Day Zero Diagnostics is Modernizing Infectious Disease Diagnosis and Treatment
Kailash Sundaram | June 4, 2018
Antibiotic resistance poses one of the most significant threats to global health and economic development today, according to the World Health Organization. This issue is catalyzed by an improper application of antibiotic treatment to microbial disease.
Enter Day Zero Diagnostics, a Boston-based company revolutionizing the diagnosis and treatment of infectious diseases with genome sequencing and machine learning. At a high level, Day Zero employs next-generation sequencing methods to generate structured clinical data. Then, algorithms match that data with a proprietary microbial resistance database to identify the strain and antibiotic resistance profile of a bacterial infection. Armed with this information, physicians can provide faster treatment with the right antibiotics to save lives and reduce healthcare costs.
In less than two years since founding, Day Zero has captured the MedTech Innovator grand prize, won the Harvard President’s Innovation Challenge, and raised $3 million in seed financing from angel investor Golden Seeds and Sands Capital Ventures. As Day Zero develops its solution ahead of a Series A round in late 2018, we spoke with Co-Founder & CEO Jong Lee on the company’s progress and long term objectives.
Beginnings at the Kwon Lab, Mass General Hospital
As an Infectious Disease physician, Kwon encountered a dearth of data-driven diagnostic tools in the treatment of infectious diseases. While unstructured data was abundant, conventional treatment methods failed to harness it. Kwan, along with Melis Anahtar, a Rhodes Scholar and Immunology graduate student in his lab, were investigating methods of augmenting conventional treatment with genome sequencing – the cataloguing of an organism’s entire genomic DNA sequence. Their research formed the cornerstone for Day Zero Diagnostics.
Kwan and Anahtar soon brought on Dr. Miriam Huntley, a computational biologist and Harvard PhD in mathematics, and Dr. Dougal MacLaurin, previously an engineer at Google Brain, developer of popular machine-learning library Autograd, and Harvard PhD in physics, to spearhead the development of advanced machine-learning research and development.
Meanwhile, Lee was in Seattle, Washington, following an expansive career in healthcare consulting at Monitor Group and medical technology at ConforMIS, Inc, when he received a call from Kwon. Kwon had been his undergraduate roommate in Lowell House at Harvard. Kwon offered a proposition for Day Zero, and Lee was a perfect fit.
What sets Day Zero’s founding team apart from other entrepreneurship in the medical space – particularly around the Harvard and MIT ecosystem – is that it is not built entirely around a senior academic. Rather, the team is a conglomeration of experts in different fields, allowing for diversity of thought with a flat organizational structure. The diversity in thought and expertise has been a perfect fit.
“We have conversations that would be highly disruptive in most companies,” says Lee. “When we have these conversations amongst our founding team, however, they’re really rational and fair, and almost easy compared to conversation that might have taken months amongst other companies I’ve been involved with.”
Addressing a Critical Public Health Issue
The five co-founders, along with six research scientists and lab technicians, are on a mission to alleviate a global public health crisis: microbial antibiotic resistance.
According to the Center for Disease Control (CDC), at least two million people each year become infected with bacteria that are resistant to antibiotics – and at least 23,000 die as a direct result. “Twenty years ago, if you had an infection that might kill you, it was pretty easy to treat you. Doctors had a high degree of confidence that whatever the pathogen was that was creating the infection would get killed,” says Lee.
Now, due accelerating antibiotic resistance, treatment has become significantly more complicated. “Doctors will try to give you a broad spectrum of antibiotics because it’s important to treat you quickly, but those antibiotics may not work,” adds Lee. “And, they don’t have a way to predict well whether it’s going to work on you.”
Day Zero intends to help physicians practice antibiotic stewardship through rapid diagnostics and epidemiological surveillance data. By practicing stewardship, physicians can make current antibiotic solutions last. However, to properly manage antibiotic treatment when faced with a dying patient, physicians must have diagnostic information that empowers them to make accurate decisions.
“In the absence of that diagnostic information, you’re just going to give that patient whatever it may seem like they need and you’re not worrying about the public health implications if you have a patient that is in dire need of treatment,” says Lee.
Armed with data from the diagnostic, Day Zero will offer a commercial clinical surveillance system targeted at identifying macro trends, such as developing resistant mechanisms. The team’s ultimate objective is to best inform researchers and practitioners about which antibiotic treatments are more likely to work and to track how quickly antibiotics are developing resistance.
The team does not intend to develop new antibiotics, although Lee indicates “it’s very possible the data [Day Zero] generates will help identify new targets.”
How the “Diagnostic” Works
At the center of Day Zero’s solution to antibiotic resistance is next-generation sequencing, also known as “high-throughput” sequencing. Unlike previous generations of sequencing, which were labor-intensive and time consuming, next-generation sequencing enables individuals to sequence DNA and RNA overnight and at lower costs.
In particular, Day Zero employs a combination of two different types of next-generation sequencing technologies: illumina and nanopore. While illumina uses an approach called sequencing by synthesis – in which an optical detection technology takes short snippets of DNA, replicates them, and reads out the sequencing – nanopore uses electric currents to read long DNA strands. “[Nanopore] enables you to get very long reads very quickly and in an order of magnitude longer than you could get with using illumina. Its disadvantage is that it might not be quite as accurate as illumina, which reads the same DNA strand multiple times,” explains Lee.
Day Zero utilizes next-generation sequencing to generate structured clinical data from unstructured microbiological samples.
Microbiologists until now have relied on microbiological culture, an organic method of increasing bacterial cells, to identify the pathogen. This process currently takes between three and five days – far too long when lives are at stake. “The unsolved problem in the microbiology space is that while you can sequence things, it’s not set up to work well in a microbiology lab. The sample prep that’s required in order to make the sample set sequenceable, is not there yet,” says Lee.
Given vast sets of clinical microbiological samples, Day Zero can generate sequenceable samples within three to five hours.
Then, Day Zero matches genomic data utilizing its Keynome™ algorithm with its proprietary database of microbial resistance profiles, called MicrohmDB™. This matching process enables Day Zero to pinpoint genome-specific resistance and generate accurate treatment recommendations.
An Initial Focus on Sepsis, A Life-Threatening Disease in the Blood
Day Zero’s initial focus is on Sepsis, a blood-stream infection that microbiologists often struggle to culture. Because blood infections generate complement activation and an active immune system, they often result in few bacterial cells. The lack of bacterial cells, in turn, make it difficult for scientists to identify the pathogen. And Sepsis can be particularly deadly. Patients with severe sepsis, for example, can experience up to a seventy-two percent mortality rate.
In the future, Day Zero plans to expand its sample prep products outside of bloodstream bacterial infections, with targets including urinary tract infections and cerebral spinal fluid infections.
Despite potential competition from other and incumbent healthcare companies, Lee indicates Day Zero is laser-focused on its mission: to meet a specific, unmet clinical need with global ramifications.
“At the end of the day, we keep in mind that the unmet clinical need is real. Doug is constantly talking about patient situations he encounters, where he says, ‘If we could do this diagnostic today, I could save this person.’ And that really brings it home: it’s infectious.” – Jong Lee