The Human Genome - A Personal Perspective

Jacksonville, Florida June 26, 2000 -- Now that the race to sequence the human genome is almost over, we want to add a few words to the many thousands that have already been penned or uttered about this remarkable feat, since we have something of a vested interest in it.

Back some years ago we started running -- maybe jogging is more like it -- in the genomics race. That was well before it became a popular pursuit. The story of how we entered the fray may say something about biomedical research and the funding of it in the United States.

Applying for a grant

We applied for a research grant. That was and still is customary. You propose the project and ask for money. Well, we proposed we would trace the passage of a chromosome through a family, a chromosome that you could easily distinguish though the microscope, thanks to a special marking on it called a fragile site, a spot where the chromosome is weak and breaks easily. And at the same time we would follow the transmission of genes, the invisible instructions on chromosomes, through the same family. Then we would link one of the genes to the chromosome and so assign (map) that gene to that chromosome and further we would map the gene in close proximity to the fragile site.

To fund this research we asked for the princely sum of $20,000 for the first year, with a 5% rise in each of the next two years ("for an increase in the cost of living"), or around $63,000 over a three-year period. We submitted this research grant request to a federal funding agency.

"Approved" but...

After several months we heard the fate of our grant application. The federal agency "approved" it but informed us that, sadly, they could not fund it. The reason -- it was an imaginative research proposal but there was, unfortunately, "no evidence" that we could even come close to succeeding in doing what we had proposed (since no one had done it before, or had tried to do it).

The denial of funds somehow motivated us more so we stubbornly continued on our way, funded our research ourselves as best we could, and in time had the pleasure of proving the federal agency wrong. We succeeded.

Research results

Working with close colleagues, we found a fragile site and followed its passage through a large family. (One member of the family was a guard at the hospital and he and his family became friends of ours and they collaborated in the research with us.)

We found that the chromosome with the fragile site in the hospital guard's family traveled together with a particular gene. The gene was for a protein called haptoglobin that binds (ties up with) hemoglobin, the oxygen-carrying pigment, whenever it is free of the red blood cell in which it is usually enclosed. So we succeeded in linking the gene (for haptoglobin) to the fragile site that we could see was sitting in plain view on chromosome 16. In fact, we could see the fragile site on the long arm of chromosome 16 and could even measure its exact location there with some precision.

The refusal of the federal agency to fund the research had slowed us down. It took us five years rather than the three we had projected. And at the three-year mark, another research team had used a similar strategy to map a gene to chromosome 1. However, we managed to map the second human gene ever assigned to a specific chromosome (other than the X chromosome which has a unique telltale pattern of inheritance).

At the starting line

Deciphering the genome is a remarkable feat but it has only been a race to get to the starting line, not to the finish line. We now have a gigantic genetic dictionary full of letters (the bases in the DNA). Aside from a few words (genes) we recognize, we still cannot make sense out of most of it. We must identify all the words (find the genes). We must learn how each of them is translated (into proteins). We must figure out how the translation (the protein) is read and how each protein affects the human body (and mind). We must learn all of the ways the genome can err and produce disease, or raise the risk of disease.

A human genome has been almost entirely decoded. But it was not your genome or mine. It was simply a genome and each of us, except for identical twins, has a different genome. There are many human genomes to be looked at in the years ahead.

And to think of it, had the federal agency funded our research, we might have gotten a minute or two's headstart on the road ahead. We predict it will take the better part of this new millennium to reach a complete understanding of the human genome.

Three Years Later - An Impersonal Perspective

Bethesda, Maryland April 14, 2003 -- The International Human Genome Sequencing Consortium today announced the successful completion of the Human Genome Project more than two years ahead of schedule. The international effort to sequence the 3 billion DNA letters in the human genome is one of the most ambitious scientific undertakings of all time.

"The Human Genome Project has been an amazing adventure into ourselves, to understand our own DNA instruction book, the shared inheritance of all humankind," said Francis S. Collins, M.D., Ph.D., leader of the Human Genome Project since 1993. "All of the project's goals have been completed successfully -- well in advance of the original deadline and for a cost substantially less than the original estimates."