Dr. Luciana Borio, Acting Chief Scientist, FDA
Dr. Luciana Borio, Acting Chief Scientist, FDA
JAN 29, 2016
Gene Wars: Targeted Mutations Will Spawn Unique Dangers, And Soon
Opinions expressed by Forbes Contributors are their own.
In 2012, scientists discovered a cheap and easy way of editing genes that determine the biological features of all living things, including humans. The method is called Crispr-Cas9, and it exploits the defenses that bacteria have evolved against viral invaders to add or subtract material from an organism’s genome. Depending on how this “editing” is done, it can permanently alter the genetic endowment of later generations. A related development called a “gene drive” bypasses the normal process of inheritance so that newly introduced traits can be quickly propagated through entire species if they reproduce rapidly.
For instance, a “germline” (heritable) mutation that leads to infertility might cause an entire species of mosquito to become extinct in a single season. Nicholas Wade of the New York Timesreports that biologists have taken to referring to this type of genetic manipulation as a “crash drive.” It is a bad sign that scientists think they need a term for genetically-induced extinction, because it indicates such outcomes have become a real possibility – whether through deliberate action or by accident. So far, all of the interesting applications of Crispr-Cas9 have occurred in labs, but the technology is spreading so fast that it is just a matter of time before some of these mutations escape into the wild.
Scientists from the U.S., Britain and China were sufficiently worried about the potentially adverse effects of the new technology to convene a conference in Washington last month that explored how Crispr-Cas9 might be regulated or restrained before it falls into the wrong hands. But it is already too late. A thousand scientific papers have been published detailing how the new approach to gene editing can be used, and the necessary materials are readily available to any postdoc in biology. The items that are not already in their labs can be ordered by mail for less money than you will probably spend at Starbucks SBUX +1.67%this month.
Some writers have referred to this as the “democratization” of gene editing since manipulation of genetic material will no longer be confined to those with deep pockets and academic connections. The next few years will undoubtedly see numerous breakthroughs as Crispr-Cas9 is employed to combat genetically-based disorders and enhance the traits of everything from food crops to laboratory rats. But the technology is so far-reaching that it could change the entire biological landscape during the next two decades, in totally unpredictable ways. Entire species could disappear, producing ripple effects across the ecosystem. Other species could see fundamental features of their genome transformed forever — including humans.
Joe Palca of National Public Radio reassured his audience in a December 28 feature that, revolutionary though the new technology may be, “most biologists aren’t interested in making designer babies or mutant species.” However, as that formulation implies, some are. History tells us that new technologies, even those as simple as barbed wire, often turn out to have unforeseen consequences. Remember all the utopian predictions about how the World Wide Web was going to transform commerce and culture in the early days after it was invented? Well it certainly managed to do that, as any Chinese hacker or ISIS recruiter will tell you.
The same will be true of Crispr-Cas9, which is spreading through the scientific community even faster than the Internet took root a generation ago. Scientists in China have already applied the technology to human embryos. Jennifer Doudna of U.C. Berkeley, one of the pioneers in the field, maintains an ever-growing list of the creatures whose genes have been altered using the new methods. Nature magazine reports Doudna was unsettled two years after her initial discoveries when she attended a scientific conclave at which a postdoc related how a virus had been engineered to alter mice for the study of lung cancer that might unwittingly have worked just as well in humans.
The point being that when so many people are working with the same technology, many of them in labs that previously had little need to worry about genetically-modified organisms escaping into the wild, it is just a matter of time before human-induced mutations begin appearing in the global ecosystem. The ecosystem is relatively resilient, but as our experience with invasive species such as kudzu demonstrates, it can be upset when genuinely new organisms appear (or old ones disappear). Unfortunately, a commenter on the arstechnica web-site probably got it right in observing that “there’s no kill switch” for reversing such impacts once an organism is introduced or removed.
And then there is the larger issue of deliberately induced changes aimed at achieving upset in the global balance of economic or political power. Anybody who has seen one of the slick propaganda videos produced by ISIS has to wonder what other technical skills its sympathizers might possess. You don’t need a lot of sophistication to engineer something highly virulent like the influenza strain that killed 50 million people in 1918 if you understand the new technology. Even well-intentioned initiatives like trying to engineer genetically-based diseases out of the human genome could have unforeseen consequences if they permanently alter the”germline” of later generations.
It appears that almost nobody in Washington, certainly not in the national security community, is paying attention to such possibilities. Scientists are excited by all the possibilities for treating diseases and enhancing traits that Crispr-Cas9 might enable, and Big Pharma has begun to invest in start-ups as it focuses on the potential for profits, but the nation’s policymakers seem oblivious to the downside that inevitably will accompany this explosion in gene editing. The scientists who met in December to discuss limits on research were on the right track, but this isn’t like earlier efforts at voluntary restraint in genetic manipulation, because the new technology is just too easy to use. Washington needs to start paying closer attention.
(I am indebted to Gregory Dahlberg of Dahlberg Strategic LLC in Washington, who encouraged me to look into the implications of Crispr-Cas9 technology. He is not responsible for any of the conclusions I have drawn.)
Dr. Lewis Rubinson talks about his experiences during the summer of 2014 at Kenema Government Hospital in Sierra Leone. The physician he replaced had been infected with Ebola and evacuated. More than 20 nurses had been infected, and 15 had died. Dr. Rubinson talks about the challenges and low-cost solutions that could have saved many lives. This film is being presented at a series of CDC-funded High Consequence Infectious Disease Response: Ebola and Other Pathogens workshops.
View video (14 minutes)
A large-scale biological attack, or campaign of attacks, against one or more US cities could lead to catastrophe, both in terms of lives lost and in economic and societal disruption. However, it is within the power of the US government to mitigate the consequences of a biological crisis through effective leadership, policy, research, and emergency response.
The anthrax attacks in 2001 galvanized government action to advance national programs in biodefense research, drug and vaccine development, medical countermeasure (MCM) stockpiling, hospital preparedness, and a range of other biosecurity and biodefense initiatives. As a result, the United States currently has a much higher level of biopreparedness than it did prior to 2001. Yet, despite the progress made since 2001, a large-scale biological attack (or the immediate threat of such an attack) against one or more American cities would require additional and extraordinary national action in short order.
This report examines a scenario in which the United States is suddenly faced with a newly emerged intentional biological threat (biothreat) that could produce catastrophic public health consequences and threaten our economy, government, and social structure. This scenario was presented to 71 biodefense, medical, public health, life science, and homeland security thought leaders who were then asked what near-term and long-term policies and programs they would recommend in response to such an emerging crisis.
Based on our analysis of expert responses, this report condenses the best ideas into an organized set of proposals for leadership in the areas of:
In other words, this report is intended to provide a Jump Start for an effective response in a time of national crisis. If the recommendations in this report are fully implemented, the effects of a biological attack on this country could be significantly reduced.
Michelle Rozo and Gigi Kwik Gronvall
Editor Mark R. Denison, Vanderbilt University Medical Center
The 1977-1978 influenza epidemic was probably not a natural event, as the genetic sequence of the virus was nearly identical to the sequences of decades-old strains. While there are several hypotheses that could explain its origin, the possibility that the 1977 epidemic resulted from a laboratory accident has recently gained popularity in discussions about the biosafety risks of gain-of-function (GOF) influenza virus research, as an argument for why this research should not be performed. There is now a moratorium in the United States on funding GOF research while the benefits and risks, including the potential for accident, are analyzed. Given the importance of this historical epidemic to ongoing policy debates, we revisit the evidence that the 1977 epidemic was not natural and examine three potential origins: a laboratory accident, a live-vaccine trial escape, or deliberate release as a biological weapon. Based on available evidence, the 1977 strain was indeed too closely matched to decades-old strains to likely be a natural occurrence. While the origin of the outbreak cannot be conclusively determined without additional evidence, there are very plausible alternatives to the laboratory accident hypothesis, diminishing the relevance of the 1977 experience to the modern GOF debate.
For full article see: http://mbio.asm.org/content/6/4/e01013-15
In late July and early August many Americans were first learning about the Ebola threat to our nation and families—and we had a lot to learn. For those of us who had read Richard Preston’s Hot Zone (Anchor, 1995), the word Ebola produced frightening images of a deadly and contagious disease that caused organs to dissolve while patients were still alive, and ended in death for more than 90 percent of those infected.
As the first patient arrived in America for treatment, these “facts” were being hyped by cable news outlets as helicopter camera crews followed an ambulance down Atlanta freeways to Emory University Hospital. (I must admit, I was one of the news junkies watching.) However, we should have all realized we had much to learn when Dr. Kent Brantly walked from the ambulance into the hospital under his own power.
We quickly learned that high-quality supportive care can significantly reduce Ebola mortality, and that certain aspects of America’s bio-response capabilities have significant deficiencies. Here is a partial list of the lessons learned from Ebola 2014. They are in no particular order, but the final one may be the most important.
Bottom line: During the past 30 years, we have seen at least a dozen newly-emerging diseases come to America each decade. As the world becomes more crowded and jet travel makes it smaller, this trend is likely to increase. We should learn the lessons from Ebola 2014 and consider it a wake-up call for pandemic preparedness.
Colonel Randall Larsen, USAF (Ret) is the national security advisor at the UPMC Center for Health Security and the former executive director of the bipartisan Congressional Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism.