By Kevin E. Noonan —

In the 19th Century, biology was an observational, rather than an experimental, science.  Without an understanding of genetics, and with evolution by natural selection being but newly proposed (and in the absence of genetics, not yet accepted), biologists (natural historians, really) spent their time expanding Linnaean systematics, cataloging new species found in remote parts of the world newly being explored (this work is not finished, with new species being discovered even today).

But the history of the biological sciences during the 20th century established it as an experimental science like the other "hard" sciences of physics and chemistry, culminating in the development of molecular biology and the explication of the molecular basis of heredity.  Perhaps the most significant achievement of biology in the last century (after the identification of DNA as the genetic material by James Watson and Francis Crick; at left) was the Human Genome Project (HGP), which deciphered for the first time the complete human genetic code of three billion bases.

The results of the HGP paradoxically showed that we were just at the beginning of understanding what the deciphered code means.  The "consensus" human genomic sequence was an amalgam of the DNA sequences of many humans (perhaps over-representing the DNA of J. Craig Venter, the maverick pioneer of human genomic sequencing; see "A Complete Diploid Human Genome Reveals Some Surprises"), and recently the sequence has been extended by the announcement of the complete human diploid genomic DNA sequences of Dr. Venter and Dr. Watson himself (see "The (As Yet) Unfulfilled Promise of Personalized Genomics").

One of the hopes and aspirations of the HGP is to provide improved disease treatments based on better-informed understanding of the causes of the disease and targets for therapeutic intervention.  On-going efforts include determinations of disease-related genetic loci comprising co-inherited genetic differences, called haplotypes, which are implicated in certain diseases (see "International HapMap Project").  These haplotypes are comprised most commonly of collections of commonly-inherited single nucleotide polymorphisms (SNPs), and have been identified for diseases such as diabetes, certain types of cancer, immunological diseases such as rheumatoid arthritis, and others.

A limitation on this type of genetic information is that it can only detect commonly-inherited variants.  At the other extreme, geneticists continue to identify specific mutations involved in well-characterized genetic diseases, such as sickle cell anemia, muscular dystrophy, cystic fibrosis, and Huntington’s disease.  What is less known are any disease-associated genetic variations that fall within these frequency classes of genetic variation.

In an effort to uncover this layer of variation, the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), announced on Tuesday an effort to determine the genetic complement of 1,000 unrelated humans from across the globe.  The 1,000 volunteers will include:  Yoruba in Ibadan, Nigeria; Japanese in Tokyo; Chinese in Beijing; Utah residents with ancestry from northern and western Europe; Luhya in Webuye, Kenya; Maasai in Kinyawa, Kenya; Toscani in Italy; Gujarati Indians in Houston; Chinese in metropolitan Denver; people of Mexican ancestry in Los Angeles; and people of African ancestry in the southwestern United States.  Researchers, also from around the globe, will be attempting to catalog variants present at frequencies of 1 percent or greater in the human population, and at frequencies as low as 0.5 percent or lower within individual genes.

These genetic analyses will identify additional SNPs in the human genome, as well as structural variants such as inversions, deletions, duplication, and translocation of genetic loci.  These types of structural variants were found at greater than expected frequencies in Dr. Venter’s diploid chromosome complement and are becoming understood to be important in defining genetic susceptibility to more complex diseases like autism.

One aspect of these studies is that the researchers will not be directing their attention (at least not initially) towards identifying or understanding any particular disease (or any disease at all — medical history information as well as personal information will not be part of the study’s dataset).  This harkens back, curiously and wonderfully, to that 19th century paradigm of observational biology (albeit on the molecular rather than the macroscopic scale).  But in a way the human genome, in its complexity, has become the brave new world needing to be charted, explored and understood, and in this way modern natural historians are once again back to observing the nature and contours of the world in hopes of better understanding it.

More information on the 1000 Genomes Project can be found here.