14 July 2005
Triple Disease Sequencing
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 Karolinska Institute, Stockholm, Sweden,
the Seattle Biomedical Research Institute, Seattle, WA and the Institute for Genome Research in
Washington DC, USA. The results are published in today’s (July 15th) edition of Science.
Professor Alan Fairlamb, from the School of Life Sciences at the University of 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:
The Wellcome Trust is an independent research-funding charity established in 1936 under the will
of tropical medicine pioneer Sir Henry Wellcome. The Trust’s mission is to promote research with
the aim of improving human and animal health. It currently spends more than £400m p.a.
The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome
Trust, was founded in 1992 as the focus for UK sequencing efforts. 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 such as mouse and zebrafish, and more than 50 pathogen genomes. In
October 2001, new funding was awarded by the Wellcome Trust to support a new range of post-genomic
programmes designed to understand the biological function of genes and their relevance to our
health. These programmes are built around a Faculty of more than 30 senior researchers.
Media Contacts:
Wellcome Trust Sanger Institute:
Don Powell
Office : 00 44 (0)1223 494956
Mobile : 07753 775397
Press.office@sanger.ac.uk
Wellcome Trust:
Barry Gardner
Office: 00 44 207 611 7329
Mobile 07711 193041
b.gardner@wellcome.ac.uk
www.wellcome.ac.uk
By Angela Durcan, Press Officer 01382 344768, out of hours: 07968298585, a.durcan@dundee.ac.uk | 
