An Interview with Manuel F. Varela and Ann F. Varela—Craig Venter and the Human Genome Project

Jan 4, 2021 by

Craig Venter

The Human Genome Project is going to succeed because I’ve got this guy who can get automated sequencers to work.”

—James D. Watson

The environment has fallen to the wayside in politics.”

—Craig Venter

One of the fundamental discoveries I made about myself – early enough to make use of it – was that I am driven to seize life and to understand it. The motor that pushes me is propelled by more than scientific curiosity.”

—Craig Venter

Michael F. Shaughnessy

1) It almost seems fitting to end this book with a chapter on Craig Venter and the Human Genome Project—but let us start at the beginning—when was he born, and where was he born?

John Craig Venter is best known for determining the DNA sequence of the human genome. He was born on October 14, 1946, in Salt Lake City, Utah. Shortly after Venter was born, his parents, John Eugene Venter and Elizabeth Jeanne Wisdom moved the family from Millbrae, California, to the San Francisco area.

2) Apparently, he was not a keen student, preferring to spend time on the water—boating and the like—What do we know?

He spent his days swimming and surfing. In his teens, he built a homemade hydroplane and launched it in the water. He was not genuinely studious at this time in his life. After high school, he worked small jobs and enrolled in the Orange Coast Junior College in Costa Mesa, California. Before long, he was drafted to join the U.S. military effort in the Vietnam War.

After serving in the Vietnam conflict, Venter started his higher learning education at a community college, College of San Mateo in California, and afterward transferred to the University of California, San Diego, with noted biochemist Nathan O. Kaplan as his advisor. He earned a B.S. in biochemistry in 1972 and a Ph.D. in physiology and pharmacology in 1975 at this institution.

As an undergraduate student, Venter had become interested in a scientific disagreement between Kaplan and other investigators. Kaplan thought that in the brain, the membrane receptor for adrenaline faced the outside of the cells. Thus, Kaplan believed that the receptor was thought to operate extracellularly. In contrast, Kaplan’s detractors felt that the receptor for adrenaline functioned intracellularly within the cell. Adrenaline is a catecholamine neurotransmitter, also known as epinephrine.

Venter had reasoned that if a catecholamine molecule were somehow attached to a glass bead, the complexes would be too large to enter a cell. The complexes were called “catecholamine-on-glass.” If the neurotransmitter worked, stuck with its glass bead outside the cell, then it would indicate that the receptor faced the outside. On the other hand, if the catecholamine-glass bead complex failed to work because the neurotransmitter remained outside, then the receptor must be working inside the cell.

Venter and colleagues Jack Dixon, Peter Maroko worked in Kaplan’s laboratory to grow heart cells beating in culture and chicken embryo cells and tumor cells. They also used intact hearts exposed to the open while still beating in anesthetized dogs. In each of these experimental systems, the catecholamine-glass bead complexes stimulated neurotransmitter activities, indicating that the neurotransmitter receptor molecules faced the outside and functioned extracellularly. The findings were significant, and they were published in PNAS in May of 1972. The undergraduate research project inspired Venter to enter graduate school.

As a graduate student, the immobilization of various biologically active molecules to the glass beads would form much of the basis for Venter’s Ph.D. thesis. Venter was also inspired to consider the catecholamines-on-glass beads as potential purification systems. He used the glass bead technique, with various molecules attached to them, to attempt purifications of essential biochemicals, such as the so-called β-adrenergic receptor-associated adenylate cyclase enzyme. In the end, Venter would publish at least eight papers with Kaplan as co-author. Thus, despite spending lots of time at the beach and surfing, Venter managed to work his way through community college, get a Ph.D. and become a university professor studying neuropharmacology.

3) Vietnam—impacted Venter as it did so many of us—how did he serve his country, and what did he attempt during those difficult times?

Venter opposed the Vietnam War, but the draft caused him to join the United States Naval Medical Corps after consulting with his father, a former Marine Officer. Venter’s IQ test had excellent scores. Hence, Venter was given a choice of jobs. He trained at Balboa Navy Hospital. While there, Venter learned how to conduct liver biopsies and spinal tap medical procedures. He even began teaching others how to perform these medical duties.

After training, he received official orders to report to a naval clinic’s emergency room near Long Beach. Instead, according to biographer James Shreeve, Venter was court-martialed for refusing to obey an order to get a haircut, and he had to report to the brig. After receiving a sentence for six months of hard labor, he was sure to be sent straight into combat as a Vietnam medic. According to Shreeve, Venter sealed his fate by unsealing the envelope containing his official papers with the brig orders and “lost” them! He then used his original orders, still in the envelope, to report to the emergency room as initially intended. At the ER, he somehow managed to talk his way into the ruse and complete his six-month duty at the naval clinic, rather than the brig.

Venter worked as a corpsman in the Da Nang Navy field hospital’s intensive-care division until the end of 1968. He preferred to work at night to avoid rats and because he could spend the daytimes on the beach. He recalled that shrapnel had damaged his unoccupied barracks bed one day while away on duty in the surgical ward. Venter took to sleeping on the operating tables in the surgical wards at night after his shifts, as the wards were better protected. While in Vietnam, he attempted to end his life by drowning but changed his mind and swam back to shore.

In Da Nang, Venter participated in double limb amputations and spent time in a clinic devoted to treating infectious disease. He performed autopsies on young men ranging from ages 18 to 22. Heart disease was a common diagnosis. During the Tet offensive, his medical facilities experienced intense bombings. He was confronted with severely wounded and dying marines daily, which instilled in him a desire to study medicine, although he later shifted to biomedical research.

Venter became an assistant professor of therapeutics and pharmacology in 1976 at the State University of New York (SUNY) at Buffalo and worked at the nearby Roswell Park Memorial Institute (now the Roswell Park Cancer Institute). His research focused principally on mammalian receptor proteins using techniques based on immunology and tissue culture, which was a unique methodology at the time. Venter was advanced to the position of professor in the early 1980s. He received the Boehringer Ingelheim Muscarinic Receptor Research Award for his work on receptors.

4) Venter saw genomics as one sure way to assist in health care—what did he realize that others did not?

Venter had realized that he could sequence the human genome faster than the publicly funded endeavor by going after the protein-encoding genes. He would go after the human genome by inventing new technologies. Venter developed an innovative system called Expressed Sequence Tags (ESTs) technology and used a shot-gun method of DNA sequencing, for instance. He would sequence the human genomic DNA by breaking-up the genome molecules into pieces, sequencing the pieces, assembling the pieces with computers, and making finicky automatic sequencers work better than anyone else.

Venter had hoped to complete the entire human genome sequencing much earlier than was anticipated and make the new data available to the world years ahead of schedule. He had hoped that by making the genetic code available sooner, the pace of biomedical research would be tremendously facilitated. Thus, prominent areas of scientific research, like cancer and genetic diseases, might be enhanced. The new work might lead to the development of new therapeutics for a host of human ailments.

In 1983 Venter accepted a new offer and moved to Maryland to start a new assignment at the National Institute of Neurological Disorders (NIND) at the National Institutes of Health (NIH). Venter became interested in cloning the gene for the adrenaline receptor, hoping it would help find new clues on how the receptor functioned. After ten years, the cloning venture proved a failure, and another research group would clone the gene, beating Venter in the molecular biological effort. Venter decided he could sequence the adrenaline receptor gene’s DNA since the gene had been cloned. Not willing to play second banana in getting the DNA of the gene sequenced, as well, Venter arranged for getting one of the field’s newest automated DNA sequencers. The equipment was a high throughput machine called a sequenator, from ABI, a company called Applied Biosystems Incorporated, a biotechnology outfit housed in California as part of the larger Perkin Elmer Corporation headquartered in Connecticut.

At the time, the automatic sequenators were quite challenging to operate. See Figure 94. Still, Venter’s laboratory surprisingly managed to make the machines work well, thanks to the help and a great deal of effort by installers of the ABI machine and a graduate student named Jeannine Gocayne. At the time, unbeknownst to Venter, James Watson, who was at the Human Genome Research Center at NIH and newly in charge of its Human Genome Project, was having a terrible time with the ABI machines. The group was failing to get the new devices to work. Investigators worldwide were having trouble, too, with their “$100,000 paperweights,” as the ABI sequencers were frustratingly called. Venter’s group had obtained useful DNA sequence data for the human gene encoding the β-adrenergic receptor and published a preliminary report in 1987.

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Figure 94. An automated sequenator machine.

Feeling emboldened with his success in using the finicky ABI sequenators to generate useful DNA sequencing data, Venter felt he could try to sequence the human X chromosome. He approached Watson and requested funding to do the work. In turn, Watson asked the “higher-ups” that Venter be provided the requisite funds, about $5 million. Watson soon encountered NIH’s legendary bureaucratic machine. Watson was duly informed that such requests had to go through its proper bureaucratic channels. Venter would have to submit a regular grant proposal, along with everyone else wishing to have funding for research. Venter submitted the funding proposal, but it was rejected, as the review committee required additional information. Venter submitted a revised application, and it, too, was rejected.

The NIH rejections of the grant applications delayed progress on the human genome project. Venter had proposed an innovative idea of getting the DNA sequences of the human genes directly. It might help the genome sequencers sort out the introns and the so-called “junk” DNA. The term junk is a misnomer, but at the time, its importance was unclear. Some considered that such non-coding sequences were meaningless, remnants of billions of years of replication. Others felt that the junk DNA had yet to harbor some undiscovered vital purpose. We now understand that junk DNA has its relevance in gene regulation and in, for instance, forensic science with the identification of human individuals.

Watson’s genome project involved mapping and sequencing the entire human genome, junk, and non-junk alike, in order. On the other hand, Venter’s innovative idea outlined in his rejected NIH proposals would address circumventing junk DNA and going straight for the genome’s coding sequences. The new venture would have its basis in the messenger RNA molecules, but the innovation would soon become controversial. Venter’s genome sequencing approach would also involve a shot-gun.

5) How is mRNA expressed in the human brain—how do we study this? How did Venter go from researching the human brain to sequencing the human genome?

In 1984, Venter became a section leader at the National Institute of Neurological Disorders and Stroke at NIH in Bethesda, MD, where he worked until 1992. His work at the NIH concentrated on neurotransmitters, specifically on genes that encode enzymes engaged in the synthesis of neurotransmitters and receptors.

Venter used his pioneering ESTs to sequence parts of many microbial organisms’ genomes, with the ultimate goal to map the human genome. Venter’s colleagues claimed that the EST technique, which appeared to be working for some bacteria’s less complicated genomes, would not be vigorous and accurate enough to map the more complex human genome. The approach to the genome that Venter invoked took advantage of the ESTs to target the expressed versions of the protein-encoding genes. He imagined obtaining the so-called cDNA, known as the complementary DNA. The cDNA molecules represented the genes without introns, keeping only the exons, known as the expressed forms of a gene.

The general method Venter would use to get the expressed genes involved first isolating the RNA. If genes are expressed, then RNA is produced. The RNA molecules that are made by transcription are sorted into versions that take out the introns. However, if the RNA is extracted from human cells first, cDNA can be made from the RNA as templates. The process is the reverse of transcription, and the enzyme called reverse transcriptase is used to produce the cDNA, the protein-encoding regions of the genes. However, since the approach meant that only the gene fragments were involved, the shortened gene versions were called “tags.” Early on in the process, Venter and his groups called these short cDNA segments “sequence tag sites” (STSs). When preparing the manuscript for Science, they adopted the now well-known term Expressed Sequence Tags (ESTs).

Venter’s team began collecting ESTs in large and ever-increasing numbers beyond the genes encoding brain neurotransmitters. In the meantime, trouble was soon encountered when Venter attempted to obtain a patent on the human DNA sequences contained with the ESTs. The quarrel over whether human DNA sequences should be patented led to a shakeup at NIH. In the next few months, both Watson and Venter would leave the NIH for good. Watson would move on to Cold Spring Harbor and become its president. Venter entered the private sector. He would become a businessperson and establish The Institute for Genomic Research (TIGR). NIH abandoned the human gene sequence patenting venture after a much public outcry.

At TIGR, Venter collaborated with Hamilton O. Smith, a Nobel Laureate (see Chapter 21) who decided to sequence an organism’s entire genome, this one being a bacterium called Haemophilus influenzae. The bacterium was colloquially called “H Flu” for short, but it does not cause the flu. The microbe called influenza virus causes the flu, not Haemophilus influenzae. There was an era that for more than a few generations, the world mistakenly thought that Haemophilus influenzae caused the flu. Hence, the specific epithet name “influenzae” was inaccurately assigned to the bacterial microbe—it does not cause the flu. The bacterium’s name nevertheless remains as a historical artifact. At some time in its scientific history, Haemophilus influenzae had been an inadvertent contaminant in the laboratory preparation of the microbe from flu specimens, along with the virus itself.

They invoked the newly discovered ETSs and a so-called shot-gun approach to the bacterial genome sequence for the Haemophilus influenzae. The shot-gun method involved breaking up the genomic DNA into smaller fragments and sequencing them using the ABI sequencers. They then assembled the sequenced fragments into the whole bacterial genome. The assembly was done by aligning the fragments’ sequences and finding the overlapping matching sequences. These matching fragments served to connect them into adjacent pairs that had the overlaps. These connected fragment pairs were called contiguous, and later “contigs” for short.

They sequenced about 9,500 shot-gunned clones, reading about 460 bases per cloned-fragment, and covered each base at least five times. They had assembled about 140 of these contigs to attain 99.3% coverage of the entire genome. The entire bacterial genome had nearly been sequenced. The genome of Haemophilus influenzae strain Rd had 1,830,137 base-pairs. They used computers to transcribe and translate the genes with their start and stop codons. About 1,749 protein-encoding genes had been discovered on the genome. They had even annotated the genome. That is, they checked each open reading frame they found with those existing in the DNA databases and assigned putative roles for their newly sequenced genes. It was considered a watershed moment when it was published in Science in July of 1995. The work was featured on the journal’s cover. The paradigm would serve Venter’s group well as they pushed for the human genome.

Venter would sequence additional bacterial genomes, publishing each of them as soon as he finished them. These bacteria proved to be quite interesting from a molecular biological standpoint. They sequenced Mycoplasma genitalium, which was thought to be one of the smallest known microorganisms at the time, with a correspondingly tiny genome. At some point, Venter and his laboratory personnel began deleting genes from it, hoping to find the minimal number of genes that a living being required for life. They had wished to know how many genes were minimally required to live. They even tried to assemble from scratch an artificially synthesized genome, using DNA-synthesizing machines to make fragments and assembling them to create the entire bacterial genome, base by base, but were thwarted by bioethicists. The work would, however, be realized in later years.

They sequenced the genome of another microbe, Methanococcus jannaschii, and it was just as impressive. It was a member of the Archaea domain of organisms. Its genome sequence was fascinating! Half of the Archaeal genome consisted of genes never seen before in the history of science. Still, a significant part of the remaining Methanococcus jannaschii genome was more closely related to eukaryotes, including humans, than to the common bacteria! In a real genetic sense, it seemed more human than bacterial! Carl Woese, who had postulated the three-domain system of classification for all living beings, would be vindicated with the sequencing of an Archaeal organism and genomic comparison with all other organisms. Woese had been correct about the three-domain system after all.

The list of bacterial genome projects expanded, and Venter published each of them. Soon many other laboratories around the world began microbial genome projects. With a postulated trillion species of microbes thought to reside on Earth, there will always be a need for genome projects.

Meanwhile, Venter would turn his attention to the coveted human genome with the successes obtained by publishing several bacterial genomes’ complete sequences. In 1998, he announced that the human genome was next on his list of sequencing agendas. Venter and his group were going to sequence the entire human genome using the now established ESTs. It would still be a monumental scientific undertaking, with thousands of laboratory workers, massive computers with unheard-of computing power, billions of base sequences, and many thousands of new human genes to annotate. See Figure 95.

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Figure 95. Idiogram of the human chromosomes in the genome.

The effort took about nine months of intense effort. Over 3.1 billion base pairs were sequenced, and each read was entered correctly into GenBank, the world’s leading repository of DNA sequence data. The first draft was completed in 2001, and the entire project was considered complete in 2007 with the sequence of a diploid genome from an individual person. The two competing groups, Venter’s outfit at Celera and NIH’s public project, published separately at the same time in different journals. Both sides of the groups’ race to the human genome could claim a victory of sorts if not an outright tie.

6) Venter was included as one of the top 100 people in the world, indeed a well-deserved honor. Can you give us the top five accomplishments?

Time magazine included Venter in the list of the world’s 100 most influential men and women twice, once in 2007 (65th) and again in 2008 (40th) under the category of scientists and thinkers. Though Venter has never garnered the coveted Nobel Prize, he has been highly regarded as an influential molecular biologist.

Of the many significant accomplishments of Dr. J. Craig Venter, it is considered by most investigators that the greatest of these is the determination of the complete DNA sequencing of 3.1 billion base pairs of the human genome. While estimates vary, depending on whether one considers open reading frames and regulatory elements, plus micro-RNA genes, mitochondrial DNA, and others, there are roughly 50,000 human genes. The feat was monumental, considered analogous to requiring the effort in scope similar to that of the atomic bomb Manhattan Project.

A second major accomplishment was Venter’s invention of the ESTs, which permitted one to find individual genes from any living organism. The process would allow a greatly facilitated means for collected many genes of known and unknown function. The ESTs would allow a faster approach to sequencing the human genome than the conventional “genome-walking” method using DNA primers, as were employed for the publicly sponsored human genome project.

Another significant accomplishment by Venter was the sequencing of non-human genomes, such as the Drosophila melanogaster genome and various bacterial genomes. Though the fruit fly genome was smaller than that of the human genome, it was quite a complex undertaking. Its propensity to undergo genetic exchange and its assembly of contigs proved far more complicated than was anticipated. It took relatively longer to complete than was hoped for, especially for such a smaller genome, known to exist in the fruit fly.

Along these lines, Venter actively partook in determining the complete sequence of a host of bacterial genomes. These prokaryotes were considered imperative for countless reasons. Many of these individual bacteria were serious pathogens, causing significant morbidity and mortality in humans. Other bacteria were useful in biotechnology or in learning about fundamental molecular evolutionary relationships between living taxa. Furthermore, many bacteria were useful for industrial purposes, such as biofuels and other essential biochemical reagents.

A fourth noteworthy accomplishment was Venter’s role in microbiome projects, such as those involved in the world’s oceans’ biological sampling expeditions. The idea was to collect seawater samples, prepare DNA from the oceans’ waters, sequence the organismal genomes, assemble the contigs, annotate the gene data, and identify each of the various species present in the world’s seas. The studies of various microbiomes, such as in the gut, is a direct extension of the genomics field that Venter helped to establish.

One of Venter’s most meaningful accomplishments involved exploiting genomes for synthetic purposes, such as cleaner biofuels. In 2005, Venter established an outfit dedicated to genetically modifying microbial organisms to produce environmentally safer biofuels, like alcohol, or highly desirable biochemical agents for basic research, or perhaps even to produce new medicines. One of these synthetic genomics enterprises is aimed at combating global warming.

7) U.S. President Bill Clinton and British Prime Minister Tony Blair were present when the Human Genome Project was launched—In the big scheme of things—how important was this, and what is its current status?

As mentioned above, Venter had left the NIH in July 1992 and became founder and chairperson of The Institute for Genomic Research (TIGR) board, a not-for-profit genomics research institute in Rockville, MD. He solicited private resources to map the human genome himself, with his methods. Venter was criticized for using the NIH’s preliminary work on genome mapping for personal gain. He served as its president until 1998.

Then, in 1998, Venter joined Applera Corporation and became president and chief scientific officer of the newly established Celera Genomics. Celera Genomics’ goal was to become the ultimate source of genomic and related medical and biological information. Now Venter planned to sequence the human genome using procedures that he and his team established. His approach to sequencing the human genome diverged from that of the NIH. Venter’s methods were faster and focused merely on genes; whereas, the NIH’s group described all of the nucleotides in human DNA. There was a race to the genome between the private and public sectors. Due to these two approaches running simultaneously, the U.S. Congress called Francis Collins, the National Human Genome Research Institute’s director of the NIH, and Venter appeared before Congress in June 1998.

After the hearings, the race to map the human genome accelerated. Venter and Collins appeared together with U.S. President Bill Clinton and U.K. Prime Minister Tony Blair to announce the initial summary of the human genome in 2001. NIH and Celera both published a summary of the human genome before their intended completion date on February 16, 2001, in Nature and Science journals, respectively. Soon after that, Venter and Collins deliberated over their discoveries while attending the American Association for the Advancement of Science’s (AAAS) annual meeting held in San Francisco, California.

In January 2002, Venter stepped down as president of Celera Genomics but continued to chair its scientific advisory board. Today, he is serving as president of the J. Craig Venter Institute. See Figure 96. Venter created the J. Craig Venter Research Institute in 2006, which combined TIGR and The Center for the Advancement of Genomics, The Joint Technology Center, The J. Craig Venter Science Foundation, and the Institute for Biological Energy Alternatives.

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Figure 96. J. Craig Venter Institute, La Jolla, California.

Starting from Halifax, Canada, he began circumnavigating the world in his yacht, the Sorcerer II, on March 4, 2004, on a voyage intending to update the fantastic scientific treks of the 18th and 19th centuries, akin to Charles Darwin’s journey aboard the HMS Beagle. Instead of collecting his finds in various containers, Venter secures their DNA on filter paper and transports them to be sequenced and analyzed at his headquarters in Rockville, Maryland. Venter is hoping to find numerous new genes, a massive collection of information regarding Earth’s biodiversity. He wishes to accrue a comprehensive Whole Earth Gene Catalog, including every gene’s function.

Investigators in modern times can sample an environment and sequence the entire genomes of all organisms present in that sample. See Figure 97 for one of these sorts of examples, the secretome, a listing of proteins secreted by a plethora of bacterial pathogens.

File:Phylogenetic distribution of zoonosis, genome size and secretome size for 191 pathogenic bacteria.jpg,_genome_size_and_secretome_size_for_191_pathogenic_bacteria.jpg

Figure 97. Comparative genome analysis of a so-called protein secretome.

In the future, molecular biologists anticipate the day when a person can use an “App” on their hand-held phones to perform a full-fledged sequencing of their genome. See Figure 98. Such personal genome projects may be used to identify a person, learn genetic history, diagnose a disease, or sample a crime scene. The positive possibilities inherent in the living genome seem limited only by our imaginations.

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Figure 98. Craig Venter, third from the right, inspecting a cell phone imager to obtain an entire human genome sequence for a person.

As of this book’s writing, the human genome’s genetic knowledge has been around for 20 years. However, February of 2011 was the tenth anniversary of the first publication of the draft human genome in Science and Nature. An entire issue of Science was devoted to the topic as a commemoration by many of the human genome project’s main participants.

Of the many essayists, Venter would contribute his evaluation of the status at that time. Venter spoke of the successes and its remaining challenges. He noted the rapid pace of sequencing rate improvements that had been realized in those ten years. He wrote, however, that further improvements were needed. Venter pointed out that the read lengths had to be longer so that genome sequence investigators could better assemble the shot-gunned fragments. Venter also spoke of the need to maintain quality assurance in sequence data. He asked for the establishment of a set of scientific standards for genome sequencing of individual human genomes. Lastly, Venter pointed out the need to develop new technologies to interpret the massive DNA sequence data that arises out of routine genome sequencing endeavors. Venter elaborated that such improvements in genomic data interpretation would be necessary to determine specific phenotypes. Such efforts would improve genetic disease diagnosis and enhance efficient therapies for diseases to minimize deleterious side effects.

In the 20 years since the first scientific publication of the human genome sequence, much has transpired in molecular biology. We have seen the establishment of genomics now as a mature field of study. We have seen vast improvements in sequencing efficiencies. The human (and other) genome projects generated a massive amount of sequence data, all of which had to be assembled, annotated, transcribed, translated, compared, and molecular structures predicted. Thus, the genome DNA data required that new computing hardware and software be continuously developed and improved. These computing necessities resulted in the establishment of the bioinformatics field. In modern times, we anticipate that bioinformatics, which uses computers to analyze biological systems, will always be necessary for most scientific investigations to progress further.

Various environments can be sampled for each of the organisms that occupy a given niche by merely assessing the nature of the genomes present in such settings. We mentioned above how Venter has studied the world’s oceans for analysis of their microbiome composition. More recently, microbiologists and physiologists have seen the emergence of the human gut microbiome as a significant investigation area. The gut microbiome has been thought to be connected to health statuses, disease, mood, and human physiological and biochemical conditions.

In modern times, laypeople can have their genomes mapped for a nominal fee. If individuals decide to splurge, they can even have their entire genomes sequenced. Many human beings have elected to study their phylogenetic histories to accompany their genealogical searches. Individuals can also evaluate their specific genomes for medical purposes. They can evaluate their immune system status against diseases. People can identify specific genes as causes of a rare ailment or cancer. Thus, such people can gauge their potential for treatments or management of their disease.

The final sequencing of the intact human genome has led investigators to develop new genome editing technologies based on bacterial resistance mechanisms against foreign phage genomes. With the specific nucleotide sequence data available in the human genome, molecular biologists can change any of these sequences they so desire. In 2020, we saw the Nobel Prize go to CRISPR inventors, the genome-editing method. Professors Emmanuelle Charpentier and Jennifer A. Doudna shared half of the Nobel in Chemistry for their genome scissors invention to rewrite the DNA code of life.

8) Human Longevity—what is he doing to lengthen our life span? What were Venter’s accomplishments in this area?

In 2014, Venter, serving as chair, launched Human Longevity, Inc., a company focused on extending the human lifespan with co-founders Peter Diamandis and Robert Hariri. Human Longevity’s mission is to extend the healthy human lifespan by using high-resolution big data diagnostics from genomics, metabolomics, microbiomics, proteomics, and stem cell use therapy. The program is aimed at determining the genome sequences of individual human beings. Another focus is aimed at sequencing the genomes of specific tumors involved in cancer. It is hoped that once cancer investigators understand the genetics of various cancer cells, their cell biology and biochemistry can be gleaned to modulate their growth. Venter retired from this venture in May 2018.

9) Is he still alive? What is he currently involved in?

Venter is, as of this writing in late 2020, still living. See Figure 99. Following a short-lived marriage to Barbara Rae-Venter, with whom he had a son, he married Claire M. Fraser, his graduate student, remaining married to her until 2005. In the latter part of 2008, he married Heather Kowalski. They presently call San Diego, CA home.


Figure 99. Craig Venter.

Venter is the author of four books: A Life Decoded: My Genome, My Life (2007), Life at the Speed of Light: From the Double Helix to the Dawn of Digital Life (2013), The New Darwin: A Revolution in Our Understanding of the Natural World (in press), and The New Darwin (in press).

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Figure 100. Craig Venter just received the highest honor from Barack Obama in the White House.

Venter is a recipient of the Gairdner Award (2002), the Nierenberg Prize (2007), the Kistler Prize (2008), the ENI award (2008), the Medal of Science (2008) (Figure 100), the Dickson Prize (2011), and the Leeuwenhoek Medal (2015).

10) What have I neglected to ask?

Venter’s inspiration for molecular biologists is widespread. He had a direct influence on many of our research investigations. Our laboratory has used genomic sequence data from GenBank to find new genes, clone them, and characterize their microbial physiological activities. In this way, we have discovered several bacterial multidrug efflux pumps from bacterial pathogens. We even studied a mannitol utilization operon, starting with genome data.

Suitably inspired by Venter, in 2013, our laboratory sequenced a complete genome for a bacterium called Vibrio cholerae, a non-pathogenic strain found in the environment of Puget Sound. In 2014, we conducted a genome comparison analysis between our Vibrio cholerae strain with the genome of a severe pathogenic strain for cholera. We found genes common to both strains, but, interestingly, we found other genes specific only to the dangerous strain but not to the harmless variety. We published that work in a scientific journal in 2014. These newly identified genes belonging to a pathogenic version of a disease-causing microbe make excellent targets for developing antimicrobials against cholera. With the new data, we employed a bioactive agent called allyl sulfide from garlic, a food spice from Allium sativum, to inhibit the growth of the multidrug-resistant form of the Vibrio cholerae pathogen.

For additional information about this remarkable molecular biologist and the human genome, visit:

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