1 00:00:02,235 --> 00:00:04,204 Coming to DARPA is like grabbing the nose 2 00:00:04,204 --> 00:00:07,207 cone of a rocket and holding on for dear life. 3 00:00:08,108 --> 00:00:09,576 DARPA is a place where if you don't. 4 00:00:09,576 --> 00:00:12,579 Invent the internet, you only get a B. 5 00:00:12,912 --> 00:00:15,915 A DARPA program manager quite literally invents tomorrow. 6 00:00:16,383 --> 00:00:18,885 Coming to work every day and being humbled by that. 7 00:00:18,885 --> 00:00:21,221 DARPA is not one person or one place. 8 00:00:21,221 --> 00:00:24,691 It's a collection of people that are excited about moving technology forward. 9 00:00:25,592 --> 00:00:28,294 Hello and welcome to voices from DARPA. 10 00:00:28,294 --> 00:00:32,699 My name is Stacy Wierzba, and I'll be your host for this episode. 11 00:00:32,732 --> 00:00:36,169 We sat down with Doctor Leonard Tender, or Lenny. 12 00:00:36,970 --> 00:00:39,973 Lenny joined DARPA in January 2023 13 00:00:40,206 --> 00:00:43,777 as a program manager in the Biological Technologies Office. 14 00:00:44,644 --> 00:00:48,181 His research interests include developing new methods for user 15 00:00:48,181 --> 00:00:52,619 defined control of biological processes and supply chain resilience. 16 00:00:53,319 --> 00:00:56,122 He earned a bachelor's degree from MIT, 17 00:00:56,122 --> 00:01:00,960 a doctoral degree from UNC, Chapel Hill, completed a post-doc fellowship 18 00:01:00,960 --> 00:01:04,731 at UC Berkeley and served as a visiting scientist 19 00:01:04,731 --> 00:01:07,734 in the Stanford University Department of Chemistry. 20 00:01:08,101 --> 00:01:12,038 He co-founded the International Society for Microbial Electrochemistry 21 00:01:12,038 --> 00:01:16,443 and Technology, and is a recipient of the Arthur S Fleming Award, 22 00:01:16,743 --> 00:01:19,746 which honors outstandingfederal employees. 23 00:01:20,280 --> 00:01:22,982 But to hear him tell it, that's all fairly standard. 24 00:01:24,551 --> 00:01:27,420 I did the normal routine - undergraduate, 25 00:01:27,420 --> 00:01:31,291 graduate school, postdoc, and then I was at the Naval Research 26 00:01:31,291 --> 00:01:34,627 Laboratory for 24 years right here in Washington, D.C. 27 00:01:35,195 --> 00:01:38,965 The Naval Research Laboratory is the Navy's in-house national laboratory, 28 00:01:39,299 --> 00:01:43,903 and I was a principal investigator and became a branch head. 29 00:01:44,404 --> 00:01:47,507 So I had been a DARPA Pi twice in my career, 30 00:01:47,841 --> 00:01:51,778 very, very early on and it actually launched my career. 31 00:01:51,878 --> 00:01:56,850 And then later in my career around 2017, 2018 or so, 32 00:01:57,550 --> 00:01:58,418 there are a number of people 33 00:01:58,418 --> 00:02:01,421 who have gone from the Naval Research Laboratory to DARPA, 34 00:02:01,488 --> 00:02:05,558 and I had engaged with one of them and started having discussions 35 00:02:05,558 --> 00:02:06,993 and realized there's a lot of overlap, 36 00:02:06,993 --> 00:02:09,996 and I thought it'd be a really great challenge for me to take on. 37 00:02:13,766 --> 00:02:16,603 My background, my formal training is in electrochemistry, 38 00:02:16,603 --> 00:02:19,772 which is studying the interaction of electrons and chemicals. 39 00:02:20,006 --> 00:02:23,877 But during the course of the 24 years I spent the Naval Research Laboratory, 40 00:02:23,877 --> 00:02:28,615 I started looking at how microorganisms are essentially little electrical machines 41 00:02:28,615 --> 00:02:32,152 and applying the tools of electrochemistry to study them. 42 00:02:32,919 --> 00:02:37,790 All living organisms fundamentally require a flux of electrons in and out. 43 00:02:37,790 --> 00:02:42,795 And so for us, when we ingest food, we're essentially ingesting, say, glucose, 44 00:02:42,795 --> 00:02:43,897 which is the simplest case. 45 00:02:43,897 --> 00:02:47,901 And we take those carbon atoms and ultimately remove electrons from them. 46 00:02:47,901 --> 00:02:50,904 And that becomes the carbon dioxide that we exhale. 47 00:02:50,904 --> 00:02:54,073 And a lot of the processes that go on in our body are about moving those electrons 48 00:02:54,073 --> 00:02:55,942 around and stripping off the energy. 49 00:02:55,942 --> 00:02:58,244 And microorganisms do the same thing. 50 00:02:58,244 --> 00:03:02,715 That became, for 20 years of my life, In fact, my first funded effort 51 00:03:02,715 --> 00:03:04,784 was a seedling effort from DARPA 52 00:03:04,784 --> 00:03:07,420 to take the very first steps of exploring that concept. 53 00:03:07,420 --> 00:03:11,424 And I could say that everything else that followed in my career for 24 years 54 00:03:11,424 --> 00:03:15,061 at the Naval Research Laboratory was based on that first set of experiments 55 00:03:15,061 --> 00:03:19,465 and sort of pioneer in understanding how microorganisms, how we can feed them 56 00:03:19,465 --> 00:03:22,869 electrons and pull electrons off of them using the tools of electrochemistry. 57 00:03:23,436 --> 00:03:27,507 And so, towards the very end of my career, I started looking at organisms 58 00:03:27,507 --> 00:03:29,042 that are involved in infection, 59 00:03:29,042 --> 00:03:32,812 pathogenic organisms, in particular wound infection, and then understanding 60 00:03:32,812 --> 00:03:36,216 that when you have a wound infection, that means that you have a wound 61 00:03:36,482 --> 00:03:39,986 that's been colonized by organisms, and the organisms disrupt 62 00:03:39,986 --> 00:03:41,921 the normal healing process. 63 00:03:41,921 --> 00:03:45,758 And I wanted to really understand how those organisms can live in a wound. 64 00:03:46,459 --> 00:03:50,396 So using the tools that we developed and working with some really great 65 00:03:50,396 --> 00:03:51,798 collaborators, in particular 66 00:03:51,798 --> 00:03:55,401 Professor Diane Newman from Caltech, who is an expert in these type of organisms, 67 00:03:55,902 --> 00:03:58,771 we figured out how the organisms are essentially breathing, 68 00:03:58,771 --> 00:04:01,674 how they're getting rid of their respired electrons. 69 00:04:01,674 --> 00:04:04,811 And we started wondering, well, would that have implications for wound infections? 70 00:04:04,811 --> 00:04:07,413 If we can start to sort of disrupt that process? 71 00:04:08,581 --> 00:04:11,651 Disruption is an accomplishment DARPA prides itself on 72 00:04:11,884 --> 00:04:13,953 and constantly strives for. 73 00:04:13,953 --> 00:04:17,824 While disruption of the wound infection process might not seem immediately 74 00:04:17,824 --> 00:04:21,861 important to national security, it can be a matter of life or death. 75 00:04:22,895 --> 00:04:25,298 Even in our last major conflict. 76 00:04:25,298 --> 00:04:28,201 So Operation Enduring Freedom, Operation Iraqi Freedom, 77 00:04:28,201 --> 00:04:31,304 even when we can get the injured warfighters off the battlefield 78 00:04:31,304 --> 00:04:34,807 into high level care within an hour, we are experiencing something 79 00:04:34,807 --> 00:04:38,911 like 27% of those people are experiencing debilitating wound infections. 80 00:04:39,112 --> 00:04:41,681 And so that's under really great conditions. 81 00:04:41,681 --> 00:04:45,885 Now we look at Ukraine, for example, and we're seeing 50% wound infections. 82 00:04:46,052 --> 00:04:47,754 And of course in Ukraine, the difference is, is 83 00:04:47,754 --> 00:04:50,757 they're not able to get people out as quickly as possible. 84 00:04:50,957 --> 00:04:54,894 And then on top of that we're seeing high levels of multidrug resistant organisms. 85 00:04:54,894 --> 00:04:56,663 The whole antibiotic resistance. Right. 86 00:04:56,663 --> 00:05:00,600 So unfortunately war is a big driver of antibiotic resistance. 87 00:05:00,600 --> 00:05:04,370 And we're seeing right now in Ukraine is very high levels of antibiotic resistance. 88 00:05:04,370 --> 00:05:07,840 And so right now the standard of care when a warfighter gets injured on 89 00:05:07,840 --> 00:05:10,843 the battlefield is you administer high dose antibiotics right away. 90 00:05:11,611 --> 00:05:12,812 There's two problems with that. 91 00:05:12,812 --> 00:05:13,813 The first is that, 92 00:05:13,813 --> 00:05:16,382 well, we're kind of running out of time on the antibiotics right. 93 00:05:16,382 --> 00:05:19,052 At some point, you know, a lot of them are just not going to be useful. 94 00:05:19,052 --> 00:05:21,321 Secondarily, there's a lot of good organisms 95 00:05:21,321 --> 00:05:25,792 that are actually, if not benign, actually beneficial to the wound healing process. 96 00:05:26,125 --> 00:05:28,561 And if we're knocking everything out, that's not good. 97 00:05:28,561 --> 00:05:29,462 Right. 98 00:05:29,462 --> 00:05:31,964 And there's nuance in there and how you define infection 99 00:05:31,964 --> 00:05:35,134 because all wounds become contaminated with organisms. 100 00:05:35,134 --> 00:05:38,871 In fact, many wounds will become very contaminate, have a high load 101 00:05:38,871 --> 00:05:41,841 of microorganisms, but they'll continue on to heal well. 102 00:05:41,874 --> 00:05:44,877 And we don't want to mess with those wounds right. 103 00:05:44,977 --> 00:05:47,580 It's the ones that the wound healing begins to fail. 104 00:05:47,580 --> 00:05:49,949 Those are the only ones we want to go after. 105 00:05:49,949 --> 00:05:54,620 The BioElectronics for Tissue Regeneration program, or BETR takes aim 106 00:05:54,620 --> 00:05:59,625 at these wounds with the intent to create what is essentially a smart bandage. 107 00:06:00,326 --> 00:06:03,930 BETR was a program that I took over when I arrived at DARPA, and in fact, 108 00:06:03,930 --> 00:06:06,966 it was led by Paul Sheehan, who was the program manager 109 00:06:06,966 --> 00:06:09,969 that I knew from NRL who came to DARPA. 110 00:06:10,002 --> 00:06:13,473 And then he left shortly after I came and took over his program. 111 00:06:13,673 --> 00:06:18,911 And so that is a program that also is looking at wounds - not infected wounds. 112 00:06:19,345 --> 00:06:20,947 But asking a fundamental question 113 00:06:20,947 --> 00:06:24,417 is, can we monitor a wound, the healing process in real time, 114 00:06:24,417 --> 00:06:29,255 and then interfere with or reprogram the natural healing process 115 00:06:29,555 --> 00:06:33,593 to either have the wound heal faster for a simple wound 116 00:06:33,826 --> 00:06:36,829 or for more complicated wound have it heal better. 117 00:06:37,163 --> 00:06:40,066 For the former., te simple wound, you can imagine, say, 118 00:06:40,066 --> 00:06:42,435 someone has had a pretty invasive surgery, right? 119 00:06:42,435 --> 00:06:45,238 And you have a big, you know, incision on your chest. 120 00:06:45,238 --> 00:06:46,806 Well, imagine if you could apply a bandage. 121 00:06:46,806 --> 00:06:49,442 It's going to make it close off a lot faster. 122 00:06:49,442 --> 00:06:51,210 That would have tremendous payoffs in terms of 123 00:06:51,210 --> 00:06:54,347 just getting people out of the hospital a lot faster, recovering a lot faster 124 00:06:55,515 --> 00:06:57,717 For the latter, in terms of the more complicated 125 00:06:57,717 --> 00:07:01,521 wounds, for example, one of the wounds that soldiers, warfighters experience, 126 00:07:01,521 --> 00:07:03,089 is what we call volumetric muscle 127 00:07:03,089 --> 00:07:06,592 loss, wounds where you have a blast and essentially, 128 00:07:06,926 --> 00:07:11,931 I guess there's no other way to say it, a big part of a limb, say a leg ,is gone 129 00:07:12,165 --> 00:07:15,401 and you're lost a lot of muscle and nerves and blood vessels. 130 00:07:16,235 --> 00:07:19,305 We have evolved naturally for those wounds to scar over. 131 00:07:19,305 --> 00:07:23,042 And scarring is sort of a way of sealing the wound to minimize infection. 132 00:07:23,376 --> 00:07:27,313 Imagine if you can reprogram that wound with a bandage or a dressing 133 00:07:27,313 --> 00:07:31,651 that is super smart so that it reprograms it not to scar, but 134 00:07:31,651 --> 00:07:35,755 to actually allow for functional tissue to regenerate and to replace the muscle. 135 00:07:36,322 --> 00:07:39,125 And that's - and we actually have performers who have done both. 136 00:07:39,125 --> 00:07:41,227 And it's super, super exciting. 137 00:07:41,227 --> 00:07:44,497 Now, that's not to say that you can go buy one of these bandages 138 00:07:44,497 --> 00:07:46,132 at your local pharmacy today. 139 00:07:47,133 --> 00:07:48,734 Developing medical 140 00:07:48,734 --> 00:07:51,737 device technology is a very long process. 141 00:07:51,971 --> 00:07:54,907 And what we do at DARPA in really any 142 00:07:54,907 --> 00:07:57,977 activity is really de-risk a concept. 143 00:07:57,977 --> 00:08:02,882 And so when BETR started, the notion is can we understand a wound physiology 144 00:08:03,216 --> 00:08:06,018 at a high enough level and then actually have the tools that we 145 00:08:06,018 --> 00:08:09,755 can actually incorporate into the bandage to sort of reprogram the healing process. 146 00:08:09,755 --> 00:08:12,825 And so we're talking about developing a whole new set of sensors 147 00:08:12,825 --> 00:08:13,893 that are monitoring. 148 00:08:13,893 --> 00:08:16,028 And the wounds a very complicated environment. 149 00:08:16,028 --> 00:08:17,430 You can have something like 150 00:08:17,430 --> 00:08:21,801 four different dozens of cell types that are all interacting, you know, 151 00:08:21,801 --> 00:08:25,137 in a coordinated, orchestrated process that's changing over time. 152 00:08:25,304 --> 00:08:27,607 And so we have to be able to monitor all that. 153 00:08:27,607 --> 00:08:30,109 And then can we know when we can intervene. Right. 154 00:08:30,109 --> 00:08:33,513 And so for example, one team, built an incredible 155 00:08:33,779 --> 00:08:37,149 digital twin, really modeling the whole wound process, 156 00:08:37,149 --> 00:08:40,353 getting all the way down and understanding how all the signaling molecules 157 00:08:40,353 --> 00:08:43,990 and all those cells interact with each other and finding those sort of points 158 00:08:44,290 --> 00:08:47,593 that if there's like one signaling molecule at this one time point, 159 00:08:47,593 --> 00:08:51,264 if we can just adjust it at this level, this can have a profound impact. 160 00:08:52,565 --> 00:08:56,102 A bandage sensing, analyzing and treating wounds 161 00:08:56,102 --> 00:08:59,972 without human intervention or additional computing sounds 162 00:08:59,972 --> 00:09:03,976 like something straight out of Star Trek, but it's being made possible today. 163 00:09:04,477 --> 00:09:08,314 So a big component of this is it’s completely closed loop control. 164 00:09:08,314 --> 00:09:10,950 So you have your sensors, you have what you're sensing, 165 00:09:10,950 --> 00:09:12,285 you have different treatment 166 00:09:12,285 --> 00:09:16,155 regimes, methods of treating the infection that are embedded into the device 167 00:09:16,556 --> 00:09:20,126 that you can control the release of and regulate the administration of. 168 00:09:20,126 --> 00:09:21,427 And that's all going to be controlled 169 00:09:21,427 --> 00:09:25,398 through closed loop control on board a device, in addition to the technology 170 00:09:25,398 --> 00:09:28,935 development and commercialization and regulatory strategies 171 00:09:28,935 --> 00:09:29,669 and all that stuff, 172 00:09:29,669 --> 00:09:32,071 we're challenging the people to also think ahead and say, well, 173 00:09:32,071 --> 00:09:35,074 imagine that., you know, you're wildly successful, 174 00:09:35,074 --> 00:09:37,443 but then you have to have all this follow-on funding 175 00:09:37,443 --> 00:09:38,911 and then you can get the clinical trials. 176 00:09:38,911 --> 00:09:42,415 The end product has to be something that is actually useful, right? 177 00:09:42,882 --> 00:09:43,349 And we want it 178 00:09:43,349 --> 00:09:46,519 to be useful on the battlefield because when a warfighter gets injured, 179 00:09:46,652 --> 00:09:48,187 the infection begins. 180 00:09:48,187 --> 00:09:50,923 The process begins there. As soon as the skin is broken, 181 00:09:50,923 --> 00:09:53,125 the microbes start contaminating the wound. Right? 182 00:09:53,125 --> 00:09:56,762 It has to be practical, you know, in terms of being useful 183 00:09:56,762 --> 00:09:58,197 in a very, very forward environment. 184 00:09:58,197 --> 00:10:00,533 So it can't be extremely delicate. 185 00:10:00,533 --> 00:10:04,470 It can't rely upon a huge instrument in an analytical lab in a hospital somewhere, 186 00:10:04,470 --> 00:10:06,806 cold chain, you know, it could be a problem 187 00:10:06,806 --> 00:10:10,209 and then, you know, has to be manufactured at a reasonable cost. 188 00:10:11,210 --> 00:10:12,845 We de-risk the concept, 189 00:10:12,845 --> 00:10:16,415 and we're actually at the point now where one of our performers is doing 190 00:10:16,415 --> 00:10:20,119 the first in-person clinical trials for not the whole bandage, 191 00:10:20,119 --> 00:10:23,456 but for the ability to monitor in real time how the wound is healing, 192 00:10:23,656 --> 00:10:27,827 and also to actually have the sensors all working, but actually use 193 00:10:27,827 --> 00:10:30,930 machine learning, training on the sensors, to say this is how the wound 194 00:10:30,930 --> 00:10:33,933 is progressing in time, which is a huge accomplishment. 195 00:10:34,033 --> 00:10:36,168 Tthere's a number of small companies 196 00:10:36,168 --> 00:10:39,705 that have been spun up and spun out as part of this effort. 197 00:10:39,705 --> 00:10:41,140 And DARPA's very big into that. 198 00:10:41,140 --> 00:10:45,011 Having companies being formed by the teams as their work is progressing to help 199 00:10:45,011 --> 00:10:47,313 with the commercial transition, because we're focused 200 00:10:47,313 --> 00:10:50,983 on delivering these technologies to the DoD, to the warfighters. 201 00:10:50,983 --> 00:10:54,086 But wound healing is a huge national problem. 202 00:10:54,086 --> 00:10:56,856 The biggest type of wounds we deal with as a nation are diabetic foot 203 00:10:56,856 --> 00:10:58,891 ulcers costing hundreds of millions of dollars, 204 00:10:58,891 --> 00:11:01,861 if not billions of dollars to Medicaid and to the VA. 205 00:11:01,861 --> 00:11:05,631 And so it's a different type of wound, the diabetic foot ulcers are more chronic, 206 00:11:05,765 --> 00:11:08,401 but there's a lot of overlap in terms of what's going on. 207 00:11:08,401 --> 00:11:10,770 And so so we're driving the transition 208 00:11:10,770 --> 00:11:14,774 of this technology so that that market then it can eventually feed into the DoD. 209 00:11:16,709 --> 00:11:19,145 DARPA's pretty much done with BETR now. 210 00:11:19,145 --> 00:11:20,746 Other groups are taking over. 211 00:11:20,746 --> 00:11:23,449 So Lenny figured it was time to revisit something 212 00:11:23,449 --> 00:11:26,452 put on the back burner when BETR first got started. 213 00:11:27,153 --> 00:11:30,256 When that program was pitched, everyone recognize that wound infections 214 00:11:30,256 --> 00:11:33,359 were a big problem, but the previous program manager 215 00:11:33,359 --> 00:11:37,430 and the leadership of DARPA decided that just handling the wound by itself, 216 00:11:37,430 --> 00:11:39,799 the wound healing without infection was a hard enough problem. 217 00:11:39,799 --> 00:11:42,601 But overlying infection would be insanely difficult. 218 00:11:42,601 --> 00:11:46,439 Well, four and a half years later, we made tremendous progress 219 00:11:46,439 --> 00:11:51,377 on that ability to monitor and reprogram the healing process to a certain extent, 220 00:11:51,644 --> 00:11:52,578 which is very exciting. 221 00:11:52,578 --> 00:11:55,781 And so now the time is ripe to build upon the lessons learned and add 222 00:11:55,781 --> 00:11:57,483 in the infection component. 223 00:11:58,517 --> 00:12:01,020 This is where Lenny's new BioElectronics 224 00:12:01,020 --> 00:12:04,023 to Sense and Treat program, or BEST comes in. 225 00:12:04,757 --> 00:12:09,662 You imagine a warfighter that's on the battlefield who is not severely wounded. 226 00:12:09,662 --> 00:12:13,466 I mean, if they were here in Arlington, Virginia, they'd go to the hospital. 227 00:12:13,466 --> 00:12:16,736 But when you're on a battlefield, they can get back up on their feet. 228 00:12:17,069 --> 00:12:20,673 If you can get that wound, you know, the bandage on and monitor for infection. 229 00:12:20,673 --> 00:12:22,842 That warfighter can return operations, 230 00:12:22,842 --> 00:12:25,845 but more likely and not given the unsanitary conditions. 231 00:12:25,978 --> 00:12:27,947 And then also the stress that they're under 232 00:12:27,947 --> 00:12:30,983 and how compromised the immune system is going to be, 233 00:12:30,983 --> 00:12:32,885 they're going to be very susceptible to infection. 234 00:12:32,885 --> 00:12:35,421 But if we can stop that, then they can stay in operations. 235 00:12:35,421 --> 00:12:35,888 Right. 236 00:12:35,888 --> 00:12:38,190 And then we have a whole other cohort that are, for example, 237 00:12:38,190 --> 00:12:41,127 the ones with the bigger wounds are going to be flown out, 238 00:12:41,127 --> 00:12:44,663 just managing the wounds, if they're infected, requires 239 00:12:44,663 --> 00:12:47,800 orders of magnitude more caregiver attention, expense. 240 00:12:48,033 --> 00:12:50,336 It's traumatic for the warfighter. 241 00:12:50,336 --> 00:12:52,772 It can mean the difference between amputation 242 00:12:52,772 --> 00:12:55,341 and not amputation or where an amputation occurs. 243 00:12:55,341 --> 00:12:59,578 And so being able to just have technology that can automatically remove 244 00:12:59,612 --> 00:13:01,881 that concern of the infection would be very powerful. 245 00:13:01,881 --> 00:13:04,250 And so that's the goal of that program. 246 00:13:04,250 --> 00:13:07,353 So part of the capability is that it has to be adaptable 247 00:13:07,353 --> 00:13:10,356 for variability in people's immune response. 248 00:13:10,456 --> 00:13:14,627 And so ideally the way this would work is you'd be looking for signatures 249 00:13:14,627 --> 00:13:17,897 of what microbes are there, but also on how the host is responding. 250 00:13:18,230 --> 00:13:19,431 There's a lot of overlap there. 251 00:13:19,431 --> 00:13:20,499 It could be, for example, 252 00:13:20,499 --> 00:13:24,403 that how the host is responding might tell you all you need to know. 253 00:13:24,670 --> 00:13:28,140 It could be which organisms are there, may tell you all you need to know, 254 00:13:28,340 --> 00:13:31,310 but people, their immune responses are very different. 255 00:13:31,310 --> 00:13:34,480 Particularly people with diabetes, for example, but also warfighters. 256 00:13:34,480 --> 00:13:36,549 You know, you take a young, healthy person in their mid 257 00:13:36,549 --> 00:13:38,818 20s here, you know, in Arlington, Virginia, 258 00:13:38,818 --> 00:13:40,753 and they get into an accident or something. 259 00:13:40,753 --> 00:13:41,220 Okay. 260 00:13:41,220 --> 00:13:45,658 But if they're on a battlefield and dehydrated and in shock and stress, 261 00:13:45,658 --> 00:13:49,295 if they're experiencing polytrauma, their immune system is going to completely 262 00:13:49,528 --> 00:13:50,596 be out of whack. 263 00:13:50,596 --> 00:13:52,865 And so we need to be able to adjust for that. 264 00:13:52,865 --> 00:13:54,767 A lot of that is overlap with the BETR program. 265 00:13:54,767 --> 00:13:56,202 Part of the big accomplishments 266 00:13:56,202 --> 00:13:59,605 of the BETR program is being able to monitor the host immune response. 267 00:13:59,605 --> 00:14:02,608 And because the immune response, which is driving the healing process, 268 00:14:03,142 --> 00:14:07,079 being able to monitor that really gave us the mindset, the framework to say, well, 269 00:14:07,079 --> 00:14:11,183 we can do essentially the same thing for the infected wound. 270 00:14:11,350 --> 00:14:14,587 Of course, it's not exactly the same, and in fact, it's 271 00:14:14,587 --> 00:14:18,390 going to be very different because of how the organisms affect the immune response. 272 00:14:20,292 --> 00:14:23,128 The actual programmatic timeline is three years, 273 00:14:23,128 --> 00:14:25,431 looking at two phases, a two year 274 00:14:25,431 --> 00:14:29,068 phase where we're looking at independently developing the monitoring capability 275 00:14:29,201 --> 00:14:32,204 and the treatment capability, but doing it in a manner 276 00:14:32,271 --> 00:14:35,541 so that in the third year they can be integrated together. 277 00:14:35,841 --> 00:14:37,276 So they have to be coordinated. 278 00:14:37,276 --> 00:14:40,279 And then the third year is bringing together the closed loop control. 279 00:14:40,446 --> 00:14:46,318 It is a DARPA hard program in that there are pieces of technology out there 280 00:14:46,318 --> 00:14:49,889 that appears could do the job, but there is really not the complete package. 281 00:14:50,222 --> 00:14:53,025 And none of the pieces can do it as well as what we're going to need it 282 00:14:53,025 --> 00:14:54,093 to do separately. 283 00:14:54,093 --> 00:14:56,462 And then thinking about tying it all together in the closed 284 00:14:56,462 --> 00:14:59,431 loop control is going to be a pretty awesome heavy lift. 285 00:15:00,733 --> 00:15:03,168 A lot of work goes into really all DARPA programs 286 00:15:03,168 --> 00:15:08,207 to make sure that you are tying it to a pressing problem. 287 00:15:08,641 --> 00:15:11,977 You know, we have in the building incredible people who are very connected 288 00:15:11,977 --> 00:15:14,947 within all their different branches of the military, 289 00:15:14,947 --> 00:15:18,517 and they're very enthusiastic and very effective at brokering relationships. 290 00:15:18,517 --> 00:15:21,220 And so we have a lot of relationships that they broker. 291 00:15:21,220 --> 00:15:23,622 Working with our team is the Uniformed Services 292 00:15:23,622 --> 00:15:27,092 University, for example, and Walter Reed, for example, among others. 293 00:15:27,159 --> 00:15:28,861 Lawrence Livermore National Laboratory, 294 00:15:28,861 --> 00:15:31,230 they provide certain subject matter expertise. 295 00:15:31,230 --> 00:15:35,034 We have what are called SMEs that provide us a lot of expertise 296 00:15:35,034 --> 00:15:39,338 in terms of how we rigorously monitor and actively manage the program 297 00:15:39,338 --> 00:15:42,875 to optimize the opportunity for success in maximizing the output. 298 00:15:43,776 --> 00:15:45,911 Speaking of maximizing output, 299 00:15:45,911 --> 00:15:49,682 there's another side of Lenny's program portfolio that seeks to do just that 300 00:15:50,082 --> 00:15:54,553 by finding value and utility in what's previously been seen as detritus. 301 00:15:56,221 --> 00:15:58,557 There's other areas that I'm exploring 302 00:15:58,557 --> 00:16:01,560 that biology is a really good solution set. 303 00:16:01,727 --> 00:16:06,932 And so one of them is biomanufacturing, which is this notion of making 304 00:16:07,066 --> 00:16:11,670 useful materials out of available waste streams, feedstocks. 305 00:16:11,971 --> 00:16:15,541 We had a program that has just ended recently called ReSource, 306 00:16:15,908 --> 00:16:19,645 and was looking at whether or not it's feasible to take waste plastics 307 00:16:20,079 --> 00:16:23,382 and then convert them into useful materials, 308 00:16:23,749 --> 00:16:28,087 specifically foods, oils, lubricants, and to do it in 309 00:16:28,087 --> 00:16:31,557 austere and remote environments and do it with low energy input. 310 00:16:31,824 --> 00:16:35,227 And it turns out that biology can play a very important role in that. 311 00:16:35,361 --> 00:16:38,797 Biology is really good at transforming one set of compounds 312 00:16:38,797 --> 00:16:41,800 into another set of compounds through microbial metabolism. 313 00:16:42,101 --> 00:16:45,104 And so we were actually very successful in that program. 314 00:16:45,237 --> 00:16:49,808 Another of Lenny's programs in this area seeks to harness energy from the ocean. 315 00:16:50,275 --> 00:16:53,879 That's the BioLogical Undersea Energy program, or BLUE. 316 00:16:54,513 --> 00:16:59,451 So BLUE is about determining whether or not an ocean deployed sensor 317 00:16:59,785 --> 00:17:01,620 can actually filter feed 318 00:17:01,620 --> 00:17:04,890 on dissolved organic matter in the ocean to generate electrical power. 319 00:17:05,557 --> 00:17:10,729 And so the background on this is a look at filter feeding animals in the ocean. 320 00:17:10,929 --> 00:17:13,298 Say take a dolphin for example. 321 00:17:13,298 --> 00:17:16,568 And the dolphin is eating fish - we're not going after fish, for sure - 322 00:17:16,935 --> 00:17:21,273 but a dolphin can eat about 30, 40kg of fish a day, 323 00:17:21,573 --> 00:17:24,243 and a dolphin can live about 40 years. 324 00:17:24,243 --> 00:17:28,647 And the average output, if you average how much power they generate over 24 hours 325 00:17:28,647 --> 00:17:29,581 is about a kilowatt. 326 00:17:29,581 --> 00:17:32,684 So if anyone's an athlete out there, if you're like an avid bike rider and know 327 00:17:32,851 --> 00:17:36,121 how much wattage you can put out, peak wattage or wattage over ride? 328 00:17:36,355 --> 00:17:40,292 You know, a dolphin is putting out 1000W essentially 24/7, right? 329 00:17:41,193 --> 00:17:46,632 And so all that fish that they're eating ultimately is the foundation of all that. 330 00:17:46,632 --> 00:17:49,034 It's just the dissolved organics that are in the ocean. 331 00:17:49,034 --> 00:17:52,905 There's a lot of biomass that's very small, below a millimeter in diameter. 332 00:17:53,105 --> 00:17:56,642 A lot of it is just runoff from rivers into coastal environments. 333 00:17:56,642 --> 00:17:59,244 You have phytoplankton blooms and etc. 334 00:17:59,244 --> 00:18:03,282 and it's a massive, massive, massive form of carbon that's involved 335 00:18:03,282 --> 00:18:06,285 in carbon cycling, biomass cycling, on the planet. 336 00:18:06,385 --> 00:18:09,755 And so it's a fundamental question, is can we take oceanographic sensors, 337 00:18:09,755 --> 00:18:12,157 which the Department of Defense uses a lot of them, 338 00:18:12,157 --> 00:18:13,792 other agencies use a lot of them. 339 00:18:13,792 --> 00:18:15,194 Industry uses a lot of them. 340 00:18:15,194 --> 00:18:16,428 They're battery powered. 341 00:18:16,428 --> 00:18:18,197 Their batteries run out pretty quickly. 342 00:18:18,197 --> 00:18:19,431 And then the logistics 343 00:18:19,431 --> 00:18:23,802 of replacing the batteries or replacing whole devices is very daunting. 344 00:18:23,802 --> 00:18:26,805 And so essentially they're very underused, right. 345 00:18:26,972 --> 00:18:31,143 If you can replicate that capability of converting that biomass into energy, 346 00:18:31,143 --> 00:18:34,079 which biology does, then that's like pretty cool 347 00:18:34,079 --> 00:18:35,514 because you can have your device 348 00:18:35,514 --> 00:18:39,218 being powered for very long periods of time, far longer than possible batteries. 349 00:18:39,218 --> 00:18:41,186 That opens up a whole range of possibilities. 350 00:18:41,186 --> 00:18:44,857 And so we have two teams that are now working on that. 351 00:18:45,090 --> 00:18:47,926 They are different variations that are called bioreactors. 352 00:18:47,926 --> 00:18:51,296 It's about replicating what goes on in our GI tract or the GI 353 00:18:51,296 --> 00:18:54,666 tract of our oceanographic animal, like our dolphin, are really the 354 00:18:54,666 --> 00:18:58,504 the nucleus -that idea came from whales, which are amazing filter feeders. 355 00:18:58,704 --> 00:19:01,273 And, you know, converting that biomass into chemicals. 356 00:19:01,273 --> 00:19:04,276 And then you can use to then generate power. 357 00:19:04,443 --> 00:19:08,380 In our case, we want to convert them into molecules, for example, that you can use 358 00:19:08,447 --> 00:19:11,750 a fuel cell to generate electrical power, but there's other pathways to do it. 359 00:19:12,151 --> 00:19:14,520 And so that's a program that's just starting. 360 00:19:14,520 --> 00:19:15,654 You know, we have a couple teams 361 00:19:15,654 --> 00:19:18,924 that started late last year and getting up and running pretty quickly. 362 00:19:18,924 --> 00:19:23,829 And it's a thrill to see that we're targeting ten watts, then 100W of power. 363 00:19:24,062 --> 00:19:27,633 And so those seem to be very low amounts of power. 364 00:19:27,633 --> 00:19:31,970 But in terms of having an oceanographic sensor, they're actually pretty high. 365 00:19:32,304 --> 00:19:34,640 And that's average power over time. 366 00:19:34,640 --> 00:19:36,842 And so a lot of oceanographic devices 367 00:19:36,842 --> 00:19:39,811 that, you know, monitor weather and environment and stuff, 368 00:19:39,811 --> 00:19:41,580 those are battery power and they get deployed 369 00:19:41,580 --> 00:19:43,282 and then retrieved and then deploy and retrieve. 370 00:19:43,282 --> 00:19:46,084 And if we can power something like that indefinitely. It'd be really pretty cool. 371 00:19:47,486 --> 00:19:49,821 Not one to shy away from a challenge, 372 00:19:49,821 --> 00:19:54,092 Leonie continues to explore new avenues for biological technologies. 373 00:19:54,459 --> 00:19:57,963 I'm thinking very hard about a future program in applied quantum 374 00:19:57,963 --> 00:20:00,365 biology, quantum mechanics. 375 00:20:00,365 --> 00:20:04,803 It turns out there are a number of physiological or biological processes 376 00:20:04,803 --> 00:20:07,773 that exhibit non-trivial quantum mechanical effects, 377 00:20:07,940 --> 00:20:11,877 which is really hard to do non-biologically, but biology 378 00:20:11,877 --> 00:20:15,647 seems to do it in noisy, messy environments and at room temperature. 379 00:20:16,048 --> 00:20:17,816 And so one of the things 380 00:20:17,816 --> 00:20:20,819 we're asking fundamentally is can you make a quantum computer 381 00:20:21,353 --> 00:20:23,855 that would operate at room temperature under noisy environments, 382 00:20:23,855 --> 00:20:28,227 which we can't do now, drawing from biology, that it seems to exhibit 383 00:20:28,227 --> 00:20:31,129 some of the necessary properties that that would require. 384 00:20:31,129 --> 00:20:34,566 And so there's a case where biology may be a unique solution 385 00:20:34,566 --> 00:20:36,501 to an interesting problem. 386 00:20:36,501 --> 00:20:39,471 Unique solutions to interesting problems is sort of 387 00:20:39,471 --> 00:20:40,872 what we're all about here at DARPA. 388 00:20:41,840 --> 00:20:42,674 This is the most 389 00:20:42,674 --> 00:20:45,677 exhilarating experience I've ever had professionally. 390 00:20:47,012 --> 00:20:50,015 All programs start, you know, with a blank page. 391 00:20:50,048 --> 00:20:51,183 And, you know, 392 00:20:51,183 --> 00:20:54,620 the program manager is thinking about them and engaging with their team. 393 00:20:54,753 --> 00:20:56,822 And then the leadership of the office. 394 00:20:56,822 --> 00:21:00,692 And if you're successful to get it through and get it funded, then 395 00:21:01,059 --> 00:21:04,062 standing up there, especially when you have like a kickoff meeting 396 00:21:04,096 --> 00:21:05,464 where you're in front of the performer 397 00:21:05,464 --> 00:21:08,934 teams is so exciting when you have the performers there. 398 00:21:08,934 --> 00:21:10,802 And it could be the professors and the industry 399 00:21:10,802 --> 00:21:14,906 people and the small company people and the students, the post-docs 400 00:21:14,906 --> 00:21:16,975 and the graduate students and undergraduates. 401 00:21:16,975 --> 00:21:19,311 And, you know, it could be, you know, 50 people there. 402 00:21:19,311 --> 00:21:22,748 And then you have the team also that as part of the government team 403 00:21:22,748 --> 00:21:25,050 who's helping us, the subject matter experts from, 404 00:21:25,050 --> 00:21:28,153 for example, from Walter Reed or from the Uniformed Services University. 405 00:21:28,553 --> 00:21:29,521 It is such a rush. 406 00:21:29,521 --> 00:21:32,658 And then we typically have every six months, all the teams 407 00:21:32,658 --> 00:21:35,661 across the whole program will meet and present, have a review. 408 00:21:35,661 --> 00:21:37,162 And when you realize that they're all here 409 00:21:37,162 --> 00:21:40,432 working on a concept that you developed, that there's nothing really like that. 410 00:21:40,766 --> 00:21:43,568 And then on top of that, just the great support that we have. 411 00:21:43,568 --> 00:21:46,872 I'm a bit of a ringleader, I'm a bit of a portfolio manager. 412 00:21:47,072 --> 00:21:49,741 I have a great team of technical experts. 413 00:21:49,741 --> 00:21:54,112 They're super smart and hard working that work under us to help us 414 00:21:54,112 --> 00:21:58,350 really rigorously, you know, put up ideas and then monitor them. 415 00:21:58,350 --> 00:22:01,386 And that whole dynamic interaction is really incredible. 416 00:22:01,820 --> 00:22:05,324 And so I would challenge anybody out there, especially if you're - 417 00:22:05,324 --> 00:22:08,327 because I'm biased, I'm in the Biological Technologies office - 418 00:22:08,827 --> 00:22:12,397 if you are at a point in your career where you're like, wait a minute, 419 00:22:12,631 --> 00:22:16,568 if I can really have an idea that if I can get the resources 420 00:22:16,568 --> 00:22:20,238 and the right people to do it, that could just really disrupt 421 00:22:20,238 --> 00:22:23,275 or blow up the whole field and have a huge impact. 422 00:22:23,275 --> 00:22:26,278 We talk about impact in terms of national security 423 00:22:26,278 --> 00:22:29,881 and that has many ways of doing that. 424 00:22:29,881 --> 00:22:33,352 But if you're at some point in your career and you're thinking, well, 425 00:22:33,352 --> 00:22:36,722 if I can really push an area and have a big impact, 426 00:22:36,722 --> 00:22:39,991 I think I have an idea, you know, give us a try, drop me a line. 427 00:22:42,361 --> 00:22:45,330 That's all for this episode of Voices from DARPA. 428 00:22:45,397 --> 00:22:48,333 For more information on any of the programs 429 00:22:48,333 --> 00:22:51,703 we discussed, or how you can get involved with the agency, 430 00:22:51,970 --> 00:22:54,973 check out the show notes or visit DARPA.mil. 431 00:22:55,440 --> 00:22:57,209 As always, thanks for listening.