RamaOnHealthcare January 15, 2022

Jon Laurent, Ph.D., Head of research and development at the Pandemic Response Lab (PRL), discusses with RamaOnHealthcare how diagnostic technologies are helping in the global COVID-19 pandemic, and how these technologies address other challenges in healthcare. He then turns to consider the opportunities, challenges, and new technologies on the horizon for diagnostic medicine.

Jon Laurent - Ph.D. - Head of research and development at the Pandemic Response Lab (PRL)

Jon Laurent, Ph.D., Head of research and development at the Pandemic Response Lab (PRL)

RamaOnHealthcare (ROH): The Omnicom variant has made it clear that continued vigilance is critical in our fight against COVID-19, and PRL reported the first discovery of the Omicron variant in New York city. How did PRL’S technological capabilities enable this discovery and how will that tech contribute to continued vigilance?

Dr. Jon Laurent (JL): I think the key technological capability we have that enabled the Omicron discovery, and other, earlier variant discoveries, is our sequencing capability. We developed and added to our pipeline a low cost, rapid whole genome sequencing workflow. PRL started developing that sequencing workflow because we knew it’d be important to be able to monitor the appearance of variants, and even more importantly, their spread once they appear. We sequence a majority of the specimens that come through our diagnostics labs, and we report those sequences to various public health authorities.

We developed and added to our pipeline a low cost, rapid whole genome sequencing workflow.

We’ve implemented some unique capabilities that have allowed us to sequence a higher percentage of our tests. And we keep a constant eye on, not just our own sequencing, but on sequencing submitted to databases by other laboratories around the world. We watch for variants of concern, and we pay attention to the World Health Organization’s guidance.

We’ve implemented some unique capabilities that have allowed us to sequence a higher percentage of our tests.

With Omicron, we’ve seen that mutations can affect diagnostic tests, for example with the S-gene dropout that people hear a lot about. Fortunately for us, our assay doesn’t use those targets, and thus our test is not affected by Omicron. But we do keep an eye on all variants as they appear and have a monitoring program in place to check our test targets against all genomes, not only sequences that come through our diagnostic labs, but ones that are being uploaded to genome databases. We’ve also developed a set of new targets that we can deploy if our targets become affected in a large way by some variant that happens to take over.

ROH: PRL was created to serve the diagnostic needs of the pandemic. What motivated PRL to form this company and contribute in this way?

JL: PRL is a convergence of two groups. Opentrons, a laboratory robotics and automation company, was already addressing the pandemic by sending their OT-2 robots to testing organizations around the world. They are based in Brooklyn and were looking for a partner to develop a higher throughput lab in the epicenter of the U.S. pandemic, New York City.

At the same time, our group at NYU had developed a high throughput pipeline for constructing and screening very large genomes, with applications in industrial yeast applications and human disease genetics. But this pipeline was capable of running tens of thousands of quantitative polymerase chain reactions a day and utilized Opentron’s robotics in the process. So, when the pandemic took hold of New York in early 2020, we pivoted to developing a COVID-19 diagnostics pipeline.

In the summer of 2020, there was a call for proposals to address COVID-19 diagnostic testing needs. We connected with Opentrons with the idea to build a homegrown diagnostic infrastructure with the goal of dramatically increasing the testing capabilities in the city and eventually elsewhere.

…the idea to build a homegrown diagnostic infrastructure with the goal of dramatically increasing the testing capabilities….

ROH: Since PRL’s inception, it has processed over six million COVID-19 tests, and handles around 30,000 tests per day, all at a low price and rapid turnarounds. How did PRL position itself to take on that workload, and what lessons did PRL learn in growing to meet these demands without increasing costs or turnaround time?

JL: From the beginning, we really wanted to address the primary shortcomings of testing as it existed at the time. Those are being able to handle large volumes, deliver test results very quickly so that people can take the proper precautions, and keep the costs down so that it’s not overburdensome to perform the testing, to purchase the testing, etc. Our expertise really lent itself to addressing these issues, because we had built our qPCR pipeline to address the same goals.

One of the big lessons that we’ve learned as we built and scaled-up PRL is that it’s not just the science and math, the automation, those things that we were good at. It’s also about the people that you bring in and train. It’s building the pride that they take in their work. It’s not just the robots doing the tests. Taking pride in that goal helps maintain high quality work.

ROH: Population level testing has been an important tool for understanding the pandemic in general. How has PRL contributed to this overall big picture awareness?

JL: An important aspect of population testing is that it needs to be truly representative across all populations. We partner with a lot of clients and public health authorities to address potential shortcomings and underserved populations. We look at our data to ensure that we are getting tests from all neighborhood areas of the city. That’s a major way in which we’re addressing the population level understanding and contributing to epidemiological knowledge.

Another way is the sequencing. In fact, we can constantly see the virus mutate, see new mutations take hold and spread. That information contributes to public health awareness. So, we can know when a variant is coming and take precautions if needed. But we also learn a lot about how viruses mutate, and how we can address these types of things in the future.

Our sequencing is on a frequency such that we can see the rise of new variants in real time. And we’re seeing it now with Omicron. Our most recent report, that we’ve released Friday, December 17th, showed that Omicron had maybe eight or ten percent of the positive tests. By December 22nd, our live internal data is already showing more than fifty percent Omicron. So, it’s taking over very fast. We can look back and say, “what happened when Delta appeared?” Well, it actually took way longer than that, about eight to ten weeks to take over.

Our sequencing is on a frequency such that we can see the rise of new variants in real time.

We provide this data for epidemiological research that can identify new characteristics in variant transmission.

ROH: You mentioned that high volume testing is an important tool for returning to normal. PRL serves large organizations from education to elder care facilities and government agencies. What are the scientific and logistical keys to serving these large organizations?

JL: I think it’s mostly logistical. It really comes down to being able to handle the testing volumes that these large organizations need. If these large organizations want to do widespread testing, they need to be working with a lab partner that can handle the volume. The Department of Education has millions of students in New York City. So high volume capacity is critical. The other piece of that is that they don’t want to have to pay exorbitant amounts of money to get testing done. We fulfill both the throughput and cost needs while maintaining highly accurate, high-quality results to keep organizations safe.

We fulfill both the throughput and cost needs while maintaining highly accurate, high-quality results to keep organizations safe.

One unique logistical challenge is receiving a concentrated bolus of tests at one time. The testing facility needs to process large batches on demand very quickly without getting overwhelmed or backlogged with that sudden arrival. The solution goes back to the attention of our people, ensuring that technicians are trained on all aspects of the lab, every step of the way from receiving all the way to PCR and final analysis. So, when we get a huge bolus of tests, we can shift people to receiving and processing so that the samples move into the pipeline as fast as possible. From there, our highly parallelized framework can handle the volume. But the key is having personnel who can flexibly switch tasks to undo the pileup.

ROH: Though COVID-19 has highlighted the value of molecular diagnostics, syndromic testing panels were already growing in popularity for infectious diseases, especially in emergency and urgent care. How does syndromic testing improve infectious disease diagnosis and patient outcomes?

JL: The simple answer is that they’re really a convenient way to assess with just one test what exactly is causing an illness, especially in a situation where you might be presenting symptoms that could be any of a number of similar things but that need to be treated differently. This is really the intent behind these panels, and why they’ve been growing so fast, so quickly in popularity.

One of the things we’ve seen is a rise in COVID plus flu testing. COVID and flu present with very similar symptoms, in the beginning. As we move into flu season, we want to be able to distinguish those two things so that we’re properly addressing isolation prescribing antivirals or other treatments. That’s a simple example of the benefits these tests have.

ROH: These testing technologies are ever advancing, and they continually shift the diagnostic landscape. How do you see syndromic testing fitting into modern diagnostics now and into the future?

JL: My primary job right now at PRL is to think about and plan for these changes. At PRL, we want to shift beyond COVID-19 to disrupting diagnostics more broadly. We’ve been developing our own syndromic panels – we have a respiratory panel in review within state regulatory bodies, and we have several other diagnostic panels in the pipeline.

At PRL, we want to shift beyond COVID-19 to disrupting diagnostics more broadly.

I see the molecular diagnostics industry going in a couple of different directions. One is a push towards bigger panels, for example testing for 25 different things at once. That’s good if a lot of those things present similar symptoms and you can treat some of them differently, but in reality, a lot of those things actually aren’t clinically actionable at all and their diagnosis is not helpful. We’ve talked with clinicians, and what a lot of them want is more custom panels, or à la carte panels. With these panels, a clinician, based on their experience and knowledge of the case, can say, “I want to test for these five things,” or “these eight things” rather than trying to order a test that’s testing for 40 pathogens.

One is a push towards bigger panels, for example testing for 25 different things at once.

Some of the technology that we’re developing and continually thinking about enables that type of optionality. The other direction that things might go is actually in the opposite direction, in technology and paradigm. New technologies might enable us to make panels so big that clinicians can test for everything at one time. We could do so potentially at such low cost and low logistical burden that issues with over-ordering are eliminated.

ROH: Antimicrobial resistance has been a critical issue in healthcare and syndromic testing. Can you speak a little about how syndromic panels can contribute to overcoming this challenge?

JL: I think that is an important topic. The main way that syndromic panels address antimicrobial resistance is by preventing over prescription of antibiotic drugs. When antibiotic drugs are prescribed inappropriately, the drugs promote the spread of antimicrobial resistance. So, being able to identify that a patient doesn’t even have a bacterial infection but a viral infection and that prescribing antibiotics doesn’t make sense prevents over-prescription. Being able to determine that fact quickly, easily, and cheaply is super important.

Another piece of it is that, as we expand the panel in terms of the number of pathogens tested, we can also test for specific anti-antibiotic genes or pathways that these bacteria might have. Then we can identify the antibiotics to avoid. So, I think those are the big ways that we can help.

ROH: PRL has leveraged Opentrons’ robotics experience to improve COVID-19 testing, specifically in regard to speed and scale. What do you see as the next key innovation that PRL will pursue to continue to impact medical technology and improve patient outcomes?

JL: I see two different directions. We can focus on our unique expertise in robotics, automation, and science, as well as process improvement lessons that we have learned along the way, but we can start applying those to different diagnostics. Right now, PCR is our focus because that’s what the COVID test is based on, but there’s all sorts of other diagnostic platforms such as antibody testing with ELISA and many others.

Another big one that we’re working on is sequencing. Sequencing-based diagnostics is growing in application to oncology. We’re working on that, again applying the same kind of thought process. So that’s one big direction that I see, applying the same thoughts, the same expertise to different areas of diagnostics.

The other direction is continually looking out for brand new technologies, brand new scientific breakthroughs that we can apply in this space. One example that we’ve thought about, and that has become popular with COVID testing, is CRISPR-based diagnostics. CRISPR is everywhere in biology and biotech, but it’s also being applied to diagnostics, and there’s really some interesting directions that that could take. Of course, there’s big hurdles to prove effectiveness, and to clear regulatory aspects for CRISPR.

ROH: What are you personally most excited about with PRL? What project do you see that PRL can have a major impact with?

JL: The major thing that I’m excited about is these next generation tests that we’re building right now. We have this platform that we’re doing COVID testing on, with some technological advancements that will support hyper flexibility and will support many other tests. The platform can run a lot of different PCR-based tests at one time on a single line, without much modification. So, we can do things like accept respiratory panels, STI tests, and GI tests, all into the same lab. We can run them on the same line and then pick out the results later, at the end. And this improvement is a huge opportunity for increased efficiency and speed for all sorts of tests, which tend to have weeklong waiting periods for results. Those tests get sent to one of the huge reference labs and get lost in a shuffle somewhere, and they cost 500 bucks. We can do it much more cost-efficiently, and much faster.

…I’m excited about is these next generation tests that we’re building right now.

About Jon Laurent

Jon Laurent received his PhD in Molecular Biology from UT Austin and did his postdoctoral studies at NYU Langone Health, helping lead development of high-throughput technologies for genetic and genomic engineering and analysis. In the face of the pandemic through 2020, he helped lead the pivot of one of those platforms for performing 10s of thousands of COVID tests per day, leading to the co-founding of Pandemic Response Lab as part of Opentrons Labworks to become NYC’s primary testing provider. He now leads the R&D group at PRL, tasked with developing new disruptive diagnostic assays and platforms, as well as advising on scientific direction for Opentrons as a whole.

 
Topics: Healthcare System, Interview / Q&A, Public Health / COVID, Trends
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