By Matt Jones
NEW YORK (GenomeWeb News) – The National Human Genome Research Institute has laid out its vision for genomics in a report published in today's issue of Nature, detailing the challenges for the field as it migrates toward the clinic.
Developed by NHGRI over a roughly two-year period, the report outlines a number of key areas that will require focus and investments in order for scientists worldwide to maximize the "many compelling opportunities" and meet the "significant challenges" confronting the next decade of genomics research.
"This new vision is ambitious and far-reaching, both in scope and timing," wrote the report's authors, NHGRI Director Eric Green and Director of Extramural Research Mark Guyer. "It goes well beyond what any one organization can realistically support, and will … require the creative energies and expertise of genome scientists around the world and from all sectors, including academic, government, and commercial," they wrote.
The planning process started in 2008 by former NHGRI Director and current National Institutes of Health Director Francis Collins. It came five years after the previous NHGRI plan was published and after a number of changes in the field. One such recent change, Guyer told GenomeWeb Daily News, was the enhanced speed and decreased cost of genomic sequencing and the development of new pharmacogenomics technologies.
When the last report was started two years ago, Guyer explained, "I don't think that the magnitude or the impact of what occurred [in next-generation sequencing] was really anticipated."
During the process, NHGRI's leadership wrote white papers, sought stakeholder input, held workshops, started web-based conversations, and held a summary meeting to develop a vision of where human genomics research stands today and what it needs to continue on the path toward informing science and medicine.
As GenomeWeb Daily News reported yesterday, In "Charting a Course for Genomic Medicine from Base Pairs to Bedside," Green and Guyer assert five core areas that will require advancement: understanding genomic structures; understanding basic genome biology; understanding disease biology, advancing the science of medicine, and improving the effectiveness of healthcare.
For each of the core areas the authors identified, they noted several needs and areas for growth and improvement.
To understand the biology of genomes, scientists will need to improve existing catalogues of genomic data and develop new ones, such as collections of genetic variation, functional genomic elements, proteins, and other biological elements.
Complete characterization of the genetics of complex diseases will require identification of the full spectrum of human genomic variation, which could be used to inform new methods for preventing disease transmission, for example.
"We have done an enormous amount in terms of understanding a lot of the basic structure of genomes, but there's still a tremendous amount to do in terms of function," Guyer told GWDN.
New technologies will be needed in this area, including cheap and accurate sequencing technologies so they may be used to screen newborn babies, as well as for other applications. Point-of-care tools also will be needed to take genomic medicine beyond the clinic, and highly specific affinity reagents should be developed for all transcription factors, nucleic-acid binding proteins, histone forms, and chromatin modifications.
Better technologies also are needed for measuring phenotypes, behaviors, exposures, and other environmental variables.
"What you want to be able to do eventually is to compare highly accurate genomic data with highly accurate phenotypic data, so there's a long way to go before we get there," said Guyer.
Genomics offers great potential for learning about the biology of disease. Genome-wide association studies, for example, have implicated hundreds of non-coding genomic regions involved in complex diseases.
Such advances pose new problems, however, and steps will need to be taken to make these studies pay off. Fully understanding disease will require capturing much of the genetic variation across the human population, and it will require the annotation and correlation of genomic information with high quality phenotypic data.
"The surest way to develop the basis for controlling or preventing disease is understanding the basic biology," including how "normal biology is disrupted by both the genetic and environmental factors that lead to disease. Once you have a basic understanding of what the biology of the disease is and what the biological mechanisms that lead to disease are, then you have ways for designing specific approaches either to prevention or therapy," Guyer told GWDN.
Many Considerations for Genomic Medicine
The authors explained that genomic discoveries will advance the science of medicine dramatically in the coming decades, but substantial amounts of research will be needed to get such advances to the clinic. Rapid diagnostic technologies and the use of pharmacogenomics in drug development and treatment and in clinical trials all will have impacts on medicine in the coming years, Green and Guyer state.
Genomics certainly will be used in the near future to begin improving healthcare, according to the report, but to get the benefits of these new tools other advances need to be made. Electronic medical records will be very useful for searching, annotating, and sharing genomic data in research, but systems will be needed to handle ethical, legal, and regulatory issues and to protect the public's privacy.
Bringing genomics into the healthcare system also will require productive interactions with regulatory systems in each country.
For genomic research to translate into genomic medicine usefully and effectively, steps will need to be taken to educate health care professionals, patients, and the public. The authors suggested a variety of pilot efforts that would test the effectiveness of educational programs in engendering "genomically literate healthcare providers, patients, and the general public."
Studying how genomic advances actually help society will require studies that look into psychosocial and ethical issues in genomic research and genomic medicine, and legal and public policy issues. Long-term, genomic knowledge and medicine also may bring up broader societal issues having to do with race and ethnicity, human origins, free will and individual responsibility, all of which may require research to consider their effects.
Guyer told GWDN that the review aimed to realistically identify a broad range of potential advancements and issues that likely will arise in the very near future, and not an argument for how genomics will be the answer to all medical problems.
He said that some of the best examples of genomic medical advances that are currently underway and paying off include the molecular taxonomy and characterization of tumors, pharmacogenomic approaches for predicting responses to drug treatments based on genotype, and the approach to drug development being led by NIH's molecular libraries and chemical genomics programs.
"The medical issues that are being addressed are complex, and most of them are not going to have magic bullet solutions," said Guyer. "What we are trying to do is describe what we think are actually reasonable or realistic expectations people should have ... and not to say that genomics is the sole answer … to understanding disease."
This effort was more an attempt to "describe what contributions genomics can make," he said.