I recently spoke with our user Ethan Perlstein, whose one-of-a-kind independent lab is flipping traditional drug discovery on its head. Check out how he is changing the paradigm of traditional research, pharmacology, and more below.
Q: What is the focus of the Perlstein Lab?
Ethan: The Perlstein Lab is focused on personalized orphan drug discovery. We take a two-pronged approach. We first create a primordial disease model for a given patients’ mutation; that involves taking a change in the DNA that you see in the disease and putting it into the model organisms.
We use yeast, worms, flies, and fish that have ancestral versions of that gene. We can use those models to do drug discovery, and we can validate the hits that we get in patient derived cells of the same genotype. So it’s a closed system where everything is personalized from the outset.
Q: How did it come into existence? What was the progression from your very first crowdfunding experience to starting your own lab?
Ethan: The science behind it has been incubating a long time, since I was in grad school, so it’s been a ten-year process. Screening using a model organism is something I did in grad school, so it’s existed for awhile. As a post-doc, I took some of those scientific concepts and drilled down deeper, so that put me in a good position to have a scientific foundation.
I spent the next 18 months leaving academia and navigating the business side. Last fall, I put together a business plan, had it reviewed by business people, improved my plan, and by the end of 2014 I began fundraising.
The team started to come together in early April. The lab started to come together in terms of equipment and structure in mid-April. And now we have a fully functional lab that has yeast, worms, and flies, and it’s off to the races.
Q: What do you think have been the crucial tools for independent lab fundraising?
Ethan: AngelList is the place where we can post progress. Twitter is a place where we build a community, build a brand, and connect with orphan disease patient groups.
But also we’ve been able to be a lean biotech startup, because we have incubator space access, where our lab is physically located. Another thing that gives us a huge leg up is the ability to outsource experiments through Science Exchange. We actually had a big contract for the construction of some personalized fly mutants and worm mutants, and we were able to do that when the lab was still virtual, pre-team. That gave us a huge head start and allows me to spend Perlstein Lab’s money wisely.
Q: How did your project on Science Exchange fit into the larger scope of the Perlstein Lab’s work?
Ethan: The idea is that we want to start with a mutation so you already know what the disease gene is, so it’s just a matter of figuring out what a patient’s presentation is. Even with these simple diseases, the complexity is apparent right away – you get a different allele from each parent, so you obviously have two mutations in that gene, but you don’t often get the same mutation. It’s already crying out for personalization.
When you know that information, whether it’s a mutation from a public database or hot off the exome presses, you can take that mutation, use CRISPR to dial it into the DNA of a simple organism, and you’re making a change in the homolog of the human disease gene. Often times the mutations that are observed in patients are altering conserved amino-acid residues within the disease-causing gene, indicating that a conserved and likely essential function of the protein is lost or defective. I think that’s pretty cool and helps validate the field of evolutionary pharmacology. We’re doing drug discovery in a bottom-up way, where the bottom is simple organisms and drug candidates are tested in progressively more complex organisms, and then translated to people.
Q: What’s your take on the post-academic workforce, how do independent labs fit into that?
Ethan: There are tons of scientists who want to do science, but they can’t find places in industry or academia, so they’re leaving bench science. It’s a tragedy because they were all publicly funded with the expectation that they would be the next generation of researchers keeping us competitive globally. It’s not a good situation. So I think independent labs are a way to absorb all these professionally trained scientists.
Q: Any advice for people starting an independent lab?
Ethan: Get out there and start branding yourself. It takes a lot of time, you get ~1000 followers per year. It’s not trivial, but it definitely rewards you. Get a blog, get a website as a place where people can find you and nucleate around your content. Lastly, get a kick-ass idea and get a bunch of people to join you.