really, really fast timeline. What's even more brilliant is that we can then bring them back down and see if those changes reverse. Once the cells are subject to uniform one g again. So, we partnered with the ISS National Lab and we were like, "Hey, let's use microgravity as a tool to really understand and try and get some new insights into different kinds of diseases. But we can also start testing therapeutics up there as well."
Adam Belmar:
Tissue Chips in Space. Who knew microgravity was the key to speeding up disease modeling? Well, to their credit, the folks at NIH and NCATS knew. And now, they have multiple projects already on the space station, and many more to go over the course of the next few years. The next part of this story is by far my favorite. You see, harnessing the promise of microgravity on the International Space Station means you have to shrink all your technology and the power supplies down to something that can fit in a shoe box. In science, as in the age of coronavirus, we realize how often we take some things for granted. Like, office space.
Dr. Lucie Low:
Well, you've just hit the nail on the head there, Adam. Because this was the most complicated thing I think our teams had to do. I think they lost a lot of sleep over those particular issues. Like you said, when you're down here on earth, it can sometimes feel like space is at a premium. But trust me, it's not. Got your tiny little tissue chip, but it might need something the size of your kitchen refrigerator to keep it going. With all the pumps, the tubing, the incubator, the refrigerator, the computer, everything else that's needed to keep it running. You can't send that up to the space station. SpaceX wouldn't let us. NASA wouldn't let us. So all of our teams had to shrink their systems. The novel technological adaptations that were needed for this were quite frankly astonishing. One of our teams actually published a paper on that.
Dr. Lucie Low:
They took something like 400 feet of tube and they had to shrink it down to like three foot tops of tubing. They had to fit 70 biological replicates into something that would have taken literally the size of your pantry in your house, down to something the size of a shoe box. No joke. Literally no bigger than a shoe box. And it had to be automated. It had to be solid enough that you can throw it around on a rocket a little bit and not fall apart, and not have leaks and not stop working.
Dr. Lucie Low:
All of our teams partnered with space implementation partners, private companies that are actually charged by NASA with helping facilitate the research that goes on on board station. The teams have just done outstanding work to create these systems that are just phenomenal. That can get real-time readouts of cell health in space, 250 miles above our head, going at 17 and a half thousand miles an hour, and downlink, almost in real-time, heart cells beating or brain cells fluorescing.
Adam Belmar:
From space. I hope that at this point you'll agree that tissue chips are indeed one of those amazing things that federal support for biomedical research through the NIH is making possible. And to be sure, having researchers like Dr. Lucie Low help lead the way makes an enormous difference, too.
Dr. Lucie Low:
I like big picture stuff. I was always thinking, "Well, hey. Well, I'm doing this one tiny thing, but how does that relate?" But I realized I wanted to be involved in helping shape the future of research, and so I worked very closely with a number of intramural scientists. But my job is to help identify how can we design programs that will answer specific questions? How can we use taxpayer's funds most efficiently, most effectively to answer a specific question or to help overcome a particular roadblock to address a specific challenge. I was just very lucky that the tissue chip opportunity came up. I'm very lucky that I still get to do a lot of pain neuroscience as part of that job, because that's my jam. But I'm really excited to work with such a phenomenal group of scientists across the country, and certainly across the globe as well, doing really exciting translational research in this area.
Speaker 4:
The Amazing Things Podcast is presented by United for Medical Research, because America's investment in medical research through the National Institutes of Health is making amazing things possible. Learn more at unitedformedicalresearch.com.