Revolution in synthetic biology: prospects and risks
The Brave New World of Synthetic Biology
Laurie Garret, Biology's Brave New World ("Foreign Affairs", USA)
Translation ИноСМИ.Ru
In May 2010, the richest and most influential person in the world of biotechnology revealed another new creation to the world. John Craig Venter, together with specialists from his company, started with DNA and built a genetic sequence of nucleotides, the volume of which exceeds one million bits of information. Seven years ago, Venter became the first scientist in the world who managed to create a living being from information. One day, looking through a long string of letters representing the DNA sequence of the phi-X174 bacteriophage virus, Venter suddenly thought: "But I can collect real DNA based on this computer information." He did so by creating a virus based on the genomic code of the bacteriophage phi-X174. Later, the scientist used the same method to assemble the DNA of a larger and more complex object. Venter's group created an artificial bacterial cell by inserting artificial DNA into it, after which scientists began to observe how the organic life form synthesized by them moves, feeds, breathes and reproduces itself.
With his experiments, Venter tried to warn too forgetful humanity and showed what awaits us all. For example, in 2009, in one of his interviews, he warned: "We believe that if we activated the genome, then this very fact will probably force people to change their ideas about the living world."
Venter called his new technology "synthetic genomics", which "will appear first in the digital computer world based on digital biology, and then learn how to create new DNA modifications for very specific purposes. ... This may mean that as a person learns the laws of the existence of various forms of life, he will be able to create self-learning robotic and computing systems. ... This means the beginning of a new era of very fast learning," Venter continued. "And this is not the only aspect of human life, which, quite possibly, will completely change thanks to new technologies."
Today, some people already call Venter's work on creating new artificial bacteria "4-D printing". Let me remind you that 2-D printing is the most common printing process that begins after pressing the "Print" key on the keyboard, as a result of which the most ordinary printer gives you a printed article, etc. However, industrial companies, design bureaus and other consumers are already switching to 3–D printing - in this case, the signal is sent to devices containing all kinds of materials such as plastic, graphite and even food, and at the output we get three-dimensional products. In the case of 4-D printing, two important operations are added: self-assembly and self-reproduction. First, the idea is formalized and gets into the computer, then it is sent to a 3-D printer, and at the output we get a final product capable of copying and transforming itself. Skylar Tibbits of the Massachusetts Institute of Technology uses solid materials to create complex physical substances, which he calls "programmable materials that build themselves." Venter and several hundred other experts in the field of synthetic biology claim that 4D printing is particularly well suited for constructing living objects using the bricks that make up living objects themselves, that is, DNA.
After his team created the phi-X174 virus genome for the first time, Venter decided to thoroughly investigate the following question: how synthetic genomics will affect the national security of the country and affect the health of citizens. As the report warns, the following two problems hinder the regulation of activities in this new field of science. The first is that the cost of work in the field of synthetic biology (or "synbio") has decreased so much, and the methodology has been simplified, that now they can be carried out even by ordinary people who have not received any fundamental biological education. It is for this reason that the principles of professional ethics, professional standards and safety standards in this new field of activity will be eroded. The second problem is that the existing standards, which in the United States and other developed countries in some cases are still regulated by government agencies, are behind the times, and therefore outdated; besides, many young professionals are usually not familiar with these standards.
Venter's group came to the conclusion that as costs in the field of synthetic biology decrease, interest in this area will increase, with ethical and practical issues coming to the fore. And here the scientists' forecast turned out to be more accurate than ever. Synthetic genomics in combination with another breakthrough direction in biology – the so-called studies of neomorphic mutations (or as they are also called function acquisition mutations or GOF studies) – not only opens up a huge number of new perspectives, but at the same time it asks a lot of difficult questions and poses threats to national security. And as a result, the scientific community has already begun to discuss the problems associated with the "artificial evolution" directed by man, and meticulously study all sorts of experiments, as a result of which a person gives relatively harmless bacteria infecting properties. And at the same time, those organizations that are supposed to be engaged in preventing global bioterrorism and ensuring biosafety are somehow very far behind, they have not yet learned how to correctly classify threats and effectively deal with them.
In the United States, Congress and the executive branch are also trying to create lists of known pathogens and toxins, as well as develop measures to monitor, control and combat them. Governments of other countries and international institutions, such as the UN and the Biological Weapons Convention, have lagged even further behind them. In a word, regulatory measures are focused on the biological world of the past – and there scientists, as of old, continue to observe life from the outside, describing its elements and processes; in the course of experiments, they change the external conditions, and then see what happens. But in the new biological science, scientists themselves have the opportunity to design life and study it from the inside. Here's what Venter said about this in 2009: "It will blow your mind if you find out what results we have achieved so far."
Programming lifeSoon after everyone learned about Venter's unique experiment, the Institute of Medicine at the National Academy of Sciences gathered a group of experts who had to figure out how the new biological world would affect ethical and scientific issues, as well as the field of national security.
Andrew Ellington and Jared Ellefson from the University of Texas at Austin argue that a new generation of biologists is already taking new scientific frontiers and is beginning to look at living organisms and DNA in the same way as the high-tech magicians who created IBM, Cisco and Apple looked at microchips and transistors. In each of these two spheres there is a significant private sector and scientific potential, both spheres interact with each other, unite and transform. And now computer scientists are starting to talk about "DNA-based computing", and experts in the field of synthetic biology are already talking about "live circuit boards". Now the biologist has become an engineer who programs new life forms as he pleases.
Gerald Joyce of the Scripps Research Institute in La Jolla, California, is concerned that as the boundaries between these fields are blurring, biologists are now increasingly able to control evolution, i.e. we are witnessing the "end of Darwinism." According to Joyce, "life on Earth has demonstrated extraordinary resilience and ingenuity, being able to adapt to a wide variety of living conditions. But perhaps the most significant invention that life has come up with should be recognized as the genetic system – that's where there is truly no limit to ingenuity! And synthetic biosystems probably won't be able to achieve such a result in the near future. However, as soon as informational macromolecules have the opportunity to inherit useful mutations through self-sustaining Darwinian evolution, they can begin to generate new forms of life."
We are not exaggerating. All the key barriers to the artificial synthesis of viruses and bacteria have been overcome, at least in experiments. In 2002, scientists at the State University of New York at Stony Brook created a live polio virus based on its genetic code. And three years later, scientists, concerned about the flu pandemic, decided for research purposes to recreate the deadly Spanish flu virus (the infamous "Spanish flu" that raged in 1918), identifying key elements of viral genes, thanks to which at one time this virus killed about 50 million people in less than two years. All this has led to the fact that the problem of dual-use technologies, which first arose a century ago in chemistry, and after a while touched physics, is now facing biology.
At one time, somewhere between 1894 and 1911, the German chemist Fritz Haber (Haber) proposed a method for mass production of ammonia. This work revolutionized agriculture, as a result of which modern enterprises for the production of fertilizers appeared. But the same work of Haber helped to create chemical weapons used by the German army during the First World War – it turns out that Haber's work led to both favorable and unfavorable consequences. Three years after Haber was awarded the Nobel Prize in Chemistry [Haber received the Nobel Prize in 1918 – approx.perev.], his compatriot Albert Einstein was given the Nobel Prize for his contribution to physics. Einstein's theory of relativity and gravity, by linking mass and energy, not only helped unravel the mysteries of the universe and paved the way for the use of nuclear energy, but also led to the creation of the atomic bomb.
In a word, the problem of the so–called dual–use studies causing concern (DURC) - those very research works that can lead to both favorable and dangerous and unpredictable consequences - has long manifested itself in chemistry and physics. As a result, international treaties have emerged designed to limit those physical and chemical studies that are potentially capable of leading to adverse consequences. But biological science was very late here, and this despite the fact that the United States, the Soviet Union and many other countries continued to develop such weapons, but there were relatively few international legal restrictions in this area. So far, all this has not led to significant military consequences, since those who seek to use biological weapons have not yet learned how to quickly spread pathogenic microorganisms or use them specifically for specific purposes. But soon the situation may change.
Concerns about dual-use technologies in biology have become widespread over the past two years, since it was at this time that GOF studies began to be conducted designed to combat potential pathogens, which were first artificially created in the laboratory. On September 12, 2011, in Malta, Ron Fouchier from the Erasmus Medical Center spoke at a conference held within the framework of the European Scientific Working Group on Influenza. He announced that he had found a way to turn the H5N1 virus, which affects almost exclusively birds, into one of its varieties capable of infecting humans. As you know, according to statistics, at that time only 565 people were infected with the H5N1 virus, presumably as a result of contact with birds; 331 people (59%) died out of the total number of infected. Now let's compare: during the 1918 flu pandemic, the mortality rate was only 2.5%, which led to the deaths of more than 50 million people. Thus, it turns out that the H5N1 virus has the potential to lead to catastrophic consequences. It is good that as a result of the mutation, a kind of virus that can easily infect a person has not been formed. During a conference in Malta, Fouchier said that his group, funded by the National Institutes of Health of the United States, managed to "create a hellish modification from the H5N1 strain," i.e. to obtain from avian influenza its variety capable of infecting ferrets (human laboratory doubles). And then, Fouchier added, he did "something very, very stupid," namely, with a cotton swab, the scientist touched the nose of infected ferrets and used the collected strains of the virus to infect another group of animals; he repeated this process until it was possible to obtain a modification of H5N1 capable of infecting mammals by airborne droplets.
"This virus is very dangerous," Fouchier said in an interview with Scientific American magazine, after which he asked a rhetorical question: "Is it necessary to conduct these experiments at all?" – and he answered in the affirmative. In his opinion, such experiments can help identify the most dangerous flu strains existing in nature, and then develop a vaccine with the right characteristics and warn the world that the H5N1 virus is quite likely capable of being transmitted by airborne droplets. Shortly after Fouchier's sensational statement, a virologist from the University of Wisconsin, Yoshihiro Kawaoka, who also received funding from the US National Institutes of Health, announced that he had also conducted similar experiments and also received a strain of H5N1 avian influenza, which is capable of infecting ferrets by airborne droplets. Kawaoka very carefully modified the prototype of the H5N1 strain in order to make it less dangerous for humans. Both researchers conducted their experiments in compliance with increased safety standards in accordance with the requirements for the third level of biological safety (BSL-3). Recall that there are four levels of biological safety in total, the lowest is BSL-1, and the highest is BSL–4.
Despite the precautions, Fouchier and Kawaoka incurred the wrath of many national security specialists and health experts, who demanded an answer to the question, what could justify the deliberate creation of strains capable of causing a flu pandemic in principle? The chorus of indignant voices was also joined by one little–known advisory committee at the US National Institutes of Health, namely, the US National Scientific Advisory Commission on Biosecurity (National Science Advisory Board for Biosecurity), which held several heated meetings in 2011-12. This advisory commission was the first to try to mitigate the negative consequences of experiments with H5N1 strains and for this reason, in December 2011, banned the publication of a methodology for creating new modifications of the H5N1 virus capable of infecting mammals. The journals Science and Nature had to remove from the texts of Fouchier and Kawaoka's articles those sections that contain the practical part, because some members of the advisory commission worried that this information could serve as a reference guide for terrorists.
Michael Osterholm, a member of the advisory commission and a health expert from the University of Minnesota, expressed particular concern. He warned that a turning point has come and therefore scientists need to pause and develop strategies that guarantee that in the future such work will be carried out for the benefit of society in compliance with safety standards. "This issue really needs to be considered by many parties at the international level," Osterholm told reporters. – In fact, the flu itself is a separate big topic. Unlike influenza, many other pathogens with which experiments were conducted within the framework of the fourth biosafety level (BSL-4) did not produce infectious strains. But I do not recall that any of the pathogens could spread as quickly around the world as the flu."
Microbiologist Paul Keim from Northern Arizona University, who chaired the US National Scientific Advisory Commission on Biosafety, greatly assisted the FBI in identifying the criminal who sent letters infected with anthrax in 2001. To determine the origin of the ulcer spores placed in infected envelopes and sent to several media offices and political leaders, Keim developed new methods of gene fingerprinting. Keim agreed with Osterholm's opinion on many public safety issues. Now, after the incident with the envelopes infected with anthrax, bioterrorism causes Keim the greatest concern. "So far, we cannot say for certain that in the course of these [experiments], a means capable of destroying the world was created. Or maybe it will be created in the course of a subsequent series of experiments, from which the threat will come, " Keim told reporters. "That's exactly what the global discussion should be focused on."
Thus, the decision to prohibit the publication of the methodology for creating new modifications of the H5N1 virus, adopted in December 2011, did not solve anything, and therefore four months later the advisory commission canceled it. In 2012, Fouchier and Kawaoka managed to publish both their works uncut in the journals Science and Nature, and the temporary moratorium on experiments with the flu virus in the framework of dual-use research was eventually lifted. In early 2013, the National Institutes of Health issued a number of biosafety directives authorizing research in the field of neomorphic mutations of orthomyxoviruses, but restrictions apply only to work on the influenza virus. Osterholm, Keim and most of the ardent opponents of such experiments retreated, allowing the advisory commission to take a step back into the darkness.
A global remedy?In the past two years, the World Health Organization (WHO) has held two summits in the hope of finding a global solution to the following issue:
what to do with the open Pandora's box as a result of experiments with H5N1 strains? The biggest problem from the WHO's point of view was that scientists investigating influenza strains did not violate fragile interstate agreements on epidemiological surveillance and the exchange of information about outbreaks of epidemics – and this is a very real problem, given that the signing of the Treaty on International Health Regulations in 2005 (this treaty gives WHO the authority to in the case of an epidemic and obliges all States to monitor infectious diseases, as well as to report any outbreaks of epidemics) it took as much as fourteen years. In addition, after its ratification, this treaty was challenged by some developing countries, such as Indonesia.
Jakarta resisted the exchange of virus samples on the grounds that, in its opinion, Western pharmaceutical companies would seek to patent products derived from the provided strains and, ultimately, would make a big profit, since they would sell vaccines and medicines to underdeveloped states at inflated prices. For example, Indonesia refused to share samples of the H5N1 influenza virus found on the territory of this country. She made wild accusations against the global medical community in general, and the United States in particular. Indonesia even expelled a US negotiator dealing with this topic. Finally, a special agreement on preventive measures to prevent pandemics was worked out; this agreement was approved at the World Health Assembly (WHO's decision-making body) in 2011 and is now an integral part of the International Health Regulations (IHR). But by 2012, the number of States that managed to meet the requirements of safety regulations, monitoring and conducting scientific research did not exceed 35. Global organizations have yet to receive and enter into databases many other samples of the H5N1 virus and other dangerous pathogens. Health experts fear that a pandemic may begin long before the authorities understand which virus they need to fight.
WHO was informed that at the time of the overthrow of the Mubarak regime in early 2011, the main laboratories of the Egyptian Ministry of Health system, located in Cairo, were suddenly emptied during the riots. As a result, ampoules with strains of various microorganisms, including samples of the H5N1 virus, disappeared. And here Egypt has big problems: the country is in second place (after Indonesia) in terms of the incidence of this type of flu. At first it was assumed that the rebels had no idea about the contents of the stolen ampoules, because they only needed laboratory electronics and refrigeration equipment. However, no one can say with certainty about the future fate of vials with a strain of influenza – no one knows whether they were destroyed or not.
From the point of view of WHO, the events in Egypt have shown that biological laboratories in many countries of the world are not going to take enhanced security measures already adopted by the Dutch to ensure the safety of Fouchier's research work and the Americans in relation to Kawaoka. WHO Director-General Margaret Chen and Assistant Director-General Keiji Fukuda recalled the SARS epidemic of 2003, during which the Chinese leadership hid the facts and did not take any action for several months, after which the disease spread to 29 countries. The Chinese authorities understood that even in those countries that met all the requirements of International Health Regulations, no MSME safety regulations for working with dual-use technologies were observed at all. In most Asian countries, the very concept of biosafety was a novelty, and besides, it created confusion. Even in Europe, there were no clear guidelines regarding dual-use research, biosafety or biosecurity. European countries were more concerned about genetically modified products than about pathogens and microorganisms; Europeans were concerned about compliance with the Cartagena Protocol on Biosafety (2000), which, despite its name, does not address issues of terrorism, national security or some topics raised during the discussion on dual-use research. Instead, the Cartagena Protocol focused only on genetically modified organisms.
The first WHO summit on dual-use research, held in February 2012, prompted Fouchier and Kawaoka to convey to their colleagues all the detailed information about their experimental methods and the results obtained. Fouchier's report on mutation experiments seemed to reassure many, as the scientist admitted that he had not used synthetic biology methods; yes, he created a virus that infected laboratory ferrets, but none of them died. As a result of consultations on the H5N1 virus, which were dominated by virologists specializing in the study of influenza, scientists came to the conclusion that research in this area is not as dangerous as previously thought, and therefore the moratorium on their conduct may soon be lifted.
An exasperated Osterholm said at the New York Academy of Sciences that the United States and WHO have not yet formed clear rules for conducting DURC studies, they have not yet developed standards defining the level of safety and they do not have any program providing for the use of globally coordinated protective measures. Unlike Osterholm, many other participants in the discussion did not show such strong concern, on the contrary, they expressed the opinion that excessive fear of the risks associated with GOF studies could offset the potential benefits that public health could receive as a result of these very studies. Shortly after the meeting, they stated that when it was necessary, neither the FBI, nor the CIA, nor other special services could either identify or assess the danger of terrorism associated with the use of biological weapons, GOF research and work in the field of synthetic biology.
I believe that children are our futureThose who speak in favor of not hindering the rapidly developing research in the field of synthetic biology, such as the experiments of Drew Andy from Stanford University and Todd Kuiken from the Woodrow Wilson International Center for the Support of Scientists (the latter is one of the leaders of the growing independent international movement in the field of biology), insist that attention should be paid not only to the threats emanating from synthetic biology, but also to the emerging prospects.
According to Andy, the share of genetic engineering and synthetic biology in the US economy is already equal to two percent, and this sector is growing by 12 percent annually. The Department of Bioengineering at Stanford University, headed by him, receives half a billion dollars in budget funding annually. Andy predicts that synthetic biology will generate an economic and technological boom in the near future, just as the Internet and social media technologies did at the very beginning of this century.
Many biology students nowadays believe that genetic engineering of life forms existing in nature and creating new ones is the cutting edge of biology. At science project fairs and during experiments, students have no time to think about the essence of dual-use research, they are in too much of a hurry to get into the future. In 2004, the Massachusetts Institute of Technology launched an International Competition in Synthetic Biology (IGEM), where student teams competed in the design of new forms of life. And recently, it was decided to allow schoolchildren to participate in this competition. Last year, more than 190 applications from young researchers from 34 countries were allowed to participate in the competition. What seems to previous generations to be fiction is becoming everyday for young people.
Over the past few years, research in the field of synthetic biology has become relatively cheaper and simpler. In 2003, the first complete sequencing of human DNA was completed as part of the Human Genome project. The cost of the project amounted to several billion dollars, while thousands of scientists and technicians from more than 160 laboratories participated in the project, the duration of the project is more than ten years. And ten years later, it became possible to buy a sequencer, paying only a few thousand dollars for it, and carry out genome sequencing at home in less than 24 hours. It will take even less time for private companies to decode the genome on commercial terms, and prices for this service continue to decline, costs have fallen so much that sequencing equipment has become unprofitable to place in developed countries, and as a result, a significant part of it has been relocated to China. In huge laboratories near Beijing, Shanghai and Shenzhen, automated sequencers are now deciphering DNA with might and main, and the amount of information uploaded monthly to databases far exceeds the total amount accumulated since 1953, when J. Watson and F. Crick discovered DNA until 2003, when Venter synthesized the phi-X174 genome.
To understand what modern synthetic biology does, let's turn to an example. Here, for example, we face such a task: how to detect arsenic contained in contaminated groundwater deposits? And now imagine that it will be possible to create harmless bacteria that will begin to glow in water contaminated with arsenic – how do you like this idea? No, there are no such creatures in nature, but there are creatures that luminesce (fireflies and some types of fish). In some cases, these organisms glow only when they mate or feel threatened – these are kind of biological switches. There are also other microorganisms that can react to the presence of arsenic. In addition, there are countless harmless bacteria for humans, with which you can safely conduct experiments.
So, we need a creature with the right properties, for this you need to install a program on your laptop and, by connecting to commercial databases, find the required parts of DNA responsible for luminescence and for the reaction to arsenic. After that, the customer can only buy these harmless bacteria. Then you just have to insert the resulting code into the DNA of the bacterium, and then make sure that the bacteria are alive and able to reproduce themselves. Now all that remains is to take a bottle of water contaminated with arsenic, add some artificial bacteria there and shake it: if the water starts to glow, then arsenic has been detected. (Here we briefly described the experiments that were actually conducted by a team from the University of Edinburgh at the International Synthetic Biology Competition (IGEM) in 2006).
The most difficult part of the task is to insert DNA fragments into the sequence, but soon this task will cease to be difficult. In the field of biosynthesis, 3-D printing is increasingly used. Now scientists can load nucleotides into a 3-D "bioprinter" that generates genomes. In addition, scientific cooperation at the global level is possible. For example, one team of scientists designs a genetic sequence on a computer in one part of the globe and sends this code to a printer located somewhere else on Earth from a completely different user connected to the Internet. But the resulting code can be used both for good purposes, for example, to create a medicine or vaccine, and for criminal purposes. In the latter case, imagine that it would be possible to turn the phi-X174 virus, with which Venter worked ten years ago, into a microorganism that kills cells of the human body, or make some dangerous bacteria resistant to antibiotics, or even create a new strain of the virus.
Information, please!According to experts in the field of national security and law enforcement, who are closely watching the biological revolution, the following problem comes to the fore – information.
On the one hand, almost all the current legislation in this area, both individual countries and international, defines the legal regime of operations with pathogenic microorganisms (for example, with the Ebola virus) and monitors them, but it is almost impossible to track all the information. Information about the genetic code can be hidden wherever you want, for example, Al-Qaeda militants hid instructions for carrying out terrorist acts inside porn cassettes, and with the help of innocent tweets, you can redirect the recipient to some illegal area of the Internet where genomic codes are stored, always ready to be downloaded on a 3-D printer. It turns out that quite unexpectedly, the problem of biology has suddenly become an information security problem.
In February 2013, at the second WHO Summit on Dual-use research (DURC), about a third of scientists and government officials came from the United States. They represented at least 15 different organizations like the FBI, the Centers for Disease Control and Prevention, the Department of Defense and the Office of the U.S. Trade Representative. Although other countries were also represented at the summit, the signal sent by the Obama administration was clear and unambiguous – concern.
Each country party to the Biological Weapons Convention should empower one of its organizations, obliging it to be responsible for ensuring compliance with the provisions of the Convention. On the American side, such an organization is the FBI, which interacts with the scientific community and tries to identify dual-use research (DURC). True, the FBI's small office has shrunk somewhat as a result of recent Congressional budget cuts and sequestration. But, unlike biologists, the FBI does not have the same experience and scientific knowledge, and therefore, in practice, the FBI must rely on the opinion of scientists to exercise control – and this situation is obviously problematic.
Other countries have tried to solve the problem of controlling DURC research in other ways. For example, in Denmark there is a licensing procedure for both public and private scientific research. At the same time, before performing experiments, researchers are required to officially inform about their real goals, and government agencies must first check whether laboratories and personnel meet safety requirements, and only after that issue licenses that determine their operating mode. Some applications and licenses are classified, thereby ensuring commercial secrecy in the private sector. However, the scale of biological research in the country is very small: currently, less than 100 licenses have been issued.
With the help of the Export Control Law, the Dutch Government sought to prevent the publication of Fouchier's work on the modification of the H5N1 virus, since the information contained in this work is considered a commodity requiring a special distribution regime. Although the government lifted the publication ban after the first WHO summit, some time later the district court ruled that Fouchier's work violated EU law. However, Fouchier decided to appeal the court's decision, which will undoubtedly seriously affect the nature of the exchange of information about such studies throughout Europe. One of the conclusions that the United States has drawn for itself after the well-known leaks of information is that it may be impossible to establish reliable control over the transfer of digital information between the parties if the parties involved act decisively and inventively.
Having assessed the prospects of biological design, many biologists now refer to their work in the field of genomics as "barcoding". Just like manufacturers who put barcodes on goods in order to demonstrate the identity of the product and the price when scanning, biologists also want to sequence the genetic sequences of plants, animals, fish, birds and microorganisms existing in the world, and to match their DNA sequence to each of these creatures – we can say a unique "barcode" for this species. And then it will be possible for each synthesized organism and each organism that has undergone GOF mutations to match its own "barcode". As a result, special services and health authorities will be able to track the movement, use and creation of artificial or modified organisms. This approach is already being applied to genetically modified seeds and agricultural products, and it can be used for dual-use research (DURC) with the same success. At the same time, the right to affix barcodes should be reserved only for researchers, not potential terrorists. In general, there are no quick and simple technological solutions to this problem.
From WHO to HajjIn 2013, the summit of the World Health Organization failed to reach any significant agreements on dual-use research (DURC).
WHO, experiencing financial problems, could not find the resources to implement the recommendations developed at the summit. Worse, the summit participants were not even able to lay a common foundation for the issue under discussion, and underdeveloped countries realized that this issue is not among the priorities. In addition, African representatives complained that their countries do not have the necessary resources to implement measures to ensure biological safety. As a representative of an African country stated on condition of anonymity, "it is we who are actually suffering from all these diseases. It is we who need these studies, but we cannot conduct them. We don't have the means. We don't have the resources. And now, due to concerns about dual-use research, our people, for security reasons, cannot get into your laboratories to work there [in the United States or Europe]. Willingly or unwittingly, all these concerns about DURC research are slowing us down."
Large developing countries like Brazil, China, India and South Africa were hardly noticeable at this three-day conference. They were only interested in the question of who would grant patents for products created during DURC research, they insisted on the need for technology transfer or tediously talked about how strictly research work is controlled in their countries. In particular, the Chinese delegates assured the audience that all necessary measures have been taken in China to ensure biological safety. Two months after the meeting, a group of scientists from the Chinese National Testing Laboratory for the Detection of Avian Influenza at the Harbin Institute of Veterinary Research used GOF methods to synthesize 127 forms of influenza virus, all based on the H5N1 strain of influenza in combination with genetic attributes found in dozens of other types of influenza. The Chinese relied mainly on the works of Fouchier and Kawaoka, modifying them somewhat. Five of the artificial strains of the most dangerous type of influenza synthesized by them were able to infect guinea pigs by airborne droplets, leading to a fatal outcome.
About ten years ago, virologists from different countries sounded the alarm. They learned that American scientists decided to insert a special gene into the smallpox virus, thanks to which the solution infected with smallpox was colored green. An innovative invention of American scientists designed to detect a deadly virus has been called a "crime against humanity."
And, conversely, at the beginning of this year, when a new type of H7N9 avian influenza appeared in China, virologists began to rely on GOF studies, emphasizing their importance for public health. After studying the genetic structure of this virus, Fouchier, along with Kawaoka, declared its danger, noting that the same genetic changes they made to the H5N1 virus are already present in the H7N9 strain. In August of this year, Fouchier's group published the results of experiments that showed that the H7N9 virus is able to infect ferrets and infect animals by airborne droplets. Fouchier, Kawaoka and 20 other virologists called for a thorough series of GOF experiments with the H7N9 virus in order to synthesize a genetic variety of influenza, creating a strain from avian influenza that can infect humans by airborne droplets, and this will allow virologists to better prepare for the fight against it.
While the authorities of the relevant countries regulating such health research are discussing the request of scientists to conduct experiments with the H7N9 virus, other microorganisms are also beginning to create problems that can be solved using GOF methods. In June 2012, "Middle East respiratory syndrome" (MERS) appeared out of the blue in Saudi Arabia, and by September 2013 132 people had suffered from this virus, half of whom died. Although MERS resembles SARS (i.e. "severe acute respiratory syndrome" – SARS), much is still unknown about its origin. There have been numerous cases of human-to-human transmission of the MERS virus, especially in hospitals, and it has reached the point that the Saudi authorities have raised the alarm about the possible spread of MERS throughout the Islamic world. Note that neither a vaccine nor another cure for MERS has been found to date. If it is allowed to conduct experiments to determine the infecting effects of the H7N9 virus, then why don't scientists ask for the same permission to conduct experiments with MERS in order to study its contagious form in order to prevent its spread, say, among pilgrims during the Hajj?
When HIV appeared in the early 1980s, no one knew for sure exactly how this virus was transmitted. Many doctors believed that the 99 percent morbidity rate with a fatal outcome could be reduced if contact with infected people was completely excluded. In all US schools, students who have a positive reaction to HIV were banned from appearing, and most sports leagues banned infected athletes from playing (all this happened until NBA star Magic Johnson officially announced that he was also infected, resulting in a movement against the isolation of HIV-infected people). If it was technically possible, maybe it was necessary to modify this virus, giving it the ability to spread by airborne droplets or through accidental touch, in order to study it later?
What should I do now?Scientists and security experts are unlikely to agree on the risks associated with dual-use research (DURC) in the field of synthetic biology.
Almost thirty–five years after smallpox was eliminated, the debate is still raging - should the last of the remaining samples of this virus be destroyed or not?
What benefits can research in synthetic biology bring? It's hard to say. Supporters believe that this field of biology will transform the world like a revolution in information technology, but opponents are skeptical. Fear of possible negative consequences of DURC research will only hinder the development of science. The US authorities, for example, would have begun to weave a huge bureaucratic web, establishing regulatory and supervisory bodies – here they would undoubtedly have succeeded more than other countries, but in this case American scientific programs would have slowed down, and the most innovative research projects would have gone to other states. Unilateral actions by any Government are doomed to failure.
This means the following: politicians should not expect that from the very beginning there will be complete clarity and completeness of information; they should not hastily impose restrictions and neglect the ability of science to self-regulate. Instead, policy makers should recognize that the revolution in synthetic biology will continue, and therefore they should closely monitor it and take adequate measures to prevent the most obvious and real risks, such as accidental leakage of dangerous bioorganisms or their deliberate spread.
The first step in this direction should be the strengthening of epidemiological surveillance bodies at the national and global levels. In the United States, oversight institutions have been weakened due to budget cuts and bureaucratic problems at the federal level, as well as at the state and lower levels. It would seem that the Centers for Disease Control and the US Department of Agriculture are the first line of defense designed to protect people, plants and livestock from microbiological threats, but the costs of both these institutions have been reduced to the maximum. Since 2010, the budget of the Centers for Disease Control and Prevention has already been reduced by 25 percent, and recently it was cut by another five percent due to sequestration, including funding for the work of 50 thousand state, territorial, city and district public health inspectors. However, it costs Congress nothing to renew this funding and provide other assistance to these people who ensure the functioning of public health in the United States.
At the same time, the Centers for Disease Control and the U.S. Department of Agriculture must improve their efficiency. An era is coming when new, hitherto unknown microorganisms will appear, and therefore there is no need to limit ourselves to a small list of pathogens and poisonous organisms such as Ebola virus, anthrax, botulism, instilling a false sense of security. Now, apparently, it is no longer enough, as recently proposed, to include the H5N1 virus in the National Register of Especially Dangerous Pathogens (NSAR), which contains dangerous pathogens and toxins, now you will have to enroll ordinary bacteria such as E. coli inhabiting the intestines of every person, because it can now be turned [with the help of methods of synthetic biology – approx.perev.] into a killer bacterium that can far surpass any of the pathogenic microorganisms of the NSAR registry.
Now we are faced with the following questions: which microorganisms need to be monitored today? How to detect them? The solution of these issues will require the unification of the intellectual forces of different states and specialists in various fields. In the United States, the heads of organizations such as the Centers for Disease Control and Prevention, the FBI, the Department of Health and Human Services, the Department of Defense, together with the special services, will have to cooperate, exchanging information and experience. At the international level, multilateral groups such as WHO, food and agriculture organizations will have to interact with agencies and institutions such as Interpol, the Association of Southeast Asian Nations, the Pan American Health Organization and the African Union.
The process of signing the Biological Weapons Convention can serve as a basis for a multilateral dialogue on dual-use research (DURC). This convention is a neutral platform open to almost any State. But at present this process is in a sluggish stage, within the framework of this convention, it is not yet possible to ensure control comparable to that provided within the framework of the nuclear and chemical weapons control system. International institutions are currently facing problems and, in fact, are not able to independently resolve the issue of DURC research. For example, for the third year in a row, the World Health Organization has been facing severe budget constraints, and therefore its size and influence have decreased, as well as its epidemiological surveillance and response capabilities have decreased.
The United States and other countries cannot but be interested in establishing an effective WHO epidemiological surveillance and response system and acting in accordance with the provisions of the International Health Regulations. It is clear that American epidemiology inspectors are not welcome in all countries with open arms, unlike, say, WHO representatives. It is for this reason that Congress should directly support the WHO epidemiological surveillance and response system by allocating $100 million annually to this organization for five years. And in order to convince WHO of the reality of its intentions, Washington could make it clear to the World Health Assembly (WHO's governing body) that part of the American financial support should be directed to building an epidemiological surveillance system in developing countries that could comply with International health Regulations. If American lawmakers fear that such financial support for WHO will suddenly turn into another long-term wasteful program of financial assistance at the expense of American taxpayers, then we can propose such a plan: Washington begins funding in early 2014 and by 2019 gradually reduces the amount of payments to zero, as other donor countries increase their financial assistance, and the recipient countries will gradually be able to rely on their own strength. In addition, Congress should continue the PREDICT project launched by the US Agency for International Development. The task of the project is to identify new epidemiological threats. To date, the project has trained 1,500 people around the world, and 200 previously unknown viruses have been detected.
Any global epidemiological surveillance programs will require the development of agreed standards, since there are currently no standards on laboratory biosafety and other issues, in particular, on neomorphic mutation research (GOF) and dual-use research (DURC). To harmonize and refine standards, as well as to facilitate their dissemination, key US agencies should work closely with their foreign counterparts. The Food Code (Codex Alimentarius), adopted by the Food and Agriculture Organization of the United Nations and the World Health Organization in 1963 and regulating the global standardization of all rules in the field of food safety, can be taken as a model.
Nowadays, information about the genome can be safely transmitted without any test tubes – directly by e-mail. At the same time, it has become more difficult to define clear export boundaries and regulate it. At the heart of DURC research, the main problem is information rather than microorganisms. Excessive regulation of information flows slows down science and hinders the conduct of international research. To deal with this problem, the US Department of Commerce, the Department of Livestock and Phytosanitary Inspection (APHIS) of the US Department of Agriculture and the Office of the US Trade Representative should create an appropriate regulatory framework for regulating DURC research. When developing a regulatory model, the experience of the International Plant Protection Convention, APHIS and the Office of Services and Investments of the US Trade Representative will be useful. If we talk about the transmission of genomes over the Internet, then many nucleotide distribution centers are already monitoring "dangerous sequences", requesting information about individuals who are looking for genetic parts of pathogenic microorganisms. This area of activity should be controlled by Governments.
What should governments and other institutions be looking for? Their task is to find evidence that someone is illegally working to change biological forms of life, trying to make a dangerous microorganism out of a living being, and if such illegal research is conducted with the permission and support of the government, then the latter are considered violators of the Biological Weapons Convention. And I would not like the United States to be blamed for this, since this country is a world leader in terms of funding for fundamental science and a global locomotive that stimulates research in biology. It is necessary to legally require that data on any research in the field of biology be made public without fail. The US State Department, together with the Office of Global Policy at the Ministry of Health and Human Services, should develop information materials for diplomatic personnel that would contain answers to questions: what is synthetic biology, neomorphic mutations (GOF) and dual-use research (DURC). In this way, it will be possible to simultaneously maintain the image of the United States as an advanced center for biomedical research and remove concerns about the creation of artificial pathogens. The State Department should promote cooperation in the detection and control of DURC and prevent the global risk of unauthorized spread of synthetic pathogens; it is also necessary to support assistance programs aimed at improving the safety of laboratories in other countries and strengthening control over them.
The identification of new forms of DNA and new forms of microorganisms should be carried out immediately, both on a voluntary and mandatory basis. Private biotech companies and distributors of DNA components must label their products in a special way for biosecurity purposes. Commercial transactions with genomes should be transparent and constantly monitored; for monitoring purposes, information on nucleotide sequences should be provided. The industrial sector that constructs genomes must, at its own expense, carry out the necessary monitoring and implement standards regulating bioengineering activities, as well as in case of violation of the rules of biosafety of laboratories and other force majeure circumstances, allow state bodies to carry out inspections.
Last year, the international network of environmental organizations "Friends of the Earth", the International Center for Technology Assessment and ETC Group jointly published a report entitled "Principles of Control over Synthetic Biology". The report recommends introducing into artificial organisms (in particular, those that were obtained as a result of neomorphic mutations) genes that can lead to the self-destruction of these organisms, i.e. to implant in them parts of the genome that are activated by some change in the environment in which these organisms exist, in order to stop their functioning. Although it is technically difficult to carry out such an operation at this stage, nevertheless, in the course of DURC research, this task should still be tried to solve. The three above–mentioned organizations also called on industrial companies to independently allocate funds to cover damage and insurance when conducting research in the field of synthetic biology and creating synthetic biological products - well, quite understandable and reasonable precautions. Meanwhile, the BioBricks Foundation, being by far the most active supporter of synthetic biology, proclaims its mission as follows: "to ensure that the methods of engineering in biology are applied on the basis of the principles of openness, ethics and for the benefit of all mankind and our entire planet. . . . We believe that synthetic biology is one of the world's forces for good." Only scientific organizations like BioBricks, which observe moral principles, are able to reliably inform about the situation in synthetic biology, without keeping silent about the problems, and quickly interact with the scientific community, only such organizations have the right to speak on behalf of society, expressing its concern, and therefore their activities should be encouraged and expanded.
Four years have passed since Venter announced in 2010 that his team had created an artificial life form, calling it "the first self-reproducing biological species on the planet whose parent is a computer." During this time, contradictions and problems concerning dual-use research (DURC) have already arisen. Before Venter's group decided, imitating the Almighty, to create an artificial organism, she went to the White House for an appointment with Obama and informed the country's top officials about the political and ethical issues that arise in connection with the creation of artificial life forms. At first, the Obama administration was thinking of classifying the Venter project, concerned about the serious problems that this project could potentially lead to. But then, to Venter's delight, the White House allowed the results to be published. "There must have been some gigantic change at the philosophical level in our way of perceiving life," Venter said at a press conference in Washington, shrugging his shoulders uncertainly. But Venter had no doubt that synthetic biology, which is a "very powerful set of tools", will lead to the creation of a vaccine against influenza, and possibly against AIDS. And the day is not far off when microorganisms capable of consuming carbon dioxide and releasing energy will create a safe alternative to traditional fossil fuels. Now that synthetic biology is beginning to take root, our task is to ensure that future generations consider it a blessing rather than a curse.
Laurie Garrett, Senior Fellow, Global Health Program
at the Council on Foreign Relations (CFR).
Portal "Eternal youth" http://vechnayamolodost.ru27.11.2013