Micro Need Macro Problem

An aspect of global health I’m learning more about is the relationship between health and nutrition, an aspect that we, in the land of the large, all-you-can-eat buffets, and a multi-billion “dieting” industry, easily ignore, but obviously, for many of the world’s citizens, especially those whose developing minds and bodies need nutrition, is a major concern.  While the more wealthy world’s response to famine and imminent loss of life is well-tuned and historically many countries quickly provide food supplies when natural or man-made disasters occur, a more pernicious and poorly-addressed problem is chronic under-nutrition which leads to a wide range of specific deficiency diseases, increased susceptibility to infectious disease, and reduced ability to earn a living.  One under-recognized, yet apparently easily addressable, condition I now know something about is iodine deficiency.

Iodine is an essential element in the human diet as a key component of the thyroid hormones that are involved in regulating metabolism and cell development.  In fact, the body’s need is so great that the classic sign of iodine deficiency is enlargement of the thyroid gland (goiter) due to hyperproliferation of the tissue needed to make the hormones.  Iodine deficiency causes fetal and neo-natal mortality and congenital abnormalities, and if that’s not bad enough, causes impaired mental function in children and adolescents, and in adults it has been linked to decreased educatability, increased apathy, and loss of work productivity.  This complex of effects is know as iodine deficiency disease (IDD) (see a Lancet review by Zimmermann et al 2008).  Iodine is a naturally-occurring component of many foods, e.g., plants grown in iodine-containing soils or in sea food, but for most of the world’s population these sources are insufficient.  The good news is that in the early 1990s, the WHO/UNICEF, advocacy groups like the International Council for the Control of Iodine Deficiency Disorders (ICCIDD) and the Iodine Network (IN), governments, and salt manufacturers launched a campaign against IDD through the simple and inexpensive (cents per ton) public health measure of adding iodine to table salt.  Currently, about 70% of households have access to and use iodized salt with the result a remarkable decrease in IDD over the past 20 years.

The not-so-good news is that IDD is still a problem for many people in both the developing and developed world.  In 2008, UNICEF estimated that 2 billion people have insufficient intake of iodine, including one-third of all school-age children in many regions with the highest insufficiency occurring in Eastern Europe (52%), Eastern Mediterranean (48%), and Africa (41%) (Table 3, Zimmermann et al. 2008).  In the same report, the organization states that iodine deficiency is the leading cause of preventable mental retardation in the world and that 38 million children born at risk each year (UNICEF press release).  The goal for governments and public health advocates is universal iodization and involves getting salt manufacturers to add iodine and food processors and people to use it, so the solution is mostly a matter of political will, modest amounts of money, and PR (see Global Alliance for Improved Nutrition Universal Salt Iodization Program).

Unlike many global health solutions, the role of new technology is minimal, although there is a hole technology could fill.  To monitor and evaluate the success of iodization programs, one needs to measure the amount of iodine in the people at risk and the current process, while not technically difficult, requires samples to be collected in the field and analyzed at a central laboratory, subject to contamination and loss (see WHO Assessment Guide).  While I couldn’t find any specific guidance on the number of samples needed for adequate monitoring, I am guessing that a half a million may need to be analyzed each year (2 billion at risk and bi-yearly statistically-meaningful sampling).  Hence back in 2008, someone at the CDC and/or NIH swung into action and put out a single paragraph request for SBIR/STTR proposals to develop a rapid field test for urinary iodine (“Simple, reliable measures for field use would be a great help.” NIH Omnibus Solicitation 2008) and a small company in Ohio, the Institute of Bioengineering Technologies, Inc. (IBET) sent in a proposal, received Phase I and II funding, developed a prototype strip-type assay, and accepted my offer to help find collaborators for the field testing, funding for the scale-up to manufacturing, and customers and licensees, which I’m doing.  So for a relatively small investment of public funds and with luck and some private investment, public health agencies may have a better tool for eliminating IDD in a couple years.  Your tax dollars at work.

The SBIR Drop in the Bucket

The capital to start or grow a company developing products for global health may come from several sources which are, in order of rapidly decreasing likelihood:  the founder’s pocket, foundations and their pass-through surrogates, the federal government, venture capital firms, and angel investors.  One would think that federal government policies would favor direct aid to global health-oriented companies given the potential for social benefit and improvement in US prestige.  After all, since 1982, the Small Business Innovation and Research (SBIR) program has required Federal agencies with extramural research and development budgets over $100 million to use an annual set-aside of 2.5% of that budget for small companies “to conduct innovative research or research and development (R/R&D) that has potential for commercialization and public benefit” (SBIR Program).  For health-related research, the National Institutes of Health, the primary agency for health-related research, has  a 2009 extramural research budget of about $24 billion in 2009 and, therefore, an SBIR set aside of about $600 million ($672 million was spent in 2008, NIH SBIR).

Through it’s SBIR program, the NIH is a relatively small investor in biotech/pharma/medical product development (the venture capital investment in biotech companies was $8 billion annually pre-crash), but SBIR money is in the form of a grant (non-dilutive of ownership), is relatively free of constraints, and is renewable, and therefore ideal for a company’s higher-risk projects (like products for global health).  Despite that fact that the initial grant is small ($100-300,000), the program is popular with more than 4000 applicants annually and about 30% of first-timers getting funded.  And although some in the research community would argue that the SBIR program is a diversion of “their” money,  it funds work that is a step closer to a tangible benefit than most NIH-funded projects (and recipient institutions’ overhead costs).

Thanks to a new reporting tool (NIH Research Portfolio Online), one can get an idea of the extent of SBIR funding overall, and an estimate of the amount going into global health product R and D.  The institute most likely to fund global health product development is the National Institute for Allergy and Infectious Disease, and in 2008, it spent about $100 million in SBIR grants, the second highest after the National Cancer Institute (NIH Databook).  This money funded about 385 projects (new and re-funded) on topics ranging from new vaccine delivery methods to preclinical testing of novel antibiotics.  Using the WHO list of neglected diseases (leishmaniasis, schistosomiasis, onchocerciasis, lymphatic filariasis, Chagas disease, malaria, leprosy, African trypanosomiasis, tuberculosis, and dengue) plus diarrheal illnesses, I looked for projects that seemed related to developing global health treatments or diagnostics and identified 59, about 15% of the total and therefore about $15 million in funding.  Malaria and tuberculosis were most popular (about 12 projects each), and filariasis and trypanosomiasis the least (1 each).

The good news is that these 59 projects represent about 50 companies that think they can make money (some day) by inventing products for neglected diseases.  The less good news is that $15 million spread over about 60 projects (or $250,000 each) does not buy much r and d.  But since many small companies cobble together multiple sources of funds and are boot-strapping themselves to a product, the money is helpful.  And any drop in the bucket for neglected disease product development is good.  But for a country that each year puts $24 billion of public money into “health research,” $700 million of which is set aside for companies doing product-related work, $15 million looks paltry.