This Startup Wants To Catch Cancer Before It Spreads

**Jared Friedman** (0:01)
One in 11 babies born in America this year will be screened by a genetic test that didn't exist a decade ago. Can you articulate like the needle in the haystack problem that you have to solve?

**David Tsao** (0:12)
There are three billion base pairs in the human genome, and a lot of the human diseases that we are detecting from mom's blood, sickle cell disease, cystic fibrosis, et cetera, it's usually only one base pair that's different. So you're looking for one base pair that's different out of billions, and that's where the BillionToOne name came from.

**Jared Friedman** (0:28)
The prenatal test from BillionToOne is already one of the most widely used genetic tests, but that's just step one. They're also working toward solving one of the most elusive problems in medicine.

**Oguzhan Atay** (0:39)
We are maybe less than a year away from launching our, you know, ultra-sensitive MRD test, minimal residual disease test for stage one to cancer patients.

**Jared Friedman** (0:50)
And that same technology could one day be used for early stage detection so that the cancer can be caught before it ever reaches stage one.

**Oguzhan Atay** (0:57)
Once we are there, I think technically we would have solved the, you know, holy grail of cancer detection.

**Jared Friedman** (1:04)
BillionToOne was built by two PhD students who started with half a lab bench and $300,000. So how did they pull it off? And what will it take to make a blood test that detects cancer early? This is the story of BillionToOne.
I met Oguzhan and David way back in 2017 when they applied to YC. They've come a long way since then. I recently visited them at their lab in Union City, California to hear the full story. I'm so excited to get to sit down with you guys today. To start with, why don't you tell everybody what BillionToOne does?

**Oguzhan Atay** (1:44)
BillionToOne is a next generation molecular diagnostics company. We detect DNA in blood samples. This is important because all of our different tissues shed this DNA into the bloodstream. This includes fetus, a developing baby, in mother's womb, it releases DNA into the bloodstream, and cancer as well. As cancer is mutating and growing, it releases its DNA into the bloodstream. By detecting this DNA, we can develop diagnostics that have been impossible even a decade ago.

**Jared Friedman** (2:20)
And all their hard work is paying off. Late last year, they took the company public at a valuation over $4 billion. Can you guys give us a sense of the scale that you guys are operating at here?

**Oguzhan Atay** (2:31)
We are processing more than 600,000 tests a year, and in terms of the overall market share, we are close to 20% market share there.

**Jared Friedman** (2:43)
Remarkably, the core idea behind BillionToOne is the same as when they applied to YC back in 2017 They were convinced it should be possible to create a prenatal genetic test that works by sequencing fragments of fetal DNA that naturally exist in the mother's blood, and that this would someday be universally adopted. This was a radical idea at the time. Before BillionToOne, most genetic abnormalities could only be detected via amniocentesis, an invasive procedure that is only used in high-risk pregnancies. How is the key insight that enabled you guys to do this when no one else was able to do it before?

**Oguzhan Atay** (3:17)
We have realized that DNA that is coming from the fetus and the tumor is both very dilute and rare. Right? So you might only have a few molecules among billions of other molecules. So every molecular diagnostics approach here requires, in the lab, using a process called PCR to amplify this DNA billions of fold.
And the problem is that this DNA amplification process can add tremendous noise, so that the small signal that you have can be lost. So what we have done is to add a synthetic DNA into the patient sample that we get before any amplification happens. The synthetic DNA allow us to know how much amplification happened at different genomic locations. You know, what are the errors that are being introduced by the amplification process. So then we can remove those errors from the sequencing data, the data that we get at the end, so that we know what was in the sample to begin with. That converts a difficult biology problem to almost a simple mathematical problem.

**Jared Friedman** (4:31)
Let's break that down even further. Every tissue in your body sheds tiny fragments of DNA into your bloodstream. Hidden inside that mix can be a fragment from a fetal condition or a sign of cancer. But detecting it is a needle in a haystack problem. Traditional genetic tests amplify everything, including background noise, which means they can't find the needle. BillionToOne has a clever trick. Before amplifying, they add known synthetic DNA molecules to the sample. Because they know exactly what they added, they can see how much distortion the amplification introduced and subtract the noise using machine learning. The result is that they can spot things no other tests can pick up. I want to go back to the first couple of years of the company and talk about how you went from PhD students who had a cool idea to an actual commercial test that was live and processing samples from real patients. Tell us about how you did it and how you did it so fast, because you guys did it in two years, which is like one of the fastest I've ever heard of a company doing this.