Publications

Synthetic biology aims to make biology easier to engineer and to program. Thanks to advances in computing power, the ability to make long tracts of DNA, new tools like CRISPR that can be used to edit genomes, and the enthusiasm of young scientists and even amateurs who want to enter the field, synthetic biology is poised to change the future of medicine, agriculture, and manufacturing. Yet, while this new field promises vast opportunities and benefits, there are also risks. There are biosecurity risks that these technologies will be deliberately used for harm; safety risks to people and the environment; ethical and social considerations for how to apply these technologies; and there are risks to the competitiveness of nations that do not invest in these technologies that are likely to spur economic growth. This volume is dedicated to a discussion of what can be done to minimize risks and maximize the benefits of synthetic biology.

On August 19, DA Henderson, leader of the successful-against-all-odds World Health Organization's global eradication campaign against smallpox, died at the age of 87. My colleagues and I at our Center will miss him very much. I wanted to reflect on some of the amazing things he did in his life and on a few of the personal characteristics that helped him contribute so much for so long.

During the past 2 years, back-to-back epidemics of Ebola and Zika have stunned even seasoned public health officials with unprecedented levels of illness and death that have been associated with these events. Both viruses, previously thought to cause only limited outbreaks, surprised the people of the world with a seemingly sudden ability to spread across multiple countries and cause illness in new, previously unthinkable ways. As we struggle to understand both the scale and impact of the Zika and Ebola crises, we are forced to once again ask: how did this happen and what can we do to prevent the next one? 

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen, first recognized in 2012, with a high case fatality risk, no vaccine, and no treatment beyond supportive care. We estimated the relative risks of death and severe disease among MERS-CoV patients in the Middle East between 2012 and 2015 for several risk factors, using Poisson regression with robust variance and a bootstrap-based expectation maximization algorithm to handle extensive missing data. Increased age and underlying comorbidity were risk factors for both death and severe disease, while cases arising in Saudi Arabia were more likely to be severe. Cases occurring later in the emergence of MERS-CoV and among health-care workers were less serious. This study represents an attempt to estimate risk factors for an emerging infectious disease using open data and to address some of the uncertainty surrounding MERS-CoV epidemiology.

The proportion of extrapulmonary tuberculosis (EPTB) cases in the United States (US) has been rising due to a slower rate of decline in EPTB compared to pulmonary tuberculosis (PTB). The purpose of this study was to characterise the clinical and treatment differences between EPTB and PTB patients, and identify patient factors associated with EPTB.

On December 2-3, 2015, the UPMC Center for Health Security hosted the second meeting of Track II biosecurity dialogue between the United States, Singapore, Malaysia, and Indonesia. The meeting took place in Kuala Lumpur, Malaysia and was co-sponsored by the Malaysian Ministry of Health (MOH). The dialogue is supported by the Project on Advanced Systems and Concepts for Countering WMD (PASCC) of the Center on Contemporary Conflict, sponsored by the US Defense Threat Reduction Agency (DTRA).

The purpose of the second meeting of the dialogue – which is the focus of this report – was to engage participants in deeper conversations around the unique biosecurity landscapes of Singapore, Malaysia, Indonesia, and the US; examine ongoing national, regional, and global biosecurity threats; identify and critique current policies and approaches to biological threat mitigation; and exchange best practices in biorisk management to strengthen responses to emerging and evolving biological threats. The dialogue featured participants representing various levels of academia, and government, including experts in the life sciences, defense, public health, animal health, journalism, medicine, terrorism, and security.

In February 2016, Wellcome Trust organized a pledge among leading scientific organizations and health agencies encouraging researchers to release data relevant to the Zika outbreak as rapidly and widely as possible [1]. This initiative echoed a September 2015 World Health Organization (WHO) consultation that assessed data sharing during the recent West Africa Ebola outbreak and called on researchers to make data publicly available during public health emergencies [2]. These statements were necessary because the traditional way of communicating research results—publication in peer-reviewed journals, often months or years after data collection—is too slow during an emergency.

A great deal of the scientific knowledge, materials and techniques required for legitimate, beneficent biological research could also be used to make a biological weapon. For instance, laboratory research conducted to uncover critical information about how a pathogen manipulates the human immune system to cause disease could be exploited to make a disease harder to treat. Yet, the aspiration to protect the life sciences from deliberate misuse is clear. As stated in the seminal National Academies of Science report, Biotechnology in an Age of Terrorism, scientists have an “affirmative moral duty to avoid contributing to the advancement of biowarfare or bioterrorism.” It is how you implement this in practice that is the real challenge. The NSABB has considered this problem, and has codified ‘Dual Use Research of Concern’ (known as DURC) as “life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel or national security.” DURC research review is now required for U.S. federally funded research with regulated pathogens; scientists are required to develop a risk mitigation plan and assess risks and benefits of the research.

This report is a compilation of the findings and recommendations discovered pursuing the Naval Postgraduate School Project on Advanced Systems and Concepts for Countering WMD (PASCC) Grant No. N00244-15-1-0028, for research entitled "Improving Security through International Biosafety Norms.” The focus of this project was the potential for a biological research laboratory accident to spark an epidemic, and become an international public health problem. We examined what norms and expectations nations should have of each other to maintain a biosafety infrastructure capable of preventing and mitigating consequences a catastrophic biocontainment failure.

This document summarizes the governmental policies and regulations for biosafety in research laboratories in the nations of Brazil, China, India, Israel, Pakistan, Kenya, Russia, Singapore, the United Kingdom, and the United States. In previous research, we found that there is a lack of international norms governing biosafety precautions for dangerous or especially contagious1; by describing a variety of biosafety governance approaches in these nations, we hoped to find areas of commonality which could be further developed into international norms.

Mosquito-borne infectious diseases such as dengue, chikungunya, and now Zika, pose a public health threat to the US, particularly Florida, the Gulf Coast states, and Hawaii. Recent autochthonous transmission of dengue and chikungunya in Florida, the recent dengue outbreak in Hawaii, and the potential for future local spread of Zika in the US, has led to the consideration of novel approaches to mosquito management. One such novel approach, the release of sterile genetically modified mosquitoes, has been proposed as a possible intervention, and a trial release of GM mosquitoes is being considered in one Florida community. However, this proposal has been controversial. The objective of this research was to increase understanding of community knowledge, attitudes, and beliefs regarding mosquito control and GM mosquitoes.

A meeting at the National Academy of Sciences (NAS) this week presents a tangible opportunity to spell out concrete steps for research that alters pathogens—and we mustn't let it pass by. We offer several approaches for moving forward.

Policy at a turning point

The NAS meeting marks a turning point in a year-and-a-half-long policy process to consider the risks, benefits, oversight, and regulation of experiments that are designed to create influenza and other viruses that are simultaneously highly virulent and readily transmissible by respiratory droplets between mammals.

On October 29, 2012, Hurricane Sandy made landfall in Brigantine, New Jersey, ravaging the mid-Atlantic region of the United States. Hurricane Sandy was the second costliest cyclone in US record-keeping history, after Hurricane Katrina of 2005, and the largest named storm on record in the Atlantic Ocean. Of the 147 deaths directly attributed to Hurricane Sandy, nearly half (n = 72) occurred in the mid-Atlantic and Northeastern United States.1 In addition to resulting in direct mortality, Hurricane Sandy had devastating impacts on the mid-Atlantic region’s health care systems, particularly hospitals.2,3 In New York City alone, to ensure safety and continuity of medical care, approximately 6300 patients were evacuated from 37 health care facilities.4 In Hurricane Sandy’s aftermath, researchers and news media questioned why hospitals that were literally adjacent and had ostensibly similar risk profiles made differing decisions about evacuation and shelter-in-place (ie, stay on-site until danger passes).

Surveillance systems in public health practice have increased in number and sophistication with advances in data collection, analysis, and communication. When the Communicable Disease Center (now the Centers for Disease Control and Prevention) was founded some 70 years ago, surveillance referred to the close observation of individuals with suspected smallpox, plague, or cholera. Alexander Langmuir, head of the Epidemiology Branch, redefined surveillance as the epidemiology-based critical factor in infectious disease control. I joined Langmuir as assistant chief in 1955 and was appointed chief of the Surveillance Section in 1961. In this paper, I describe Langmuir's redefinition of surveillance. Langmuir asserted that its proper use in public health meant the systematic reporting of infectious diseases, the analysis and epidemiologic interpretation of data, and both prompt and widespread dissemination of results. I outline the Communicable Disease Center's first surveillance systems for malaria, poliomyelitis, and influenza. I also discuss the role of surveillance in the global smallpox eradication program, emphasizing that the establishment of systematic reporting systems and prompt action based on results were critical factors of the program.

In December 2015, the Centers for Disease Control and Prevention (CDC) published a report titled “Clinical Framework and Medical Countermeasure Use During an Anthrax Mass-Casualty Incident,” which provided guidance on crisis standards of care for large-scale anthrax incidents. This report follows the 2014 CDC anthrax treatment and prevention guidelines in addressing incidents during which high demand for medical care will necessitate that healthcare providers prioritize allocation of limited resources to where they provide the most benefit.

On Monday, the World Health Organization (WHO) declared the Zika virus a public health emergency of international concern, with the potential to infect up to four million people in the Americas by year’s end. Under increasing pressure to slow the spread of the disease, the Brazilian government has stepped up its response, including mobilizing 220,000 military personnel to cities across the country.

Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative—additional investments will expand markets—but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized.

Recent developments in the ongoing West African Ebola outbreak have, according to the media, prompted doctors to “tear up” everything they know. The events in question are the “relapse” of Scottish nurse Pauline Cafferkey, Dr. Ian Crozier's battle with an Ebola-caused eye infection, and the possibility of sexual transmission of the virus long after recovery.

While these phenomena are important and perhaps not widely known, they are not unprecedented and are fully consistent with known pathophysiological principles of disease. The key to understanding why these events occur—and could have been anticipated—is the concept of “sanctuary sites.”

Biosecurity risks are an increasing concern in Southeast Asia. An outbreak of infectious disease in the region, whether the result of a deliberate attack, an accidental release, or a natural occurrence, could threaten global commerce. It could also affect the security and stability of US allies and interests along the increasingly contentious South China Sea. In addition to the persistent threat of emerging diseases, porous borders and increased terrorist activity in Southeast Asia are continuing to add to this region's biosecurity concerns. In response to the growing biosecurity risks, it is important for the United States to work with partner nations in the region to build bridges of cooperation, share information, and identify practices to manage and diminish the risks posed by biological threats.

During the past few years, there has been substantial debate concerning the risks and benefits of certain experiments with pathogens—initially motivated by two publications in 2012 that described laboratory efforts to enhance the mammalian transmissibility of the avian H5N1 influenza virus. One of these two reports was particularly noteworthy because the experiments were designed to yield new viruses with a set of properties that together might confer pandemic potential, such as high transmissibility, high pathogenicity, and resistance to commonly available countermeasures. Not all research on pathogens generates such concerns; in fact, it is only a rare experiment that might lead to the creation of a novel pathogen with pandemic potential (PPP). The term “gain?of?function” has also been used to describe this realm of research, but it refers to a much broader range of widely accepted non?controversial research techniques and goals. For that reason, we think it should not be used in this discussion and refer to this work with the more precise term of PPP.