Editor's Note: Science Scan is a roundup of recently published, biotechnology-relevant research.

First of all came the Stone Age, the earliest stage of human culture. That gave way to the Bronze Age, which in turn was overtaken by the Iron Age, beginning around 800 years B.C. People relied mainly on all-purpose iron until steel came along a few centuries ago. There's more to iron and steel than tools and weapons. Elemental iron alone provides the lifeblood of mammalian life. Blood is red for the same reason that iron objects turn rusty red when exposed to oxidation. Iron is an essential mineral in the human diet because it is needed for the blood cells to distribute oxygen in the erythrocytes (red blood cells) to refuel and feed the entire body. Unfortunately, too much iron accumulates in the bodies of people who have inherited the genetic disorder hemochromatosis. Its excessive absorption of ingested ferric iron can upset the functioning of many of the body's essential organs.

Heart failure might occur, particularly if large amounts of iron are absorbed orally, by injection or as consequence of blood transfusion therapy.

Now, a research study published in the Nov. 30, 2003, online issue of Nature Genetics identifies a new gene and its protein, crucial to iron metabolism in the body. The journal article is titled "Mutations in HFE2 cause iron overload in [the long arm of chromosome 1]-linked juvenile hemochromatosis." The paper's collaborating co-authors are in Athens, Greece; British Columbia, Canada; and France.

They jointly studied the inheritance of the disease within 12 unrelated affected families in Greek, Canadian and French university centers. They found that the protein hemojuvelin modulates the expression of hepcidin, another protein. That molecule already is known to be involved in controlling iron levels and to be altered in cases of hemochromatosis disease. The article confirms absence of mutations of hepcidin in all 12 Greek families. Orthologs of human hemojuvelin were found in the mouse, rat and zebrafish. Loss of function of hepcidin in mice also led to severe iron overload in the animal models, mimicking the human biochemical and clinical phenotypes of juvenile hemochromatosis.

The paper notes that the disorder was recognized in ancient times, and the traditional treatment, bloodletting, led medieval physicians to be known as "leeches." Modern therapeutic approaches also aim to remove the excess iron built up in the blood. However, those therapies are costly, and might cause further complications in patients. The authors suggest that the iron-controlling proteins are likely to eventuate into therapies. Juvenile hemochromatosis is an early onset autosomal recessive disorder of iron overload resulting in cardiomyopathy, diabetes and hypogonadism that present in the teens and early 20s of its victims.

Pursuit Of Alzheimer's Cause, Cure, Focuses On Hippocampal Brain Center Neurogenesis

Neurogenesis - the growth of new brain cells - occurs in the adult mammalian brain and tends to increase during a stroke. However, the status of neurogenesis during neurodegenerative diseases, such as Alzheimer's, was unknown. To plumb that depth of ignorance, David Greenberg measured markers of early stage brain cell growth in the hippocampus, a brain region specializing in memory and cognition. By definition, it's disproportionately affected in Alzheimer's disease patients. He observed increased neurogenesis in their brains compared to those of normal controls.

Greenberg, a neurobiologist at the Buck Institute for Age Research in Novato, Calif., is senior author of a paper in the Proceedings of the National Academy of Sciences (PNAS). Its title: "Increased hippocampal neurogenesis in Alzheimer's disease."

"Stimulating this growth," he suggested, "might provide a new treatment strategy. Alzheimer's disease," Greenberg recalled, "a common cause of dementia, is characterized by senile plaques containing B-amyloid peptide derived from amyloid precursor protein and neurofibrillary tangles containing hyperphosphorylated t-protein. Ab and phospho-t may be neurotoxic, leading to progressive neuronal degeneration and death. Despite progress in understanding molecular mechanisms in AD, effective treatment remains elusive."

Virologists Raise Vexing Question: Did Smallpox Or Bubonic Plague Lead To HIV/AIDS Resistance?

Researchers studying a gene for resistance to HIV challenge the prevailing theory of the gene's origin. Certain populations appear resistant to the AIDS virus. The cells in their immune systems lack the protein that HIV uses to dock and gain entry. People lacking that gene have a mutated form (or allele) of the CCR5 gene, which holds the key to the entry kingdom. Most populations that carry the mutant allele originate from Europe, suggesting that it is a relatively recent introduction to the gene pool, some 700 years ago. For a mutant allele to be sustained in the population, that one at a rate of about 10 percent, there must be some selective advantage to its presence, but HIV infection did not appear until the mid-1900s.

The prevailing theory suggests that the CCR5 mutation was perpetuated by selective pressures from another disease. Would you believe the bubonic plague? A paper titled "Do we owe HIV resistance to smallpox?" was published in the Nov. 17, 2003, issue of PNAS. Its senior author and her co-author challenge the bubonic plague theory. They suggest that smallpox offers a better explanation for the appearance and maintenance of the mutant CCR5 allele.

Using mathematical models, they analyzed historical data on each epidemic and the current frequency of the CCR5 allele. They assert that smallpox, because it was more likely to kill children before they reached reproductive age and because it has been around longer than the plague, can better explain the high frequency of the mutant allele. In addition, the authors suggest that since smallpox also is a virus like HIV, it is easier to imagine a common biological mechanism by which the CCR5 mutation prevents infection.