Bobbi Pritt, M.D. (00:04):

Hello, I'm Dr. Bobbi Pritt, a clinical microbiologist and laboratory leader at Mayo Clinic, and your host for today's episode. Dr. Bill Morice is back again with me to discuss some trending topics. Then Dr. Chris Garcia will join me during the deep dive for a discussion about biopharma diagnostics and how Mayo Clinic Laboratories’ biopharma team is helping advance medicine with collaborators around the world. So Bill, welcome back.

William Morice II, M.D., Ph.D. (00:31):

Hi Bobbi. It's great to be here.

Bobbi Pritt, M.D. (00:33):

Oh, it's always wonderful to have you, Bill. So, we get to talk about what's new and noteworthy in clinical diagnostics, and there's a couple things. I thought we could start first with revisiting PAMA reform and the RESULTS Act that we had touched upon and you had given a really nice discussion on the last time we met. When we last connected, you shared three potential pathways for PAMA reform, and I was curious where things stand now that the government has reopened?

William Morice II, M.D., Ph.D. (01:01):

Yeah, I think the big news between the last time we talked and now is that the anxiety was that, as of January 1 without any congressional action, we would have to comply with PAMA as written, which would involve data reporting going back before the pandemic and all sorts of things. I think for today, probably the most important thing for people to know is that the continuing resolution was passed to reopen the government, that included a provision to delay that implementation of PAMA to the end of January. So, there's an extra 30 days that have been included before we would have to comply. Why is that important? It's important because the agreement when we reopened the government was that the government and Congress would use January to get a number of different healthcare things addressed legislatively that have to happen. There's a whole host of them. We can maybe talk that about that some other time because it is interesting. But this allows the potential passage of the RESULTS Act, which would be a permanent fix to PAMA, to be included in the dialogue around a healthcare package in Congress in January of 2026.

Bobbi Pritt, M.D. (02:11):

Yeah, thanks for that update. It's definitely something we'll keep an eye on and like you said, we'll update everyone on this probably the next couple of times we meet since it's such an important issue for all laboratorians.

William Morice II, M.D., Ph.D. (02:24):

And the only thing I would add is, like I mentioned, I had the opportunity to visit D.C. before this happened. A couple of the people I met with, the representatives, had visited clinical laboratories and that makes a big difference. It's actually a big deal. Because as you can imagine, a lot of people were trying to jam stuff into that bill and the need was to get it passed. So, the fact that we got this included is a really positive sign. But also, people who kinda weighed in and made their voice known about the importance should feel proud of themselves, and don't take your foot off the gas now. It's important that we keep this front and center with your representatives in Congress.

Bobbi Pritt, M.D. (03:02):

Yeah, great point. It's probably good advice to continue having our listeners keep up to date on what's going on. Work with our professional societies. If there's a call for action, see what you can do. I think having our voices out there, like you said, keeping it front and center on our legislators’ minds.

William Morice II, M.D., Ph.D. (03:20):

Absolutely.

Bobbi Pritt, M.D. (03:22):

All right. Well more to come on that. But meanwhile, I also wanted to talk to you about some news about a very sad case of the very first alpha-gal syndrome-related death in an otherwise healthy 47-year-old man who died in his New Jersey home. And we've talked about alpha-gal before, this fatal reaction to non-primate mammalian meat. And he had this fatal anaphylactic reaction, and the testing was actually done here at Mayo Clinic. Unfortunately, it was from the autopsy.

William Morice II, M.D., Ph.D. (03:55):

It's interesting because even as you say that, my mind immediately goes to the first known death attributable to alpha-gal syndrome. Because as you know, you and I talked about this, it was actually one of my residency mates who made me aware of this disorder, and he actually had an anaphylactic reaction. But because he is an anesthesiologist, knew he needed to get into the hospital. Anaphylaxis is a life-threatening condition. That's why people carry an EpiPen for bee stings; that's the kind of thing we're talking about here. I would hazard a guess that alpha-gal syndrome is probably underdiagnosed, which means there probably are patients who may have succumbed to anaphylaxis that just were never diagnosed.

Bobbi Pritt, M.D. (04:37):

You know, that's a really good point, Bill. It does make you wonder how many people are not diagnosed. And if you look at the article that was published, it was in the Journal of Allergy and Clinical Immunology by first author Dr. Thomas Platts-Mills. And you listen to the story or you read the story. It was a 47-year-old airline pilot who first had an episode about two weeks before the fatal episode where he had beef steak. And that was unusual for him. He usually had chicken. So he had this about 10 o'clock at night. Woke up at two in the morning with abdominal discomfort, which became so severe. He was in pain, he had diarrhea and vomiting. But then he got better. And this was during a camping trip, so it was probably not immediately easy to get to the local hospital.

Bobbi Pritt, M.D. (05:28):

Since he got better, he went back to sleep and then he felt well enough to walk five miles. So he just said, you know what, let's not worry about this. But then it was two weeks later that he had a barbecue, ate a hamburger, and then suffered an anaphylactic reaction. His wife wasn't there and he died. So you could see very easily how even that first time could have been fatal and how many people out there have a reaction like that. But then they get better and then they're like, oh, OK, I'm fine. So it does make you worry, and I think it's really important to recognize that food allergies can be fatal.

William Morice II, M.D., Ph.D. (06:07):

Yeah. Food allergies and allergies can be fatal, right? Anaphylaxis, it basically is a runaway train immune reaction from reacting to your allergen that causes it. It ultimately can result in death. But the stuff you described in terms of diarrhea, the blood pressure gets low, the nausea, difficulty breathing. All those things also just show that if you have some kind of severe episode, just because it goes away doesn't mean you shouldn't go in. Your body is telling you something that you probably need to listen to. And I think this was a professional, airline pilot or something. Professionals are prone to discount their symptoms because we're all busy people, but it’s important to remember.

The labs are the key. And the other thing is as a laboratorian to really understand what we test for, what are some of the symptoms that they would manifest with so that you can guide the use of the laboratory. In this case, interestingly, they used a tryptase also to postmortem diagnose the anaphylaxis. Because it's typically a clinical diagnosis, but tryptase released by a cell called the mast cell, which is a big part of this pathology. So that's the other thing for all of us is that's why it's important to not just think about ourselves as running tests. We have to really think about how to use tests to get accurate diagnosis.

Bobbi Pritt, M.D. (07:26):

Yes. And we are the subject matter experts on these particular tests. It just gets back to what I always say, we're part of the clinical care team, helping to care for these patients and what we do matters so much. It could potentially save someone's life.

William Morice II, M.D., Ph.D. (07:40):

That's right.

Bobbi Pritt, M.D. (07:42):

Well Bill, thanks for joining us. As always, great discussion and I look forward to future talks.

William Morice II, M.D., Ph.D. (07:50):

Yeah, I do too.

Bobbi Pritt, M.D. (07:57):

Welcome to today's deep dive. We're going to go beyond the headlines with Dr. Chris Garcia to bring you a discussion about biopharma diagnostics. Chris is Mayo Clinic Laboratories’ chief digital innovation officer. But today, we're going to focus on his role as medical director of the biopharma team. Thank you for joining me, Chris.

Christopher Garcia, M.D. (08:17):

Thanks for having me, Bobbi. I'm really excited to be here.

Bobbi Pritt, M.D. (08:20):

It's a pleasure to have you. And you know, there's a lot we could talk about. Many people associate diagnostics with patient care, but in your world, diagnostics play a critical role in research and development as well. Can you explain how biopharma diagnostics supports healthcare innovation?

Christopher Garcia, M.D. (08:38):

Absolutely. And there's a million ways to go down through this, but I think, as you mentioned, lab's role in bringing new diagnostics and therapeutics to market is key. The bedrock for biopharma diagnostics at Mayo Clinic has been clinical trial testing. That's where we partner with biopharma companies and contract research organizations to provide Mayo Clinic laboratory testing for clinical trials. The high-quality, well-differentiated testing that's performed in our laboratories really does provide meaningful diagnostic and monitoring on patient response to therapy. This has been where Mayo Clinic Labs Biopharma Diagnostics started, and it's still a foundation. So really taking these great tests that you and all of our colleagues provide is key. There's also some really exciting collaborations that we provide through Mayo Clinic Laboratories BioPharma Diagnostics, and that is sponsored research with Mayo clinical and research consultants. Sometimes a biopharma company has a drug in the cardiovascular space, and they need to know when that drug is working and when it's not for the patients.

Our laboratories not only provide that testing, but they're also seeking guidance from a cardiologist on designing their trial or really understanding the impact. So we get to pull in the testing, we get to pull in the Mayo Clinic researchers, and we create this really great sponsored research opportunity that can also lead into analytical or clinical validation of assays. I can think of quite a few opportunities where there's a new drug out there and they don't really have a script for which test is going to provide the most value. And so we'll do a sponsored research with either a novel assay or one that's already set up, and we'll show how that provides answers for patients and for clinicians as they're treating. That's really exciting to see how we can use either existing tests or even set up new tests to provide that. And it makes it really diverse because the level of collaborations is always different and you never know what's coming through the door. But to be able to help shape diagnostics that select patients for therapeutics or monitoring is really key.

The last thing that we really do as biopharma is always under pressure to do things faster and to do things better and to do things with less risk is to move toward their data-first hypothesis testing. So, they're really looking at how do we use the information generated from patient care to either make better calls on our clinical trials or choose better therapeutics for specific patient populations. Because we're here at the Mayo Clinic, where we've invested a ton of resources into our information, whether it's in our electronic medical record, our LIS, or we have colleagues at Mayo Clinic Platform. There's amazing research systems that are being set up. There's an opportunity for us to connect with biopharma and really dive deep into the diagnostic data as well as the clinical data and help provide answers faster. It can speed up their research. So those are the three major areas where, like you're saying, it's not normally what we think of when we think about Mayo Clinic Lab testing. But that's where BioPharma Diagnostics is providing value outside of direct patient care.

Bobbi Pritt, M.D. (12:06):

Yeah, that's great Chris. There's a lot of innovation and that's really exciting. It must also be really rewarding.

Christopher Garcia, M.D. (12:13):

It really is. It is so exciting to partner with these different colleagues that come from all over the world, and they're usually very passionate about either this new treatment or this new diagnostic, and to see how can we be a good partner with them as Mayo Clinic?

Bobbi Pritt, M.D. (12:30):

Yeah, that's neat. What drew you to this area of diagnostics then?

Christopher Garcia, M.D. (12:34):

You know, honestly, it kind of happened through training. I was able to train out at ARUP and I had a lot of clinical mentors that did sponsored research. I think a lot of people are familiar with Dr. Mohamed Salama. He was one of my mentors when I was training there, and we did a lot of digital pathology work together. So I saw some of that, but it wasn't until I actually did my fellowship out in Boston and was just kind of inundated with that whole world, right? There's so many biopharma and biotech companies out there, and I had this chance to do a master's program out at MIT, and one of the courses was called Principles and Practices of Drug Development, taught by Stan Finkelstein and Pete Sorger. And they pulled in everybody that they knew, and we had all these guest lectures and got to understand what really was going on in that world. And it was exciting because when I took the course, it was during COVID, so we learned about Operation Light Speed and how everybody was pulling together to make things happen as soon as possible. That really was exciting.

And at the same time, another thing that happened was I was working at LabCorp as a medical director, and I was over a lot of our digital pathology initiatives. And this was right after LabCorp had acquired Covance, which is a long, large contract research organization. And we had lots of discussions and work about how do we use digital pathology to accelerate and provide new services for biopharma. So all this kind of happened at the same time. And I had projects but I didn't necessarily own anything in the biopharma space. And it was a few years ago that I came to Mayo Clinic and was working mostly on AI, and I was asked to pitch in as the medical director for BioPharma Diagnostics, as the previous one had to take a leave, and it was mostly on the digital capabilities. And so I've been working there and enjoying that, of course. But also been getting a lot of exposure to how much work is actually done here by you and by our colleagues. So while it wasn't something that I went into a hundred percent saying I know what this is, it's been a real pleasure to learn on the job and to draw from those past experiences and training.

Bobbi Pritt, M.D. (14:52):

It's really a perfect lineup with all of your skills and past experiences, and we're so happy to have you, Chris.

Christopher Garcia, M.D. (14:58):

Thanks, Bobbi.

Bobbi Pritt, M.D. (14:59):

So as both a medical director for BioPharma Diagnostics and chief digital innovation officer, maybe we'll just shift a little. How do you see data and digital tools reshaping the future of diagnostics and research and development?

Christopher Garcia, M.D. (15:14):

Oh, that's such a great question. And to be honest, I feel really grateful to be able to witness all that's going on. Even though I kind of chose my career because I thought, “Oh, this pathology informatics thing has something to it,” I had no idea that it would have this level of effect. And so, I would say it's been really impressive to see what data and those tools can do for us. I know I've seen in your lab with digital pathology and microbiology what can be done there. And I think it brings up one of the major things that I keep on being impressed in, and that would be how digital tools are reshaping what we do through automation and data integration.

So it's a lot of what we do, but can we scale it up? Can we improve the quality in any way? How can we support what we do and kind of give our team the superpowers we need to meet the patient care at the level that we need to do? And just seeing what we have today is astounding, the large language models. I know I was talking to a radiology colleague, and he was talking about a tool that they have that summarizes all the outside radiology reports and saves him 30 to 40 minutes, and it was just a big highlight for him. And I know that those kinds of tools, when they come to us, it really does allow us to do what we want to do for patients faster and with the quality that we need. And it's just nice to know that it's not science fiction that we're actually using it today, you know?

Bobbi Pritt, M.D. (16:41):

I'm still waiting for the tricorder, you know, or you can just scan a person and get all the answers. Oh, and transport.

Christopher Garcia, M.D. (16:47):

I'll lend you mine, I'll lend you mine. It'll be fine. It would be great. Although speaking of that, like I just came back from ASCP and it kind of hits on one of the other topics of how data is transforming our field, and it's the high dimensional analytics and we heard from Francis Collins, I think formerly the NIH, and he was talking about the first genome project and that it took $2.7 billion and 13 years. So it took a lot, right? A lot of work. And then today you can have a whole genome for under a thousand dollars and in a much shorter period of time. And so this high-dimensional analytics that we have allows us to provide services that we never would've been able to have a decade ago. And some of these things, like the genomes, are not as widely spread as we hoped they would be, but they are way more routine.

And talking to people who are really innovating in this space, the thought is the level of cognition and thought that we can provide now is really astounding in being able to solve answers for patients. The last key topic, so above automation and high-dimensional analytics, would be the AI-enabled discovery. And so this is kind of wearing the other hat, but going towards biopharma diagnostics. There's a lot of work and a lot of money put into trying to find what is the next drug, what is the right candidate that we can use to treat patients. I just returned from a client visit. We were talking with a really exciting company, and they were showing us their drug discovery process and this amazing team that they built with data scientists and wet lab scientists, just really top-notch teams. And they said, two years ago when they built this team, they were expecting to find one, maybe two candidates per year. And now with the advances in technology that they have, they had found six in the last 10 months and they were hoping to find quite a few more before the end of the year. And it's just amazing that these things are gonna come together and provide new answers for our patients. It is really amazing that they're not just faster, but they're really unlocking new capabilities that we've never had before. I can't even imagine what this looks like, you know, 20 years down the road.

Bobbi Pritt, M.D. (19:11):

It really is amazing and it's exciting. Obviously, we need to keep a close eye on things and make sure everything's done ethically and responsibly, but the tools we have now are amazing. That's one of the reasons we have this podcast, is because we see this need to educate everyone on how our field is changing. So, I have one more question for you. Getting along these lines of innovation beyond data and digital tools, are there other new scientific advances or technologies that have the potential to expand biopharma capabilities in the next, say two to three years?

Christopher Garcia, M.D. (19:47):

Yes, I think there are, and it is a very exciting space, and it will be interesting to see which of these actually make that progress and meet where we're hoping they'll be. I feel really fortunate not only to be in BioPharma Diagnostics but also to be in DLMP and to work really closely with the whole team. And I think some of this is informed by Dr. Lucas and his research initiatives, but the first one I would say is spatial biology and multiomics integration. So that spatial omics is really so exciting. It is amazing to go and talk to these biopharma diagnostic companies and see the things that they're thinking about, like really smart, dedicated people trying to solve problems with these new tools. And I really think there's a lot of promise there, whether it's for drug development, looking at the tumor microenvironment or immune infiltration pattern. I mean, there's so much work around the immunome right now that's really exciting, but it's also exciting to see that not only are other folks investing heavily in this but so is Mayo Clinic. So yeah, I'd say that's one, the spatial omics.

The second one, I have to admit, I was initially a bit of a skeptic. I'll not spend too much time into that, but I think I'm starting to understand it better. It is really the liquid biopsy and how it's expanding beyond oncology. You know, I've been really, really impressed. The more I've learned, not being a microbiologist, but more I've learned about shotgun and metagenomics, what can be done with these biopsies is really impressive. And so, I think that's exciting. I think it's going to transform a lot of different areas beyond oncology. And I imagine that its use in oncology is gonna be solidified in the next five years pretty clearly.

And the last one that I'm really passionate about, so it's probably me wearing my, I wouldn't say a fanboy hat, but definitely a champion, is the AI native diagnostics. So that would be where you're using AI to provide answers, not just to automate but to provide answers that we didn't have beforehand. And some of these are really correlative, but we're seeing some really exciting things looking at patient outcome. So, you do analytics, pull in some imaging, and provide an analysis on that and pull in some demographic information or something else about the care pathway and being able to decide, does this patient get this course of treatment or this course of treatment? And really seeing that folks figuring out ways to use AI to really impact patient care. It's exciting to see that there's research done at Mayo as well as really fantastic companies outside. I think using AI, or let's just say data science to be able to provide new answers will really impact patient care and is exciting.

Bobbi Pritt, M.D. (22:37):

That is very exciting. I love those examples and I love how you're honest about the liquid biopsy, you weren't quite sold on it until you saw it in action. And that's definitely a hot area in our field in clinical microbiology right now.

Christopher Garcia, M.D. (22:53):

It is very exciting. Even walking through the lab and seeing the level of care and thought that's put into that is pretty astounding. So thank you.

Bobbi Pritt, M.D. (23:01):

Well, Chris, this was great. Thank you so much for sharing all of your insights. It was great having you on the podcast again. I will definitely keep you in mind because your area's changing so much and there's always something hot and new to talk about, so I'm sure we'll be talking to you again.

Christopher Garcia, M.D. (23:17):

Thank you, Bobbi. Always love listening to the podcast. I learned a ton, so thank you.

Bobbi Pritt, M.D. (23:21):

Thanks Chris. All right, bye-bye.

Christopher Garcia, M.D. (23:23):

Bye.

Bobbi Pritt, M.D. (23:29):

Let's wrap up with the top takeaways and how to learn even more on the topics we discussed on our news summary. Dr. Morice provided a post-shutdown update on PAMA reform, and we discussed a unique alpha-gal syndrome case. We also continue to encourage you to connect with your professional organizations for the latest on PAMA reform and have included a link in the show notes if you'd like to learn more about testing for alpha-gal syndrome. Then, we moved on to the deep dive, and Dr. Chris Garcia joined us, where we explored biopharma diagnostics and he shared more about this fascinating field of diagnostics. If you want a deeper dive on that topic, there is a link in the show notes to several resources. Thank you for joining us today. For our next episode, Dr. Morice and I will share news updates before reflecting on some of the more significant industry advancements and trends that we've seen in 2025. I hope you'll join us.