Jurassic Park, Neanderthal and You: Genomics Pioneer Rothberg Comes to Yale

jonathan rothberg yale
In the past 15 years, biotechnology entrepreneur Jonathan Rothberg has introduced the first low-cost DNA sequencing technologies, helped produce one of the first full genomes of an individual human being, and co-led a team that sequenced the Neanderthal genome.
According to Rothberg, who will speak at Yale on Feb. 3, the motivation for these innovations was personal. In 1999, after his newborn son, unable to breathe, was rushed into intensive care, Rothberg contemplated how much easier it would be to treat the boy if doctors had complete access to his DNA information.

On Campus

Jonathan Rothberg will discuss the history of DNA sequencing and what it could mean for humankind and the environment at 5 p.m. Feb. 3 in Burke Auditorium, Kroon Hall. A reception sponsored by 4Catalyzer will follow the presentation. Register for free.

“I wanted to understand why this was happening by looking at his genome,” says Rothberg, who received his M.S., M.Phil., and Ph.D. in biology from Yale. “That was the genesis of the sequencing technology.”
At the event — hosted by the Yale Peabody Museum of Natural History and the Yale School of Forestry & Environmental Studies — Rothberg, chairman of 4Catalyzer, will discuss the evolution of DNA sequencing, what it has taught us about life on earth, and its potential to transform humankind and the environment.
In an interview with F&ES, he shared a preview of his discussion, which is free and open to the public. Registration is required.

Q: Was it your experiences after the birth of your son that pulled you into this field of study? 

ROTHBERG: Absolutely, and ‘pull’ is the right word. I thought I was on top of the world. I was the CEO of a public company, and when my son was brought to newborn intensive care, I realized I wasn’t interested in the human genome as a map of humanity — I really just wanted to understand my son’s genome. That led me to develop the first technology that enabled low-cost sequencing. It ended up becoming not just a company but also an industry known as Next Generation Sequencing (NGS). And then, once my son was fine, I wanted to do some of the things I’d been thinking about for decades, which included decoding Jurassic DNA. I called Svante Pääbo, who was the world’s authority on ancient DNA, and said, ‘Let’s sequence a dinosaur.’ He didn’t hang up. But he said let’s try something a little more recent. I said, ‘OK, let’s do Neanderthal.’ Again, he didn’t hang up, even though Neanderthal DNA is the most precious DNA in the world. Instead, he said, ‘I can give you cave bear, which is the same age as Neanderthal’ — about 35,000 years old. After he did that, we decoded more ancient DNA than had been done cumulatively in the history of science to that point. He did send us Neanderthal DNA after we successfully sequenced the cave bear.

Q: What did you learn about life on this planet from that research?

ROTHBERG: The research on ancient DNA touches on two big questions: How does life adapt to climate change in the course of millions of years, or hundreds of thousands of years? And more specifically, because we looked at Neanderthal, how has modern man adapted over the last 500,000 years? In general, ancient DNA can teach us how we’ve adapted as mammals and how we’ve done it as humans. Specifically, we’ve seen genes that give a competitive advantage in all the human populations are out of Africa, from Neanderthal. When you look at those genes, they have adapted us for climate, so that one could survive in a northern climate, and given us the ability to create fantastic technologies. 

Q: What are some of the practical applications coming out of these discoveries, particularly when it comes to tackling environmental challenges?

ROTHBERG: At the environmental level, the research has had some broad applications. If you apply it to medicine, for instance, right now we have a crisis in the number of children with autism. What we’ve learned from the work on Neanderthal are the genes that are likely to have given us the ability to have some of our complex thought processes and speech. You can now look for those genes in people with developmental disorders to better understand autism. And so the practical side of these discoveries has been its impact on our understanding of things as important as autism and as global as how do we adjust to a changing climate.
Sequencing itself has become the single most important tool across the life sciences and medicine.
— Jonathan Rothberg
In terms of NGS, more broadly, it’s really teaching us how to feed, fuel, heal, and secure the world. There is no medicine being developed, and there will be no medicine given in the future, that isn’t based on some understanding derived from DNA sequencing. From Steve Jobs’ cancer genome being sequenced to patients showing up at a Yale hospital for treatment, sequencing is used to give people the right medicine and to develop new medicines. Sequencing is also used to fuel the world — as it aids in the development of bio-fuels. Sequencing is used to secure the world, as we trace outbreaks from ebola to anthrax. And when it comes to feeding the world, modern crop development involves sequencing. Sequencing itself has become the single most important tool across the life sciences and medicine. It’s probably becoming as important as clean water, antibiotics and imaging have been to humanity over the past 100 years.
It’s really an amazing tool. You see it on [the television show] CSI, where it’s used for forensics in murder cases, but you can also use it to find out what’s killing the honeybees, which is an environmental study we did.

Q: What has your research revealed about honeybee collapse disorder?

ROTHBERG: As you would expect, honeybee collapse is a complex problem that has two components. It has an environmental component and a genetic component, which is no different from our understanding of any complex disease, such as diabetes. What we found was that there was a virus that was associated with the death of the honeybees. But what in the environment is making these honeybees so susceptible to this virus? During my talk I’ll draw parallels with a situation where we saw transplant patients who were dying as a result of a virus that normally doesn’t hurt people. The transplant patients were immune-suppressed. In the same way, that virus may have been completely harmless the last few hundred years to honeybees, but now there is some environmental stress that is allowing a virus that shouldn’t kill honeybees to collapse their colonies.

Q: You mentioned Steve Jobs earlier. Some have called you the Steve Jobs of the biotechnology world because your work has brought these sequencing technologies beyond a relatively few number of researchers. What do you see as the impact of this democratization of these technologies?

ROTHBERG: As you lower costs, you make these technologies ubiquitous. Since we first brought our products to market, we really pushed the market to lower costs, which has allowed it to go from just developed countries to the developing world. There was a very specific case where we sold one of our machines to people funded by Bill Gates, so that they could better understand the crops that people were growing. So we’ve seen it spread from tertiary care centers at Harvard and Yale to Africa and the Amazon. There’s also a scientist, Nathan Wolfe, who uses DNA sequencing to find out what diseases animals catch in the wild are potentially getting exposed to human populations in Africa. So we’ve seen that as NGS prices have gone down, not only has that opened up scientific venues and medical venues in the developed world, but it has also started to help feed and help secure the developing world. 
– Kevin Dennehy    kevin.dennehy@yale.edu    203 436-4842
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PUBLISHED: January 29, 2015

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