How A Biotech God Gave Birth To Synthetic Life
We feel most attached to this thing called life when it’s about to be taken away, robbed, cheated, or destroyed. Then we try to cling to it, at whatever cost, in whatever manner, even if it means reconstructing the damn thing from scratch.
That’s how Synthia was born.
At age 20, three decades before he became the most influential biotechnologist on earth, John Craig Venter, now 70, swam into the warm waters of the South China Sea to drown himself.
Venter was determined to get away from the “bullshit, the madness, and the horror” of Da Nang Navy Hospital in Vietnam, the epicenter of the Tet Offensive that led to more than 75,000 casualties in 1968.
As a Navy Hospital Corpsman, Venter regularly saw a hundred lives perish under his hands in a single shift. Some of the boys who landed on his gurney had no limbs; others had their guts lying in a vase. A just-in-time napkin applied on a bullet wound could mean the difference between a tin casket or R&R. For the young corpsman, life bled in an arbitrary and meaningless manner.
Sharks persuaded Venter to turn back and save his life for something meaningful.
Fast forward half a century to March 25, 2016, the birth of Syn 3.0, an artificial, autonomously reproducing biological organism with only 473 genes. In the midst of the genome is a digital watermark that spells out the name of its creator in amino-acid code.
The Modern Epic Of Gilgamesh
“DNA provides the music. Our cells and the environment provide the orchestra.” —J. Craig Venter
In Venter’s autobiography, Life Decoded, he describes his early life as a rebel, a pyromaniac, an ADHD, and an academic failure who “willed himself” to a Ph.D. and a scientific career, after the horrors of Vietnam.
Many of these traits were written in his DNA, Venter believes, which happens to be the first DNA ever completely sequenced by man (by Venter himself) during the Human Genome project. Venter’s full DNA sequence, the first such signature in history, is attached to his book, as if inviting future readers to clone the author in case they miss the book’s gist.
The gist goes like this. Humans are composed of 100 trillion cells which organize themselves according to the “software of life,” a DNA packet that fits onto a thumb-sized USB drive and contains 23,000 genes scattered among 46 chromosomes. Inside the genes lie simple three-letter codes that tell amino acids to fold into proteins in a particular way. If you learn how to work this software, you become God.
“If you change the software, you change the species,” as Venter likes to point out.
The idea that pure science can create life from scratch is at odds with vitalism, the theory that our precious experience depends on more than just a bonding of chemical or physical forces. It means that anything outside the scope of human ingenuity becomes irrelevant, at least for the construction and evolution of life’s diverse forms.
The ability to transfer digital DNA data into a living genome approached reality only three decades after Venter became frustrated with life. He couldn’t bear the fact that a community of 100 trillion cells could perish from a single bullet. There had to be a system behind the randomness.
From The Heart To The Genome
“Many geneticists are content with finding an association between a piece of DNA and a trait,” Venter writes in his autobiography. “To me it’s like saying ‘I have this friend who knows Madonna!’ I wanted to understand what animated Madonna, and everybody else, for that matter.”
Venter’s biotech career began with his research on the one chemical that makes our heart race. To understand how adrenaline worked, Venter needed to break down the DNA of the protein molecules tied to adrenaline. Early results led him to his own NIH (National Institutes of Health) lab and a fair share of scientific fame that would monetize his name.
The U.S. Department of Defense fleshed out funds to Venter to “detect biological warfare agents in the field,” while the private, fledgling biochemical industry began to shower him with offers, with the hopes of patenting human DNA strings. By the late 1990s,Venter was knocking on the human genome, the biological moonshot of the 20th century.
Venter approached the task of deconstructing the genome with a novel method known as “shotgun sequencing,” under which you chop up chromosomes into small pieces, digitize them by reading out the order of the base pairs, and subsequently have a supercomputer reassemble the random bits based on the overlapping ends of multiple reads. It was like throwing a puzzle piece on the floor to find random matches, repeatedly, until the picture is complete. In the case of the human genome, it meant 26 million sequence reads, with some 680 trillion comparisons.
The shotgun method was rejected as too unreliable by the leaders of Human Genome Project, Francis Collins, and the NIH. But a determined Venter decided to use it anyway with financing from a private equity-funded venture, the Celera Corporation, with Venter as co-founder in 1998.
By then, Venter had already successfully sequenced the adrenaline receptor and the first bacterial genome, that of the Haemophilus influenzae bacterium, with The Institute For Genomic Research (TIGR), a nonprofit he had founded in 1992. He had also developed a technique – the Expressed Sequence Tag (EST) methodology – that could rapidly identify expressive genes that were active in protein construction. EST was a relatively easy way to spot neurological conditions that were linked to specific DNA strings, and therefore offered the potential for medicinal applications with a high likelihood for patentability. The commercial promise paved the way for more funding and computing resources.
Venter completed the Human Genome Project independently of NIH’s team, using just $100 million out of the budgeted $3 billion.
“Today, we are learning the language in which God created life. We are gaining ever more awe for the complexity, the beauty, the wonder of God’s most divine and sacred gift,” voiced President Bill Clinton on June 26, 2000, not realizing that God stood next to him.
“The book in which all human life is written, belongs to every member of the human race,” Clinton continued, causing hundreds of billions of dollars to drain from the biotech market in a day. The future of biotech belonged to Silicon Valley, not Main Street. It was a momentary communication glitch that Clinton fixed a day later by saying that his “statement had not intended to have any impact on the patentability of genes.”
One of the big hopes of the Human Genome Project is to use the data to cure chronic disease, especially cancer. As the past decade illustrates, this has been a slow endeavor. Metabolomic tests, for example, have indicated that cancer has very little correlation with genetic markers. So far, the data has also been of relatively marginal value to medicine, except for identifying a host of genetic disorders. Sixteen years after its initial publication, 99 percent of the data remains unanalyzed. Meanwhile, sequencing costs have dropped to about $1,000 per human genome, down from the original $3 billion budgeted for the first genome. A wider scale adoption for practical medicinal purposes is still pending.
Genome sequencing has been useful in other areas. It has shown how little we vary from the simplest organisms, such as the roundworm. With 21,000 protein-coding genes, humans carry only 5 percent more gene data than a parasite.
With Venter’s help, the technology has also been used to identify the victims of 9/11, as well as the semen samples from a blue dress belonging to one Ms. Lewinsky. Soon after the completion of the human genome, Venter became persona non grata in the White House due to his association with the FBI agent in charge of the Lewinsky investigation.
He was also fired from Celera in 2002, due to a management conflict – a “stroke of luck.” He finally had free reign to create his own reality. Now that he knew what animated Madonna, the obvious next step was to build a Madonna.
From The Genome To The Biome
In 2003, Venter disappeared on the Global Ocean Sampling Expedition (GOS), circumnavigating the globe with Sorcerer II, a personal yacht stacked up with biotech from bow to stern. His stated goal was to identify “microbial lifeforms that could help combat global warming.”
His proposed methodology was to shotgun sequence the entire ocean biome, a vast microbial pool which in his estimation represented “millions of unique species, or a billion trillion organisms for every human on the planet, 99 percent of which remain hidden on the seabed.”
Cracking the ocean code required a new level of magnitude of processing power and funding. To prove that shotgun sequencing entire ocean biomes was even possible, Venter fractured a hundred known microbial genomes into a random smoothie and ran it through his genome assembler, only to reconstruct the DNA again correctly.
The Sorcerer II collected sample data every two hundred miles from the Panama Canal to the Galápagos Islands for two years. The resulting microbial sludge was then shotgun sequenced by the same computers that simulate hydrogen bomb blasts.
In a paper that Venter released in 2007, he describes 400 newly discovered microbes and 6 million new genes, including over 9,000 new sequences that control nitrogen metabolism, a soil bug that converts CO2 into cell material, a microbe that can transfer carbon to ocean depths, protein forms that predate multicellular life, and other novel genetic material plentiful enough to double the number of genes known to science.
The century’s data catch, Venter expected, would contain the data on how to manufacture a self-replicating synthetic microbe that could eat up excess CO2. In this manner, Venter was hoping to teach the planet how to take “deeper breaths.”
In 2006 Venter set up J. Craig Venter Institute (JCVI), a nonprofit research institute to “research genomic medicine, environmental genomic analysis, clean energy and synthetic biology,” with over 400 employees intent on helping the planet recover its lungs.
And Then There Was Light
“A new variety raised by man will be a far more important and interesting subject for study than one more species added to the infinitude of already recorded species.” —Charles Darwin, On the Origin of Species (1859)
The ultimate prize for a biotech god is to become father to an artificial life form. But how does one begin to assemble life from scratch? The answer is, by first breaking it down to its most essential components.
Before Venter had his mind on the human genome project, he and his partner, microbiologist and Nobel laureate Hamilton Smith, were trying to figure out whether there was a “minimal operating system for life” and if so, how to define it. Why did one bacterial species require e.g., 1,800 genes for life, and another only 482? If they could figure out the essentials, it would be possible to build a rudimentary life form, and then start adding features.
Venter’s protagonist for a basic bacteria OS was a tiny bacteriophage by the name of Phi X 174, which was originally discovered in the sewers of Paris, a virus that inhabits the human-intestine bacterium Escherichia coli. The X 174 infects and replicates within a bacterium with as little as 11 genes and 5,384 base pairs. In 1997, Venter’s team first began to break down the virus into oligonucleotides (base DNA or RNA molecules that could be assembled in any user-specified sequence).
By 2003 the team was able to synthesize X 174 in vitro. It was the first time a digitally designed virus began replicating inside a bacterium. It was also the proof of concept for a technology that could translate digital DNA data into a chemical synthesis, the bridge between zeros and ones, and living organisms.
The next hurdle was to create an error-proof process of transcribing the data to larger genomes. Having accurately done this with 5,000 base pairs of the X 174, Venter had a clear path to replicate the success with even more complex forms of life.
Like the Mycoplasma genitalium, a small pathogenic bacterium that lives in the cells of the urinary tract, that had 580,070 nucleotide base pairs inside 525 genes. Until 2003 it was regarded as the cellular unit with the smallest genome size, and therefore the simplest candidate for synthesis.
Venter’s team carved the M. genitalium into 101 overlapping digital “cassettes” that knit together by binding to the correct base pairs. The DNA was cloned and replicated inside another bacterium, E. coli, for faster nucleotide production and sequencing, and eventually replicated inside a yeast cell to help synthesize long enough strings to contain the 580,070 nucleotide base pairs.
The exact same data was replicated digitally in a 128-core Linux cluster, in order to build a virtual M. genitalium. The virtual and the real M. genitalium shared similar life habits. They both required 10 hours for a single cell division.
The trial and error phase of transcribing the data took half a decade.
The digital genome was successfully transplanted for the first time into a living cell in 2008. The first organism with a synthetic genome, aka Mycoplasma genitalium JCVI-1.0, carried a watermark identifying its creators “J. Craig Venter Institute” and “Synthetic Genomics Inc.”
Venter added another watermark to his baby which quoted the Nobel Prize-winning quantum physicist Richard Feynman: “What I cannot create, I do not understand.”
The subsequent research found that the new cells with the synthetic genome were fully self-replicating and capable of logarithmic growth, “slightly faster” than their natural peers.
The hand clapping and congratulations were soon followed by an equally thunderous rebuke from environmental groups. The Canadian ETC, for example, nicknamed the new life form “Synthia” and called for a “global moratorium on synthetic biology.”
The Affair With Big Oil
On May 20, 2010, Venter announced Synthia to the world, and mentioned that they had “started work to produce vaccines and create synthetic algae to turn carbon dioxide into fuel,” without giving more detail.
The financial partners Venter chose to rebuild Earth’s lungs weren’t the obvious candidates for an environmental mission.
In June 2005 Venter co-founded Synthetic Genomics, a company “dedicated to using modified microorganisms to produce clean fuels and biochemical,” and raised $600 million from ExxonMobil and an undisclosed equity injection from British Petroleum.
Both BP and Exxon have a history of distributing disinformation designed to protect carbon mining, rather than combat climate change.
Venter’s collaboration with BP and ExxonMobil are conspicuously absent from his speeches, his biography and his follow-up sequel, Life At The Speed Of Light: From The Double Helix To The Dawn Of Life.
The partnership fueled Venter’s research with practically unlimited resources, without being clear what Big Oil was seeking out of the collaboration. The omission gave birth to speculation.
On April 22, 2010, the Deepwater Horizon, an oil rig leased to BP, exploded and sunk in the Gulf Of Mexico, spilling an estimated 4.9 million barrels of crude oil over 68,000 square miles of ocean, an area the size of Oklahoma. In an effort to emulsify the oil into tiny droplets that would be easier to digest by ocean bacteria, BP added 1.84 million gallons of Corexit from Illinois-based Nalco, a “purely experimental” oil dispersant, despite being highly toxic to marine life.
In the wake of the Gulf Oil Spill, ETC, the Canadian watchdog, alleged that a synthetic oil-eating microbe designed by Synthetic Genomics may have been released into the ocean, causing mysterious illnesses, birds dropping from the sky, collapsing ecosystems, and human flesh eating pandemics.
The alleged purpose of the collaboration between BP and Synthetic Genomics, according to ETC, was to help create synthetic bacteria that would lead to improved oil recovery rates, aka Microbial Enhanced Oil Recovery (MEOR). In MEOR, microbes help propel oil out of the well at a faster rate, thereby significantly boosting the return on investment per well. The “uncontrollable bursts of gas and pressure” that were observed before Deepwater Horizon blew up may have been due to a “logarithmically replicating Synthia,” which then proceeded to “mutate and eat other forms of carbon-based life in its path,” causing the “flesh-eating microbes” that began to propagate along the coast of Florida.
The BP oil spill is estimated to have affected 10 to 20 million people in the U.S. with over 100,000 claims filed against BP. Most of the health effects can be explained without a synthetic microbe conspiracy, thanks to the massive use of the highly toxic dispersant Corexit alone.
But even if Synthia never saw more than an LED light to date, the story raises a flag. The partnerships that design life deserve more than scrutiny. It’s only a matter of time that synthetic life form is out of the box, free to mingle, mutate and propagate in earth’s biosphere. The question is: to whose advantage?
From Synthia To Madonna
The genie itself is already out. On one end of the spectrum lies the unlimited potential of transforming the world for the better. On the other, a synthetic microbe gone postal, and the promise of ultimate biological weapons.
Today, Venter and his team are spearheading several technologies that could fit either side of the spectrum. But Isaac Asimov’s Fourth Law Of Robotics (“robot may not injure a human being or, through inaction, allow a human being to come to harm”) will keep us safe, if we trust the biotech god’s perspective.
Progress is the only game in town.
“Never, never, was one of my robots to turn stupidly on his creator for no purpose but to demonstrate, for one more weary time, the crime and punishment of Faust,” wrote Isaac Asimov.
The first genome took nine months and $100 million to construct. Today Venter’s labs are cranking out 100,000 human genomes per year, with half a million times more computing power than in 1999. By 2020, Venter hopes to have 5 million genomes analyzed and correlated with other phenotypes, like facial characteristics, voice, disease prevalence, drug response, and hereditary data. One pinprick will be enough to predict human behavior through gene-expression.
Other projects in pipeline, include:
- The Human Epigenome Project
Designed to categorize how epigenetic factors, such as nutrition, lifestyle and the environment can turn certain genes on or off. These factors may include transgenerational habits of our great grandparents.
- Rewiring genomes
Rewiring pig DNA, for example, for human organ transplantation.
- DNA Vaccines
Manufacture of vaccines that can attack new biological strains with fractional lead times.
- Eliminating the cell altogether
Creating DNA in a cell-free environment will make the transference of life even simpler and more immediate.
- Biological teleporters
Transmit DNA molecule data at the speed of light, using electromagnetic waves, to send and receive data and autonomously construct living organisms.
Then there is Synthia. The new Synthia 3.0 announced in March 2016 marks a new milestone. It has the smallest genome, and the fewest genes, of any freely living organism.
She is our new definition for minimal OS of life. Now it will be possible to start adding new features, line by line, from Synthia to Madonna.
It’s the first time that we are playing with our own operating system, responsible for our own evolution.