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- Subject: [DOEWatch] Human Genome Promise
- From: Magnu96196@aol.com
- Date: Fri, 9 Jul 1999 14:32:32 EDT
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<A
HREF="http://www.rdmag.com/features/0699rd/06venter.htm">http://www.rdmag.com/
features/0699rd/06venter.htm</A>
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Human Genome Promise
A wealth of genomic knowledge will expand understanding of biological
processes and lead to new diagnostic tools that can assess health risks and
create personalized medicine.
Based on remarks by J. Craig Venter,
president of Celera Genomics.
The Human Genome Project was officially launched in 1990 as a $3 billion,
15-year federal initiative to map and sequence the complete set of human
chromosomes and those of several model organisms. As a result of this
commitment by the U.S. government, our biotechnology industry now leads the
world in the science it undertakes, the jobs it creates, and the products it
delivers to improve human health. Also largely through the success of this
relatively small federal program, whole pharmaceutical companies are
restructuring their drug discovery and development process to be based on
genomics.
Unfortunately, a misunderstanding occurred when the Human Genome Project was
initially explained to Congress and the American public. The scientists who
helped organize the program indicated that sequencing the human genome was
the key to improving our knowledge of human biology. This statement led many
to believe that obtaining the complete human DNA sequence would mark the end
of the project. In fact, the acquisition of the sequence is only the
beginning. The sequence information provides a starting point from which the
real research into the thousands of diseases that have a genetic basis can
begin. So, the sooner we can get to this starting point, the sooner we can
begin to see a payoff in ultimately improving human health.
It was in this spirit that, on May 11 of last year, Perkin-Elmer Corp.,
Norwalk, Conn., and Venter announced their intention to create a new company,
Celera Genomics, that would sequence the Drosophila fruit fly genome and the
human genome by the end of 2001, as part of its initial projects. These two
sequencing projects are being undertaken using DNA sequencing technology
developed by Perkin-Elmer and a DNA sequencing strategy that was pioneered by
Venter and his colleagues at The Institute for Genomic Research (TIGR),
Rockville, Md., known as the whole-genome shotgun sequencing method.
Human Genome Sequencing Goals
The aim of the project is to produce a highly accurate, ordered sequence that
spans more than 99.9% of the human genome. The accuracy of this sequence is
intended to be comparable to the standard now used in the genome sequencing
community of fewer than one error in 10,000 base pairs. Celera has begun
working with other genome centers to ensure that the sequence meets the
requirements of the scientific community for accuracy and completeness.
As with the federally funded project, the goal is not to obtain the sequence
for its own sake, but to obtain it to serve as a foundation of data upon
which new research into human health can be built. The goal is to develop the
definitive resource of genomic and associated medical information that will
be used by scientists, in both the public and private sectors, to develop a
better understanding of human biological processes to deliver improved health
care in the future.
An essential feature of Celera's business plan is to provide public
availability of the sequence data. A major consequence of the data generated
by this project will be the creation of a comprehensive human genome
database. Because of the importance of this information to the entire
biomedical research community, key elements of this database, including
primary sequence data, will be made available. The plan is to release data
into the public domain at least every three months, including the complete
human genome sequence at the end of the project. Celera also anticipates
providing a connect fee for online access to this data and many of the
informatics tools that researchers can use to interpret the information.
In addition, Celera intends to build the scientific expertise and informatics
tools necessary to extract valuable biological knowledge from this data. This
will include discovering new genes, developing polymorphism assay systems,
and developing a variety of databases. There is a significant infrastructure
already in place in public sector research institutions that will greatly
benefit from this data. Celera sees access to this information as valuable
because it will ultimately transform the fundamentals of health-care delivery
and medical practice and improve the lives of millions of people.
Such use of genomic information will transform the life sciences by
increasing the understanding of biological processes, allowing scientists to
target specific processes that affect health and disease. The commercial
areas that Celera believes will benefit include pharmaceutical drug discovery
and development, medical diagnostics, and agriculture, to name only a few.
One of the most important factors inhibiting the development of new drugs is
the limited number of known target molecules for which new drugs can be
developed. Disease target molecules are those that can be affected by a drug
and cause a subsequent, desired biological reaction in the body.
Historically, the process of discovering new target molecules has been
extremely slow and very expensive, due to reliance on trial-and-error
approaches to discovery. Genomic research will reduce this reliance by
enabling drug designers to go directly to target molecules of interest. This
should not only produce new and better drugs, but also shorten the time and
reduce the cost of bringing new drugs to market.
Identifying Genetic Variations
Approximately 2.2 million Americans are admitted to hospitals every year as a
result of adverse side effects from drugs; more than 100,000 die annually
from these adverse (and often unpredictable) effects. Organ-specific gene
expression profiles for drugs already available will enable researchers to
study the toxicity of new drug compounds with more certainty. In addition,
gene expression data, combined with polymorphism information related to
metabolic pathways, will provide important indications of the way an
individual patient will react to drugs of various dosage levels, thereby
significantly reducing the unwanted side effects of therapy.
Another area to be impacted by human genome data is pharmacogenomics, which
focuses on identifying genetic variations among patients that may affect the
efficacy of drug treatment (an individual's absorption and metabolism of a
specific drug) to develop more personalized drug therapy. Pharmacogenomics
has become so important to the pharmaceutical and biotechnology communities,
due to increasing evidence that a given drug does not have the same effect on
all people, that nearly all drug companies are developing pharmacogenomics
units.
In particular, pharmacogenomics is believed to offer at least three benefits:
•Increase the success rate of clinical trials by improving the process of
selecting patient populations.
•Identify new uses for existing drugs.
•"Rescue" drugs that have failed previous drug trials by identifying more
appropriate populations for the drug. Candidates for rescued drugs include
those where particular sub-populations react adversely to that drug.
In addition, Celera expects that two major areas of diagnostics-risk
assessment and personalized medicine-will benefit from genomics.
Genomic-Based Diagnostics
Predicting whether someone is at special risk for a particular disease has
historically focused on measuring general indicators in the body, such as
blood pressure and cholesterol levels. These measurements reflect general
physiology, but do not explain the specific genetic basis of disease in an
individual patient. As a consequence, these diagnostic tests do not address
the underlying cause of disease and can result in compromised medical care
and increased risk of litigation.
New genomic-based diagnostics will focus on determining an individual's risk
to developing a particular disease by looking at specific genes and any
disease-related changes in that patient. These new diagnostic tools will
likely lead to far better preventive care by offering more accurate
assessments of a patient's potential risk for developing a particular disease.
21st Century Essentials
Computer and software experts will need a strong background in biology.
We will require increasingly powerful computing capabilities.
Genomic information will be used to develop molecular diagnostic tests to
identify the genetic make-up of individuals. These tests will revolutionize
medicine by enabling physicians to establish therapies that are designed for
each patient. For example, many types of cancer that are distinct at the
cellular level nevertheless have similar symptoms. Because these symptoms may
be similar between one genetic type of cancer and another, it is important to
know everything possible about cancer genes and their interactions in
prescribing an effective treatment. Physicians will be able to use a
molecular/genomic test to help select the most effective drug with the
minimum number of side effects. As a result, this approach should benefit the
patient through more customized care, reduced length of illness, and
ultimately a better and longer life.
Additional Benefits
Agriculture is another major area likely to benefit from genomic research.
The ability to diagnose plant and animal diseases and develop treatments
targeted against those diseases should produce better agricultural products
and improved yields. For example, the comparison of genetic information from
disease- or pest-resistant plant strains with non-resistant strains and the
use of selective breeding programs for favorable traits will significantly
increase the number and success of new strains available to various
agricultural areas around the world. This has major implications for not only
increasing the quantity of food, but also its nutritional quality.
Genomic information should also be important in forensics and veterinary
medicine-and even in textile production, waste control, and environmental
remediation.
There are many issues that sequencing the human genome, as well as other
genomes, will raise in the very near future. This increased knowledge of
evolution, and ultimately ourselves, will likely prompt many questions that
society has never even considered. If anything, this new information will
require us to strengthen our scientific infrastructure and improve scientific
education. We must work to ensure that the science involved remains of the
highest quality, and is appropriately interpreted and peer reviewed. If these
areas are addressed, Venter believes we can appropriately assimilate the
wealth of new knowledge and technology that genomics will provide.
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