Craig Venter, A Force of Nature

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J. Craig Venter (1946 to present)

 

 

Editor’s note: This history of medicine piece is longer than usual, because like the article on (the great) Oliver Sacks, Craig Venter is another highly unusual person, who spent the first part of his life pursuing interests that no one could have predicted, would lead to global contributions of the first order. Individuals like these two, don’t come along often. For those readers who look forward to history of medicine each week, we guarantee a highly interesting, read:

 

Genomic entrepreneur, J. Craig Venter, plans to sell genetic workups for as little as $250; however, $25,000 gets you “a physical on steroids.“

 

Companies are looking for ways to get consumers interested in their genes.

 

Fifteen years ago, scientific instigator J. Craig Venter spent $100 million to race the government and sequence a human genome, which turned out to be his own. Now, with a South African health insurer, Venter says he will sequence the medically important genes of its clients for just $250. Human Longevity Inc. (HLI), the startup Venter launched in La Jolla, California, 18 months ago, now operates what’s touted as the world’s largest DNA – sequencing lab. It aims to tackle one million genomes inside of four years, in order to create a giant private database of DNA and medical records. In a step toward building the data trove, Venter’s company says it has formed an agreement with the South African insurer Discovery to partially decode the genomes of its customers, returning the information as part of detailed health reports. The deal is a salvo in the widening battle to try to bring DNA data to consumers through novel avenues and by subsidizing the cost of sequencing. It appears to be the first major deal with an insurer to offer wide access to genetic information on a commercial basis.

 

Jonathan Broomberg, chief executive of Discovery Health, which insures four million people in South Africa and the United Kingdom, says the genome service will be made available as part of a wellness program and that Discovery will pay half the $250, with individual clients covering the rest. Gene data would be returned to doctors or genetic counselors, not directly to individuals. The data collected, called an “exome,“ is about 2% of the genome, but includes nearly all genes, including major cancer risk factors like the BRCA genes, as well as susceptibility factors for conditions such as colon cancer and heart disease. Typically, the BRCA test on its own costs anywhere from $400 to $4,000. “I hope that we get a real breakthrough in the field of personalized wellness,“ Broomberg says. “My fear would be that people are afraid of this and don’t want the information – or that even at this price point, it’s still too expensive. But we’re optimistic.“ He says he expects as many as 100,000 people to join over several years.

 

Venter founded Human Longevity with Rob Hariri and Peter Diamandis (see “Microbes and Metabolites Fuel an Ambitious Aging Project“), primarily to amass the world’s largest database of human genetic and medical information. The hope is to use it to tease out the roles of genes in all diseases, allow accurate predictions about people’s health risks, and suggest ways to avoid those problems. “My view is that we know less than 1% of the useful information in the human genome,“ says Venter. The company this year began accumulating genomes by offering to sequence them for partners including Genentech and the Cleveland Clinic, which need the data for research. Venter said HLI keeps a “de – identified“ copy along with information about patients’ health. HLI will also retain copies of the South Africans’ DNA information and have access to their insurance records. “It will bring quite a lot of African genetic material into the global research base, which has been lacking,“ says Broomberg.

 

Deals with other insurers could follow. Venter says that only with huge numbers will the exact relationship between genes and traits become clear. For instance, height – largely determined by how tall a person’s parents are – is probably influenced by at least hundreds of genes, each with a small effect. Citing similar objectives, the U.S. government this year said it would assemble a study of one million people under Obama’s precision – medicine initiative (see “U.S. to Develop DNA Study of One Million People“), but it may not move as fast as Venter’s effort.

 

 

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A full – body MRI scanner at the “health nucleus“ of Human Longevity, where it offers $25,000 medical workups.

 

 

HLI has assembled a team of machine – learning experts in Silicon Valley, led by the creator of Google Translate, to build models that can predict health risks and traits from a person’s genes (see “Three Questions for J. Craig Venter“). In an initial project, Venter says, volunteers have had their facial features mapped in great detail and the company is trying to show it can predict from genes exactly what people look like. He says the project is unfinished but that just from the genetic code, HLI “can already describe the color of your eyes better than you can.“ Venter also said that this October the company will open a “health nucleus“ at its La Jolla headquarters, with expanded genetic and health services aimed at self – insured executives and athletes. The center, the first of several he hopes to open, will carry out a full analysis of patients’ genomes, sequence their gut bacteria or microbiome, analyze more than two thousand other body chemicals, and put them through a full – body MRI scan. “Like an executive physical on steroids,“ he says. The health nucleus service will be priced at $25,000. These individuals would also become part of the database, Venter said, and would receive constant updates as discoveries are made.

 

While the quality of Venter’s science is not in much doubt, this is the first time since he was a medic in Vietnam that he’s doled out medicine directly. “I think it’s a good concept,“ says Charis Eng, chair of the Cleveland Clinic’s Genomic Medicine Institute, which collaborates with Venter’s company. “But we who practice genomic medicine – we say HLI has absolutely no experience with patient care. I want to inject caution: it needs to be medically sound as well as scientifically sound.“ Venter has a history of selling big concepts to investors and then using their money to carry out exciting, but not necessarily profitable, science. In 1998 he formed Celera Genomics to privately sequence the human genome, but he was later booted as its president when its business direction changed. The economics of his current plan are also uncertain. Venter’s pitch is that with tens of thousands and ultimately a million genomes, he will uncover the true meaning of each person’s DNA code. But all those discoveries lie in the future. And at a cost of around $1,000 to $1,500 each, a million completely sequenced genomes add up to an expense of more than a billion dollars. HLI has so far raised $80 million, but Venter says he is now meeting with investors in order to raise far larger sums. Venter says he intends to offer several other common kinds of testing, including pre – conception screening for parents (to learn if they carry any heritable genetic risks), sequencing of tumors from cancer clinics, and screening of newborns. Those plans could bring HLI into competition with numerous other startups and labs that offer similar services. “It would be just one more off – the – shelf genetic testing company, if the entire motivation weren’t to build this large database,“ he says. “The future game is 100 percent in data interpretation. If we are having this conversation five to 10 years from now, it’s going to be very different. It will be, ?Look how little we knew in 2015.’“

 

John Craig Venter, born October 14, 1946, is an American biotechnologist, biochemist, geneticist, and entrepreneur. He is known for being one of the first to sequence the human genome and the first to transfect a cell with a synthetic genome. Venter founded Celera Genomics, The Institute for Genomic Research (TIGR) and the J. Craig Venter Institute (JCVI), and is now working at JCVI to create synthetic biological organisms. He was listed in Time magazine’s 2007 and 2008 list of the 100 most influential people in the world. In 2010, the British magazine New Statesman listed Craig Venter at 14th in the list of “The World’s 50 Most Influential Figures 2010“. He is a member of the USA Science and Engineering Festival’s Advisory Board.

 

Venter was born in Salt Lake City, Utah, the son of Elizabeth and John Venter. In his youth, he did not take his education seriously, preferring to spend his time on the water in boats or surfing. According to his biography, A Life Decoded, he was said to never have been a terribly engaged student, having Cs and Ds on his eighth – grade report cards. He graduated from Mills High School in Millbrae, California. Although he was against the Vietnam War, Venter was drafted and enlisted in the United States Navy where he worked in the intensive – care ward of a field hospital. While in Vietnam, he attempted suicide by swimming out to sea, but as he got closer to the deep blue sea and was approaching the circling of a shark, he changed his mind more than a mile out. Being confronted with wounded, maimed, and dying [marines] on a daily basis instilled in him a desire to study medicine – although he later switched to biomedical research. Venter began his college education at a community college, College of San Mateo in California, and later transferred to the University of California, San Diego, where he studied under biochemist Nathan O. Kaplan. He received a BS in biochemistry in 1972, and a PhD in physiology and pharmacology in 1975, both from UCSD. After working as an associate professor, and later as full professor, at the State University of New York at Buffalo, he joined the National Institutes of Health in 1984.

 

Venter himself recognized his own ADHD behavior in his adolescence, and later found ADHD – linked genes in his own DNA. While an employee of the NIH, Venter used a technique for rapidly identifying all of the mRNAs present in a cell and began to use it to identify human brain genes. The short cDNA sequence fragments discovered by this method are called expressed sequence tags (ESTs). The NIH Office of Technology Transfer and Venter decided to use these ESTs to attempt to patent the genes they identified, based on the ESTs alone. When Venter disclosed this strategy during a Congressional hearing, a firestorm of controversy erupted. The NIH later stopped the effort and abandoned the patent applications it had filed, following public outcry.

Venter was passionate about the power of genomics to radically transform healthcare. Venter believed that shotgun sequencing was the fastest and most effective way to get useful human genome data. The method was rejected by the Human Genome Project however, since some geneticists felt it would not be accurate enough for a genome as complicated as that of humans, that it would be logistically more difficult, and that it would cost significantly more. Frustrated with what Venter viewed as the slow pace of progress in the Human Genome project, and unable to get funds for his ideas, he sought funding from the private sector to fund Celera Genomics. The goal of the company was to sequence the entire human genome and release it into the public domain for non – commercial use in much less time and for much less cost than the public human genome project. The company planned to profit from their work by creating a value – added database of genomic data to which users could subscribe for a fee. The goal consequently put pressure on the public genome program and spurred several groups to redouble their efforts to produce the full sequence. DNA from five demographically different individuals was used by Celera to generate the sequence of the human genome; one of the individuals was Venter himself.

 

In 2000, Venter and Francis Collins of the National Institutes of Health and U.S. Public Genome Project jointly made the announcement of the mapping of the human genome, a full three years ahead of the expected end of the Public Genome Program. The announcement was made along with U.S. President Bill Clinton, and UK Prime Minister Tony Blair. Venter and Collins thus shared an award for “Biography of the Year“ from A&E Network. On the 15 February 2001, the Human Genome Project consortium published the first Human Genome in the journal Nature, and was followed, one day later, by a Celera publication in Science. Despite some claims that shotgun sequencing was in some ways less accurate than the clone – by – clone method chosen by the Human Genome Project, the technique became widely accepted by the scientific community. Although Celera was originally set to sequence a composite of DNA samples, partway through the sequencing, Venter switched the samples for his own DNA.

 

After contributing to the Human Genome, and its release into the public domain, Venter was fired by Celera in early 2002. According to his biography, Venter was ready to leave Celera, and was fired due to conflict with the main investor, Tony White, that had existed since day one of the project. Venter writes that his main goal was always to accelerate science and thereby discovery, and he only sought help from the corporate world when he could not find funding in the public sector. Venter’s Global Ocean Sampling Expedition (GOS) is an ocean exploration genome project with the goal of assessing the genetic diversity in marine microbial communities and to understand their role in nature’s fundamental processes. Begun as a Sargasso Sea pilot sampling project in August 2003, Venter announced the full Expedition on 4 March 2004. The project, which used Venter’s personal yacht, Sorcerer II, started in Halifax, Canada, circumnavigated the globe and returned to the U.S. in January 2006.

 

Venter is currently the president of the J. Craig Venter Institute, which conducts research in synthetic biology. In June 2005, he co-founded Synthetic Genomics, a firm dedicated to using modified microorganisms to produce clean fuels and biochemicals. In July 2009, ExxonMobil announced a $600 million collaboration with Synthetic Genomics to research and develop next – generation biofuels. Venter is seeking to patent the first partially synthetic species possibly to be named Mycoplasma laboratorium. There is speculation that this line of research could lead to producing bacteria that have been engineered to perform specific reactions, for example, produce fuels, make medicines, combat global warming, and so on. In May 2010, a team of scientists led by Venter became the first to successfully create what was described as “synthetic life“. This was done by synthesizing a very long DNA molecule containing an entire bacterium genome, and introducing this into another cell, analogous to the accomplishment of Eckard Wimmer’s group, who synthesized and ligated an RNA virus genome and “booted“ it in cell lysate The single – celled organism contains four “watermarks“ written into its DNA to identify it as synthetic and to help trace its descendants. The watermarks include:

 

1. Code table for entire alphabet with punctuations

2. Names of 46 contributing scientists

3. Three quotations

4. The secret email address for the cell.

 

On September 4, 2007, a team led by Sam Levy, published the first complete (six – billion – letter) genome of an individual human – Venter’s own DNA sequence. Some of the sequences in Venter’s genome are associated with wet earwax, increased risk of antisocial behavior, Alzheimer’s and cardiovascular diseases. This publication was especially interesting since it contained a diploid instead of a haploid genome and shows promise for personalized medicine via genotyping. This genome, dubbed HuRef by Levy and others, was a landmark accomplishment. The Human Reference Genome Browser is a web application for the navigation and analysis of Venter’s recently published genome. The HuRef database consists of approximately 32 million DNA reads sequenced using microfluidic Sanger sequencing, assembled into 4,528 scaffolds and 4.1 million DNA variations identified by genome analysis. These variants include single – nucleotide polymorphisms (SNPs), block substitutions, short and large indels, and structural variations like insertions, deletions, inversions and copy number changes. The browser enables scientists to navigate the HuRef genome assembly and sequence variations, and to compare it with the NCBI human build 36 assembly in the context of the NCBI and Ensembl annotations. The browser provides a comparative view between NCBI and HuRef consensus sequences, the sequence multi – alignment of the HuRef assembly, Ensembl and dbSNP annotations, HuRef variants, and the underlying variant evidence and functional analysis. The interface also represents the haplotype blocks from which diploid genome sequence can be inferred and the relation of variants to gene annotations. The display of variants and gene annotations are linked to external public resources including dbSNP, Ensembl, Online Mendelian Inheritance in Man (OMIM) and Gene Ontology (GO). Users can search the HuRef genome using HUGO gene names, Ensembl and dbSNP identifiers, HuRef contig or scaffold locations, or NCBI chromosome locations. Users can then easily and quickly browse any genomic region via the simple and intuitive pan and zoom controls; furthermore, data relevant to specific loci can be exported for further analysis.

 

On March 4, 2014 Venter and co – founders Peter Diamandis and Robert Hariri announced the formation of Human Longevity, Inc., a company focused on extending the healthy, “high performance“, human lifespan. At the time of the announcement the company had already raised $70 million in venture financing, which was expected to last 18 months. Venter is the chairman and chief executive officer (CEO). The company said that it plans to sequence 40,000 genomes per year, with an initial focus on cancer genomes and the genomes of cancer patients. Human Longevity’s mission is to extend healthy human lifespan by the use of high – resolution big data diagnostics from genomics, metabolomics, microbiomics, and proteomics, and the use of stem cell therapy.

Venter is the author of two books, the first of which was ostensively an autobiography titled A Life Decoded. Venter’s second book was titled Life at the Speed of Light in which he announced his theory that this is the generation in which there appears to be a dovetailing of the two previously diverse fields of science represented by computer programming and the genetic programming of life by DNA sequencing. He was applauded for his position on this by futurist Ray Kurzweil.

 

Venter has been the subject of several biography books, several scientific documentary books, TV documentaries, numerous magazine articles, and many speeches. Venter has been the subject of articles in several magazines, including Wired, The Economist, Australian science magazine Cosmos, and The Atlantic. Additionally, he was featured on The Colbert Report on both February 27, 2007, and October 30, 2007. Venter appeared in the “Evolution“ episode of the documentary television series Understanding. On May 16, 2004, In a 2007 interview with New Scientist when asked “Assuming you can make synthetic bacteria, what will you do with them?“, Venter replied: “Over the next 20 years, synthetic genomics is going to become the standard for making anything. The chemical industry will depend on it. Hopefully, a large part of the energy industry will depend on it. We really need to find an alternative to taking carbon out of the ground, burning it, and putting it into the atmosphere. That is the single biggest contribution I could make.“ He was on the 2007 Time 100 most influential people in the world list made by Time magazine. In 2007 he also received the Golden Eurydice Award for contributions to biophilosophy. On December 4, 2007, Venter gave the Dimbleby lecture for the BBC in London. In February 2008, he gave a speech about his current work at the TED conference. Venter was featured in Time magazine’s “The Top 10 Everything of 2008“ article. Number three in 2008’s Top 10 Scientific Discoveries was a piece outlining his work stitching together the 582,000 base pairs necessary to invent the genetic information for a whole new bacterium. For an episode aired on July 27, 2009, Venter was interviewed on his boat by BBC One for the first episode of TV show Bang Goes the Theory.

 

On May 20, 2010, Venter announced the creation of first self – replicating semi – synthetic bacterial cell. On November 21, 2010 Steve Kroft profiled Venter and his research on 60 Minutes. In the June 2011 issue of Men’s Journal, Venter was featured as the “Survival Skills“ celebrity of the month. He shared various anecdotes, and advice, including stories of his time in Vietnam, as well as mentioning a bout with melanoma upon his back, which subsequently resulted in “giving a pound of flesh“ to surgery. Venter is mentioned, in the season finale of the first season of the science fiction series Orphan Black, a joint production of Space and BBC America. In the episode, Venter is referenced as patenting an organism and encoding a message in the genome of that organism, an act repeated by the character of Aldous Leekie (played by Matt Frewer). While the clones fear that this renders them as nothing more than property, in reality, in the United States and Canada, where the show primarily takes place, such a patent became unenforceable due to constitutional provisions and laws against owning human beings. Sources: MIT Technology Review; Wikipedia; Wired Magazine

 

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