At high school graduation parties recently, other parents were eager to quiz Jeffrey Kahn about news of the first man-made genome — the first living, reproducing creature to be born not of a natural parent but rather of a computerized plan for assembling strings of DNA.
Could scientists construct bacteria that would clean up oil, asked a parent who obviously had in mind the disastrous BP spill. Others asked about tailoring creatures to manufacture life-saving drugs.
No one asked the question that bothers Kahn, the director of the University of Minnesota’s Center for Bioethics: Could somebody forge the genome for, say, smallpox?
“No one went there,” Kahn said.
We should go there. Most of the public concern over this latest product of genetic laboratories has focused on moral questions of whether scientists were usurping the prerogative of the gods by seeking to create life from scratch. That is an important focus.
But in an age when students can tinker with DNA in their basements — assembling and breaking down the building blocks of life as if they were so many Legos — we also need more serious conversations about the risks that could arise through malicious intent or innocent accident.
Ordering up the ingredients for life
The parents at those graduation parties were reacting to the latest breakthrough in the fast-moving field of synthetic biology: Researchers at the J. Craig Venter Institute synthesized a bacterial genome to create the first man-made cell that was capable of reproducing. (MinnPost’s report is here.)
Venter Institute scientists said they used computers to design their creation and identify 1,078 specific “cassettes of DNA” they would need to build it. They then ordered the cassettes from DNA suppliers that routinely fill such orders around the world.
The suppliers draw from the four chemicals signifying DNA’s alphabet — A, C, T and G — and use micro-plumbing to connect them in the desired sequences.
Researchers use such ordered-up sequences for a wealth of legitimate projects. In Minnesota, one group is engineering bacteria to function as microprocessors which could help detect cancer and other diseases. Other Minnesota researchers have transformed bacteria and yeast molecules into tiny factories that put out the ingredients for healing drugs, nutritional supplements and cheap biofuels.
Until recently, scientists who ordered such designer DNA “all were sitting in universities or large research labs where they were subject to stringent rules,” Khan said.
But with the explosion in genetic research, even high school and college students were able to shop online and order the tools for tinkering with life.
The Guardian newspaper in the UK set off alarms in 2006 when its investigative reporters successfully ordered sections of smallpox DNA over the Internet and had them delivered to a private residence in London.
The deadly virus has existed only in laboratories since it was eradicated from the general population 30 years ago. But the DNA lineups of smallpox and many other dangerous pathogens were available in online databases.
“The DNA sample we ordered had, at our request, three small modifications to render it harmless before it was sent by post,” the Guardian reported. “The company has since conceded that it was not aware it was sending out a sequence of modified smallpox DNA.”
The report concluded, “Because this industry is so new and unregulated, companies are selling custom-made DNA without making thorough checks on the identities of the people who are placing the orders or what the sequences are.”
At Blue Heron Biotechnology, the Washington-state company that supplied most of the DNA for the Venter team, orders are screened to make sure they are from “a country that is not on a red list,” said company spokeswoman Dorene Farnham. They also are screened against a watch list from the Centers for Disease Control and Prevention to determine whether the DNA sequences carry codes for toxins and pathogens, she said.
Last fall Blue Heron and four other companies announced they’d formed a consortium to standardize such security screening. And the U.S. Department of Health and Human Services also has issued screening guidelines. [PDF]
Similar steps have been taken in Europe and to a lesser extent in China, the journal Nature reported this week.
But explosive growth of synthetic biology around the world leaves some dissatisfaction with those initial steps — especially, at the do-it-yourself research level.
To be sure, building a destructive bug from scratch would be beyond the reach of garage science right now. For the Venter breakthrough, world-class genomics experts spent $40 million and worked for years to create a single living cell. And they still are several steps short of the creation of truly artificial life that could be deployed into the world to function for good or for ill.
But Nature predicts that the construction and transplantation of whole genomes “may be routine within five years.” Meanwhile, it said, “the ability to undertake hazardous biology in the garage is already with us.”
A whole new level
Michael Osterholm, the U of M professor who is an internationally recognized expert on bioterrorism, said he was not particularly worried by the Venter creation.
A bioterrorist wouldn’t necessarily need a new genome to create bacteria that resist antibiotics or to enable a bug to slip past our immune systems. That could be done with tools that already were available.
Still, synthetic biology is taking bioterrorism concerns to “a whole new level,” Osterholm said.
“The whole discussion of synthetic biology has become so complicated, so quickly that there aren’t a lot of citizens who fully understand the implications or what it means,” Osterholm said.
If it’s that complicated, I asked him, why worry that terrorists could figure it out.
Sure Al Qaeda has tried for years to come up with tools of bioterrorism. But recent attackers in the name of jihad have seemed baffled by technology that is far less complicated. The would-be Times Square bomber bungled well-known basics of explosives this month. And the “Underpants Bomber” became something of a grim joke for his inept efforts to detonate plastic explosives on a Northwest Airlines flight in December.
“We have become so focused on a Middle Eastern-type terrorist scenario that we forget there are people all over the world who may have different reasons for doing something, reasons that don’t have anything to do with jihadist intentions,” Osterholm said.
It took some level of sophistication to deploy deadly anthrax spores in 2001 and to bomb the Alfred P. Murrah Federal Building in Oklahoma City in 1995.
Add to that record the shadowy history of computer hacking. Synthetic biology is computer driven, and therefore a potentially appealing target for clever hackers.
“In the computer world we have a lot of people who try to infect systems for reasons that vary from just seeing if they can do it, to intentionally damaging government or corporate-sponsored information systems and everything in between,” Osterholm said.
Add up the various factors, and you find justification for the urgent tones a congressional commission used in February to warn that the United States has failed to understand the nature of biological threats — including but not limited to the manipulation of genes to come up with weapons of mass destruction.
“Each of the last three Administrations has been slow to recognize and respond to the biothreat,” said a report issued by the Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism.
Now, it said: “The danger has grown to the point that we no longer have the luxury of a slow learning curve. The clock is ticking, and time is running out.”
President Obama seemed to heed that warning. In reaction to news of the Venter breakthrough, he asked [PDF] his bioethics commission to report to him within six months on the benefits and risks — including any security risks — associated with such research.
Education vs. McCarthyism in the lab
Osterholm sits one of the leading groups responsible for assessing synthetic biology as it relates to our security, the National Science Advisory Board for Biosecurity.
Oversight mechanisms already in place or in the works can address most of the concerns, the board said in a draft report [PDF] in April.
Research involving genetic engineering already is subject to guidelines issued by the National Institutes of Health and to institutional review panels at the university level. Further, the board already had proposed a framework for stepping up some oversight of related research.
But the report acknowledges worrisome gaps. As techniques for manipulating and rearranging genomes became easier and less expensive, there has been a rush of researchers from many disciplines — engineers, chemists, material scientists and others — into the work.
“Moreover, the allure of synthetic biology has attracted the private sector, students at all levels (including high school), and amateur scientists who may lack formal institutional affiliations,” it said.
Because the field is so new, “it will continue to be difficult to predict with any reasonable certainty the biological risk of a synthetic entity, especially one that bears little resemblance to natural organisms,” the report said.
For starters, the board recommended stepped up programs to educate students at all levels of synthetic biology.
The FBI already has jumped into the education campaign.
FBI agents appeared at a recent synthetic biology competition at Massachusetts Institute of Technology, The Scientist reported. The agents handed out brochures giving 56 direct phone lines to the regional offices of the Weapons of Mass Destruction Directorate. And they asked students and biologists alike to call if they spotted anything suspicious in their labs.
It remains to be seen how scientists will react.
“We don’t want to create a kind of McCarthyism in our laboratories that really dampens down some of this good research,” Osterholm said.
“What we’re trying to do is to find the triggers that don’t hold back the science but basically give us a relatively high degree of effectiveness in sensing when something nefarious is potentially underway,” he said. “That’s going to be a tough balance, and we don’t have any magic answers on it.”
Sharon Schmickle writes about national and foreign affairs and science. She can be reached at sschmickle [at] minnpost [dot] com.