GE Mosquitoes and the Zika Virus.

                                                      Comments due by March 14, 2016
— In the expanding realm ruled by Randal J. Kirk, sliced apples don’t brown. Salmon grow twice as fast without swimming upriver to spawn. Beloved cats are reborn. And male mosquitoes are unleashed with the sole mission to mate, pass on a gene that kills their offspring, and die. A few decades ago, the foods and creatures nurtured by Mr. Kirk would have been found only in dystopian fantasies like those written by Margaret Atwood. But Mr. Kirk’s company, Intrexon, is fast becoming one of the world’s most diverse biotechnology companies, with ventures ranging from unloved genetically engineered creatures to potential cancer cures and gene therapies, gasoline substitutes, cloned kittens and even glow­in­the­dark Dino Pet toys made from microbes. Until recently, Mr. Kirk, 62, was a relatively unknown, self ­made billionaire, buying up or investing in companies in the biotech world. So when Intrexon acquired the British company Oxitec last summer, it attracted little attention as he extended his reach into genetically modified insects. But that move has thrust Mr. Kirk into the forefront of a scramble to control the Zika virus, suspected of causing babies to be born with tiny heads and damaged brains. It is rampant in Latin America and threatening the United States. While Zika was not on his radar when the deal was announced, Mr. Kirk now appears to be the prescient owner of a potential bioweapon — Oxitec’s genetically engineered mosquitoes, which he says could save millions of people from Zika by causing the population of wild disease ­transmitting mosquitoes to self ­destruct. “I think that we have the only safe, effective, field ­proven and ready­to-deploy solution,” Mr. Kirk, who is usually called R.J., said in an interview in his office here overlooking the Intracoastal Waterway. In Piracicaba, Brazil, the population of wild mosquitoes has fallen 82 percent in the neighborhood where the mosquitoes are being tested, he said. If his plans to sell the engineered mosquitoes succeed, Mr. Kirk will fortify his near cultlike status among some investors and colleagues who marvel at his shrewd (and somewhat lucky) investments. Perhaps more important, a victory against the rapidly spreading epidemic could weaken opposition to genetically engineered organisms of all sorts, propelling many others out of the lab, onto the dinner table or into the environment. Now Mr. Kirk must persuade federal agencies, foreign governments and nonprofit health organizations to place orders. He must counter caution from the World Health Organization and federal officials, who question whether the technique will be effective on a large scale. And he must overcome qualms about genetic engineering that have prompted opposition to the mosquitoes in the Florida Keys and elsewhere.
“We don’t have experience about living transgenic mosquitoes in the air,” said Dr. Artur Timerman, an infectious disease specialist in Brazil. “What will be the midterm or long­ term consequences of this?” Mr. Kirk is assembling a powerful lobbying effort, employing the law firm Sidley Austin in Washington as well as relying on one of Intrexon’s board members, Cesar Alvarez, the senior chairman of the prominent law firm Greenberg Traurig, and Intrexon’s head of corporate communications, Jack Bobo, who once directed biotechnology trade policy at the State Department. Dr. Luciana Borio, acting chief scientist at the Food and Drug Administration, told a House subcommittee on Wednesday that the agency was “greatly expediting” Oxitec’s application to test the mosquitoes in the Florida Keys and would issue a draft environmental assessment very soon. But when asked by Representative Morgan Griffith, a Republican who represents the Virginia district in which Mr. Kirk has a farm, Dr. Borio said the F.D.A. would not eliminate the opportunity for the public to then comment on the draft. “What we don’t know right now is where the public stands on this in the setting of Zika,” she said later in the hearing. Golden Age of Biotech Selling his mosquitoes to combat an international epidemic could help relieve the pressure Mr. Kirk is under to prove that Intrexon is more than just a collection of odd science projects, and that it can actually make money and fulfill his vision for a new golden age of biotechnology. He considers this time to be a seminal moment in history, one in which the rapidly improving ability to read and write — and rewrite — the DNA code of life will make it possible to engineer all manner of organisms to perform specific tasks.
“I think this is the most significant industrial vector to occur in history,” he said, comparing it to semiconductor technology that gave rise to smartphones and the web. And the same DNA tools can be applied to numerous areas. Intrexon’s scientists, he says, “don’t care if they are working on a primary human T cell or an avocado.” Reflecting that vision, Intrexon uses the web domain name dna.com. The engineering of life is often called synthetic biology, a vaguely defined term meant to convey more systematic genetic manipulation than the cutting and pasting of a single gene that gave rise to early biotechnology companies like Amgen and Genentech. At its most distant point, synthetic biologists would sit at a computer designing life forms from scratch, then hit “print” and have the necessary DNA made to order to be inserted into a cell. Numerous companies are moving into the field, but Intrexon is “literally the elephant in the room of the synthetic biology industry,” said John Cumbers, chief executive of SynBioBeta, a fledgling trade group. His supporters say that if anyone can pull off such an enterprise it is R. J. Kirk, whom they call an uncommon visionary and quick study, though he lacks formal training in science. When Mr. Kirk tells people, as he often does, that he is just a country lawyer, they know they’re about to get a schooling in biology or business, interlaced with references to history, philosophy and opera. “He has an astonishing grasp of science,” said Dr. Samuel Broder, a former director of the National Cancer Institute who now runs Intrexon’s health division. Dr. Broder recalled one instance in which it took him a day to understand the intricacies of a genetic disease. Mr. Kirk, after hearing Dr. Broder’s explanation, got it in five minutes. Even the hedge fund manager Thomas U. Barton, who made his mark as a skeptical short­seller, gushes. “He understands all businesses,” he said. Still, there are skeptics. It is hard to judge the strength of Intrexon’s core technology, known as UltraVector, which is a computerized system for putting together modular DNA pieces to make complex genetic circuits. The company, saying it wants to protect its trade secrets, has not published articles about it in scientific literature. Some start­up companies, not Intrexon, have taken the lead in the hot new genome editing technique called Crispr. The biggest criticism is that Intrexon keeps announcing new acquisitions and new collaborations, dozens of them in all. Yet no product made with the company’s technology has reached the market, and it is not clear when any will. “There’s a mixture here of spectacle and speculation,” said Jim Thomas of the nonprofit ETC Group, which says that synthetic biology needs to be more rigorously regulated. “What’s curious about this is the way in which they are putting together all these controversial and often failing one
 trick companies and trying to wrap them up in a fancy synthetic biology front.” Intrexon’s shares have fallen to about $37 from near $70 in July, though biotech stocks in general have also fallen. The company’s market value is $4.3 billion, making Mr. Kirk’s 53 percent worth over $2 billion. One big commercial opportunity could be Intrexon’s pilot project to use genetically altered microbes to turn natural gas, which is cheap and abundant, into isobutanol, a liquid fuel that can be used in cars. Investors want to see if Intrexon’s partner, the energy giant Dominion, commits to building a commercial plant, which Mr. Kirk hopes could happen as early as this year. And the Oxitec mosquitoes, while not something Intrexon developed itself, offer a bonus that Mr. Kirk could not have predicted. The mosquitoes were developed mainly to fight dengue fever, and that alone, Mr. Kirk said, made it worthwhile to pay about $160 million for Oxitec. 3/6/2016 A Biotech Evangelist Seeks a Zika Dividend ­ The New York Times http://www.nytimes.com/2016/03/06/business/a­biotech­evangelist­seeks­a­zika­dividend.html?ref=international 6/10 But because Zika is spread by the same type of mosquito, the Oxitec insects, which contain a lethality gene — can be used. When the male mosquitoes are released to mate with wild females, the offspring die before reaching adulthood.
(NYT 3/6/2016)