The Human Genome Project

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The Human Genome Project:

An Interview with Dr. Francis Collins
Clyde S. White
Carolina Multimedia Group

Editor's note: Francis Collins, M.D., Ph.D., pioneered the development of a powerful new gene-finding method known as "positional cloning," which utilizes the inheritance pattern of a disease within families to pinpoint the location of the gene. Dr. Collins is perhaps best known for using positional cloning techniques to isolate the genes responsible for cystic fibrosis, neurofibromatosis type 1, and most recently, Huntington's disease. He was appointed Director of the National Center for Human Genome Research in April of 1993. In this interview with Carolina Biological Supply Company, Dr. Collins discusses the Human Genome Project and how it will impact human health.

Would you give us a brief overview of what genes and chromosomes are, and what role they play in the development of an organism?
DNA is the blueprint of the human organism, of all living organisms. It contains the instruction set. And DNA is made up of this four-letter code so that each position on the DNA double helix is an A, a C, a G or a T. But you have to have a certain stretch of that, a packet of that, to actually create an instruction to do a particular thing, and that instruction is called a gene. So a gene is a stretch of DNA that codes for a particular protein. Genes can be variable in size. There are about a hundred thousand of them all together in the human genome. The genome is all the DNA. That's all that word means is just all the DNA. DNA is also packaged into chromosomes. There are 46 chromosomes inside each human cell. Each chromosome, therefore, has thousands of genes. It just happens that for purposes of copying the DNA and keeping it all straight, it helps to have them separated into chromosomes instead of just one big piece.

What happens in our DNA to cause disease?
Disease comes about, genetic disease, because of a misspelling in the DNA sequence. It may be a very subtle misspelling, as simple as an A that should have been a T or a G that should have been a C. If it's in a crucial place where it's coding for a protein that does something crucial and you change that A to a T, you may change that amino acid from a glutamic acid to a valine, or something like that, and that may be sufficient to cause that protein not to function anymore or to function in an abnormal way. Then a genetic disease results. So it is similar to having a misspelled word somewhere on one page in a very large encyclopedia. It doesn't look like very much, but the consequences can be profound.

Would you explain the purpose and goals of the Human Genome Project?
The Human Genome Project is an unprecedented effort to get at this human blueprint. It is rather audacious, in fact, to imagine that we might by the year 2005 actually be able to have the entire DNA sequence decoded, laid out in front of us, in a computer database once and for all. The Human Genome Project in that process will discover all of the 100,000 genes that are in that DNA and have a reasonably good idea what a large number of them do because the spelling predicts what the function might be, not in a perfect way but in a partial way.

Figure 1 Scientists use information emerging from the Human Genome Project to map strategies to treat disorders such as Alzheimer's disease.

Many of those genes will turn out to be involved in human disease; that is, misspellings in those may be associated with a particular disease coming about and we'll learn a huge amount about that by doing this project. So there are many reasons to do it. I think the medical reason is the one that is most commonly sighted, and I believe it's the reason the public is interested in this project and wants to put up the funds for it. But there will be other consequences, as well, in terms of our understanding of science.

Figure 2 Extensive laboratory experiments using procedures such as gel electrophoresis help scientists map and sequence the human genome.

What have been the most significant discoveries that have come from the Human Genome Project since its inception in 1990?
The Human Genome Project officially got underway in October of 1990, so we're not that far into this 15-year effort. But already there are very significant consequences for discovery of diseased genes... Forty percent of the genes that had ever been found were found in 1993 as compared to all the rest of them that were found before that, and that number will continue to rise rapidly. Some of those are pretty important genes.

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