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Scientists have found that a specific defect in the male sex (Y) chromosome, known to cause azoospermia, or the inability to make sperm, can also cause the most common form of male infertility-low sperm production, or oligozoospermia. This study is the first to definitively show that genetic defects can cause low sperm counts in some males and suggests that intracytoplasmic sperm injection (ICSI)—the now popular technology of injecting a single sperm into an egg to circumvent low sperm counts—may cause the sons of these men to inherit infertility.

Dr. Rudolf Jaenisch, a Member of the Whitehead Institute for Biomedical Research, and Dr. Mario Capecchi from University of Utah in Salt Lake City have received the prestigious Molecular Bioanalytic Prize from the Boehringer Mannheim Group in Germany. In awarding this prize, the Group cited the scientists' pioneering work in establishing transgenes as a basic tool for research in molecular biology and medicine.

The Whitehead/MIT Center for Genome Research has received a three year, $26 million grant from the National Institutes of Health (NIH) to begin sequencing specific portions of the human genome. The Center's effort, along with others in the country, launches the final and most important phase of the Human Genome Project-decoding the exact sequence of the 3 billion DNA letters that make up the human being. Ultimately, sequencing the genome will help researchers identify disease-related genes and result in unprecedented advances in health care.

Scientists at the Whitehead Institute for Biomedical Research have achieved a major goal of the international Human Genome Project with the completion of the world's first comprehensive genetic map of the mouse genome. The mouse map appears in the March 14 issue of Nature along with a comprehensive genetic map of the human genome created by researchers at Genethon in France.

Circumventing a long-standing problem in drug design, scientists have developed a novel way to identify a new class of protein building blocks that could serve as valuable leads for drug development. The new method, called mirror-image phage display, represents an important advance in the rapidly growing field of drug-design. It will also offer new insights into the structure and function of important proteins.

Researchers at the Whitehead Institute for Biomedical Research and Boston's Children's Hospital have found a new way to rev up the engines of the mammalian immune system. They have taken an organism used worldwide to vaccinate against tuberculosis and packaged inside it mammalian genes that stimulate immune cell function. This achievement could lead to more effective vaccines for a broad range of human diseases and also-because the same organism is used in immunotherapy for bladder cancer-to safer, more effective cancer therapy.

Map Provides Landmarks Needed to Begin Large-Scale Sequencing of Human Chromosome

A team of U.S. and Finnish scientists has found that a specific defect in the male sex chromosome (the Y chromosome) may be responsible for 13 percent of cases of azoospermia, the complete inability to make sperm and the most severe form of male infertility. The study is one of the first to demonstrate that genetic defects can sometimes explain infertility in otherwise healthy couples and could lead to a better understanding of the molecular mechanisms required to make healthy sperm. This research, reported in the August issue of Nature Genetics, was led by Dr. David Page of the Whitehead Institute for Biomedical Research and the Howard Hughes Medical Institute (HHMI).

Scientists at the Whitehead Institute and the Albert Einstein College of Medicine have shown that a single surface protein called IscA is all that the bacteria Shigella flexneri needs to propel itself inside and among host cells-a characteristic that enables the organism to infect human colon cells and cause diarrhea. Eschericha coli, when engineered to express the Shigella protein, acquire the same ability to move inside and among frog egg cells. The finding has implications for understanding cancer, building vaccine delivery systems, and finding new ways to combat bacterial resistance. The results are reported in the July 3 issue of the Proceedings of the National Academy of Sciences.