14th July 2005

Triple Disease Sequencing

Code to killers of 150,000

A Tsetse fly (Glossina morsitans) full of blood from a human arm. This is an important vector for African sleeping sickness.

A Tsetse fly (Glossina morsitans) full of blood from a human arm. This is an important vector for African sleeping sickness. [Wellcome Trust Medical Photo Library.]

The genomes of parasites that cause three major diseases in the developing world - sleeping sickness, Chagas' disease and leishmaniasis - have been decoded by international teams of scientists, it was revealed today.

These three 'neglected diseases' together kill more than 150,000 people every year and more than half a billion are at risk of contracting one of them. They also cause the annual loss of over 4m productive days of life.

The genomes of Trypanosoma brucei, Trypanosoma cruzi and Leishmania major were sequenced at the Wellcome Trust Sanger Institute, Cambridgeshire, UK, the Institute for Genomic Research in Washington DC, USA the Seattle Biomedical Research Institute, Seattle, WA, USA and the Karolinska Institute, Stockholm, Sweden. The results are published in the July 15 2005 edition of Science.

Professor Alan Fairlamb, from Dundee, one of the 250 researchers involved in the project, said scientific details about the three trypanosomatids - 'TriTryps' - were already being put to good use: "The genomic information has been made immediately available to scientists worldwide, so that no time is lost in trying to find new cures. We have already found this immediate release policy immensely useful in identifying new drug targets and are actively working to sort which ones are the best candidates for drug discovery."

Sleeping sickness - or Human African Trypanosomiasis - is caused by Trypanosoma brucei and is prevalent in 36 African countries and reduces victims to a zombie-like state. Melarsoprol, one of the drugs used to treat it contains arsenic and kills around one in twenty patients. Suramin, another remedy for the disease, which is spread by the tsetse fly, was discovered in 1921, when David Lloyd George was British Prime Minster.

N'gana, the animal version of sleeping sickness, results in annual cattle losses estimated at £2bn.

The Trypanosoma cruzi parasite causes Chagas Disease and is carried by blood-sucking 'assassin bugs'. It can lie dormant in victims for up to 20 years before causing severe internal damage, normally to the heart.

The Leishmania major parasite is carried by the female sandfly which passes it on to humans. The resulting infection often leaves heavy scarring leading to its victims being ostracised by their communities. It is prevalent on five continents and in 88 countries.

Dr Matt Berriman, who led the Wellcome Trust Sanger Institute team said: "A major aim of these projects was to produce a biochemical roadmap of how these parasites work. Parts of this map include at least 40 unusual steps that resemble those found in bacteria rather than humans. These are candidate targets for new drug development."

"The lack of success in the past should not discourage us from hope for the future. To have the genome sequence of all three parasites is a unique opportunity to understand these diseases. Comparing them, we can see how they are similar, what makes each tick and how they differ. The catalogues of genes - and hence the list of new drug targets - are more reliable because we have the three sequences."

Dr Jimmy Whitworth, Head of International Activities at the Wellcome Trust biomedical research charity, which provided just under £5m of funding* for the sequencing project, said: "The completion of this work may well give us a good opportunity to find new ways of treating these diseases which wreak devastation on disadvantaged people living in many resource-poor countries."

"Sleeping sickness and leishmaniasis are quite rightly called neglected diseases because so relatively little effort has been applied over the years to finding cures. The lack of safe, effective and cheap drugs to control them has been painfully obvious for too long. Hopefully, with the sequencing of these genomes, we can press on and discover ways to help the millions whose lives are made a daily misery by them."

Professor Sanjeev Krishna, a Wellcome Trust clinical scientist based at St George's, University of London, who carries out trypanosomiasis research in Angola, said: "Treating sleeping sickness is like a form of medical Russian Roulette because you don't know who will be saved or killed by the treatment available."

"Of course it shouldn't be like that and now we have completed this sequencing programme we can concentrate on finding the 'magic bullet' medicines that will help eradicate this disease."

The three parasites share many common features that are unusual elsewhere in biology - structures that are vital to their metabolism - but are in fact only distantly related - about as close as a fly is to a human. They contain between 8000 and 12,000 genes, but the teams have worked out that over 6000 genes are found in all three.

There are important differences between the parasites: They are transmitted by different insect vectors and have adopted distinct ways of hiding from the human body's immune system. Differences between the genomes - the 1000 or more genes that are not shared - provide a unique insight into the parasite's biology. Within these subsets of genes are those, for instance, that permit white blood cell invasion, in the case of Leishmania, or development within a tsetse fly in T. brucei.

Dr Karim Laouabdia, Director of Medecins Sans Frontieres' Campaign for Access to Essential Medicines, said: "There is a very urgent need to develop simple, rapid diagnostic tests for these diseases which can be used by medical staff in remote settings without high-tech laboratory facilities to identify which stage of sleeping sickness the patient is suffering. For these diseases we also need affordable, easy-to-use treatments at point of care - preferably these would be oral and combinations of molecules to combat resistance to any one drug."

Dr Bernard Pecoul, Executive Director of Drugs for Neglected Diseases (DNDi), a non-profit drug development initiative focused on harnessing public and private sector research and investment to develop new medicines and diagnostics, said: "People suffering these diseases are too poor to provide a profitable market for new medicines. The results of this sequencing project confirm that the science exists for neglected diseases."

"What we need now is public investment to turn this knowledge into affordable, useable medicines for patients and to stimulate much-needed research and development in neglected diseases."

*Funding for these research projects was provided by the Wellcome Trust, the National Institutes of Allergy and Infectious Diseases, the Burroughs Wellcome Fund, EU (BIO4-CT98-0079 to the EULEISH consortium) and the WHO Special Programme for Research and Training in Tropical Diseases.

Notes to Editors

Publication details

  • The genome of the African trypanosome Trypanosoma brucei.

    Berriman M, Ghedin E, Hertz-Fowler C, Blandin G, Renauld H, Bartholomeu DC, Lennard NJ, Caler E, Hamlin NE, Haas B, Böhme U, Hannick L, Aslett MA, Shallom J, Marcello L, Hou L, Wickstead B, Alsmark UC, Arrowsmith C, Atkin RJ, Barron AJ, Bringaud F, Brooks K, Carrington M, Cherevach I, Chillingworth TJ, Churcher C, Clark LN, Corton CH, Cronin A, Davies RM, Doggett J, Djikeng A, Feldblyum T, Field MC, Fraser A, Goodhead I, Hance Z, Harper D, Harris BR, Hauser H, Hostetler J, Ivens A, Jagels K, Johnson D, Johnson J, Jones K, Kerhornou AX, Koo H, Larke N, Landfear S, Larkin C, Leech V, Line A, Lord A, Macleod A, Mooney PJ, Moule S, Martin DM, Morgan GW, Mungall K, Norbertczak H, Ormond D, Pai G, Peacock CS, Peterson J, Quail MA, Rabbinowitsch E, Rajandream MA, Reitter C, Salzberg SL, Sanders M, Schobel S, Sharp S, Simmonds M, Simpson AJ, Tallon L, Turner CM, Tait A, Tivey AR, Van Aken S, Walker D, Wanless D, Wang S, White B, White O, Whitehead S, Woodward J, Wortman J, Adams MD, Embley TM, Gull K, Ullu E, Barry JD, Fairlamb AH, Opperdoes F, Barrell BG, Donelson JE, Hall N, Fraser CM, Melville SE and El-Sayed NM

    Science (New York, N.Y.) 2005;309;5733;416-22

  • The genome of the kinetoplastid parasite, Leishmania major.

    Ivens AC, Peacock CS, Worthey EA, Murphy L, Aggarwal G, Berriman M, Sisk E, Rajandream MA, Adlem E, Aert R, Anupama A, Apostolou Z, Attipoe P, Bason N, Bauser C, Beck A, Beverley SM, Bianchettin G, Borzym K, Bothe G, Bruschi CV, Collins M, Cadag E, Ciarloni L, Clayton C, Coulson RM, Cronin A, Cruz AK, Davies RM, De Gaudenzi J, Dobson DE, Duesterhoeft A, Fazelina G, Fosker N, Frasch AC, Fraser A, Fuchs M, Gabel C, Goble A, Goffeau A, Harris D, Hertz-Fowler C, Hilbert H, Horn D, Huang Y, Klages S, Knights A, Kube M, Larke N, Litvin L, Lord A, Louie T, Marra M, Masuy D, Matthews K, Michaeli S, Mottram JC, Müller-Auer S, Munden H, Nelson S, Norbertczak H, Oliver K, O'neil S, Pentony M, Pohl TM, Price C, Purnelle B, Quail MA, Rabbinowitsch E, Reinhardt R, Rieger M, Rinta J, Robben J, Robertson L, Ruiz JC, Rutter S, Saunders D, Schäfer M, Schein J, Schwartz DC, Seeger K, Seyler A, Sharp S, Shin H, Sivam D, Squares R, Squares S, Tosato V, Vogt C, Volckaert G, Wambutt R, Warren T, Wedler H, Woodward J, Zhou S, Zimmermann W, Smith DF, Blackwell JM, Stuart KD, Barrell B and Myler PJ

    Science (New York, N.Y.) 2005;309;5733;436-42

  • The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease.

    El-Sayed NM, Myler PJ, Bartholomeu DC, Nilsson D, Aggarwal G, Tran AN, Ghedin E, Worthey EA, Delcher AL, Blandin G, Westenberger SJ, Caler E, Cerqueira GC, Branche C, Haas B, Anupama A, Arner E, Aslund L, Attipoe P, Bontempi E, Bringaud F, Burton P, Cadag E, Campbell DA, Carrington M, Crabtree J, Darban H, da Silveira JF, de Jong P, Edwards K, Englund PT, Fazelina G, Feldblyum T, Ferella M, Frasch AC, Gull K, Horn D, Hou L, Huang Y, Kindlund E, Klingbeil M, Kluge S, Koo H, Lacerda D, Levin MJ, Lorenzi H, Louie T, Machado CR, McCulloch R, McKenna A, Mizuno Y, Mottram JC, Nelson S, Ochaya S, Osoegawa K, Pai G, Parsons M, Pentony M, Pettersson U, Pop M, Ramirez JL, Rinta J, Robertson L, Salzberg SL, Sanchez DO, Seyler A, Sharma R, Shetty J, Simpson AJ, Sisk E, Tammi MT, Tarleton R, Teixeira S, Van Aken S, Vogt C, Ward PN, Wickstead B, Wortman J, White O, Fraser CM, Stuart KD and Andersson B

    Science (New York, N.Y.) 2005;309;5733;409-15

  • Comparative genomics of trypanosomatid parasitic protozoa.

    El-Sayed NM, Myler PJ, Blandin G, Berriman M, Crabtree J, Aggarwal G, Caler E, Renauld H, Worthey EA, Hertz-Fowler C, Ghedin E, Peacock C, Bartholomeu DC, Haas BJ, Tran AN, Wortman JR, Alsmark UC, Angiuoli S, Anupama A, Badger J, Bringaud F, Cadag E, Carlton JM, Cerqueira GC, Creasy T, Delcher AL, Djikeng A, Embley TM, Hauser C, Ivens AC, Kummerfeld SK, Pereira-Leal JB, Nilsson D, Peterson J, Salzberg SL, Shallom J, Silva JC, Sundaram J, Westenberger S, White O, Melville SE, Donelson JE, Andersson B, Stuart KD and Hall N

    Science (New York, N.Y.) 2005;309;5733;404-9

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The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease.

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The Wellcome Trust is the most diverse biomedical research charity in the world, spending about £450 million every year both in the UK and internationally to support and promote research that will improve the health of humans and animals. The Trust was established under the will of Sir Henry Wellcome, and is funded from a private endowment, which is managed with long-term stability and growth in mind.

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