Starting with Why

A common trope of childhood is a kid questioning a parent with an infinite series of increasingly vague "Why"s. It starts simply:

Child: Why do we have to go to the grocery store?

Parent: Because we need to buy food.

Child: Why do we need to buy food?

Parent: So we can cook it and eat it this week.

Child: Why do we eat food?

Parent: Because our bodies burn energy, and the food replaces the energy.

Child: Why do our bodies burn energy?

Parent: Because physics! Get in the car!

This post takes the opposite approach. It starts with the broadest of "whys" and gradually addresses more specific questions to explain how we arrived at this point. Why was Lodestar founded? Why should you care about Lodestar? 

People are inherently drawn existential questions and we ascribe them importance. Why am I here? What is real? What's my purpose? Does anything matter? In discussing is book 21 Lessons for the 21st Century,  the historian and philosopher Yuval Harari says:

Ultimately, there is a reality. The best test of reality that I know is the test of suffering. Suffering is the most real thing in the world.

So much of life is subjective and debatable. Is building AI at Facebook a net positive for humanity? Maybe. Should people be working towards the electrification of the auto industry given its requirements on mining rare-earth elements? Probably. Is it bad when a young woman—who has spent much of her life in the hospital because she has a small genetic mutation that causes her lungs to be incapable of clearing mucus—dies of an infection? Yes. It is.

One of the conclusions of 21 Lessons is that people should do what they can to minimize suffering, both for themselves and for the beings around them. I agree, although, I would frame it slightly differently. People should strive to maximize the wellness of others. To be clear, the goal is wellness, not happiness or excitement, or any other single component emotion. Each of these component emotions is an important contributor to wellness. It's impossible to be well if you're never happy. However, emotions like happiness are inherently ephemeral and make for poor goals. The goal is robust and holistic wellness.

Why does Lodestar exist? To enhance the wellness of others.

Okay, but there are many ways to help people. Building homes, battling climate change, providing entertaining, conducting basic research—why Lodestar specifically? Humans have been practicing medicine for a long long time. But there's something special about being a part of the biotech healthcare space right now. We're at an inflection point in our efforts to form a comprehensive picture of the puzzle that is human biology. The previous three decades, since the advent of the Human Genome Projects, have centered around constructing a framework. Three puzzle pieces needed to be assembled.

First, the fields of molecular biology and genomics have begun to comprehend the importance of many complex biological mechanisms: regulatory region behavior, chromatin interaction maps, alternative splicing, and epigenetic modifications, to name a few. In pursuit of our understanding of these mechanisms we've created technologies like long-read sequencing, and CRISPR-Cas9, and functional saturation assays. These technologies, in a positive feedback loop, have enabled scientist to begin understanding even subtler biological phenomenon. As a result, scientists have generated data that is as diverse as it is massive. 

Second, on the computational side, bioinformaticians have made substantial strides in algorithm development, AI adoption, and software engineering. The community now has broad consensus on which algorithms to use for daily tasks like short-read alignment and variant calling—consensus that was not always present. Artificial intelligence isn't only a buzzword: DeepVariant can find variants in previously uncallable regions, while AlphaFold begs the question of whether protein-folding is a solved problem. And while bioinformatics and software engineering may seem nearly identical, there's a meaningful difference between writing code that works on one specific laptop and code that's capable of processing thousands of samples a day and is maintainable by a team of two dozen; thankfully, software engineering best practices are gradually permeating bioinformatics. These improvements to the field have created powerful computational tools which are now in the hands of thousands of scientists who can quickly apply these tools to their own unique datasets.

Third, across all aspects of the industry, we're vigorously redefining what is means to operate at scale. Computing power as increased 1000x since the HGP began. The reduction in sequencing costs has outpaced Moore's Law. Ultima and Illumina are vying for the "$100 genome". Meanwhile, the EU and the US have initiatives to collect the genomic and paired phenotypic data of millions of individuals. These projects might seem like end goals, but they're not; they're our initial steps towards deeply understanding human genetic diversity and the relationship between our variants and our identities as individuals.

We've assembled these three core sections of the puzzle: tools for collecting diverse biological data, computational techniques for understanding the collected data, and the necessary infrastructure to collect and process at scale. In the coming decades, with these sections assembled, the remaining puzzle pieces will rapidly fall into place. The actual end goals of this endeavor will start to be realized. Lodestar's vision, for example, is that every child with a rare disease can expect a diagnosis. Other organizations envision patients never receiving therapeutics that their bodies can't process, or of detecting cancerous cells before they spread in the body. All of these visions have a couple things in common. First, their purpose is to enhance human wellness. That's our why. Second, all of these visions are poised to become possible in the coming decades.

Why Lodestar specifically? Because the biotech field currently presents an opportunity to have an outsized effect not only on the wellness of the people we treat today, but on the future trajectory of all humanity.

Sure, biotech is an interesting field; but plenty of companies exist in the sector, many of them making similar claims. Why start a new company? I'm starting Lodestar to test what's possible. I mean that in two different ways. 

On the level of the biotech field broadly, I believe there are many unrealized opportunities to help patients. Some of these opportunities, I believe, are easily attainable; and yet, nobody has seized them. Why is that? An easy explanation is "Well, those 'easy opportunities' are significantly harder than they appear." Alternatively, I've been part of conversations that sound like this:

(PM = Project Manager, TL = Tech Lead, IC = Individual Contributor, SME = Subject Matter Expert)

PM: This feature is blocking our launch next week. What are we going to do? 

TL: I don't really know this system, but I'd guess it's a medium-sized lift. We can meet the day after tomorrow and scope the tickets. To speed things up we we'll have to find a way to split it half, and we can assign chunks to IC1 and IC2.

IC1: I don't know this code either, but I can start learning after we have our scoping meeting.

IC2: I'm not finished with the other ticket blocking our launch, but I'm happy to jump on this as soon as I'm done.

PM: How long do you think it'll take once you two get started?

IC1 + IC2: Maybe a week? Hard to say, it could be a little more.

TL: So counting planning time, we're probably looking at a full sprint. 

PM: It sounds like I'm going to have to announce a launch delay?

SME: Hey everyone, I know exactly what needs to be done with for this feature. If I can clear my full calendar today, I can have this in code review by the end of the day. Maybe tomorrow morning.

Then the SME delivers on their promise. The moral here is that it can be tricky for even people adjacent to the task to accurately estimate the effort required to solve a problem. The only way to know what's possible is to do it.

On a personal level, I am starting Lodestar for the joy and challenge of testing if I can create a successful company. Younger versions of me were the opposite of the founder archetype. I was so shy that people would ask me if I was mute. And my parents, who raised me on on a dead-end gravel lane in rural Appalachian Kentucky, hoped I'd grow up to be either a dancer or a pastor. But I've always been viscerally drawn to difficult problems. My initial interest in biology emerged from stumbling on the "protein folding problem" in a high school textbook. My first thoughts were, "What makes this problem so difficult? Every other paragraph in this book is about what we already know. Why is this one different? Could I solve it?" 

Analogously, I've spent the last few years as an employee observing obstacles while growing a successful biotech company. I've generated a long list of opinions about what a company I'd appreciate as an employee would look like. Now I'm going to use that list to do one of my favorite things in life: build something awesome alongside people I enjoy and respect. The awesome thing I'm going to build is Lodestar. I believe it's going to be a company that will be amazing to work within, and  I believe that we will accomplish amazing things. It's one thing to believe you can do something, but there's only one way to test what's possible: do it.

We're building Lodestar, a company testing what's possible in biotech, in order to enhance the wellness of others. Our first goal is to ensure every child with a rare disease can expect a diagnosis. 

If this purpose resonates with you, let's talk. 

— jessime@lodestar.bio