Posts Tagged ‘influenza’
By: Samuel Porter, PhD
In 2012, a pair of studies were published in Nature and Science weeks apart igniting one the biggest national debates about science in recent memory. These studies demonstrated that a few mutations in the highly pathogenic H5N1 strain of influenza virus (colloquially known as “bird flu”) could enable it to be transmitted through the air to mammals. At the heart of controversy was the question of whether scientists should be creating more virulent and/or pathogenic strains of deadly viruses in the lab. This controversial research is known as “gain of function” studies.
Critics claimed that the research was too dangerous that the risk of an accidental or deliberate release of these lab strains was far greater than the scientific and public health benefits. In an attempt to respond to the growing concern over their work, the community of researchers working with these pathogens voluntarily agreed to suspend this gain of function research for 60 days to discuss new policies on conducting the research safely.
But that was not enough to satisfy critics of the research, who continued to lobby the Obama administration to take official action. On October 17, 2014 the White House Office of Science and Technology Policy (OSTP), abruptly announced a pause on all U.S. Government funding of gain of function research on influenza, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS) coronavirus until the National Science Advisory Board for Biosecurity (NSABB) could make recommendations for policy regulating the research going forward. The NSABB was formed in 2005 (in the wake of the anthrax attacks in 2001), and is composed of scientists from universities around the nation, and administrators from 14 separate agencies in the federal government. The board reports to the Secretary for Health and Human Services (HHS) and is tasked primarily with recommending policies to the relevant government entities on preventing published research in the biological sciences from negatively impacting national security and public health.
The move drew harsh criticism from researchers in the field, many of whom thought that it was too broad. They claimed it would jeopardize their ability to predict, detect, and respond to potentially emerging pandemics. In the private sector, several companies said that the order would prevent them from working on new antiviral drugs and vaccines. Furthermore, many young scientists worried that an inability to do their experiments could jeopardize their careers. In an effort to bring attention to the issue, many scientists (including the two flu researchers whose research triggered the pause) formed the group Scientists for Science, which advocates against blanket bans on research. In addition, researchers were especially upset by the recommendation of the NSABB to censor the publications resulting from the experiments due to fears that this research could have a “dual use” that would threaten national security. However, not all researchers in the field support gain of function research (the opposition group is called Cambridge Working Group) and maintain that the risks of the research outweigh benefits.
The moratorium lasted until January 9th, 2017, when the OSTP released the guidelines for funding this research in the future. The new rules are essentially the same recommendations put forth by the NSABB seven months earlier. The NSABB had concluded that these studies involving “potentially pandemic pathogens” (PPP) do indeed have important benefits to public health, but warranted additional screening prior to funding approval. It directed federal agencies to create a pre-funding review mechanism using eight criteria (including whether the pathogen is likely to cause a naturally occurring pandemic, and if there are alternative methods of answering the scientific question). The results of these reviews must be reported to the White House OSTP. Importantly, the policy was implemented in the final days of the Obama administration rather than leave it to the incoming Trump administration, who, as of this date, has yet to fill nearly any top science positions, and may not have issued guidance for months, if at all. Researchers welcomed the decision to finally lift the ban, but questioned when the projects would be allowed to resume.
What can we learn from this situation from a science policy perspective? First, we must learn not to overreact to hysteria regarding the risks of this type of research. Indeed, there are risks in performing research on potentially pandemic strains of influenza and other pathogens, as there are with other types of research. But issuing overly broad, sweeping moratoriums halting ground breaking research for years is not the answer, nor is government censorship of academic publication. While in the end, the studies were given the green light to resume, and were published without modification, there is no making up for the lost time. These studies are not machines than can simply be turned on and off on a whim without repercussions. When we delay research into learning how viruses become pandemic, we hurt our ability to detect and respond to naturally occurring outbreaks. Additionally, when American scientists are prevented from doing research that other countries are still pursuing, American leadership in the biomedical sciences is at a competitive disadvantage. (The European Academies Science Advisory Council also recently updated its recommendations for PPP research in 2015, but did not institute a moratorium.) What we learn from these studies could potentially save countless lives. Secondly, the freedom to publish without any government censorship must be valiantly defended in any and all fields, especially with a new administration with an aggressively anti-science and anti-climate stance. Lastly, the scientific community must do a better job educating the public both on the importance of these studies from a public health perspective, and on the precautions put into place to ensure that these studies are conducted safely.
In the future, there will inevitably be debates over the safety or ethics of the latest experiments in a particular field. In attempting to wade through the murky waters of a complex controversy, science policy makers should make decisions that balance public health, safety, and ethics, rather than reactionary policies like censorships and moratoriums.
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By: Kaitlyn Morabito
On October 17th, the Obama administration announced a funding pause on new gain of function (GOF) research and a voluntary moratorium of current research on Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS), and both highly pathogenic and low pathogenic influenza viruses. The re-evaluation of the potential risks and benefits of federally funded GOF research will be pioneered by the National Science Advisory Board for Biosecurity (NSABB) and National Research Council (NRC) of the National Academies. These organizations will consult with the biomedical community and are responsible for developing a new policy on “dual use of research of concern” (DURC), which includes GOF research, using a deliberate process that is expected to be decided in 2015. Formation of the new policy will determine what DURC research can be done and whether the funding pause will be lifted. Although this funding pause is limited to MERS, SARS, and influenza, this policy will have implications for many other areas of research. While a discussion on the future of DURC is merited, the funding pause has broader implications that may affect our ability to prepare for potential pandemics.
When life science research has the potential to be used for malicious as well as beneficial intentions, it may fall into the category of DURC. Although a lot of the recent debate has surrounded GOF studies involving avian flu virus transmission, the definition of DURC is wide reaching. Infectious pathogen research is a major component of DURC, with a particular focus on agents and toxins which fall into the Federal Select Agent Program, including Ebola and anthrax among others. There are seven kinds of experiments that may be considered DURC and are generally referred to as GOF research. These involve creating mutations within the pathogen, allowing it to gain a function such as increased host range or tropism, transmissibility, or ability to be disseminated. Additionally, changes to pathogens that lead to resistance to prophylactic or therapeutic agents, or make a vaccine or natural immunity less effective, are considered DURC experiments. The final categories involve enhancing vulnerability of a host population and generation of new pathogens or regeneration of previously eradicated or extinct Select Agents. These experiments are considered to be biosecurity threats since modified agents can be used for bioterrorism or accidently released. There has been a lack of open discussion between researchers and policy makers regarding DURC research and there are four major issues that need to be addressed. What dual-use research should be allowed to be done? Should the public fund this research? Who should determine which research can and cannot be done? Should the details and results of these studies be published and available to the public? While these issues are important and need to be discussed and a DURC policy developed, the moratorium on GOF research is not the solution.
The major problem with the GOF moratorium is the overall vagueness of it. There is no end date to the moratorium in which a new policy has to be decided. The initial controversy regarding avian flu transmission studies appeared over two years ago; however, prior to the funding pause, NSABB has failed to hold any scientific meetings to work on DURC policy. Although they have already organized a meeting of scientists in December, without a deadline for the funding pause, there is no motivation to determine the policy. Additionally, the definition of the types of research that fall into this category is vague; the funding pause applies to any work by which researchers could “reasonably anticipate” an increase in pathogenicity or transmission. This definition could apply to nearly any research involving passaging or mutating these viruses.
The timing of this moratorium may hinder work on pandemic preparedness particularly in the case of the recently emerged MERS coronavirus. There is currently no small animal model for the pathogenesis of MERS. Animal models that recapitulate human disease are often developed by passaging a virus through a small animal such as a mouse. However, this type of research is not allowed under the funding pause because the virus may be gaining host range or pathogenicity in the animal. Animal models allow researchers to better understand the virus as well as test treatments and vaccines. Without these models, there is a real hindrance in the development of new prophylactics and treatments, which may prevent epidemics from becoming pandemics.
Another important aspect of pandemic preparedness is surveillance of naturally occurring genetic mutations in viruses. By collecting samples from sick patients or animals and then sequencing the viruses, a researcher can monitor the spread and mutation of different viruses throughout the world. This surveillance is a powerful tool in predicting outbreaks, drug susceptibility, and determining the contents of the influenza vaccine. However, monitoring genetic changes without understanding the level of functional changes is not very informative. This surveillance needs to be used in conjunction with reverse genetics in the laboratory to determine the effects of these changes on pathogenicity, transmission, drug susceptibility, treatment, and immunization. Using laboratory data to supplement surveillance is one aspect of the relationship between surveillance and GOF research. It is also very important to have the reverse relationship with laboratory research informing surveillance. Genetic mutation in viruses is fairly noisy, with many changes having little or no effect on the virus or a detrimental effect. Determining potential mutations in the laboratory that may increase pathogenicity can help determine signals above the noise. Without the ability to supplement knowledge gained by surveillance in the laboratory, the data obtained through surveillance is insufficient to understand the potential outcomes of genetic mutation in viruses.
When talking about DURC, it is impossible for one to avoid the debate swirling around two avian flu studies (1, 2), which involved increased transmission among ferrets. In these studies, an important aspect is often overlooked. Increased transmission among ferrets decreased the pathogenicity of these viruses, with fewer ferrets dying from the transmitted virus. So while this study increased one aspect of GOF, transmission, there was a compensatory loss of function since lethality decreased. This is an important aspect of DURC. By doing these GOF experiments, researchers can also discover loss of function (LOF) mutations, which can be exploited for drug development and also better understand the potential costs of these mutations to the pathogen.
The risk of dual-use research or accidental release of these altered pathogens is real. This moratorium comes on the heals of a number of highly publicized laboratory incidents including the discovery of a vial of smallpox in an FDA laboratory and the CDC’s distribution of anthrax that had not properly been inactivated. However, the pausing of new research and cessation of current research involving these viruses, which have the potential to cause pandemics, is a bigger threat. A new policy and guidelines for DURC and oversight of research is needed, but until that has been established, researchers should be trusted to determine which DURC should be done.