This is the way heritability is found: not with a bang, but with many, many whispers

In previous posts, we’ve alluded to the ever-expanding wealth of Big Biological Data, and the increasing capacity of biomedical informatics to convert this data into knowledge, cures, and cash. Here, I’d like to clarify the source of this approach’s power. Rather than relying on strong individual signals to reveal the causes and answers to disease, bioinformaticians are unearthing the complex webs of weak associations that underlie biological (mal)function.

The need for such methods is illustrated by the “missing heritability problem”. As Gregor Mendel was lucky enough to find and rigorous enough to observe, many traits such as plant seed color are passed from parent to offspring in a predictable manner. With the advent of molecular biology, it became clear that these traits are determined by variants in parental DNA, called alleles, which are inherited by the cells that make up the next generation. However, many other traits such as height, diabetes and Crohn’s Disease, though clearly heritable, can’t be traced to single allele and neatly predicted by a high schooler’s Punnett Square. For instance, a casual glance around one’s social network will confirm that parental height often corresponds to their child’s chance at making the basketball team. Tall parents beget tall children, seems simple enough. Yet height is determined by at least 40 different genes, which when combined still only explain 5% of the height variance of tens of thousands of people!  How is it that 40 supposedly clear signals can’t pinpoint inheritance patterns we can plainly see? In the past decade, it’s become clear that most complex traits can’t be understood by finding a few smoking guns, but rather by connecting hundreds of scattered embers. Thus, to understand complex diseases, we must untangle the weak, noisy contributions of many, many genes.

Believe it or not, this is the type of problem that twoXAR’s software architect Carl worked on at NASA. To study extraterrestrial objects, NASA scientists record their electromagnetic emissions using instruments such as radio telescopes. As these objects are really frickin’ far away, radio signals they emit are extremely weak and noisy. However, what this data lacks in clarity, it makes up for in abundance.  The concept goes like this: if a signal is even slightly more consistent than random noise, over lots and lots (and lots) of measurements, its pattern will manifest. All you need then is some clever algorithms to detect it. Fortunately, Carl’s and his ilk are some pretty clever folks.

When seven leading geneticists were interviewed about how to solve the missing heritability problem, one common theme that emerged was the need for more data, and more different types of it. Here at twoXAR, we’ve taken that concept to heart by querying multiple measurements, databases and tissue types in our search for protein networks linked to disease, and hiring folks like Carl to help build effective telescopes.

Identifying Solutions for Neurodegenerative and Psychiatric Diseases

I suppose you could call me one of the men behind the curtain at twoXAR. I’ve been here all along, you just haven’t heard much from me. I’m a Data Scientist on the team, and I’m a graduate student at MIT where I’m developing techniques for studying the molecular mechanism of neurodegenerative diseases. My passion is rooted in this research, and I’m excited to tell you about it and how I’m using it to develop our company.

I share Andrews’ excitement for blazing new trails. My work gains insights into how diseases exert their detrimental effects and charts the process of technology development, which involves a lot of hacking and tinkering. My focus is on neurodegenerative diseases because very few effective drugs have been found to treat them. twoXAR is interested in them for the same reason.

In my opinion, it is the lack of mechanistic understanding of these diseases that makes drug discovery for them very difficult. This is also true of psychiatric diseases like autism and schizophrenia. twoXAR’s approach is a promising alternative to testing individual molecular targets experimentally, which academia has spent many earnest years searching for with very poor results. As an experimental scientist, I dream that the data that I work so hard to generate can be used not only by me, but by other scientists, doctors, pharmaceutical companies, and beyond, who can leverage them to better effects. (Side note from Andrew A.: We’ll have a post soon about our take on the benefits of capitalism for medicine and society as a whole.)

As you already know, twoXAR has developed an algorithm that can discover new drugs through a computer, rather than a wet lab. However, that algorithm still relies on gene expression data from patients and healthy individuals, so we’re using the same hard data from flesh and blood samples. Instead of using them ourselves, we borrow data from scientists who actually processed these samples. In order for our algorithm to work accurately, these data are carefully inspected and annotated, which is where I come in. My role is to identify the most suitable data sets about the diseases we’ve chosen to focus on from published scientific studies for our algorithm(s).

We’ll get into the nitty gritty of my work for twoXAR in a later post. For now, I’ll jump on the band wagon Desiree started and let you guess which of these three facts is false. It’s another round of Two Truths… and a Lie!

  1. I went as an enzyme to last year’s Biology department Halloween party.

  1. In my off-time, I enjoy a solid game of table tennis and a good cookie.

  1. This picture captures me injecting brains into a tube.

 

We’re Growing: A Warm Welcome for Dane Bedward

Dane Bedward is no stranger to the pharmaceutical business. After ten years working as a product manager and then director of marketing at Johnson and Johnson and MDS Nordion, Dane was tapped to open the offices of Genzyme Canada. In little more than fifteen years, Dane worked his way up to the top of Genzyme, one of the largest international pharmaceutical companies in the world. He eventually became a Senior VP at the mother ship office in Boston. Needless to say, Dane knows the pharma industry inside and out.

Dane has just joined our advisory board this week. We’re pretty sure that with the the wealth he accumulated from Genzyme, a leader in biotechnology, he is acting as Boston’s unofficial Batman. But we don’t have any hard evidence yet.

Dane is filling a lot of those gaps we talked about in our previous posts: he is someone who has years and years in the business Andrew and I are entering for the first time. Genzyme in particular is a company that focuses on rare diseases, which is a popular topic of conversation in our discussions with potential investors. Genzyme also prides itself on its cutting edge research, and as a former leading member of the team there, Dane is very familiar with our unique methods of drug discovery. In a future post, we’ll explain why the world of biomedical informatics isn’t just for very special nerds.

[In husky, deep Batman voice:] It’s the wave of the future.

Computational Pharma: An Emerging Rotation

After three years of medical school and a whirlwind year of clerkships, I’m taking a detour from the strictly medical and enjoying a trek through the biotech pharma universe. It’s Day 10 on this special Silicon Valley incarnation of my medical, technological, and entrepreneurial interests, and I’m into it so far.

I recently decided to take a break from clinics and get to know the startup world, and I attended a Hacking Medicine event at Stanford to get a sense of what was out there and meet some interesting people. Andrew M. was one of them, and our conversation wooed me to join the team in business development at twoXAR, while also offering my medical know-how when and where it’s needed. Here are a few things they didn’t know about me before signing me up. The catch: one of them is false. That’s right, here’s a good old-fashioned game of Two Truths and a Lie:

  1. I performed in a med school a cappella group called the “Lymph Notes.”
  2. I consider biking a superior form of transportation to skateboarding, though it’s not always faster in Palo Alto traffic.
  3. My beverage of choice is butterbeer. I’m obsessed with Harry Potter.

Before I reveal the Lie, I’ll tell you a little more about why I’m excited about being at twoXAR that may or may not help you figure out which it is.

I’ve always been interested in computation as a way to push forward and improve on existing systems and processes. When it comes to work I’m passionate about, I’ll step outside my comfort zone to solve a problem from multiple angles. Thus, I’ve gone from cutting cadavers in medical school to investigating ways that technology can expedite cures by making sense of countless tissue samples of data. Of course, now I don’t have to touch or interact at all with human tissue, which is totally okay with me. I’m more than happy biking to the twoXAR office and spending the day tackling problems in pharma.

Have you figured it out yet? Here’s a hint: I’m keeping twoXAR well-stocked with buckwheat tea. No butterbeer here.

A Dose of Weekend Hacking: Hosting Stanford Medical School Hackathon

Last weekend, as part of MIT Hacking Medicine, I helped host the CareInnovations Patient Engagement Hackfest at Stanford Medical School. The Hackathon is an innovative weekend program that aims to create “more effective and reliable connections between patients, clinicians, and the information that can improve the quality and cost efficiency of healthcare” (Find out more here).  You may have seen my tweets about it all weekend. The event was sponsored by CareInnovations, (an Intel and GE joint venture) and went from Friday through Sunday, with about 100 participants attending the event. It was a really exciting crew of people with extremely varied backgrounds – it was just my type of crowd.

A large percentage of participants were clinicians, business & medical school students, software developers, and designers with industry experience. When you collect brilliant doctors, organization leaders, and computer scientists in the same room to discuss solutions in the healthcare space, you hear a lot of creative and fresh ideas about how to revolutionize medical care.

This weekend’s focus was on patient engagement, so we concentrated on questions like how to make it easy for patients to take their medication, how to collect accurate patient data in a useable format for physicians, and how to create medical tools that allow the patient to directly engage with their own health. It started with 30- and 60-second pitches on problems and solutions in the space and over the course of the weekend, teams self-assembled based on the specific problems they wanted to solve. In the end, 9 teams hacked and presented some pretty innovative hardware, software, and service-based solutions.

The most valuable element of this experience was seeing that these diverse teams could create incredible and unexpected solutions to a given problem and it reminds me that a diverse team is what makes for a successful business venture. I’ve worked on teams made up completely of engineers and teams composed of MBAs, and inevitably teams of people with the same ways of thinking will miss something important. The best way to create a sustainable solution to a problem is to have a team that can ideate from as many angles as possible.

I came out of the event energized and ready to tackle big issues in healthcare. As an entrepreneur in the space, I was inspired by the teams at the hackathon. I got to see firsthand and with immediate results, how unconventional and diverse approaches to old problems are not only effective: they can change our world.

At twoXAR we embrace this mindset and strive to build a team with radically different backgrounds and ways of thinking who can effectively come together to improve lives through computation. In fact, post the hackathon, Stanford medical student Desiree Li joined the team to support us both on the science and business development side. I guess Silicon Valley is the place to find the crossover between doctor and entrepreneur.

Building the Team: Adventures in Finding a Chief Science Officer

We have titled this post Adventures in Finding a Chief Science Officer because it has definitely been adventurous. There have been rained out tennis games, planes and buses to and around the east coast, and lots and lots of phone interviews with some… interesting characters.

In Andrew M.’s travels to the east coast a couple of weeks ago, he got on a Megabus and rode six hours from Boston to New York for one special guy. The guy said he was super interested, then he stood us up. So that wasn’t great.

There’s a different guy who says he knows the pharm biz like the back of his hand. He won’t answer any of our specific questions, but he emails us everyday. We don’t really get it.

There was somebody else who explained that Google was a competitor we should watch out for because of their new research into how to end death. We don’t really get that either. And yet another explained to us that we shouldn’t be looking for a Chief Science Officer, but a new CEO. So those didn’t really work out either.

Between Andrew M. and me, we’ve got computational biology and business strategy covered, but we need someone who really knows drugs. You know what I mean. Someone who can further validate the technology we’ve created with the science pharmaceutical companies already know and trust in a wet lab.

And, s/he has to be cool too. We’re kind of hoping to find an Andrew Z. Radin (since we’ve already got an A and an M Radin) who has had extensive experience managing CROs in drug discovery. The Andrew Radin bit is probably optional.

What’s in a Name?

Call it fate or a series of wild coincidences, but the way in which the twoXAR team has come together is uncanny.

A few years ago, I was approached by a stranger looking to buy the rights to a url I own, www.andrewradin.com. That happens to be where you are, by the way. It seemed strange—it’s my name after all, and I couldn’t imagine why someone else would want the rights to a url with my name. It turned out that it was the stranger’s name as well, middle initial M instead of mine, A. The two of us got to talking and discovered that though we are at different stages of life and were living on opposite coasts, we both had an interest in entrepreneurship and the sciences. Aside from that, we just got along.

I didn’t sell Andrew M. Radin (I’m Andrew A. Radin) the url—he didn’t have anywhere near the dollars it would take for me to let it go. But over a few years, we became good friends. As I am a few years further along in my career, he would call for suggestions or advice, and I would call to toss ideas around.

When I realized the power and potential impact of what I had developed that would become the basis for twoXAR, Andrew M. was one of the first people I thought of. I asked him if he wanted to be a co-founder at my new company and build a business plan. I also offered him a place to crash in my house (twoXAR’s Co-Founder Moves West), and he, my wife, Xelda the beagle, and I have been one big happy family for the last couple of months while twoXAR gets ready to launch.

Meeting Andrew M. also inspired the name for the company. Have a closer look at it if you don’t understand why. The image on our company page (have a look at the image) gives a clue about how to pronounce it.

twoXAR’s Co-Founder Moves West

I live and work in my co-founder’s house, and it’s not weird at all.

But it was a little at first. About six weeks ago when I moved to the Bay Area from Cambridge to start twoXAR, a lot of people thought I was crazy. I was turning down job offers at established organizations doing work that I would have probably found very fulfilling. Besides that, my parents’ worried voices rang in my ears, “Are you sure you should be doing this?” And then there were my own doubts about taking up space in this man’s home, not to mention the trouble it might be for his wife, Wendy, or their beagle, Xelda.

But the excitement far outweighed the concerns. If you know the startup world, then you know that it is all about taking that leap – taking risks – big, calculated risks. I had this in common with my friend, mentor, and new business partner: we were both more interested in cutting new paths than in going down the safe route. Our pasts overlap with stories about independent and wandering trips to China, sailing and various other adventures and – ya know – investing all we’ve got in an idea we believe in.

On the floor of our 10’x12’ office is a two-hundred-dollar computer equipped with an algorithm that we believe can change the way pharmaceuticals are discovered and developed. The office is about 12’ from the house where you might find Wendy and Xelda if you step outside the French doors. The pale yellow walls reflect the California sun all day as we jam away making twoXAR happen. Despite the hard work in this small room, we have a lot of laughs, as we share ideas, plans, and stories around many things we have in common, including our names (we can tell you about that and how we chose the name of the company next time).

The doubts I had about moving here are replaced with excitement. We’re a weird Bay Area family now – part scientist, part entrepreneur, part artist (that’s Wendy’s role), part hound. And we can’t wait to tell you about what we’re cooking up in our little yellow science lab/office/bonding chamber.