miércoles, 5 de enero de 2011

Taking DNA Sequencing to the Masses

Jonathan M. Rothberg fancies himself the Steve Jobs of biotechnology. While much less known than the Apple leader, Dr. Rothberg is also a wealthy entrepreneur with a reputation as a visionary, a masterful promoter and a demanding boss.
ROSLYN HEIGHTS, N.Y. — But what Dr. Rothberg really means is that he wants to do for DNA sequencing what Mr. Jobs did for computing — spread it to the masses.

Dr. Rothberg is the founder of Ion Torrent, which last month began selling a sequencer it calls the Personal Genome Machine. While most sequencers cost hundreds of thousands of dollars and are at least the size of small refrigerators, this machine sells for just under $50,000 and is the size of a largish desktop printer.

While not intended for the general public, the machine could expand the use of DNA sequencing from specialized centers to smaller university and industrial labs, and into hospitals and doctors’ offices, helping make DNA sequencing a standard part of medical practice.

“It’s the same 200 people around the world who buy all these machines,” Dr. Rothberg, who has a Ph.D. in biology, said of the sequencing centers. “I want to make this ubiquitous. I want to move this into the clinic.”

Rather than culturing a bug to identify what is infecting a patient, for instance, a hospital might determine its DNA sequence. Massachusetts General Hospital is already sequencing 130 genes from patient tumor samples, looking for mutations that might predict which drugs will work best. It has won an Ion Torrent machine in a contest and hopes to put it to that use.

“I think all the other technologies could not be easily implemented in a lab like ours,” said Dr. John Iafrate, director of molecular diagnostics at the hospital. Ion Torrent, he added, would “democratize” sequencing.

While most experts agree that sequencing will become commonplace in medicine, some say they think Dr. Rothberg is overselling his machine. Like the early Apple II of Mr. Jobs, it is too puny for many tasks, including sequencing the entire genome of a person.

“It dies on its output,” said David I. Smith, a director of technology assessment at Mayo Clinic.

Dr. Rothberg acknowledged that the existing model was good for sequencing a virus or bacterium or a handful of genes, and indicated that future models would be more powerful. The Ion Torrent machine uses chips like those in a computer to do sequencing, rather than the complicated cameras and lasers most other sequencers use. That allows it to piggyback on the continuous improvement in semiconductor technology.

“We’re using that entire electronics industry supply chain,” he said.

One believer is Life Technologies, a big sequencer manufacturer. It raised eyebrows in August by acquiring Ion Torrent for $375 million in cash and stock upfront, plus as much as $350 million later if sales reach certain levels.

That produced a windfall for Dr. Rothberg, 47, who had put up much of the money as well as raising $37 million from a total of 17 investors, according to a regulatory filing in March.

The three-year-old Ion Torrent, based in Guilford, Conn., is the fifth company started or bankrolled by Dr. Rothberg. That includes another sequencing company, 454 Life Sciences, which was sold to Roche for $140 million in 2007.

His track record has given him the luxury to indulge his passions. Using 700 tons of granite imported from Norway, he had his own version of Stonehenge, which he calls the Circle of Life, built near his home overlooking Long Island Sound in Guilford. Interested in wine-making, he acquired Chamard Vineyards in nearby Clinton, though he does not drink. He has a collection of art by Andy Warhol, Keith Haring and Roy Lichtenstein and an elaborate model railroad set.

He and his wife Bonnie, who has a medical degree, have five children, whom Dr. Rothberg often refers to in his speeches. The couple started the nonprofit Rothberg Institute for Childhood Diseases, which works on treatments for tuberous sclerosis, a rare disease that affects one of their children.

Entrepreneurialism runs in the family. Dr. Rothberg’s father, a chemical engineer, developed a new way of laying ceramic tile and started a company, Laticrete, which is now run by one of Dr. Rothberg’s brothers.

Backing from the family allowed Dr. Rothberg to start his first company, CuraGen, a pioneer in genomics, after he earned his doctorate at Yale in 1991. Stocks of genomics companies soared and Dr. Rothberg made Fortune magazine’s 2001 list of the 40 richest Americans under 40, with an estimated net worth of $168 million.

But CuraGen’s shares, and Dr. Rothberg’s wealth, fell rapidly when investors realized that genomics was not going to lead to a plethora of new drugs. Dr. Rothberg resigned as chief executive of CuraGen in 2005. In 2009, after a cumulative loss of $469 million, CuraGen was acquired by Celldex Therapeutics for $93.5 million in stock.

In 2000, Dr. Rothberg started 454 — he won’t say what the number means — initially as part of CuraGen. As he often tells it, in 1999, his newborn son Noah was rushed to the hospital, unable to breathe.

“I switched from being interested in genomes to being interested in his genome exclusively,” Dr. Rothberg said. In the hospital waiting room, Dr. Rothberg saw a picture of Intel’s Pentium microprocessor, with its millions of transistors, on the cover of a computer magazine. That gave him the inspiration to speed up sequencing by working on numerous DNA snippets in parallel.

“If somebody is to get the Nobel Prize for next-generation sequencing, it should be Jonathan,” said Michael Weiner, who worked for Dr. Rothberg for many years.

With collaborators, 454 published one of the first two full genomes of a specific person — the DNA scientist James D. Watson — and also the genome of Neanderthals. But the company was passed by Illumina, which now dominates the sequencer business.

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