The articles on sequencing the human genome (THE SCIENTIST, October 20, pp. 11-12) were noteworthy not so much for the arguments they put forward in support of the project as for their failure to realistically assess the cost, need and impact of such a project. Certainly, one can scan DNA sequences with computers and determine open reading frames, enhancer sequences, RNA polymerase binding sites, etc. However, without supporting data, these determinations are purely hypothetical.
The magnitude of the project also needs to be put into perspective. While genomes the size of bacteriophage lambda (49,133 bp) have been determined with considerable effort, the sequence of the entire Escherichia coli chromosome (4 million bp) is still not available, let alone a complete physical map. Gilbert underestimates the problems and time it will take to generate the library of cosmids containing unique 40,000 base-pair inserts. DNA fragments of this size are at the upper limit of our current cloning technology. Such large cosmids tend to undergo spontaneous shortening. In addition, there is ample evidence that many human DNA sequences will not be stably maintained in the bacterial hosts currently available.
The next issue that needs to be addressed is who is going to do the work. Gilbert suggests large numbers of technicians. This sounds like a job for a company, not an academic research laboratory. However, a company would not want to touch this project because there would not be a financial payback in terms of new products.
Another point that is never discussed relates to the quality of the data obtained. Different laboratories that have sequenced the same gene report significant numbers of discrepancies in relatively small regions. This problem will only be alleviated if sequencing technology improves.
The final issue that needs to be assessed more carefully is the cost of such a project. The goal of sequencing the human chromosome is attainable, but in the context of limited funding, other areas of research will clearly have to be slighted. Bodmer's assertion that this work "subsumes much of what is now done in molecular genetics" is simply not correct. Overall, there are many good reasons why the human genome should be sequenced. However, the need for such a major effort clearly is not worth the cost of ignoring other areas of basic research.
University of Georgia, Athens, GA 30602
For related article, see page 12