National Security Implications of CRISPR-CAS9

JAN 29, 2016

Gene Wars: Targeted Mutations Will Spawn Unique Dangers, And Soon

Loren Thompson

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.)


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If Not Me, Then Who?

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)

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UPMC logo

July 2015

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:

  • Governance and Strategy
  • Public Health Response
  • Medical Countermeasures
  • Healthcare System Response
  • Decontamination and Remediation
  • Environmental Detection

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.

See full report

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The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate

The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate

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:

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Ebola 2014: Pandemic Preparedness Lessons Learned

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.

  • Ebola is a horrifying disease that is causing major public health, social, economic, political and security problems in West African nations. It is also an international public health threat that requires a unified international response, but as predicted in August by Dr. Tom Frieden, the Director of CDC, Ebola is not a serious public health threat to the United States.
  • The best strategy for protecting American families from Ebola is to focus efforts (spending) on West Africa, including the use of the U.S. military for what it does best: logistics, communications, transportation and organizing international relief efforts.
  • The Food and Drug Administration has demonstrated remarkable flexibility in rapidly responding to requirements for Ebola medical countermeasures (diagnostic tools, vaccines, and therapeutics). This was partially due to the fact that a lot of basic science and advance development research has been underway for a decade with funding for defense against bioterrorism. This is the dual-benefit aspect of spending on biodefense—improvements in rapid diagnostics, the ability to produce vaccines and therapeutics faster and less expensively, improved capacity for surge medical care are good for defense against bioterrorists, but also for defense against naturally-occurring diseases.
  • However, erratic funding for research and development of medical countermeasures (basic science, advance development and regulatory science) has caused serious delays in many programs critical to biodefense. Investments in medical countermeasures (MCMs) must be made years before the pandemic, not during it. MCMs are similar to sophisticated military weapon systems, they have very long lead times for development and deployment.
  • America does not have the capability to rapidly produce medical countermeasures in a crisis. Even if one of the Ebola candidates currently in testing proves to be a “silver bullet” as a vaccine or therapeutic, America does not the capacity to rapidly produce significant quantities. We need to understand that in the 21st century, America’s pharmaceutical and biotech industries are part of our defense industrial base. Today, more than 80 percent of the active pharmaceutical ingredients in prescription drugs sold in America are made in Asia. (Would we allow China to make our next-generation fighter jet?)
  • The federal government needs a single leader with authority, responsibility, and accountability for pandemic preparedness and response. Today, these three leadership issues are spread out among more than two dozen presidentially-appointed, Senate-confirmed individuals in more than dozen departments and agencies. Not one of these leaders has pandemic preparedness and response as a full time job. It is like an NFL team with 24 assistant coaches, but no head coach. Do you think this team would make it to the Super Bowl?
  • America needs significant improvements in the ability of federal, state and local governments to work in unison during any major disaster, including public health. There were many stumbles during the early response (or as they say in DC, mistakes were made). This lack of coordination could be catastrophic during a major pandemic.
  • State and local public health departments will always be the frontline of our pandemic response capabilities. Since 2008, reduced federal funding has driven a 20 percent reduction in public health personnel at the state and local level.
  • We must improve messaging. Leaders need to be open and honest with the American public. One sentence from President Obama on September 16th caused many problems with public confidence.
    • “First and foremost, I want the American people to know that our experts, here at the CDC and across our government, agree that the chances of an Ebola outbreak here in the United States are extremely low.”
    • I am sure that the people who wrote this sentence for the President knew what they meant by the word “outbreak”, but the American public did not, particularly when two weeks later Ebola came to Dallas.
    • It would have been far better for the President to say that in the 21st century, disease can come to America from the most remote corners of the world within hours; however, Ebola is not the type of disease that could rapidly spread in America.
    • It would have also been helpful for political and public health leaders in federal, state and local governments to say that there will be a learning curve as we deal with this new threat—as we saw during the SARS epidemic of 2003—a deadly contagious disease that was contained. There will likely be some mistakes, but we will admit them and take immediate action to correct them and make sure that all public health and medical personnel are informed.
    • Ron Heflin, Program Manager NASA Space Shuttle, set the example for senior government leaders to follow on February 1, 2003. During the first press conference after the breakup of the space shuttle Columbia, he said: “We wanted to meet with you and be as fair and open with you given the facts as we understand them today. We will certainly be learning more in the coming hours, days and weeks. We will tell you as much as we know, and we will be as honest we can with you and will certainly try to fill in blanks in the coming days and weeks.”

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.


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Mitigating the Risks of Synthetic Biology

A superb new paper by Dr. Gigi Kwik Gronvall.

Mitigating the Risks of Synthetic Biology

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Tracking Down Smallpox Before It Kills Anew

A brilliant idea from Ken Bernard and Ken Coleman from the op-ed page in yesterday’s WSJ.


Tracking Down Smallpox Before It Kills Anew

Do more samples of the virus lie hidden in labs? Pay scientists who find them.

Sept. 4, 2014 7:04 a.m. ET

Ebola is now the infectious disease of international concern, but many have forgotten what a massive killer smallpox once was. Before it was declared eradicated in 1977, smallpox killed as many as 300 million people in the 20th century alone—far more than all the wars of that century combined. The danger is that it could become a killer again.

In early July, the Centers for Disease Control and Prevention announced that six previously unknown vials of freeze-dried variola, the smallpox virus, had been found in a cold-storage room at a research facility in Bethesda, Md. No one at the lab, which is used by the Food and Drug Administration, was exposed or fell ill. But the virus in the sealed vials, which likely had been sitting there for more than 50 years, was still viable and potentially infectious.

We believe other vials exist in other labs, and propose a market-based solution to help ensure that something worse—either accidental or as a form of terror—doesn’t happen next time.

The recent lab discovery raises two immediate questions. One is why the smallpox vials weren’t found years ago. Even more important is the question of how many other laboratories world-wide may still have samples of this deadly virus sitting in their storage freezers. Experienced microbiologists are often compulsive collectors and many are recipients of long-neglected and uncataloged collections of samples. Passed down from an earlier generation of researchers, the samples lie disregarded like so many old textbooks sitting in a dusty library basement. Unlike books, these old sample collections can be lethal. Fortunately, their current guardians may also provide the solution to this problem.

In 1980, three years after the disease had been eradicated, the World Health Organization urged all countries to either destroy their existing smallpox lab samples or send them to two high-security labs, one at the CDC in Atlanta, and one in Moscow. But the WHO did not have the ability or authority to independently verify that every country and laboratory complied with its request. Such was the concern that in 2011 the U.S. urged the WHO to ask every country to examine its laboratories and recertify that they retained no unauthorized samples of smallpox. Many governments objected, noting that there was no reason to repeat a certification done more than 30 years ago. The latest find—in a U.S. lab, no less—argues otherwise.

While the WHO has taken a government-based approach to eliminating the samples, a way is needed to reach out directly to laboratory directors and staff scientists who could ferret out those last remaining samples. We propose that an incentive program be created to buy back any smallpox samples that may have been inadvertently overlooked. It could be set up at an international institution with WHO oversight and with government or private foundation funding.

Because a mistake resulting in a virus release could cost many lives and potentially billions of dollars, we suggest buying back all samples of variola, of any vintage or source in the world, for between, say, $25,000 or $50,000 or even $100,000 for each confirmed sample.

Whether such a program is privately or publicly funded, this would not be the first pay-for-performance scheme to spur the removal of unwanted and potentially dangerous stockpiles from around the world. Gun buyback programs are the most well known, but outdated electronics, exotic fish and reptile pets have also been targeted for what is in effect surrender by their owners for a reward. These programs are generally successful when they are well funded and focused. Ours would be both.

There is little downside to this proposal. The cost could be low, as one hopes relatively few vials will be found. The details, including funding levels, oversight, and protection from people trying to game the system could be relatively easy to work out, with the CDC, for example, having responsibility for confirming and destroying any submitted samples. It would be a win-win-win for society, the public health community and the individual or laboratory that submits a found sample.

The risk of a global pandemic resulting from an inadvertent smallpox release—or the virus’s acquisition by terrorists—is low. But recent events show that it also is not a risk to be dismissed as negligible. Let’s find the lost and forgotten smallpox samples before they find us.

Dr. Bernard, a retired Public Health Service rear admiral, was a senior director for global health security in the Clinton administration and special assistant for biodefense policy to President George W. Bush. Dr. Coleman is a microbiologist and entrepreneur.

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