Double Success In Fight Against Malaria
A six-year project to sequence the genome of the Plasmodium falciparum parasite, which causes the most deadly form of malaria and kills one child every 20 seconds, has been completed.
In a separate project, an international consortium of researchers has sequenced the genome of the Anopheles gambiae mosquito*, which transmits the parasite to humans.
These latest developments mean researchers now have a detailed insight into the DNA or “book of life” for humans, parasites and mosquitoes- the three components in the malaria cycle. The draft human genome was published by an international consortium in February 2001.
The £ 18.5m Plasmodium falciparum project was funded in the UK by the Wellcome Trust (£ 8m) and in America by the Burroughs-Wellcome Fund (£ 4.9m) ; the National Institute of Allergy and Infectious Diseases (£ 2.2m) and the US Department of Defense (£ 3.4m).
Data from the project is already being used by researchers working on drug and vaccine development and its website, The Plasmodium genome database: http://www.plasmodb.org/ is receiving around 3,000 hits a day from more than 100 countries.
More information
Dr. Mike Dexter, Director of the Wellcome Trust, said: “Some scientists believed it would never be possible to finish this project because of the technical difficulties. But a high-calibre international collaboration has shown that sometimes you can achieve what other people thought would be impossible.”
Malaria kills up to 2.7 million people a year, most of them children under five-years old in sub-Saharan Africa**. Experts estimate the equivalent of 45 million years of productive human life are lost annually through premature death and disability caused by the disease***, which threatens 40% of the world’s population. Along with HIV/AIDS and TB it is one of the biggest infectious disease killers in the world.
Kofi Annan, Secretary General of the United Nations said: “The Anopheles gambiae and Plasmodium falciparum genome sequences constitute a potential major breakthrough for the development of novel strategies in combating malaria. If this technology and its potential clinical advances can be distributed fairly among the world’s population it could offer new opportunities for improving global health and for helping developing countries break free of the shackles of this devastating disease.”
“Malaria not only imposes an appalling degree of human suffering – it also constitutes an obstacle to development itself.”
Results of the work by a team of 150 researchers engaged in the Plasmodium falciparum sequencing project are published in Nature (3rd October 2002). The work was carried out in the UK at the Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, which also carried out one-third of the human genome sequencing programme, and in the USA at The Institute for Genomic Research and Stanford University.
Dr. Neil Hall, who led the 50-strong team at the Sanger Institute, said: “This is a major breakthrough in malaria research. For the first time we have all the genetic information we need to understand how the parasite works and can find the weak spots in its armoury.”
“The sequencing was difficult because parts of the DNA are very unstable, which means some pieces just fell to bits when you tried to work with them and some of the chromosomes were very hard to separate. We had to use all available technologies to tackle these problems.”
“The amount of data involved was phenomenal. It was a bit like tearing up half a dozen bibles, scattering the pieces over a playing field then trying to put them together again.”
The Plasmodium falciparum genome, which consists of 24 million base pairs of DNA is divided into 14 chromosomes- compared to 23 in the human genome. The Sanger Institute sequenced chromosomes 1, 3, 4, 5, 6, 7, 8, 9 and 13 : The Institute for Genome Research (TIGR) sequenced 2, 10, 11 and 14 : Stanford sequenced chromosome 12.
The Plasmodium falciparum sample was taken from a 10-year-old Dutch schoolgirl who contracted malaria near Schiphol Airport, Amsterdam in July 1979.The isolate was cultured at Nijmegen University and a clone – 3D7 – was eventually made in 1985.
The simultaneous publication in Nature of the Plasmodium falciparum genome and in Science of the Anopheles gambiae genome has been welcomed by researchers and agencies involved in the fight against malaria.
Professor Chris Newbold of Oxford University, who helped initiate the Plasmodium falciparum project said: “This represents a quantum leap in our understanding of malaria. The challenge to researchers worldwide is to use the genome sequence in imaginative and innovative ways and ensure that the efforts of the teams from both sides of the Atlantic are rewarded with new ways of tackling the disease.”
Dr. Carlos Morel, director of the UNDP-World Bank-WHO Special Programme for Research & Training in Tropical Diseases said: “This is an extraordinary moment in the history of science. At last, the enormous power of modern technology is penetrating the mysteries of an ancient disease which continues to kill millions. With the knowledge gained from this molecular dissection of the malaria parasite and its major insect vector, we have moved far ahead on the path toward new approaches, new therapies, that have the potential to save countless lives.”
Over the last five years the Wellcome Trust has invested more than £70m in malaria research, much of it through its units in Kenya, Thailand, Vietnam and Malawi.
Related Links
The Wellcome Trust malaria website can be found at http://wellcome.org/malaria/
Footnotes
*** The International Anopheles Genome Project has sequenced the genome of Anopheles gambiae, the major African malaria vector. The project was funded largely by the US National Institute of Allergy and Infectious Diseases and by the French Government, with the World Health Organization/Tropical Disease Research programme providing a coordinating role and assisting in database development.
The genome has been sequenced by Celera Genomics and Genoscope, and annotated by Celera and Ensembl -the latter being a collaboration between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute. The European Molecular Biology Laboratory, the Institute of Molecular Biology and Biotechnology in Crete, the Institut Pasteur in Paris, TIGR, and the Universities of Iowa, Rome and Notre Dame also contributed to the collaboration. The sequence is available at http://metazoa.ensembl.org/Anopheles_gambiae/Info/Index
** “The Intolerable Burden of Malaria: A New Look at the Numbers” – Multilateral Initiative on Malaria report 2001.
*** Malaria Foundation International
