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J. Craig Venter, scientist who decoded the human genome, dies at 79

By Nicholas Wade New York Times

J. Craig Venter, a scientist and entrepreneur who raced to decode the human genome, died Wednesday in San Diego. He was 79.

His death was announced by the J. Craig Venter Institute, a nonprofit research organization founded by Venter and based in San Diego and Rockville, Maryland. The institute said in a statement that Venter had been hospitalized recently for side effects from cancer treatment.

In the 1990s, Venter, a risk-taker and intense competitor, made a bold move when he decided that the Human Genome Project, a $3 billion government program for decoding the human genome, was moving slowly enough that he could enter the race late and beat it with a much faster method.

His gamble paid off. In 2000, his company, Celera, made a joint announcement with a rival group saying that they had assembled the first human genomes, a landmark step toward uncovering the genetic basis of human disease and origins.

Venter had a powerful ego. That was clear when he let slip that the anonymous donor whose genome Celera had sequenced was none other than his own.

But his drive and management skills helped him inspire loyalty and assemble teams of exceptional scientists, including Nobel Prize-winning microbiologist Hamilton O. Smith. Together, they achieved one landmark after another in the nascent field of genomics.

In 1995, Venter revolutionized microbiology when he published the sequence of DNA letters in the bacterium Haemophilus influenzae, the first bacterial genome to be decoded, along with annotations of all the organism’s genes.

The moment electrified science. For the first time, researchers could see all the genetic components of a free-living organism, giving microbiologists a manual for bacterium’s genetic tool kit. It also set off a race to sequence the genomes of known pathogens, with the aim of identifying their genetic arsenals and devising countermeasures.

His team next turned to the fruit fly genome to test whether their approach, known as a whole-genome shotgun sequencing, could work on its biggest target: the human genome. The fruit fly genome was successfully decoded in 2000, providing a wealth of information that would help scientists study both the fly and human genomes.

Decoding the human genome, Venter’s next big challenge, became the focus of a competition between his team at Celera and a consortium of academic rivals led by the United States and Britain. The National Institutes of Health, a major patron of the effort, refused to cooperate with Venter, who instead secured private funding from the Celera Corp.

Venter’s whole genome shotgun method enabled him to erase his rivals’ head start. With ample time and money, he might have seized this greatest of scientific prizes. Instead, he agreed, reluctantly, to accept the consortium’s offer of a formal draw, with the trappings of a White House ceremony with President Bill Clinton.

For his contributions to sequencing the human genome, Venter received the Nierenberg Prize for Science in the Public Interest from the Scripps Institution of Oceanography in 2007. President Barack Obama presented him with the National Medal of Science in 2009.

A Rebel by Nature

John Craig Venter was born on Oct. 14, 1946, in Salt Lake City to Elisabeth and John Venter. Both parents had served in the U.S. Marine Corps during World War II. His father, an accountant, and his paternal grandfather were members of the Church of Jesus Christ of Latter-day Saints.

The young Venter, a rebel by nature, inherited no appetite for the disciplines of the military or the church. His high school grades were dismal, though through his passion for competition he became a champion high school swimmer. But rather than accept a swimming scholarship that he had been offered at Arizona State University, he headed off to the beaches of Southern California, where he devoted himself to the pursuit of “drink, girls and bodysurfing,” as he wrote in his autobiography, “A Life Decoded — My Genome: My Life” (2007).

The pleasures of the beach were abruptly halted by the Vietnam draft. He applied to the Navy which told him, to his amazement, that he had an IQ score of 142 and could choose any Navy career he wanted. He signed up for Hospital Corps’ school.

Sent to Vietnam, he joined a Navy hospital in Da Nang, where he became a senior corpsman in the intensive care unit. He witnessed several hundred soldiers die, often as he was massaging their hearts or giving artificial respiration, he recalled. At one point, the relentless stream of mangled young bodies needing his care became overwhelming. He decided to swim out to sea until he was exhausted and so end his life. But after an encounter with a shark, fear replaced depression.

“I wanted to live, more than I had ever done in the previous 21 years of my life,” Venter wrote. Though by now, out of sight of the shore, he managed to regain the beach.

Seeing how medicine could improve lives, he decided that if he survived the war, he would become a doctor.

But gaining entry to medical school was no easy task. His goofing off in school as a youth had left him barely able to spell, but with the help of the GI Bill, he was accepted by the University of California, San Diego. In 1975, some 7 1/2 years after his return from Vietnam, he gained a doctoral degree.

By now his interest had switched to research. His doctoral topic was the receptor proteins with which a cell responds to adrenaline, a subject he pursued at the State University of New York at Buffalo (now the University at Buffalo). Invited to join the National Institutes of Health in 1983, he decided to isolate the gene that makes the adrenaline receptor and then to sequence it.

A method for determining the order of the bases, or code letters, in DNA had been developed by Frederick Sanger, a two-time recipient of the Nobel Prize in chemistry; he had used it to decode the DNA of a virus. But Sanger’s method was manual and very laborious. It was not until his process was automated that it became feasible to decode long stretches of DNA.

Venter was quick to appreciate possibilities of a DNA-sequencing machine made by Applied Biosystems, and he became the company’s first client. He bequeathed the adrenaline receptor project to his colleague and second wife, Claire Fraser, and plunged into the new field of DNA sequencing.

Encountering Roadblocks

Venter quickly devised a method for fishing out the genes, which constitute less than 2% of the human genome, and was advised by an NIH official to apply for patents on the many gene fragments he discovered. These two developments led to frontal disagreements with James D. Watson, the director of the NIH’s genome project and a co-discoverer of the structure of DNA. Watson didn’t want genes to be patented and feared that Congress would refuse to fund the $3 billion human genome project if Venter had skimmed off all the genes.

Venter’s research career might well have stalled at this point. But the human genome was of high interest to the pharmaceutical industry. Wallace Steinberg, a biomedical entrepreneur, agreed to fund him with $70 million. Because Venter insisted that he was interested only in research, not in commercial applications, Steinberg set up twin organizations, the Institute for Genomic Research, or TIGR, headed by Venter, and Human Genome Sciences, a company directed by William Haseltine to exploit Venter’s discoveries.

At TIGR, Venter, looking for scientific glory, wanted to announce his discoveries about human genes but was hampered by Haseltine, who sought to block publication until he had filed patents on anything of value. Venter then turned his sequencing machines on the bacterium Haemophilus influenza. Haseltine could not block bacterial work, and Venter saw the chance of trouncing the government, whose work on the first bacterial genome was going slowly and would eventually take 13 years.

Just as Venter had been the first researcher to grasp the potential of the new DNA sequencing machines, he was also the first to understand the power of allying them to powerful computers. The government approach to sequencing a genome was first to make a map of where each fragment belonged, and then to decode each fragment. With a big enough computer and a clever assembly program, Venter realized, he could skip the tedious mapping process and have the computer string together all the tiny 600-letter fragments decoded by the sequencing machines. He sequenced the Haemophilus genome in just a few months in 1995.

The triumph was particularly sweet because the National Institutes of Health, which funds most academic biomedical research, had turned down his grant application on the grounds that his novel decoding method, known as a whole genome shotgun, could not work. With another source of funds he had available, Venter went ahead and proved the NIH’s experts wrong.

Venter now felt that his institute could make a serious contribution to the government’s human genome program, but his attempts to participate were rejected. He was then approached by Applied Biosystems, the leading maker of the DNA sequencing machines, which suggested that he sequence the human genome himself. It had not escaped the company’s attention that if it could generate a rival effort to the government’s, it would double the market for its sequencing machines, selling for $300,000 apiece (about $660,000 in today’s currency).

Gaining Riches

Venter accepted the challenge and in 1998 agreed to head a company, Celera Genomics, set up by Perkin Elmer, the parent company of Applied Biosystems. At this point he was riding high. With his grants of stock in TIGR and Celera, he had gained riches beyond the dreams of most researchers. He owned a $1 million yacht, named Sorcerer, which cost $300,000 a year to maintain. His public feuding with establishment scientists kept him at the center of media attention.

“Here was a serious scientist who did not take science or himself that seriously,” science journalist James Shreeve wrote in his book “The Genome War: How Craig Venter Tried to Capture the Code of Life and Save the World” (2004), “who glowed with self-possession and wealth but seemed invitingly vulnerable, a 50-something veteran of Vietnam who had fought with people in power throughout his career but still exuded the now bashful, now boastful charm of a high school heartthrob.”

In pursuing the high prize of the human genome, Venter was exposed to many opposing forces. His academic competitors derided the profit-making involved in his efforts and continued to assert that his method could not work. Their policy of making their human DNA data public complicated Celera’s business plan of selling subscriptions to its information. Venter found himself increasingly at odds with his new boss, Tony White, the president of Perkin Elmer.

In addition, the technical problems of assembling the human genome were complicated by its extensive number of repeats, making it like a jigsaw of identical pieces. The adventure took Venter to peaks of exhilaration as his team overcame one technical challenge after another, “and then plunged me into black pits of depression as I faced opposition from Nobel laureates and government officials, my colleagues, and even my wife,” he wrote in “A Life Decoded.”

Such factors persuaded him to settle for a public draw with the government’s human genome project in June 2000. Eighteen months later, in January 2002, White fired him. His wife, Fraser, who had successfully run TIGR in his absence, was reluctant to hand the post back to him. He had enough money to endow a new institute, now known as the J. Craig Venter Institute, with $100 million.

He and Fraser divorced in 2005, and Venter then married Heather Kowalski, who had been his press officer at Celera. He had a son, Christopher, from an earlier marriage to Barbara Rae. Complete information about survivors was not immediately available.

At his new institute he pursued projects such as energy-producing microbes, defining the minimum number of genes required for life, and synthesizing bacterial genomes.

In later years, Venter returned to his early interest in medicine and, as a serial entrepreneur, founded two companies involved in aspects of human health. Human Longevity aimed to increase life span by combining artificial intelligence with recent advances in aging research. Diploid Genomics was launched this year with the idea of using patients’ genomes to diagnose disease.

Notably, Venter’s pioneering sequencing methods are now obsolete. They have been replaced by altogether different methods of providing high-quality sequencing of human genomes.

This article originally appeared in The New York Times.