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Jonathan Rothberg, PhD

Professor (Adjunct) of Research of Genetics
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Professor (Adjunct) of Research of Genetics

Biography

Dr. Jonathan Rothberg is best known for inventing high-speed, “Next-Gen” DNA sequencing. He founded 454 Life Sciences, bringing to market the first new method for sequencing genomes since Sanger and Gilbert won the Nobel Prize in 1980. Dr. Rothberg sequenced the first individual human genome (The Watson Genome, Nature), and initiated the Neanderthal Genome Project with Svante Paabo. Under his leadership, 454 helped understand the mystery behind the disappearance of the honey bee, uncovered a new virus killing transplant patients, and elucidated the extent of human variation—work recognized by Science magazine as the breakthrough of the year for 2007. The New England Journal described Dr. Rothberg’s innovation as "The New Age of Molecular Diagnostics", Science magazine called it one of the top 10 breakthroughs for 2008. His contributions; cloning by limited dilution, and massively parallel DNA sequencing, are the basis of all subsequent high-speed sequencing methods.

Dr. Rothberg went on to invent semiconductor chip-based sequencing, and sequenced Gordon Moore (Moore’s law) as the first individual to be sequenced on a semiconductor chip (Nature). In 2010, Ion Torrent was acquired by Life Technologies for $725 million, the largest acquisition of its kind. In addition to founding 454 Life Sciences and Ion Torrent, Dr. Rothberg Founded CuraGen Corporation, Clarifi, RainDance Technologies, Lam Therapeutics, Quantum-Si, Hyperfine Research and Butterfly Network.

Dr. Rothberg was born in 1963 in New Haven, Connecticut. He earned a B.S. in chemical engineering from Carnegie Mellon University and an M.S., M.Phil, and Ph.D. in biology from Yale University. He is the first person to be named a World Economic Forum's Technology Pioneer four separate times, is an Ernst and Young Entrepreneur of the Year and received The Wall Street Journal's First Gold Medal for Innovation. He received Nature Methods First Method of the Year Award, The Irvington Institute's Corporate Leadership Award in Science, the Connecticut Medal of Technology, the DGKL Biochemical Analysis Prize, and an Honorary Doctorate of Science from Mount Sinai School of Medicine. Jonathan is a member of the National Academy of Engineering, the Connecticut Academy of Science and Engineering, and is a life trustee of Carnegie Mellon University.

Appointments

  • Genetics

    Professor Adjunct of Research
    Primary

Other Departments & Organizations

Education & Training

PhD
Yale University, Biology (1991)

Research

Overview

My goal with 454 Life Sciences was both to enable the sequencing of individual humans, as well as to utilize sequencing in a research capacity. I led the effort to complete the first sequence of an individual human genome, successfully sequencing James D. Watson's genome. I also initiated the first large-scale sequencing of ancient DNA, the Neanderthal Genome Project, in collaboration with Dr. Svante Paabo (Nature, and Cell Covers).

Under my tenure, 454 Life Sciences worked with collaborators to crack the mystery behind the disappearance of the honey bee, uncover a new virus killing transplant patients, and elucidate the extent of individual human variation—work recognized by Science magazine as the breakthrough of the year for 2007. The collective work of my team, their collaborators and ultimately customers, included projects as diverse as uncovering the complexity of life in the World's oceans and sequencing the extinct wooly mammoth. We also with Mathew Myerson where able to do the first deep sequencing of a tumor (Nature Medicine), and much to the chagrin of my attorney's, Dr. Myerson was able to change the therapy of the patient based on the information we uncovered. Sequencing of tumor DNA is now a critical part of cancer patient care.

The New England Journal described our sequencing innovation as "The New Age of Molecular Diagnostics for Microbial Agents." Science magazine called it one of the top 10 breakthroughs for 2008. Our contribution to sequencing, include both the first non-bacterial cloning systems (cloning by limited dilution), as well as the first massively parallel DNA sequencing method (sequencing by synthesis on a single substrate in parallel), concepts that have formed the basis for all subsequence next generation sequencing technologies.

In 2007, my son again inspired me to start a new business. After telling Noah that I'd successfully read Dr. James Watson's genome, Noah responded that that I should invent something to read people's minds instead. I quickly realized that Noah's intuition was correct: what scientists really needed was a direct way to get information from any biological system—the brain, chromosomes, biochemical pathways—and translate it directly into digital information. I founded Ion Torrent to directly link the language of chemistry and the binary language of computers, and developed the ION torrent chip, a novel semiconductor device that creates a portal between the two worlds. My team went on to invent semiconductor chip-based sequencing, and sequenced Gordon Moore as the first individual to be sequenced on a semiconductor chip (as published in Nature), and the first post-light Genome, paving the way to the $1,000 Genome. In October 2010, Ion Torrent was acquired by Life Technologies for $725 million, the largest acquisition in the history of sequencing technology. This gave me time to think, and led to the creation of a healthcare focused incubator, 4Catalyzer.

In addition to founding 454 Life Sciences and Ion Torrent, I was the founding CEO & Chairman of CuraGen Corporation, an early company dedicated to using genome technologies in drug development, RainDance Technologies, a company developing general droplet microfluidic lab-on-chip technologies, and Clarifi Corporation, an analytical software company. My team was early to recognize the importance of genomics to medicine, and produced the first global proteomic maps of eukaryotic and metazoan organisms (Nature and Science covers respectively), and developed a series of novel human antibody-drug conjugate medicines, now in clinical trials for the treatment of metastatic melanoma and breast cancer (Glembatumumab vedotin, now showing promise in triple negative breast cancer, the most aggressive form of breast cancer), and advanced a new HDAC inhibitor now approved for therapy.

The majority of my research is now carried out in start-ups including, Butterfly Network, which developed the first ultrasound on a chip, and is creating devices to both image and do non-invasive surgery, LAM Therapeutics (CuraGen 2.0), Hyperfine Research, Quantum-Si, Tesseract - just getting started with a great Yale M.D., Ph.D. student, and Deep Learning Corporation - we own the domain. As with our earlier companies we collaborate with academics to open up new fields for the technologies we develop. Currently, we are working with Max Tegmark of MIT (Our Mathematical Universe), and David Ferrucci (Principal investigator behind IBM Watson, and computer Jeopardy champ) on creating a virtous circle enabled by our new semiconductor based instruments, and AI.

Along with my commercial interests, I run a non-profit focused on Childhood diseases, and Cancer. At TRI we have large-scale sequencing projects leveraging the Neanderthal Genome, and the Genomes of individuals with extraordinary math abilities, to try to uncover genes that make us unique. We also were early to sequence centenarian genomes, and have a collaboration with Craig Venters Human Longevity, Inc., to uncover modifier alleles that keep us healthy, work we are now extending with large-scale cancer genome sequencing.

We only work on projects that no one has been able to do before. While we don't publish often, our work has been featured on the covers of Cell, Nature, and Science. If you want to do great work, with significant impact, with the ability to improve the life of someone you love, email me at jonathan.rothberg@yale.edu.

Medical Research Interests

Chemicals and Drugs; Health Care; Information Science; Technology, Industry, Agriculture

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