Pat Pataranutaporn

Speaker 1: So, we are halfway through the talk sessions. And so, in this next session, we’re going to be looking and unpacking the word augment, or how can we use biology and synthetic biology to improve or enhance the things that already exist? So, maybe before, it was a little bit about making completely new things. Now, it’s about looking at the things that we have and improving them and augmenting them with these really great tools and technologies that we have in biological engineering. And so, to do that, we’re going to have four speakers in this section. The first is Pat, who’s going to be talking about wearable organs.

00:42 - And then, we’re going to hear from Yihyun Lim, the director of the MIT design lab, who’ll be talking about wearables and a really cool collaboration with Puma. And then, Ritu Raman, from the Langer Lab, will come up and speak about bio hybrid materials. And then finally, we’ll conclude with Deepak Mishra, who will be talking about some of the really cool work that he’s doing in biological circuits. He’s actually my TA for a course on that subject, so that’ll be cool to hear from him. All right, great. Pat: Okay, as an organizer, I also feel I need to kind of contain myself so we kind of finish and have lunch on time.

01:26 - I’m Pat from the Fluid Interfaces group, and I’m going to talk about the programmable bio digital organ. And usually, I begin with dinosaurs, but now, I’m going to begin with space exploration. So, we say that space is the final frontier of humanity, we try to augment ourselves so we can go to space, and many technologies that we saw in sci fi, about space, have actually inspired many technologies, from smartphone to Google Glass, wearable, and so on. And one of the most profound technologies, for me, is the idea of cyborg, which stands for cybernetic organism, something that we saw a lot in science fiction. But it’s actually a technical concept that was proposed by Professor Manfred Klein and Nathan Klein, nine years before Apollo 11 in 1970.

02:10 - And the idea of cyborg is augmenting biological organ with digital and artificial part that we put on our human body. And this is actually the concept that inspired the very, very first space suit that allowed humans to go and explore space. Pat: However, one thing about cyborg that I think is really interesting is that cyborgs are supposed to allow us to be free so we can explore more. So, instead of having these clunky machines, we should make things kind of seamless and fluidly integrate with ourselves. So, that’s the philosophy of our group, the Fluid Interface, where we create technology that seamlessly senses the context, and not just senses, but also intervenes at the right moment.

02:49 - Create the condition for the body to thrive and enhance us in multiple ways. Most of the current wearables look at electrophysiological signal, EEG, heart rate, and so on. This is kind of easier to sense because it’s purely electrical. The world that we are presenting and exploring here are looking at the biochemical signal, the DNA, the RNA biomarkers, and so on, which are really interesting and more difficult. However, as you see in many of the presentations, this is an emerging area that we are super excited about.

03:21 - Pat: So, the idea of programmable organ that I’m going to present today is centered around these biochemical signals. How do we sense better and also intervene in the right moment? Right now, the two projects that I’m going to present is kind of not working together yet, but this is our vision for the future. So, start from sensing. There’s no hospital in space. If you’re sick, there is a medical officer onboard that will come and put these different kinds of device on you to check your body. This is the process usually done in the laboratory, whether you take the saliva, urine, blood sample, and so on. But instead of having this giant lab that do multiple things, what if we can put the lab on the human body, and then allow the human body to have access to all kinds of information that we are actually already streaming out? And what I mean by this is that in the human body, when we sweat, when we have saliva coming out, when we pee, go to the bathroom, we release chemicals from our body all the time.

04:17 - And these chemicals can reveal about the state of the human body. Pat: We are interested in saliva, particularly, because as we know, in Boston, we don’t sweat all the time. We are kind of cold and in our sweater, so saliva is something that is produced constantly, and also contain chemicals that we also take in. So, not just measuring the body information, but also the thing that you input into your body. And saliva have been used to measure depression, fatigue, health failure, all kinds of biomarkers.

04:46 - As you see, the bio fluid from the blood also [inaudible] saliva. And on the prototype that we are working on, we call it Wearable Lab on The Body is a on-body fluid handling device, taking saliva and put it on all kinds of biosensors. Right now, the device is kind of huge, but we are working on miniaturizing it. Essentially, it has a tube that goes inside your mouth, constantly taking your saliva out and place it on biomarkers. As you already seen in many presentations, people are developing all kinds of biomarkers to send different types of information.

05:15 - Pat: And what we create is a platform that you can integrate different kinds of biomarkers into strips, and the device will keep rolling them so we have new sensors every time you want to do a new measurement, and also be able to switch between different kinds of sensors. If you want to send a hundred things, you just add it into the strip. So, we kind of think of it as iPhone for biosensor. Instead of having different devices for different things, why not having one device that you can integrate multiple sensors and have that be able to scale? And in the device, we have colorimetric sensor that can word the reaction that happened on the strip into digital concentration of our different biomarkers. And we can also contextualize it with the accelerometer information that’s coming from the device.

05:58 - So, we know if the person is speaking, drinking, chewing, and then use that to contextualize. If you see a high spike in glucose, and you know that the person is eating something, then you know that it’s probably from the food, not from the body. And in the future, when there is a pandemic like this, where we have Coronavirus everywhere, having a lab on the body can help you kind of check whether you are being contaminated or not. And if our vision is successful, we should have something much smaller and more fluidly integrated with the human body. This is the vision we are working toward. Pat: So now, augmentation, right? Not just a sensing, how do we intervene in the right moment? When we think about biochemical intervention, sounds scary, something you might think of coming out Gattaca or to sci fi, but it’s actually something that all of you might already had earlier, just in the break.

06:44 - When you take caffeine, drink coffee, take serotonin before going to sleep, or even taking medicine, these are compounds that our body cannot biologically produce. We kind of have these biochemical inputs to the body to intervene and make our body kind of heal better or be more active. So, what if we can have an organ that can be programmed to produce these kinds of molecule to help us have a healthier lifestyle or augment our ability? So now, we are kind of focusing more on the bio-synthesis reactor. This is building on top of many exciting research on bioproduction, where we are using living cells to produce all kinds of bioactive compounds, from therapeutic molecule and so on. And many more molecules are being researched and have been engineered for the bacteria to produce.

07:33 - For example, one of the most exciting things is to produce our cannabinoid compounds, so we can get high… No, so we can get more healthier. Pat: Actually, Gingko and [inaudible] have been looking into bioproduction of cannabinoid and molecules from this family. So, what we are proposing is a wearable bio-synthesis reactor, an on body fluid device for programmable cellular manufacturing. But how do we control the cell to produce what we want? We need to communicate with the cell. One thing that we have been looking into, in collaboration with [inaudible] group, is to use light as the medium because light can be something that digital can produce, also, the cell can receive.

08:15 - So, this genetic circuit allows the cell to be able to sense different wavelengths and activate different genetic pathways, allowing us to have a switchable program. So, not as programming bacteria to make one thing, you can now switch them using digital output, which is the light, and you can kind of switch out the output to produce, kind of, three different compounds, different molecules, and so on. And to demonstrate these, we are using a circuit engineered to produce three different proteins as the output. And when we kind of [inaudible] circuit inside, kind of, light activated reactor, we can see that we have a corresponding protein when we shine a different light on them, allowing us to digitally control gene expression. We still have some leakage problem because when we turn off the light, there’s still some leakage of production, but that’s something that we are working on, to solve it.

09:04 - Pat: But essentially, the vision is not just to have synthetic biology, but have bio-digital interface that allows the cell to be in communication with digital system. And we also, thanks to the support from Farm Lab, be able to collaborate and characterize different ways that we can integrate this digital controlled cell inside microfluidic channel, that we can wear on the body. The ultimate vision is to have a device that you can wear like an Apple Watch that, in the future, can produce molecules to help you stay healthier, and so on. We are most focusing on for astronaut because this is more of an extreme environment, and in the longterm vision, we want to be able to have this closed loop system where we can sense the state of the body and then actuate at the same time. Pat: Also, how do we enable this beyond astronauts in the future, far, far away? We hope that instead of drinking the caffeine, you can produce the molecule on the body, so then you reduce the risk of overdosing, and then having the personalized, kind of, chemical intervention for each person.

10:04 - If you want to be more creative, maybe a little bit of you know what. We really believe that human augmentation is something that we need to think serious about, so our group also cares deeply about ethics of our work. Who has the right to control your metabolic system, and how do we prevent people from thinking that, “Oh, a cell is a computer, so human is a group of cells, so we can treat human like computer?” We want to get away from that and think that this is an enhancement of human expression, rather than exploitation. And there’s a lot of things that we need to think about. However, biotech is still in fantasy mode, so we have a little bit more time to think about.

10:45 - But I encourage everyone to look at different ethical arguments and discussion around this. NSF has a nice report on nano tech and human enhancement that outlines all the important questions we should think about when we think about augmentation. Pat: And with that, I would like to thank our amazing team and support, Professor Pattie Maes, and all my collaborators, David Kong, George Church, for being on my thesis committee. When we do biotech, we also have a huge team because it’s good to fail together, and also to succeed together as well. So, with that, I end with a dinosaur. Thank you so much. Yeah. .