Royal Society of NSW News & Events

Royal Society of NSW News & Events

1139th General Monthly Meeting

"TB: controlling the old scourge"

Professor Warwick Britton, Head, Mycobacterial Research Group
Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney

Wednesday 5 October 2005, 6 pm for 6.30
Conference Room 1, Darlington Centre, City Road


Nine million people contract tuberculosis every year and two million die. Over 95% initially control the infection, but may develop tuberculosis later. Why some patients resist and others develop the disease is not fully understood. At least 10 different genes have been shown to influence the control of tuberculosis. This will be illustrated by our work on a purinergic receptor on macrophages, which triggers killing of mycobacteria. The current BCG vaccine is only partially effective. More effective vaccines are urgently needed. One approach is to improve the effect of BCG by expressing parts of the M. tuberculosis organism in BCG. Another approach is to create attenuated strains of M. tuberculosis which may be more effective than BCG as vaccines and are safe because of their reduced virulence. The third approach is to use genes or proteins from M.tuberculosis as sub-unit vaccines. All of these approaches will be discussed.


Warwick Britton is Bosch Professor of Medicine, Head of the Disciplines of Medicine, and Infectious Diseases and Immunology at the University of Sydney and Head, Mycobacterial Research Group, Centenary Institute of Cancer Medicine and Cell Biology. He has made extensive contributions to the study of mycobacterial infections over the last 20 years. From 1986 to 1989, he established the Mycobacterial Research Laboratory in Kathmandu for the study of human immune responses to Mycobacterium leprae. His studies have spanned the definition of mycobacterial antigens, the cloning and manipulation of mycobacterial genes, the characterisation of human and mouse host responses to mycobacterial infections and the development of recombinant mycobacterial, viral and DNA vaccines. He has additional research interests in cellular immune responses in allergic disease and the epidemiology of asthma.

Report on the General Monthly Meeting by Jak Kelly

TB has been well controlled in Australia but unfortunately not in many other parts of the world. The organism which causes TB, Mycobacterium tuberculoses, identified by Robert Koch in the 1880s, is one of the most successful and infectious pathogens. It is extremely well adapted to humans. It secretes numerous proteins to protect itself and has twelve different mechanisms to overcome our immune system. It infects a third of humanity and kills 5-10% of those infected. TB has returned to many communities and interacts with AIDS. About a third of AIDS deaths are now due to TB and a million new TB cases a year are added because of AIDS. This is because a specific type of T-cell is involved in the control of both diseases and their depletion by AIDS weakens their ability to destroy M. tuberculosis.

Genetic studies show that about 30% of TB cases are due to multiple genes, each having a small effect. The wealth of information now available on the human genome enables some of these base differences to be related to differing susceptibilities to specific diseases. Such work on relating vitamin D receptor variations to osteoporosis has proved useful in TB studies. Migrant Gujirati people in the unsunny London climate suffer a vitamin D deficiency, particularly the women whose traditional attire exposes little skin to the sun to make vitamin D, a vitamin also involved in defending against TB. This gene-environmental interaction gives these people a TB rate eighty times that of NSW.

ATP is the energy source of all cells but can have other functions. It can leave the cell and bind to the surface of other cells. Professor Britton and his colleagues have studied the role of ATP in killing TB bacteria and relating it to small genetic variations between populations and individuals. For example one snip reduces bacterial killing by 50% but two reduces it to nearly zero. This has been investigated in two independent groups, a population of refugees, who have been followed for 20 years having been screened for TB on entering Australia and a population of Australian TB sufferers. Both population studies supported the above findings. There were however some notable exceptions which are now under study. Clearly many other genes are involved in the ability to kill TB and the same is true of other diseases such as asthma.

After an extended and interesting number of questions from the floor were answered in detail by the speaker, a vote of thanks was proposed by Professor Bill Sewell and the President presented a Society Speaker's Medal to Professor Britton.

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