A very good place to start!

Lucky for me I long ago got over my fear of asking dumb questions — because as a software engineer suddenly responsible for code dealing in advanced biology, dumb questions come up a lot. And they start right at the basics — what are we looking for and why does it matter? I thought that especially for my traditional HIT homies it’d be interesting to start a post or two there.

Adaptive’s technologies quantify the adaptive immune system. That is, they allow us to measure specific features that help describe what the immune system is doing at a given point in time, and as things change over time. All well and good, but what are those features and why do they matter?

Our immune system is broken into two parts. The first is the “innnate” immune system, which can respond quickly but pretty generically to attackers. Barriers like skin, flytraps like snot and mucous, and general-purpose killer cells like macrophages are all part of our innate immune function.

The second part — the “adaptive” immune system — is slower to respond, but is way more targeted and effective against hardcore nasties. The adaptive system coordinates laser-focused attacks against specific antigens (e.g., chicken pox).

In order to respond with this kind of specificity, the cells of the adaptive immune system (in particular T-Cells and B-Cells) first have to be able to recognize specific antigens. This recognition is done by expressing proteins that work like a lock and key — they present a surface area that only a very specific antigen fits into. When something lands in the “lock” — it’s time to go to work.

So we make “receptors” that match specific antigens. But there are millions of possible bad guys, and worse they’re changing and evolving all the time. So how do we possibly keep up? This stuff just gets cooler and cooler.

As with everything, it starts with our genes. Our bodies are constantly just randomly “recombining” certain genes (called “V”, “D” and “J“) into new sequences and throwing them out into the wild. Some of these “naïve” cells actually attack our own healthy cells, so those get filtered out (assuming all is working properly). The rest wait around, hoping that eventually an antigen will fit into their “lock.”

When that happens — the activated cell starts replicating itself and recruiting other parts of the immune system to fight. Eventually (hopefully) the battle is won, and many of those specific cells fade away, but a few remain and create a “memory” for that specific antigen. When it shows up again, the system can respond much more quickly. If this sounds like a vaccine; it’s because that’s exactly what it is.

Tons and tons of detail left out, but that’s the basic story — we are constantly creating random receptor cells, each of which can match up with one specific antigen. When a match happens, that receptor gets cloned into an army to fight on our behalf. After the battle when the drawdown occurs, we leave a few scouts out in the field so we don’t get caught by surprise again.

With that, we can get back to Adaptive. Our stuff can pick out the millions of different receptor sequences floating around in your body and create a report that shows how much of each one you have in your “repertoire”. There are great things we can do right now with this information — like track the effectiveness of cancer treatments, and even greater things we’re working on with collaborators in our labs. It’s not so crazy to imagine that by matching specific sequences to specific antigens, we will one day be able to custom-create treatments to super-charge focused immune response. In fact, this exact idea is already showing promise in the real world.

WOO HOO indeed.

More to come.


How hard can it be?

Back in 1994 I joined the team that was building the “online” component of Windows 95 — a competitor to America Online that eventually became known as MSN. None of us really knew what we were doing, but trusted we could figure it out along the way, a state of mind my then-boss Jeff Lill immortalized with the following shirt:

As it turns out, this has been kind of a repeating theme for me — one of the best things about writing software is that it applies to everything, so there’s an endless supply of new problems to explore.

Cut to my new home at Adaptive Biotechnologies — a company that has developed insanely awesome new techniques to measure and quantify the adaptive immune system. Our tools isolate the sections of T-Cell and B-Cell DNA that bind to specific antigens, amplify and sequence those fragments using next-generation sequencing machines, error-correct and normalize the data, and finally make it available to researchers and clinicians for custom online analysis.

The resulting picture of the immune system is many, many times more granular than anything the world has seen before … which opens up the door to some pretty amazing applications. For example, our clonoSEQ diagnostic tool can monitor residual disease in post-treatment cancer patients far more accurately than traditional approaches — and that can save real lives.

The team at Adaptive also believes that software has to be a key differentiator for the company. There is a metric ton of additional value we can create on top of the raw data, from better error-correction at the front of the process to new ways of analyzing and sharing data at the end. It’s a wide open world — and the most exciting problem I’ve attacked in a long time. I may be a biology newbie, but hey, how hard can it be, right?

Anyways — the point of this new blog is to share some of the great things I’m learning here at Adaptive. There’ll be some biology-for-dummies, conversations about software challenges both unique to and shared across industries, and when it makes sense a bit of personal anecdote as well.

If you spent any time reading about my last gig at http://familyhealthguy.com, you’ll be right at home here. You can also find me on Twitter as @importimmunity. Woo hoo!