Greg Hamalian, a 10-year-old boy from West Bridgewater, Massachusetts, may be $18 poorer, but at least he can be assured that his hard-earned pocket money is going toward a good cause. Greg gave half of all the money he had to Science with a Mission (SMI), a nonprofit organization whose objective is to develop, manufacture, and distribute immunoassay-based diagnostics for diseases prevalent in developing countries. In recognition of his gift, Greg was awarded a plaque honoring him as the first donor of the fledgling organization.

The idea for SMI came to Alynne MacLean, its president and founder, upon her return from a two-week trip to Tanzania in the winter of 2000. While there she realized that if she were to sell her stock in Biogen, in Cambridge, Massachusetts, where she worked as a scientist in the analytical development department, she would have the funds to survive for at least a year, during which time she could get SMI off the ground. Concrete steps soon followed. After having been with Biogen for six years, she left her stable job and an impressive salary for the more shaky ground of a biotech start-up. SMI became incorporated in February 2001, a few weeks after MacLean left Biogen.

The Need for Diagnostics

Those in the public health arena are increasingly drawing attention to the need for rapid, low-cost diagnostics. Definitive diagnosis of tuberculosis (TB), one of the world's biggest killers, requires both a microscope and expertise, scarce resources in the rural areas of the developing world. Diagnosis based on examination of the patient is problematic as it can be difficult to distinguish between TB, AIDS, and several other diseases based on physical examination alone. The high rate of TB infection among AIDS sufferers and the appearance of TB in geographic areas previously untouched by the disease compound the problem. A correct diagnosis is critical. In much of the developing world, AIDS is essentially a fatal disease, while TB is treatable with effective, albeit somewhat expensive, drugs.

There is also an acute need for improved diagnostics for the sexually transmitted diseases (STD): chlamydia, gonorrhea, and syphilis. Currently, their diagnoses are more complex and costly than their treatments. It is difficult to distinguish between the STDs because many of their symptoms are overlapping, and in many cases infection is, in fact, completely asymptomatic. Bacterial culture is the most accurate and sensitive means to make a diagnosis, but this requires several days - an enormous disadvantage in rural areas where patients travel long distances to reach a clinic. As a result, many patients with STDs do not return for diagnosis or to obtain treatment, and the spread of disease continues unhindered. STDs can have serious consequences, especially for women, including increased risk of sepsis, cervical cancer, ectopic pregnancy, and a higher rate of stillbirth and blindness in their babies.

HIV is another devastating disease for which diagnostics are unavailable in much of the areas where it is endemic. However in this case, the formidable financial and social obstacles to treatment are dwarfing the lack of diagnostics, at least for the time being.

In many cases, however, once correctly diagnosed, the drugs to treat a disease are available. The World Health Organization (WHO) has initiated the concept of the Essential Drug List (EDL) and has provided selection guidelines to be used by individual countries. Over 140 countries have compiled national EDLs, which list the drugs necessary to meet the basic health needs of the majority of the population. EDLs have, in fact, improved access to the most needed drugs by focusing the attention of international aid organizations on the priorities.

Finally, the paucity of diagnostics in much of the developing world is contributing to the emergence of drug-resistant bacteria, an important global threat. Inaccurate diagnosis can result in inappropriate use of antibiotics, an important factor in the development of resistance. A current challenge to the biotech community is the generation of sophisticated diagnostics that, in addition to identifying the disease-causing pathogen, also recognize the drugs to which it has become immune. With the growing prevalence of drug resistance among the world's most deadly microbes, such diagnostics will increasingly become necessities if they are to assist physicians in making treatment decisions.

Why the Scarcity of Low-Cost Diagnostics?

According to David McNeeley, assistant professor of pediatric infectious diseases at the Weill Medical College at Cornell University, who has worked extensively in Haiti, public health organizations have been aware of the need for better diagnostics for some time. "The question," he says, "is what industry is going to do about it." The low health budgets of developing nations have been an important factor in the lack of interest on the part of the biotech industry. On the other hand, the market is huge.

One-third of the world's population is infected with TB, approximately 98 percent in the developing world. Infection with STDs is also extremely widespread, with 20 to 30 percent of the population in some areas infected with chlamydia, gonorrhea, or syphilis. Thus, the size of the market may counterbalance the low profit margins, and, according to Mark Perkins, manager of the Diagnostics Discovery Research program at WHO, many of the smaller biotech companies are now beginning to take an interest in developing diagnostics for the major infectious diseases. Even some of the big players are becoming involved. Roche Diagnostics recently entered into an alliance with Innogenetics, a smaller Belgian biotech company, to develop rapid microbiological point-of-care diagnostics.

The Short-Term Goals of SMI

In the next six to eight months, MacLean expects to develop a prototype immunoassay for the detection of human serum albumin. Altered levels of the protein are used as markers for many forms of nephritis, but currently expensive equipment is required for the test. She is focusing on transferring the technology already available into a "dipstick" format, much like a home pregnancy test. The beauty of this approach is that analysis of the result requires little technical expertise and no expensive equipment. The relative stability of the antibodies used in the assay is critical because the assays are shipped to remote areas and are subjected to extremes of temperature and environment

Stephanie James, chief of the Parasitology and International Programs Branch at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, explains that there is a good precedent for the use of immunodiagnostics rather than the nucleic-acid-based diagnostics in a field setting. "There's been a lot of success in adapting those kind of assays [immunodiagnostics] into a rapid, inexpensive field-applicable kind of setting," she says, giving the example of the rapid monoclonal antibody test for filariasis, marketed by AMRAD, an Australian pharmaceutical and biotechnology company. "We're just beginning to work on that kind of thing with the genetically based assays," she says.

MacLean presently works in the laboratories of Salem State College in Massachusetts. Her sister, a chemistry professor there, realized that the college laboratories were not in use much of the time and suggested an arrangement in which MacLean has use of bench space when lab courses are not in progress; in return, MacLean supervises undergraduates carrying out research projects. The faculty was delighted, and MacLean has free rein of lab equipment while fortunate undergraduates obtain expert training in the development of immunoassays.

The Long-Term Goals

By the end of three years, MacLean expects to have reached the point of manufacturing the human serum albumin immunoassay and to have begun work on the development of a second one. In selecting the second disease to target, she will make use of a set of criteria she has devised. Firstly, she plans to focus on geographical areas with which she is familiar. She has firsthand information and contacts in the Dominican Republic, Jamaica, Bolivia, and Colombia. Secondly, using disease statistics, she will determine which are the most prevalent and debilitating in these countries; and, finally, she will focus on ailments for which treatment is available. As MacLean points out, "It's not a benefit to be able to give a name to a patient's agony yet not be able to treat it!"

Once the immunoassays are developed and produced, distribution of the product within the framework of a foreign country will be the final hurdle. As Perkins of the WHO points out, "For many diseases and situations, it's not just the specific tool or drug or vaccine that's needed, it's the infrastructure and the political will to distribute it." Giving the example of the millions of lives that continue to be lost to measles despite the existence of an effective but poorly distributed vaccine, he says, "Just coming up with a good product is not the whole answer."

MacLean does not view distribution as the biggest hurdle. She plans to overcome political barriers by forming partnerships with nonprofits already operating in the areas she targets. She gives the example of Compassion International, which is active in educating, feeding, and meeting the medical needs of children in Bolivia and a number of other countries. "In the United States, many people haven't even heard of Compassion, but in some countries it's a household word," she says. By working with organizations that already have the goodwill of the people and a health infrastructure in place, she expects to be able to effectively deliver the diagnostics to those who need them.

The Biggest Challenge

MacLean sees funding as the biggest challenge to SMI. "At this point," she says, "I have 13 years' experience designing and optimizing immunoassays and feel pretty comfortable that if it can be done I have a pretty good chance of doing it." Obtaining funding is another matter. Few charitable organizations donate to nonprofits that are both start-ups and that plan to operate abroad, preferring instead to donate toward those with a proven record and for projects that will benefit the local community.

Thus, as MacLean continues to scour the lists of organizations that donate to nonprofits at the Associated Grant Makers of Massachusetts library, health care workers across the world are making diagnostic decisions based on their intuition and with what tools they have available. The breadth of available tools may very well soon be expanded, thanks to Science with a Mission and others like it.