YSM Issue 86.1

ALUMNI PROFILE
FEATURE
Dr. Jonathan Rothberg’s journey in next-generation personal genome
sequencing began in the neonatal intensive care unit. His newborn son
Noah was completely blue from the inability to breathe properly, and
Rothberg and the doctors did not know why. Noah would be okay, but
little did Rothberg know that this heart-pounding experience, combined
with his passion for engineering, would lead to one of the most widely
used technologies for genomic sequencing and one of the most important
recent inventions in medicine.
As Rothberg’s father was a chemical engineer, Rothberg spent much
of his childhood exploring and tinkering around in his father’s lab in the
basement of their home. He remembers stumbling upon a collection of
various scientific books, conducting chemical experiments, and programming
his own computer. In some ways, Rothberg began his engineering
career in the lab, building his own communication systems and using
pyrotechnics to build fireworks as a personal hobby.
After majoring in chemical engineering with an option in bioengineering
at Carnegie Mellon University in 1985, Rothberg went to Yale
University to earn his M.S., M.Phil., and Ph.D. in biology. With the new
molecular biology program, he was able to delve into genomic sequencing
and began to think of a more systematic way for automating highly
manual, costly DNA sequencing used at the time. Eventually, his project
led to one of the earliest understandings of genes involved in the wiring
of the nervous system.
The silicon semiconductor chip used for DNA sequencing
measures the charge of the ions released during DNA replication.
The chip allows the DNA sequence to be read directly
without the physical information or optical systems that other
sequencing machines require. Courtesy of MIT Technology
Review.
Just two years after finishing his doctorate program, Rothberg launched
his first startup company, CuraGen, which developed drugs by using
information from the human genome. It was a huge success. In 1998,
CuraGen went public and, in subsequent years, raised over $600 million
from public markets — and the company was worth more than either
American Airlines or U.S. Steel.
Although he had a secure career with CuraGen, Rothberg’s interest
shifted to personal genomics. It was amidst this success that his son was
born with breathing troubles. He realized then that he did not want to
mine the consensus human genome but rather to understand “what
made Noah unique and why he wasn’t breathing.” Thus, despite much
criticism from his peers who said the human genome had already been
sequenced, he shifted his efforts from drug development to personal
From Engineering to Entrepreneurship:
Jonathon Rothberg, Ph.D. ’91
BY JOSHUA RYU
Forbes praised the Ion Torrent and Rothberg’s personal genomic
techniques as the “Next $100 Billion Technology Business,”
for its potential to sequence the entire human genome in a few
hours and make the sequencing viable for the public. Courtesy
of Kris Krug on Flickr.
genomics, starting another company, 454 Life Sciences.
Rothberg brought about a scientific breakthrough in personal genomics.
He developed a parallel sequencing technique to produce millions of
DNA sequences at once, selling more than $100 million worth of new
sequencing machines in the first year on the market. He was shocked
to find one morning that his company had been sold to another company,
but the event could not stop him from pursuing further research
innovation. He founded Ion Torrent, a new company that would invent
semiconductor sequencing, enabling sequencing machinery to exist on
a tiny disposable chip. His technique leveraged an innovative approach
to sequencing; it directly translated chemical information to digital
information by detecting the number of hydrogen ions released with the
addition of each nucleotide during DNA replication. More importantly,
it had the potential to decode the genome in a few hours for less than
a thousand dollars.
One can only imagine the excitement this semiconductor sequencing
discovery would have brought to molecular biologists. The World
Economic Forum called it a “pioneer of new approach to genetic
sequencing,” the CT Medal of Technology praised it as the “first personal
genome machine,” and Rothberg was featured on the covers of leading
science journals such as Nature, Cell, and Science. From its onset, Life
Technologies offered more than $375 million for the technology and
eventually bought the company for a total of $725 million.
It is not an easy task to build three companies in a lifetime and nurture
all three to success. Rothberg attributes much of his achievement to his
training as a scientist. “Researchers know that you have to be smart; you
have to go through the ups and downs,” he says. “And you can’t quit
until you have solved the problems.” Taking such a progressive attitude
into entrepreneurship has been one of his greatest assets. He believes
that the key to his entrepreneurial success has been meeting the bright
people determined to achieve their goals.
Just last summer, Rothberg’s sequencing machines rapidly analyzed E.
coli that caused foodborne illnesses in Germany, allowing prompt treatment
of patients in hospitals. His techniques have been useful in efficient
agriculture and fuel production, directly affecting the lives of millions.
With his sequencing techniques, Rothberg is, as he describes it, “feeding
the world, fueling the world, and healing the world.”
www.yalescientific.org
January 2013 | Yale Scientific Magazine 35