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President Barack Obama awards the National Medal of Technology and Innovation, the nation's highest award for achievement in technology, to Dr. Jonathan Rothberg during a ceremony at the White House in 2015.
Rothberg is awarded the National Medal of Technology and Innovation, the nation's highest award for achievement in technology, by President Barack Obama in 2015.

Jonathan M. Rothberg (born 1963) is an American scientist and entrepreneur. He is the founder of CuraGen, 454 Life Sciences, RainDance Technologies, Ion Torrent Systems,[1] Butterfly Network,[2] and the medical device incubator 4Catalyzer.[3] Rothberg is best known for his contributions to next-generation DNA sequencing. He was awarded the National Medal of Technology and Innovation by President Barack Obama in 2015 for his “pioneering inventions and commercialization of next-generation DNA sequencing technologies, making access to genomic information easier, faster and more cost-effective for researchers around the world."[4]

Early Life and Education

Rothberg was born in New Haven, CT[5] to Lillian Rothberg and Henry Rothberg, a chemical engineer who invented a new way of laying ceramic tile and founded Laticrete International, Inc., to commercialize it.[6] Rothberg earned a BS in Chemical Engineering with an option in Biomedical Engineering from Carnegie Mellon University in 1985[7] and went on to earn a MS, M.Phil., and Ph.D. in biology at Yale University.[7] His graduate work at Yale focused on sequencing the 9,000-base gene Slit, a project that took him six years and earned him the John Spangler Nicholas Prize for Outstanding Doctoral Candidate in 1991.[8][9]

Career and Research

CuraGen

In 1991 Rothberg founded his first company, CuraGen, with financial backing from his family.[6] CuraGen's goal was to use newly emerging data from the Human Genome Project, which had launched shortly before, to discover drug targets and diagnostic tests.[10] [11] Rothberg and colleagues at CuraGen published the first complete map of protein-protein interactions in yeast, work that was featured on the cover of the journal Nature in February 2000.[12] The company also produced the first global proteomic maps of eukaryotic and metazoan organisms (Science cover).[13] CuraGen went public in 1999 and in October of 2000 was valued at over US$3.3 billion. [WHAT CAN WE FILL IN HERE] CuraGen was acquired by Massachusetts-based Celldex Therapeutics in 2009 for $94.5 million.[14]

454 Life Sciences

In 2000 the Human Genome Project released the first complete draft of a human genome, a process that took 13 years and cost $2.7 billion.[15] Rothberg's second company, 454 Life Sciences, focused on reducing the cost and time required to sequence genomes.[16] Rothberg and colleagues at 454 developed a massively parallel, miniaturized and solid phase pyrosequencing system on a single substrate[17][18] that allowed for real-time sequencing-by-synthesis[19] via cloning by limiting dilution.[20] Whereas Sanger sequencing processed 96 individual reactions and was capable of sequencing 1 megabase of DNA per run, 454 Sequencing processed one million sequencing reactions in parallel and eventually sequenced 400-600 megabases of DNA per 10-hour sequencing run, with read lengths of 400 to 500 base pairs.[21]

Rothberg used the 454 sequencer to undertake a variety of projects. In 2006, Rothberg and Dr. Svante Pääbo initiated the Neanderthal Genome Project, publishing cover articles in Nature and Cell that year.[22][23] Rothberg collaborated with Dr. Matthew Meyerson in 2006 to study the genetic basis of a patient’s drug response by applying next-generation sequencing to a cancer, which was published in Nature Medicine.[24][25]

In May 2007, Rothberg and colleagues used a 454 device to sequence Dr. James Watson’s complete genome for $1 million and published in Nature.[26] It was the first individual genome to be sequenced using next-generation rapid-sequencing technology, and the first to be sequenced for under $1 million.[27][28]

Roche Diagnostics acquired 454 Life Sciences for $154.9 million in late March 2007.[29] In October 2013, Roche shut down 454 when the technology became non-competitive with the introduction of sequencing machines from competitors including Illumina and Ion Torrent.[30]

Ion Torrent

Rothberg's next company, Ion Torrent, again sought to reduce the time and cost needed to sequence DNA. Ion Torrent technology sequenced DNA on a semiconductor chip using an architecture similar to the complementary metal-oxide-semiconductor (CMOS) chips found in cell phone cameras.[31] Rather than photosensitive pixels, the Ion Torrent chip is covered in millions of wells where sequencing reactions take place, translating ions, not photons, into digital information.[32][33] The wells on the Ion Torrent chip are flooded with a single type of nucleotide every 15 seconds[32] and detect the change in pH from the release of a hydrogen ion upon a nucleotide's incorporation into the DNA template.[34][35][36][37] Detecting pH directly allowed Ion Torrent to eliminate optical components that drove the cost of existing sequencing machines as high as $500,000 to $1 million,[38][39][40] enabling Ion Torrent to sell their Personal Genome Machine for $50,000.[41]

In 2010 Life Technologies acquired Ion Torrent at a valuation of $725 million.[42] Life Technologies was later purchased by Thermo Fisher Scientific purchased Life Technologies for $13.6 billion in February of 2014.[43]

On Jan 10 2018, Illumina announced a partnership with Thermo Fisher to license the AmpliSeq chemistry developed at Ion Torrent.[44] Launched in 2011, AmpliSeq technology employs polymerase chain reaction (PCR) to capture DNA or RNA targets from limited samples for sequencing on NGS platforms.[45]

4Catalyzer

In 2014 Rothberg founded 4Catalyzer, a medical device and biotech incubator based in Guilford, CT to develop life science research tools, medical devices and therapeutics.[3] The first two of 4Catalyzer's portfolio companies, LAM Therapeutics and Butterfly Network Inc., launched publicly in 2013 and 2018, respectively.

Lam Therapeutics

LAM Therapeutics, which launched in 2013, develops therapeutics for cancer and rare diseases.[46] LAM has advanced three drugs into clinical trials: LAM-001 for lymphangioleiomyomatosis, LAM-002 for B-cell non-Hodgkin lymphoma, and LAM-003 for acute myeloid leukemia.[47]

Butterfly Network

Butterfly Network, founded by Rothberg in 2010, develops medical ultrasound technology.[48] Rothberg and colleagues replaced the 128 hard-wired crystal transducers found in a typical ultrasound device with a single chip containing 9,000 capacitive transducers -- tiny drum heads -- used to send and receive ultrasonic vibration.[48] The transducers are bonded to a single complementary metal-oxide-semiconductor (CMOS) chip, providing a direct signal transfer from the transducers to the signal processing components on the CMOS chip to form a single "ultrasound-on-a-chip".[49] The company has stated it seeks to make ultrasound more accessible and affordable.[48]

Rothberg Institute and Foundation for Childhood Diseases

Rothberg founded the Rothberg Institute and Foundation for Childhood Diseases in 2002 to support research on tuberous sclerosis and epilepsy.[50] The institute ran a distributed computing project called Community TSC based on technology known as the Drug Design and Optimization Lab (D2OL) to use volunteers' personal computers to model interactions of drug candidates with their target molecules.[51] Through his foundation, Rothberg seeded a healthcare-focused hardware hackathon, known as the Rothberg Catalyzer, at five schools: Yale, Carnegie Mellon, UPenn, Brown, and Choate Rosemary Hall.[52][53][54]

Personal Life

Rothberg and his wife, Bonnie Gould Rothberg, MD, PhD, MPH, an Oncology Hospitalist in the Yale-New Haven Health System, have five children. Rothberg has stated that his son Noah served as inspiration for Rothberg's first sequencing company, 454, and that his daughter Jordana inspired him to found Butterfly Netowork.[51] Rothberg and his wife Bonnie reside in Guilford, CT. Their home is noted for containing a replica of Stonehenge made from Norwegian granite and known as "The Circle of Life".[55]

Awards and nominations

  • 2015: The National Medal of Technology and Innovation for "pioneering inventions and commercialization of next generation DNA sequencing technologies, making access to genomic information easier, faster, and more cost-effective for researchers around the world."[56]
  • 2015: The World Economic Forum’s Technology Pioneer, for Butterfly Network Ultrasound on a chip[57]
  • 2014: John A. Quinn Lecture in Chemical Engineering, University of Pennsylvania[58]
  • 2012: Wilbur Cross Medal for most distinguished alumni, Yale University[59]
  • 2011: DGKL Biochemical Analysis Prize for development of massively parallel DNA sequencing
  • 2011: Doctor of Science Honoris Causa Mount Sinai School of Medicine for inventing massively parallel DNA sequencing[60]
  • 2010: The World Economic Forum’s Technology Pioneer, for the Ion Torrent Semiconductor Sequencing[61]
  • 2010: Connecticut Medal of Technology for inventing Next-Generation sequencing[62]
  • 2009: $2.2 Million NIH/NHGRI technology development award to ION for the $1,000 genome[63]
  • 2008: The World Economic Forum’s Technology Pioneer, for the Raindance microfluidics system[64]
  • 2007: The World Economic Forum’s Technology Pioneer, for 454 Life Sciences' invention of Next-Gen Sequencing[65]
  • 2006: R & D 100 Awards to 454 Life Sciences[66]
  • 2005: Wall Street Journal 2005 Technology Innovation Awards, Gold Medal Winner for inventing Next Generation sequencing[67]
  • 2005: Member Connecticut Academy of Science and Engineering[68]
  • 2004: National Academy of Engineering[69] 
  • 2000: The Irvington Institute’s Corporate Leadership Award in Science[70]
  • 1998: Ernst and Young Entrepreneur of the Year[71]
  • 1991: John Spangler Nicholas Prize for the outstanding Doctoral candidate

References

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