Biology’s Brave New World: The Promise and Perils of the Synbio Revolution
The Principles for the Oversight of Synthetic Biology
The possibility of the deliberate creation of living organisms from elementary materials that are not themselves alive has engaged the human imagination for a very long time. Putting aside Genesis I, which is singularly lacking in any physical details on the bringing forth of life from the waters and the dust, we think immediately of the classical Greek story of the sculptor Pygmalion. Enamored of the unresponsive goddess Aphrodite, he creates an ivory statue of her, which, under the warmth of his caresses and the powers of Aphrodite herself, slowly softens and warms into a living woman, Galatea. Nor is Galatea any less a biological woman, for she becomes the mother of two children from her union with her human creator.
By the middle of the seventeenth century, Descartes had described the life activities of animals as the functioning of a bête machine and in 1748 La Mettrie extended this metaphor to humans as l’homme machine. The acceptance of the machine metaphor has the implication that, just as we can deliberately design and build a mechanical device from manufactured parts, so it must be possible to create new kinds of living organisms through the deliberate design and assembly of manufactured elements once the chemical and structural properties of already existing natural life forms have been understood.
But if the machine metaphor for living organisms is to work, we require more than a description and construction of the gears and levers. Somehow a dynamic force must be introduced. Even a mechanical clock requires an input of energy to wind it up over and over, and an electrically driven machine must have a constant input of energy from physical sources or chemical reactions. The view of living organisms as machines was then incomplete without the addition in the last quarter of the eighteenth century of the discoveries by Volta of the chemical generation of electric energy and of Galvani’s demonstration of the induction of twitching in the dissected muscles of frogs by bringing them in contact with combinations of different metals.
The question that remains is why one would want to commit oneself to such a project of creating a living organism from basic elements, given the great resources that are required and the considerable possibility of failure. In part it is a reflection of the power of a commitment to fulfillment of an intellectual program. Mary Shelley and her brother, as well as Lord Byron, belonged to an intellectual circle of Galvanists who believed that the life activities of organisms, including their mental processes, are basically manifestations of chemical reactions in the body. While Mary Shelley did not specify the details, in addition to the bones and other anatomical parts that Dr. Frankenstein collected for his project of creating a living organism, he included “instruments” with which he could “infuse a spark of being into the lifeless thing” that lay before him.
There is also, of course, ambition for achievement and fame. Over the door of what was originally Harvard’s Germanic Museum is this conveniently ambiguous line from Schiller’s Death of Wallenstein: “Es ist der Geist der sich den Körper baut.” (It is the spirit that builds the body.)1 Victor Frankenstein’s soul cries out to him:
So much has been done…more, far more will I achieve…. I will pioneer a new way, explore unknown powers, and unfold to the world the deepest mysteries of creation…. What had been the study and desire of the wisest men since the creation of the world was now within my grasp.
In modern times Craig Venter, the head of the J. Craig Venter Institute, announced the creation of a living, functioning, self-reproducing artificial bacterial cell containing a laboratory-produced DNA sequence that, according to Laurie Garrett’s Foreign Affairs essay “Biology’s Brave New World,” “moved, ate, breathed, and replicated itself.”
An element that was not yet present in the early-nineteenth-century interest in the artificial creation of life was the possibility of great financial profit. Biotechnology was still a century and a half in the future. Garrett characterizes Venter not only as the most powerful man in biotechnology but as the richest. The J. Craig Venter Institute has already worked with fuel companies and the pharmaceutical industry to create microorganisms that could produce new fuels and vaccines.2
What did concern those in the nineteenth century who imagined the possibility of the artificial creation of life, a concern that is at the core of Shelley’s Frankenstein, is the nemesis that is the inevitable consequence of the creators’ hubris. We now face the same problem on a huge scale. In an interview in 2009, quoted by Garrett, Venter declared, “There’s not a single aspect of human life that doesn’t have the potential to be totally transformed by these technologies in the future.” Not a single aspect! Does that mean he is promising me that I might literally live forever?
Nothing in history suggests that those who control and profit from material production can really be depended upon to devote the needed foresight, creativity, and energy to protect us from the possible negative effects of synthetic biology. In cases where there is a conflict between the immediate and the long-range consequences or between public and private good, how can that conflict be resolved? Can the state be counted on to intervene when a private motivation conflicts with public benefit, and who will intervene when the state itself threatens the safety and general welfare of its citizens? Garrett provides a frightening real-life example.
In 2011 two scientists, one from Erasmus Medical Center in Rotterdam and one from the University of Wisconsin, independently reported that they had turned a bird flu virus, H5N1, which could very occasionally be transmitted from birds to humans, causing their death in about 60 percent of cases, into a strain that could be directly passed easily between laboratory mammals. Were this virus then capable of infecting humans, a catastrophe would occur, judging from the infamous flu epidemic of 1918, which killed more than 50 million people, about 2.5 percent of the world’s population.
A special committee of the National Institutes of Health tried to prevent the inclusion of the details of the method in the subsequent publication of these experiments on the grounds that it would amount to the worldwide dissemination of a recipe for genocide. This attempt at censorship failed and the complete methods were published in the two most widely read scientific publications, Science and Nature, in 2012. Last year the Chinese produced five new H5N1-type viruses that can be spread through the air to guinea pigs, killing them.
The question that emerges from the H5N1 case is what motivates such science in the first place. There is, of course, the desire of governments to create biological weapons in pursuit of military power in what they assume (probably correctly) to be inevitable international conflict and, reciprocally, to find ways of protecting themselves against these same weapons in the hands of their international competitors.
But there is a broader and seemingly more constructive motivation. Garrett cites Drew Endy, who is on the faculty of the Bioengineering Department at Stanford, as estimating that 2 percent of the US economy at present is derived from genetic engineering and synthetic biology and that this proportion is growing at an annual rate of 12 percent. We can see the results in such genetically engineered products as corn and tomatoes and the new micro-organisms that are now being created for the detection of toxic environmental pollutants.
The vitality of this sector of the economy is reflected in the International Genetically Engineered Machine contest, in which college and high school students compete in building new life forms. (This contest started at MIT and is now organized by a separate nonprofit.) An example, created in the 2006 contest, was a bacterium that detects arsenic in water by glowing. It was created by inserting DNA sequences that code for luminescence and arsenic sensitivity into a harmless bacterium and making sure the bacteria were healthy and could reproduce. The bête machine has ceased to be a mere metaphor and become a competitive construction game for late adolescents that, in turn, might be put to horrific uses, among them new weapons.
The central issue of Garrett’s article “Biology’s Brave New World” is the risk to human health and political stability of our power to manipulate the heritable biological properties of pathogenic organisms and even of the possibility of creating new living pathogens with attendant new risks. But there is a very different domain of action of biological engineering that is of potential interest to the manipulator of genomes that, at first sight, promises to open up grand opportunities for the enhancement of human productivity. By manipulating the genomes of plants and animals we could, in principle, increase the productivity of farms and forests, of lakes, rivers, and seas, which, again in principle, would be of benefit to human existence. But as always, what is good for some is not necessarily good for all. The Principles for the Oversight of Synthetic Biology, a manifesto endorsed by 117 organizations on six continents, is introduced by a characteristic cautionary statement by Vandana Shiva:
Synthetic biology, the next wave of genetic engineering, allows seed, pesticide and oil companies to redesign life so that they can make more money from it.
While it is undoubtedly true that the entrepreneurial desire to make more money motivates much of the innovation in agriculture, as in all other fields of production in a capitalist economy, there are other goals listed by the authors of The Principles for the Oversight of Synthetic Biology and any reasonable person must be in sympathy with most of them. They include “Protect public health and worker safety,” “Protect the environment,” and “Require corporate accountability and manufacturer liability.” There will be rather more ideological divergence, even among politically liberal readers of The New York Review, on what is meant by such unconditional principles stated in the manifesto as “Guarantee the right-to-know and democratic participation” or “Require corporate accountability and manufacturer liability.” Hours of discussion will occur on what is intended by the manifesto’s statement “Protect economic and environmental justice.”
The Principles for the Oversight of Synthetic Biology gives the impression of being primarily intended as an opportunity to challenge present societies by making generalized demands that are in direct contradiction with existing economic and social structures. So, for example, Principle I, “Employ the Precautionary Principle,” demands “a moratorium on the release and commercial use of synthetic organisms, cells, or genomes until government bodies, with the full participation of the public, have developed a research agenda guided by the public interest” (my emphasis). But the research agenda of the United States Department of Agriculture is, and always has been, largely guided by the interest of the producers of agricultural products and inputs to agriculture. The voters around Manhattan, Kansas, matter more to the USDA than do the shoppers on the Upper West Side.
Then there is the matter of medical interventions at the level of the genes themselves. The manifesto states that “the use of synthetic biology to change the human genetic makeup…must be prohibited.” This is preposterous but is stated as if it were self-evident. If someone carries a mutation whose serious medical consequences could be avoided or reversed by the insertion of a normal form of the gene in question, without, at the same time, introducing other genetic defects, why should that person and future generations in the family be denied the treatment? At present such gene introductions have a long history in experimental organisms, but we have insufficient evidence of any side effects because they have not been systematically investigated. The techniques for the transfer of single genes exist. There is no reason in principle why such single-gene alterations should be unconditionally prohibited into the indefinite future.
Some of the safety principles for oversight discussed in the manifesto are indeed sensible extensions of the already existing rules for safe practice in conventional biological science involving infectious organisms, and they must be extended appropriately to the growing field of synthetic biology. These include the principle that the facilities being used must be rigorously isolated to minimize the probability of the spread of infective organisms to the surrounding community. Also, that the community, in any event, must be informed of the general nature of the enterprise and of the health risks involved. A problem here is that the “community” may extend far beyond the institutions in which enterprises take place. The manifesto asserts that those health risks and the potential environmental impact of any new organisms produced must be extensively investigated. In addition, all employees at facilities engaged in synthetic biology, including workers who are not themselves engaged in the production of the synthetic biological organisms, must be informed of the general nature of the work being carried out and be notified whenever such products are present in their immediate work environment.
The chief problem with the recommendations in The Principles for Oversight is that the public at large lacks the ability to enforce any meaningful realization of those recommendations. Near the end the authors assert:
Closely linked with the right-to-know is our essential right-to-participate in decisions about environmental and social hazards that affect our lives.
The public must have the legally enforceable right to halt dangerous applications, not just comment after decisions have been made. Governments must provide meaningful involvement throughout the entire decision-making process related to the development of synthetic biology and the products of synthetic biology, including setting the research agenda, the context and the scope of risk assessment.
The idea that governments can “provide meaningful involvement” of the public “throughout the entire decision-making process” ignores the fact that “the public” lacks the necessary technical knowledge to decide between conflicting assertions of technical experts. Government agencies like the National Science Foundation and the National Institutes of Health that support biological research have always depended entirely on recognized scientific experts to decide which research programs should be funded, precisely because the requisite technical knowledge is not possessed by the population at large. Moreover, the decision to fund such projects has been based not only on narrow technical details, but also on the broader implications for further research.
Governments exist both to protect their citizens and to promote the interests of various constituencies. What we all know, but the authors of The Principles of Oversight ignore, is that there are, alas, frequent circumstances in which these two functions are in conflict, so that the action or inaction of the state will benefit some constituencies while harming others. In understanding the resolution of those conflicts we must also take into account the obvious fact that both the elected and appointed functionaries of the state come to their jobs with a set of prejudices about whose interests are to be served. This is especially true for agricultural research when the potential risks and benefits are at the level of farm production. How much money should the state spend on agricultural research whose sole purpose is to reduce the field labor required for farming, and therefore the cost to the farmer of hired labor, even if it results in a higher cost to the consumer? The answers will be different for the congressional delegation from Iowa and the representatives of the Bronx.
An important element of The Principles for Oversight is its emphasis on “costs” that are not fiduciary but corporeal. Section III concerns risks to public health and worker safety. It insists that
adequate and effective synthetic biology oversight requires an immediate emphasis on preventing known and potential human exposures to synthetic organisms not proven safe.
Its concerns begin with workers in synthetic biology laboratories, but a consciousness of the risks in medical microbiology is already high in government organizations that regulate workers’ health and safety. It is not clear what added safeguards must be put in place for the workers in synthetic biology. The danger that they will transport potentially infective forms that have been newly created does not seem greater than for the already existent pathogenic microbes. If such added dangers are discovered they must, of course, be added to the current precautions.
In addition, The Principles of Oversight specifies that
workers should be allowed to refuse work without fear of retaliation or termination if they report safety concerns regarding the use of synthetic biology products and associated technologies.
“Without fear of retaliation” by whom? The farm owners and managers who have deliberately recruited large numbers of desperate and impoverished illegal Mexican workers, confident that very few of their recruits would dare to complain? It is hard to see how, in the absence of a specific agreement in a labor contract, an employer can be prohibited from terminating a worker who refuses to carry out an assigned legal task. Either the task itself would need to be defined by the state as illegal, or else specific conditions of work protective of workers would have to be both legally and practically enforceable. In either event the workers in the enterprise would need to be sufficiently well organized and motivated to challenge the employer. A single complainant would be unlikely to procure relief.
At the end of the discussion of public health and worker safety a passing reference is made, without any developed discussion, to the possibility of altering the human species as a whole, reminding us of Victor Frankenstein’s construction gone wrong:
Any alterations to the human genome through synthetic biology—particularly inheritable genetic changes—are too risky and fraught with ethical concerns. [My italics.]
The question of the relative risks and advantages of various programs in synthetic biology, like all such cost-benefit analyses, cannot be considered without asking, “The costs and benefits to whom?”