Santa Clara University

STS Nexus

The Agilent Technologies Foundation Health Award

Health Award


Craig Stephens

Introduction

                Good health is intimately tied to the physical, mental, and spiritual well-being of mankind. Lacking a healthy populace, societies cannot reach their full potential; poverty and strife, though, make decent health care a distant dream for much of humanity. Can science and technology offer a ray of hope for the the health problems of  the world’s poor?  Innovative (and often expensive) technology has had a significant mpact on health care in wealthy nations; to what extent can innovative and inexpensive technology compensate for the lack of health care resources in developing countries? One of The Tech Museum Awards is dedicated to human health. Choosing Laureates from the wide ranging applications is a tricky, somewhat subjective job.  How does one compare an advanced imaging technology for cancer detection with a clever well-drilling technique for accessing clean water in an African village? The judging panel’s task was to try to identify the most innovative, useful, and beneficial technologies, regardless of complexity. An attractive project had to involve a reasonably novel design or application of technology, be highly functional in its context, and have a demonstrable impact on as many people as possible.

                The 2005 Agilent Technologies Foundation Health Laureates were chosen from the strongest applicant pool seen in the five years of the Tech Awards, with 57 applications from 19 countries. Many applications were eminently worthy of recognition––indeed, we hope to see some applications again as projects mature—but only five could be chosen as this year’s Laureates. A Cuban/Canadian collaboration led by Dr. Vicente Verez-Bencomo of the University of Havana developed an economical synthetic polysaccharide vaccine for Haemophilus influenza type B (Hib), a major cause of pediatric meningitis and pneumonia. OraSure Technologies developed a simple, rapid test for HIV infection that encourages more people to be tested for the virus, and thus could help slow the spread of AIDS. Partners in Health created a practical electronic medical records system that is improving treatment of AIDS and tuberculosis patients at clinics in the Caribbean and Latin America. Project Impact engineered high quality, low cost digital hearing aids and intraocular lenses for cataract surgery. And finally, Professor Joshua Silver of Oxford University invented self-adjustable lenses for inexpensive spectacles that could dramatically improve vision for millions of people in poor regions with little or no access to eye care.

Hib Vaccine Team, Havana, Cuba/Montreal, QC, Canada

                Vaccines are the unsung heroes of modern medicine, saving untold millions of lives each year, and billions of dollars that would otherwise be devoted to treating infectious diseases. The bacterium Haemophilus influenza type B (Hib), for example, causes invasive diseases in humans that include meningitis and pneumonia. Prior to 1990, Hib infections were the leading cause of bacterial meningitis for much of the world. Vaccines targeting Hib were introduced in the U.S. around 1990, and since then the efficacy and widespread use of these vaccines have virtually eliminated childhood mortality attributable to Hib in the U.S. and other industrialized nations. But current Hib vaccines are relatively expensive, and as a result they have not achieved global coverage. Consequently, Hib still causes as many as 600,000 childhood deaths annually around the world.

Hib uses a polysaccharide capsule (a sugar-based coat around the cell) to help protect itself from our body’s defenses systems. “Type B” actually refers to a specific sugar structure in the capsule; other strains of H. influenzae have slightly different polysaccharide structures in their capsule. Vaccines that help the immune system to quickly recognize the Hib capsule are extremely effective in preventing the disease. These vaccines are made from polysaccharides purified directly from Hib grown in laboratory cultures. Since pure polysaccharides turn out to not be great at stimulating the immune system, they are subsequently linked (“conjugated”) to a carrier protein to make them more effective. Conjugate vaccines based on antigens purified from bacteria have some potential pitfalls—batch-to-batch variation and contaminating molecules present major challenges for quality control, and preparing antigens this way tends to be expensive.

                Recognizing these potential problems, Dr. Vicente Verez-Bencomo of the University of Havana set out to develop an Hib vaccine based on synthetic polysaccharides. This turned out to be an arduous task that took over a decade to come to fruition. The polysaccharide structure is complex, and synthesizing it in sufficient scale and purity for commercial vaccine production was accomplished in collaboration with Dr. Rene Roy of the University of Ottawa (now at Universite du Quebec a Montreal). A suitable synthesis procedure was eventually developed, after which conjugation strategies were investigated, and candidate conjugate vaccines were tested in animals. The project culminated with years of clinical trials in adults and children demonstrating the safety and efficacy of the synthetic Hib vaccine. Following approval by the Cuban health ministry, over one million doses of “QuimiHib” (the trade name of the product) have now been safely delivered through the Cuban health system, innoculating virtually every child born in Cuba in 2004. Not a single case of Hib-caused invasive disease has been detected in the vaccinated population to date. Approval of QuimiHib by the WHO and U.N. agencies for purchasing by international vaccination programs, which could happen this year, would expand the market considerably outside of Cuba.

                QuimiHib is the first synthetic polysaccharide vaccine in commercial production. It thus serves as a “proof of principle” for the manufacturing and efficacy of such vaccines. Surface polysaccharides are important antigens in many pathogens, and the focus of many vaccine efforts. The success of QuimiHib should stimulate efforts to generate synthetic vaccines for other diseases. On a cautionary note, it remains to be seen how much QuimiHib realizes (theoretical) cost advantages over alternative Hib vaccines. Manufacturing costs and/or the ultimate per dose cost of the vaccine used in Cuba have not been disclosed. One can anticipate that it will be very competitive with existing Hib vaccines, since the Cuban authorities are sufficiently confident of international demand to have invested in dedicated GMP manufacturing facilities for large scale production of QuimiHib.

                The success of the Cuban biotechnology sector over the past decade is nothing short of extraordinary. The U.S. embargo complicates importation of research equipment and technology into Cuba, and slows the cross-border exchange of scientific knowledge. With the disintegration of the Soviet Union and the communist regimes of Eastern Europe, Cuban science was left fairly isolated in the 1990s. In spite of a collapsing economy, though, the Cuban government continued to invest heavily in biotechnology. Cuba is now reaping the rewards in the form of more than a dozen therapeutic proteins, diagnostic reagents, and vaccines the industry has brought to market. The Cuban biotech enterprise benefits from a high degree of integration between the efforts of public educational/research institutions, clinically-focused research institutes, and government-owned “companies” with manufacturing expertise. The Hib project, for example, ultimately involved the University of Havana, the Pedro Kouri Institute for Tropical Medicine, and the Center for Genetic Engineering and Biotechnology. As its homegrown biotechnology industry flourishes, one hopes that the Cuban people will benefit from improved health care, jobs, and economic development.

                For more information on QuimHib, see http://www.gndp.cigb.edu.cu/QuimiHib/%20hybprodescription.htm, or articles in the July 24, 2004 issue of Science magazine (Verez-Bencomo et. al., “A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type b,” 522-525, and J. Kaiser, “Synthetic vaccine is sweet victory for Cuban science,” 460). 

 

OraSure Technologies, Inc., Bethlehem, PA, U.S.

                Acquired Immune Deficiency Syndrome (AIDS) is one of the great tragedies of the modern world. World Health Organization (WHO) statistics indicate that in 2005 there are over 40 million people worldwide infected with the human immunodeficiency virus (HIV), the cause of AIDS. Over 3 million people will die as a consequence of AIDS this year. Effective drugs that restrict viral replication and slow progression of the disease have been developed, but they do not cure the infection. We eagerly await the day when we can give an award to the developer of a vaccine preventing HIV infection, but that day seems to be well off in the future. Until then, identifying infected individuals as soon as possible, so that they can begin treatment and avoid passing the virus to others, is critical for stemming the epidemic.

Diagnostic tests for determining whether a person has been infected with HIV were first developed two decades ago, but there is still room for improvement. Testing blood samples in professional laboratories, by trained technicians, using sophisticated equipment is an expensive and time consuming process, not well suited to resource-poor settings where most HIV infections are seen. Even in wealthier nations that have the necessary medical infrastructure for widespread testing, the time lag between testing and communication of results is problematic. In the U.S., many people tested for HIV infection in public clinics never return for their results. There is thus a great demand for fast, accurate, and cheap diagnostic tests for HIV infection.

To address this problem, OraSure Technologies developed the OraQuick ADVANCETM  Rapid HIV-1/2 Antibody test. This versatile test can be applied to blood from a simple finger stick, drawn blood or plasma, or an oral swab. OraQuick Advance uses immobilized HIV antigens to detect anti-HIV antibodies, an indicator that a person has been infected with the virus. Tests have shown that OraQuick Advance has accuracy and sensitivity rates of over 99 percent. As with all antibody-detecting diagnostics, there is an unavoidable lag of a few weeks between when a person was actually infected, and when they have generated enough of an immune response to test positive. OraQuick Advance is the only rapid test FDA-certified to detect both HIV-1 and HIV-2 in blood. (Though the HIV-1 strain of virus is dominant in the U.S. and globally, HIV-2 is particularly common in parts of Africa.)

            The advantages of OraQuick Advance as an initial screen for HIV infection are manifold. It is simple enough that the FDA has approved its use in clinics and other test sites, eliminating the need to send samples to laboratories. The ability to use oral fluids as an alternative to blood is doubly beneficial: oral sampling reduces the risk to the worker administering the test, and some people would just rather not give a blood sample, however small. Most importantly, OraQuick Advance is fast—only 20 minutes are needed for results. According to one HIV program administrator in the U.S.:                             

“Rapid testing has revolutionized our HIV testing program. Prior                                                            to the introduction of OraQuick, clients had to wait 1-2 weeks to                                                               identify their HIV status. Many did not return for (their) results.                                                     Hence, many did not receive follow up referrals to care or preven                                                           tion messages. Post-test counseling (PTC) rates hovered around 50-                                        60%. With the advent of rapid testing, clients can now get their                                                              status identified within 20 minutes. PTC rates at rapid testing sites                                                                 are now 98 percent. Referrals to care and treatment are near 100 per                                      cent. Our state is finding a greater percentage of HIV positive people                                               at sites that provide rapid testing because people are seeking places                                         where the test is available.”

            OraQuick Advance is not the only rapid HIV diagnostic available on the world market, but it has certainly had the biggest impact in the U.S.. Since initial FDA approval in 2002, more than 2.6 million units have been distributed, including 750,000 provided by the U.S. Centers for Disease Control to public health clinics. OraQuick Advance is being rapidly adopted by public and private health care providers and AIDS outreach organizations, and is starting to penetrate international markets. The WHO has given high marks to OraQuick Advance for accuracy and ease of use, but at a current bulk price of $12-$15 per unit, more widespread adoption in resource-poor settings may require further cost reductions.

            For more information on OraSure and OraQuick Advance, http://www.orasure.com.

 

Partners in Health, Boston, MA, U.S.

                AIDS and tuberculosis are drastically different diseases, but they share some common features. Along with malaria, they are the most lethal infectious diseases afflicting the world today, impacting primarily the poorest regions of the globe. Both AIDS and TB require intensive and prolonged drug treatment, and interruptions in treatment can facilitate the emergence of drug-resistant mutant strains of the respective pathogens (HIV and the bacterium Mycobacterium tuberculosis, respectively). Drug-resistant infections are more difficult to treat, requiring either higher drug doses, or alternative (and often more expensive) medications. Moreover, if the drug-resistant pathogen is transmitted to new hosts, those people also will require more intensive and expensive treatment.

The non-profit organization Partners in Health (PIH) encountered just such a situation in the slums of Lima, Peru in 1995, which were rife with strains of TB resistant to standard antibiotics. These “multi-drug resistant” (MDR) strains of TB were a virtual death sentence for their victims. The public health system in Peru, backed by conventional wisdom and the WHO, viewed treating MDR cases with more advanced second-line drugs as far too expensive and complicated. The pioneering efforts of PIH and its Peruvian partner Socios en Salud Sucursal eventually established that MDR cases could be treated in a cost-effective manner, even if second-line antibiotics had to be used.

                In developing their TB program in Peru, PIH staff recognized the importance of intensive monitoring and documentation during the treatment of each patient. Physicians and staff had to be aware of what drugs and dosages were being used for each individual, what had been used previously, and what options were available in the dispensary. Drug stock outages could be disastrous, but given the expense of the second-line drugs often being used, large stockpiles were out of the question. The PIH Electronic Medical Record (EMR) system, the first such system created explicitly for use in resource-poor environments, was created to satisfy these demands. The EMR, built using open source software, is used to capture patient data ranging from lab results to drug regimens and other clinical data. It also integrates systems for supply management (critical for tracking drug supplies), data analysis (e.g.. for research purposes), and reporting (for donor organizations).

                EMR is a Web-based system, with data transmitted from each clinic to a central server so it can be accessed from anywhere. It can transition smoothly between online and offline modes, a necessity for dealing with periodic Internet access disruptions that are unavoidable in settings such as Cange, a remote village in central Haiti where PIH operates a large clinic. EMR is designed for the realities of operation in resource-poor settings. For example, data entry can be done by locally-trained workers not versed in complex computer systems, and a variety of patient identification tools are incorporated, because the spelling of patient’s names and addresses is somewhat “fluid” in low-literacy environments like rural Haiti. The bottom-line for the PIH EMR system is functionality: a sophisticated, stable, and secure system that serves the needs of patients, local healthcare workers, physicians, research scientists, accountants, and donor organizations.

                PIH currently operates two versions of the EMR, the original system developed for the Peruvian TB project, and HIV-EMR, which focuses on management of HIV-infected patients in Haiti. Both systems contain several thousand patient records after only three years of operation in Peru and one year in Haiti, a testament to the scale of the TB and HIV problems. The EMR software was recently exported to the Philippines, where it is being used to manage an MDR TB treatment program. PIH is discussing its use on HIV projects in Africa, as well as adapting it for managing malaria treatment programs.

                More information on Partners in Health can be found at www.pih.org. Interested readers might also want to check out the best selling book Mountains Beyond Mountains: The Quest of Dr. Paul Farmer, a Man Who Would Cure the World, by Tracy Kidder. This outstanding book chronicles the extraordinary work of Paul Farmer, the founder of Partners in Health, and discusses their work in Haiti and Peru on MDR TB and other public health issues of the developing world.

 

Project Impact, Berkeley, CA, U.S.

                Functional hearing may be as important as functional eyesight in terms of effects on personal development, education, employment, and community involvement. WHO estimates that there are 250 million hearing impaired people globally who would benefit from a hearing aid, but as with vision care, cost and access are limiting factors. The average cost of a hearing aid in the U.S. is well over $1000, greater than the annual per capita income of most of the world’s population. Hearing aids also need to be carefully fitted and adjusted, and the global demand for appropriately equipped hearing clinics and trained audiologists vastly exceeds the supply.

Enter Project Impact and the Affordable Hearing Aid Project. Project Impact  is a non-profit organization “dedicated to making medical technology and health care services accessible, affordable, and financially self-sustaining.” They work toward this goal by transferring design and manufacturing technologies to partners in developing nations. Project Impact’s primary manufacturing partner is Aurolab, a division of Aravind Eye Hospital in Tamil Nadu, India. Project Impact founder David Green played a key role in setting up Aurolab, which operates under a non-profit, sustainable business model whose goal is to ensure that their products are affordable to all who need them. Aurolab’s first product in 1992 was an intraocular lens (IOL) used in cataract surgery. Aurolab now produces a whole line of IOL’s, and has reduced the cost of high quality IOL’s to less than $5 per lens, compared to over $100 in the U.S.. Aurolab also manufactures ophthalmic sutures and needles and various pharmaceuticals, all priced affordably under the same guiding principle.

                Aurolab recently began production of the “Impact 1,” a digital hearing aid designed by Project Impact to be manufactured and sold at less than one-tenth the price of comparable hearing aids in the U.S. Savings are achieved partly through a design that minimizes component costs. Production in India also results in relatively low labor costs. The final major price factor is that Aurolab and Project Impact only seek sustainability, not profit maximization. As with their IOL’s, Project Impact/Aurolab employs a tiered pricing model in which customers in wealthier markets pay higher prices intended to subsidize products and services for lower income markets.

                The Impact 1 has FDA and CE Mark approval for sales in the U.S. and Europe, but in terms of social benefit the most important markets will continue to be developing nations, which currently account for only 12 percent of annual hearing aid sales, despite containing the majority of the world’s population. A major hurdle in such markets is the availability of clinics equipped to test hearing, and staffed to fit patients with hearing aids and make appropriate adjustments. Project Impact is working with partner organizations such as Lion’s Club International to distribute Impact 1 through a growing network of clinical affiliates that can fit the hearing aids in a single three hour visit. Even with affordable hearing aids, it will take time to develop the infrastructure to meet the hearing needs of millions of people around the world. But with more than 10,000 Impact 1 units distributed in their first two years, and a second generation design underway, Project Impact, Aurolab, and their partner organizations have made a promising start. For more information, see www.project-impact.net.

 

Dr. Joshua Silver, University of Oxford, UK

                Nearly every reader of this article has ready access to professional vision care. We take it for granted that vision problems are easily diagnosed, and that poor eye sight can usually be corrected by glasses or contact lenses, or even permanently repaired by quick and virtually painless (and very expensive) laser surgery. Nevertheless, there are hundreds of millions of people globally who could benefit from vision-correction, but who cannot get even simple eye glasses because they have no access to, or cannot afford, professional services to diagnose them and provide appropriate corrective lenses. The consequences are serious; limited vision, even when short of blindness, exacts a toll on personal development, educational achievement, social interaction, and economic productivity. Recognizing this heavy cost, the “Vision 2020” initiative of the World Health Organization (www.v2020.org) aims to eliminate avoidable blindness and visual impairment by the year 2020.

                Joshua Silver, a Professor of Physics at Oxford University set out to meet this challenge by developing an inexpensive pair of lenses that could actually be adjusted by the wearer to provide vision correction. Silver developed a spherical lens system composed of a fluid-filled compartment surrounded by two membrane sheets inside a plastic shell. Pumping fluid into the compartment changes the curvature of the lens, altering refractive power. Two such lenses are fitted into spectacle frames. To customize the lenses for a particular individual, each is adjusted independently using valves that allow fluid to be pumped into the chamber. Once the necessary adjustment is made, the valves are closed and the pump mechanism removed and “Voila! “ the wearer immediately has customized spectacles, without the need for lens grinding or full-fledged optometry facilities.  

                Dr. Silver’s Adaptive Spectacles, or “AdSpecs,”  have been tested extensively in Africa, where they provided satisfactory vision correction to about 80 percent of test subjects. These lenses are not a panacea for all vision problems; significant astigmatism cannot be corrected, and there are many other eye defects and medical problems that can compromise vision. Still, an innovation that might help 80 percent of the hundreds of millions of people around the world who suffer from poor eyesight is a big deal. AdSpecs are currently being manufactured in China at a cost of roughly $10 per unit, a cost which may come down further as production is scaled up. Distribution of AdSpecs in remote locations and underdeveloped regions where there is no access to professional eye care could make a huge difference, restoring productivity and community interactions to adults, and improving literacy rates by allowing children with poor eye sight to continue their education.

                For more information, see www.adaptive-eyecare.com. 

               

Conclusion

                Meeting the diverse threats to human health faced by the world today will take all the resources and creativity we can muster. The 2005 Agilent Technologies Foundation Health Laureates range from a for-profit company (OraSure Technologies), to non-profit organizations (Project Impact and Partners in Health), an academic scientist (Joshua Silver, Oxford University), and a multidisciplinary team of scientists, physicians, and engineers (the Hib vaccine project). The Laureates took different paths in developing the technological innovations honored here, from a solo inventor (Dr. Silver) to an international collaboration that involved more than 300 people (the Hib vaccine project). The unifying feature of these projects is that innovative people saw a need as an opportunity, and put their talents to work with vision, dedication, and persistence. These qualities are especially vital in medical technology, where years of testing are often required before a new device, drug, or vaccine can be introduced to the public and start to have a significant impact. 

                The Laureates and projects honored this year have each demonstrated some degree of success, but they all may be on the cusp of much greater things. How many millions of people will eventually find out their HIV status using the OraQuick Advance test, or be vaccinated with QuimiHib? Could the Partners in Health EMR system be used for chronic disease management by health care providers throughout the developing world? Will millions of people eventually wear AdSpecs or Impact 1 hearing aids? What if clinics could be set up throughout the developing world where locally-trained technicians could test hearing and vision, and outfit patients in a single visit with AdSpecs or a hearing aid? Such possibilities! But, at this point, we do not know what the future holds for the Laureates and their projects. Every Silicon Valley entrepreneur can tell you that no matter how great the idea, there are countless stumbling blocks on the road to long term success. The pragmatic focus of these projects, and the attention to sustainability embedded in them, give them a fighting chance. At the very least, the work of these innovators inspires in us an optimistic vision of the future, where technology can help to bring about a healthier world.

 

The Panel

Craig Stephens, Chair, Associate Professor

of  Biology, Director, Biotechnology

Program, Santa Clara University

 

Marie Barry, Former Director, Global

Partnerships, ALZA Corporation

 

Steve Eglash, Senior Associate,  Worldview

Technology

 

Leilani Miller, Associate Professor of

Biology, Santa Clara University

 

Jonathan Showstack, Professor of Medicine

and Health Policy, Academic Information

Technology Coordinator, Office of the

Executive Vice Chancellor, Associate

Director, Institute for Health Policy Studies,

University of California, San Francisco

 

Russel Sampson, Vice President, Research

and Development, Cytyc Surgical Products

 

Peter Sullivan, M. D., Vice Chairman,

Emergency Medicine, California Pacific Medical Center

About the Author

Craig Stephens

Craig Stephens is an Associate Professor of Biology at Santa Clara University, and Chairman of the Department of Biology. He received a B.S. degree from Roanoke College in 1985 and a Ph.D. from the University of Virginia in 1991, after which he was a postdoctoral scholar at Stanford University (1992-1996).His research focuses on how genes and enzymes function in microorganisms, for which he has been awarded grants from the National Science Foundation, the National Institutes of Health, and Smith-Kline Beecham. He teaches courses in microbiology, biotechnology, and molecular biology at SCU.

Printer-friendly format