Blood Test to Detect Prenatal Genetic Defects to Soon be a Reality

FIT interviews an Indian scientist behind non-invasive prenatal blood tests to detect genetic abnormalities.

Sukrit Silas and BillionToOne is behind non-invasive blood tests to detect genetic abnormalities in a fetus

(Photo: Sukrit Silas/Altered by FIT)

A unique healthcare innovation by a young Indian scientist has the potential to radically change how prenatal genetic testing is done to identify fetal abnormalities.

FIT interviews Sukrit Silas, a PhD from Stanford and the Chief Science Officer at BillionToOne, a Y Combinator Company. They’ve developed a non-invasive prenatal test from maternal blood that allows doctors to detect genetic abnormalities in a fetus.

Currently, if the doctors suspect any abnormalities, expectant mothers go through an invasive and risky procedure called amniocentesis. The procedure involves a large hollow needle that is inserted into the uterus to pull out a small amount of amniotic fluid from a sac that surrounds the fetus. The fluid is then screened for chromosomal abnormalities and infections.

Tell us a little about how you started BilliontoOne and the prime motivation for starting it?

I started BillionToOne along with a couple of old roommates from my college days at Princeton university, as we were all finishing our PhDs. I had been working on an extremely sensitive method for detection of rare nucleic acids, and in conversations with my friends, I realized that the same method could be used to “count” DNA molecules as well. We started the company in early 2016 and were lucky enough to be picked up by the Y Combinator fellowship program that winter.

Back then, the primary reason for starting the company was to prenatally detect genetic diseases such as beta-thalassemia, which are endemic in India. Since then we have diversified to focus on the US market, but the overall purpose remains the same. To provide affordable testing for expectant mothers everywhere.

The non invasive prenatal tests developed by you are at what stage of development? How soon can we see them in the market?

The tests are basically ready! That was my role here, to set up and run clinical trials for our technology, to see how well they perform in the real world, and not just in the esoteric environment of the lab. The trial for the beta-thalassemia test is almost concluded, so we’re planning on launching as soon as we are able. The trial for the affordable Down’s syndrome test is on going at AIIMS and will probably take several more months, but there’s only so much we can handle at a time ourselves!

Currently, if the doctors suspect any abnormalities, expectant mothers go through an invasive and risky procedure called amniocentesis. (Photo: iStock) 

What made you choose India as the base for clinical trails – can you share the broad results/interesting findings with us?

There was a very simple reason for doing the trials here: We chose India for the trials because we were trying to solve a problem that is endemic in India. That was really the entire motivation for starting the company, and also the vision which we pitched to get our seed funding.

Of course, as we proceeded down this path, it turned out that we also had to launch US trials and set up an operation out West, if we were to be able to properly market the test in India. So now we also have a core study for the beta-thalassemia/sickle-cell anaemia test in the US, in collaboration with the Baylor College of Medicine. All I can say for now is that the trial in India is concluded and the data are being analyzed!

What makes these tests different from amniocentesis, that is currently used to detect genetic abnormalities?

Amniocentesis is a “diagnostic”. It pretty much always gives you the right answer, but it’s also an invasive test. That means that a sample needs to be taken from the amniotic fluid - the fluid that’s surrounding the developing foetus. Now, if you’re looking for a rare disease - let’s say 1 in200 newborns is affected -  and you have a detection technique like amniocentesis that results in a miscarriage 1 in 200 times, you can’t really use that test on a population scale. Our tests are non-invasive. It’s like getting a blood sugar test done - all we need is a tube of blood from the mother.

The key innovation here is how to reliably get the signal of a single-gene mutation in the baby, which is pretty much the most minute genetic change you can hope to detect, from the mother’s blood, which is obviously full of her own DNA.

What abnormalities can the tests developed by you detect?

We’re focusing on beta-thalassemia and Down’s syndrome for now, but the same principle will very soon be used to make tests for cystic fibrosis, spinal muscular atrophy, and alpha-thalassemia. Essentially, if it’s a common genetic disorder that is worth trying to detect, we can detect it.

Down Syndrome (DS) is a genetic disorder that leads to mental issues and abnormal physical growth.(Photo: iStock)

How do you see the pricing working out for these tests– the success will lie in their affordability I presume.

Absolutely. And especially in the Indian market, where medical expenses are usually borne out of pocket. We’ve placed the emphasis at every step on keeping the costs down, with an eye to making the tests successful in India. Of course, the game is entirely different in the US, where the crucial thing to do is to get insurance to pay for your test.

At what stage of pregnancy should a woman get these tests done?

We’re targeting 10-14 weeks gestational age. So pretty much as early as possible in the late-first/early-second trimesters.

Social innovation in healthcare is a must if we want to achieve healthcare for all. How difficult or easy is it to get funding for something like this and to sustain it.

It was definitely a bit rough initially, because we were several steps removed from the kinds of things Silicon Valley investors are comfortable investing in. We are a biotech company, and biotech investments are not like“tech” investments. We have to deal with laws and regulations,ethics, standards that our product must meet before it can be launched, and all this makes investors edgy. To top it off, we were a biotech company in India,so you really need an adventurous investor, dedicated to the possibility of making social change, to make this work.

Fortunately, there are plenty of people like that in the world... you just have to find them! After we participated in the Core Accelerator Program at YC in2017, that’s when we found the investments we needed to launch this ship off the ground. Once you start making progress, getting funding gets easier,because you have more to show for your idea.