Banana and mosquito research

Two researchers from Queensland are contributing to a $436 million global plan to improve the health of millions of people in some of the world's poorest countries.

This hugely ambitious project is based on the realisation that far too little is being done for the health needs of poorer countries. For example, 100 million die each year from dengue fever while in Uganda 38% of children under five are growth stunted because they are undernourished through just eating their staple diet of bananas.

The work facing the researchers is a mixture of adopting existing health tools such as laboratory tests to technology that is practical for developing countries. Other projects in the plan seek to redefine the understanding of how to treat and prevent diseases, potentially leading to new vaccines and drugs.

The project is called Grand Challenges in Global Health and is funded through a series of 43 grants covering a broad range of research projects involving scientists from 33 countries.

The goal is to create health tools that are not only effective but also inexpensive to produce, easy to distribute and simple to use in developing countries.

Australia's contribution comes from James Langham Dale, Queensland University of Technology, the lead investigator, who has received $1.1m to genetically modify Ugandan bananas to give them increased levels of pro vitamin A, vitamin E and iron. Dale is being joined by researchers from Uganda and the US to provide these essential nutrients.

Also from Queensland comes lead investigator, Dr Scott Leslie O'Neill, University of Queensland, who has received a grant of $6.7m to head a multinational team that will look into interfering with a mosquito's ability to transmit the dengue virus by altering its lifespan. They hope to introduce a bacterial parasite that occurs naturally in other insects, into mosquitoes. The parasite causes them to die before they are old enough to transmit the disease. The insects would then inherit the parasite and pass it from generation to generation for a long-term solution.

The money for this major effort comes from a $450m commitment by the Bill and Melinda Gates Foundation along with $27.1m from the Wellcome Trust and $4.5m from the Canadian Institutes of Health Research (CIHR).

Managing the initiative are global health experts and the Foundation for the National Institutes of Health (FNIH), the Gates Foundation, the Wellcome Trust and CHIR.

The chosen fields of activity were selected from more than 1500 research projects that were proposed by scientists from 75 countries in 2003. Forty-three of those now make up the Grand Challenges and will be managed by teams of researchers working in partnership across many disciplines and with private industry. Leaders from fields such as chemistry, engineering, statistics and business will all be involved.

Each of the 43 projects seeks to tackle one of 14 major challenges. These include:

• Developing improved childhood vaccines that do not require refrigeration, needles or multiple doses to improve immunisation rates in these countries where each year 27m children do not receive basic immunisation. An estimated 151m vaccine doses delivered to developing counties this year will be spoilt because they are not properly refrigerated. In addition, most vaccines are given by injection, which increases the risks of HIV and hepatitis through using unsterile or reused syringes and needles. An estimated 500,000 serious infections could be avoided this year by using needle-free vaccines.
• Studying the immune system to guide the development of new vaccines, including those to prevent malaria, TB and HIV which together kill more than 5m people a year. The world still lacks vaccines for these, some of the world's biggest killers. Three key areas will receive attention: identifying the specific types of immune responses that vaccines must work on; identifying new antigens for obtaining these immune responses; improving the reliability of animal tests that are used to evaluate vaccines.
• Developing new ways of preventing insects from transmitting diseases such as malaria, which affects more than 2 billion people worldwide. Traditional insecticides are becoming ineffective as mosquitoes grow resistant to the chemicals in them. More powerful insecticides tend to be too poisonous or expensive for developing countries to use on a large scale. Genetic control and cutting-edge chemistry are being looked at as possible answers to the problem.
• Growing more nutritious staple crops to combat malnutrition, which affects more than 2 billion people around the world. Poor nutrition contributes to more than half the 11m deaths of children under five each year. It is estimated that half the population of sub-Saharan Africa suffers from iron deficiency and a third from zinc deficiency, and 90% of children in the region receive inadequate amounts of vitamin A. This diet can lead to impaired immune systems, blindness, low birth weight, impaired neuropsychological development and stunting. Arid climates with poor soil cannot support the fruits, vegetables and grains needed for a balanced diet leading to the people relying on rice, which is one of the poorest sources of essential nutrients. A promising long-term solution might be to genetically modify crops to contain more nutrients.
• Discovering ways to prevent drug resistance because many drugs that were once successful at treating diseases are now losing their effectiveness. Once upon a time chloroquine was an effective and relatively cheap anti-malaria treatment but the parasite has mutated to become resistant to the drug. Alternative treatments are up to 20 times more expensive but new medicines being developed may be harder for the microbes to resist.
• Discovering methods to treat latent and chronic infections such as TB, which is harboured by nearly a third of the world's population. Treating people with latent infections before the onset of the active disease could reduce illness and death and limit disease transmission. Up to 10% of the two billion people estimated to be infected with TB will develop the disease at some point during their lives. Because the biology of latent and chronic infections is not well understood, the development of effective drugs has been slowed. Drugs that would kill or slow infection and immunotherapies that would stimulate the immune system will be studied during the Challenge.
• More accurately diagnosing and tracking diseases in poor countries that do not have sophisticated laboratories or reliable medical record keeping. There are two major challenges to collecting better information on health problems: inadequate or expensive diagnostic tests that can identify the causes of illness and inadequate or incomplete medical records such as death certificates. The latest statistical methods and using 'miniaturising' technology to reconfigure diagnostic tests is experienced to raise the standard of record keeping.

There is little doubt that these various challenges have been taken up with enthusiasm and commitment by those taking part. There also seems to be a realisation that rich nations have a duty to support the poor nations.

"Science has revolutionised health in wealthy countries while developing countries have been left to fight disease with only a handful of tools that are either grossly inadequate or far too expensive for widespread use," says Dr Numal Kumar Ganguly, a member of the Grand Challenges scientific board and director general of the Indian Council for Medical Research.

"These challenges have provided the resources needed to bring together top scientists in both developed and developing countries to help address these imbalances," he said.

The Challenges are hugely ambitious, with researchers taking important risks that others have shied away from, according to Dr Elias Zerhouni, director of the National Institutes of Health. He believes there will be many breakthroughs in technology that will have the potential to transform the health of poor countries.

"Decoding the human genome and the genomes of many important pathogens of humans such as malaria and TB, combined with advances in chemistry, have opened up countless avenues for improving health," says Dr Mark Walport, director of the Wellcome Trust.

However, making advances in medicine is only part of the story and they remain theoretical unless those who need them have ready access. This is recognised by Dr Richard Klausner, executive director of the Global Health Program at the Gates Foundation.

"Researchers will pursue affordable and practical health solutions that have access built in from the very start," he promises.

This is the first time that such a focus on such a scale has been brought to bear on the health and welfare problems of developing countries. As an on-going project it promises to have far-reaching effects for the future of third world nations. Some of the research will go beyond the boundaries of our current knowledge and perhaps open up quite new areas for research.

Whatever the outcome of these unique and challenging efforts may be, in the end it may be not only the poorer countries who will benefit.

Mike Smyth