Illumina’s Phil Febbo on Sequencing, Coronavirus and Viral Outbreaks

Rapid sequencing of viral genomes is giving physicians and epidemiologists new ways to identify, track, and potentially slow outbreaks of viral infections such as the novel Wuhan coronavirus. That means high-throughput genome sequencing—which had predominantly been a research tool—is taking its place as a front-line weapon in the fight to prevent pandemics, says Febbo, a medical oncologist. “Last year, 40 percent of our consumables in sequencing were for clinical testing, and we see the clinical testing increasing at a pace that’s faster than research testing,” he says.

Whole-genome viral sequencing, as a supplement to more traditional PCR-based testing for RNA sequences, can not only reveal exactly which virus is afflicting a given patient but can reveal where a virus originated and how it is evolving to evade vaccines or other interventions.

“The fact that the WHO heard of the first cases [of the Wuhan coronavirus] at the end of December, and the New England Journal published the full genome on January 24, within a month, because of the availability of sequencing, already, places like the CDC are using that information to design the probes for the RT-PCR to develop front line tests—never before has anything like that happened,” Febbo notes.

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MoneyBall Medicine – Phil Febbo

Harry Glorikian:  Hello, I’m Harry Glorikian. And this is Moneyball Medicine. The show where we meet executives, entrepreneurs, physicians, and scientists using the power of data to reinvent healthcare from machine learning to genomics, to personalized medicine. We look at the biggest trends in patient care and healthcare management.

And we talk to people behind the trends to find out where data is making the biggest difference.

So let me take you through a brief timeline of a series of events to discuss our next topic on infectious disease data. And the impacts it’s late December of 2019, a number of patients present with a form of viral pneumonia due to an unidentified microbial agent. After some investigation, a novel Corona virus was identified as the culprit.

As of January 26, 2020, more than 2000 cases of the novel Corona virus infection have been confirmed. Most of which involved people living in or visiting Wuhan and human to human transmission has been confirmed. Some facts Corona viruses can beat can cause fatal respiratory illnesses. Corona viruses are also, a large family with some notoriously infectious members.

Sometimes when these viruses affect infect animals that can also evolve and spread to humans. Researchers have been using modern DNA sequencing methods. To monitor how viruses evolve in animals so they can better understand the potential impacts on humans. Reading the genome allows researchers to monitor how an infectious disease such as this Corona virus is changing and provides a roadmap for developing diagnostic tests as well as potential treatments.

My next guest is the chief medical officer of Illumina, and he is responsible for the developing and execution of the company’s medical strategy to drive genomic testing into healthcare practice, please welcome Dr. Phillip Febbo, Phil. Welcome to the show.

Phil Febbo: Thank you. It’s great to be part of your podcast,

Harry Glorikian:  Phil it’s, it’s really good to catch up.

I mean, it’s, it’s, it’s been a while. Um, so how are things going lately? Something tells me you’ve been busy.

Phil Febbo: Well, uh, the more people understand how an individual genome, uh, can. You know, have significant impact on their health, uh, their decisions as far as, uh, dietary and lifestyle choices and their, their, their medical management, um, the, the busier it gets and, and you’re right.

Harry, it’s been, it’s been quite busy. Um, it’s really exciting to see, uh, a lot of breakthroughs happening. It’s exciting to see the, the interest in incorporating, uh, genomic information into healthcare. Um, and it’s. You know, it’s, it’s really privileged to be, uh, a medical oncologist who’s now in industry and have kind of the privilege, see that at Illumina to see what’s coming, uh, what’s possible with the technology and to really engage with many healthcare providers and, and leaders and pioneers to see how they’re bringing it into care now.

Harry Glorikian: Yeah, I’m sure there’s not a boring day. Um, I mean, I remember. You know, we were getting this off the ground at Applied Biosystems. I remember somebody saying, why would you want to sequence anything? And now it seems like there there’s nothing that we’re not trying to sequence. Um, But, but let’s-

Phil Febbo: until you know how to, to use that sequence information, to solve a problem for a patient, for a healthcare provider, there’s no reason to sequence anything, right?

No one gets better through DNA sequencing alone there. That information has to inform. Management decisions and informs, you know, treatment decisions and, you know, apropo of our conversation today inform approaches to population health and biosecurity at once that connection is made, then people understand why you would sequence.

Harry Glorikian: Yeah. And it, it, you know, although it is a chicken and the egg, right, you, you do need to get sequence information to then do the analytics to then figure out how to manage appropriately. So I think there’s. Yeah, without the data, you can’t do the analytics you need to do to then figure that next part out.

Phil Febbo: No, absolutely. Um, and that’s why, you know, sequencing has been such a workhorse in the research community, right? There’s broad recognition. How research has fundamentally changed, how sequencing has fundamentally changed our understanding of biology. Um, And it’s, it’s that transition now. And that’s the lion’s share of Illumina’s business on the research side, but now we’re seeing a shift this last year, 40% of our consumables, uh, in sequence thing were for clinical testing.

And we see the clinical testing increasing at a pace that’s faster than what reachers testing is growing. Um, because now people are taking that research. They’ve understood. And now they’re understanding how to apply that clinically.

Harry Glorikian: Yeah, no, that’s fantastic. And the faster it goes, the better, because I’m not getting any younger.

Um, but, but, but, but, but you know, let’s talk sequencing and infectious disease, right? Cause this is a timely topic and you know, my show and the keys are, you know, talking about data, how data is changing the landscape across life sciences and healthcare. And as far as I know, and have experienced, I don’t think anything has had a larger impact than sequencing.

I mean, maybe PCR, but this is. If we’re not using this every day, sort of on the monitoring side of infectious disease or understanding what’s going on. I just knowing the antibiotics and the tools that we have, I feel like we’d be in trouble.

Phil Febbo: Yeah, well, I think you should be, feel very proud about the time at ABI and the pioneers in our TPS NPCR.

And, you know, RTPCR, you know, the PCR is still, you know, an incredible technology and, you know, it’s inexpensive, it’s relatively straightforward to set up and it really is the frontline of identification of, uh, outbreaks and infected patients. And certainly it’s the approach that. Is being broadly adopted now, uh, to address the novel coronavirus outbreak that we’re experiencing, but you know, it doesn’t give you completeness of understanding of the virus.

Uh, as far as the whole genome, it doesn’t allow you to understand whether that virus is evolving and moving and changing. Genome in a way, uh, to get around, um, any therapeutic interventions, be them medicines or vaccines. It doesn’t allow you to say, well, if it’s not coronavirus, what other virus is there?

I mean, coronavirus manifestation is fever and, uh, you know, uh, lower respiratory symptoms, shortness of breath, cough. We’re in the middle of flu season. There’s a lot of other viruses can do that. And you know, it’s very, if you’ve been traveling, maybe you’re concerned and you want to understand what’s going on.

So, you know, there is a lot of value to considering, you know, a more comprehensive approach, uh, that compliments that kind of focused, uh, frontline testing that PCR provides

Harry Glorikian: And correct me if I’m wrong, but I also. Understand, like from a genomic perspective, it can actually give us a true sense of timing of when the outbreak truly started.

Phil Febbo: Well, you certainly can, you know, follow, uh, the, the viruses, uh, genome, uh, and use changes over time, uh, to assess, uh, the origin and the pace of, uh, of spread and to map it, um, you know, we’re very early in this, uh, in this outbreak, uh, to really understand that, uh, and also Corona viruses that are RNA viruses, uh, and, uh, coronavirus specifically have, uh, have, uh, you know, kind of a nucleic acid spellchecking.

So they don’t evolve as rapidly as some other viruses. Um, but. What we’ve seen. And, you know, to my knowledge, the fact that, you know, the WHO heard of the first cases at the end of December and the new England journal, uh, published the full genome of the virus. And on January 24th, you know, within a month of the WHO hearing about this outbreak, There was a published full genome, uh, because of the availability of sequencing and, you know, already places like the CDC are using that information to design the probes for the RTPCR to develop those frontline tests.

And, you know, never before I think has anything like that happened.

Harry Glorikian: No. And I’m thinking about the speed, right? Cause I’m trying to remember back to the timeline of SARS and I don’t remember it. I mean, I know we were involved when we were sequencing source, but I don’t remember it happening. Anywhere. I mean, we thought it was fast back then, but what you’re talking about is sounds like, you know, Warp speed.

Phil Febbo: Yeah. It’s it’s, it’s it’s I don’t know the timing of the SARS. Uh, but I promise you, it was nowhere near 24 days.

Harry Glorikian: So, so how do you look at, at sequencing in this realm of infectious disease of, you know, what it’s bringing to the research community, the clinical community, and then. You know, information that will drive how someone will create some form of treatment.

Phil Febbo: Yeah. So we feel that, uh, the sequencing technology can, uh, by comprehensively assessing the viral genome. You know, in an outbreak like this first and foremost, like it already has it established as a ground truth of the viral genome of which additional assets can be developed. Um, it also does check as the outbreak spreads and as different areas are infected it, it does let you understand how rapidly the genome is evolving and, you know, allows you to be prepared.

Uh, Should your interventions be specific to any part of that genome or any specific variation? Um, thinking about that, you know, we move from diagnostics and understanding where there’s infections to therapeutics and whether it’s antivirals or vaccine based therapies. Those are often, you know, dependent on the viral genome and, uh, the, what the viral genome is coding for.

And, uh, you know, viruses are not smart, but they are very good at evolving through sheer numbers. And so incorporating next generation sequencing into. The workflow and into the monitoring of the outbreak, lets you stay ahead of the virus and understand if as you put in interventions treatments, how quickly it’s adapting so that you can stay one step ahead and manage your, your treatments.

It also. Doing next generation sequencing. And especially if you have a test that assesses for, you know, the 20 other viruses that can cause upper respiratory and lower respiratory symptoms, the influenza viruses that can are we’re in the middle of the season. And we have a vaccine that doesn’t quite fit with the outbreak that we’re seeing.

Um, you know, it lets you kind of reassure those patients that yes, you have an infection, but it’s not Corona virus. It’s influenza. It’s one of these other respiratory viruses. You know, there’s a lot of fear about the coronavirus and rightfully so, because there’s a lot we don’t know. And we do know that.

You know, it’s caused some fatalities, uh, in China. Um, so it’s, you know, next generation sequencing can also reassure those who may have upper respiratory tract infection, but not have coronavirus.

Harry Glorikian: Yeah. I mean, but let’s face it. Influenza kills a lot of people on an annual basis. I think people lose sight of the numbers of people that are affected just by that alone.

Phil Febbo: Yeah. I think the, the, the estimates are it’s, you know, on an average year, it’s about half a million individuals pass away due to complications of influenza virus.

Harry Glorikian: Yeah. And somehow that doesn’t make the top of the news, but, um,

Phil Febbo: um, it’s like anything, you know, Harry it’s like anything it’s, what’s the, that’s a known risk.

Right. So we understand influenza. We understand that each year from. Different reservoirs, whether it’s, you know, animal reservoirs or, uh, that there will be an influenza. Um, uh, and we try to anticipate that, you know, work very hard to come up with the right vaccine. Uh, I I’ll use this as a plug, everyone, you know, who’s healthy should get the vaccine.

It’s, you know, it really does show to improve, um, you know, uh, outcomes, uh, at a population and individual level. Um, and then, um, but, but that happens every year and you know, uh, it’s important, but it’s known what happens with something like coronavirus has just thought to have come from a rare animal market and we’ll hunt.

Is, we don’t know that we don’t know how infectious it is yet. We don’t know it’s, uh, it’s kind of, um, how aggressive it is. Um, and so there’s a lot, we don’t know. So that creates a lot of fear.

Harry Glorikian: Right? Well, and, and, and rightfully so. I mean, I, you know, the big thing is we, we don’t know what we. What mother nature is going to throw at us that we can manage accordingly.

Um, so looking at this information, being available on a global scale, right. And, you know, enabled by the technologies, how do you see that affecting, you know, population health and, and, you know, down to the individual? Uh, because we can communicate this information or, or have the technology available locally.

Phil Febbo: Yeah, well, uh, you know, making the genome publicly available allows multiple stakeholders across the globe and, you know, engage their efforts to, to add population health and to protect individuals. Um, so at a population health level, the CDCs across the globe, can develop tests and bring those tests to market as rapidly as possible.

I know our very own CDC is working very hard to get a test that is robust and available for the United States. Clearly the CDC and China’s working on the same thing. And I know of activities in Africa and Europe that are going on. So having that. Kind of sequence that is now available globally really allows many stakeholders who are in charge of the health of their populations to move quickly.

It also, and that’s the first stage of like diagnostics. The next stage is it also allows, uh, individuals who are going to start looking at therapeutics. And I know that you’ll be talking about that later on this podcast. Start just giving them the understanding of this virus and the genome of the virus.

So they can start planning therapeutics, you know, are what are the likely antiretroviral, antiviral therapies that’ll work? Are there vaccine approaches that are logical based on the sequence and really starts the, that movement as well. And without that kind of base ground truth, it’s very hard to start those efforts.

Harry Glorikian:

So, I mean, in some ways what we’re talking about, it seems like it’s, I don’t know, it’s the technology and the data that it gives you is almost fundamental in a sense of how could you ever live without it.

Phil Febbo: Well, you know, we’ve certainly over the years, figured out how to come up with therapies and, and how to come up with vaccines, uh, to viruses without that information.

But it’s also clear that with the information you can move much faster and you can save lives because you can accelerate those activities.

Harry Glorikian: Well, yeah, and I, I mean, I, I, I mean, it’s interesting. I’m just trying to think of if countries or areas don’t have this capability, are they at a. Uh, you know, disadvantage or, um, You know, do they put themselves in harm’s way?

Phil Febbo: Well, there, you know, there is always, you know, uh, challenges, uh, there can be different challenges to have access to cutting edge technology. What I will say is that, uh, at Illumina, uh, we’re specifically focused on making sure that any region that wants access to sequencing to help fight the coronavirus outbreak.

We’re working very hard to make sure they have access to that. We’ve um, we would have our technical staff standing ready. We have our supply chain ready. So we’re working very hard to enable those areas that you’re right. May not have ready access and yet can still benefit from access. Um, we see that as just.

Again, it’s a way that we can provide some modest help, um, to, to control this outbreak. So,

Harry Glorikian: so Phil, you have, uh, you have a front row seat to, you know, people, what are people doing on a global basis, as well as, you know, what Illumina is doing and so forth and not specific to the company itself, but where do you see sequencing?

Going, and maybe you can talk about the impacts that it will have or is having,

Phil Febbo: you know, it’s a big question, Harry. Um, I think, you know, if we consider our discussion on infectious disease, um, I see, you know, increasingly. Sequencing will provide a efficient means of, of surveillance for, uh, febrile illnesses in a way that allows, uh, different countries regions to be much more proactive.

And rapid in how they respond to what is undoubtedly going to be recurring episodes of viruses? I mean, viruses are a major risk to humans and will continue to be such. We’re going to continue to have viruses that come out of maybe, uh, other mammal species or elsewhere, or maybe a, you know, an endemic virus to humans, uh, mutates and.

Becomes more variant. Um, we have to be aware that that’s just part of the world in which we live and with the globally connected world, we’re seeing that when that happens, it can spread globally very quickly. I see sequencing and, you know, especially these tests, which were with one test, you can survey all the common viruses, not to mention other bacterial infections, fungal infections.

Uh, you can very rapidly. I believe screen and identify the causes of febrile earliest so that you can take the appropriate, uh, treatment approach for that individual and the appropriate containment approach for populations. Right now, you know, and sequencing really doesn’t, hasn’t been used in that way, but increasingly I think it will, a couple of things have to happen.

We have to have clinically validated data tests available. A lot of what I’m talking about. A lot of the backbone. It’s still kind of research and needs to be clinically validated. The other thing is, uh, you know, uh, next generation sequencing is still expensive, especially relative to PCR and other point of care tests.

So, you know, we have to continue to work to bring down the cost of the test as well, make the tests very efficient so that they can be, uh, they can, they’re affordable as well.

Harry Glorikian: : Well, it’s interesting. You say that it’s expensive, but I always weigh, like how much information am I getting for? What am I spending?

Right. I sometimes I think it’s almost the interpreting. The data is expensive compared to actually doing the actual wet chemistry.

Phil Febbo: Yeah, no, it’s in, especially when you’re talking about, you know, and when you move outside of infectious disease and you’re talking about whole genome sequencing, I’ve already heard, you know, the, the directors at the laboratories who are running these tests, they’re like, well, you know, I can now sequence, uh, for, do they get the whole genome for, you know, 700, $800, but.

Analyzing that data is, you know, a bigger cost you more money, uh, because of the time and then the expertise required. And so, you know, obviously you have to address costs holistically and, you know, certainly we’ll see software solutions and advanced analytics to address the challenge of the data. But, you know, I think what you really have to look at is the cost value ratio when you’re talking clinically, right.

In, in, in medicine, uh, technology could be free and still not utilized unless it has value because of opportunity costs. Right. You know, healthcare professionals, healthcare systems are extremely strained. Time is a premium. And unless a test is answering a solving a problem, it’s not going to be used. What I see happening over the next five to 10 years with respect to sequencing is yes.

We’ll continue to bring the price down. Illumina has shown that we can do that. Um, consistently we’re also going to see that people recognize the value more and more. So we’ll see the costs go down the value, go up. And that’s where, you know, in certain areas like oncology reproductive health, Genetic disease and infectious disease.

That ratio gets such that it just makes sense that to do the sequencing.

Harry Glorikian: Yeah. I mean, but at the same time, I mean, we, we need to make sure that the users or the people ordering this or educated in it too. That’s where I see a major disconnect of, you know, there’s a lot of people out there that. Don’t understand what it can provide and don’t understand what it’s telling them.

If you don’t know it’s there, you’re not going to order it and what it can do for you, like you said, but at the same time, the answer has got to come back and they’ve gotta be able to make sense of it and know what to do with it. So I think there’s, you know, that’s not a luminous. Issue, right. It’s the medical schools and everybody else.

But I think there’s a, a handshake that needs to go on there for this to continue to have the growing impact. We’d all like to see it have.

Phil Febbo: Yeah, I, I agree with that. Um, you know, w. The sequencing has to solve a problem for healthcare providers in a way that they can make their decisions to take care of the patient that’s in front of them.

For that to happen, there has to be awareness of the technology. Um, but certainly we’re not going to be able to turn healthcare providers into genomics experts. So the information has to be brought back into uh, the, the resources they use to manage patients. So it has to, you know, test results have to come back into the electronic health record.

There has to be decision support to help physicians prioritize their time with their patient, to, you know, optimize their management and really make sure that patient has the best care possible. I do get really excited. Um, about data analytics about artificial intelligence, because I am not so worried about artificial intelligence, you know removing as a physician.

I’m not worried about AI removing the physician. What I’m excited about is AI helping to assimilate the vast digital data. That’s. Increasingly available to help physicians prioritize their time with patients so that they can focus on the most important questions for that specific patient. And I think if it’s incorporated with decision support in that way, whether it’s pharmacogenetics, polygenic risk scores, uh, the ACM G 59, um, and or other genetic, uh, determinants of disease.

Those get emphasized or deemphasized based on that patient and that patient’s, you know, record of that as a manifestation of their electronic record, the digital imaging, you know, eventually demo digital pathology, all coming together in a way that, you know, physicians just couldn’t possibly assimilate, but AI is pretty damn good at it.

Harry Glorikian: No, no, no, no, no. I’m, I’m, I’m seeing it being used in a lot of interesting, you know, places. And it’s, you know, when it, when it’s focused on a particular area, it can be very fast and very accurate and, you know, can almost highlight things or show you things that, you know, a human being could have missed. Um, and so it’s, it is it’s moving rapidly.

Um, it’s just, we don’t, we haven’t graduated enough people that have both the medical understanding as well as the computer science understanding together to move it faster than it currently is, which in my opinion is sort of slow.

Phil Febbo: Yeah. And you know, the, and when I’ve talked to medical schools about this and I’ve seen some really innovative approaches, I’ve seen, you know, some medical schools incorporate um, genomics and whole genome into their anatomy lab. So, you know, when they’re, you know, working with a cadaver and learning anatomy, they also have the genome that they’re working with and, you know, and other manifestations like that. So we’re seeing that more and more, and it is exciting to see how medical schools are gonna address that.

But, you know, the medical school curriculum is not like theirs. A lot of time there. So how do you efficiently incorporate that? Is it remains a challenge? Yep.

Harry Glorikian: Nope, absolutely. Um, Phil, uh, this was great. Um, appreciate it. And, and, uh, look forward to our continued conversations on this because it’s, uh, we could spend a whole day if we went through the, went round, the circle here on oncology and everything else and, and, uh, and how sequencing is having a dramatic impact on, on all these disease areas.

Phil Febbo: Yeah, Harry great conversation. Look forward to future, uh, and uh, certainly no lack of things for us to discuss.

Harry Glorikian: Excellent. Take care. Bye.

And that’s it for this episode. If you enjoyed Moneyball medicine, please head over to iTunes, to subscribe, rate, and leave a review. It is greatly appreciated. Hope you join us next time until then. Welcome.