Dr. Joe Pickrell

"Alter connections, encoding now / Initial sequence is loading"

   Duran Duran,"Virus", 2003. 

Look out, Boston and San Francisco.

 

Behind a swell of developer interest and investments in the last decade, New York is making moves to expand its "center of the universe" claim to include biotech, too, and my most recent interviewee, Dr. Joseph Pickrell, is co-founder and CEO of Gencove, one of the New York-based science and engineering companies that, in total, has secured over $1B in funding in the last month. 

Exciting times, right? Dr. Pickrell is taking it all in stride. As a former Core Member and Assistant Investigator at the New York Genome Center, he told me his previous and current positions have more in common than you'd think. "The jobs are surprisingly similar!" he said, adding that he's still as much a practitioner of his craft, computational and statistical genomics, as he is managing daily operations. His lab at NYGC was focused on developing statistical tools that could transform huge banks of genomic data and root out patterns,  actionable insights, connections between people, genes and disease; in short, unraveling the mysteries of human biology due to genetic variation.

He's also worked with Yaniv Erlich to create DNA.land, a database of crowdsourced DNA reports shared by consenting individuals who have purchased a consumer genetic test from a company like 23andme. Once uploaded, the data is freely available to be used in others' research. At over 150,000 genomes, the project speaks to Pickrell's vision of democratized science. 

In 2017, Pickrell founded Gencove with Tomaz Berisa. Their mission is to make genomic data accessible and interpretable. With a low-pass sequencing platform, they've become a valuable resource for researchers and companies with large-scale genomic projects as the predecessor technology, genotyping arrays, lack the accuracy, scalability and cost effectiveness of genomic sequencing. Here, Dr. Pickrell tells us about his graduate work, transition to start-up CEO and the true value of a PhD.

The following interview took place on March 12 and March 25, 2019. 

 

INTERVIEWER

Where’d you grow up?

 

PICKRELL

Wilmette, IL, a suburb of Chicago.

INTERVIEWER

Was science a calling from an early age? If not, what turned you toward genetics?

 

PICKRELL

I was definitely interested in science from a young age. Used to have chemistry sets at home and things like that.

 

INTERVIEWER

You got your PhD from the University of Chicago. Can you briefly explain your thesis work in Jonathan Pritchard’s lab (now at Stanford University)?

 

PICKRELL

We worked on a broad set of projects, including identifying genes that evolved under natural selection in different human populations, identifying genetic variants that influence gene expression levels, and statistical methods for learning how different human populations are related.

I’m sure I wrote in my thesis that there was some unifying theme around these

projects, but really the question was ‘What are the best datasets on human variation that exist or that we can generate, and can we develop new data analysis approaches that use these datasets to answer important questions?”

 

INTERVIEWER

Looking back, is there anything you wish you would’ve known before starting in your thesis lab?

PICKRELL

Not really! A lot of the most important things I learned in the process of obtaining a PhD would be impossible to know ahead of time. Specifically, I think the most important conceptual thing I learned is how to choose what to work on in a situation where it’s unclear if a problem can be solved with the knowledge that exists in the world today. Before a PhD (like in a class), you’re given a problem and tasked with finding a solution, but there’s no doubt that a solution is in fact possible. In a PhD program, it’s possible to choose a problem that literally cannot be solved with the state of human knowledge, and it takes a while to start to understand how to operate in the face of uncertainty on that scale.

INTERVIEWER

So, you're the founder of a new company (Gencove). How has the transition from bench-side researcher to running a lab to CEO of a start-up changed your day to day mode of life? 

PICKRELL

You'd be surprised to find out how similar running a lab is to running a small company. It's still a small group of people working together on important problems, and as the leader, things like fundraising and managing, those tasks don't change too much. 

 

INTERVIEWER

Tell us a little more about Gencove. How did it start and

where is it going? How many employees? Are you hiring?

 

PICKRELL

Gencove started from a project in my lab at the New York Genome Center where we developed software to enable cost-effective and scalable sequencing-based tests for different applications. The areas of genomics with the highest growth (consumer genomics, agriculture, etc.) are dominated by an older technology called genotyping arrays, and we saw that some of the approaches we’d developed could make sequencing truly accessible and useful in these markets.

We’re just under 10 people now and are hiring!

INTERVIEWER

Can you explain the difference between low-pass genetic sequencing and genotyping arrays?

PICKRELL

From an input standpoint, the primary issue with genotyping arrays is that you need to decide ahead of time what genetic variants to look at. This is not the case with sequencing technologies, so low-pass sequencing enables discovery of new genetic variants and easy use across populations and species.

INTERVIEWER

Since starting Gencove, have your aspirations changed? You have a brand now. What's your vision for the company? What are you ultimately trying to do?

 

PICKRELL

It's fun to think about, ya know - where do I want the company to be in five years?  How will the world have changed in that time? How do I position Gencove to still be relevant? I think about it all the time. I'm constantly working on the answers to those questions.

INTERVIEWER

Were you surprised to see the University of California terminate their contract with Elsevier or are you more surprised it’s taken this long for an American institution to do so?

 

PICKRELL

I’m definitely surprised to see institutional pushback against publishers since institutions tend to be extremely conservative about these things. It’s really a testament to the growing power of the mix of legal, semi-legal, and illegal ways of accessing papers.

INTERVIEWER

What has been or will be the biggest discovery in population genetics in our lifetime?

 

PICKRELL

The entire field of ancient DNA is a revolution. I remember reading the Denisovan paper as a graduate student and struggling to wrap my head around the observation.

INTERVIEWER

Okay, wrapping up here. This is related to an earlier question, but part of my reason for doing this is the desire to provide prospective and current graduate students with some fresh perspective on all the different career paths they can pursue with a PhD. What the PhD can do for them. But I'm also curious to know what a PhD means to the owner. What does a mean to you? What did it establish in you?

PICKRELL

It's definitely this idea of confronting the unknown, and figuring out whether the unknown is unknowable or if you just haven't done the work yet. It's tough to explain. The key skill is this sort of balance, like it takes a supreme arrogance and supreme humility to think, alright, this really important question hasn't been answered, other people have spent their careers trying to answer this question - can I do it? Sometimes the answer is no, and you could plug away for six or nine months or a year, but the tools just aren't there. It's understandable. Science is hard, right?

At the same time, figuring out, OK, how has the state of the world changed? How

have technologies changed? What are the facts that people 15 or 20 years ago didn't have that you can now use to answer these questions? Being able to operate in that world of extreme uncertainty where you don't know if you're on the right track is probably the most important skill that I took away from my PhD.

INTERVIEWER

Alright, last question: Led Zeppelin, Beatles, Rolling Stones, or Pink Floyd?

PICKRELL

The Beatles.

Learn more about Dr. Pickrell by visiting his Medium page and make sure to follow him on Twitter at @joe_pickrell. Also, huge shout out to Gencove for recently securing a $330K NIH grant that will fund work on tech validation for estimating polygenic risk scores. Read more about it here. 

Feel free to leave your thoughts on the interview in the comments section.

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Check Joe's Medium post for a more in-depth explanation.

©2019 by EG Lund.