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Jonathan Rothberg, PhD

Professor (Adjunct) of Research of Genetics

Contact Information

Jonathan Rothberg, PhD

Research Summary

I am best known for inventing high-speed, massively parallel DNA sequencing. The idea for massively parallel DNA sequencing (next gen sequencing) came to me after my infant son was rushed to intensive care and I realized how critical individual genome sequencing was to human health. I subsequently founded 454 Life Sciences, bringing to market the first new method for sequencing genomes since Sanger and Gilbert won the Nobel Prize in 1980. My invention introduced the era of personal genomes and is now in use at major pharmaceutical companies, universities, genome centers, and medical centers around the world

My work now focuses on extending this paradign, creating additional novel semiconductor based devices to collect phenotypic, and genotypic information at a level never before possible, and the mining of that data using deep learning. Our goal is to create a virtous cycle, where the ease of use and analysis capabilities of the devices are constantly improving, as they gather more information.

My primary research vehicle has been startups - I run a medical technology, and drug start up incubator, 4Catalyzer. However, with my appointment to Yale, I am now looking for gifted individuals, from engineers to chemists, that seek an opportunity to work on innovative projects as joint students with collaborating full time Yale faculty.

Currently I'm looking for biochemists, and molecular biologists, who want to engineer a new type of molecular machine - one that can improve upon itself. The molecular embodiment of that great M.C. Escher Image of a hand drawing a hand. I also have summer internships available at startups in Connecticut and New York City.

Extensive Research Description

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

Research Interests

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

Research Images