This Startup Wants To Catch Cancer Before It Spreads

Billion to One is a company that specializes in next-generation molecular diagnostics, focusing on detecting DNA in blood samples. This capability is significant because all tissues, including those from a developing fetus and cancerous growths, shed DNA into the bloodstream. By detecting this DNA, Billion to One can develop diagnostics that were previously impossible. The company, founded by two PhD students, recently went public with a valuation exceeding $4 billion and processes over 600,000 tests annually, holding close to 20% market share in its field. The core idea behind Billion to One, conceived in 2017, was to create a prenatal genetic test by sequencing fragments of fetal DNA in the mother's blood, aiming for universal adoption. This was a radical concept at a time when most genetic abnormalities required invasive procedures like amniocentesis. The key insight that enabled Billion to One's breakthrough was recognizing that both fetal and tumor DNA are very dilute and rare in blood samples, existing as only a few molecules among billions. Traditional molecular diagnostics use PCR to amplify DNA, but this process introduces significant noise, obscuring the faint signal. Billion to One's innovation involves adding synthetic DNA to the patient sample before amplification. These synthetic DNA molecules serve as internal controls, allowing the company to quantify the amplification biases and errors introduced during the process. By subtracting this noise using machine learning, they can accurately detect the original DNA signal, transforming a complex biological problem into a mathematical one. The founders, Ozan and David, met as undergraduates and later pursued PhDs in biology-related fields. Their journey began with identifying the potential to detect conditions like sickle cell disease, cystic fibrosis, and thalassemias directly from maternal blood samples by reducing noise. They recognized the interdisciplinary nature of the problem, requiring expertise in both data analysis and the chemistry of DNA generation, a gap they were uniquely positioned to bridge. After applying to YC with just an idea, they developed and proved the accuracy of their first test within six months. Their initial lab space was a shared facility, and securing basic supplies was a challenge due to their lack of established financial history. The first $300,000 in fundraising was particularly difficult, taking six months to secure. Even after launching their prenatal test, initial adoption was slow, with only one physician using it for one or two tests per week two months post-launch. This led to an emergency meeting where they pivoted their sales strategy, rapidly hiring more sales representatives and focusing on patient-led marketing. By educating patients about the test, they empowered them to advocate for its use with their physicians, which proved effective in gaining traction. Once they overcame the sales hurdle, Billion to One scaled up, building a state-of-the-art lab in 2022. The lab processes samples through a multi-day workflow, from logging and tracking samples using AI and computer vision to centrifuging blood to separate plasma, where cell-free DNA resides. Liquid handling robots precisely extract the plasma. Their proprietary quantitative counting templates (QCTs), manufactured in-house, are added to every sample to measure and remove biases. A remarkable aspect of their process is the ability to combine and sequence thousands of patient samples simultaneously by "barcoding" each sample's DNA with a unique sequence before mixing. This allows computational analysis to trace each sequence back to its original patient. While most samples follow a "happy path" for automatic analysis, complex cases are reviewed by a team of laboratory directors and genetic counselors, sometimes involving up to 20 people discussing a single sample. Billion to One's technology extends beyond prenatal testing. The same core method for detecting free-floating DNA is applicable to detecting cancer through a blood test, known as a liquid biopsy. They commercially launched an early version of this cancer test in 2023, demonstrating their capability to operate in two markets simultaneously. This aligns with their long-term strategic plan, conceived in their first year, to progress from prenatal genetics to late-stage cancers and then to early-stage cancers. They recognized that cell-free fetal DNA and cell-free tumor DNA are fundamentally similar, allowing the same technology to be applied to both. Starting with oncology would have been more difficult for initial commercialization, so prenatal testing provided the necessary resources to expand. A poignant patient story highlights the impact of their cancer products. A young individual in their 40s with metastatic colorectal cancer, who had exhausted treatment options and was facing hospice, was tested with Billion to One's Northstar Select test. The test identified microsatellite instability in the tumor DNA in the patient's bloodstream, indicating eligibility for immunotherapy, a therapy not suggested by previous tumor biopsies. The patient responded remarkably well, with the cancer "melting away," leading the impressed doctor to widely adopt Billion to One's blood tests for his cancer patients. Billion to One emphasizes building an interdisciplinary team, seeking individuals who can bridge different scientific domains. Their research teams are small, with principal investigators leading two to three research associates, reporting directly to the founders. This structure minimizes bureaucracy and accelerates product development, creating "many startups within the larger company." Their long-term vision, a three-step plan, began with prenatal testing, moved to late-stage cancer (their current focus), and aims for early-stage cancer detection. Step three involves using their technology for stage one and two cancer patients who undergo curative surgery. Approximately 20% of these patients have microscopic residual disease undetectable by scans, which Billion to One believes it can detect. Step four, the ultimate goal, is universal cancer screening in the general population, enabling the detection and removal of tumors before they spread. This "holy grail" of cancer detection has been elusive due to the immense resources required for early detection without a step-by-step approach. The founders acknowledged that as first-time founders, raising over a billion dollars without initial revenue was impossible. Their phased approach, however, allows them to build on successes and move towards solving problems for millions of cancer patients, potentially making a significant impact on cancer treatment in the next century. The company fosters a culture where "pressure is a privilege," attracting individuals seeking challenging work that can profoundly change healthcare. Despite going public, employees remain driven by the growth, challenges, and love for their mission.