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How a Child Inspired Me to Bring Microbial Cell-Free DNA Research from the Lab to the World

By Mickey Kertesz, PhD

As a new entrepreneur, I often get asked “Why did you start Karius?”

I will answer this question with a story.

While I have always felt that there is great potential in using DNA sequencing to accurately probe microbes, it was a specific event in the spring of 2014 that showed me the urgent need of applying next-generation sequencing to infectious disease diagnostics.

This trajectory-changing event happened while I was a visiting scholar at Stanford Bioengineering (in Steve Quake’s lab), where I had the privilege to collaborate with other scholars and faculty looking at cell-free DNA samples from bone marrow and solid organ transplant patients.

During our study of transplant patients, we learned that in addition to the strong human signal found in cell-free DNA, there was also a faint microbial signal that could be attributed to the microbes infecting the patient.

While this was an interesting finding that led us to further investigate the signals (both human and microbial) found in cell-free DNA, it wasn’t until a crisp Saturday morning in March 2014 that the utility of our research would take a marked turn.

On this particular Saturday, one of the transplant doctors with whom we were collaborating explained the dire state of a 4-year-old bone marrow transplant patient.

The child was suffering from a severe infection that could not be diagnosed, despite numerous attempts using all advanced methods available to the treating medical team.

Since no additional biopsies could be performed due to the child’s deteriorating health, the doctor asked whether we could try using our prototype technology in the hopes that we would be able to diagnose the infection directly from blood, where all other means had failed.

So with a very sick child in need, we started our race against time.

After getting the necessary regulatory approvals (which took most of Saturday), we drew blood from the patient on Sunday, worked around the clock to prepare the sample for sequencing and finally loaded the DNA sequencer on Monday afternoon.

We were working non-stop, day and night — pushing enhanced versions of our software, refining the algorithms, and tweaking the computational pipelines to get rapid results as soon as the sequencing data became available. Given the child’s deteriorating health, we had to make sure we would identify the pathogen causing the infection as quickly as possible.

On Wednesday, data outputs finally started streaming off the DNA sequencer into our computational pipelines, which was a welcome sight and triggered the next stage of our analysis. Things seemed to be progressing fairly well when, around noon, one of the treating clinicians walked into the lab.

He broke the sad news that the sick child had died earlier that morning.

We must have been in a state of shock, so focused on trying to identify the pathogen, so tired from the work that I don’t think we fully digested what the doctor had said.

I remember initially just turning back to my computer to continue the ‘race against the clock’ by fixing another bug or two in the system before the reality of the news sank in. Feeling physically and emotionally drained, I shut my computer down and went for a long walk around Stanford campus to absorb the news and come to grips with our lost battle.

None of our academic research or exciting scientific discoveries mattered in that moment.

We failed to find an answer in time.

This little child with a weakened immune system, trying to hang on, struggling with merciless pathogens made it all tangible and urgent.

Days later, we were able to correctly identify the infectious disease (eventually confirmed upon autopsy). I thought to myself, “If only we had this system in a more stable format and with a shorter turnaround time, we could have made an impact in this case and perhaps many others.”

With renewed energy, I spent the next few months at Stanford, working with our team to further develop and refine the technology platform and spending time with clinicians to learn everything I could about their needs and where such technology could be used.

Once we determined that the platform could work, I called Tim Blauwkamp — my friend and colleague from earlier Moleculo days — and together we started Karius to bring this technology to routine patient care.

The painful loss of this vulnerable patient is now a driving force for each of us at Karius to work on winning the next million battles.