The brave new world is here: privacy issues and the Human Genome Project: governments and courts must step in to provide protections and regulations for the use of individuals' genetic testing results.

• Author: Curley, Jr., Robert A.

SCIENTIFIC discoveries and advances in biological understanding during the 20th century paved the path for the Human Genome Project.

"We used to think our fate was in our stars. Now we know, in large measure, our fate is in our genes," said James Watson, who co-discovered the double-helix structure of DNA with Francis Crick in 1953. (1) As for Crick's thoughts, he stated, "You, your joys and your sorrows, your memories and your ambitions, your sense of personal identity and free will, are in fact no more than the genetically determined behavior of a vast assembly of nerve cells and their associated molecules." (2)

DNA was discovered in the mid 1800s. In 1868, a Swiss biologist, Friedrich Miescher, identified DNA in the nuclei of pus cells obtained from discarded surgical bandages. But it was during the 20th century that there were great advances in biological understanding of DNA.

In 1943, American Oswald Avery proved that DNA carries genetic information. He even suggested that DNA might actually be the gene. Most people at that time thought the gene would be protein, not nuclei acid, but by the late 1940s, DNA generally was accepted as the genetic molecule. In 1952, Alfred Hershey and Martha Chase performed the definitive experiment that showed that DNA was, in fact, the genetic material.

Once more was known about DNA, the next step was to figure out the molecule's structure. The race was on. At Cambridge University, there were Watson and Crick. At the same time, at King's College in London, Maurice Wilkins and Rosalind Franklin also were studying DNA. In 1953, building from the King's team's research, Watson and Crick presented a model of the structure of DNA. In 1962, Watson, Crick and Wilkins shared the Noble Prize for physiology and medicine. Franklin had died by 1962, and the Nobel Prize rules do not allow an award to be made posthumously, and interestingly nor do they allow more than three scientists to share the award.

Franklin actually was the one who discovered and first stated that the sugar-phosphate backbone of DNA lies on the outside of the molecule. She arrived at this discovery after examining the DNA molecule under an x-ray beam, a technique called x-r. ay crystallography. It would be interesting to know which three of the four scientists would have received the Nobel Prize had Franklin not died before the award was given.

Although genetics dates back to the mid 1800s, the last decade has proved to offer the milestones in genetic history, what with technology advances and revolutionary scientific endeavors like the Human Genome Project. DNA's discovery has been called the most important biological work of the last hundred years, and the research that it has sparked will lead to monumental developments in the next hundred.

HUMAN GENOME PROJECT

1. What Is It?

   The Human Genome Project (HGP) is an international research effort to determine the sequence of the three billion chemical base pairs that make up the human DNA and to identify the approximately 35,000 genes in human DNA. While the HGP was conceived as early as the mid 1980s by scientists in the U.S. Department of Energy, the initial planning process culminated in 1990. Since then, researchers from the United States, the United Kingdom, Germany, Japan, China and France have been reconstructing DNA sequences to produce detailed physical maps of the human genome.

   The international consortium is supported mostly by the U.S. National Institutes of Health and the Wellcome Trust, a philanthropic organization based in London and directed by Dr. Michael Dexter. Other governmental agencies and charitable institutions in the various countries also fund the project. The driving force behind the project is the identification and eradication of all genetically based diseases.

   The U.S. Human Genome Project is a 13-year effort coordinated by the Department of Energy and the National Institutes of Health. The project originally was planned to last 15 years, but effective resource and technological advances have accelerated the expected completion date to 2003. Francis Collins, the director of the project at the National Institutes of Health, has said, "It's hard to overstate the importance of reading our own instruction book, and that's what the Human Genome Project is all about." (3)

   The United States also is home to the prominent private endeavor to map the human genome being done by Celera Genomics, a company in Rockville, Maryland, headed by J. Craig Venter.

2. Basic Science

   For a better understanding of the work being done by the HGP, it may be useful to review Biology 101. Every human cell (except for red blood cells and the platelets that are critical to normal blood clotting and wound healing) contains a nucleus that has within it roughly six feet of a special chemical called deoxyribonucleic acid, or DNA. DNA consists of a backbone of repeating sugar and phosphate units, each of which binds a simple chemical structure called a nucleotide (more commonly, a "base"). There are four kinds of bases found in DNA, and these are abbreviated: A for adenine, C for cytosine, G for guanine, and T for thymine.

   There are 46 strands of DNA in each human cell, and they coil into the condensed double helix shape contained in 23 pairs of chromosomes. The 46 molecules of DNA contain an estimated 35,000 genes. Each nucleus-containing cell in an individual's body has the same DNA. There are three billion DNA bases in a cell, called the genome. Technically, there are six billion base pairs of DNA; at conception, three billion bases in an unfertilized egg are joined with three billion from the male sperm. Scientists think the two sets differ by about one DNA base in every one thousand, differences that can be explored after one set has been sequenced.

   Encoded within the structure of the nucleotide DNA chain is the information necessary for cell structure and function. The DNA strand includes coding regions, called genes. The sequence of nucleotide sub-units in genes directs cells to produce proteins, which provide structure to and mediate chemical reactions within a cell. Thus, proteins determine the characteristics of cells, which in turn collectively determine the characteristics of the individual. There are an estimated 35,000 genes in the human genome.

   It is interesting to note that the remaining DNA, which may exceed 95 percent of the total and is unknown at this time, does not code for proteins and is often referred to as "junk" DNA. Further scientific exploration is necessary to determine the function of this DNA.

   Genetic disorders may occur when there is a mutated gene. Sometimes full segments of DNA may be missing, multiplied or transposed--that is, found on a different segment of the chromosome. A classic unusual example of a mutation-based genetic disease is sickle-cell anemia, in which precisely one A (the nucleotide, or base, adenine) has been replaced by a T. These mutations may be either inherited or acquired. Such mutations may then lead to genetic disease.

   Genetic disorders may be classified as either "multi-factorial" or "single-gene" genetic conditions. (4) Multi-factorial conditions may not manifest themselves in the absence of certain behavioral or environmental factors. These conditions rely on the interaction of numerous genetic and environmental factors. In the case of single-gene diseases, such as cystic fibrosis and Huntington's disease, the carrier received a gene in which the disease will manifest itself regardless of environmental factors.

   It is important to distinguish between the terms "predisposed genetic condition" and "pre-symptomatic genetic condition." People who are predisposed to a genetic disease do not have the disease. Rather, they have an increased likelihood that the disease will develop. On the other hand, people with pre-symptomatic genetic conditions will develop the disease if they live long enough. An example of such a condition is Huntington's disease.

   Another aspect of genetic diseases is the gene's penetrance and expressivity. Penetrance is the likelihood that a gene will express itself. For example, the BRCA1 gene, which predisposes an individual to breast cancer, is about 85 percent penetrant, while the Huntington's gene is 100 percent. Expressivity deals with the severity and manner in which the gene manifests itself once it has penetrated. For instance, two women with the BRCA1 gene may develop breast cancer at different ages and in varying degrees of severity. It is important to remember that not everyone who develops breast cancer has the BRCA1 gene; some may have "acquired" this genetic disease because of mutations that may form spontaneously from environmental factors, such as radiation, or age-related factors. The BRCA1 gene is responsible for approximately 5-10 percent of breast cancer, while 90-95 percent of breast cancers are spontaneous genetic disorders. (5)

   Wondering if you missed a day of Biology 101.9 Rest assured, whatever you missed, you will learn as the Human Genome Project's discoveries continue to make headlines. With the project's growing popularity, good or bad, it is likely that what may not have been part of the curriculum of the past, will be common knowledge in the future.

3. HGP's Goals

   The ultimate goals of the Human Genome Project are to identify the approximately 35,000 genes in human DNA and to map out and sequence the three billion chemical base pairs that make up human DNA. (6) In other words, to produce the human blueprint.

   Mapping is a process that results in knowing the location of the gene on a chain of DNA. Sequencing is breaking down the biochemical parts of the DNA that composes each gene into its nucleotides. The DNA sequence refers to the order of the nucleotides (A, C, G, and T) in the DNA chain.

   The scientific techniques used by the Human Genome Project to detect altered genes result in the mapping of genetic diseases. Once a section of an individual's DNA is...