Topic: Experts from the the American Society of Mechanical Engineers (ASME) will discuss and take questions on how engineers are helping medical professionals in the fight against COVID-19 and other urgent medical needs. Topics include cryopreservation, fluid mechanics and transfer, Targeted delivery of therapeutics via ultrasound (to infections and tumors), fast-tracking clinical trials through modeling and simulation (this was done with the COVID vaccine as noted in this study published in The Lancet), and nanobot tech.
Journalists and editors are invited to attend this live virtual event and ask questions either on camera or we can relay your questions to the panelists. Register to attend and receive the on-demand recording after the session is concluded.
- Christine Reilley - Senior Director of Strategy and Innovation for the Technology Advancement and Business Development (TABD) unit of the American Society of Mechanical Engineers (ASME)
- Giovanni Traverso, Ph.D. - Assistant Professor in the Department of Mechanical Engineering at the Massachusetts Institute of Technology and in the Division of Gastroenterology, Brigham and Women’s Hospital (BWH), Harvard Medical School
- Arlen Ward, Ph.D., PE - Modeling and Simulation Principal, System Insight Engineering, LLC
- David Odde, Ph.D. - Professor of Biomedical Engineering at the University of Minnesota
When: March 11, 3PM-4PM ET
Where: Newswise Live Zoom Room
This live event will also be recorded and transcribed for use by media and communicators after it is concluded. All registered participants will receive a copy of the transcript, so even if you can't make this event, we recommend you register.
Thom: Hello and welcome to this Newswise live expert panel. We have with us today 4 panelists connected to the American society for mechanical engineers and they are going to be discussing how computer modeling and simulation are taking part in advancing medical discovery. The panelists have a lot of examples to share about things like fast tracking vaccines as well as medical devices and the response to the Covid pandemic, so they are going to tell us a little bit about ways that engineers are able to work with health and science researchers to figure out better solutions. I want to introduce first, Christine Reilly, she is the senior director of Strategy and Innovation for the technology advancement and business development unit at the American Society for Mechanical Engineers. Christine thanks so much for joining us, and I want to give you the opportunity to kind of set the framework for our discussion and tell us as we have been discussing as we prepared for today. What does mechanical engineering have to do with modeling and simulation in medical research? I think this is something that most of the people are not familiar with that engineers play a big part in medicine.
Christine: So mechanical engineers use modeling and simulation typically to analyze physical phenomena like fluid flow, heat transfer or the impact of stresses on different material. So, this is used across many industries, but specifically with respect to medical devices, mechanical engineers can use these techniques to for example model blood flow through a heart valve or to understand how different types of stresses can affect materials that are within for example an artificial knee replacement. So, the examples are new ones, but those are just two.
Thom: So how engineers participate in this, I understand they often collaborate with health care professionals or medical researchers - what are some of the processes that they can get involved in and speed up getting a new treatment to the clinic from the lab for example or a medical device from an early prototype to something that can be used in those kinds of settings? What are those kinds of processes like?
Christine: So, modeling and simulation can be applied across the entire life cycle of the development of the product, like you mentioned, in prototyping, if you are in physical prototyping, that could take certain amount of time, but by applying modeling and simulation again to go back to our example of understanding how stresses impact certain materials by using computational modeling we can do that much more quickly and iterate on a design much more quickly. If you want to move that all the way to the end of the life cycle when one is getting prepared to submit a new device for example to a regulatory body such as the FDA, one can use models and simulations to demonstrate something like say the inefficacy noting that this won’t replace for example something like a human clinical trial, but will supplement that data, in fact ASME, the American Society of Mechanical Engineers have produced a document that in concert with the FDA, to help engineers demonstrate credibility in their models when communicating with the regulatory bodies such as the FDA.
Thom: So, I understand there are a lot of ways that engineers have taken part in the unprecedented effort to get the Covid vaccines out and testing Covid treatments, so what are some of those lessons in this past year with these unprecedented efforts, that we can take away those lessons, apply them to future projects and use the same sort of urgency that engineers can help to supply some of that possibility?
Christine: Absolutely, I think just the fact that it’s been demonstrated succeed fully will inspire more confidence in these different types of processes and the execution of these different types of projects, I think we will be seeing a lot more of that on the road, and we will also see greater collaboration between engineers, medical professionals and those at pharmaceutical companies and devices companies and we will also see an uptick in the application of data analytics across the board.
Thom: ASME has some upcoming virtual meetings and workshops, is there anything you want to tell us about some of those events coming up and some information that may be available coming out of those?
Christine: Sure, so April 14th and 15th ASME will be hosting an event called “visualized med” where we will explore further all of these concepts around use of modeling and simulation in medical application whether its medical devices, pharmaceuticals or even clinical applications such as treatment planning, or even the use of something we’re calling digital dentistry, so again the application of modeling and simulation is far and wide. Before the event on April 13th, we are holding Cryo preservation and supply chain workshop. Mechanical engineers focus very heavily on heat transfer and this is had a significant effect of course on supply chain, cold storage vaccine, but we are also seeing that cryo preservation also applies to cells tissues and storage of organs, so we are looking again at the broader view of Cryo preservation and broader medical applications, and finally on April 16th we are having a pharmaceutical road mapping workshop, because we are also taking a deeper dive in to understanding how modeling and simulation can be used to further the development of pharmaceuticals, so it’s going to be an exciting week.
Thom: Yes, it sounds like it and to kind of get in to some more of the topics and detail I want to introduce our next panelist, Dr. Giovanni Traverso, he is an assistant professor in the department of mechanical engineering at the Massachusetts Institute of Technology and in the division of gastroenterology at Brigham Women’s Hospital at Harvard Medical School, Dr. Traverso, thank you so much for joining us.
Giovanni: Thank you so much, Thom and thank you Christine and the ASME team for allowing me to join the panel today.
Thom: Absolutely, tell us some examples to put into more concrete terms what some of the concepts that Christine set out for us about modeling, simulation and the collaboration between health care professionals, researchers and engineers, that are better able to help with these kinds of breakthroughs.
Giovanni: I would be happy to, and I just have a couple of slides, a picture or video is worth a thousand or ten thousand words for that matter, so let me share with you some of the work and this is work that is supported by the NIH and Nova Nordisk and part also by the Gates foundation. And really it’s taken place now within the past decade with significant contribution from the folks here that you see, graduate students - Carl Schoelhammer and Alex Abramson from MIT, Ester Caffarel scientist previously at MIT and Ulrik Rahbek from Novo Nordisk. So let me just walk you through this journey and as you mentioned, I wear a couple of different hats and what I would like to do is just share with you how we sort of came to some of the solutions to some of these challenges bringing together clinical medicine with engineering with the modelling aspects really to bear in a major challenge and let me start with 2 clinical cases, and these are cases - patients that I looked after, over 10 years ago now, that really helped motivate a lot of work at this area, so this is a case I will never forget and that I was a fellow at gastroenterology at Mass General at the time, and I was called down on a Friday to the emergency department to see a gentleman who had ingested shards of glass, and it was a witness event, these shards of glass were under 2 centimeters in sort of their maximum dimension and I went down to the emergency department and I purged this gentleman I see that he has a half-eaten sandwich on one hand and on the other hand - he was an inmate at a local prison, he was handcuffed, but he had eaten half his sandwich and I examined him and he seemed okay, but I shared with him and the team there -that wasn’t much from the GI perspective, the gastroenterology perspective, from the procedure side of things that we would be able to do, and we observed this gentleman, this to me was an extremely instructive case with respect to the capacity of the GI tract to tolerate sharp objects, and with this gentleman we observed him over the weekend and these shards of glass which we could actually see on x-ray, passed, and they passed without any harm and this was really remarkable to me, and really motivated me to look at the literature and subsequently present in rounds a series of cases where folks had ingested sharp objects. And what’s interesting is, below the threshold of 270 there is in general- the GI track will be fine, which is really remarkable.
The second case is really a much more common case that we tend to see as gastroenterologists, in its someone had taken Ibuprofen, I am sure that many have taken Ibuprofen, it’s a wonderful drug, I take it if my back is sore, my knees are sore after running or what have you, but this lady had been taken it because of joint pain, and she had been taking quite a bit of it, and she presented to the emergency department complaining of light headedness, her stools had changed color, she had belly pain, and this constellation of symptoms and signs really are suggestive to us of ulcer. And we actually did an endoscopy and we saw a bleeding ulcer, and the way that we treat it, by injecting the ulcer with epinephrine, with adrenaline, and the reason we do that is the drug induces the blood vessels to contract, so the blood stops coming out, and allows us to then get a clean view and then intervene whether it would be with clips or cautery. What’s really remarkable, as soon as we give the injections, the heart starts racing away and all the alarms start bing bonging behind us in the endoscopy suite, so we know that - even though we are giving it for a local effect, there are clearly systemic effects following that injection.
So, putting these two elements together, we developed a basic concept which was around capsules that give an injection from inside, and this, at the time seemed a little bit outlandish and we tried to de-risk this and we created these prototypes, we did some basic modelling, and some of the basic aspects of the system, and we fed them to pigs, the pigs are fine, there was no injury, and then we injected insulin, actually in different parts of the GI tract. Our vision at the time was - could we create capsules that administer drugs that today require injection?
Now this was really reassuring but there were a lot of key sort of challenges left on the table and these can be broken up into 3 areas.
One is we need a device that could engage the mucosa, could engage the tissue in a predictable way, in a reliable way in everyone.
Number two, we needed that device to autonomously trigger and therefore we needed the material that could sense its environment potentially and then trigger an injection, and number three, we needed to deliver a drug, and we needed to so it in a form factor that was small enough so that the device could transit safely through the GI tract. So, let me just walk you through on how we did this. So how to engage we took a page from the tortoise, and here actually there was a lot of modelling, even though you see a cartoon here, there was a lot of modelling and optimization on the shape, as well as the density distribution of an optimal device that could self-orient and remain in that self-oriented state across a range of stresses, whether it be movement, disturbance with liquid, and we developed prototypes, we tested those systems using high speed photography, we tested them in animals and pigs also and we found that our optimization in the model we had done really translated into effective devices that could self-orient in a reliable way in spite of the animals being moved or for example other stresses being imposed on these systems in the stomach.
Now the next challenge was how do we sense the environment? How do we trigger the device to give an injection? And the cue that we settled on was -humidity. In that we recognized that everybody’s stomach is humid, and so we needed to identify material that could sense that, but at the same time could actually store energy and potentially what we initially thought was to storing energy from a compressed spring, and so we wanted a material that displayed brittle fracture mechanics, so that it could actually hold, essentially retain that energy and then upon exposure in the human environment would have the capacity to control the solution and therefor time that injection event. So, we identified sugar glass, so I want you to think candy cane and not toffee, as that material and actually showed, we modeled how this dissolution occurs, and actually experimentally showed that we could control how these system were triggered so we want to show you here some high-speed photography as an example how we went from that initial concept to initial basic modeling to actually bench top testing that we actually translated in Vivo. And finally the challenge we had was how do we fit enough drug in the system, and so typically insulin and antibodies and other drugs that require injection are generally administered in a liquid format, and so we looked at the challenge in a completely other way and so we honed in on solid formulations and created very small needles that were up to a 100% insulin in this case as the initial description, and we showed that we could deliver the systems, I should say the drugs, using these systems in pigs and achieved levels that are comparable to an injection. We did quite a bit of modeling also on the mechanics as far as interaction with tissue that then we evaluated in stomachs both from pigs but also actually human tissue. So, with that we developed a self-orienting system that’s capable of sensing its environment and then autonomously triggering an injection event. So, let me pause there, and hopefully that gave you a little bit of sense that how we brought in many pieces together to bear in a major challenge.
Thom: Yeah that’s really quite fascinating Dr. Traverso. I just want to remind the audience that you are welcome to ask any questions. Please do chat those to me and will either relay those to the panelists or will call on you to ask them yourself if you like.
Dr. Traverso that has such a series of little puzzles that you had to solve, it’s so fascinating. When it comes to the speed of the development of these kinds of things, production, safety and efficacy, getting them through regulatory processes, things like that, what examples can you share about some of those other aspects of this whole process from concept to actually delivering it to a patient.
Giovanni: Absolutely, so this is one example and this is something that is actually going into humans very soon, and I think what’s critical is its really working as part of the team that pulls together all of these elements including the mechanical aspects as well as the modeling, heavy computational modeling that both informs the potential safety but even earlier the fundamental design as you saw with respect to the self-orienting shape and density distributions. But certainly, we work in many other areas and some of those areas include what I have in the upper left is a schematic, or I should say a drawing from the economist talking about another system we developed where we are now in humans but that started again with a major challenge, that challenge being how to create an orally developed depot system, and there again there were many elements that had to come together from the mechanical side as well as pharmaceutical sciences, biological engineering, clinical sciences. We also do a lot of work in models that look at the GI tract. So, what you see in the middle is some recent development that we have made in modeling the GI tract. So actually using tissue, and this is tissue from pigs, we showed that we could actually approximate what happens in the intestines of humans with near perfect predictive capacity as far as absorption is concerned, and there again in the modeling side, in order to develop a high throughput system, we had to not only do all of the fundamental biology as well as cell contour system development to maintain tissue viable outside of the body and also the actual interface system which required modeling on the compression for example of tissue to ensure individual valves while retaining the viability of the tissue.
We have also done a lot of work on ingestible electronics, really thinking about how we harvest energy to do a number of things, and like many of my colleagues, as part of Covid 19, we really rallied around some fundamental areas to really try and help the community both from the patient, but health care provider sides as well. On multiple fronts and here bottom left what I am showing is a system for ventilator splitting and this is something that we continue to support through a not for profit called Project Corona, [inaudible 19:06] the middle what you see here is some modeling essentially again being applied to masks, we developed some reusable masks, and we focused on using liquid silicone rubber as the main framework for that, recognizing its fit, comfort and also the re-sterilizability. Then more recently we have been working on collaboration with a women’s hospital, the medicine department there as well as Boston Dynamics on interactions with patients and measuring vital signs in contactless ways.
So hopefully that gives you a little bit of a sense of the different activities how we approach them, we are happy to dive into a little bit more details if helpful too.
Thom: Absolutely especially in terms of the aspects of the Covid pandemic that you may have worked on, but I also recall you telling me a little bit about using ultrasound to activate some things as well as some other examples. What else can you share about these that can help to shed light on how engineers really are so crucial to developing these solutions.
Dr. Traverso: Absolutely, so let me just share one of the big challenges that we’ve been addressing now for 10 years and it’s also extremely relevant now, which is how do we make it easier for patients to receive medication and here it's whether its treatments for malaria or HIV, in Africa or here in Boston for example, adherence rates are really sub optimal and this is something that we recognise and that drugs don’t work if people don’t take them, but in spite of that – and this is Everett Koop and a quote that he's very well known for. What we actually see in practice is that around 50% of folks actually take medications, this is in the long-term chronic side as prescribed and it’s a problem that affects really folks around the world.
One of the key observations that we honed in on, was the observation that if we dose drugs more infrequently, that actually what’s been observed – and this is a trail done in Japan, but there are similar trials here in the US as well as Europe, if drugs are dosed more infrequently, actually folks continue to fill their prescriptions and take medications with higher adherence or compliance rates. And so with this in mind, what we settled on is exactly that – the cause of of that I showed earlier, conveyed by the cartoon, which is trying to develop an orally delivered depo system that gives you essentially metered dosing over a prolonged period and essentially that’s what we did, hopefully in a bit of a small fashion than what you see here, and we developed a star like system, so it comes out of a capsule and it sits in your stomach and you see here is a video – one of the early experiments when we started this work in pigs, so there was a tremendous amount of modelling around the design, the mechanical properties which are essential for gastric residency or retention because of the compressive forces of the stomach and so that was really essential in ensuring that these systems would remain and these systems have led to the development of treatments for malaria, for HIV and what I'm showing here was the most recent publication now, about a year and a half ago, a once a month oral contraceptive system but I think here the key being that these systems now enable the delivery of a drug over the course of a month after a single administration of it. These systems are now in humans and those trials are ongoing right now.
I want to be mindful of time – I'm happy to share some of the ultra sound work or –
Thom: We do have time to hear more about this next example too, I think its quite fascinating and shows about really the physics involved in some of this that simply medical researchers alone maybe wouldn’t have come up with without input from engineers.
Dr. Traverso: Yeah happy to and this is work supported by the NIH, and really was led by Carl Schoelhammer, he was a graduate student at MIT and now leads this work in a company called Suono that we cofounded a few years ago, and so let me start with a case again, this is another patient of mine, this is now a young lady that I looked after 11-12 years now, but this was a young woman that was referred to me because she had blood in her stools and also some loose bowel movements and what I diagnosed her with was a condition that affects the end of the colon, referred as ulcerative colitis and we treat it with an anti-inflammatory that’s usually where we start, anti-inflammatory is called Mesalamine and initially we started with a suppository but it was very difficult, it was uncomfortable for her so we switched to enema’s which she tolerated but it was difficult, its harder for patients who are suffering from active diarrhoea to hold the enema in, but it’s really important to hold the enema in and this is one of the things we reviewed in the out patient consults and the reason that its important to hold it in is that the more drug in the tissues, the higher the tissue concentration of the drug or the 5-ASA or the Mesalamine, the lower the disease activity or the inflammation, so there's an inverse correlation between those. And so with that we started to think about systems that might enhance or accelerate delivery of the drug and so one of the – there had been an observation back in the 80’s that had actually been applied in patients – of ultrasound being applied on the skin for the enhancement and delivery of drugs, so we wondered – maybe we can apply it to the GI tract to accelerate the delivery, so what you see here is a concept being shown in an animation and so how this – the vision was could we administer the enema, so we’re not going to change it being administered, but could we enhance that enema by applying ultrasound briefly and what the ultrasound is doing is inducing transient cavitation – so what happens because of the pressure wave, this oscillation of micro bubbles present in the solution and some of those will implode, and when they implode they induce a microjet that helps drive that drug into the tissue. So that was a hypothesis, that was our vision at the time. We started off actually by testing this in pigs and what we saw was really remarkable that we could enhance the amount of drug that was in the tissue by about an order of magnitude and this was extremely motivating and reassuring to us and it seemed that we were at least on the right part – but we really wanted to test this in some kind of meaningful model, and this was actually a really big challenge because there aren’t really good models of colitis and inflammation of the rectum in pigs, and so we had to do this in mice. So the challenge was that now we had to make miniature probes that were stable in mice and that’s exactly what we did. And so there are several models of inflammation, we happened to use one that’s called the DSS model that uses a chemical to induce the inflammation and then we score these animals for inflammation. This is what on the left you see the beautiful architecture of the colon, that’s a cross section of the colon of a mouse, on the right hopefully you can appreciate – there is no architecture. Its gone, and that is the other extreme – that’s severe inflammation. And so with that, what we observed that here being low is good and so what we found is when we administered ultrasound we could really suppress that inflammation from taking hold.
So let me pause there, I want to be mindful of the time – but hopefully gives folks a little bit of a flavour of how we’ve approached and bring together different expertise to really bear on major clinical challenges.
Thom: Thank you so much Dr. Traverso, those are very enlightening examples and quite interesting- tell me real quick before we move on to Dr. Ward – how long once you administer the ultrasound probe- how long did it take to surpass the drug absorption when adding ultrasound?
Dr. Traverso: About a minute. A minute of ultrasound really enhanced the amount of drug by an order of magnitude, it was really dramatic.
Thom: Fascinating, thank you so much for sharing. We’ll go on next and introduce our next panellist – Dr. Ward thank you so much for joining, Dr. Ward is a PhD and PE and he’s the modelling and simulation principal at System Insight Engineering – Dr. Ward thank you so much for being here with us. I wonder if you can tell us and add on to the wonderful examples that Dr. Traverso has told us, ways that modelling and simulation can play role in subjects such as vaccine development and what you’ve seen in terms of best practices that have been used in the fight against Covid and what you’ve learnt through that process.
Dr. Ward: Sure, first of all thanks for the invite and the chance to talk through some of these things. As you mentioned in the very beginning, it’s not that well know the role that engineering and medicine play in concert for a lot of these things, so it’s good to get that out there. I think Dr. Traverso’s examples are a great cross -section of the types of things that we’re talking about across the board, our company focuses a lot on that interaction between energy and tissue’s so that ultrasound example is exactly that sort of thing where we’ve got to learn how to translate between what is needed clinically and how do you then put that into terms of an engineering design for a specific design. And that’s what happened with Covid too – whether you're talking about the cold storage side of things or whether you're talking about the vaccine development itself. There is very specific places where you can attack the virus and I think Dr. Odde is going to talk specifically about that here in a little bit, but there's so many different issues along the way and we don’t really get into – how do you scale the production of something like this inside these pharmaceutical companies, because that’s also part of the problem. Once you come up with a vaccine that works for Covid, all of a sudden you need 300 million of them just for the US and the answer to the question of when you want them is – three days ago – so you’ve got to be able to move fast with a lot of those things and to leverage modelling and simulation – we’re finding throughout a lot of medical applications, whether its on the pharmaceutical side or whether it’s on the device side, the dentistry that Christina mentioned or the orthopaedics, we’ve got all these different places where we’ve got to make that translation between what is needed from a patient standpoint, what do we need for these treatments and then how do we put that in terms of a design of a device or even the variability of that device or how much room do we have for manufacturing tolerances and all of those traditional engineering type of questions that have to really be tied all the way back to what is the impact on the patient?
Thom: What other ways have you seen engineers and you yourself contribute to the speed of that process, really an emphasis on getting things from early research in the lab to clinic ready treatments for patients, things like FDA approval, what kind of processes have you participated in that you can share with us that can help elucidate more about that?
Arlen Ward: Sure, primarily the focus in my career has been on the device side of things, so looking at surgical devices which really always starts from a standpoint of how do you want to affect the patient in the end – whether that’s – like the example that Dr. Traverson had of the injectable – it’s like there's a goal somewhere in that system of what you want to do and every surgery has something like that that is kind of the end point in the efficacy of that treatment. Traditionally to get there you build prototypes, you test them, you test them in pigs, you test them on benchtop tissue and things like that and you learn from those tests and you iterate those tests and build a second-generation prototype which hopefully works a little bit better and you learn a little bit more and you iterate that a few more times. Each one of those takes time and money to create, so at the end of the day when we’ve got something like modelling and simulation where we can start to investigate more of those interactions and more of those relationships earlier in the process before you start building prototypes, you might be able to do more of the optimisation of how that device works, that first round prototypes going to work quite a bit better – maybe you don’t have to iterate quite as many times, that means that you have a shorter time to bring that device to market, you can affect patients earlier because you did bring something to market that maybe wasn’t available to them before that point and for me personally I think one of the biggest impacts there is that lower cost of development of that shortened timeline really frees up the ability to work on diseased states that would normally have been outside of the realm of cost of effectiveness for some of these device companies to take on. So, to be able to use simulation and get these things to market faster, really in the end means that we’re bringing devices to market that are targeted towards patient populations that would normally have been ignored or had to have some sort of compromise in terms of devices and treatments that aren’t targeted for their specific disease state, but are modified from something else that already existed in the market. So using simulation is one of the ways that you can bring a new technology to bare, because it has changed significantly over the last 20-30 years in terms of what we can model – how accurate that looks, the interaction between the different things that are going on from a biological aspect and taking that technology advancement and applying it to the real world problems of how do we make safer and more effective devices on a shorter timeline, really can transform a lot of how medical devices and pharmaceuticals are made today and Covid is a perfect example of that.
Thom: With one of the upcoming events that Christine mentioned earlier, there's going to be a roadmap as part of the discussion and workshop among these experts – in a lot of the examples that we’ve heard about today there's a kind of synergy that develops between engineers and healthcare experts where engineers can provide some input about something that they are experts on and then some feedback from the healthcare professional adds different insight to that and it’s a building process of layering upon layering of that knowledge. What’s been your experience with that phenomenon and how can we leverage that in more cases and make that more widespread?
Arlen Ward: Well I think that roadmap is a direct result of really what’s happened over the last year and it really was a call to everyone in the engineering profession as well as the health sciences to say what are the possibilities for how do we attack this? We know that Covid is a significant impact on society, how do we leverage what we know already today? I mean there were many calls out to – how do you – lets hear your ideas, you were telling us how crazy you think they are, lets prove them out one way or another, there is funding available to look into those, I mean there are collaborations between companies you would have never expected, like between Medtronic and SpaceX or Tesla I guess – we’ve got car manufacturers building parts for ventilators and things like that, that really it was seen as a national emergency and it was – that call to bring all ideas to the table, resulted in the ability of how can we do those interactions between the engineering side of things and the medical space where we know what the end result needs to be, and we just don’t want to lose that. So I think that’s the big part of that roadmap, just to say – we learned a lot over the last year, lets make sure that we capture that, so that going forward a lot of those really great ideas are things that can change the landscape of treatments developed over time, in saving time and saving money, leverage computational volume and simulation as part of that but along the way really bringing more of the understanding from different industries into what we’re doing on the healthcare side.
Thom: Thank you for sharing those insights Dr. Ward – I want to introduce our final panellist here, Dr. David Odde, he’s Professor of Biomedical Engineering at the University of Minnesota, Dr. Odde thank you so much for joining us. Tell us something about your work in infectious disease and the modelling to test potential treatments for Covid, what’s been the track record for these kinds of predictive models that you’ve utilised to have some prediction about the efficacy of drugs like hydroxychloroquine and remdesivir for example?
Dr. Odde: Yeah well like all of us I think a year ago or so we didn’t really know – I just heard of it and I had been working on cancer and developing models for trying to predict cancer outcomes based on the bio physics of how cells migrate but we just felt like we need to figure out how we’re going to treat patients when we don’t really know about this virus. But we did know about the Sars-COV-1 virus that had previously come by and so along with infectious disease experts and immunologists here in Minnesota and other engineers, we started to develop a bio physics based model for the Sars-COV-2 lifecycle based on the data that we could get a hold of at that time, and the goal was to predict where the vulnerabilities are in that lifecycle as it replicates inside a cell and there are lots of drugs that could be tried – you mentioned - a couple that were tried – one not successful, one somewhat successful – hydroxychloroquine and remdesivir and there were literally – there have been hundreds of compounds that have gone into clinical trials around the world, there are thousands of trials – and if you think of the possible combinations of drugs that could be tried, it just blows up exponentially. So how do you make it rational? Modeling and simulation is a way to do that because it can identify the drug treatments that are less likely to be effective and the ones that are more likely to be effective and so in May of last year we put out our first version of this motto and basically started making predictions about things like you said – hydroxychloroquine, we predicted that that was unlikely to be successful based on where it was targeting, whereas Remdesivir based on where it was targeting was more likely to be successful, and we’ve continued to track drugs that have moved forward in to clinical trials to reach a point where you could say something more definitively about being reasonably effective or not, and so far we’re 7 for 7 on those predictions, we’ve predicted two failures including hydroxychloroquine and five successes including Fluvoxamine which you might have seen on 60 minutes last weekend.
Thom: Very interesting, you mentioned doing research on oncology because turning to work on some of these topics related to the pandemic, and in a case like that with drug development for cancer therapy, its often quite a long shot. Having the speed and predictability that your modelling and simulation can provide, seems like that could really focus the efforts and so if you're dealing with a topic like oncology where very, very few drugs are ultimately going to make it all the way through and be proven effective, how does that process of the modeling and simulation really inform how you move forward and what difference even the slight improvement in that process can make?
Dr. Odde: Yeah I was kind of shocked when I started to see this literature about a decade ago, how poor the success rate is in clinical trials in oncology, of the drugs that enter phase I trials, only 5% of them actually make it all the way through to obtain FDA approval, and so the other 95% - there are costs associated with their development that just aren’t recouped and they have to be built into the price of the very few successes, and this makes those that come through kind of rare, infrequent, the development slow and its very costly and then we all bear the cost for that, so if we could even move that up from a 5% success rate to a 10% success rate through modelling and simulation, what an impact that would have. It would by itself potentially cut costs in half and if we could go further and be more iterative in how we develop therapies and predict in advance and start to track failures that are happening early in clinical trials and could pull the plug on them or redirect or move to the next version in the pipeline sooner, this would close the loop – like engineers do, close the loop through iterative design development. Maybe like the Wright Brothers, just keep iterating and you get to something that actually is amazing where we can fly around the world in airplanes.
Thom: Tell us about this upcoming conference that you're going to be participating in, the Road mapping and what you hope to achieve with that and what you'd like for the world to know about how engineers are really going all in on supporting these kinds of medical discoveries.
Dr. Odde: Yeah this is a really exciting new aspect of this meeting and I'm grateful to Christine and ASME for helping to make this possible and am inspired by – what you just heard from Giovanni and Arlen – how in the device area in particular, modelling and simulation has really accelerated those areas, no question. And to the point where now the Food and Drug Administration actually pays attention to these things and its becoming more the norm of the applications for approval, but we’re not seeing that in pharma, biotech applications, in the drug and biologics area, at least not yet. So what we hope - in the sessions that I’ll be chairing in addition to myself, I’ll have speakers from industry and other academics as well, so Allison Claas who is modeller at Novartis and Cambridge, Massachusetts and John Burke who is also in Boston, who is the CEO of Applied Biomath, who will be speaking, so a large company and then a smaller company and then Stacey Finley who’s professor at University of Southern California, also an engineer, will be talking about modelling for cancer. So what we’d like to do then after that is move into this road mapping phase and really try to riff off the successes of the device people and what can we learn there to leverage in pharma biotech space, so that we get from this 95% failure rate to something that’s actually much lower and much less costly. So that’s the goal of the road map is – how do we get there, what are the next steps that we need to take.
Thom: Wonderful, I know everyone will look forward to the results of that road mapping workshop and Christine I understand that there will be some kind of paper issued from that, is there anything else you want to tell us about these upcoming events and help us wrap things up?
Christine Reilley: Sure, yes we will be producing a white paper that really captures what we learn about the road mapping session, so those who register – and I believe the link has been placed in the chat box, will have access to that final outcome, so again our intent is to take those lessons learnt and distribute that broadly through that white paper. Again, as just to recap on what my colleague said on this call is that we really hope to bring together the engineers as well as clinicians and scientists to really take this deeper dive into modelling and simulation and move the needle in advancing whether it’s the production of medical devices or pharmaceuticals, so again that’s April 13th through 16th – we look forward to seeing everyone there.
Thom: Thank you so much Christine and with that we’ll go ahead and wrap things up, thank you so much to everyone who attended and to our panellists Dr. Ward, Dr. Odde, Dr. Traverso and Christine Reilley from ASME, thank you so much for joining us to share more light on the role engineers are playing in so many of these important advances and I feel quite inspired by all this and hope to see more of this happening in the future and I know that I will look at new medicines and new devices with a completely new outlook and I’ll always be wondering – I wonder if some engineers had some role to play in that development and I hope that we can hear more about that, cause the world needs to know and more kids need to go into STEM fields to be able to do these kind of things in the future – so this has been a great opportunity to shed more light on this.
Thank you so much for doing that with us Christine and thank you to the ASME and with that we’ll go ahead and close, so thank you very much everyone.