Our growing ability to decode and re-encode genomes has enabled rapid responses to emerging diseases, but also potentially empowers would-be bio-terrorists. It is urgent that we develop national and international policies to regulate this dual use technology to ensure its benefits and minimize its risks.
Venture capitalists are betting on the emerging field of synthetic biology for the future to create useful products and transform our lives. In the future, it may be possible to order novel DNA sequences for fabrication of novel biological parts and organisms similar to building a customized Dell computer. Bioengineers are rewriting genetic code to create biofuels and medical treatments.
Synthetic biology builds on other biotechnologies including DNA sequencers, DNA synthesizers, PCR, and genetic engineering. When genetic engineering, a process to recombine existing genetic code from different species emerged in the early 1980s, the leaders of the field met at the Asilomar Conference to discuss how to proceed with the new technology. After adopting a voluntary code of self governance, the technology has remained harmless. Similarly, the leaders of the synbio field have debated on how to best deal with a number of social and legal issues through a series of international conferences following the proactionary principle approach.
Scientists in the field are aware of the possibility of unknown consequences from mutations and emergent properties as well as deliberate misuse. In a report financed by the Alfred P. Sloan Foundation, The Venter Institute teamed up with MIT and The Center for Strategic and International Studies to provide guidelines to proceed with issues related to synthetic biology and biological engineering, and controlling new life forms.
Despite the success of Asilomar, a number of groups collectively called The Civil Society including the ETC Group claim the participants are not objective since they have a stake in the field. The ETC Group has issued a barrage of press releases warning of the perils of synthetic biology, an extreme precautionary principle approach.
Patent Pending
While heading the private Human Genome Project, Craig Venter relied predominantly on venture capital and was expected to provide profits to shareholders and was derided by the members of the public Human Genome Project. Similarly, bioconservative groups have mounted a campaign against patenting DNA on moral and economic grounds. The economic criticisms claim patents will stifle medical research. Numerous studies and surveys among scientists investigating this claim reveal that it is not the case.
What these studies determined was that the USPTO issued broad patents and downstream rights derived from original patents on medical devices and treatments. The current infrastructure for scientific research, as determined by The Bayh-Dole Act (1980), using federal grants mandates patents on any inventions in order for society to receive benefits of a discovery.
Bioconservative groups are concerned that a patent rush will certainly take place. Because of the nature of synthetic products, they are novel and will only have to meet obvious and useful thresholds. The ETC Group has chosen Craig Venter, a leader in synbio as well, as their whipping boy for synthetic biological parts and organisms, and process patents. Of primary concern to these groups is Venter’s creation of a chassis for making synthetic organisms by knocking out the original genes and replacing them with selected novel genes to produce useful products. The ETC group compares the potential process patent to Microsoft Windows that revolutionized word processing which would create a monopoly making Venter the first trillionaire.
Fearing a monopoly on standard biological parts, these bioconservative organizations have called for openness through public databases for sharing information. Several researchers in the field have responded by creating BioBricks and The Registry of Standard Biological Parts. Other groups have created The Science Commons and Biological Innovation for Open Society (BIOS).
Too much information
Ironically, the same bioconservative organizations that called for openness in public databases now realize in some cases sharing information is not always in the best interest of public health. Due to the dual use nature of synthetic biology, the placement of genetic code of lethal pathogens in public databases compromises biosecurity.
A trend began in 2001 when Australian scientists reported in The Journal of Virology that while developing a contraceptive vaccine to control rodent populations they inserted a gene for an immune system protein into a mousepox virus. This unexpectedly made the normally mild virus lethal in mice, even those that were naturally resistant to mousepox or had been vaccinated against it. The journal received criticism for publishing the article because rogue groups may want to develop a vaccine resistant strain of poxvirus, smallpox or monkeypox.
Then in 2002, a group of researchers at SUNY led by Eckard Wimmer, a virologist, assembled a DNA template for the RNA poliovirus using a published nucleotide sequence from the internet and from customized mail order DNA sequences, 50-100 base pairs called oligonucleotides. Wimmer proved the capability for synthesizing a pathogen from its nucleotide sequence. The synthesized poliovirus caused paralysis in animals. Wimmer claimed the process was so tedious that terrorists would find it much easier to use an existing virus found in nature.
Then evolution created a controversy of a different sort, this time attempting to understand the evolution of influenza viruses. In preparation for the next pandemic, scientists are searching for answers to puzzling questions. What are its origins? Why was it so fatal? Why did some waves of the virus target healthy people while other waves target the most vulnerable; the young, elderly, and infirm? Nearly half of the victims of the 1918 pandemic were in the 20-40 age group. Why do some viruses hit at certain times of year? Why was the death rate much higher than expected? The 1918 Spanish influenza pandemic killed an estimated 50 million people.
Most people have some immunity to the 1918 virus because they have exposure to more recent strains which are partially derived from it. However, the CDC reports even with current vaccines and antiviral drugs, it is possible that a new strain of the virus could potentially kill over 100 million people.
Anticipating the next pandemic bought on by a lethal mixture of bird, pig and human influenza viruses, synthetic biologists may have provided the necessary step to stay a step ahead of these rapidly mutating pathogens. Scientists went directly to the pathogen that was so destructive during the 1918 pandemic for answers. Jeffery Taubenberger of the US Armed Forces Institute of Pathology attempted to sequence the virus, but preserved tissue samples from victims which were stored at his institute had degraded.
Fortunately, researchers were able to recover viral RNA from lung tissue samples found in an Inuit woman in northern Alaska which remained preserved in the frozen ground. In 2005, a group of scientists determined the genetic sequence of the responsible pathogen including its eight genes. The U.S. Centers for Disease Control and Prevention (CDC) used the DNA sequence to synthesize the virus in the laboratory. The synthetic virus was tested on lab animals, and in a matter of days it killed mice and chicken embryos. Although kept in a secured government facility, these bioconservative groups were outraged because of the possibility the virus could escape from the laboratory.
In a controversial move, the federal government labs placed Taubenberger’s viral sequence in an online database maintained by The National Institutes of Health. At a 1996 Bermuda gathering sponsored by the Wellcome Trust, a British charity that funds large-scale sequencing at the Sanger Centre in the U.K., scientists agreed to two principles referred to a the Bermuda rules. First, they pledged to share the results of sequencing as soon as possible, releasing all stretches of DNA longer than 1000 units. Second, they pledged to submit the data within 24 hours to the public database known as GenBank. Without government restrictions preventing open access to the sequence, this set a precedent for other deadly viral sequences becoming public.
After deliberating on covering the story the editors of Nature and Science decided to publish articles giving the details of how scientists sequenced and brought to life the lethal virus. Both publishers decided the benefits of publication outweighed the risks. According to Donald Kennedy, the former editor-in-chief of Science, Scientists need access to the research as they try to develop vaccines and antiviral medications against potential future pandemic agents. Currently, researchers are looking for properties that made the virus so lethal and comparing them to adaptive changes that have led to newer and possibly more lethal strains potentially causing future pandemics.
Who is the real enemy?
Now that scientists established a proof of principle for creating a deadly virus from genetic code, the only thing left for evildoers is a how-to manual. As synthetic biology became more in popular literature, a persistent journalist from Britain decided to investigate how easy it would be to order the biological parts necessary for creating a deadly virus.
In 2006, the science reporter with The Guardian contacted synthetic biology pioneer Drew Endy, formerly at MIT and now at Stanford, for advice on the story. In a dialogue with Endy, they discussed a partial sequence of the smallpox virus which was slightly altered for safety reasons to see what would happen. The reporter ordered the partial sequence via the internet and had it delivered to the Guardian headquarters.
In this case, the supplier was not aware the sequence coded for a destructive organism. As part of self governance, the sybio community has attempted to close the loophole by boycotting DNA synthesizing companies that do not screen their orders for sequences placed on a list determined to be public health concerns to prevent rogue groups from creating a biological weapon.
The purpose of DNA sequencing companies is to provide oligonucleotides for synbio research adding to the knowledge of basic science, namely better understanding how cells work and for commercial companies to make useful products. In another ironic twist, a British researcher responded to another Guardian article in the series declaring that the necessary tighter laws on DNA sales will hinder scientific research.
So, who is the real enemy; capitalists, nature, the media, or militarization by rogue groups? The fight card has The Civil Society against capitalists, scientists fighting nature, the National Security Agency battling rogue groups. As for the media, is the role of responsible journalism is to suppress potentially destructive information or bring the weaknesses in biosecurity a higher profile for discussion?
In my analysis, the government has chosen not to step in to prohibit such irresponsible journalism, rather permitting placing the sequence of deadly viruses in government databases. So, The Civil Society should redirect their criticisms to this government failure in order to achieve the desired results, making it harder for rogue groups to fabricate bioweapons.
On the bright side, synthetic biology is crucial in battling influenza pandemics, may soon offer an affordable and effective treatment for malaria, and synthesize enzymes used by termites to digest cellulose for use in biofuels. Synbio is also a partial cure for the current unemployment situation, creating a number of jobs in the field. Also, it will no doubt keep the members of the Civil Society busy for a while.
Links
Open letter by 38 Civil Society members
Guardian articles on biosecurity
http://www.guardian.co.uk/world/2006/jun/14/terrorism.topstories3
http://www.guardian.co.uk/science/2006/jun/14/weaponstechnology.uk
http://www.guardian.co.uk/commentisfree/2006/jun/28/comment.science
E-mail dialogue between Endy and Guardian reporter Randerson
Nature article on reconstruction of 1918 influenza virus
ETC Group precautionary principle approach to regulating synthetic biology position papers
Venter, MIT, CSIS proactionary principle approach to regulating synthetic biology position papers
IEET Blog