The Human Genome Project, Part 2

Public vs Private Efforts to Map the Human Genome

Who is the major competition for the HGP?

Competition from the private sector has put much pressure on the HGP to work harder and faster to achieve its goals. However, there is a key difference between the goals of most of the private companies and the HGP. The sequence produced by the government-backed HGP will map the entire, 3-billion-base human genome, in contrast to the private sector's emphasis on identifying genes. For this reason, when private sector competitors make announcements regarding human genome mapping, it is often in reference to mapping only certain regions of DNA with important genetic information. The key private competitor against the publicly funded Human Genome Project is Celera Genomics. 
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Celera Genomics (Celera is Latin for swiftness) was established in May 1998 by the PE Corporation and J. Craig Venter, PhD, for the purpose of generating genomic information to accelerate the understanding of biological processes. Dr. Venter is now President and Chief Scientific Officer of Celera and before that was the founder and President of The Institute for Genomic Research (TIGR). TIGR is a non-profit genomics research institution that Dr. Venter guided from 1992 until August 1998. Prior to 1992, Dr. Venter worked at the National Institutes of Health, which is also one location where the HGP program takes place. At the NIH, Dr. Venter was a Section Chief and a Lab Chief in the National Institute of Neurological Disorders and Strokes. In fact, it was while working in the NIH laboratories that Dr. Venter developed his unique shotgun sequencing method, a new and very rapid strategy for gene sequencing called EST. Dr. Venter and his team of scientists at TIGR used his EST method, discovering and publishing one half of all the human genes that have been sequenced. 

Dr. Venter began his private genomics company and also started the race between Celera and the government's HGP to map the human genome. Celera Genomics' corporate mission statement is as follows: 

"To become the definitive source of genomic and related medical and agricultural information. Users of Celera's information, available on a subscription basis to academic and commercial institutions, will have access to the most comprehensive databases in genomics and related fields, as well as proprietary software tools for viewing, browsing and analyzing data in an integrated way that can accelerate the understanding and use of genomic and related information. To support this objective, Celera has established the largest genomic production plant in the world, supported by one of the largest civilian supercomputing facilities."

Venter, however, had a greater and more ambitious goal in mind when he claimed that he could beat the publicly funded teams and finish the human genome sequencing in three years. Leaders of the HGP viewed such an announcement as an attempt to make the government's efforts look sluggish and inadequate. However, little known to the public, Venter's privately owned Celera Genomics depended heavily on utilizing the public work that is regularly published and updated on the Internet. 

What techniques is the HGP using and what techniques is Celera using?

The public and private projects use similar automation and sequencing technology, but different approaches to sequencing the human genome. The HGP uses a "hierarchical shotgun" (or "clone by clone") approach in which individual large DNA fragments of known position are subjected to shotgun sequencing (i.e., shredded into small fragments that are sequenced, and then reassembled on the basis of sequence overlaps). The hierarchical shotgun method has an advantage in that the global location of each individual sequence is known with certainty, but it requires constructing a map of large fragments covering the genome. The Celera project uses a "whole genome shotgun" approach developed by Dr. Venter, in which the entire genome is shredded into small fragments that are sequenced and put back together on the basis of sequence overlaps. 

The whole genome shotgun strategy involves breaking the entire genome into several hundred thousand random clones. After sequencing each clone, Celera then reassembles the sequences of several hundred thousand fragments into their proper order using pattern-recognition software. This results in the reconstruction of the linear sequence of the 23 pairs of human chromosomes. The whole shotgun method does not, however, require knowing the global location of individual sequences presenting challenges in the assembly phase. It is quicker than the hierarchical shotgun method (which explains how Venter was able to claim a three-year goal to complete the human genome), but many skeptical scientists have been disapproving of Dr. Venter's whole genome shotgun method, labeling it as a less accurate method. James Watson, Nobel Prize winner and co-discoverer of DNA, described them as "sloppy" and said that Venter's work was "not science". Both approaches align the sequence along the human chromosomes by using landmarks contained in the physical map produced by the HGP.

What is Celera's role in mapping the human genome?

Celera began to sequence the human genome on September 8, 1999, using the whole genome shotgun technique that its scientists pioneered in sequencing the first complete genome in 1995 at The Institute for Genomic Research (TIGR). Celera began its project later than the HGP, but uses a faster method powered by the world's largest private assemblage of supercomputers. The firm announced earlier this year (2000) that it had sequenced all of the genes from one human being, an unidentified male, and in June 2000 announced that they had reassembled them into the correct order and location on the 23 pairs of human chromosomes. Gene sequences produced by Celera are not being made immediately available to other researchers, but company officials said the data would eventually be posted on a website and available to subscribing universities and pharmaceutical companies. 

The relationship between the public and private sectors originally started out as one of competition to see who could sequence the human genome first. Shots were fired from both sides about motives, practices, and quality of work. Celera's style did not go over well with the public project. However, the relationship between the two is now much less confrontational. Instead of fierce competitiveness, there is now a working collaboration between the two to better serve public interests. After years of public sniping and several failed attempts at reconciliation, the two sides are taking a step toward peaceful coexistence. When announcing the completion of the working draft, HGP head Francis Collins, Ari Patrinos of the Department of Energy and Dr. Venter held a joint press conference to declare that the race was over, both sides had won, and the hostilities were resolved.,,,

Genome Project, Part 1 | Genome Project, Part 2 | Genome Project, Part 3 | Genome Project, Part 4 | Genome Project, Part 6