What is it?
the New Genetics
Websites en Español
Primer Molecular Genetics
List of All Publications
Search This Site
Site Stats and Credits
On the Shoulders of Giants: Private Sector
Leverages HGP Successes
Data, Technologies Catalyze a New, High-Profile Life Sciences Industry
The deluge of data and related technologies generated by the Human Genome Project
(HGP) and other genomic research presents a broad array of commercial opportunities.
Seemingly limitless applications cross boundaries from medicine and food to
energy and environmental resources, and predictions are that life sciences may
become the largest sector in the U.S. economy.
Established companies are scrambling to retool, and many new ventures are
seeking a role in the information revolution with DNA at its core. IBM, Compaq,
DuPont, and major pharmaceutical companies are among those interested in the
potential for targeting and applying genome data.
In the genomics corner alone, dozens of small companies have sprung up to
sell information, technologies, and services to facilitate basic research into
genes and their functions. These new entrepreneurs also offer an abundance of
genomic services and applications, including additional databases with DNA sequences
from humans, animals, plants, and microbes.
Other applications include gene fragments to use for drug development and
target identification and evaluation, identification of candidate genes, and
RNA expression information revealing gene activity. Products include protein
profiles; particular genotypes associated with such specific medically important
phenotypes as disease susceptibility and drug responsiveness; hardware, software,
and reagents for DNA sequencing and other DNA-based tests; microarrays (DNA
chips) containing tens of thousands of known DNA and RNA fragments for research
or clinical use; and DNA analysis software.
Broader applications reaching into many areas of the economy include the following:
From the start, HGP planners anticipated and promoted the private sector's participation
in developing and commercializing genomic resources and applications. The HGP's
successes in establishing an infrastructure and funding high-throughput technology
development are giving rise to commercially viable products and services, with
the private sector now taking on more of the risk.
- Clinical medicine. Many more individualized diagnostics and prognostics,
drugs, and other therapies.
- Agriculture and livestock. Hardier, more nutritious, and healthier
crops and animals.
- Industrial processes. Cleaner and more efficient manufacturing in
such sectors as chemicals, pulp and paper, textiles, food, fuels, metals,
- Environmental biotechnology. Biodegradable products, new energy resources,
environmental diagnostics, and less hazardous cleanup of mixed toxic-waste
- DNA fingerprinting. Identification of humans and other animals, plants,
and microbes; evolutionary and human anthropological studies; and detection
of and resistance to harmful agents that might be used in biological warfare.
A Public Legacy
Substantial public-sector R&D investment often was needed in feasibility
demonstrations before such start-up ventures as those by Celera Genomics,
Incyte, and Human Genome Sciences could begin. In turn, these companies
furnished valuable commercial services that the government could not provide,
and the taxes returned by their successes easily repay fundamental public
investments. Following are a few key public R&D contributions that made
some current genomics ventures commercially feasible. These examples describe
DOE investments, but substantial commitments by NIH and the Wellcome Trust
in the United Kingdom were equally important.
Scientific Infrastructure. The scientific foundation for a human genome
initiative existed at the national laboratories before DOE established the first
genome project in 1986. Besides expertise in a number of areas critical to genomic
research, the laboratories had a long history of conducting large multidisciplinary
Genomic Science and Pioneering Technology. GenBank, the world's DNA
sequence repository, was developed at Los Alamos National Laboratory (LANL)
and later transferred to the National Library of Medicine. Chromosome-sorting
capabilities developed at LANL and Lawrence Livermore National Laboratory enabled
the development of DNA clone libraries representing the individual chromosomes.
These libraries were a crucial resource in genome sequencing.
Sequencing Strategies. When the HGP was initiated, vital automation
tools and high-throughput sequencing technologies had to be developed
or improved. The cost of sequencing a single DNA base was about $10 then;
by 2001, sequencing costs had fallen about 100-fold to $.10 to $.20 a
base and still are dropping rapidly.
DOE-funded enhancements to sequencing protocols, chemical reagents, and enzymes
contributed substantially to increasing efficiencies. The commercial marketing
of these reagents has greatly benefitted basic R&D, genome-scale sequencing,
and lower-cost commercial diagnostic services.
Sequencing Technologies and Biological Resources. Other major
factors in cost and time reduction were greatly improved sequencing instruments
and efficient biological resources such as the following:
- DOE-funded research on capillary-based DNA sequencing contributed
to the development of the two major sequencing machines. The core optical
system concept of the Perkin-Elmer 3700 sequencing machine (used by
Celera and others) was pioneered with DOE support. The instrumentation
concepts that matured as the MegaBACE sequencer were pioneered by Richard
Mathies (University of California, Berkeley). The DOE JGI chose this
sequencing hardware platform after competitive trials.
- DNA sequencing originally was done with radiolabeled DNA fragments.
Today, DOE improvements to fluorescent dyes decrease the amount of DNA
needed and increase the accuracy of sequencing data.
- Bacterial artificial chromosome (BAC) clones, developed in the DOE program,
became the preferred starting resource in sequencing procedures because
of their superior stability and large size. A critical component of
public- and private-sector sequencing, BACs were used to assemble both
the draft and final human DNA reference sequences.
- Further extending the usefulness of BACs, the DOE HGP funded the production
of sequence tag connectors (STCs) from BAC ends. This early information
enabled the selection of optimal BACs for complete sequencing, thus
saving time and money. STC use for the HGP was advocated by Craig Venter
and Nobelist Hamilton Smith (Celera), and Leroy Hood (now at the Institute
for Systems Biology).
A Successful Transformation
These successes transferred much of the repetitive labor from humans to automated
machines. In addition, new software for data processing both alleviated and
sped human decision making. Over the last decade, advances in instrumentation,
automation, and computation have transformed the entire process. Further innovations,
however, still are needed for completing many large sequences and increasing
the effectiveness of sequencing.
HGP and the Private Sector: Rivals or Partners?
With the June 26, 2000, announcement by the publicly funded Human Genome Project
(HGP) and Celera Genomics that the draft sequence of the human genome was essentially
complete, the complementary aspects of the public and private sectors sequencing
projects were realized.
After the spring of 1998, when Celera Genomics announced its sequencing
goal, other private companies also declared their intention to sequence
or map genomic regions to varying degrees. Some people questioned whether
the HGP and the private sector were duplicating work, and they wondered
who would win the race to sequence the human genome. Although the HGP
and private companies did have overlapping sequencing goals, their finish
lines were different because their ultimate goals were not the same.
In a sense, through its policy of open data release, the HGP has all
along facilitated the research of others. Additionally, the HGP funds
projects at small companies to devise needed technologies. DOE, NIH, the
National Institute for Standards and Technology, and other governmental
funding sources also supported further application and commercialization
of HGP-generated resources.
HGP products spurred a boom in such spin-off programs as the NIH Cancer
Genome Anatomy Project and the DOE Microbial Genome Program. Genomes of
numerous animals, plants, and microbes are being sequenced, and the number
of private endeavors is increasing. Technology transfer from developers
to users and participation in collaborative, multidisciplinary projects
closely unite researchers at academic, industrial, and governmental laboratories.
Scientific vs Commercial Goals
The HGP's commitment from the outset was to create a scientific standard
(an entire reference genome). Most private-sector human genome sequencing
projects, however, focused on gathering just enough DNA to meet their
customers' needs—probably in the 95% to 99% range for gene-rich,
potentially lucrative regions. Such private data continue to be enriched
greatly by accurate free public mapping (location) and sequence information.
Celera's shotgun sequencing strategy, for example, created millions of
tiny fragments that had to be ordered and oriented computationally using,
in part, HGP research results.
Most data at Celera, Incyte, and other genomics information-based companies
are proprietary or available only for a fee. In addition, companies are
filing numerous patent applications to stake claims to genes and other
potentially important DNA fragments. See patenting page.
More than the Reference Sequence
DNA sequencing will continue to be a major emphasis for the foreseeable
future as gene sequences are surveyed across various populations. Both
the DOE and NIH genome programs continue to support the development of
fully integrated and innovative approaches to rapid, low-cost sequencing.
Other HGP goals from the final 5-year plan were to enhance bioinformatics
(computational) resources to support future research and commercial applications.
The HGP also aimed to explore gene function through comparative mouse-human
studies, train future scientists, study human variation, and address critical
societal issues arising from the increased availability of human genome
data and related analytical technologies.
Congressional Hearing Explored Controversies,
Benefits of Public Genome Project
Why was a public project needed if the work could be done in
the private sector?
In April 2000 the Subcommittee on Energy and Environment of the Committee on Science
of the U.S. House of Representatives conducted hearings
on the status and benefits of genome sequencing in the public and private sectors.
Speakers included representatives of the U.S. HGP and Celera Genomics, members
of Congress, and the director of the Office of Science and Technology Policy.
Robert Waterston, directory of the HGP sequencing center at Washington University,
St. Louis, pointed to fruitful data sharing by the HGP and the private
sector. Examples included (1) collaborations led by the pharmaceutical
company Merck to develop partial sequences identifying genes and (2) the
fruit fly sequencing project by Celera and the HGP.
Examples of private-sector enrichment of public data included the SNP
consortium, which generated a publicly available map containing human
DNA variations. (See article.) In
September 2000, Celera Genomics announced a reference database with more
than 2.8 million unique SNPs, including those screened from public-sector
databases. In October a public-private consortium announced the joint
sequencing of the laboratory mouse. (See article.)
Also, a Monsanto-University of Washington project generated a draft sequence
of the rice plant genome for release to the public. These efforts show
the value of sharing data to increase knowledge and ensure future discoveries
for mutual benefit.
Neal Lane (formerly Assistant to the President for Science and Technology
and Director of the Office of Science and Technology Policy) echoed the
importance of partnerships between public and private sectors in his testimony
to the House committee. His observations follow.
"Sequencing the genome...is only the beginning of genomics," he said. "It
is the first step into a future of discoveries and innovations that genomics
will enable, that the public and private sectors must pursue together...An expanding,
evolving partnership has made human genomic discoveries possible and is now
poised to make those discoveries beneficial for everyone...I believe that the
policies we have pursued will help to strengthen this partnership, allowing
genomic discoveries and innovations to move steadily forward for the benefit
of our nation and for all humankind."