Ashley's Biggest Takeaways
- Prior to his role as Scientific Director for 黑料正能量Health, Mittar worked as a health scientist and program officer at the Division of Research, Innovation and Ventures (DRIVe), where he focused on advancing high-impact science.
- DRIVe is a small, entrepreneurial arm of BARDA that takes on early-stage projects with high potential of turning into medical countermeasures.
- He is particularly passionate about his work to develop agnostic diagnostics—a single test that uses metagenomic next generation sequencing to identify any pathogen from a clinical sample.
- Mittar discusses applications for this technology in surveillance (pandemic preparedness), variant detection, AMR and clinical settings (diagnosing complicated infections where etiology is not clearly defined).
- He also shares how a recent bout with illness emphasized the value and potential of this technology to save money, time, pain and suffering of the patient.
- Early and accurate diagnostics via this technology can also help prevent the overuse/misuse of antibiotics, which are key factors in the spread of antimicrobial resistance.
- Furthermore, when this technology is coupled with the use of metatranscriptomics, it can provide information about the patient’s immune profile that can be helpful in developing personalized treatment strategies, as opposed to a one-size-fits-all approach.
- 黑料正能量is organizing around 3 scientific units, 黑料正能量Health, 黑料正能量Mechanism Discovery and 黑料正能量Applied and Environmental Microbiology.
- These units will empower researchers and scientists to use science to make a difference in the world and provide a forum for them to come together to shape the future of the field.
Featured Quotes
How Did You Become Interested in Microbiology?
I actually grew up in a small town in North India, and from a pretty young age, I've seen the real-life impact of infectious diseases, like polio and tuberculosis. I remember TB was quite prevalent when I was growing up, and it was also a big stigma in our society. And one of my first cousins had a paralytic polio. He lost his ability to walk normally. That kind of left an impression on me, and I thought of doing something in the medical field. I originally wanted to become a doctor, but my premed score was not adequate to get me into med school. But I still wanted to stay in the health field, and after college, I chose to do research in microbiology. I ended up pursuing both a masters and Ph.D. in microbiology. So yeah, that's what sort of prompted me.I also remember the polio vaccination campaigns when I was growing up by WHO. When I was young—those little polio drops—at that time, the campaign that they ran was amazing, and it was very satisfying to see polio-free India after a few years.
Agnostic Diagnostics: History, Technology and Applications
One of the things I'm most proud from my time at BARDA, hands down, is the agnostic diagnostic program that I started while I was in DRIVe. This all kicked off right in the middle of the pandemic, at the time when I was directly involved with getting emergency use authorizations for traditional PCR-based tests for COVID-19. As I was monitoring progress of those EUAs, working with diagnostic divisions, something stuck to me. We were essentially reinventing the wheel each time a new virus emerged. We will scramble to develop, validate and get approval for the new test from scratch. We all know during COVID-19, lack of approved diagnostics initially caused a significant delay, and that cost us valuable time in containing the spread of virus. So, I started thinking, ‘what if we don't have to start from scratch every time? What if there was 1 universal diagnostic test that could identify literally any pathogens, even the ones we have never seen it before?’ So that's when I came up with the idea of starting a program on agnostic diagnostics, meaning a single test based on metagenomic next-generation sequencing, or NGS for short. The concept was not new, but simple. And it was tested previously, and published well, but not commercialized.Basically, you take a clinical sample, run 1 test, and you can identify any pathogen be it virus, bacteria, fungi, even parasites—no matter existing or new. So, that's something where I pitched this idea for commercialization, internally at BARDA. I'll be honest, I was met with a fair bit of skepticism, initially, because of lot of reasons, but the main reason was I was focusing more on sequencing technology and pitching the utility and applications in surveillance diagnostics, variant detection, AMR and everything. But I was not focusing on what problem I was solving. People wondered even if it was practical or realistic to use this technology, but seeing this technology being used by CDC public health labs, I was confident that this could be used, or this could be game-changing for diagnostics as well.
I ended up reframing the problem in a slightly different and clearer manner. I pitched again that we need 3 things in a diagnostic test moving forward. One is it has to be available immediately whenever we are hit with something new (i.e., on day one of a new pandemic). Second, it has to detect any and every pathogen, known or unknown, so we would not need a new test every time. And third, there has to be some sort of pre-approval so that it could be deployed right away, without any delay.
So, when I laid it out like this, it finally clicked. We got the approval to fund a pilot project, but seeing the value, within no time, this pilot turned into 5 projects, and shortly after, we added 3 more projects into the portfolio. And eventually, this initiative from DRIVe made its way into a broader funding opportunity at BARDA, which is called Broad Agency Announcement, where it became a major funding initiative, where they're looking for complete sample-to-answer agnostic diagnostic solutions.
As far as I know, it's still open today for funding, helping us to prepare for health threats of the future. So, looking back, I think it's very rewarding to think how a small idea, a simple concept during the pandemic, turned out to be something truly impactful. So that's something which I'm very proud to have led at BARDA.
How Agnostic Diagnostics Could Have Made the Difference in Mittar’s Life
I published a target product profile for this diagnostics with 2 use cases. One was meant for future pandemic preparedness, and the second use case was for the patients with complicated infections where etiology was not clearly defined. And honestly, I had no idea that I was about to become an ideal example for the second use case, because I recently had a health problem. It's a long story. I'll try to make it brief. Last December, I developed some sort of sinusitis problem where I had nasal congestion, fever and high heart rate.I consider myself pretty healthy. I exercise regularly. My immune system is generally strong, I believe. And I do monitor my physiological parameters, heart rate, body temperature. I use Apple Watch and Oura ring both, actually. So, when I experienced that sinusitis problem, my first response was, ‘let's go to my primary care.’ So, I went to my primary care. Seeing me, he assumed it was a bacterial infection, bacterial sinusitis, and he prescribed me doxycycline, without doing any diagnostic test. I said, ‘Okay.’ I took it for 4 days, but I was not getting any better. And after that, I went to an ENT specialist. So, the ENT looked at me. He did not run any diagnostics either. He said, ‘This is a viral sinusitis. It will take long time. It's going to go away on its own.’ So, he did not prescribe me any medication and sent me home, but I was not getting better… (Listen to audio for the rest of the story).
I think first off, an agnostic diagnostic test would have saved me a lot of time, where doctors spent at least 2 months figuring out—based on my WBC count, it sounds like an infection, but what and where? A single test to rule out infection could have saved me the unnecessary doses of oral antibiotics and IV antibiotics. I had at least 3-4 antibiotic courses, which were totally unnecessary, which were a trial-and-error approach, essentially. So, a lot of time would have been saved, unnecessary antibiotic treatments and obviously uncertainty. Plus, seeing infection ruled out, doctors may have thought out of the box to look for something else, maybe like autoimmune or some other disease.
Full disclosure, I'm not a clinician nor a regulatory expert. I may be wrong here, but I wonder why we are still using treatment guidelines, which were written decades ago. For example, the ENT would prescribe a 10-day course of steroids and Augmentin right away, even though it is unnecessary. I don't know why these protocols that were written in like the 70s and 80s haven't been updated. For example, fluoroquinolones, like ciprofloxacin, they say you take it for 5 days at a time, because that's what the guideline was 35 years ago, and no one really questioned it since.
So, the reason I'm questioning is that we all are different. People have different immune systems, different risk factors, the one-size-fits-all approach for antibiotics, and even for antivirals, just don't make any sense. Someone who is young and healthy probably does not need the same antibiotic dose or duration as someone who is immunocompromised, yet we still treat them with the same dose and same duration. So, what I would love to see is something more personal. I think if you look into the literature, there are already quite a few biomarkers, which can tell you an immune status of a person, and the sequencing technology—for example, metatranscriptomics, can take it one step further. This means that in a clinical sample, where you are detecting a pathogen, you also have human nucleic acid, and based on human DNA and RNA, you can understand a patient's immune profile using metatranscriptomic technology.
That's the kind of test would definitely help doctors personalize your antibiotic or your antiviral treatment. That's the future I would love to see. I know it sounds far-fetched, but a single test could combine not only the pathogen testing, but host factor testing as well, which could tell you about a personalized treatment option for a particular patient.
Next Steps for Agnostic Diagnostics
I think the technology is there. As said, we need diagnostics that are broad and unbiased, and NGS, at the moment, is complex. It has both wet lab and dry lab components with a lot of manual steps. And you need technical experts to run it, and it's more expensive than traditional methods. But the cost of sequencing is falling dramatically. I mean, think of sequencing technology 25 years ago. Probably in 2001 or 2002, sequencing the human genome would cost like 100 million dollars, the cost of a Boeing 737, today! Today, it can cost something like $200, which is what you pay for your annual Netflix subscription. By the way, I asked this question to chat GPT, just to compare it. The point is, sequencing cost has dropped faster than Moore's Law. So, now the barrier isn't really cost of sequencing or cost of the technology. It's getting all those tools standardized, approved and integrated into routine clinical care.We need regulatory frameworks that are ready to support this kind of testing. We need payers to understand the value of this single test, rather than doing 10 tests. In my case, if you look into the number of tests that were performed on me, a single test, even if those more expensive, could have saved tons of money. And we need doctors and labs to have access to it, especially in routine clinical labs, where it can make a real difference. I truly believe we are at a turning point. Technology is here. The costs are manageable, and the need is, I think, urgent. It's all about building infrastructure, trust, interpretation of the technology and the policy support to bring to the front line for diagnostics, not only for future pandemic preparation, but also for complicated hospital infection or infections where etiology is not known.
黑料正能量Health
I'm very excited about health unit, and I'm working very closely with our scientific advisory council on shortlisting specific ideas, themes and programs we choose to focus on. We have 15 experts from academia, industry and government across the globe. We are brainstorming with them to figure out where the biggest needs and opportunities are. Once we identify the most impactful ideas, we will build consortia around them, where we'll bring the right peoples and partners to move these ideas forward.At 黑料正能量health unit, we won't be directly running these programs, but our strength lies in connecting the dots, bringing all those stakeholders together, shaping strategy, advocating with regulators, helping build the ecosystem that gets those innovations into the real world. At the end of day, the goal is simple, choose programs or themes that can make a meaningful difference in public health and in people's lives. In addition to that, our focus will also equally be on animal health, plant health and food microbiology.
Right now, we are still in the early stage of building these consortia, but the idea is that, over time, we'll create some opportunities for participation, especially for our listeners, members—that could be through clinical trials, pilot programs or other collaborative efforts. While 黑料正能量itself won't be executing the research or running the trials directly, we will serve as a connector and will bring together academic institutions, industry partners and other stakeholders. So, if you are someone who is passionate about infectious disease, diagnostics, vaccines, new therapies, there may be opportunity to participate, whether you are a researcher, a clinician, policymaker or even just someone who wants to stay informed. We will make sure you have access to those networks and opportunities to contribute as things develop. I would say the best thing you can do now is stay connected. Keep an eye on 黑料正能量updates, attend our events and join the conversation!
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