EPIGENETIC EPILOGUE
+1 YR, THE END OF THE
BEGINNING, TRANSHUMANISM,
AND THE PANSPERMIA ERA
Societal Risks and Countermeasures
A popular theme in techno-thriller novels is the story of mutant microbes running amok and almost, but not quite, wiping out the human race. The locus classicus for this scenario is Michael Crichton’s The Andromeda Strain (1969). Here a deadly microbe of extraterrestrial origin lands near the fictional town of Piedmont, Arizona, and the invading organisms slaughter the town’s entire population, with the exception of two residents who mysteriously survive. The microbe responsible, the Andromeda strain of the title, mutates with each cell division and acquires new and even more destructive biological properties. The fate of humanity hangs in the balance, until a government scientist working inside a secret and secure biological containment facility somewhere in Nevada heroically carries out a last-minute save. The Andromeda microbes then depart for the upper atmosphere, whose lower oxygen content better suits their growth. (This story line seems to be a Michael Crichton specialty. His 2002 novel, Prey, depicts a race of artificially alive nanorobots that escape from the lab, collect themselves into swarms, and then hunt down and kill people.)
Paranoia about exotic microbes is not confined to fiction, however. In real life it underlies the hostility toward, and temporary suppression of, the first generation of recombinant DNA experiments during the mid-1970s. It’s what motivates panic reactions to genetically modified foods. And it’s also what incites some knee-jerk criticisms of synthetic biology. “Scientists are making strands of DNA that never existed,” claims Jim Thomas, a synthetic biology critic with the ETC Group, a technology monitoring organization based in Ottawa. “So there is nothing to compare them to.”
Well, not exactly. Every two parents who conceive a child are creating “strands of DNA that never existed” Bacteria are constantly exchanging genes in a process called conjugation, thereby giving rise to yet more “strands of DNA that never existed.” In fact, the creation of DNA that never before existed is a constant and pervasive feature of life on earth.
Despite the fear evoked by the idea of genetically modified organisms, those of the natural variety are hard to beat when it comes to posing serious threats to humanity. Yersinia pestis, the causative agent of bubonic plague, is estimated to have killed as many as a third to a half of all Europeans in the Black Death epidemic of the mid-fourteenth century. The bacterium made a comeback appearance in the Great Plague, another wave of annihilation that swept through the Continent in 1665-1666. The smallpox viruses, Variola major and minor, are thought to have caused more deaths than any other disease in human history, wiping out as many as 300 to 500 million people in the twentieth century alone. (The disease was eradicated in 1979.) Tuberculosis, malaria, cholera, AIDS—all are products of microbial agents of mass destruction that are natural in origin.
So it’s not as if we have to look to genetically altered microbes to find models of successful microbial killing machines. Still, the question has to be faced whether the process of genetic engineering is likely to make existing microbes even more deadly, giving rise to one or more Andromeda strains that originated in biotechnology labs here on earth.
And if genetically modified microbes pose a threat, what about genetically enhanced human beings, so-called transhumans? It’s a cliché that the human being is the most dangerous animal. Would a race of trans-humans be even worse?
The term “transhuman” harnesses the prefix “trans,” as in across or beyond, or acts as an abbreviation for transitional human. The transhuman occupies an intermediate stage between a normal biological human and one of the posthuman variety, a being whose capacities so far outstrip those of ordinary, everyday mortals as to constitute a new and separate species. The nomenclature is a bit imprecise, however, owing to the fact that the concept of improving human qualities to the point where they make up a species difference is a blend of ideas from science fiction, science, folklore and legend, and sheer crackpottery.
Nonetheless, transhumanism (sometimes symbolized as H+) has been taken seriously enough by some as to warrant attention and criticism. In 2004, for example, the magazine Foreign Policy published a special report, “The World’s Most Dangerous Ideas” In it, Francis Fukuyama, a professor of international political economy at the Johns Hopkins School of Advanced International Studies, proposed the idea of transhumanism as one of the most dangerous and revolting products of those he referred to as “genetic bulldozers” (such “bulldozers” apparently being people who push their transhumanist agenda with lots of force).
This was puzzling inasmuch as the author acknowledged that trans-humanism (which he defined as the attempt to “use biotechnology to make ourselves stronger, smarter, less prone to violence, and longer-lived”) had a certain inherent logic and appeal. Part of the contemporary biomedical research agenda, he admitted, was focused on procedures and technologies that were designed as much to enhance ourselves psychologically and biologically as to cure illness; medical science presented us with a range of mood-altering drugs, prenatal genetic screening tests, and gene therapies, among other things. Moreover, the author also conceded that “the human race, after all, is a pretty sorry mess, with our stubborn diseases, physical limitations, and short lives.”
Fukuyama, nevertheless, was an implacable foe of transhumanism, his reason being that “the first victim of transhumanism might be equality.” By this he meant political equality, or equality before the law, not economic equality or uniformity of outcomes. He imagined that transhumans, with their heightened powers, better health, better looks, smarter minds, and longer life spans, would claim comparably outsize rights for themselves.
But by any standard this was an odd argument. There is already a wide variation in talents among members of the human race, but those with great intelligence, strength, and good health do not claim special rights for themselves on that account. Conversely, those with severe physical and/or mental disabilities are nevertheless accorded full human rights by the legal structures of enlightened democratic governments.
This is not to say that transhumanism presents no dangers whatever or that it entails no unintended or unwelcome consequences. A small number of individuals already exist who possess qualities that could be regarded as “transhuman” in a limited and qualified sense of the term. Rare double mutants in the myostatin gene (a.k.a. MSTN) have lean muscle and low body fat. Rare mutants in the LRP5 gene have extra-strong bones. Mutants in PCSK9 have 88 percent lower coronary disease. Double mutants in CCR5 are HIV resistant (see Chapter 9). Double mutants in FUT2 are resistant to stomach flu (e.g., noroviruses).
On the other hand, consider those blessed, or cursed, by the condition known as hyperthymesia, the ability to recall autobiographical events in extraordinary detail. First reported in the scientific literature in the journal Neurocase as “A Case of Unusual Autobiographical Remembering” (2006), the subject was “a woman whose remembering dominates her life. Her memory is ‘nonstop, uncontrollable, and automatic.’ [She] spends an excessive amount of time recalling her personal past with considerable accuracy and reliability. If given a date, she can tell you what she was doing and what day of the week it fell on.”
The woman, who later revealed her identity as Jill Price, of Los Angeles, wrote a book about herself called The Woman Who Can’t Forget (2008) in which she described her condition as if it were a plague: “My memories are like scenes from home movies of every day of my life, constantly playing in my head, flashing forward and backward through the years relentlessly, taking me to any given moment, entirely of their own volition”
The team of neurophysiologists who examined her reported that Price, “while of average intelligence, has significant deficits in executive functions involving abstraction, self-generated organization and mental control,” as well as “obsessive-compulsive tendencies” and more. Her superior memory, in other words, was counterbalanced by
deficits in other areas.
Others with prodigious memories also have exhibited anomalous capacities elsewhere. Solomon Shereshevsky, a Russian journalist with a nearly photographic memory, also displayed synesthesia, a condition in which the stimulation of one of the five senses produced a reaction in one or more of the rest. Hearing a musical tone, for example, caused him to see a certain color, whereas the sensation of touching an object gave rise to a taste sensation.
Conventional wisdom, going back to the ancients, has it that genius and madness are often coupled in the same individual. In its less extreme form, this is the idea that those who are exceptionally talented in one area suffer compensating defects somewhere else in their personalities. And so we have the standard examples of Vincent van Gogh hacking off part of his ear and later committing suicide; Ludwig van Beethoven with his slovenly personal habits, absentmindedness, delusions of royalty, plus persecution fantasies and assorted other manias; and Isaac Newton, who was obsessively secretive and paranoiac, and who had fixations with astrology, alchemy, and the color red.
Among more run-of-the-mill geniuses, personal idiosyncrasies amount to mere quirks. Paul Dirac, for instance, the notoriously tight-lipped and taciturn physicist, once explained his uncommunicativeness: “My father made the rule that I should only talk to him in French. He thought it would be good for me to learn French in that way. Since I found that I couldn’t express myself in French, it was better for me to stay silent than to talk in English. So I became very silent at that time.”
Makes sense to me. Still, the question remains whether creating a race of transhumans would unwittingly produce a population burdened with a variety of unknown but severe dysfunctions or handicaps. And if we run that risk with benign and well-intentioned people (or even with benevolent amplified people), how much worse would be the potential for damage wrought by an actively malicious supergenius? After all, the power of individuals is growing. In ancient times one person might murder a couple of enemies with a rock. Later, he could destroy a village with fire. Today a small team might kill millions of people with nuclear, chemical, or biological warfare agents. In the future, could a single transitional human having a bad day (a Columbine teenager, for example) release a doomsday WMD?
Some of these same questions also arise with respect to synthetic genomics itself, and their relevance is especially clear in the case of iGEM, whose avowed purpose is to make biological engineering “easy.” Considering the numbers of college undergrads, and even high school students, engineering novel organisms with special properties and engaging in competitions for best design, best engineered biological part, and so on, there are plenty of opportunities for things to go wrong in a big way, whether by accident, deliberate misuse, or through the normal mutation and evolution of organisms.
David Donnell, adviser to the Citadel’s iGEM team, had doubts about the safety of engineering E. coli for appetite control. The idea was that the bacterial population would oscillate around some fixed mean that was sufficient to allow steady production of the appetite-suppressing peptide PYY. Supposedly, the supply of microbes would be kept in check by an engineered quorum-sensing circuit that would regulate gene expression in response to fluctuations in cell population density levels. Researchers at Duke had shown how quorum sensing could be used to limit the size of a bacterial population, and Team Citadel hoped to wire this same ability into their microbes. But could such quorum-sensing circuitry be made fail-safe?
“I’d like to say that we should be able to build in sufficient fail-safes that would allow us to pull the plug on the engineered bacteria if they got out of hand,” David Donnell said. “But of course, with a thick layer of oil sludge coating the ocean bottom in the Gulf of Mexico following the failure of a whole series of fail-safes designed to prevent oil spills by drilling rigs, I am somewhat skeptical of our ability to design a fail-safe fail-safe.”
There are no fail-safe fail-safes in biological lab work. Laboratories that handle natural microorganisms (including pathogens) that are expressly designed to prevent mishaps from occurring and are staffed by highly trained and experienced professionals have nevertheless had numerous accidents. In Biological Safety: Principles and Practices, two biosafety experts, Diane O. Fleming and Debra Long Hunt, reviewed accounts of biolab accidents published in scientific journals from 1970 to 2004. Over this thirty-four-year period there were a reported 1,448 symptom-causing infections resulting in thirty-six deaths. And as for the possibility of a high-level expert working in a well-equipped biosafety lab suddenly going berserk and wreaking havoc, recall Bruce Ivins, the perpetrator of the 2001 anthrax letter attacks. Ivins worked at USAMRIID, the US Army Medical Research Institute for Infectious Diseases, with the mission of protecting people from diseases like anthrax, not spreading them.
Facts like these have prompted synthetic biology researchers to think critically about safety and security. (The concepts of safety and security are not the same. Safety involves preventing accidents with hazardous organisms, especially the unintentional release of an engineered microbe into the environment, where it could have unknown but potentially damaging effects. Security, by contrast, refers to preventing the deliberate misuse of engineered organisms, whether by rogue states, terrorist groups, or lone agents working by themselves.) For all the benefits it promises, synthetic biology is potentially more dangerous than chemical or nuclear weaponry, since organisms can self-replicate, spread rapidly throughout the world, and mutate and evolve on their own. But as challenging as it might be to make synthetic biology research safe and secure within an institutional framework such as a university, industrial, or government lab, matters take a turn for the worse with the prospect of “biohackers,” lone agents or groups of untrained amateurs, working clandestinely, or even openly, with biological systems that have been intentionally made easy to engineer. The problem with making biological engineering techniques easy to use is that it also makes them easy to abuse.
In 2008 Markus Schmidt, an adviser to iGEM and a member of the Biosafety Working Group at the Organization for International Dialogue and Conflict Management in Austria, published a paper, “Diffusion of Synthetic Biology: A Challenge to Biosafety.” In it he portrayed iGEM’s attempt to make bioengineering easy as a “de-skilling” of biotechnological processes and as a “domestication of biology [that] could easily lead to unprecedented safety challenges.” In the extreme case, he said, “imagining a world where practically anybody with an average IQ would have the ability to create novel organisms in their home garage without adhering to a professional code of conduct, filing a reporting system, and lacking a sufficient biosafety training is a thrilling thought.”
In the early years of synthetic biology, researchers spoke of “do-it-yourself biology” as essentially a metaphor referring to the prospect of amateurs creating organisms in their kitchen at some unspecified time in the future. “Garage biology,” likewise, was a jocular term of abuse. A decade or so later, however, those possibilities had become realities, sooner than many of us would have thought. The website biohack.sourceforge.net, for example, offers an “open, free synthetic biology kit [that] contains all sorts of information from across the web on how to do it: how to extract and amplify DNA, cloning techniques, making DNA by what’s known as oligonucleotides, and all sorts of other tutorials and documents on techniques in genetic engineering, tissue engineering, synbio (synthetic biology), stem cell research, SCNT, evolutionary engineering, bioinformatics, etc.”
And in 2008, Jason Bobe, director of community outreach for the Personal Genome Project, and Mackenzie Cowell, a web developer, formed an online do-it-yourself biology discussion group calling itself DIYbio: An Institution for the Amateur Biologist (diybio.org). On May 1, 2008, about twenty-five hardcore DIYbio members got together in a back room of Asgard’s Irish Pub in Cambridge, just a few blocks from MIT, and discussed topics such as: Can molecular biology or biotechnology be a hobby? Will advances in synthetic biology be the tipping point that enab
les DIYers and garage biologists to make meaningful contributions to the biological sciences, outside of traditional institutions? Can DIYbio.org be the Homebrew Computer Club of biology? Good questions!
Two years later there were local DIYbio communities all over the globe, including several in the United States and Europe, three in India, and three more in South America. In addition, there were about 2,000 subscribers to the DIYbio mailing list. With this kind of rapid ideational diffusion, it was not long before agents from the FBI’s Weapons of Mass Destruction Directorate were showing up at DIYbio meetings, which were openly announced on the group’s website.
In 2009 the inevitable finally happened: garage biology came of age. Technically, the first garage biology operation began in 2005, when physicist Rob Carlson set up a private one-man lab in the garage of his Seattle home. Carlson had learned molecular biology techniques while working at Sydney Brenner’s Molecular Sciences Institute in Berkeley, California. Eventually he realized that if he could put together parts of different protein molecules in a certain way, then he might have a commercial product on his hands. And so with reconditioned micropipettes and a used centrifuge bought on eBay, plus the usual array of lab glassware and other machinery and instrumentation, he started working nights and weekends as a sort of biotech hobbyist. His garage lab, Carlson joked, was “half start-up company and half art project.”
Four years later, John Schloendorn, who had a doctoral degree in molecular biology from Arizona State, and Eri Gentry, a Yale economics grad who was his business partner, founded a biotech lab in Gentry’s garage in Mountain View, California, and started doing paid anticancer research. The idea for the garage lab arose after a friend of theirs died of esophageal cancer. Schloendorn knew about several lines of evidence suggesting that a natural immune response to cancer existed in some people and he was brash enough to think that, working by himself in his own private lab, he could play a direct role in advancing the scientific understanding of such immunity. With $30,000 (much of which was Schloendorn’s own money, the rest coming from Gentry and donations from friends), Gentry started outfitting the place. By shopping for used equipment at liquidations and auctions, as well as on eBay and Craigslist, she managed to purchase an estimated million dollars worth of machinery, including a custom-made clean bench, inverted phase contrast microscope, incubators, centrifuges, a fluorescence microplate reader, and so on.
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