Non-obvious choices

My film school classmate Heather shared this video of Henry Thomas’ audition for E.T. Take a look.

What stands out are the choices he made. Before becoming an investor, I spent some years in film. I’ve auditioned children for roles and most of them make the obvious choice – screaming, shouting, being loud. That is likely what most of the kids who auditioned for this role did, too. “NOOOO!!! You can’t take him!!” etc.

But what Henry Thomas did was so unexpected. With such little information, he decided to very quietly cry. He made the creature his friend, he asked how the agent even knows all this. He decided to be extremely vulnerable. These are the choices that got him hired.

I’ve often said that there are a ton of similarities between tech and film1. This is one small example – when you are interviewing candidates, a majority will pick the obvious answers. That’s fine. They could be journeymen in the company. But when there is a candidate who makes an entirely non-obvious choice, something that makes you sit back and think in a new and different way, those are the candidates who can change the trajectory of the company. Hire them.


  1. That’s for another post 

Scaling Genomics

Joseph Pickrell and Tomaz Berisa, Gencove

Joseph Pickrell and Tomaz Berisa


Genomics is on the verge of enabling a torrent of data-driven invention, personalization and decision-making. 
Applications will extend across all forms of life?—?from humans to animals to plants to microbes.

In healthcare, genomics could pervade nearly every aspect of patient care, from prevention strategies to decisions about treatments. It also will provide the basis for a new generation of targeted drugs and therapies that can extend and improve the quality of life for billions of people. In agriculture, genomics will optimize plant and animal productivity while aiding in disease resistance and food safety/traceability. Genomics will also play a role in animal conservation, environmental monitoring, and public health and safety.

All these new opportunities will lead to the creation of new markets, products and services, requiring new tools and platforms.

At Spero Ventures, we invest in technologies that make life worth living. We believe genomics will be foundational to advancing the health and well-being of humanity and the planet. It will inform decision-making and touch lives in ways we cannot yet imagine and may not even see. And so it gives us great pleasure to announce our investment in Gencove.

Gencove, led by co-founders Joe Pickrell and Tomaz Berisa, is developing and commercializing a software platform to support low-pass whole genome sequencing. Low-pass sequencing sequences the whole genome at low depth (0.4–4x) and uses imputation algorithms to fill in missing data. The platform empowers decision-makers across consumer, clinical, research, and agricultural fields with easy and affordable access to rich genomic data and insights.

Whole genome sequencing is the most expensive form of sequencing and the most exhaustive. It maps all three billion base pairs within a (human) genome, providing a massive volume of data for analysis. It serves as the foundation for generating new knowledge of how and why living beings develop. And it is becoming the gold standard for discovering new genetic variants and new relationships between genotypes and phenotypes.

The cost of whole genome sequencing has declined dramatically since the early days of the Human Genome Project, famously outpacing Moore’s law. Reductions originally owed to the introduction of Next Generation Sequencing1, followed by hardware improvements, and more recently software that shifts cost and computational burden to later stage analysis2. Despite these reductions, the $500–1000 price point (and even the widely-touted yet still aspirational $100 price point) for whole genome sequencing remains out of reach for a wide range of applications. Without an affordable alternative, these applications will either fail to be commercialized, remain niche and unaffordable for most, or rely on the limited subset of data offered by less expensive DNA microarrays3 (which typically cover 0.03% of the genome).

Low-pass sequencing (LPS) is this affordable, data rich alternative. And Gencove is making LPS available to customers at price points beginning at $50 per sequence?—?on par with microarrays. In addition to offering comprehensive coverage, LPS outperforms microarrays in detecting both common and rare genetic variation. LPS does not require a priori knowledge of the genome making it suitable for new variant discovery and free from the bias inherent in microarrays (which are widely seen as unsuitable for non-Caucasian/European populations not well covered by reference databases).

Gencove’s customers are integrating low-pass sequence data into personalized consumer product offerings, new research modalities, novel diagnostics, plant/animal breeding programs, and more.

We are excited partner with Gencove in its mission to bring affordable genomic insights to customers and industries that have never before been able to affordably integrate them at scale?—?potentially unlocking discoveries and innovations we have yet to imagine.


  1. Next Generation (or High-Throughput) Sequencing became the most widely used technique in the early-2000s due to its ability to handle large-scale, automated genome analysis. 

  2. Including genome assembly, variant calling, quality control, etc. 

  3. Microarrays examine a predetermined set of sites on the genome from which one can infer ancestry, genetic relationships, and some disease risks. 

We + me

David Brooks wrote about his efforts to improve social isolation with his project, Weave:

The first core idea was that social isolation is the problem underlying a lot of our other problems. The second idea was that this problem is being solved by people around the country, at the local level, who are building community and weaving the social fabric. How can we learn from their example and nationalize their effect?

Brooks found these “weavers” all across the nation. When you can connect people around shared interests, common goals and mutually-experienced problems rather than the things that separate and divide them, you build communities.

This is something we think about since one of our key investment areas is human connection. So how can we use tech to do this better? Technology scales and can cross local/geographic boundaries. And it can be used to form deep relationships (remember Twitter in the early days when you formed friendships?). How can tech recreate the feeling of presence and attention? The feeling of a small group intimacy? If we can do this, we open up such interesting ways to make people feel less alone.

The only tweak I’d make to Brooks’ article is his statement that “We precedes me.” Relationships and compassion can live side by side with the idea of self-interest and self-expression. It’s should be in my own self-interest to want my community to thrive and be healthy because I live here. One does not have to precede the other and when we realize that we are all inter-connected and have to coexist is when there will be balance.

Subhasweekaram

Celebrating and honoring my father’s life today, the 13th day, the Subhasweekaram. These beautiful songs are composed by his mother and sung by some of the great Carnatic artists of our time.

1 comment

The Things that Make Life Worth Living

In the past couple of months, we’ve seen some dizzying headlines: “World’s first gene-edited babies created in China, claims scientist,” “AI expert warns automation could take 40% of jobs by 2035” and “Man Marries Virtual Reality Hologram.”

All of these headlines are troubling for various reasons. But they aren’t reasons to reconsider investment in science and technology. I think the opposite is true. We need to support entrepreneurs and technologists who want to use technology to benefit humanity at scale.

Just like nuclear technology can be used to light up a city or annihilate a country, many things have the potential to be used to create or destroy. Yes, genomics, outside the bounds of agreed-upon ethics, might be abused to create designer babies. At the same time, millions of lives could be saved when clinicians are able to harness genomics for preventive and personalized medicine. Yes, artificial intelligence will lead to some job displacement; but it can also assist robots in taking on dangerous tasks, as well as help us understand and solve complex problems such as climate change and patterns of infectious disease. And when someone wants to marry a virtual being, we should see it as one more call to solve the global loneliness epidemic.

About this time last year, my partners and I were thinking about what kind of fund we wanted to bring into the world and the types of businesses we wanted to invest in. As part of the process, we thought a lot about what the future might look like.

After much discussion, we came to the conclusion that regardless of what it looks like, the fundamentals are likely to stay the same. The things that matter most to us today will continue to be the things that matter most to us in the future. They are:

  • Well-being – health, the environment and the food we eat
  • Work and a sense of purpose
  • Human connection

These are the things that make life worth living.

We founded Spero Ventures to partner with revolutionary entrepreneurs who drive progress by building successful companies that both scale and inspire…

…like Tim at Roam Robotics, which makes a flexible, affordable exoskeleton that helps people in sports, life, rehabilitation and work; Ivonna and Gabby at Fathom.ai whose mission is to support every athlete to perform at their full potential; Michael and Matt at Skillshare, which aims to turn the new economy into an open meritocracy by making it possible for people to gain the skills they need; Porter and Ryan at Jopwell, which empowers underrepresented minority candidates to advance their careers; Anthony at SafeTraces, which helps ensure the safety and traceability of our food supply; or Grant at Droneseed, which uses drones to make reforestation safe, efficient and scalable.

We help companies scale their products and businesses to serve billions of customers?—?we’ve done it as operators and product leaders at startups and multi-billion-dollar publicly-traded companies, and now as board members.

If you’re building a company that aims to make an impact on the word at scale, please reach out to us at info@spero.vc.

True Product Leadership is Product Stewardship -

True Product Leadership is Product Stewardship

As product leaders, we all want people to love what we create. But people often use our products in ways we never could have predicted. Once we release something into the world, it belongs to the users?—?and sometimes they use our products in unexpected and negative ways. We can’t be held responsible for what they do with it… right?

It’s time we take more ownership of the impact our products have on the world. The stakes are too high to claim ignorance?—?particularly in tech, where our products can reach billions of people. True product leadership extends beyond creation: True product leadership is product stewardship.

We have become painfully aware of what can happen when the tools we use encourage our worst instincts and amplify the most virulent voices. In past few months, there have been several violent efforts where the suspects behind them had been vocal about their beliefs on social media. Do the platforms really have no control over the ways in which their products are used? That feels both naive and untrue.

When I led product at eBay, we wanted to be “a well-lit place to trade.” The company’s mission was “to empower people by connecting millions of buyers and sellers around the world and creating economic opportunity.” That was the intention. But as we scaled, people began to use eBay in ways we hadn’t predicted. At one point people began trading disturbing items, including Nazi memorabilia. As we thought about how to solve it, we asked ourselves a few questions: Who are we? What do we believe? Why did we create this product? Once we framed it in terms of core values, the decision about what to do became clear. The company decided to ban all hate-related propaganda, including nazi memorabilia.

Product leadership teams can do more than curb bad behavior. They can also work to encourage good behavior. Last year, during the refugee crisis when governments around the world turned them away, Airbnb’s product team worked on a solution. In June 2017, Airbnb launched Open Home?—?a way for people to give refugees a place to stay. This was not just a marketing stunt. Airbnb invested in building a brand new product: a marketplace that allows people to offer their homes for free to refugees and victims of disasters.

Thoughtful product stewards can also protect us from ourselves. Plenty of studies have shown that technology can be addicting. Apple is taking some admirable first steps to help us resist temptation. Screen Time, launched as part of iOS 12, offers new tools for managing screen time. Jony Ive was recently interviewed about it. “If you’re creating something new, it is inevitable there will be consequences that were not foreseen,” he said. “It’s part of the culture at Apple to believe that there is a responsibility that doesn’t end when you ship a product.”

How do we create that kind of a culture? Here’s a stab at a few steps we could take towards regaining control over the way our products live in the world.

Step one: Define.

Before you begin designing, sit down with the team to define how you want your product to be used, as well as what people shouldn’t be able to do with your product. Drawing this line upfront will provide clarity for a muddy future when the world changes around you.

Step 2: Imagine.

Think about all the things people could do with your product, including edge cases. What unintended consequences come up? What could happen if the “worst” person got their hands on your product? How can you incentivize people to use it in the right way, and penalize people who don’t?

Step 3: Communicate

Communicate your beliefs, values and intentions to everyone at your company. If a stranger asked anyone how the product should and shouldn’t be used, every employee should give the same answer. This ensures that everyone is on the same page, morally. Instead of making hard decisions when things are blowing up, you’ve already agreed what to do.

Step 4: Measure

Product people measure everything. How can you measure the ways people misuse your product? What early warning systems could you put in place? Review the data and the signals it’s sending you at least once a quarter.

Step 5: Do Something.

There will always be unexpected surprises. But since you already know your moral line in the sand, when you see something that crosses that line, you’ll know it. And you can take action.

Technology should enhance human connection. It should help make the world better. The first step is for us all to begin to see product leadership as product stewardship.