 By:
Susan A. Ehrlich, J.D., LL.M. (biotechnology & genomics); Judge (ret.),
Arizona Court of Appeals
Synthetic biology seemingly is an oxymoron, making artificial what is
natural, but actually it is an important new discipline with the extraordinary
promise to make better every aspect of life. But an adequate jurisdictional
and regulatory context is lacking, largely because these legal constructs were
written for known organisms, and thus arises a host of unaddressed legal
issues.
The phrase “synthetic biology” was first known to be used by the
French biologist Stéphane Leduc in 1912 to refer to the creation of artificial
life. Nearly 100 years later, in 2005, Drew Endy described “synthetic
biology” as “engineering biology” or thinking about organisms in an engineering
context, biology as information. Synthetic biology later was defined by the
Royal Academy as “aim[ing] to design and engineer biologically based parts,
novel devices and systems as well as redesigning existing, natural biological
systems” and contemporaneously defined by the Synthetic Biology Engineering
Research Center (SynBERC), of which Dr. Endy is a director, as:
… the design and construction of new biological entities such as
enzymes, genetic circuits, and cells or the redesign of existing biological
systems. … The element that distinguishes synthetic biology from traditional
molecular and cellular biology is the focus on the design and construction of
core components (parts of enzymes, genetic circuits, metabolic pathways, etc.)
that can be modeled, understood, and tuned to meet specific performance
criteria, and the assembly of these smaller parts and devices into larger
integrated systems that solve specific problems.
Advances likely will include genomes and cells that use non-natural
components such as non-standard nucleotides and non-genetically encoded amino
acids.
The lack of a singular definition reflects that “synthetic biology”
does not refer to a specific technology as much as it refers to a diversity of
enabling technologies and approaches. Researchers include not only those
engaged in what may be considered the traditional life sciences, biology and
biochemistry as examples, but chemists, materials scientists, engineers and
computer modelers or, in other words, individuals from multiple scientific and
engineering professions. Their purpose is to understand the nature of living
organisms, the organisms’ forms and functions, and to use that understanding
both to redesign natural biological systems and to design and build new
biological parts, devices and systems for improved and/or novel purposes.
The potential of synthetic biology is unlimited, but a short list of
what is underway includes:
- Helping agriculture feed a growing
world population with fewer resources by developing crops that can better
withstand environmental adversity such as drought, heat, flooding and salt;
improving the disease and pest resistance of plants; increasing the nutritional
content of food; and advancing land-management practices for efficient,
less-wasteful and sustainable use and for conservation.
- Bettering the environment by
developing biofuels from engineered microbes that convert plentiful, renewable
resources into diesel, ethanol or hydrogen; formulating alternatives to
petroleum-based products; engineering organisms to detect and eliminate
contaminants in air and water; treating wastewater; bioremediation, and
reducing trash as well as turning trash into commodities such as plastic that
itself can be recycled.
- Improving health, and providing
greater safety and security.
Amyris scientists
created microbial strains that produce artemisinic acid, a precursor of the
potent anti-malarial drug artemisinin. The company then agreed with
Sanofi-Aventis to license the technology, royalty-free, for the purpose of
manufacturing artemisinin-based drugs to treat malaria.
Adam Arkin
(University of California – Berkeley) is studying microbial inflammation in
Crohn’s Disease.
Harvey Lodish
(MIT) is researching laboratory-made red blood cells that will get rid of a
virus in the course of the cells’ natural development.
Douglas Melton
(Harvard University) is working on perfecting a process of programming stem
cells to replace the glucose-sensing and insulin-producing cells that are lost
in those who have Type 1 diabetes.
Novartis
scientists synthesized the genomes of a new strain of flu virus and within a
week determined the best design for a vaccine. If executed on a large scale, a
process of vaccine development that now takes so long that the peak of an
outbreak can pass will become timely.
Ron Weiss (MIT)
is investigating the production of organ tissues that can be used for medical
and pharmaceutical research.
Producing
morphine from yeast, thereby replacing the trade in opium poppies.
Deriving
only the beneficial ingredients from marijuana, eliminating the psychoactive
components.
Engineering
bio-responsive nano-materials for use in diagnostics and in the delivery
of drugs.
Detecting
and defending against biological and chemical threats.
The lists suggest that the growth of synthetic biology seemingly is
unequaled except by the computer industry. Not surprisingly, the business is
estimated by SynBERC to approach $16 billion by 2016.
Concomitant with the extraordinary advances and promised benefits are
the dangers posed by synthetic biology because of its dual-use potential, that
is its capability for use for malevolent as well as benevolent purposes.[1]
Those with criminal or terrorist intent can employ the advances of synthetic
biology to threaten public health, safety and security. Existing pathogens or
toxins can be modified to create novel, highly dangerous tools of terror, and
the menace is as likely, if not more likely, to come from a single individual
or a group of individuals as from a nation-state. Indeed, the increasing ease
and decreasing cost of 3-D printing could make it possible for a malefactor to
design a genetic sequence on a computer, send the plan to a 3-D “bio-printer”
loaded with nucleotides, and generate a lethal virus. The code can be hidden
in an innocuous transmission, the computer can be at a far-distant location,
and the printer can be at yet a third, remote site.
How well does the current regulatory system for biological products
address the introduction of products manufactured by synthetic biology? How
satisfactory are our legal systems in providing rules and oversight?
The United States regulatory posture is a pieced quilt of laws,
guidelines and policies, each with a different focus and span. The U.S.
approach largely is regulation by element and/or product and not by process, so
there is neither a particularly clear nor a cohesive approach, and such
authorities and procedures as exist are divided among a plethora of government
agencies, some of which have overlapping jurisdiction.
The European Union’s approach is premised
more on process than product, and the E.U. takes a precautionary attitude as
stated in “Communication from the [European] Commission on the precautionary
principle,” Communication 2000/0001 (final), a detailed document from which the
following quotations are only snippets:
The Commission considers that the Community, like
other [World Trade Organization] members, has the right to establish the level
of protection ― particularly of the environment, human, animal and plant
health ― that it deems appropriate. Applying the precautionary principle
is a key tenet of its policy … .
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Recourse to the precautionary principle presupposes
that potentially dangerous effects deriving from a phenomenon, product or
process have been identified, and that scientific evaluation does not allow the
risk to be determined with sufficient certainty.
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The Community has consistently endeavoured to achieve
a high level of protection, among others in environment and human, animal or
plant health. In most cases, measures making it possible to achieve this high
level of protection can be determined on a satisfactory scientific basis.
However, when there are reasonable grounds for concern that potential hazards
may affect the environment or human, animal or plant health, and when at the
same time the available data preclude a detailed risk evaluation, the
precautionary principle has been politically accepted as a risk management
strategy in several fields.
Additionally, while not directed at products of synthetic biology,
E.U. Regulation 428/2009 puts stringent limits on the export, trade or transfer
of a host of materials, excepting “basic scientific research” and information
already “in the public domain.” This regulation applies to technical knowledge
also.
The Biological and Toxin Weapons
Convention is pertinent howsoever a benign organism is converted into a
dangerous one. From Article 1:
Each State Party to this Convention
undertakes never in any circumstances to develop, produce, stockpile or
otherwise acquire or retain:
(1) Microbial or other biological
agents, or toxins whatever their origin or method of production, of types and
in quantities that have no justification for prophylactic, protective or other
peaceful purposes … .
Further, the International Association
Synthetic Biology and the International Gene Synthesis Consortium together
wrote codes of conduct based on customer screening, order screening, detailed
record-keeping and the maintenance of close associations with law-enforcement
agencies. The U.S. Department of Health and Human Services also has guidelines
for customer- and sequence-screening for sales of synthetic genes. In part,
these actions were responses to The Guardian journalists who in 2006
successfully ordered a segment of the smallpox genome from a DNA-synthesis
company. Earlier, researchers at the State University of New York at Stony
Brook had made a living polio virus, and other researchers had re-created the
deadly Spanish flu virus.
The various approaches, even if not
directly applied to synthetic biology, give rise to the question whether there
are organisms that should not be synthesized. Governments already have decided
that certain pathogens and toxins require a high level of security and/or should
not be shared, but in the context of synthetic biology, are there those that
should not be created? In that same context, can such organisms even be
defined? If so, as decided by whom or by what institution?
In reality, regulation is a response to risk assessment,
the identification of potential hazards or harmful outcomes, a determination of
the probability of the occurrence of the hazard and a management plan. Among
the regulatory tools are funding controls, the issuance of permits and licenses,
transfer and trade restrictions, labeling requirements, and legal guidelines
and laws.
The National Institutes of Health,
the largest funder of scientific research in the United States, and an entity
within the Department of Health and Human Services, changed its NIH
Guidelines for Research Involving Recombinant DNA Molecules to NIH
Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid
Molecules. It divided agents into categories of “risk groups”
based on a calculation of the likelihood of an agent’s “ability to cause
disease in humans and the available treatments for such disease.” Often,
compliance with the NIH Guidelines is the prerequisite for federal funding,
but the application of these Guidelines is limited as its title
suggests. Most of the other U.S. Government agencies such as the Department of
Agriculture, the Food and Drug Administration and the Environmental Protection
Agency also have regulations that arguably are applicable to categories of
synthesized organisms, but, again, each focus is particular and each scope is
narrow.
It is a common suggestion that synthesized organisms be
required to be “bar-coded” as some already are, meaning that the organism is
tagged with a unique DNA sequence. This would facilitate the tracing of an
accidental or negligent release, although the practice still would not be
employed by a criminal or terrorist.
To require that the organism must be
synthesized such that it cannot replicate outside a defined environment or that
it be unable to exchange functional genes with another organism would serve to
protect the environment should there be an unfortunate release. Monitoring
compliance is the difficulty – as is true of a bar-code requirement.
The lurking menace of regulation is the
degree to which it is not commensurate with the risk so that compliance will
unnecessarily burden investigators and stifle scientific research. In the
context of synthetic biology, however, the additional jeopardy is that of
confusion because the regulatory construct by and large addresses known
organisms, and the jurisdictional and regulatory environment is ambiguous.
One of the most problematic issues is
that of intellectual property, that is how to implement an approach that is
fair and yet reasonable in cost.
The Registry of Standard Biological Parts
is a collection of thousands of standardized “parts” called BioBricks, which
are DNA sequences with specific functions that that can be combined to build
synthetic biology devices and systems. The BioBricks Foundation sets the
standards to make these parts widely available. Elsewhere, I have suggested a
tiered system with such parts as the free library at the base. Above that, in
a closed but not limited system, the holder of the patent or license that
accompanies such “products” would establish the terms of use, starting with a
nominal fee for academic research and scaling up for a company according to the
size of and use by the company. Always the terms of use would include
regulatory compliance, and there would be an administrative overseer to monitor
compliance and arbitrate disputes. The fee would be less than what amount
could be obtained in the open market, but the benefits would be having the
products disseminated more readily because of the shared terms and therefore
more widely, and from the use of other such products for a reduced fee.
Then there is the matter of our values.
There is the organic farmer whose profits have disappeared because of the
proximity of his or her crop to synthetically modified plants, but this has to
be balanced against blanket applications of insecticide or the use of less
water and fertilizer as examples. There is the laborer whose job has vanished
because a synthetic medicinal agent, spice, herb, flavoring or fragrance has
replaced what he or she harvested, but what if the continual harvesting of that
item devastated a forest or what if the synthesized product will save or
improve lives or provide more jobs? Artemisinin provides a case on point; the
synthetic version has deprived growers of sweet wormwood of their livelihood,
but because of the quantity that can be synthesized, tens of thousands of
children will be saved from the horrors of malaria.
Synthetic biology has established itself
as a vital new discipline, offering solutions to some of the world’s most
intractable problems. Ultimately, though, it is our collective responsibility
to educate ourselves so as to ensure that these technologies are developed in a
manner consistent with our values and with our priorities as reflected in our
laws.
[1] In 2012, the United States Government issued its “Policy for
Oversight of Life Sciences Dual Use Research of Concern.” “Life sciences” was
defined to include synthetic biology. In its Policy, the U.S. Government denominated
a subset of dual-use research as dual-use research of concern (DURC), which it
defined as “research that, based on current understanding, can be reasonably
anticipated to provide knowledge, information, products, or technologies that
could be directly misapplied to pose a significant threat with broad potential
consequences to public health and safety, agricultural crops and other plants,
animals, the environment, materiel, or national security.”
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International
Judicial Monitor