[extropy-chat] New Genome Project

[Olga Bourlin]

http://www.nytimes.com/2005/03/28/health/28cancer.html?hp&ex=1112072400&en=e1f5e3e46bd5feb4&ei=5094&partner=homepage
March 28, 2005
In Battling Cancer, a Genome Project Is Proposed
By ANDREW POLLACK

pening a new front in the battle against cancer, federal officials are 
planning to compile a complete catalog of the genetic abnormalities that 
characterize it.

The proposed Human Cancer Genome Project, as it is being called for now, 
would be greater in scale than the Human Genome Project, which mapped the 
human genetic blueprint. It would seek to determine the DNA sequence of 
thousands of tumor samples, looking for mutations that give rise to cancer 
or sustain it.

Proponents say a databank of all such mutations, which would be freely 
available to researchers, would provide invaluable clues for developing new 
ways to diagnose, treat and prevent cancer.

"Knowing the defects of the cancer cell points you to the Achilles' heel of 
tumors," said Dr. Eric S. Lander, director of the Broad Institute, a genetic 
research center in Cambridge, Mass., that is affiliated with Harvard and the 
Massachusetts Institute of Technology.

The project would cost roughly $1.35 billion over nine years, but where the 
money will come from is still uncertain. For now, the government is likely 
to start with some smaller pilot projects, officials said.

Some scientists are dubious about the cost and are concerned that a big 
science project could take money away from smaller ones run by individual 
scientists.

Dr. J. Craig Venter, who led a private project to determine the human DNA 
blueprint in competition with the Human Genome Project, said it would make 
more sense to look at specific families of genes known to be involved in 
cancer.

"Diverting a billion or two dollars from other areas of research when it's 
not clear what answer we'd get, there might be better ways to move cancer 
research forward," Dr. Venter said.

But Dr. Lander and other proponents say the time is right for such an effort 
because the Human Genome Project has provided the underlying human DNA 
sequence with which tumor cells can be compared. In addition, the cost of 
sequencing is dropping. And discoveries of individual cancer-related genes 
have already helped lead to new drug therapies.

The proposal, presented last month to an advisory committee to the National 
Cancer Institute, was drawn up by a group led by Dr. Lander and Dr. Leland 
H. Hartwell, a Nobel laureate who is president of the Fred Hutchinson Cancer 
Research Center in Seattle. Drafters included Dr. Harold Varmus, a Nobel 
laureate and a former director of the National Institutes of Health, and Dr. 
Bruce Stillman, president of the Cold Spring Harbor Laboratory on Long 
Island.

Dr. Varmus, president of the Memorial Sloan-Kettering Cancer Center in New 
York, said the project could "completely change how we approach cancer."

Leaders of two agencies within the National Institutes of Health that would 
likely take the lead in financing the project said they were eager to go 
ahead.

"We are committed to do the sequencing of the cancer genomes," Dr. Anna D. 
Barker, deputy director for advanced technologies and strategic partnerships 
at the National Cancer Institute, said in an interview. "What we're trying 
to do is accelerate progress against this disease."

Dr. Francis Collins, director of the National Human Genome Research 
Institute, said, "I can confidently tell you that something will happen 
here."

The federal officials and Dr. Lander acknowledged that finding money for the 
project would be difficult in a time of tight budgets. They said that new 
money would probably have to be appropriated by Congress and that the 
pharmaceutical industry might contribute because the information would be 
useful for drug development.

The project, which might end up with a different name, would determine the 
sequence of the DNA in at least 12,500 tumor samples, 250 samples from each 
of 50 major types of cancer. By comparing the order of the letters of the 
genetic code in the tumor samples with one another and with sequences in 
healthy tissue, it should be possible to pinpoint mutations responsible for 
cancer.

But the proposition is extremely daunting. In general, each tumor cell holds 
a full panoply of human DNA, a string of three billion letters of the 
genetic code. So determining the full sequence of all the tumors would be 
the equivalent of 12,500 human genome projects. At a cost of many millions 
of dollars for one genome, the full project would be out of the question for 
now.

So the cancer proposal for now is to sequence only the active genes in 
tumors, which make up 1 percent to 2 percent of the DNA, Dr. Lander said. 
Even that would require at least 100 times as much sequencing as the Human 
Genome Project.

The work would cost nearly $1 million per tumor sample today, or a total of 
about $12.5 billion, according to the committee's proposal. The estimated 
cost of $1.35 billion is based on an expectation that sequencing costs will 
decline to one-tenth of what they are now in the next few years.

The Human Genome Project, now all but complete, cost $3 billion, but only 
about $300 million was spent on the actual DNA sequencing, with the rest 
going to development of technology.

"The technology available today would not be up to the task of doing this 
entire project," said Dr. Lander, who was a leader of the Human Genome 
Project. But he added, "The cost of sequencing is dropping enough that this 
is no longer unthinkable."

Indeed, he and Dr. Collins said, the project would promote further 
improvements in sequencing and show that it is still a useful technology.

"Some people have assumed that the genome project was over and sequencing 
wasn't worth investing in," said Dr. Collins, whose institute financed most 
of the Human Genome Project.

The Broad Institute, Dr. Lander's group, is a major DNA sequencing center 
and would presumably be a candidate for contracts for the cancer genome 
project. Many of the other people on the committee that put together the 
proposal represent institutions that might also receive grants from it.

There have already been some notable successes in using information about 
mutations to fight cancer, which is really a class of diseases in which 
cells in the body grow out of control because of the accumulation of 
mutations. While some of these mutations are inherited, most occur after a 
person is born.

Most cases of chronic myelogenous leukemia, a blood cancer, are caused by a 
particular chromosomal defect that leads to production of an aberrant 
protein. The drug Gleevec, which is designed to block this protein, has had 
remarkable success against this disease. Scientists have since found other 
genetic mutations that confer resistance to Gleevec, and companies are now 
using such information to design drugs to overcome that resistance.

The lung cancer drug Iressa can be very effective, but only in about 10 
percent of patients who use it. Last year, scientists discovered that the 
drug seemed to work best in people whose tumors have mutations in a 
particular gene.

Just in the last few days, researchers led by Dr. D. Gary Gilliland of 
Brigham and Women's Hospital in Boston and Harvard reported that three types 
of leukemia appear to be caused by mutations in the same gene.

There are already some smaller projects under way looking for mutations, 
either in a particular type of cancer or in particular types of genes.

The Wellcome Trust Sanger Institute in Britain, a major participant in the 
Human Genome Project, has had a cancer genome program for several years. It 
has discovered a particular mutation in about two-thirds of cases of 
melanoma, a deadly skin cancer.

Scientists at Johns Hopkins University have unraveled some genetic changes 
involved in the origin of colon cancer. They are now working with Perlegen 
Sciences, a genomics company in California, on a comprehensive genetic scan 
of colorectal tumors.

But backers of the cancer genome project say faster progress could be made 
with one big, coordinated effort. And they say that despite the progress so 
far, scientists understand only a minority of the genetic changes involved 
in cancer.

There are other potential obstacles besides the cost of sequencing. One 
would be distinguishing which mutations are important, because many of those 
found would have nothing to do with cancer. The proposal says researchers 
should focus on mutations that occur in at least 5 percent of tumors of a 
certain type.

Yet another problem is that tumors can mutate so rapidly that two cells in 
the same tumor may have different mutations. So some mutations may be 
missed, depending which cells are used for the genetic analysis. "We can 
spend $2 billion on something and get a lot of data, but I'm not convinced 
it will do us much good," said Dr. Garth Anderson, an expert on cancer 
genetics at the Roswell Park Cancer Institute in Buffalo.

And in some cases cancer is caused not by changes in the sequence of DNA but 
by so-called epigenetic changes, in which the attachment of a chemical to 
DNA turns off a gene.

"To concentrate only on mutations, you might pick up 50 percent of what you 
need to know or even less about what goes into the initiation and 
maintenance of cancer," said Dr. Stephen B. Baylin, a professor of oncology 
and medicine at Johns Hopkins.

The proposal for the project does mention looking for epigenetic changes, 
but says the technology to study them is not well developed.

Supporters of the project say that the barriers can be overcome and that the 
project should proceed.

"Whether it's practical, whether it's doable, how much it costs, I take that 
out of the picture," said Dr. Brian Druker, a professor at the Oregon Health 
and Science University who helped develop Gleevec and also served on the 
committee that drew up the proposal for the cancer genome project. "These 
are the starting blocks that we need to develop a cure."



Copyright 2005 The New York Times Company | Home 
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