Part 9 (2/2)

According to some estimates, the Chinese government has spent well over $100 billion on life sciences research over just the last three years, and has persuaded 80,000 Chinese Ph.D.'s trained in Western countries to return to China. One Boston-based expert research team, the Monitor Group, reported in 2010 that China is ”poised to become the global leader in life science discovery and innovation within the next decade.” China's State Council has declared that its genetic research industry will be one of the pillars of its twenty-first-century industrial ambitions. Some researchers have reported preliminary discussions of plans to eventually sequence the genomes of almost every child in China.

Multinational corporations are also playing a powerful role, quickly exploiting the many advances in the laboratory that have profitable commercial applications. Having invaded the democracy sphere, the market sphere is now also bidding for dominance in the biosphere. Just as Earth Inc. emerged from the interconnection of billions of computers and intelligent devices able to communicate easily with one another across all national boundaries, Life Inc. is emerging from the ability of scientists and engineers to connect flows of genetic information among living cells across all species boundaries.

The merger between Earth Inc. and Life Inc. is well under way. Since the first patent on a gene was allowed by a Supreme Court decision in the U.S. in 1980, more than 40,000 gene patents have been issued, covering 2,000 human genes. So have tissues, including some tissues taken from patients and used for commercial purposes without their permission. (Technically, in order to receive a patent, the owner must transform, isolate, or purify the gene or tissue in some way. In practice, however, the gene or tissue itself becomes commercially controlled by the patent owner.) There are obvious advantages to the use of the power of the profit motive and of the private sector in exploiting the new revolution in the life sciences. In 2012, the European Commission approved the first Western gene therapy drug, known as Glybera, in a treatment of a rare genetic disorder that prevents the breakdown of fat in blood. In August 2011, the U.S. Food and Drug Administration (FDA) approved a drug known as Crizotinib for the targeted treatment of a rare type of lung cancer driven by a gene mutation.

However, the same imbalance of power that has produced dangerous levels of inequality in income is also manifested in the unequal access to the full range of innovations important to humanity flowing out of the Life Sciences Revolution. For example, one biotechnology company-Monsanto-now controls patents on the vast majority of all seeds planted in the world. A U.S. seed expert, Neil Harl of Iowa State University, said in 2010, ”We now believe that Monsanto has control over as much as 90 percent of [seed genetics].”

The race to patent genes and tissues is in stark contrast to the att.i.tude expressed by the discoverer of the polio vaccine, Jonas Salk, when he was asked by Edward R. Murrow, ”This vaccine is going to be in great demand. Everyone's going to want it. It's potentially very lucrative. Who holds the patent?” In response, Salk said, ”The American people, I guess. Could you patent the sun?”

THE DIGITIZATION OF LIFE.

In Salk's day, the idea of patenting life science discoveries intended for the greater good seemed odd. A few decades later, one of Salk's most distinguished peers, Norman Borlaug, implemented his Green Revolution with traditional crossbreeding and hybridization techniques at a time when the frenzy of research into the genome was still in its early stages. Toward the end of his career, Borlaug referred to the race in the U.S. to lock down owners.h.i.+p of patents on genetically modified plants, saying, ”G.o.d help us if that were to happen, we would all starve.” He opposed the dominance of the market sphere in plant genetics and told an audience in India, ”We battled against patenting ... and always stood for free exchange of germplasm.” The U.S. and the European Union both recognize patents on isolated or purified genes. Recent cases in the U.S. appellate courts continue to uphold the patentability of genes.

On one level, the digitization of life is merely a twenty-first-century continuation of the story of humankind's mastery over the world. Alone among life-forms, we have the ability to make complex informational models of reality. Then, by learning from and manipulating the models, we gain the ability to understand and manipulate the reality. Just as the information flowing through the Global Mind is expressed in ones and zeros-the binary building blocks of the Digital Revolution-the language of DNA spoken by all living things is expressed in four letters: A, T, C, and G.

Even leaving aside its other miraculous properties, DNA's information storage capacity is incredible. In 2012, a research team at Harvard led by George Church encoded a book with more than 50,000 words into strands of DNA and then read it back with no errors. Church, a molecular biologist, said a billion copies of the book could be stored in a test tube and be retrieved for centuries, and that ”a device the size of your thumb could store as much information as the whole internet.”

At a deeper level, however, the discovery of how to manipulate the designs of life itself marks the beginning of an entirely new story. In the decade following the end of World War II, the double helix structure of DNA was discovered by James Watson, Francis Crick, and Rosalind Franklin. (Franklin was, historians of science now know, unfairly deprived of recognition for her seminal contributions to the scientific paper announcing the discovery in 1953. She died before the n.o.bel Prize in Medicine was later awarded to Watson and Crick.) In 2003, exactly fifty years later, the human genome was sequenced.

Even as the scientific community is wrestling with the challenges of all the data involved in DNA sequencing, they are beginning to sequence RNA (ribonucleic acid), which scientists are finding plays a far more sophisticated role than simply serving as a messenger system to convey the information that is translated into proteins. The proteins themselves-which among other things actually build and control the cells that make up all forms of life-are being a.n.a.lyzed in the Human Proteome Project, which must deal with a further large increase in the amount of data involved. Proteins take many different forms and are ”folded” in patterns that affect their function and role. After they are ”translated,” proteins can also be chemically modified in multiple ways that extend their range of functions and control their behavior. The complexity of this a.n.a.lytical challenge is far beyond that involved in sequencing the genome.

”Epigenetics” involves the study of inheritable changes that do not involve a change in the underlying DNA. The Human Epigenome Project has made major advances in the understanding of these changes. Several pharmaceutical products based on epigenetic breakthroughs are already helping cancer patients, and other therapeutics are being tested in human clinical trials. The decoding of the underpinnings of life, health, and disease is leading to many exciting diagnostic and therapeutic breakthroughs.

In the same way that the digital code used by computers contains both informational content and operating instructions, the intricate universal codes of biology now being deciphered and catalogued make it possible not only to understand the blueprints of life-forms, but also to change their designs and functions. By transferring genes from one species to another and by creating novel DNA strands of their own design, scientists can insert them into life-forms to transform and commandeer them to do what they want them to do. Like viruses, these DNA strands are not technically ”alive” because they cannot replicate themselves. But also like viruses, they can take control of living cells and program behaviors, including the production of custom chemicals that have value in the marketplace. They can also program the replication of the DNA strands that were inserted into the life-form.

The introduction of synthetic DNA strands into living organisms has already produced beneficial advances. More than thirty years ago, one of the first breakthroughs was the synthesis of human insulin to replace less effective insulin produced from pigs and other animals. In the near future, scientists antic.i.p.ate significant improvements in artificial skin and synthetic human blood. Others hope to engineer changes in cyan.o.bacteria to produce products as diverse as fuel for vehicles and protein for human consumption.

But the spread of the technology raises questions that are troubling to bioethicists. As the head of one think tank studying this science put it, ”Synthetic biology poses what may be the most profound challenge to government oversight of technology in human history, carrying with it significant economic, legal, security and ethical implications that extend far beyond the safety and capabilities of the technologies themselves. Yet by dint of economic imperative, as well as the sheer volume of scientific and commercial activity underway around the world, it is already functionally unstoppable ... a juggernaut already beyond the reach of governance.”

Because the digitization of life coincides with the emergence of the Global Mind, whenever a new piece of the larger puzzle being solved is put in place, research teams the world over instantly begin connecting it to the puzzle pieces they have been dealing with. The more genes that are sequenced, the easier and faster it is for scientists to map the network of connections between those genes and others that are known to appear in predictable patterns.

As Jun w.a.n.g, executive director of the Beijing Genomics Inst.i.tute, put it, there is a ”strong network effect ... the health profile and personal genetic information of one individual will, to a certain extent, provide clues to better understand others' genomes and their medical implications. In this sense, a personal genome is not only for one, but also for all humanity.”

An unprecedented collaboration in 2012 among more than 500 scientists at thirty-two different laboratories around the world resulted in a major breakthrough in the understanding of DNA bits that had been previously dismissed as having no meaningful role. They discovered that this so-called junk DNA actually contains millions of ”on-off switches” arrayed in extremely complex networks that play crucial roles in controlling the function and interaction of genes. While this landmark achievement resulted in the identification of the function of 80 percent of DNA, it also humbled scientists with the realization that they are a very long way from fully understanding how genetic regulation of life really works. Job Dekker, a molecular biophysicist at the University of Ma.s.sachusetts Medical School, said after the discovery that every gene is surrounded by ”an ocean of regulatory elements” in a ”very complicated three-dimensional structure,” only one percent of which has yet been described.

The Global Mind has also facilitated the emergence of an Internet-based global marketplace in so-called biobricks-DNA strands with known properties and reliable uses-that are easily and inexpensively available to teams of synthetic biologists. Scientists at MIT, including the founder of the BioBricks Foundation, Ron Weiss, have catalyzed the creation of the Registry of Standard Biological Parts, which is serving as a global repository, or universal library, for thousands of DNA segments-segments that can be used as genetic building blocks of code free of charge. In the same way that the Internet has catalyzed the dispersal of manufacturing to hundreds of thousands of locations, it is also dispersing the basic tools and raw materials of genetic engineering to laboratories on every continent.

THE GENOME EFFECT.

The convergence of the Digital Revolution and the Life Sciences Revolution is accelerating these developments at a pace that far outstrips even the speed with which computers are advancing. To ill.u.s.trate how quickly this radical change is unfolding, the cost of sequencing the first human genome ten years ago was approximately $3 billion. But in 2013 detailed digital genomes of individuals are expected to be available at a cost of only $1,000 per person.

At that price, according to experts, genomes will become routinely used in medical diagnoses, in the tailoring of pharmaceuticals to an individual's genetic design, and for many other purposes. In the process, according to one genomic expert, ”It will raise a host of public policy issues (privacy, security, disclosure, reimburs.e.m.e.nt, interpretation, counseling, etc.), all important topics for future discussions.” In the meantime, a British company announced in 2012 that it will imminently begin selling a small disposable gene-sequencing machine for less than $900.

For the first few years, the cost reduction curve for the sequencing of individual human genomes roughly followed the 50 percent drop every eighteen to twenty-four months that has long been measured by Moore's Law. But at the end of 2007, the cost for sequencing began to drop at a significantly faster pace-in part because of the network effect, but mainly because multiple advances in the technologies involved in sequencing allowed significant increases in the length of DNA strands that can be quickly a.n.a.lyzed. Experts believe that these extraordinary cost reductions will continue at breakneck speed for the foreseeable future. As a result, some companies, including Life Technologies, are producing synthetic genomes on the a.s.sumption that the pace of discovery in genomics will continue to accelerate.

By contrast, the distillation of wisdom is a process that normally takes considerable time, and the molding of wisdom into accepted rules by which we can guide our choices takes more time still. For almost 4,000 years, since the introduction by Hammurabi of the first written set of laws, we have developed legal codes by building on precedents that we have come to believe embody the distilled wisdom of past judgments made well. Yet the great convergence in science being driven by the digitization of life-with overlapping and still accelerating revolutions in genetics, epigenetics, genomics, proteomics, microbiomics, optogenetics, regenerative medicine, neuroscience, nanotechnology, materials science, cybernetics, supercomputing, bioinformatics, and other fields-is presenting us with new capabilities faster than we can discern the deeper meaning and full implications of the choices they invite us to make.

For example, the impending creation of completely new forms of artificial life capable of self-replication should, arguably, be the occasion for a full discussion and debate about not only the risks, benefits, and appropriate safeguards, but also an exploration of the deeper implications of crossing such an epochal threshold. In the prophetic words of Teilhard de Chardin in the mid-twentieth century, ”We may well one day be capable of producing what the Earth, left to itself, seems no longer able to produce: a new wave of organisms, an artificially provoked neo-life.”

The scientists who are working hard to achieve this breakthrough are understandably excited and enthusiastic, and the incredibly promising benefits expected to flow from their hoped-for accomplishment seem reason enough to proceed full speed ahead. As a result, it certainly seems timorous to even raise the sardonic question ”What could go wrong?”

MORE THAN A little, it seems-or at least it seems totally reasonable to explore the question. Craig Venter, who had already made history by sequencing his own genome, made history again in 2010 by creating the first live bacteria made completely from synthetic DNA. Although some scientists minimized the accomplishment by pointing out that Venter had merely copied the blueprint of a known bacterium, and had used the empty sh.e.l.l of another as the container for his new life-form, others marked it as an important turning point.

In July 2012, Venter and his colleagues, along with a scientific team at Stanford, announced the completion of a software model containing all of the genes (525 of them-the smallest number known), cells, RNA, proteins, and metabolites (small molecules generated in cells) of an organism-a free-living microbe known as Mycoplasma genitalium. Venter is now working to create a unique artificial life-form in a project that is intended to discover the minimum amount of DNA information necessary for self-replication. ”We are trying to understand the fundamental principles for the design of life, so that we can redesign it-in the way an intelligent designer would have done in the first place, if there had been one,” Venter said. His reference to an ”intelligent designer” seems intended as implicit dismissal of creationism and reflects a newly combative att.i.tude that many scientists have understandably come to feel is appropriate in response to the aggressive attacks on evolution by many fundamentalists.

One need not believe in a deity, however, in order to entertain the possibility that the web of life has an emergent holistic integrity featuring linkages we do not yet fully understand and which we might not risk disrupting if we did. Even though our understanding of hubris originated in ancient stories about the downfall of men who took for themselves powers reserved for the G.o.ds, its deeper meaning-and the risk it often carries-is rooted in human arrogance and pride, whether or not it involves an offense against the deity. As Shakespeare wrote, ”The fault, dear Brutus, is not in our stars, but in ourselves.” For all of us, hubris is inherent in human nature. Its essence includes prideful overconfidence in the completeness of one's own understanding of the consequences of exercising power in a realm that may well have complexities that still extend beyond the understanding of any human.

Nor is the posture of fundamentalism unique to the religious. Reductionism-the belief that scientific understanding is usually best pursued by breaking down phenomena into their component parts and subparts-has sometimes led to a form of selective attention that can cause observers to overlook emergent phenomena that arise in complex systems, and in their interaction with other complex systems.

One of the world's most distinguished evolutionary biologists, E. O. Wilson, has been bitterly attacked by many of his peers for his proposal that Darwinian selection operates not only at the level of individual members of a species, but also at the level of ”superorganisms”-by which he means that adaptations serving the interests of a species as a whole may be selected even if they do not enhance the prospects for survival of the individual creatures manifesting those adaptations. Wilson, who was but is no longer a Christian, is not proposing ”intelligent design” of the sort believed in by creationists. He is, rather, a.s.serting that there is another layer to the complexity of evolution that operates on an ”emergent” level.

Francis Collins, a devout Christian who headed the U.S. government's Human Genome Project (which announced its results at the same time that Craig Venter announced his), has bemoaned the ”increasing polarization between the scientific and spiritual worldviews, much of it, I think, driven by those who are threatened by the alternatives and who are unwilling to consider the possibility that there might be harmony here.... We have to recognize that our understanding of nature is something that grows decade by decade, century by century.”

Venter, for his part, is fully confident that enough is already known to justify a large-scale project to reinvent life according to a human design. ”Life evolved in a messy fas.h.i.+on through random changes over three billion years,” he says. ”We are designing it so that there are modules for different functions, such as chromosome replication and cell division, and then we can decide what metabolism we want it to have.”

ARTIFICIAL LIFE.

As with many of the startling new advances in the life sciences, the design and creation of artificial life-forms offers the credible promise of breakthroughs in health care, energy production, environmental remediation, and many other fields. One of the new products Venter and other scientists hope to create is synthetic viruses engineered to destroy or weaken antibiotic-resistant bacteria. These synthetic viruses-or bacteriophages-can be programmed to attack only the targeted bacteria, leaving other cells alone. These viruses utilize sophisticated strategies to not only kill the bacteria but also use the bacteria before it dies to replicate the synthetic virus so that it can go on killing other targeted bacteria until the infection subsides.

The use of new synthetic organisms for the acceleration of vaccine development is also generating great hope. These synthetic vaccines are being designed as part of the world's effort to prepare for potential new pandemics like the bird flu (H5N1) of 2007 and the so-called swine flu (H1N1) of 2009. Scientists have been particularly concerned that the H5N1 bird flu is now only a few mutations away from developing an ability to pa.s.s from one human to another through airborne transmission.

The traditional process by which vaccines are developed requires a lengthy development, production, and testing cycle of months, not days, which makes it nearly impossible for doctors to obtain adequate supplies of the vaccine after a new mutant of the virus begins spreading. Scientists are using the tools of synthetic biology to accelerate the evolution of existing flu strains in the laboratory and they hope to be able to predict which new strains are most likely to emerge. Then, by studying their blueprints, scientists hope to preemptively synthesize vaccines that will be able to stop whatever mutant of the virus subsequently appears in the real world and stockpile supplies in antic.i.p.ation of the new virus's emergence. Disposable biofactories are being set up around the world to decrease the cost and time of manufacturing of vaccines. It is now possible to set up a biofactory in a remote rural village where the vaccine is needed quickly to stop the spread of a newly discovered strain of virus or bacteria.

Some experts have also predicted that synthetic biology may supplant 15 to 20 percent of the global chemical industry within the next few years, producing many chemical products more cheaply than they can be extracted from natural sources, producing pharmaceutical products, bioplastics, and other new materials. Some predict that this new approach to chemical and pharmaceutical manufacturing will-by using the 3D printing technique described in Chapter 1-revolutionize the production process by utilizing a ”widely dispersed” strategy. Since most of the value lies in the information, which can easily be transmitted to unlimited locations, the actual production process by which the information is translated into production of Synthetic Biology products can be located almost anywhere.

These and other exciting prospects expected to accompany the advances in synthetic biology and the creation of artificial life-forms have led many to impatiently dismiss any concerns about unwanted consequences. This impatience is not of recent vintage. Ninety years ago, English biochemist J. B. S. Haldane wrote an influential essay that provoked a series of futurist speculations about human beings taking active control of the future course of evolution. In an effort to place in context-and essentially dismiss-the widespread uneasiness about the subject, he wrote: The chemical or physical inventor is always a Prometheus. There is no great invention, from fire to flying, which has not been hailed as an insult to some G.o.d. But if every physical and chemical invention is a blasphemy, every biological invention is a perversion. There is hardly one which, on first being brought to the notice of an observer from any nation which has not previously heard of their existence, would not appear to him as indecent and unnatural.

By contrast, Leon Ka.s.s, who chaired the U.S. Council on Bioethics from 2001 to 2005, has argued that the intuition or feeling that something is somehow repugnant should not be automatically dismissed as antiscientific: ”In some crucial cases, however, repugnance is the emotional expression of deep wisdom, beyond reason's power completely to articulate it.... We intuit and we feel, immediately and without argument, the violation of things that we rightfully hold dear.”

In Chapter 2, the word ”creepy” was used by several observers of trends unfolding in the digital world, such as the ubiquitous tracking of voluminous amounts of information about most people who use the Internet. As others have noted, ”creepy” is an imprecise word because it describes a feeling that itself lacks precision-not fear, but a vague uneasiness about something whose nature and implications are so unfamiliar that we feel the need to be alert to the possibility that something fearful or harmful might emerge. There is a comparably indeterminate ”pre-fear” that many feel when contemplating some of the onrus.h.i.+ng advances in the world of genetic engineering.

An example: a method for producing spider silk has been developed by genetic engineers who insert genes from orb-making spiders into goats which then secrete the spider silk-along with milk-from their udders. Spider silk is incredibly useful because it is both elastic and five times stronger than steel by weight. The spiders themselves cannot be farmed because of their antisocial, cannibalistic nature. But the insertion of their silk-producing genes in the goats allows not only a larger volume of spider silk to be produced, but also allows the farming of the goats.

In any case, there is no doubt that the widespread use of synthetic biology-and particularly the use of self-replicating artificial life-forms-could potentially generate radical changes in the world, including some potential changes that arguably should be carefully monitored. There are, after all, too many examples of plants and animals purposely introduced into a new, nonnative environment that then quickly spread out of control and disrupted the ecosystem into which they were introduced.

Kudzu, a j.a.panese plant that was introduced into my native Southern United States as a means of combating soil erosion, spread wildly and became a threat to native trees and plants. It became known as ”the vine that ate the South.” Do we have to worry about ”microbial kudzu” if a synthetic life-form capable of self-replication is introduced into the biosphere for specific useful purposes, but then spreads rapidly in ways that have not been predicted or even contemplated?

Often in the past, urgent questions raised about powerful new breakthroughs in science and technology have focused on potentially catastrophic disaster scenarios that turned out to be based more on fear than reason-when the questions that should have been pursued were about other more diffuse impacts. For example, on the eve of the Bikini Atoll test of the world's first hydrogen bomb in 1954, a few scientists raised the concern that the explosion could theoretically trigger a chain reaction in the ocean and create an unimaginable ecological Armageddon.

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