We recently announced the launch of an exciting new Challenge series with BeyondPolio, an initiative of the Jonas Salk Legacy Foundation and the investment firm Spencer Trask to help support the global eradication of polio. Though rare in the Western world today, wild polioviruses are still circulating in a few remaining countries in Asia and Africa, where more than 1,000 new cases of paralytic polio are diagnosed each year. The initial Challenge in the series Increasing the Affordability of Inactivated Poliovirus Vaccine in Low- and Middle-income Countries, seeks novel ideas to significantly reduce the cost of using IPV in countries where it is currently unaffordable. The solution to this Challenge will form the basis for a series of larger Challenges, aimed at helping to eradicate polio completely and maintain success once eradication is achieved. We asked Dr. Peter Salk, President of the Jonas Salk Legacy Foundation, to give us some background about the state of polio eradication and this Challenge series.
Hi Peter, and thank you for speaking with us today. Your Challenge aims to help close the final chapter on eradicating polio. People may be surprised to learn that polio is still a problem in some parts of the world. Can you tell us why it has been so difficult to rid the world of this disease?
Let me give you some background so that an answer to this question will make sense.
Polio has been around for a long time (an Egyptian stele from around 1400 BC shows a man with the typical signs of a leg paralyzed by polio). The disease became a huge problem in the early part of the last century when improvements in sanitation meant that children were not exposed to polioviruses while still protected by antibodies from their mothers. As a result, large scale epidemics took place, the worst of which in the U.S. occurred in 1952 when nearly 58,000 individuals -- mostly children -- were paralyzed or died.
With the development of the inactivated poliovirus vaccine (IPV), which entered use in 1955, and then the live attenuated oral poliovirus vaccine (OPV), which was initially deployed between 1959-1963, it became possible to envision eradicating polio completely. This goal is feasible since humans are the only natural hosts for polioviruses -- unlike influenza, for example, which is carried by many other animal species.
A Global Polio Eradication Initiative, spearheaded by Rotary International, WHO, the CDC and UNICEF, was undertaken beginning in 1988, relying primarily on the use of OPV, which is inexpensive and easy to administer. Since the start of that campaign, the number of cases of paralytic polio caused by wild polioviruses has fallen from approximately 350,000 cases per year around the world to fewer than 2,000 cases a year over the last decade. That’s a decrease of over 99%.
Why did you decide to post your Challenge to the InnoCentive Solver network?
The BeyondPolio program is the brainchild of Kevin Kimberlin, Chairman of Spencer Trask & Co., the investment firm that is helping carry out the BeyondPolio initiative in conjunction with the Jonas Salk Legacy Foundation. Kevin had played a major role in the HIV vaccine project my father had devoted himself to in the last years of his life, and he and my father had a close and meaningful relationship. The idea for using InnoCentive as part of the BeyondPolio initiative derived from Spencer Trask’s familiarity with InnoCentive as a result of having helped with its initial financing, and from Spencer Trask’s awareness of the track record of effectiveness of InnoCentive’s Challenge Driven Innovation programs. The InnoCentive platform appeared to be a good way to get the word out to a large number of creative and intelligent “Solvers”, and it seemed well-suited for BeyondPolio’s series of Challenges.
OK, so if the eradication program reduced the number of cases of polio in the world caused by wild polioviruses by 99%, that means there still is another 1% of the way to go. Why has it been so hard to get the job finished over the last 10 years?
There are several problems. Here’s the first. Despite enormous efforts and dedication of resources, in several countries it has been very difficult reaching all of the children that need to be immunized in order to produce an adequate level of immunity in the population to suppress the transmission of wild polioviruses from one person to another. In Afghanistan and Pakistan, for example, two of the four countries left in the world in which transmission of wild polioviruses has never been interrupted, local conditions have made it hard to reach children in areas where there is conflict or discord. In Nigeria several years ago, rumors spread that the polio immunization program was a Western plot to harm Muslim children, and many parents refused to allow their children to be immunized. As a result, not only did polioviruses continue to circulate within Nigeria, but they also spread to many of the neighboring countries in Africa where wild polioviruses had previously been eliminated. A lot of attention has been focused on restoring confidence in the program, gathering local support, and improving the effectiveness of the field teams that administer the vaccine.
And what are some of the other problems?
One of the problems that we want to address with the BeyondPolio initiative has to do with an unintended side effect of using OPV. OPV contains live polioviruses that have been “tamed”. The vaccine viruses have been weakened by genetic mutations that allow them to cause a poliovirus infection in the intestinal tract -- but not to infect the nerve cells in the brain and spinal cord that wild polioviruses can infect and kill, resulting in paralysis. However, sometimes these weakened vaccine viruses can revert to virulence. In other words, mutations can occur in the viruses when they grow in a person’s intestinal tract that restore the viruses’ ability to infect nerve cells in the brain and spinal cord. As a result, on rare occasions individuals who receive OPV can develop paralytic polio. This can also occur in close contacts of immunized individuals who become exposed to the revertant viruses -- for example, mothers who change infants’ diapers. The WHO estimates that this sort of “vaccine associated paralytic polio” occurs in around 2-4 individuals for every million children born in countries routinely using OPV. All told, WHO estimates that there are around 250-500 cases of “VAPP” in the world each year.
That seems like a lot of cases, given that there are now fewer than 2,000 cases of polio a year caused by “wild” polioviruses.
I agree. When you also consider cases of polio caused by vaccine-derived viruses that have, in addition, regained the ability to spread from person to person and cause outbreaks of their own, you end up with a figure of around a quarter of all cases of polio in the world over the last decade being caused by viruses originating in OPV. It has to be remembered that this high percentage of vaccine-related polio goes along with the overall success of the eradication program to date. Nevertheless, it would seem to me desirable to avoid these cases of vaccine-related polio -- which total somewhere around 3,500-6,500 cases since the year 2000 -- if at all possible.
What will happen, then, if the global polio eradication program finally succeeds in getting rid of the last wild polioviruses?
There’s been a lot of talk about that. Once wild polioviruses are gone, there will still be viruses around that originated in OPV, and if OPV continues to be used, then it will just introduce more vaccine viruses that could spread and cause polio. The idea now is that once eradication of wild polioviruses has been officially certified -- three years after the last case of polio caused by wild poliovirus has been observed -- routine use of OPV will be stopped everywhere.
But then what will happen with the remaining viruses from OPV?
That’s a good question, and exactly the one that we are concerned with in the BeyondPolio initiative. With luck, even if nothing else is done, the last remaining OPV-derived viruses would just die out without causing any problems. However, mathematical studies suggest there is a high probability that the vaccine-derived viruses will end up causing polio outbreaks if there are not high enough residual levels of immunity in countries where these viruses are circulating. The best way to avoid this outcome, in my mind, is to make IPV available as a substitute so that immunity levels will remain high and OPV-associated polio outbreaks can be avoided.
Are there plans for this to be done?
The major problem is that IPV is more expensive than OPV, and low- and middle-income countries do not have the resources to purchase and utilize this alternative vaccine. Many of the wealthier countries in the world have already switched from OPV to IPV in order to eliminate the risk of OPV-related polio. The costs of using IPV will need to come down if it is to be widely available to the less affluent countries.
And BeyondPolio is hoping to do something about that?
Yes, and we’re not alone. The World Health Assembly in 2008 passed a resolution requesting the Director-General of WHO to develop affordable strategies for the use of IPV in the final stages of the polio eradication program. Both the Polio Research Committee of the Global Polio Eradication Initiative and the Bill & Melinda Gates Foundation have been supporting research aimed at making IPV more affordable.
With these important organizations supporting research of this type, what do you hope to add that might be of help?
There are a lot of people in the world with experience in areas either directly associated with immunity and vaccines or in related -- or perhaps even seemingly unrelated -- fields who might have some novel approaches to suggest. We won’t know until we ask whether some of these ideas could turn out to be of real value.
And you’ve begun to ask?
That’s what this first Challenge is all about. We are asking people who are interested in helping to solve problems to take a look at what is currently being done in an attempt to reduce costs associated with IPV use and to offer ideas of their own as to whether there might be some opportunity areas for further reducing costs that have not yet been adequately explored.
So you’re not asking for specific technological suggestions at this time?
That will come next. First we want to see if there are any new areas of focus suggested that could conceivably be taken advantage of towards lowering final vaccination costs. We will then follow up on any such focus areas with additional Challenges asking for specific technological “solutions” aimed at effecting significant cost savings.
Might there be any spin-offs resulting from this Challenge program for diseases other than polio?
Absolutely. The kinds of questions we expect to be addressing could have implications for delivery of other injected vaccines. In a world confronted with many health problems, savings of any sort would result in resources being freed up to deal with other important issues.
Are there any other kinds of Challenges you have in mind related to the polio eradication effort?
We are planning to begin a second Challenge series early next year to address the question as to whether IPV might be deployed more quickly than now seems possible, even given existing price structures. It turns out that the need to supplement OPV may happen sooner than had been anticipated. The current goal of the Global Polio Eradication Initiative is to rid the world of wild polioviruses by the end of 2012. That is an ambitious goal, and it may not be possible to accomplish this difficult task that soon. If the goal were indeed to be reached that quickly, then IPV would need to be phased in by 2015 (when the eradication of wild polioviruses would be certified) in order to replace OPV and maintain population immunity. I had not mentioned this before, but there are three types of poliovirus -- types 1, 2 and 3. Both IPV and OPV have included polioviruses of all three types to insure that immunity is induced against all possible polioviruses encountered in the wild. However, the Global Polio Eradication Initiative has been so successful that no type 2 wild polioviruses have been found circulating since 1999. Since it turns out that most of the polio associated with the use of OPV is caused by the type 2 vaccine virus, there has been a call to consider whether the weakened type 2 virus should be removed from OPV altogether -- as it has been in a number of areas already. If this course of action is recommended and followed, then a more rapid introduction of IPV would be helpful in order to maintain immunity to type 2 polioviruses at least during the interim period following type 2 OPV cessation, when revertant type 2 vaccine viruses may still be circulating with the ability to cause polio outbreaks.
How would your second Challenge series be helpful?
I would like to ask for suggestions from people with knowledge of vaccination programs in particular low- and middle-income countries about the design of roadmaps for introduction of IPV in these countries that could be undertaken sooner rather than later. Again, we would not be alone in asking these questions and seeking solutions for a more rapid introduction of IPV in these countries, but I am hoping that we might come across some new ideas that could help in the overall project.
Is there any chance that BeyondPolio’s efforts might be of help in other ways even before wild polioviruses are eliminated from the world?
That depends, of course, on how quickly any practical ideas that come from our Challenges can be implemented, and on how quickly the wild poliovirus elimination phase of the eradication program is accomplished. There are some parts of the world where OPV doesn’t work as well as elsewhere -- perhaps because of the circulation of other kinds of viruses that interfere with the growth of attenuated (weakened) OPV viruses in the intestinal tract. In such areas, some children may receive multiple doses of OPV without developing adequate levels of immunity. IPV is not likely to have that problem. Also, there have been several studies suggesting that using both OPV and IPV together in some areas may be more effective than using either of the vaccines alone. Thus, depending on timing, IPV might have a role to play in the eradication program even before the OPV cessation phase.
Will BeyondPolio end up profiting from any innovations that come from its Challenges?
BeyondPolio is a designated program of the Jonas Salk Legacy Foundation, which is a charitable organization under Section 501(c)(3) of the Internal Revenue Code. Any practical outcomes of Challenges sponsored by BeyondPolio are intended for the benefit of humanity and will be made publically available.
I see from its website that the Jonas Salk Legacy Foundation was organized to preserve and extend work begun by your father. Can you explain the role of this new initiative, BeyondPolio, in relation to the Foundation?
My father began his career studying vaccines -- in particular, he wanted to see if it was possible to develop inactivated vaccines against virus diseases, since he had been told in medical school that it was not possible to do so. After working on a successful inactivated virus vaccine against influenza with his mentor, Thomas Francis, Jr., at the University of Michigan at the end of World War II, he went on to Pittsburgh to start his own laboratory in 1947. He was very soon recruited by the National Foundation for Infantile Paralysis (subsequently known as the March of Dimes) to work on polio, and he and his research team came up with an inactivated vaccine to protect against that disease that was found to be safe and effective in 1955. He then went on to found the Salk Institute for Biological Studies in La Jolla, California, in 1960, which not only is an architectural masterpiece (designed by the great American architect, Louis Kahn), but is one of the top-ranking biological research institutes in the world today. He continued his own immunological research on cancer, autoimmune disease (in particular, multiple sclerosis) and vaccines, including collaborative work to increase the potency of the inactivated poliovirus vaccine and a project to develop an inactivated vaccine against HIV/AIDS. He also thought, wrote and lectured extensively about the human condition -- humanity’s place in the scheme of things and what internal and external changes we need to undertake in face of the challenges and opportunities confronting us today. The Jonas Salk Legacy Foundation is dedicated to preserving the history of this broad career and making it accessible for scholarly and educational purposes, to finishing “unfinished scientific business”, and to extending my father’s ideas and desires for humanity in ways that he might not have been able to accomplish during his own lifetime. BeyondPolio might be considered to fall within the “unfinished business” category. Helping to complete the eradication of polio, in whatever ways the Foundation and its BeyondPolio program might contribute, would be a gift not only to his memory, but to the many thousands of people who have committed their own professional careers and volunteer efforts to this cause.
Is there anything else you’d like to share?
Just my appreciation for your interest and questions, and the hopes that something good will come of these efforts. And also my own request that anyone with some background relevant to the issues we are concerned with in these Challenges should consider becoming a Solver and contributing your own ideas that might help facilitate the successful completion of the polio eradication campaign.
Thanks Peter - and good luck with your Challenge.