Terasaki Institute Top Biomedical Innovations Transforming The World In 2022

Terasaki Institute Top Biomedical Innovations Transforming The World In 2022

The Terasaki Institute for Biomedical Innovation (TIBI) operating three research facilities with its original base working with UCLA (University of California, Los Angeles), is leading the world across multiple domains. The non-profit, founded by the pioneering work of the renowned Dr. Paul Terasaki, continues his legacy for biomedical innovation. As noted on the TIBI legacy page, “The Terasaki Institute will continue the work of Dr. Terasaki to address the barriers to long-term success in the field of organ transplantation.” As you will discover in this article, the research has greatly expanded from this original mandate.

This article reflects insights and experiences gained working daily pro bono across more than 200,000 CEOs, investors, scientists and experts.

BIOMEDICAL INNOVATION GLOBALLY

There are daily headlines involving interdisciplinary significant contributions in biomedical innovation.

Biomedical innovation is supported by rapid advancements in computing such as those pioneered by Jack Dongarra, recipient in 2022, of the ACM A.M. Turing Award, the Nobel of computing, for his foundational working in algorithms and software fueling the growth of high-performance computing (HPC). HPC is powered in 2022 by Exascale supercomputing which can perform a billion billion operations per second. In the USA, these computers include El Capitan, Frontier, Aurora. The computers will impact healthcare, drug discovery, understanding molecular interactions and protein folding, cancer research, omics (genomics, transcriptomics, proteomics, metabolomic), solving large problems critical to advances in life sciences combining HPC / data science / bioinformatics / systems biology (example horizontal gene transfer). At Oak Ridge National Laboratory, hybrid computing systems combining HPC with quantum computing will lead to advances not possible in the past. I outline his work in this Forbes article.

The work in biomedical innovation is further supported by tremendous advances in AI/ML and Robotics. Pieter Abbeel, recipient in 2022, of the ACM Prize in Computing, pioneering work produces major contributions. Abbeel pioneered teaching robots to learn from people (imitation or apprenticeship learning), how to make robots learn through their own trial and error (reinforcement learning), how to speed up skill acquisition through learning-to-learn (meta-learning), and how a robot is able to learn to perform a task from just one demonstration after having been pre-trained with a large set of demonstrations on related tasks (few-shot imitation learning). His work continues to be the foundation for the next generation of robotics. His robots create new opportunities in surgical suturing and vision-based robotic manipulation. I detail his work in this Forbes article.

A frontier area of biomedical innovation is in aging. An example is Altos Labs, which has billions in investment.

Aging is a mystery where scientists are gaining a better understanding of factors such as:

-epigenetic changes increasing as we age via DNA methylation where chemical markers modify the function of genes;

-telomeres at the ends of our cell’s DNA which shorten each time the cell divides;

-cell senescence where cells stop dividing, are arrested in function, and accumulate with aging;

-microbiome health linked to aging;

-blood from young mice linked to regeneration in older mice;

-added tools such as reverse CRISPR genetic manipulation; optogenetics to control cell activity with light;

-proteins found in brain cells such as hypocretin attracting attention in sleep research and molecules such as microRNS-137 helping regulating hypocretin;

-Nobel laureate Yamanaka, four molecules known as Yamanaka factors or OSKM factors (Oct3/4, Sox2, Klf4, c-Myc) that can reverse (reprogram) adult cells into stem cells that can be coaxed into forming most types of body tissue. Cells treated with Yamanaka factors, erases marks on the epigenome, losing their identity thus the reversal to the embryonic state (stem cell). Marks (epigenetic markers) gained through aging are also lost, with cells exhibiting a more youthful state. When applied to mice with finely tuned care, reverses signs of aging.

From a practical use case, SCI (spinal cord injury) research and solutions, are heavily integrated in interdisciplinary work in biomedical innovation. To illustrate I had a chat appearing with the non-profit IEEE TEMS (search for interviews with Stephen Ibaraki). The unscripted dialogue is with Bill Barrable, CEO, and Arushi Raina, Director of Commercialization, for the non-profit Praxis Spinal Cord Institute. Bill from his prior work as CEO of BC Transplant, is intimately familiar with and utilized the pioneering work and leadership of Dr. Paul Terasaki and Arushi speaks of the utility of the solutions offered by the present day Terasaki Institute (TIBI) in SCI. SCI integrates technologies focused on the person in areas such as wound healing, brain computer interfaces (BCI) and neuro brain research, preventing pressure injury through electrical stimulation, VR /AR (mixed reality) and extended reality, AI and sensor technologies, robotics and exoskeletons for mobility, stem cells and regeneration. More generally this is about translational research which is moving beyond research and into scalable practical solutions meeting specific needs. They have adopted a model for working with and accelerating startups. The interview is detailed and focuses on the practical which is the foundation for SCI. SCI is an ideal practical driver for biomedical innovation centered on real solutions.

TERASAKI GLOBAL LEADERSHIP

The Terasaki story is compelling beginning with Dr. Terasaki and now continuing with the non-profit Teraski Institute for Biomedical Innovation (TIBI).

TIBI’s pioneering work is organized around these initiatives: personalized nutrition; personalized physiological models; personalized implants; personalized devices; personalized cells; personalized biomaterials.

To capture TIBI’s narrative, I reached out to CEO Ali Khademhosseini, President Stewart Han, Chief Innovation Officer Maurizio Vecchione. Interviews appear with the non-profit IEEE TEMS. Due to the length of the interviews, about 3 hours of content, only small portions of the interviews are provided by AI-produced transcripts which are then edited and summarized for clarity and brevity. The transcripts are about 70% accurate thus I recommended going to the full video interview for precision. Direct links to the interview page, with profile, and link to video are provided below.

TIBI PRESIDENT STEWART HAN

Stewart was one of the original founders of One Lambda Inc. with Dr. Terasaki, a company focused on improving the lives of transplant patients worldwide. This became the flagship of the transplant diagnostic industry.

Dr. Terasaki has many notable contributions to the field of organ transplant, such as the development of the microcytotoxicity test in 1964, which by 1970, became the international standard. Dr. Terasaki became professor of surgery at UCLA and held that position from 1969-1999. Dr. Terasaki established the kidney transplant registry, which would eventually become the United Network for Organ Sharing registry.

After retiring from his position at UCLA in 1999, Dr. Terasaki continued his work in transplant research and specifically, the role of antibodies in transplant, with the establishment in April 2000 of the Terasaki Foundation Laboratory (TFL). He entered into an affiliation agreement with UCLA to create the Terasaki Institute (formerly TFL) and began the process to locate the newly created Terasaki Institute in Westwood. This history is captured in the interview with Stewart.

As there is overlap between the three interviews, with Stewart, I focus on the journey that led to the founding of TIBI. I summarize added areas such as in the science of biomedical innovation and commercialization. I delve deeper in the science with the interviews of Ali and Maurizio though the Maurizio interview has a scaling and commercialization lens. Though there is overlap, you will find the repeats of use in having a greater and more nuanced understanding of biomedical innovation due to the differing and yet complimentary perspectives.

Stephen Ibaraki

<I ask about inflection points in Stewart’s career path and life.>

Stewart Han

The first person that comes to mind is Paul Terasaki. I started working for him fresh out of college. It was one of those laboratories that if you are a bio major at UCLA, you knew about Dr. Teraski’s laboratory. It was a lab you wanted to get into so that you can get some work experience. And maybe if you were good enough in the laboratory, you might be able to get a good reference letter. I had just applied to marine biology schools, and I got in there. And at the time, this laboratory, had a staff of about 250 people. I was awestruck; first of all, getting into the laboratory, because it was difficult; I started to realize that the place was really just this finely tuned machine and Dr. Terasaki pulled the best out of people. As a student coming into the laboratory, you really wanted to excel at what you were doing. Once I did get to meet him, and really increase my interaction with him, … you really tried to engage with him; it wasn’t any type of hierarchy thing with him. He was just a shy, soft-spoken individual. But he did take me under his wing. I did do some projects for him. He let me loose on doing some projects, which I found completely refreshing. I am an undergraduate that was doing research work and being able to publish. I was doing the same things as some of the postdocs and some of the faculty in the laboratory. If you engaged with him, he was always there willing to give his advice and be a fantastic mentor. One of the inflection points in my career because I originally was just all about the ocean and marine biology. I was waiting for applications to come back. And although I did end up getting into some of these schools, I decided, I’m having so much fun working in transplant immunology. It just opened up a whole new kind of area for me that I wasn’t aware of. I took immunology in college, but I just didn’t know about transplant immunology. I just knew I was hooked. I wanted to stay in the field. So, I ended up staying with Dr. Terasaki. He ended up spinning out a company in 1984. I started with him in 1979. He invited a few of us to come into his company. There were five of us that he asked to come. I was fortunate to be one of those individuals. We started the company in 1984 and the company <One Lambda> was sold to Thermo Fisher Scientific for almost a billion dollars in 2013. I’ve had one boss my entire life, and that was Paul Terasaki. It’s just a blessing that I come back now into research, at this phase of my career, and I’m working with a bunch of scary smart scientists. They are all very passionate about what they do. I’m just happy that I can really try to carry on Dr. Terasaki’s legacy.

Stephen Ibaraki

That’s a remarkable story. You’re talking about a humble, shy individual, but brilliant and transformational in terms of his thinking and innovative capability. He saw something in you and that’s your brilliance as well. Your passion, your commitment to doing well and working hard. He takes you into initially into the research group. You get the opportunity to publish but then also on the founding of one of the miracles in startups which became a major enterprise. Then, a remarkable acquisition as well. That led to the Terasaki Institute for Biomedical Innovation (TIBI). Can you give some of that legacy history from your company One Lambda to Terasaki Institute?

Stewart Han

The Terasaki Institute (TIBI) was founded in the year 2000. I started with the Terasaki Institute in 2018. The original founding premise of the Institute was for Dr. Terasaki, to continue his research that he wasn’t able to finish off with his career at UCLA. He had retired from UCLA in 1999. And quickly realized, within weeks, that he wasn’t going to be happy, sitting at home; he didn’t enjoy golf, he did some swimming. But really his pastime was his science, right? That was what he was really passionate about. And again, improving the quality of transplant patients around the world. So, he had a lot of unfinished business, as do all great researchers. You don’t when you retire, all of a sudden accomplish everything that you’ve wanted to accomplish. He felt like he had a lot of good years left in him. He was in a financial position to be able to start a Foundation Laboratory, which he did. In addition to wanting to continue his work and research, he had always wanted to delve into looking at the intersection of cancer and transplantation. He had a number of family and friends that had been affected by those conditions. He always wanted to figure out a way to be able to address some of those concerns as well. He started looking at all his data and trying to correlate cancer outcome with the HLA <human leukocyte antigen> data that he had established, or that he was looking at. He was always looking at connecting dots. He was one of those types of individuals, could always think outside the box, looking at things from a 30,000-foot level and then be able to zero in. He did that type of work. Fast forward to 2018. I started and we had just opened the Institute here in Westwood. One of his last big initiatives before he passed in 2016 was to start in an Institute that was closer to UCLA. He wanted this institute to have an affiliation with UCLA. He wanted it geographically close to the university; we are now across the street from UCLA. Unfortunately, he passed in 2016; he wasn’t here to see the opening, which was later in 2016. To continue his studies, working with the folks at UCLA, because he was a tremendous Bruin <athletic teams at UCLA>, he was a tremendous alumni and supporter of UCLA. He felt that without UCLA, he wouldn’t have been in the position that he had. Really to benefit of the good graces that came with his success at UCLA. He always wanted to give back to the university. This was one of his ways of doing that. That being said, I was still at One Lambda till about 2014. I thought I had done everything. Time for me to consider moving on. I left One Lambda. Shortly after that, I got contacted by a number of companies that were interested in my consulting services. So, I said, sure what the heck I wasn’t too busy. I quickly realized, like Paul Terasaki, I like to stay busy. So, I helped do some target acquisition analysis for being able to purchase a company to get into the HLA space and the transplant space…They are one of the strongest companies in HLA now as well, and that company’s called CareDx. That being said, shortly after I finished that project, which took the better part of a year, Dr. Steve Hardy, who was the president at the Terasaki Institute, contacted me and said, Stuart want to come over and visit me? Let’s see how we can work together. I wasn’t aware that he was thinking about succession at the time. I just thought he might need my help in terms of some of the commercial aspects of the Institute, but quickly realized that he was really trying to groom his successor. That was just a stroke of luck that I happened to know, Dr. Hardy, who had been a longtime colleague of mine since the days at UCLA. We continue to work through it together throughout the years. And now I’m here. I came here in 2018. We were doing a lot of data work, a lot of analytics, a lot of AI, a lot of machine learning, in the attempt to create an app to help transplant patients be more compliant with their medication. The old adage is if you feel good, you don’t want to take medicine, but that’s not necessarily the case. For transplant patients, they feel good because they’re taking their medication, right. They want to avoid any kind of possibility of acute rejection or chronic rejection. Chronic rejection is really the main enemy of transplanted organ. And chronic rejection is not necessarily identified until too late. So, you always want to be on top of your transplant medication and you want to be very compliant. That was a common kind of issue with transplant patients; they start feeling good and then they don’t want to take their medication. They think that they don’t need to take medication because they don’t understand the immunologic aspects of really trying to keep control of the immune response of the body. So, we thought that, if we create an app here at the Institute, that transplant patients around the world could use to kind of monitor how they’re feeling. Are they having a good day? Are they having a bad day? Have they taken their medication? There was a module in the app that recorded your medication for the day, because some patients had to take up to 30 different medications a day. It’s really cumbersome. And it’s really tedious. And yes, it’s work, it’s a job. So, we started working on that which required all our analytic expertise. And we had a fairly large staff of data scientists and app developers and UI developers here. That was our main effort as we met Dr. Khademhosseini <Dr. K>. I met him. I was very enamored by his approach to solving problems in transplantation. I’m an immunologist by background, so I was always looking at immuno antigens and antibodies, and the possibility for mismatches. Just the solutions that Dr. K came up with him being a bioengineer, of even addressing some of the common problems and in transplants such as organ shortage. He said, why don’t we synthesize an organ? Why don’t we bio print an organ? Why don’t we think about addressing that problem in that way? I just was blown away by his approach to addressing some of the problems. I just had this tunnel vision of looking at it from an immunologist aspect. I was enamored by him; we kept in contact. I introduced him to the Terasaki family; he saw an opportunity and pitched it to the family. They loved what they heard and made him the new director of the laboratory. It has been a couple of years now, all under the auspices of this pandemic that we’ve all been dealing with over the last 24 months. He’s one of those individuals that reminds me of Paul Terasaki. Back in the day, running around handling multiple priorities. He’s one of those people that can definitely multitask much better than I can do. He does it with a smile on his face, and with a high level of energy. He is really diversified the revenue stream here at the Institute. He has brought in a number of NIH grants. He’s always working on possible collaboration with industry. Rather than being funded just by the very generous endowment of the Terasaki family, he has already really added to that. He’s making it so that we are sustainable. That’s what his ultimate goal is; for the Institute is to sustain the growth. We’ve been in constant hiring mode for the last 24 months. We had one laboratory researcher when he started and we now have 25. That’s over the past two years. We’ve purchased a new facility in 2020. We are in the midst of getting the building built out. This building should go online later this year. We’re super excited about all the growth and all the possibilities of the new Institute. We’re in constant growth mode. We’re always hiring and bringing in postdocs, and faculty. That’s a very quick encapsulation of what’s happened to me in the last couple of years in here at the Institute.

Stephen Ibaraki

<I summarize Stewart’s journey from One Lambda, to consulting, to being invited to take work with TIBI.> Are there three locations for TIBI?

Stewart Han

It’s three locations; one of the locations has two large buildings, and that’s our West LA facility. Westwood, which will be more kind of a showcase facility for demoing technology and having events. And then we’ve got our flagship facility, which will be coming online later this year, which is 50,000 square feet and will be the home of 100 different investigators.

Stephen Ibaraki

<I ask for an overview of the TIBI work.>

Stewart Han

<This is provided in overview with Stewart since Ali and Maurizio go into their perspectives on the TIBI work.

Stewart goes into detail about TIBI expertise and that of Dr. Ali Khademhosseini and the TIBI team:

The bioengineering perspectives of organs on a chip technology for drug discovery, micro fluidics & sensors; personalized nutrition; innovation group translating the technology into the market (commercialization) and getting this technology to the patients as quickly as possible.

More details on organs on a chip for drug discovery which is improved over the classical prior long process of inventing molecules, testing on small animals, testing on medium sized animals, into human trials and then it doesn’t work in humans; that happens quite often in the therapeutic industry. There are improvements when creating human physiology on a chip; heart on a chip; kidney on a chip; Alzheimer’s, liver disease, cardiac disease, eye disease — devise the technology to mimic that physiology, put it on a chip, connect all these complex micro fluidics onto the chip, and be able to do exactly what he had set out to do with drug discoveries.

Biomaterials in different applications; biomaterials are made out hydrogel type of material. It can be injected into the body to treat wounds on the heart or treat wounds on the liver. Inject in, it’s sticky enough to be able to help the healing of these different organs, because the bio gel or the hydrogel is infused with either medication or stem cells to really promote the healing of these different organs.

Illuminates using materials to create micro needles. Either use these micro needles in some sort of a sensing device, to be able to try to measure certain biomarkers in the body, or to use these micro needles as an alternative to an injection. When you put a microneedle patch onto your skin, you don’t really feel it; it’s not as invasive as a syringe needle.

The technology that Apple uses — those types of sensors can be made much more sensitive and much more specific. If you’re diabetic, you can potentially measure your blood sugar; if there are other markers that we can identify that are associated with different other disease conditions. We can create sensors to be able to detect those different biomarkers as well.

Personalized nutrition; come up with alternatives for your nutrition. One of the areas that he’s focusing on, which happens to leave a very big footprint on the planetary health situation is with agriculture. Agriculture is responsible for (according to some estimates) 15% of greenhouse gases in the world. There are other impacts like ranch land, and water, the effect on our water tables. It’s just not sustainable … how much meat that they will require in the next 10 to 20 years. The Institute is really focusing on planetary health. One of those initiatives that addresses both planetary health as well as nutrition. He’s come up with technology for cellular agriculture, which is basically, it is meat, but it’s without having to employ animals or what have you. It’s developing meat in the laboratory. >

Stewart Han

<Stuart shares TIBI technology translation model from research to commercialization: spin out a company, create an IP around the technology, and then license it. In the interview with Maurizio, this is discussed from the viewpoint of the Chief Innovation Officer.>

TIBI CEO ALI KHADEMHOSSEINI

Ali brings a remarkable history of accomplishment and continuing notable contributions to biomedical innovation to TIBI. Annually for the past five years, he has been selected by Thomson Reuters as one of the World’s Most Influential Minds as a Highly Cited Researcher. Dr. Khademhosseini’s interdisciplinary research has been recognized by over 60 major national and international awards.

Prior to joining, Ali was Levi Knight Professor of Bioengineering, Chemical Engineering, and Radiology at the University of California-Los Angeles (UCLA). He was the Founding Director of the Center for Minimally Invasive Therapeutics at UCLA. He joined UCLA starting from Nov. 2017 from Harvard University where he was a Professor at Harvard Medical School (HMS) and faculty at the Harvard-MIT’s Division of Health Sciences and Technology (HST), Brigham and Women’s Hospital (BWH) as well as an associate faculty at the Wyss Institute for Biologically Inspired Engineering. At Harvard University, he directed the Biomaterials Innovation Research Center (BIRC) a leading initiative in making engineered biomedical materials. He is a leader in applying bioengineering solutions to precision medicine.

His large and interdisciplinary group is interested in developing ‘personalized’ solutions that utilize micro- and nanoscale technologies to enable a range of therapies for organ failure, cardiovascular disease, and cancer. In enabling this vision, he works closely with clinicians (including interventional radiologists, cardiologists, and surgeons). For example, he has developed numerous techniques in controlling the behavior of patient-derived cells to engineer artificial tissues and cell-based therapies. He is also developing ‘organ-on-a-chip’ systems that aim to mimic human physiology and pathology to enable patient-specific evaluation of drug candidates. In addition, his laboratory is a leader in utilizing biofabrication to form vascularized tissues with appropriate microarchitectures as well as regulating stem cell differentiation in microengineered environments. He has also pioneered various high-performance biomaterials that can respond to each patient’s needs.

Stephen Ibaraki

What are two or three inflection points that created this remarkable journey of yours?

Ali Khademhosseini

I have two. One of them is when I went to MIT for my PhD, that was a really incredible experience. When I went to MIT, I went to the lab of Professor Bob Langer, who’s really a high-level pioneering thinking and historic person. That just changed my perception of what’s possible, what a single individual can do, how thinking big and aiming bigger; really important than how small questions take as much time to solve as big questions, but the impact is ultimately very different. So that was the first. Pushed me to my academic career. And where I was really focused on the academic journey of going through and solving scientific questions. This second inflection point happened when I really was thinking about what I wanted to do. Here in Los Angeles; I spent about 16 years in Boston. When I came over to Los Angeles four years ago, I initially joined the faculty at UCLA. And then pretty quickly after that, I met the Terasaki family. They had this very wonderful foundation that has its own endowment and buildings. And when I was thinking about that opportunity, I talked to the family about how one can actually create an innovation engine here in Los Angeles area and be able to focus on not only doing scientific research, but actually solving and helping spin out these ideas into real world impactful initiatives.

Stephen Ibaraki

When I work with academic communities, there’s this idea of people coming up with concepts, and then they need to do research and development, but it’s very difficult for them to translate that work, and transfer that work into something that’s commercial. And then once you do the commercialization, you still have to get usage and scale that adoption. All those steps beyond the R&D are very difficult. The fact that you have already built a system so that you can span the entire range is just remarkable. And you get the scenario where you get this amazing, globally changing work, but you can scale it to any part of the planet as well.

Ali Khademhosseini

That’s right. And, I think the way universities do it, they are massive institutions where there lot of stuff is happening. And once in a while, something randomly happens, that becomes a success, but it’s not designed for that. Whereas at the Institute <TIBI>, we’re much smaller, but at the same time, we’re much more careful about what kind of questions we want to answer. What kind of projects we want to fund and what kind of outcomes we’re looking for from those projects. The whole cycle becomes much more focused, and to some degree the inverse, because instead of just having people that work on anything that they want, we actually say, work backwards from problems that we’re interested in and then try to find solutions for them.

Stephen Ibaraki

You also have a unique funding model as well, right? Can you describe the different ways you’re able to fund your projects?

Ali Khademhosseini

Definitely. One of the amazing things about the Institute is it has the endowment, so we can actually use the endowment for initiatives that we want to push forward. Of course, one of the things that I really appreciated while I was a professor at Harvard Medical School, was that Harvard, what it does is really interesting, because it keeps the bar pretty high for faculty to be part of that community. It means that you have to be very sharp all the time. Your ideas have to be fundable; you need to be able to get lots of great science performed and published in really high-quality journals. So having external funding, that are peer reviewed, and from government or other agencies, foundations, is also something we care quite a lot about. We definitely encourage our faculty to be federally funded and also get grants from lots of different places. And then the third avenue is the industrial interactions that what we call the innovation team. We have a team headed by Maurice Vecchione that actually focuses on how we partner, how we create win-win situations with different entities. These could be small startups that exists elsewhere or have spun out of the Institute, or large conglomerates that are interested in particular areas … we have a lot more leeway. And that has generated a lot more interest in working with us.

Stephen Ibaraki

Back to some of your early lessons, when you were at MIT, and you go work on a small problem or a big problem. It’s the same amount of effort. But if you work on a big problem, you can make systemic system wide changes for the good. Let’s explore that a little bit further. What are some of your primary solution-oriented work that you’re doing?

Ali Khademhosseini

Definitely so. I’ve been doing tissue engineering for 20 years. Ultimately, for people who may not know, tissue engineering is basically making tissues for transplantation. That’s the end using cells and materials to, and techniques like 3D printing to actually create living tissues. I fundamentally been thinking that the ultimate impact of the kinds of stuff that we’ve been doing is not really going to be in transplantation. I think there’s a lot of other impacts that we’re making. For example, the Institute is focused on quite a bit, is trying to create models of human disease and human physiology, and then be able to use these models to predict everything about how drugs or different compounds influence our tissues. So being able to look at how different compounds could be drug candidates, and what would be their side effects. And this is, of course, a huge problem for pharma industry and lots of other kind of areas. Similarly, you can test these to understand what compounds are going to be toxic, for example, as for environmental impacts, and things like that. The other aspect of using these physiological models is to actually understand the variability between different people in a population. So, one of the things that I found quite fascinating is that in the top 10, selling drugs in the US, they’re actually very ineffective, they only work on about 20% of the population. And the other 80% don’t not only have no effect on, they may actually have side effects on. Being able to understand this variability by being able to create physiological models that creates recreates individuals’ behavior. So, by being able to take, let’s say, a piece of a few skin cells, and then be able to turn those cells into primitive stem cells that can make the different tissues of that individual, then we can also really have predictiveness. In medicine, this whole concept of personalized medicine, precision medicine, where you can understand which cancer drug is going to work on which person’s tumor or the kinds of things that so far, we haven’t been able to do. This is one example of the kind of things that we’re dealing with at the Institute, which is kind of comes from a different world of tissue engineering, and then being able to address a challenge in medicine. And we have similar kinds of things for projects related to climate change, and a number of other diseases too.

Stephen Ibaraki

When you talk about tissue reengineering, and you talked about stem cells, or skin cells, or regression, based on Yamanaka factors?

Ali Khademhosseini

That’s right. Lot of these types of work that we do is really integrating a lot of different sorts of things from different disciplines. So obviously, the cell part is related to the work, for example, that a lot of stem cell scientists, including Yamanaka have done. But there’s other components. For example, we take the cells and we often put them in different types of materials, so that the cells kind of feel as if they’re inside the right environment in the body, that Biomaterials Research comes from a whole different community. At the same time, we take these cells and materials and then we try to create structures out of them. And then that gets us to our 3D printing community. And then at the end of the day, we put all of these in controlled environments that we can flow liquids through … so interfaces or work with micro fluidics community. These are all bringing what we call convergent science, bringing together areas of science that are traditionally not been interacting with each other and putting them together to solve problems.

Stephen Ibaraki

The interesting work about micro fluidics gets into organ on a chip technology?

Ali Khademhosseini

Right. There’s a lot of opportunity in those concepts. I think it’s starting to get out there, but definitely the sky’s the limit. For example, when it comes down to testing cosmetics, many places, including the EU are starting to ban animal use for cosmetic testing. Being able to create skin models that can be used for testing, whether you know, a specific cosmetic is going to be having issues with the skin, etc. Or using these things in pharma. Right now, again, pharma still uses that same kind of platforms and technologies that they’ve developed 50 years ago, to do their drug development and drug discovery process. So being able to apply more of these organs on a chip systems and being able to use it in real world applications, I think it’s starting to happen, but there’s definitely a lot more that can happen as well.

Stephen Ibaraki

You’re growing cells, right? You’re taking stem cells and coaxing them; you’re building some kind of structure or scaffolding perhaps of some sort. You get into these biomaterials’ science that you’re an expert at, you’re talking about 3D printing, and then this leads to even things like new kinds of proteins rather than having to harvest animals, right, can you talk more about that work?

Ali Khademhosseini

Definitely. I had been a tissue engineer for a long time…cells from cow and fish and other things, and be able to grow those cells in things that kind of look like beer brewing factories, these are bio reactors in which you have cells, and you can grow the cells and then afterwards, collect the cells and process them into meats of different sorts… And I think it’s one of those really game changing opportunities that we have as humanity right now.

Stephen Ibaraki

<I ask about growing cells into organoids and their practical applications>

Ali Khademhosseini

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So definitely, there’s a lot of opportunities creating organoids, which are basically, aggregates of cells, which are typically driven from primitive cells like stem cells. And what people have seen is that, as you start creating these organoids, they actually mimic a lot of the aspects of a developing tissue. So, these would be the way different cells interact with each other, the way different tissues are formed… these organoids have become one of the really important things in biology these days. One of the faculty that we recently hired at the Institute in the US recently came to us from Duke University, his name is Xiling Shen, and what he’s done is quite incredible, because he actually takes tumor cells and forms them into these organoids…been able to then test different drugs, different chemotherapeutics on these tumor cells, and then see which drug works on which person’s tumor. And they actually have done clinical trials and have demonstrated that this works and how now have a company that recently raised its series A to be able to translate these kinds of technologies into a real-world application. The organoid technologies are, I think, really the cutting edge of where we are in biology and being able to create models of human physiology.

<From TIBI May newsletter …These challenges have been addressed in a multi-organizational collaborative effort, which included scientists from the Terasaki Institute for Biomedical Innovation (TIBI) and Duke University, led by TIBI’s chief scientific officer and professor, Dr. Xiling Shen. As outlined in their recent publication in Cell Stem Cell, the team developed a droplet-based microfluidic technology to produce micro-organospheres (MOS) from cancer patient biopsies within an hour. Patient tumor, immune, and connective tissue cells quickly form miniature tumors that retain the original microenvironment within thousands of these MOS, which can be used for testing many drug conditions. Tests on MOS of various cancerous origins demonstrated the retention of the cells’ genetic profiles, as well as gene and immunosuppressive marker expression of the original tumor tissues. Initial tests using MOS from a small cohort of metastatic colorectal cancer patients were screened against a panel of therapeutic drug candidates. When the drug sensitivity results were compared against actual clinical treatment outcomes, there was almost perfect correlation. What’s more, the MOS could be generated from small numbers of cells, as typically collected from biopsies, and the whole MOS generation and drug screening process took less than two weeks.>

Stephen Ibaraki

<I ask for forecasts and upcoming projects> What are some of the big ideas that you want to tackle?

Ali Khademhosseini

Some of the things that we have coming, which are I think very interesting, is new ways of delivering drugs and different types of molecules like vaccines or other things through non-invasive or very minimally invasive technologies. So, for example, we’ve been working with a bunch of our collaborators on being able to create patches that have very, very tiny needles that you wouldn’t even be able to feel and through these tiny needles, you can actually deliver drugs, or be able to actually extract solutions, and be able to sample what’s inside an individual, you know, potentially even in real time, and one of the things that we’re doing is that we’re creating these arrays of micro needles to not only deliver compounds like vaccines in a way that you can just apply yourself, but also be able to integrate these platforms with wearables and sensors and electronic sensors to be able to, in real time, monitor what’s happening inside individuals. So, one of the things that I think it’s really interesting is that the technology, again, is converging. There’s a lot of work that has been done in taking normal electronics, being able to put them on flexible substrates, substrates that are stretchable, and at the same time, be able to manufacture these at low enough prices, and with the integrated batteries and all that stuff. So that creating wearables, that can actually interact with a person’s body; I think it’s becoming more and more realistic. And these interactions don’t need to be just like something like an Apple Watch. That is, it’s passive. So, you just look at something like that’s basically you know, your motion or just kind of sending light to the tissue. But these could be actually, at the molecular level, you can have real interactions as well. So be able to sense disease, in real time, are the kinds of things that we’re interested in doing in the future.

Stephen Ibaraki

And I guess if you combine that with computational systems that are out the cloud, integrate with AI machine learning systems, then you could anticipate through machine learning models, some of the early markers that are, in essence, biomarkers of upcoming issues or opportunities for better health, right? I could see a lot of possibilities, even integrating this with the metaverse?

Ali Khademhosseini

I haven’t really talked about that integration much. But in virtually everything that we do, there is this opportunity to really use data sciences. For example, we’ve been talking about creating models of human physiology. But what really is going to happen is that we’re going to create models that predict individuals behavior, but we’re going to link them to the genome of that person, and be able to do that over and over with lots of different people to be able to create an atlas of how the genotype of the person and basically the proteins and other types of molecules that are present in an individual cell can correlate with a particular outcome. And all of this, again, will involve a lot of data collection, machine learning AI algorithms that can actually make these kinds of interactions happen. So in the future, if we’re very good, we will actually put ourselves out of business because we will be able to, not have to do the kinds of experiments that I’m talking about where you take cells, and you see which drug works on which persons tumor, you can actually do all of these in a computer by being able to look at the person’s genetic profile, and say, based on what we understand this drug would work best. So that’s the kind of stuff that we think we can enable, by doing a lot of things that we talked about, again; it’s convergence, data science, plus …

Stephen Ibaraki

You know, it’s interesting. I know personally, within my network, they have some of the largest food companies in the world. They definitely would be interested in your work; replicas of real meat products, and, of course, addresses climate and energy, and so on. Then you have this idea of micro needles and the ability to do real time sampling and combine that with some kind of computational framework. I also happen to know the largest textile manufacturers in the world, and they’re looking at all of this work. Are there some other areas that you’re going to hope to achieve by let’s say, 2025?

Ali Khademhosseini

We definitely have a few different projects that are, I think, are really exciting. One of the ones that I’m fairly excited about is some of our work in trying to create basically neurological models; these could be models that mimic blood brain barrier or actually the human brain and be able to really dive in and try to understand how different types of things that we do disturb those systems. So, one of the things we know with our current ability to really make small tissue with microscale resolution, being able to put the right cells in the right place, and create vasculature and be able to control that we can actually do the kind of experiments that you can never do in an animal model. Allowed us to actually form really interesting partnerships as well, with the kinds of companies that have really innovative devices, these could be companies that either make really powerful imaging systems, or, ways in which they deliver drugs, and then we can test these in our platforms as well. I think this neurological aspect, being able to understand the human brain outside of the body is something that’s super fascinating. And these types of models, I’m hoping that we’re going to make a lot of advances in them in the next two, three years.

Stephen Ibaraki

And I guess it goes back to your tissue work and your cell work, and then you can create realistic models and real time, living models of the brain.

Ali Khademhosseini

I’ll tell you another thing, which is a little bit different. I’ve been talking a lot about kind of things that are tissues. But I haven’t really talked about a whole different category, which is materials, basically therapeutic materials. We are actually have been working a lot in that space as well. I think actually making materials for medical applications. That turnaround to getting real world application is much less, whereas when you have cells and things you really have long regulatory approval. If you have a material that does something — much faster turnaround. We’ve been interested in a few different areas of just using materials and solving medical problems. For example, when there are defects in the blood vessels like aneurysms or what they call VMs <venous malformations>, which are malformations in the blood vessels. There are very few approaches to solve them. The latest is to be able to kind of go in with a catheter through the blood vessels and maybe try to deploy a catheter, like a coil or something like that in those spaces; we fundamentally think that you can actually do a lot more. We’ve been developing new classes of materials that you can put in those regions; you can deliver these materials through the catheter, they’re like, to somebody like a toothpaste, you can kind of deliver them. But once they go in the right area, then they can have functionality. So, for example, if you put these materials inside the blood vessels of tumors, then they can actually release drugs and be able to destroy the tumor; if you put them in an area like an aneurysm, then they not only provide mechanical strength to prevent that aneurysm <rupture and cause internal bleeding> but they also can induce regeneration of the blood vessel and healing. These are smart materials that you can deliver inside the body and be able to use the body’s innate ability to do things to basically regenerate or induce, you know, tumor cell or things like that, with that, and you can actually integrate these sorts of materials with immune therapies. So being able to have cells in the body work with the materials to provide a specific activity, like go after tumor cells, etc. So that’s a whole different area of work that we do, which is fundamentally I think, is also very impactful.

Stephen Ibaraki

In this material science, then you find the greatest sort of creative inspiration as a catalyst from things that are in nature, and then you’re adapting it, synthesizing, and then creating sort of nano versions of it that you can inject into the body in some way.

Ali Khademhosseini

Yeah, that’s a really interesting question. Definitely. Bioinspiration is something that’s been done a lot in this area. When we look at a lot of different things, we really think about how does nature do it? For example, some of the things we’re trying to do is make materials that are really sticky. And these materials, we’d like them to be used as surgical sealants, or adhesives in different applications. When you look at and you want them to work in spaces that are wet, like have blood around it, or things like that, so it’s not trivial; the normal kinds of materials that you use to stick two pieces of plastic together don’t really work in those environments. When you look at nature, for example, what a mussel does to stick to the bottom of the sailboat; they actually have unique types of molecules in there, which are molecules, like polydopamine, or other types of molecules, and these, being able to get those inspirations and say, oh, that kind of molecule works in nature in this application, and then being able to engineer it in some of the materials that we’re developing is exactly the kind of stuff that’s done. So, you know, there’s a lot of bioinspired work that me and others in the field are doing.

<We talk about optogenetics and recommendations to the audience. Ali talks about a new model for innovation and this sets up the snapshot from the Maurizio interview who focuses on innovation.>

TIBI CHIEF INNOVATION OFFICER (CIO) MAURIZIO VECCHIONE

Maurizio Vecchione is also jointly serving as the CEO of Washington Global Health Alliance, a non-profit organization that plays a pivotal role in fostering collaboration among leading global health institutions. From 2014 until 2020, he was the executive vice president for Global Good and Research at Intellectual Ventures (IV) where he oversaw collaboration with Bill Gates to invent and deploy technology to address some of humanity’s most daunting challenges. He simultaneously managed the Global Good Fund, the research programs of the Intellectual Ventures Laboratory and the Institute for Disease Modeling. He has been a pioneer of the use of Artificial Intelligence in medical applications, including being involved in breakthroughs in cervical cancer screening through machine learning as well as automatic interpretation of ultrasound images via AI. He serves on the Leadership Board of the University of Washington Department of Global Health and the Advisory Board of the UCLA Ronald Reagan Medical Center; from time to time an advisor to the US Government, the EU and multilateral organizations such as WHO and UNICEF in matters of innovation and population health. Throughout his career, Maurizio has blended scientific research and innovation with impact investing delivering a double bottom lines of investor return and social impact.

Stephen Ibaraki

What are inflection points that guided your journey?

Maurizio Vecchione

I started on my journey to innovation; the way most people I think, that are involved in innovation do, which is I started building companies — a successful serial entrepreneur in mostly tech, but then branching into the biomedical space, both on the biotech side and on the medical device side. In that process, I began to learn, the nuances that are associated with academic research were often the innovation starts, and the breakthroughs that are surrounding both the academic as well as the government funded activities to speak of the US, but there’s parallels elsewhere in the world, and the corporate priorities of returning to shareholders, which often can be not entirely aligned to the economic priorities. I started asking the question, how do we align pure research and academic research to the needs of the private sector, to really sort of drive the scale up of discoveries and technologies and really the product in ways that are compatible? And then for me, the sort of inflection point was really when Bill Gates called me to ask a similar question…My takeaway was that when you’re really thinking about using science and technology to solve problems, especially really large problems, global problems, planetary scale problems, whether it’s human health or climate change, or other things like that, if you don’t pass through the private sector, in other words, if you don’t build companies with the key ingredients, it’s very difficult for a purely academic, often grant funded effort to provide meaningful solutions. So, this idea that you have researchers addressing some of these problems, perhaps even having big innovation, and those innovations are ready to go; they become product at scale, and ultimately solve the problem. That’s a bit naive. The reality really is that there is a step in between; that translates that academic innovation into products and companies that then have the capacity and the funding to make them into global impacts. So, this idea that impact is really ultimately the thing that moves us from academic research into the product world, and ultimately into the global scale of this product world was really something that I got to experiment with during the Gates years. And at Global Good, which was the fund we created. To do this within the Gates ecosystem; we got to experiment with how do you affect the sort of translational work? And there were a number of lessons that maybe we’ll talk about in a minute. But to answer your initial question, as I exited, Global Good, and the Gates ecosystem, I was looking for a place that could apply the learned lessons of that sort of translational innovation. And, the approach of going from academic research, to corporate product development. And I found it in the Terasaki Institute <TIBI>, which really from its inception, the reason why it’s called the Terasaki Institute is because Paul Terasaki, a professor at UCLA, back in the 60s, and 70s, and 80s, pioneered diagnostic technologies that ultimately ushered the modern day of organ transplantation. And in order to scale those technologies up, he took the courageous step of starting a company. And that company became very successful for the exact reasons that I said in a minute ago, and ultimately became part of the Thermo Fisher component. As a result, he and the family were in a position to invest very significant funds in a foundation that operates the Institute, and ultimately, is committed to repeating that translational success that Paul himself has done across a variety of other really impactful problem spaces. And, so today, I get to design, not the science part, but I get to design how we take the science into that innovation ecosystem that we’re trying to build. And that’s, to me, almost the combination of what has been a lifelong effort of trying to accomplish this.

Stephen Ibaraki

You talk about the science part. And now you’re really focused on that translation innovation part. But I should mention that you were a prodigy and continue to be in science and innovation. You did some remarkable work at a very early age, and you were mentored as a result. And that led to then creating innovation and starting companies and creating commercial products and so on, before Bill approached you…

Maurizio Vecchione

I represent, I think, a group of people that are coming together at the Terasaki Institute, which you could qualify or classify as academic entrepreneurs, we all are scientists first. But understand that for the science to actually have an impact, you can’t just limit it to, getting the cover of Nature, or other scientific journals. That’s an important ingredient in academic research, publishing it. But if you’re really serious about, taking it all the way to the impact, you can’t stop at the lab experiment, you got to build products and to build products, you need to build companies. And that is the ethos that we are incorporating within the Terasaki community, where if I had to give you a one line, headline of why should scientists work at Terasaki, versus working at 10 other research institutes of excellence, is because we’re probably ideally suited for academic entrepreneurs, if the scientist wants to do science, but also build companies. We are set up to do that. And by the way, I talked about building companies, but that also means partnering with companies. If you think about the ecosystem of biomedical innovation, and you think about the complexities that a lot of companies’ face, to license out of universities and dealing with the patchwork and complexities of IPs, as well creating structures that allow those companies to take risk on new technologies, without necessarily getting into a quagmire of relationship. Part of what we have accomplished, I think is creating a very streamlined, let’s call it tech transfer component that is really designed for our academic entrepreneurs to choose a path of partnership, or company startup that is very business friendly. And that’s language that should be welcomed to anybody in your audience, who is looking to essentially input into the product pipeline. You know, R&D rich innovation.

Stephen Ibaraki

Your language and sort of your narrative, spurs in me these three ideas. You can work on a small problem and have some impact. And it’s not scaled. You can work on a big problem, but typically the same amount of effort. That’s an advantage of a big problem. You have effective solutions. And you have a model where you can scale and commercialize it means that you can have huge impact. So, you’re focusing on the big problem, big impact, and scalable. And then I get to this idea, because I work in science communities as well. In my scientist colleagues, there’s this idea, concept; then they do research and development, and then the difficult part; some translational work or transfer tech. And then you have to commercialize, which is almost impossible for a lot in the science community. And then you have to get usage and adoption, and then you have to scale it. That’s almost impossible for most communities, but not for the Terasaki Institute. So, what I’m hearing from you is, you got impact, you got big, and you can go right across the entire spectrum from idea to scaling, because you’ll take in corporate partners, you have licensing models, that are business friendly; you’ll incubate startups. You have all of that. Let’s delve into that more, because that’s a differentiator from what I’m hearing.

Maurizio Vecchione

That’s right. And I think, to be clear, I’m not suggesting that the Terasaki Institute can literally do the scaling and all those other steps that you’re talking about. But that we are acting as a bridge to the entities in what I would describe as an ecosystem, corporate as well as startups that can then be positioned to scale. I want to start by triggering on a comment you made, which has big problems. And solutions to the big problems are often just as much work as incremental, non-disruptive solutions to small problems. And again, I certainly don’t want to suggest that, that there is no need to do incremental work. And there is not a value to do incremental work. As a matter of fact, I would say most innovation is incremental type of work. They are improving it and lowering the cost, they are making it easier to use and it builds and over time, you might even get solutions to big problems. But we like to think of ourselves as a moonshot factory. We like to think of ourselves, as really driving to us, and really bold and courageous problems that often are difficult for a company to tackle upfront. And can be tackled in the context of academic research, but then you’re missing the whole translational capability that actually turns it into something practical. If you go to our website, and you see our mission statement; we have these words that suggest that part of what our metric for success is the reduction of the science into practical solutions. And why big problems? Well, big problems, if you can truly solve them, will almost without fail, produce the Unicorns of tomorrow. This is a lesson I actually learned firsthand, working with Bill, that, there is a connection between high impact and ultimately high shareholder return and scalability and performance and this is a place where business profits and the metrics associated with that. And social responsibility and impact are actually converging. What I’m suggesting to you is that the choice of chasing big problems and high impact is more than a socially responsible and noble thing to do. It’s also a hardcore business strategy to develop disruptive Unicorns of tomorrow, that have the potential to unleash the next trillion-dollar companies. We believe that, and that is why we have this really strong appetite to chase really hard problems. It’s also because we are a hybrid, and we straddle the nonprofit academic research and then ultimately, the corporate and corporate world, we are uniquely set up to take some of these hard problems that are essentially too early or too risky, for classic business to take on and incubate them for lack of better words inside the Institute, where we’re able to use non-diluted capital, such as grant funding, such as endowment funding, and other things to essentially de-risk the proposition before we have to ask investors to put in their money. And by the time we’re ready to do a spin out or a corporate partnership, what we have is solutions to big problems that have actually be reasonably de-risked and now will become a profile that makes them investable from a private capital perspective. And I think that is a really unique model. When you’re tech transferring something from a university, that’s not necessarily the risk. That is still mostly lab experiment. And it is generally the investors or the companies that partner with that institution that need to put up the de-risking capital, which is not just dollars, sometimes it’s time. If you think about the regulatory risk and the timelines that are associated with some of these projects, that’s a significant risk. And it’s I think, the reason why tech transfer from universities, the old-fashioned way typically has been that successful; has been successful, but not that successful. Well, you know, what this idea of having, essentially an incubation period that is funded with non-diluted of capital, in a place that has access to state of the art equipment, technologies, laboratories, as well as scientists, and more importantly, can operate in an interdisciplinary way so that you can begin the steps that are necessary to take a lab experiment into a product that often require engineering, require sample and prototype manufacturing, require things that are not typically part of an academic laboratory—is an important ingredient.

Stephen Ibaraki

Your model then is a return on value. It’s not just the financial return. It’s a return on value that is a measurable value across all of the stakeholders, and global or planetary in scale because of the problems that you’re solving. And as you mentioned, you’re mitigating risk. Throughout this whole process. It’s just the way your model is set up. And it’s unique — the leading researchers are doing in this entire journey; your capability to bring in the right partners, because you have a relationship network globally. And then being able to scale it to those relationship networks, to the different models, and even the incubation capability that you have. Marriage between private sector and public sector granting and funding, both from the government but also from your foundation, and also to your partners. It is a confluence, a convergence of all the different parties for a greater good and ultimately sustainable with big returns as well if you just think on the financial side. You’re so entire model oriented; it’s the entire ecosystem and system wide. Then it’s a prime vehicle for the innovation you talk about and to continue work that you did before. Can you talk about some of the key projects that you’re really excited about in the near term, let’s say this year, next year, and then I’ll do a follow up question and the more the longer term?

Maurizio Vecchione

Sure. We like to think about the technologies that we’re developing as being platforms. When we make a commitment to one of these platforms, we see the opportunities to use them as a sort of Lego blocks for solution-earing across multiple problem spaces. I’ll give you an example. We recently made some significant progress in the future of food. We can’t quite announce the specifics of it yet. But let’s just say we have breakthroughs in the broad subject of cellular agriculture, that promise to create a more sustainable way of producing protein that will ultimately be potentially a real solution to how are we going to feed 11 billion people on this planet, as we’re heading into it. Now, that came out. That was not though, the problem that we started out solving initially. When we started solving for initially was, are there technologies that we can bring to bear that are the convergence of things like, modern omics, including proteomics, metabolomics, etc. But also tissue engineering, and then advance, cell and cell biology. And when you converge all that, what you end up having is a platform that can build tissue, in the lab; tissue for various applications, and we started out doing tissue engineering for medical applications, and pretty soon realized that we can also create tissue of the type that you would eat. And that was the transition into the food problem. Part of the trick, I think, of the strategy at the Institute is to orchestrate our science teams around these platforms. What was really exciting, because we’re relatively young and new, is certainly as in the incarnation that I’ve described to you, which is really sort of the successor to Paul Terasaki, his original vision, where he really was focused on the transplantation problem. Now we’re sort of opening up to these broader problems. And as we think about these broader problems, we think there are a group of maybe five critical platforms that work in concert to provide meaningful differentiated solutions to, these broad problems and this platform, what we’re building right now, one of them, I already mentioned that to you is the whole subject of tissue engineering. And, if any of your viewers ever saw the relatively dark, so we’ll use this as an example of application, TV show Westworld, where essentially robots were built using tissue engineering, and there was 3D bioprinting involved. Well, I don’t want to say we can do that in the lab; we’re not suddenly building humans in the lab. But there are many of the ingredients. That type of technology and as you think about regenerative medicine, as you think about being able to 3D print, things that will go into your body and they are biocompatible, and they mimic original tissue, there’s all sorts of medical applications that are very disruptive, that are emerging from that area. And by the way, 3D bioprinting is actually a critical expertise of the Institute, and some of the scientists that could play claim of being the most cited authors in the world, in the 3D bioprinting area actually work for the Institute. You know, some of them, specifically Dr. Khademhosseini is considered the 3D bioprinting guru. The second platform, which is related is what has come to be known as organs on a chip. We prefer to use the word physiological models on a chip. So, as you think about applying again, the omics and cell biology, and all of these other factors, plus the ability to actually create living tissue, that is a bio mimic of the real thing. Then you could think about creating these physiological models so that you can actually use them for drug development and drug testing. And, if you think about the sort of conundrum of modern-day drug discovery, where essentially, we’ve never spent as much money on drug discovery, and we’ve never had fewer drugs that make it through the end of the gauntlet in terms of pipeline, it shows you that the way we’re approaching drug discovery is not only inefficient, but possibly starting to be a diminishing return. And in part it is because we’re using high throughput processes that are basically saying, let’s take a bunch of molecules, let’s throw them at an indication. And in animal models first, and then later in human models, see if something sticks. Well, that’s the biotech equivalent of the proverbial paradox of having monkeys randomly typing on typewriters and if you wait long enough, they’ll eventually type a novel. Okay, statistically, that’s true. But the timelines are very long. And we’re basically doing that for drug discovery. So, part of the vision here is if you had physiological models that truly mimic the performance of the human organ or tissue, or system of organs, then you can use them as a real tool, with potentially much higher efficiency than an animal model for drug discovery. And you can start applying modern day mechanistic understanding of how drugs should be constructed to create highly targeted, highly personalized application. We think that this is a revolution in drug discovery and drug development. And we have been very successful at building very complex organs that are critical for the success of drugs, for example, the liver. And we’ve been so successful using and applying some of our tissue engineering, that we can take complex organs or complex tissues, and they can operate like the real thing. For example, we have cardiac models, where the organs on a chip actually begins to pulsate, the way the real heart does, and we’re now working on, for example, neural models where we have brains on a chip, and more importantly, we’re able to start building disease on a chip. So, you know, for example, we have an ongoing program for breast cancer on a chip, including some of the breast cancers that are most difficult, …, we’re starting to explore metastasis on a chip.… And these are just examples of the kinds of things you can do. And by the way, when you have these different organs, you can also integrate them. And so you can study, for example, metabolic factors, and toxicity in the liver, while you are also looking at cardiotoxicity, and a target that may be for cardiovascular disease. So that’s our second platform, it has me super excited in what the potential is. And we’re starting to see for the first time the translation of these technologies into real life drug discovery. So, we have a lot of collaboration starting to happen with the biopharma sector, where they’re actually putting this into the discovery pipeline. And that tells you that these models are becoming sophisticated enough to begin to really, not only approach animal studies, but in some cases surpass animal studies in terms of predictive value. The third area that has me very excited is biomaterials. These are materials that are rooted in biology. Often, they’re highly biocompatible. So, you can put them in the body and that have what I would call magic properties, because they are smart. And so, for example, they can react to the chemistry in the body. They can react to physical conditions, like … materials that become hard under certain conditions, but they’re liquid when you first inject them so they can travel the body and react to specific positions and for example embolize, a vessel without the need for surgery. And those are, I think, super exciting and frankly, are going to be the future, of many devices. Biomaterials also allow you to create constructs, like moving away from injections into, say micro needles. And those micro needles can be smart. So, they can detect, for example, your blood sugar, and trigger the delivery of insulin on demand automatically, as a wearable. There’s a whole class of whatever, say, next generation medical devices that these new biomaterials could do that could affect drug delivery, that could affect sort of responses, and treatments, in a very sort of personalized and smart manner. So maybe I’ll stop there, but I think those are some of the revolutions that we feel are occurring that we’re writing. And ultimately, the application really spans what I would consider planetary health on one side, the food example would be an example of that. And on the other side, of course, human health with a specific emphasis of personalized medicine, and, you know, personalized medicine has been misunderstood, I think, by the general public; people think of it as an elitist thing, where I’m going to make my own drug, because I can afford it. Okay, for whatever disease I have, but that’s not really it. Personalized medicine really is a way to target disease, at the stage, and genetic composition, that it’s at. So, it’s not about making special drugs for the elite. It’s about, improving the mechanism of action of, and ultimately, the efficacy of treatments and devices…much more compelling treatments. So, to me, the reason why personalized medicine is important, is because as disease gets more complex, we’re going to have to get very targeted in the delivery, in what our drugs and devices do in order to be effective…when you think about cancer therapies, for example, it’s all about targeting, and it’s all about stage of the cancer, and it’s all about the heterogeneity of the cancer, as it moves across its phases, and its patients. And if you’re not able to morph what you’re doing accordingly, you’re going to be ineffective.

Maurizio Vecchione

<Maurizio gives more details on the low translation of drugs tested on animals but not effective with humans. He talks about organoids accelerating the pipeline process. We discuss microfluidic technology; and using micro needles for drug delivery>

The other thing that micro needles allow you to do. You can think of them as sponges that penetrate deep enough in the skin, but not deep enough to break blood. That means it’s an ideal collection item for matrices in the body that haven’t been studied before, such as interest tissue fluid. Interstitial fluid is fluid in between the cells; think of it that way. And there is a fair amount of research evidence that shows that it’s a better marker for many areas, many diagnostic applications, it’s a better matrix, because it doesn’t have all the other stuff that you find in blood or urine, or other matrices. But no one has had an effective way to collect it. And we think of microneedle using hydrogel materials are actually going to be the first way to collect in relatively large volume interstitial fluid, which opens up a whole new area of diagnostic capabilities, probably centering on proteomics that hasn’t been exploited before. And I think these are also very short-term projects for us.

Maurizio Vecchione

<I ask about ways to partner. We discuss engagements with institutions, corporations, and incubation of startups.>

Stephen Ibaraki

<I ask for closing comments>

Maurizio Vecchione

I think one thought I would want to leave your audience is that, we keep talking about digital revolution and the role of digital in changing everything. And that is very true. And it’s also very true that we’ve begun, we’ve only started scratching, but there is a system biology revolution that is powering the digital revolution. And system biology is going to transform human life and human condition fairly significantly. And when you combine the digital revolution, including machine learning, and all that, with our system biology revolution, honestly, I believe the trillion-dollar companies of tomorrow are going to come out of that. And, I think Terasaki brings the system biology component to that digital revolution. And, there’s lots of opportunities, I think, to accelerate working together. So, my key message is, don’t think that everything good has been invented. And we are just scratching the surface of where we’re heading with a certain system biology revolution. But to do it, it takes a highly interdisciplinary approach. And it takes a real close connection with those that are doing pure science, to those that are doing applied science and ultimately, private sector work. And I think, institutes like Terasaki are pioneering the model for that.

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