On January 1, 2014, I sent a tweet that changed my professional life. I wasn’t soliciting investors, but rather chiming in on a fleeting conversation about orphan diseases, like I’d done for months before on a range of topics that interested me. Little did I know at the time that that Twitter exchange would lead to an email exchange, which would lead to a face-to-face pitch at the annual JP Morgan biotech meeting in San Francisco in mid-January, which in turn would lead to a signed term sheet a month later. Perlstein Lab PBC was born.

Eric Ries originally popularized the lean concept in 2011 in his book The Lean Startup, though the idea was first promulgated on his blog. As a professionally trained scientist, the parts of the book on running controlled experiments (e.g., A/B tests), discarding invalidated hypotheses, reformulating new hypotheses, and iterating this process over and over again was old hat. However, the most noteworthy aspect of the burgeoning lean culture was that an insider was openly demystifying the startup process. Most biotech startups operate in stealth mode, sometimes for years, even after they emerge from behind a carefully crafted 450-word press release. What better way to be lean than to reap the fruits of openness on social media?

Without Twitter I can confidently say that my transition from academic trainee to biotech entrepreneur would not have been possible. I joined Twitter in early 2011, after initially dismissing the platform for years as the province of Justin Bieber and other inanities. But I couldn’t resist joining Twitter after I learned that several scientists whom I respected were avidly tweeting – about science! Not only were scientists tweeting about science in general they were tweeting about their science in particular, and as a result forming communities of mutual interest and support.

After leaving academia, I felt dead to my former mentors and colleagues. They didn’t have the experience or connections to help me through my transition, so it was up to me to brand myself, do my own diligence, and convince strangers to part with significant sums of money to pursue a novel approach to orphan disease drug discovery based on phenotypic screens of simple model organisms.

Maintaining a blog was also critical to my success. In the summer of 2012, I commissioned a lab website and personal science blog from a professional web developer. Like others, I was able to express myself on a range of topics and get feedback in the form of comments, and a growing Twitter following. My most read post is called “Postdocalypse Now,” a cri de coeur and a call to action in the weeks immediately following my exit from academia. That post and others created a digital archive of content that served as a touchstone for networking and collaboration. I was used to a small number of scholars discovering me on PubMed, the search engine for the primary biomedical literature. Now anyone on Earth could Google me and learn about what I was doing. And I could quantify pageviews and referral traffic on Google Analytics in real-time to assess impact.

So what elements of my story are generalizable? My recommendation to compatriots in Generation Postdocalypse is: to thine own brand be true. Find your scientific voice on Twitter and on your blog. Anyone can set up a Twitter account or start a blog in minutes these days, though be forewarned that it takes years to garner a following and readership. Politely crash conversations between experts in a field you know or want to learn more about. Follow up Twitter threads and blog comments with informational interviews on Skype or G+ Hangout. Use this online engagement to filter the folks you want to meet IRL (in real life). Most importantly, inure yourself to failure. That part should be easy for any scientist, and especially for academics.

Finally, find a mission worth getting up for every morning and that keeps your mind abuzz late into the night. I’m biased. I want to see an orphan disease moonshot, which would accomplish three goals: (1) identify treatments for orphan disease patients; (2) gainfully employ legions of under- or unemployed professionally trained scientists; (3) discover serendipitous connections to common diseases. That’s my mission. What’s yours?

Ethan Perlstein

As of this writing, I can report that I’ve been academically sober for one year, six months and two weeks. Before I departed academia, I was like many of my Gen Y and Millennial contemporaries: dreaming of a tenured professorship since my first summer internship as a high school student in a biological research lab; working as a grad student seven days a week for five years on a small stipend but with big hopes; postdoc-ing for another five years to prove my mettle in a new subfield and to gird my CV for the assistant professor job search.

Then I ran into the buzz saw of Postdocalypse. This phenomenon goes by many names: UCSF Professor Henry Bourne calls it the “postdoc holding tank;” the dons of the biomedical research enterprise lament it as “hyper-competition.” Basically, it’s the systemic oversupply of professionally trained and academically acculturated scientists relative to open faculty positions. Some of the 27 departments I applied to received over 300 applications from postdocs and even current assistant professors, many of whose CVs were likely indistinguishable from mine – at least that’s what I gleaned from the departments that bothered to send me a stock rejection email.

So like generations of pioneers before me, I packed up my bags, declared (scientific) independence, and moved to Northern California, the nation’s top biocluster. My goal was to found Perlstein Lab, which would direct curiosity-driven research toward unmet medical needs. I found the perfect balance between basic and applied impulses in the orphan disease space. There are an estimated 7,000 orphan (or rare) diseases. The definition of an orphan disease is one that afflicts 200,000 or fewer patients in the United States, though most orphan diseases afflict on average 6,000 people on Earth! I received my education in orphan diseases on Twitter, which is also where I picked up an informal MBA and a degree in marketing. (See my post on the usefulness of Twitter).

During my independent postdoctoral fellowship – the first incarnation of Perlstein Lab – my team and I validated an approach that I dubbed evolutionary pharmacology. This contrarian approach involves using simple model organisms to study and discover complex small-molecule drugs. Simple model organisms are baker’s yeast (Saccharomyces cerevisiae), nematode worms (Caenorhabditis elegans), fruit flies (Drosophila melanogaster) and zebrafish (Dano rerio). After feeling spiritually depleted by the academic job search, I wanted to do mission-driven science that mattered to real people, and not simply score notches on my professional belt for the approbation of a few colleagues scattered around the world.

Being fresh off the academic boat and having never had an email address that didn’t end with “.edu” I knew that I needed to train myself for the coming marathon. Thankfully, I was privileged enough to have some savings and a spouse willing to quit her job and move across the country with me from the Northeast. When I arrived in the Bay Area in the Spring of 2013, I was fortunate to land on my feet as a part-time consultant and blogger for a science crowdfunding startup called Experiment (formerly Microryza). I was also lucky to have my younger brother in the Bay Area working on his own startup ideas, and he became a key entrepreneurial advisor and ultimately a co-founder of Perlstein Lab. I paid bills and did my homework for six months as I prepared to hunker down and write a business plan for Perlstein Lab, craft a pitch deck, and mount a seed fundraising campaign.

By the Fall of 2013, I was circulating a draft of a prospectus to trusted confidantes and also to experts whom I’d never met other than in conversations on Twitter. These reviewers included venture capitalists, biotech veterans, patient advocates and scientists. By the 2013 holiday season, I had a legitimate business plan and a concise slide deck. I had met many Silicon Valley investors and entrepreneurs who shared their fundraising war stories, so I knew that fundraising would take anywhere from six to twelve months. Years in academia had prepared me for delayed gratification.

In my next post, I recount the story of how the second incarnation of Perlstein Lab was born in the 140 characters of a tweet.

Ethan Perlstein