BioEd Online

Imagine being able to do away with vaccines and instead reprogramming the immune system to attack all kinds of disease. That's the vision of Caltech's president David Baltimore, who won a Nobel Prize in 1975 for his work on virology and cancer, and who now has a US$13.9 million grant to pursue this dream.

Baltimore’s project is one of 43 that have secured a portion of $440 million handed out by the Bill and Melinda Gates Foundation today, 27 June, for their Grand Challenges in Global Health. The cash has been allocated to daring, innovative projects that aim to beat some of the world’s most problematic diseases.

Baltimore's approach is inspired by the continuing failure to find vaccines that work against the human immunodeficiency virus (HIV), malaria, cancers and many other diseases

Vaccines work by stimulating the immune system. But they often use a partial or deactivated form of the disease agent to provoke this response. Sometimes this results in a very weak immune response that isn’t capable of fighting off illness, either because the wrong type of immune cells are kicked into action, or because there simply aren’t enough of them to do the job. And the immune response provoked by a jab sometimes wears off with time.

Baltimore wonders if one could get a more complete, stronger response by tapping in directly to where the body manufactures immune cells such as killer T cells. These protective agents, which bind onto infected cells and kill them, are produced by stem cells in the bone marrow.

If researchers could genetically modify these stem cells they could be programmed to create perfectly designed immune cells, in great quantity and throughout life. Ultimately, a single shot in infancy could pre-program the immune system with life-long protection against many diseases.

Long shot

Gene therapy of bone marrow stem cells has been done in mice, by using a virus to introduce genes into the cells. Baltimore has begun experiments to see if he can give mice lifelong immunity against cancers using this method, with promising initial results¹. But the technique is in its infancy and has never been used therapeutically in humans.

The idea is a long-shot, says Richard Klausner, executive director of global health at the foundation. As an investment, he says, "it’s very high risk, very visionary".

The aim of the Grand Challenge grants, says Klausner, is to attract top basic-research scientists into work on neglected diseases that mainly affect the poor in developing countries. The 43 winners were selected from proposals by over 1,500 teams in 75 countries.

Other winners include a project to build a credit card-sized electronic device which could diagnose a wide range of diseases from a drop of blood, efforts to boost the nutritional content of staple crops such as rice and bananas, a project to develop edible vaccines that don’t need to be refrigerated, and an HIV vaccine designed to better protect women by provoking an immune response directly in the vaginal lining.