news feature

Credit: Colin Beatt

One year, 1 lab, 16 spinouts
In one year, George Church’s group spun out 16 different startups. What explains the lab’s incredible output
of entrepreneurs?

Laura DeFrancescoIn the early 2000s, Jay Shendure was a
graduate student in George Church’s
lab at Harvard University. Back then,he says, there was “hardly an inkling” thatthe lab would become a hotbed of startup
activity. Of course, licensing was ongoing,
and Church had his tentacles into various
companies, but there were only a smatteringof ventures coming out of the lab — maybe
one every year or so.
Fast forward to 2018, and the drip hasturned into a deluge. Some 16 Churchcofounded companies came into being lastyear (Table 1). And several more added
him to their scientific advisory boards(SABs). What explains the slew of venturesand incredible entrepreneurial output ofChurch’s acolytes? Alumnus Dan Mandellof GRO Bioscience, a 2017 startup he spunout of the lab, puts it down to an ‘esprit decorps’: “We want everybody to succeed
but we all know that the odds are not goodfor any particular biotech startup. All the
cofounders share a delusional optimism.”
It’s that optimism that keeps them going,
he says. “It allows you to function in anenvironment where the odds are stacked
against you but you somehow believe thatyou are going to make it work.”

The secret sauce

Shendure feels the inflection point camein 2010, with the founding of AbVitro by
Church and his then-postdoc Francois
Vigneault. AbVitro may to this day holda special place in the annals of startups

Nature Biotechnology | www.nature.com/naturebiotechnology

from the Churchlab. After startingfrom only a little
over $3 million instartup funding
from a single
VC firm, Sante
Ventures, in 2012,
the company was
George Church,
Harvard, MIT, Blavatnik snapped up by Juno
Institute, Wyss Institute, for $125 million
four years later. That
Broad Institute,
was followed byRegenesis Institute,
Celgene’s purchase
Shenzhen Institutes ofof Juno, and more
Advanced Technology
importantly led
and cofounder of 16
to several cellcompanies in 2018.
therapies now in
Credit: Wyss Institutenews feature

Table 1 | Companies spun out of the Church lab in 2018
Company

Church alumnus and/or founder

Employees

Business focus

64-x

Alexis Rovner

5

Genome recoding

FitBiomics

Jonathan Scheiman4

Microbiome therapy

Dyno Therapeutics

Eric Kelsic

16

AAV engineering

Kern Systems

Henry Lee5

DNA data storage

Jura Bio

Julie Norville, Elizabeth Wood

2

CAR-T autoimmunity

GC Therapeutics

Parastoo Khoshakhlagh, Alex Ng

4.5

Cell therapies

Tenza

Anik Debnath4

Secretory delivery

Nebula Genomics

Kamal Obbad, Dennis Grishin

14

Genomics

IXBio

Mike Chou

Transformative technologies

Calypso

Denitsa Milanova

Gene delivery via skin

Ally

Kai Chan

AAV immunity

Manifold Bio

Gleb Kuznetsov, Pierce Ogden

Protein engineering

NuProbeDavid Zhang

Diagnostics

Rejuvenate Bio

Noah Davidsohn

Age reversal gene therapy

SNIPR Biome

Morton Sommer

Microbiome therapy

Feles

John Min

Lab-in-a-box

Source: George Church

the investigational new drug (IND) phase,according to Vigneault. “[Church] never hada really big success until we decided to do
AbVitro and that one ended up knocking it
out of the ball park. That triggered a lot of
people to start companies because it looks
easy from the outside,” he says. “It’s not,”he adds.
Whether or not AbVitro was the
bellwether, the pace began picking up
around 2015, and reached a fevered pitch in2018 (Fig. 1).
That year’s rich vintage of ventures
come in all shapes and sizes. Most are
working with pre-seed or seed funding,but a couple have garnered VC funding.
A few have a decent sized team of a dozen
or so, whereas others are operating with
only a founder or two, who are doing it all.
Several have set up shop side by side in oneof the incubators in Cambridge, where theyshare not only core facilities but also
war stories.
According to Grant Zimmermann,
managing director of businessdevelopment at Harvard’s Office ofTechnology Development (OTD), thebiggest change from the past is that lab
members are stepping up to take the roleof CEO, rather than chief scientific officer(CSO) or chief technology officer (CTO).
He sees an upswing in entrepreneurial
verve across the university, but especiallycoming out of the Church lab. “They reallyhave a desire to take on that businesschallenge of managing the company andgrowing the opportunity, seeking out the

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

2017

2018

Fig. 1 | Timeline of ‘newcos’ from the Church laboratory. Source: George Church.

financing, seeking out the collaborations,and really focusing on the business aspect,”
Zimmerman says.
It is not without its personal risks for thefounders, but the cadre has plenty of support
both from within the Church lab and its
network of successful entrepreneur–alumni,
and from the commercial ecosystem aroundCambridge. The OTD office brings inmentors to work with aspiring CEOs. And,
as for other investigators at Harvard and its
sister institution the Wyss Institute, various
accelerator and incubator programs provide
money and lab space, grooming researchers
for success.

Starting off small

It doesn’t always take millions of dollars toform a biotech startup. For Julie Norville,

a former postdoc
in the Church lab,
it took just an idea.
She saw a real-world
problem and, in thetrue Churchian spirit,
set about solving
it. A friend of hers
was in need of an
Julie Norville,organ transplant,
cofounder and coand Norville worried
managing director,
about the ordeal
Jura Bio. Credit: Ryuji
her friend would
Suzukiencounter and thesteroid immune
suppressants she would be dependent on.
As a response, she founded Jura Bio witha fellow former MITer, Elizabeth Wood,based on an idea for engineering chimeric

Nature Biotechnology | www.nature.com/naturebiotechnology

news feature
antigen receptor(CAR)-T cells totreat autoimmunity(rather than cancer).
She floated theidea by her former
mentor, Church,
who encouraged herto go with it, with
Elizabeth Wood,the added bonus
cofounder and coof signing on as amanaging director,
cofounder. Now,
Jura Bio. Credit: Ryuji
roughly a year later,
Suzuki
Norville and Woodare still a companyof two, but have shelved the program
focusing on immune rejection to tackle
more tractable single-epitope autoimmune
conditions. They have devised a ‘decoy’using the human major histocompatibility
complex (MHC) to target both T and B cells,
which expands potential targets and makes
for better binding, according to Wood. The
company is currently engaged in raising
additional fund.
Alexis Rovner,
CEO of 64-x, is also
running her company
lean. She says this ispossible because of
the relative ease of
doing experimentswith the synthetic
biology platforms now
Alexis Rovner,
available. “Basicallycofounder and CEO,you are able to invent
64-x. Credit: Alexis
technology aroundRovnerproblems easily, that’s
just what is motivating
scientists to spin their tech out into somekind of company. Before, it wasn’t thiseasy to engineer biology. It’s getting easier,the tools are easier, the things we are able
to do to cells — it’s amazing what’s now
available,” she says. Rovner was a student at
Yale University with Farren Isaacs (himself
a former postdoc from the Church lab),working on a technology for recoding
organisms, an area of intense interest to
Church. A collaboration between the twolabs led to Rovner’s joining the Church
lab as a postdoc. At that point, her onlyinterest was in developing the technology
wherever, in academia or in industry, but she
eventually opted for industry. To learn how
to do that, she did a stint at Y Combinator in
the San Francisco Bay Area, which provides
space and resources for budding CEOs tolearn the basics of starting a company. Threemonths later, Rovner returned to Cambridgewith a small seed fund and the tools she
felt she needed to go forward. She credits
Church with giving her not only the space

to develop the technology but also the timeto allow her passion to gel. “Once I realizedthat I wanted to more of the applied side oftrying to commercialize science, it takes aleap of confidence to do it. I feel that George
gave me that confidence. That’s the power of
the Church lab, to be honest,” she says.
Y Combinatorsupport is factoring
into another oneof the 2018 startup
cohort, Kern
Systems, headed up
by Henry Lee, whojoined the Church
lab as a postdoc inHenry Lee, cofounder
2012. Trained as an
and CEO, Kernelectrical engineer,
Systems. Credit: Aiden
Lee came to the
Rhaa
area to learn somebiology, startingin Jim Collins’ lab, which was then at
Boston University. Given his backgroundin electrical engineering, the way Collins
framed genes and cells as circuits “spoke
to him,” says Lee. But another aspect of
being an engineer is addressing realworld problems; he moved to the Church
lab to work on a technology for reading
and writing DNA at scale. Together they
developed a method for enzymatic synthesisof DNA, an essential but still lagging
technology, for the ‘DNA-Write’ sectorof the synthetic biology movement. This
technology forms the basis of Kern Systems,
which, in addition to support from Y
Combinator, has received grants from andworked in partnership with Technicolor
Research and Innovation Lab. Lee echoes
Rovner’s sentiment in seeing a shift coming,
where biology is getting to the point
where you can do “bite-size events” witha shoestring budget. “We don’t have to go
through the long rigid process where there is
only one way to assess progress. That’s been
fantastic, has provided a lot of opportunities
for young ambitious scientists to really go
out there and make an impact,” he says.

Hoop (and other) dreams

What many founders have in common isa vision or a dream, and the Church lab
appears to be a place where people are given
space to follow their dreams. For Jonathan
Scheiman, CEO of FitBiomics, it was his
hoop dreams — he had contemplated acareer in the NBA after playing on a two
championship basketball teams at St. John’s
University in the early 2000s. But when hejoined the Church lab as a postdoc, he came
to explore cutting-edge technologies, freshfrom a thesis in molecular oncology. During
his initial meeting with Church, his intense

Nature Biotechnology | www.nature.com/naturebiotechnology

interest in athletics
came up, to which
Church responded,“That’s good! We
want people who
think differently.”
After contributing
to various projects
ongoing in the lab,
Scheiman came up
Jonathan Scheiman,
the hook that would
cofounder and CEO,become the basis
FitBiomics. Credit:
for FitBiomics, a
FitBiomics
venture looking at
the microbiomes of
elite athletes. “What if instead of looking
at diseased populations, we looked at
super-fit or healthy people and see what
is unique or enriched in them. Can we
identify a molecular component that drives
optimal fitness?”, he wondered. This did
not come totally out of left field; there werepeople already engineering microbes andmicrobiome communities to do various
things. Scheiman’s idea of working withelite athletes led to a Nature Medicine paper(Nat. Med. 25, 1104–1109, 2019), coveragein pretty much all the major news outlets,
and a company. He says coverage wasalmost automatic; he only had to “mention
three things: microbiome, athletes andGeorge Church.” Now back in his beloved
Manhattan, ensconced in BioLabs New York,an incubator in trendy TriBeCa, Scheinman
and a small crew of experienced advisors arelooking for funding.
Anik Debnath, CEOof Tenza, had nothoughts of startinga company when hejoined the Church lab
in 2103, but he, too,
had a dream — toengineer the vaginal
microbiome to deliver
Anik Debnath,a prophylactic HIV
cofounder and CEO,vaccine. He came up
Tenza. Credit: Mariah with this idea from
Torpeyhis observing workon prophylactic
vaccines going on at Caltech when he wasan undergrad there, and from his exposure
to clinical problems while participating ina special program at Harvard that provides
PhD candidates with clinical experience.
Even though he was only beginning his
graduate work, Church allowed him topursue this idea. There was nothing quite
like it going on in the lab, but what was there
were many experienced researchers who
could guide Debnath, a physics major withno prior lab experience, around the lab.
“I was starting at zero, total lack ofnews featureexperience with molecular biology. I wastaught everything I knew from the postdocs
I was sitting with. Even though I was alone
in building this project, at the same time, I
wasn’t,” he says. Ultimately, Debnath’s visionof a vaginal-microbiome-based vaccine
was set aside — the bacterial strains weredifficult to work with — but he was inspired
to pursue the wider application of using the
microbiome as a delivery vehicle. Debnathstayed on as a postdoc to flesh out this idea,
but eventually it came time to take it outof the lab. With a modest budget derived
from private investors and from winningseveral startup competitions, Debnathfounded Tenza with a team of four people,
all, like himself, willing to work at what hecalls postdoc-level wages. The group has
set its sights on targeting large needs likeinflammatory bowel disease.
The lure of cuttingedge science in the
Church lab is also
what brought Alex
Ng there for his
graduate studies. In
the group, he says,“You feel like you
are bringing science
Alex Ng, cofounderfiction into reality
and CSO, GC
but in a meaningful
Therapeutics.
way.” Church was theCredit: Parastoo
catalyst in connecting
Khoshakhlagh
Ng with Parastoo
Khoshakhlagh, abiomedical engineer
who at the time was a
postdoc at the Wyss.
Khoshakhlagh had
had the experience ofdeveloping an organon-a-chip technology
using neural stem
cells, which waslicensed out toneurotech biotech
ParastooAxoSim, and had been
Khoshakhlagh,CSO of an all-womencofounder and CEO,startup, Tympanogen,
GC Therapeutics.
which developed
Credit: Alex Nga patch to repair
ruptured ear drums.
When she joined the lab, Church teamed
her up with Ng on his thesis problem, which
they then turned into the foundation for GC
Therapeutics. They have created a platform
exploiting thousands of human transcription
factors (the ‘TFome’, encoded by >1,500
genes) to create reprogramming cocktails
capable of differentiating human pluripotent
stem cells into potentially any desired typeof mature cell type — a system Ng claims has
higher yields and is much faster than mostother differentiation methods. Although
they initially found the idea a hard sell toinvestors (who have since come around),companies immediately understood thepower of the platform. “Already eightcompanies are knocking on our door to
make sure they have a hand in this,” says
Khoshakhlagh. And the local innovation
ecosystem has stepped up and provided
seed funding; the pair were accepted
into several local competitions, winninga couple that were enough to launch thecompany. They also received support fromboth the Wyss Institute and the Harvard
Blavatnik Accelerator, maintaining theirties to Harvard while they de-risk thetechnology and build their team. Of Church,
Ng says, “He wants to have people withdifferent skill sets with different things tobring to the table and a mindset open tocommercialization and entrepreneurship.”

Going big

Like Debnath, Erik
Kelsic, CEO of Dyno
Therapeutics, had nothoughts of startinga company when
he started graduate
school at Harvard.
“I started grad
Eric Kelsic, cofounderschool thinking I
and CEO, Dyno
was on the academic
Therapeutics. Credit:
track,” he says. His
Dyno Therapeutics/
graduate project, on
Sam Sinai
multiplexing reading
DNA sequences,intersected with technology being developedin the Church lab, specifically multiplex
automated genomic engineering, or
MAGE. “Multiplexing [is] George’s favorite
thing. Everything he does, he does bymultiplexing,” he says (on a recent podcast,
Church said that “multiplexing should be
my middle name”). In fact, Kelsic worked
on a technology called MAGE-seq as partof his thesis, so Church was a natural
fit for his doctoral committee as well as
for a postdoctoral mentor. As Kelsic wasworking on his degree, he also helped afriend develop pitches for business-plancompetitions, and this is where he caught
the startup bug. In the Church lab, Kelsic
led a team that took on the challenge ofdesigning adeno-associated viral (AAV)
vectors for protein delivery by marrying
three technologies — DNA synthesis,sequencing and machine language (recently
published: Ogden et al. Science 366,
1139–1143, 2019). The group intuited thegene therapy community’s appetite forbetter vectors, and after being granted seedfunding from Harvard and the Wyss, set
up the nascent company in the Cambridge

incubator LabCentral, starting with one
bench, but quickly getting the attention of
local VCs who have provided funding thatenabled them to move up into a private suitewith 16 full-time staff. Kelsic sums up histime in the Church lab this way: “What’s
unique… is that George is supportive of
doing projects where a startup is the end
goal. I was able to think about that from thevery beginning, which is different from theway things go at most universities. You think
about a company at the very end.”
Nebula Genomics
has also amassed
a respectably sizedgroup in a shortperiod of time —14 people in two
locations. This
company, which
created a secure
Kamal Obbad,
environment forcofounder and CEO,sharing and storing
Nebula Genomics.
genomic information,
Credit: Anthem
may at last succeed
Multimedia
at something Church
has been trying to
do for decades. In
2007, he set up a venture called Knome
to sequence individual genomes (for aconsiderable sum of money). Although
this business never really took off, thenonprofit ‘Personal Genomics Project’ —a free and totally accessible database ofindividuals’ health data, including genomes— followed and was more successful. The
new idea for Nebula (Nat. Biotechnol. 37,
1115–1117, 2019) came from now-CEO
Kamal Obbad, who was at Google when hecontacted Church with the idea of creating
a blockchain for sharing sensitive genomic
information. He barely had gotten out theword “blockchain” when Church chimed inthat he had been mulling over the same idea,
and had a student in his lab, Dennis Grishin,
who was a perfect partner for Obbad. After
only a couple of years at Google, Obbad
was ready to move on, and he lived on his
savings for six months while the trio crafted
the Nebula platform. It has paid off; they
have already raised a series A round fromno fewer than 12 investors and establisheda partnership with a major pharmaceuticalcompany, and are now raising revenues
from people using the platform. Church hastaken an interest in the company, and it’s
paid off. “George is a great way to get the
flywheel started and to get a big respected
experienced name involved with yourcompany. At the end of the day, the businessneeds to have solid footing for VCs to getinterested,” says Obbad. Being part of the
Church ecosystem helps too, as Church

Nature Biotechnology | www.nature.com/naturebiotechnology

news featureencourages his companies to work together.
“We do genetic testing, we can work withcompanies, creating new sequencing
technologies, giving us access to cheaper
platforms. There’s a lot of interesting things
that you can do with Church lab ecosystemthat has proved valuable.”

New world order

Church has worked on the cutting edgeof technologies for decades, yet in recent
years, activity coming out of his lab hasreached a fevered pitch. According to
his long-time friend and collaborator
Jorge Conde, who back in 2007
cofounded Knome, one of the few failed
Church enterprises, the current startup
environment is different from that of thepast in several significant ways. There isa very rich ecosystem of infrastructure
for startups to launch into. “Places like
LabCentral or Alexandria LaunchLabs
are where you have a full BSL2 [biosafetylevel 2] lab ready to go and you can rent abench on and have access to equipment for
relatively small amounts of money,” he says.
Access to capital is high for these kinds ofventures, he says, adding that a new breedof scientific founder is also emerging.

“They have grown up in the era of startups,
and have technology, multidisciplinary
backgrounds across biology, computerscience and engineering,” he points out.
In addition, the technology may now becatching up with some of the Church “crazy”
ideas of years past. Cain McCleary, of KdT
Ventures, which has invested in two fromthis cohort and one a few years back, says, “Ifeel like he’s consistently been ahead of histime in creating tool sets, but all of a sudden,
our analysis and manufacturing has caught
up to it, so it’s a particularly special time forfolks in his lab,” he says.
Church himself doesn’t pretend to know
why 2018 was such a productive year, but hesays that there is a positive feedback loop,
dating back to the founding of AbVitro,
which had a nice exit, and the recent startup
by Luhan Yang, eGenesis Bio, which had
a nice entrance, with an A round of $39
million in 2017, followed by a $100 million
B round in late 2019. There’s also a massaffect. The Church lab has one of the highest
densities of people at Harvard. “Having all
the crazy interdisciplinary people in the samelab — there’s something to be said for highconcentration. People bounce around ideas
more when they are close to each other,” heNature Biotechnology | www.nature.com/naturebiotechnology

says. Zimmerman would agree. “Church has
an amazing number of innovative teams in
his orbit. It creates a gravity that pulls in likeminded people,” he says.
Conde sums up the current situation withhis former mentor: “My sense is what he does
is to try experiments and see what works anddoesn’t work. By spinning out companies, he’s
running a social experiment to see if an idea
is better served in academia or industry. He’s
certainly not afraid of failure.”
In fact, Church himself sees failure as animportant component of his success. “A lotof people reject ideas without even trying
them. Other people will try them and thenthrow them in the trash. We put them up on
the wall and glorify our failures as challenges
for the future. If you’re not failing, you’re
not trying,” he says.
For a complete transcript of aconversation with George Church, go to our
Bioengineering Community page.
❐Laura DeFrancesco

Senior Editor, Nature Biotechnology.

Published: xx xx xxxx
https://doi.org/10.1038/s41587-019-0369-7