Making the pieces fit

Aug. 1, 2002
Results of the Human Genome Project promise to revolutionize everything from medicine and dentistry, to agriculture, to how we look, act, and even behave.

by Cathleen Terhune Alty, RDH

Results of the Human Genome Project promise to revolutionize everything from medicine and dentistry, to agriculture, to how we look, act, and even behave.

Imagine traveling to a world of dental miracles where a diseased pulp is removed and a new one grows in its place. There is no periodontal disease or caries, because the bacteria that cause the diseases have been genetically disarmed and are now harmless to teeth and tissues. Orthodontic treatment can begin with genetic manipulation in children before their teeth erupt. Sound like science fiction? No, it isn't! Many of these things will be a reality in the near future due to the mapping of the gene sequences in the human body.

Much has been in the news during the past year about the progress of the Human Genome Project (HGP). This project, a 15-year effort coordinated by the U.S. Department of Energy and the National Institutes of Health, was designed to identify all of the genes and gene sequences in the human body, store the information in databases, and share it with researchers worldwide. The rough draft - which maps 90 percent of the entire human genetic code - was released in 2000 to much fanfare and surprise, because the task was completed earlier than expected. The final draft will be released in 2003, but research based on the rough draft is already underway. It promises to revolutionize everything from medicine and dentistry, to agriculture, to how we look, act, and even behave!

For example, researchers have already discovered more than 30 disorders directly associated with genes. Scientists at the National Institute of Dental and Craniofacial Research (NIDCR) knocked out a tooth-specific gene in mice so the enamel crystal of the teeth was malformed. This was done to study amelogenesis imperfecta. The Institute for Genomic Research (TIGR) in Rockville, MD, reported it has sequenced the bacterium believed to play a major role in adult periodontitis (Porphyromonas gingivalis), and it hopes to use this to prevent or eradicate periodontitis. Learning how the gene code works may help scientists understand both diseases caused by defective genes (inherited diseases) and genes which cause a person to be susceptible to disease.

The study of gene sequencing has been given the name "genomics." To better understand the project, it helps to go back and review what genes are. Each cell has 24 chromosomes, made up of coiled strands of DNA. The entire DNA in a cell is called a "genome." The coiled, double-helix structure of DNA contains a particular side-by-side arrangement of genes, much like beads on a string. Genes are specific sequences of nucleotide bases that encode protein-making instructions for the cell. The bases are abbreviated A, T, C, and G. They are in a particular order and vary in length. More than 99 percent of human DNA sequences are the same across the population. Variations in DNA sequences can have a major impact on how people respond to bacteria, virus, toxins, chemicals, drugs, etc.

The genes often get the attention, but it's actually the proteins that perform most of our life functions and make up most of the cell structures. These proteins made by the genes determine many things, such as how the organism looks, how well it fights infection, and, sometimes, even how it behaves. These protein chains fold up into specific three-dimensional structures in the cell. All the protein in a cell is called its "proteome," and they have been found to change minute by minute in response to environmental signals. Studying the molecular basis of disease has become the big focus of biotechnology researchers around the world.

Mary MacDougall, PhD, an associate dean of research at the University of Texas Health Science Center Dental School at San Antonio, has indicated that a lot of the research will center on the cell proteins made by the genes. That's because, currently, there is little under stand ing of what they are and what they do.

"The complexity we have as an organism is on the protein level, which has been found to be dynamic and diverse," she noted.

It was hoped that mapping the genetic code would be a Rosetta Stone of sorts to decipher the chemical soup of all biological life, but the initial draft reports this is not the case. Research has discovered that we are more than the sum of our genes and that we have fewer genes than scientists expected.

As Dr. MacDougall pointed out, "Our complexity is not on the order of the magnitude that we originally thought. There were surprises in the report, and we're just starting to get a handle on it." Among the surprises were the organization and patterning of the genes and the variations found in the strings. The most common variation is called SNPs (snips), which stands for single nucleotide polymorphisms. This occurs about once in every 100 to 300 bases. These SNPs may help scientists identify our genetic susceptibility to ailments such as cancer, diabetes, and vascular diseases. Scientists are hoping to be able to create profiles of our personal SNPs to help us identify our own disease vulnerabilities.

The HGP draft also reports that of the 35,000 genes in our bodies, the human genome contains 3,164.7 million nucleotide bases (A, C, T, and G). The average gene consists of 3,000 bases, most of which are G and C types. Only about 2 percent of the genome is involved in the synthesis of proteins, and 50 percent of base sequences don't seem to have a purpose and are now labeled "junk DNA." More information will be forthcoming as the project completes the final draft.

According to Dr. MacDougall, dentistry will be greatly affected by the research as more ways of protecting teeth and gum tissue at a molecular level develop. Dr. MacDougall says, "This is the beginning of a very brave new world with limitless possibilities. We will dramatically increase the understanding of the diseases that affect the dentition," she said, "and understand the broader syndromes affecting oral structures. We will better understand what changes occur in what gene sets to help provide testing and treatment strategies."

Some of these strategies will focus on changing the human genetic code and some will change the bacteria's genes, as well as provide better information to counsel people regarding treatment choices and more targeted drug therapies. The days of one treatment modality for a person with a particular disease will be over. People will soon be treated medically, as the individuals they are, and at their own precise molecular level. The possibilities for researchers to discover major breakthroughs are huge!

The ethical questions surrounding the entire Human Genome Project are huge as well:

  • Who will have access?
  • Who owns and controls the genetic information?
  • Do I own my own genetic sequencing or does the research organization own it?
  • What access will for-profit corporations have?
  • Will the products created be useful to society as a whole at the expense of the individual?
  • How will privacy issues be managed?
  • In a world where human appearance and function can be manipulated, what is considered acceptable diversity?
  • People want to look better, live longer, and increase their quality of life, but who will control these applications?
  • Who will be responsible when gene manipulations go wrong?
  • Where will the line be drawn between medical treatment and enhancement?

The ethical, legal, and social issues surrounding this project will be debated and discussed for years to come. One thing is clear: There is no stopping this speeding-train technology. What remains to be seen is whether it takes us on a one-way trip to the world of medical miracles, or whether it becomes a train wreck of profit-driven, look-alike humanity. Only time will tell.

Cathleen Terhune Alty, RDH, is a frequent contributor. She is based in Clarkston, Mich.

The evolution of the Human Genome Project

It may seem strange that the Department of Energy is in charge of the Human Genome Project. In 1945, Congress charged the DOE to develop new energy resources, and to discover the potential health and environmental risks to the population with the production and use of these new energy sources.

The Genome Project was begun in 1986, because the human-risk assessment would be easier to determine if there was a human genome sequence to reference. However, additional applications were quickly noted. The applications fields include medicine, agriculture, environment, and energy resources, not to mention the hundreds of biotechnology-research companies that will spring up to create for-profit products.

For more information about the Human Genome Project, visit the following Web sites: