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GENOME CANCER

Partnership Brazil-USA moves ahead

Joint work with the Americans enters a more ambitious phase

After a year and a half of work with some significant results, the Human Genome Project, which is a consortium involving the Onsa network financed by FAPESP and the Ludwig Institute of Cancer Research, enters a new phase. A meeting to be held in October in Geneva is expected to consolidate the partnership of the group with the National Cancer Institute (NCI) in the USA and mark the adoption of more ambitious targets. Based on the information already obtained, the two groups will begin not only to place fragments of genes in sequence but also entire genes.

Furthermore, strategies will change and the targets will be expanded: the intention is not only to work with specific genes in cancerous cells but also with the entire human genome. Robert Strausberg, coordinator of the research at NCI and Andrew Simpson, coordinator of the Human Genome Cancer Project (HGCP) are both convinced that the two groups will be the greatest  responsible in the world for the placing in sequence of the human genome (see box).

The Brazilian end of the work helps the joint effort thanks to technology developed in Brazil: this is represented by the Orestes strategy which allows the sequencing of the center of the gene where most of the most relevant information is stored for the genes to perform their functions. It is a complementary technique to American research, which is dedicated to the sequencing of the tips of the genes.

Agreements such as these are always productive, “as long as they really represent collaboration and all the parties involved benefit”, observes Maria Aparecida Nagai, coordinator of one of the sequencing centers of the Human Gemone Cancer Project  at the Medical School of USP – University of São Paulo.

The announcement of the new phase was made at a seminar held on August 29 at FAPESP, in the presence of Strausberg, Simpson, Victor Jongeneel, coordinator of bio-information technology of the Ludwig Institute in Lausanne and Kenneth Buetow, head of the Laboratory of Population Genetics at the NCI.

Strausberg declared himself to be  “proud of the partnership with the Brazilian scientists,” and spoke of the research that he coordinates in the NCI, where the data base is being made available for helping map the various genetic systems related to cancer. According to Strausberg, the object of this work is to intervene in the molecular functions of the cancerous cells: “it is a genetic expressed data base which is aimed at the molecular pharmacology of cancer. It represents a new era in the treatment of cancer”.

The new stage
Strausberg and Simpson revealed that the joint effort has reached a new stage following completion by the Americans of one million sequencings and 500 thousand by the Brazilians. With these advances, it has been necessary to adopt new procedures, since the efficiency of the techniques used up to now tended to decline.

On the Brazilian side, the use of the Orestes strategy will have served its purpose by the end of the year. Simpson reveals that from then on, the group will begin to work with complete sequencing of genes identified from the US database. The NCI researchers will also begin to work with complete sequencing and, in addition, physically produce a copy of the genes.

“This work has enormous value for the world community”, says Simpson, “because based on the complete transcription of the gene, proteins and anti-bodies can be produced”. According to him, this does not represent cloning but rather to “build ” the gene based on computer-produced information”. In essence, the two sides – in Brazil, working with the virtual gene and in the USA, with the physical gene also – will seek to fill gaps left over from the initial phase of the research.

Strausberg and Simpson emphasize that the collaboration is mutual and open to other groups, which is in line with the target of building the widest ranging data base possible. Thereafter, it will be up to each participating country to use the information on the genome that is held in the GeneBank to produce medicines or diagnostic tests. “It is the responsibility of Brazil to continue providing the incentives to the laboratories”, says Maria Aparecida, of USP.

Expanded targets
Robert Strausberg, assistant director of the NCI, Victor Junheneel, coordinator of bio-information technology at the Ludwig Institute in Lausanne and Andrew Simpson, coordinator of the Human Gemone Cancer Project, comment below on the outlook for the joint work of the Brazilian and American research scientists in the sequencing of the human genome.

You only work with cancer tissues?
STRAUSBERG: The reason we have drawn closer to Brazil was to study cancerous tissues, but the cooperation has grown. Collectively, we now are talking of studying all the tissues.

You are not going to limit yourselves anymore to the study of cancerous cells?
SIMPSON: That’s quit right. There has been a globalization of the project. The two projects have grown and we took over the space that exists in the world to identify all the human genes. We have grown and we have ambitions to grow much more. Throughout the whole world there are many people trying to do what we do based on databases. But only we use high quality computer methods in the project. Everything indicates that we can lead the world in this technology.

Brazil, then, would lead the world in bio-information technology?
SIMPSON: We are not the greatest but we are respected among academic groups around the world.
JONGENEEL: The Brazilian research workers have a major specialization in bio-information technology as well as one of the most important projects in the world in this area. You can count on your fingers those groups that exist worldwide.
SIMPSON: There are a lot of theoretical groups, but few with the experience to execute and manage projects. The research scientists of the NCI have and we have as well. Few have the experience of executing a sequencing project of the size of “Xylella fastidiosa”. We have the capacity to blend bio-information technology with experimental biology and that is very costly.

It seems as if the American and the Brazilian projects will be responsible for revealing a major part of the mystery of the whole human genome.
SIMPSON: Your impression is correct. Nearly all the genes that have already been identified, and there are about 10 thousand, have sequences that originated from the two projects.

What are the differences between the Brazilian and the NCI cancer programs?
STRAUSBERG: The objective is the same, the strategies are different. But the scientific approaches are complementary.
SIMPSON: Plans and targets have not restricted us because a characteristic of the two programs, which defines its affinity, is flexibility. We will discover new technologies that have still not been invented. Because we are visionaries. We think that the larger part of the genes that have still to be identified, will be done by us.

What have you got which the others do not have?
SIMPSON: We have vision.
STRAUSBERG: We have the funds and the specialization. We are already the largest producers of sequences of specific human genes in the world.
SIMPSON: We understand that this work, which is very arduous and complex, is worthwhile. Other groups have an interest in a single gene. They clone the gene and study it in a biological context. Our vision is different: we have a global vision that it is essential to have the totality of human genes identified. Based on this, we are going to understand cancer and not just the cancer gene. We have a common vision that the most important objective is the definition of the overall human genome.
JONGENEEL: There are other projects in the world but I think we are doing better than the others are.
SIMPSON: Others that share our vision and want to join us are welcome. We have an objective which is to work for the good of humanity.

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