Oncologists Must Make Transition to ‘Post-Genome World’

MIAMI BEACH—Ultimately, historians may call the sequencing of the human genome the “defining event of our age,” Barry S. Coller, MD, of Mt. Sinai School of Medicine, New York, said at the annual meeting of the American Society of Hematology (ASH). Dr. Coller, the outgoing president of ASH, chaired a policy symposium on the post-genome world.

“We are beginning to make the transition to the post-genome world, but the pace will accelerate remarkably over the next several years as we move from knowing 7% of the genome to knowing 100%,” Dr. Coller said.

Richard Klausner, MD, director of the National Cancer Institute, defined the post-genome world as “the shift to a systematic approach to biologic systems, processes, and phenomena based upon knowledge of all the relevant components and the ability to query, analyze, and interpret these systematic data sets.”

The implications of this shift are fourfold, Dr. Klausner said. First, scientists will have the advantage “of playing with a full deck as opposed to one where many or most of the cards are missing. We can finally bring rigor and meaningful effect to scientific exploration.”

Second, he said, it raises the possibility of taking a “synthetic rather than purely reductionist approach to medical research, enabling us to observe and intervene in the complex networks of pathways of cells and organisms that reflect actual biology.”

Third, the principles of genomics, or systematic biology, can be generalized to produce new and productive interfaces between chemistry or computation science and biology.

Fourth, true scientific paradigm shifts alter how we think, and they yield new insights.

Bringing Order Out of Chaos

Dr. Klausner compared the transition to the post-genome world in biology to the shift in chemistry after the periodic table was developed. “It brought order out of chaos and revealed the underlying rules that govern matter,” he said. In terms of biology, genomic research can reveal “organizational principles that reflect the manifest rules of more than 3 billion years of evolution.”

Biologically, he said, cancer is “a strange and remarkable disease best described as a disease of genomic instability. It is always a genetic disease, not heritable but due to the accumulation of a number of genetic changes. The central challenge of cancer biology, he said, is to read and interpret these genetic changes, “to translate this Rosetta stone of altered genetic information.”

To accomplish this, Dr. Klausner said, the NCI has set on a project to identify all, or as close to all as possible, human genes over the next few years—the Cancer Genome Anatomy Project (CGAP). “This is different from the Human Genome Project. It is a post-genome project, although we are not waiting for the genome project to finish,” he said.

A part of this project involves developing the Gene Annotation Index, which aims to annotate where and when oncogenes are expressed. “For our purposes, we are annotating them across all cellular lineages, during cancer development, and in cancer,” Dr. Klausner said.

What will scientists do with all of this new information? Dr. Klausner said that it is time “to move from a pathologic to a molecular classification and description of cancer.” The NCI, he said, will be providing $50 million for researchers who wish to help develop this new classification system based on gene expression.

Genetic information can also be used to help researchers understand how carcinogens work, he said, for example, the relationship between alcohol and nasopharyngeal carcinoma. “We can’t interpret carcinogens if we don’t understand the genetic filter they must pass through,” he noted

The NCI is also funding Chemistry Biology Centers that will “map out the predicted structure and function of gene products, using the remarkable level of evolutionary conservation seen across all of life.” Researchers at these centers will be challenged to apply simple principles of Darwinian biology to chemistry, he said.

Finally, Dr. Klausner outlined four challenges for scientists in the post-genome world:

They must learn new technologies to support the development of genomic information and then “figure out how to export this information to the scientific community and the clinical research community. We need to be prepared to use this technology for new ways of thinking about experimentation and describing populations, individuals, and disease states.”

Should Be Developed Jointly

Dr. Klausner emphasized that these fundamental enabling technologies should be developed jointly by academia, government, and industry, so that they are not “tied up in short-sighted patents and licenses that take this information, our shared heritage, and hide it from the public good.”

Scientists must move forward with informatics, tools to deal with these new data. “I predict that a tremendous fraction of biological and biomedical research will be in developing a new mathematics and a new set of analytic, informatics, and communication approaches,” he said.

Scientists must be able to work in a multidisciplinary setting. “We need to examine our academic structures to make sure that these structures are not rigid and frozen in the past but are able to respond to the multidisciplinary research that the post-genomic world demands,” Dr. Klausner commented.

He also noted the need for academia “to find a way to evaluate contributions to collaborations so that we can value them and link individual contributions to career development, and not penalize researchers for collaborating.”

Scientists need to be part of a clinical research interface that provides “good mechanisms for the rapid assessment of these new technologies in the clinic and for their rapid dissemination and use.”