Global Health Threats

Can technology help win the race against pandemic flu? This is the question that is in everyone's mind. Dr. Ajay Royyuru from IBM has a simple answer: technology might be essential! Being the IBM leading researcher of a supercomputing project named "Checkmate" that uses advanced algorithms and complex antibody libraries and tries to predict the mutations that are most likely to occur in the H5N1 virus that will make it more transmissible to humans, he believes high tech is an integral component in stopping a possible outbreak. The key, he argues, lies in determining how many mutations away is the virus from becoming more airborne. What if we could anticipate what form the virus may take before it really occurs? If we could be ahead of the curve mitigation of the virus will be a reality, from the standpoint of molecular biology.

But this isn't the only field where technology plays an essential role. When it comes to epidemiology, Dr. Dan Ford from IBM Research also believes staying ahead of the curve is at the heart of the fight. D. Ford is in charge of the STEM project that aims at developing models that will recreate what-if scenarios for the progression of the virus throughout a definite space-time frame. Which geographic regions or areas have the potential of being hit next, when might this occur... are some of the questions he looks to answer. Airports, highways and county infraestructure could all be battlegrounds where Government action may need to be enforced. His project may also be critical in determining where distribution of vaccines should be handled first. As such, it may prove invaluable to health authorities that at some point may have to face decisions on closing airports or establishing quarrantines.

Whether it is a macro approach for the prevention of a large epidemic or a microscopic one that aims at neutralizing the severity of the virus, it is clear that technology plays a leading role in any successful outcome.

In order of appearance,

Dr. James Kaufman
Dr. Joseph Jasinksi
Dr. Ajay Royyuru
Daniel Pelino
Dr. Deborah Mosca
Dr. William Roush
Dr. Andrew Leigh Brown
Dr. Nicholas Tsinoremas
Dr. Harry Orf
Dr. Alive McHardy
Pete Martinez
Dr. Daniel Ford

Much like war and famine, infectious diseases are capable of incapacitating large segments of the human population in a devastatingly short amount of time. Throughout history, outbreaks of disease such as plague and influenza have left the world reeling in their wake. Only as recently as the nineteenth century did scientists understand the nature of bacteria, viruses, and infection. Since then the research into infectious diseases has grown by leaps and bounds, but as the most recent influenza A(H1N1) pandemic has shown us, there is still a lot of ground to be covered.

With regard to influenza, it is important to understand the genetic makeup of the viruses causing the disease. Learning the origins of influenza virus strains and their subsequent evolution is necessary in curbing the spread of disease, developing vaccines and treatment, and possibly predicting the emergence of future strains and pandemics.

In 2003, a group of scientists headed by Dr. David Lipman and Dr. Steven Salzberg proposed to sequence the genomes of thousands of influenza virus isolates. Under the auspices of the National Institute of Allergy and Infectious Diseases (NIAID) in the United States, the proposal was approved. By 2005, over two hundred genomes of the influenza A virus had been sequenced, and the results were published in the scientific journal Nature. Since then, the project has continued publishing completed sequences in GenBank, a free, publicly accessible database of nucleotide sequences funded by the National Institutes of Health. Currently, in addition to the NIAID, other groups on board the project are the National Center for Biotechnology Information and the J. Craig Venter Institute. As of September 2009, a total of 4,077 isolates have been completely sequenced and available to the public.

One of the worst pandemics was the influenza pandemic of 1918, which killed an estimated fifty to one hundred million people. The effects of that pandemic are still felt today, as almost all influenza A viruses present in the world today are descended from the 1918 virus. A thorough understanding of the 1918 pandemic, therefore, is essential in understanding and predicting the spread of influenza in these times. The cause of influenza was discovered in the 1930s, when viruses were isolated from both pigs and humans. However, the isolated viruses were not what caused the 1918 pandemic. It was not until the 1990s that an exhaustive investigation into the genetic makeup of the 1918 virus was begun, as the technology and material needed to sequence the virus had not been previously available.

In 1997, Dr. Jeffrey Taubenberger, with a team of other scientists in the Armed Forces Institute of Pathology, began sequencing fragments of RNA from preserved lung tissue of a victim of the 1918 pandemic. However, Dr. Taubenberger’s team did not have enough tissue to continue sequencing the genome completely.

Help came in the form of a pathologist by the name of Johan Hultin, described by his colleagues as "the Indiana Jones of the scientific set." Digging in Brevig, Alaska, an area known to have been severely affected by the 1918 pandemic, Hultin hoped to find a body of an 1918 influenza victim that was preserved enough to be useful. His efforts did not go unrewarded. Hultin unearthed a female corpse, whom he dubbed "Lucy." The corpse had been preserved by the cold weather, and its lungs had been further insulated by body fat. Lucy was found to contain enough genetic material to complete the sequencing of the virus’s genome. After completely sequencing the 1918 influenza virus genome, Dr. Taubenberger, along with other scientists from Mount Sinai and the US Centers for Disease Control and Prevention (CDC), used this information to recreate the virus itself. Mice were infected with this resurrected virus so that scientists could observe the virus’s behaviour first-hand.

The knowledge gained from the 1918 influenza virus genome contributed to the foundation of studying subsequent influenza outbreaks. One of the most important conclusions drawn from the project was that the 1918 influenza virus was most likely a mutation of an avian influenza virus. Furthermore, current influenza strains causing disease in humans also showed links to avian influenza strains. Information from the 1918 influenza pandemic still guides researchers and health-care policymakers today.

When humans are infected by avian influenza, the symptoms they exhibit can be very severe. Although there are less than a thousand cases worldwide of human infection with the avian influenza H5N1 virus, the disease this virus causes can be very severe, even fatal. A pandemic involving this virus would be devastating, and all efforts should be made to avert such a situation. Knowledge of the avian influenza virus may help in keeping the incidence of the disease low.

A researcher with major contributions to our understanding of avian influenza is Kennedy Shortridge. He discovered the avian influenza H5N1 virus in Asia. For several decades, he served as an adviser to the World Health Organization (WHO) regarding influenza viruses. He has also done research on other infectious diseases in Asia, such as SARS. In recognition of his significant body of work, he was awarded the Prince Mahidol award in Public Health. In addition, his investigation into the behaviour of avian influenza viruses highlighted an important way of limiting the spread of disease: reforming current farming practices. Along with his colleagues in the University of Hong Kong, he continues to investigate the different mutations of H5N1 and other strains of influenza viruses.

Another noted authority and considered by his colleagues to be "the godfather of flu research" is the virologist Robert Webster. His work on the structure of influenza viruses paved the way for the manufacture of modern influenza vaccines. Today he continues to research on ways to prevent outbreaks of avian influenza, as well as to educate the general public about the spread and prevention of disease.

In 2006, the H5N1 avian influenza outbreak prompted Peter Bogner, along with scientists Ilaria Capua, David Lipman, Nacy Cox, and other experts from the scientific community, to form the Global Initiative on Sharing Avian Influenza Data (GISAID). The GISAID involves scientists from around the world collaborating on research regarding avian and other strains of influenza. Currently, the GISAID has a global database of influenza gene sequences. The GISAID also contains additional information regarding the clinical and virological aspects of influenza viruses, as well as their epidemiological characteristics. By facilitating the flow of information about influenza, the GISAID hopes to contribute to the development of vaccines and treatment of influenza.

In 2007, efforts to avert an H5N1 avian influenza pandemic were still ongoing. In line with this, several technologies were developed in order to have better organized data as well as models to help in the understanding of diseases. Of note are some programs developed by IBM as stated at the beginning of this presentation. In the spirit of easing the sharing of health information, IBM developed the Interoperable Healthcare Information Infrastructure (IHII). This software framework was designed to make it easier and faster for different organizations to collect, share, and analyze data, especially those relating to infectious diseases and epidemiology. IHII also provides support for tools such as the Spatio-Temporal Epidemiological Modeler (STEM). STEM uses several variables to simulate the spread of a certain disease. By changing the data inputted, STEM can help researchers and health care officials predict the time frame and pattern of disease spread based on current conditions. Projecting different scenarios regarding disease outbreaks may help guide scientists and policy makers in formulating treatment options and preventative measures that will provide the most benefit.

Another project focusing on pandemic research was instituted by IBM in collaboration with The Scripps Research Institute. Called "Project Checkmate," the initiative aims to study the mutations of HPAI A (H5N1) virus in order to predict possible changes and ways to limit the spread of disease. The IBM team is headed by Dr. Ajay Royyuru, and the Scripps Research Institute is represented by a team headed by Dr. Nicholas Tsinoremas. The combined team is headed by Dr. Richard Lerner.

The war against influenza A(H1N1) is a concerted effort fought on several fronts by the world’s scientists, health care organizations, and governments. Ways to minimize the impact of the disease involve research into the virus’s origins, formulation of treatment plans and vaccinations, and dissemination of information. At the forefront of this effort is the World Health Organization (WHO). Other institutions involved are the Centers for Disease Control and Prevention (CDC) in the United States and the World Influenza Centre in the National Institute of Medical Research in London. Many scientists all over the world have also contributed their efforts and knowledge toward a better understanding of this pandemic.

One of the breakthroughs in influenza A(H1N1) research came about when its genome was fully sequenced. This was done by scientists in the CDC by April 27, 2009, a little over a month since the first outbreak of illness caused by influenza A(H1N1). In May, the National Microbiology Laboratory in Canada, headed by Dr. Frank Plummer, completed genetic sequencing on an H1N1 virus from Mexico and Canada.

Other researchers investigated the origin of this new strain. Noted virologist Yi Guan, known for isolating the SARS virus, worked with fellow scientists of Andrew Rambaut and Oliver Pyrus to examine the virus’s genetic sequence for clues to its source. They found that closely related strains of the virus may have already been infecting pigs for years, and that there may have been humans infected earlier than the first reported cases in Mexico. Still others focused on finding treatment. A project termed the Influenza Antiviral Drug Search was instituted by IBM and the University of Texas Medical Branch. The Influenza Antiviral Drug Search aims to find chemical compounds effective against influenza A(H1N1). To achieve this, the project utilizes the World Community Grid, a public network used for scientific research.

Aside from treatment, developing a vaccine was also given top priority. Talks with pharmaceutical companies regarding this endeavour were spearheaded by WHO Director-General Dr. Margaret Chan. Another significant personality associated with the WHO and influenza research, Dr. Keiji Fukuda, was also involved. In the end, the following pharmaceutical companies were slated to develop and produce vaccines against the influenza A(H1N1) virus: Novartis AG, Sanofi Pasteur, CSL Limited, MedImmune, Baxter International, AstraZeneca PLC, and GlaxoSmithKline.CSL Limited, an Australian-based company, was the first to begin human clinical trials of the vaccine in July 2009. In August, Novartis, Baxter, Sanofi Pasteur, then GlaxoSmithKline followed suit. Administration of the vaccines worldwide is expected by October 2009.

From pandemic to pandemic, the lessons of history have guided us to prepare for future catastrophes. Recalling the casualties of previous disease outbreaks spurs us to prevent the same from happening again. Work on the 1918 influenza pandemic helped scientists to better understand viruses afflicting mankind today. Research on avian influenza has influenced treatment of and vaccination against other kinds of flu. The free sharing of information regarding infectious diseases, especially influenza, has quickened the progress on current studies. Each new discovery gives future scientists a jumping-off point for further knowledge. All these can be applied to the world’s current infectious disease problem.

The 2009 influenza A(H1N1) pandemic spread rapidly and, despite global efforts, could not be contained. However, through the united efforts of scientists and governments worldwide, the otherwise devastating impact of the disease was minimized. Technology and research led to a swift understanding of the virus strain. This enabled scientists to make more accurate predictions about the behaviour of the virus, come up with proper treatment guidelines, and begin work on vaccinations against the disease. Fast information dissemination worldwide regarding preventive measures may have contributed to limiting the spread of this pandemic.

Even so, the pandemic is far from over. A surge of new, more severe cases of influenza A(H1N1) make the world even more eager to see this disease stopped. Hopefully, all the hard work and knowledge contributed by people worldwide will help diminish its impact, if not help to completely eradicate this current health problem from the face of the earth.