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Genomics in Public Health Preparedness: Chance Favors the Prepared Mind

Categories: genomics, investigation

 triangle with dashed lines and arrows on all points- text on top point: Environment - text on left line: Why was the agent present? What made it dangerous? -text on left point: Agent-  text on right dashed line: Who was exposed? When? How? - text on right point: Host -text on bottom dashed line: Who got sick? How sick did they get?

Contagion, catastrophe, even “zombie apocalypse”— whatever the threat, an all hazards approach goes a long way toward protecting individuals and communities. But besides delivering broad-spectrum medical and technical support, the public health system has to be ready to investigate. Public health sciences help keep “better safe than sorry” from becoming “better luck next time” by building the capacity to anticipate, detect, prevent, and respond to future threats. That’s the essence of preparedness—and genomics is part of the toolkit.

Rapid advances in laboratory, information, and communication technologies in the last decade have enhanced the efficiency of public health surveillance and investigation. Pathogen genotyping has become routine; studies that used to take months or weeks can now be done in days or hours. For example, earlier this year German and Chinese scientists used new technology to sequence the 5.2-million-base-pair genome of a Shiga toxin-producing E. coli (STEC) implicated in a massive foodborne outbreak in Germany. They shared the data online and within 24 hours, researchers from around the world had identified special features of the outbreak strain. Open-access, online publishing models like PLoS Currents also aim to speed up the exchange of scientific results and ideas in areas like Influenza (launched in 2009) and Disasters (forthcoming).

New technologies can accelerate public health investigations but science supplies the rationale and the strategies. In a commentary titled Epidemic science in real time*, Harvey Fineberg (president of the Institute of Medicine) and Mary Elizabeth Wilson wrote:

“Few situations more dramatically illustrate the salience of science to policy than an epidemic. The relevant science takes place rapidly and continually, in the laboratory, clinic, and community…. What additional information could lead to a different course of action? The answer is precisely what should drive a research agenda in real time today.”

A classic model for public health research is the epidemiologic triangle, which describes interactions among host, agent, and environmental factors that cause disease in populations. Studying them together suggests opportunities for intervention. For example, in the 2009 influenza pandemic, knowledge of genetic mutations in the virus (agent), immune status of individuals (host), and conditions fostering transmission from person to person (environment) led to development of a strain-specific vaccine, targeted vaccination campaigns, and school closure policies.

Pathogen genomics has been a mainstay of public health investigations since the mid-1980’s but only recently has genomic technology become robust, fast, and cheap enough to study host genetics at the population level. An important application of human genomics is in studying extreme responses to a common exposure. For example, discovery of the CCR5 delta32 polymorphism in people with exceptional resistance to HIV infection has informed research on HIV vaccines. The multi-agency Foodborne Diseases Active Surveillance Network (FoodNet) has incorporated human genetics into an epidemiologic study of risk factors for hemolytic uremic syndrome, a severe complication of STEC infection. CDC has also collaborated with a network of clinical investigators (Pediatric Acute Lung Injury and Sepsis Investigators (PALISI)) in a study of severe influenza illness in previously healthy children, collecting genetic and other biomarker information along with clinical data.

 Key research opportunities may be overlooked during public health investigations because of perceived conflict between immediate and longer-term public health objectives. Clearly, controlling immediate threats to health comes first and already-vulnerable people must be protected from unnecessary research risks. Research protocols have to be adapted to the context and Institutional Review Boards (IRBs), which review the ethics of proposed health research at academic centers and public health agencies, have to be capable of rapid response. Events like the response to the World Trade Center attack of September 2001 and the outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003 have highlighted the importance of preparedness for scientific investigations in emergency settings. Last year, researchers at the University of Toronto, Canada—one of the cities hardest hit by SARS—published A framework for research ethics review during public emergencies. The World Health Organization has also published a consultation on Research Ethics in International Epidemic Response.

Some threats, like hurricanes, are “known unknowns”: although they can’t be prevented, systems now in place, like increasingly sophisticated forecasts and detailed evacuation plans, can help mitigate their impact. Other threats are “unknown unknowns”—largely unanticipated events or conditions that are recognized only as they unfold, like the SARS outbreak in 2003 or last summer’s Gulf oil spill. Controlling such threats requires more than men and materiel: it requires prepared minds.   

 “In the field of observation, chance favors the prepared mind.”
–Louis Pasteur, 1854

* Note: this article is available online with free registration:
   Fineberg HV, Wilson ME. Epidemic science in real time. Science. 2009   May 22;324:987.

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