Jungla and Unknown Significance

How Jungla went from IndieBio to a $65m exit in three years

Arvind Gupta
IndieBio
5 min readAug 5, 2019

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It’s a simple idea, really, that if you could read every letter in your genome, we would understand completely what makes you, you. Of course, that’s too easy to be true.

Whole genome sequencing was the holy grail of genetics in the 1990s and the Human Genome Project was finally completed in 2003. We learned it may be a simple idea, but way more complex in practice. What makes you you may be in the genes, but what do those genes mean? And what about the ones we haven’t seen before? It was a mystery that was the difference between seeing the syllables in Romeo and Juliet and weeping when Romeo wakes to find Juliet dead — because you understand what was being written.

The new gold rush was on. Correctly interpreting our genome and its regulation will affect everything from how we have children to how we eat. It will create both legal and social dynamite based on what we learn about ourselves, our history and our relationships. It will take the nascent $20 billion gene sequencing industry and explode into a multi-segmented market worth hundreds of billions of dollars yearly, changing medical care forever.

Three years ago Nick Ouzounov, CSO of IndieBio portfolio company Geltor, introduced me to two exceptional founders.

Carlos Araya and Alexandre Colavin struck an immediate impression when we first met at the IndieBio lab in downtown SF. Both were quick to smile but from opposite angles; Carlos’ machine gun speech and Alex’s more shy glances downwards.

They were working on Variants of Unknown Significance (VUS), a subset of genomic interpretation. A huge problem in genetics is understanding what a particular mutation in a gene will do if it has not been observed before. BRCA1 is a well known mutation that causes susceptibility to breast cancer. We know that at the 185th nucleotide a deleted Adenine or Guanine can predispose one to breast cancer. This is because after sequencing thousands of breast cancer genes we observe this deletion event over and over and therefore have correlated the two events.

Genetic mutations like BRCA 1 and 2 are inherited from both mother and father. Knowing if the inherited gene will cause cancer depends on if that gene sequence has been observed in other patients before.

And here’s the billion dollar problem. If if you sequenced your gene for breast cancer and they found a sequence that wasn’t normal but also not seen as cancer causing, what would you do? That sequence is called a Variant of Unknown Significance, or as is said in the industry, a VUS. This may seem like an incredibly rare event, but it’s not. Every time you pass on your DNA to your kids, 100–200 mutations are generated, which they carry for life. This is about one mutation every 20 million base pairs, across the three billion we all carry. It is also why our DNA is a unique fingerprint and 99% of our DNA fingerprint is still a mystery.

While doing their PhDs and postdoctoral work at Stanford, Carlos and Alex had developed an approach to solve the mystery of VUSs. They used machine learning to look at the particular variant and predict its effect on the protein and the level of harmfulness of the variant. Later on, they developed a lab based assay to corroborate the interpretations, and further train the network (a critical piece of the puzzle we call “wet-in-the-loop”).

A more accurate representation of how a BRCA gene can vary within just one family tree. The problem is much more complicated in real world applications.

By the end of our conversation I was convinced their approach could shed light on VUSs with the proper interpretation and assay cycle. The critical business and product milestone in the IndieBio seed round would provide enough confidence in the interpretation that a doctor would use this in a Laboratory Diagnostic Test to counsel a patient. We funded Jungla, to build out the algorithm and data platform and achieve customer traction, all in four months.

IndieBio HQ in downtown San Francisco

Carlos and Alex were up for it. Jungla was incorporated on February 18th, 2016.

Over the next four months Carlos and Alex put their heads down and built the product and became entrepreneurs — which meant, according to Carlos, “getting out of their comfort zone and building a business through sales”. They learned to cold-call, cold-email and hustle their way to contracts. They learned to follow-up, understand the difference between an investor’s curiosity and interest and what customers will will pay for and not. Carlos mentions that “one of the most valuable things they got at IndieBio was the ability to see customer interactions as a conversation about value rather than a transaction of yes or no.” “In fact, I understood that being a good CEO was as critical to Jungla as having the best science,” Carlos continues. “As a scientist I thought it would be no big deal but it is a big deal.” With their growing confidence they developed the business model in real-time with the product. Jungla won IndieBio Batch 2 Killer of the Week for their data contracts and framed the result. That award still sits in their office.

Just after graduating IndieBio demo day, Jungla received a $2.5m investment from A16Z in which IndieBio/SOSV participated. “The seed round went smoothly because we were so well prepared”, Carlos explained.

A year later, genomic interpretation was becoming more important than ever. And within this competitive market, Jungla was looking for the perfect customer for their latest product build.

VUS discoveries are increasing exponentially as more sequencing data are being generated.

Invitae is the largest genetic testing service to individuals and healthcare providers and they needed a solution to the VUS interpretation problem. With his skillset in hand, Carlos approached and closed, within four months, a pilot with Invitae to interpret VUSs in their samples. The pilot went so well that Invitae offered to acquire Jungla to incorporate their technology into Invitae’s offering. We all thought it was a great move.

Together, Invitae and Jungla will accelerate the final interpretation step in genetic testing to help millions of people understand themselves better. This acquisition will guide treatment options and prevent unnecessary procedures for thousands of patients every year. I’m so proud of what the Jungla team has created and the positive impact they are having on society.

And there is so much more to do. IndieBio is looking forward to funding more companies innovating in the genetic screening and interpretation space. If you have an idea to change how we experience our world through genetics, please email me.

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Arvind Gupta
IndieBio

Partner @Mayfieldfund, Founder @Indbio, Former Design Director @IDEO, I invest in human and planetary health