How do astronomers know when they have looked too far into space? Maybe when they have run out of galaxies to view.

That hasn't happened yet. There are still far reaches of space that have not been explored by even the most powerful telescopes, innumerable galaxies that have not been seen by human eyes.

But astronomers using NASA's Hubble Space Telescope are getting closer, with new images that reveal some of the farthest galaxies ever seen, from when the universe was just 400 million years old.

Called the Hubble Ultra Deep Field, the view represents the deepest portrait of the visible universe ever achieved by humankind. The snapshot reveals the first galaxies to emerge from the so-called "dark ages," the time shortly after the big bang when the first stars reheated the cold, dark universe. The new image should offer new insights into what types of objects reheated the universe long ago.

This historic new view is actually two separate images taken by Hubble's Advanced Camera for Surveys (ACS) and the Near Infrared Camera and Multi-object Spectrometer (NICMOS). Both images reveal galaxies that until now were too faint to be seen by ground-based telescopes, or even in Hubble's previous faraway looks, called the Hubble Deep Fields, taken in 1995 and 1998.

The combination of ACS and NICMOS images will be used to search for galaxies that existed between 400 and 800 million years (ranging from redshift 7 to 12) after the big bang. A key question for astronomers is whether the universe appears to be the same at this very early time as it did when the cosmos was between 1 and 2 billion years old.

The Ultra Deep Field contains an estimated 10,000 galaxies. In ground-based photographs, the patch of sky in which the galaxies reside (just one-tenth the diameter of the full Moon) is largely empty. Located in the constellation Fornax, the region is so empty that only about seven stars within the Milky Way galaxy can be seen in the image.

The Ultra Deep Field observations represent a narrow, deep view of the cosmos. Looking into the Ultra Deep Field is like peering through an eight-foot-long soda straw.

This galaxy-studded view represents a "deep" core sample of the universe, cutting across billions of light-years. The snapshot includes galaxies of various ages, sizes, shapes, and colors. The smallest, reddest galaxies, about 100, may be among the most distant known, existing when the universe was just 800 million years old. The nearest galaxies -- the larger, brighter, well-defined spirals and ellipticals -- thrived 1 billion years ago, when the cosmos was 13 billion years old.

In vibrant contrast to the rich harvest of classic spiral and elliptical galaxies, there is a zoo of oddball galaxies littering the field. Some look like toothpicks; others like links on a bracelet. A few appear to be interacting. These oddball galaxies chronicle a period when the universe was younger and more chaotic. Order and structure were just beginning to emerge.

The Ultra Deep Field observations began Sept. 24, 2003 and continued through Jan. 16, 2004. The telescope's ACS camera, the size of a phone booth, captured ancient photons of light that began traversing the universe even before Earth existed. Photons of light from the very faintest objects arrived at a trickle of one photon per minute, compared with millions of photons per minute from nearer galaxies.

Just like the previous Hubble Deep Fields, the new data are expected to galvanize the astronomical community and lead to dozens of research papers that will offer new insights into the birth and evolution of galaxies.

A mild, experimental smallpox vaccine known as modified vaccinia Ankara (MVA) is nearly as effective as the standard smallpox vaccine in protecting monkeys against monkeypox, a study by researchers of the National Institute of Allergy and Infectious Diseases (NIAID), one of the National Institutes of Health, has found. Monkeypox is used to test the effectiveness of a smallpox vaccine because of its similarity to the smallpox virus. The study appears in the March 11 issue of Nature.

"These findings are important to the search for a replacement vaccine for people with health conditions that would prevent them from using the current smallpox vaccine," says. Currently, Dryvax is the only commercially available smallpox vaccine in the United States. "In addition, because an initial MVA injection may help lessen the side effects experienced from Dryvax, MVA may serve as an important pre-vaccine for large-scale vaccination efforts in the event of a bioterror threat involving smallpox."

NIAID's Bernard Moss, M.D., Ph.D., the senior author on the paper, adds, "This study shows that the MVA vaccine holds great promise as an alternative to the current vaccine. Although MVA may not quite equal Dryvax in its effectiveness, it did extraordinarily well, with all of the monkeys who were vaccinated with MVA surviving a potentially lethal monkeypox infection and, aside from a few minor lesions, showing no clinical signs of disease."

In a separate study published in the March 11 online early edition of the Proceedings of the National Academy of Sciences, Dr. Moss and colleagues found that, in addition to protecting healthy mice against a lethal form of the vaccinia virus, MVA protects mice with certain immune deficiencies as well. The researchers found that mice survived a deadly dose of vaccinia virus if they'd been immunized with MVA-even those mice that were lacking antibody-producing immune cells or special proteins that help alert killer T cells to an infection. The findings indicate that MVA may be a promising alternative to Dryvax in humans who are partially immunodeficient.

Licensed in 1931, Dryvax is made from a live form of vaccinia virus that, although related to the smallpox virus, cannot cause smallpox. (Smallpox is caused by the more dangerous variola virus. The ability to prevent smallpox by injecting a person with either cowpox or vaccinia virus was demonstrated by Edward Jenner in the late 18th century.) Dryvax and similarly effective vaccines made in other countries led to the eradication of smallpox in 1980.

While most reactions to the Dryvax vaccine are relatively mild, some people may have more serious complications. Individuals at risk for such complications include those with weakened immune systems or skin conditions such as eczema, infants less than 12 months of age and women who are pregnant. For this reason, a primary goal of health officials is to develop a vaccine that is as effective as Dryvax, but safer.

MVA is a highly weakened form of the vaccinia virus that cannot multiply and infect mammalian cells. Although MVA was tested for safety in humans at the time of its development in Germany in the 1960s, it has not been tested for effectiveness against smallpox. According to the Food and Drug Administration, humans cannot be exposed to smallpox to test a vaccine's effectiveness: such exposure is unethical because smallpox is an infectious, deadly disease; and it is unfeasible because smallpox has been eradicated. Therefore, animal studies, such as those involving monkeys and mice, are critical to the development of a replacement vaccine.

Dr. Moss and his research team discovered that the immune responses elicited by the MVA vaccine were similar to those produced by Dryvax in regard to both antibodies and killer T cells.

Two months after the second vaccination, all 24 monkeys were exposed to monkeypox. Remarkably, all the immunized animals remained healthy with no signs of disease, except for a small number of lesions seen on several monkeys from the MVA-only group.

Dr. Moss and his team will continue their studies on monkeys to determine, among other things, the duration of protection offered by MVA versus Dryvax as well as the effect of dosage. In addition, NIAID is currently supporting clinical trials to evaluate the immune response to MVA in humans.

Other researchers involved in the study represented the Henry M. Jackson Foundation, Rockville, MD; the University of Pennsylvania, Philadelphia, PA; and the U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD.

Smallpox is a serious, frequently fatal infectious disease that generally spreads from person to person through the air and is marked by fever, head and body aches, rash and large, fluid-filled bumps on the skin. The last case of smallpox in the United States occurred in 1949, and the last case in the world was in 1977. However, the smallpox virus still exists in laboratories and represents a potential threat because it could be used by terrorists. Monkeypox is primarily a disease of animals, but more than a hundred human cases a year have been reported from central and western Africa. The first monkeypox outbreak occurred in the United States in June 2003 when several people were sickened by infected pet prairie dogs. Symptoms of monkeypox are similar to smallpox, though often milder.

An underlying principle of female reproductive biology appears to have been overturned by a report from researchers at Massachusetts General Hospital (MGH). In an article in the March 11, 2004 issue of Nature, the investigators report that female mice retain the ability to make new egg cells well into adulthood. It has been believed that most female mammals are born with a finite supply of these cells, called oocytes, that are lost at a steady rate until the supply is exhausted, leading to menopause in women.

For several years Jonathan Tilly, PhD, of the Vincent Center for Reproductive Biology at MGH and his group have been studying the mechanisms behind the death of oocytes and follicles, the tiny sacs in which the eggs grow. In both mice and humans, the vast majority of oocytes are destined to die through a process called programmed cell death or apoptosis, the body's natural way of eliminating unneeded or damaged cells. The team's earlier research confirmed that oocytes destroyed by chemotherapy drugs or radiation also die through apoptosis, opening the possibility of designing ways to stop ovarian damage in female cancer patients and perhaps to postpone normal ovarian failure. However, to provide an essential context to their efforts to inhibit oocyte apoptosis, the researchers decided to measure the numbers of healthy and dying follicles in mouse ovaries through the animals' lifespan.

What they found was remarkable. Measurements taken during the early stages of life found a steady, low level of dying follicles, but as the mice reached adulthood the number of dying follicles increased markedly. In young adult animals, the researchers measured 1,200 dying follicles per ovary, compared with about 3,000 healthy follicles remaining. Similarly elevated levels of dying follicles were measured well into maturity. Although such a surprisingly high rate of follicle loss would be expected to completely deplete a fixed population of oocytes within a matter of days or weeks, female mice retain healthy egg cells well past one year of age.

To make sure they were accurately measuring the rate at which follicles were dying, the researchers evaluated whether dead and dying follicles were being cleared from the ovaries. Their results confirmed that the dying follicles were being cleared within three days of death and thus represented a continuing level of cell death, not an accumulation of "cellular corpses."

To investigate such a potentially revolutionary possibility, the researchers ran several additional experiments:
-Careful examination of ovaries of young and mature mice identified cells on the organs' outer surface that resembled germ cells, which are the source of oocytes that develop in fetal animals. These cells were found to express a gene known to be present only in germ cells and were shown to maintain the ability to undergo cell division in juvenile and adult ovaries.
-A key stage in the development of any germ cell is meiosis, which results in egg or sperm cells with a single set of chromosomes instead of the paired sets found in most cells. Finding a protein that is only produced at the onset of meiosis in ovarian cells of young and mature mice indicated that this aspect of oocyte development continues after birth.
-Busulfan is a chemotherapy drug known to target proliferating germ cells in males but have no effect on mature sperm cells. Three weeks after being injected with busulfan, female mice were found to have only 5 percent the supply of primordial (immature) follicles than control mice had. The investigators went on to show this difference was not due to increased death of primordial follicles, implying that the busulfan-related drop in the number of primordial follicles resulted from an absence of follicular renewal.
-The researchers grafted ovarian tissue from normal adult mice onto the ovaries of adult transgenic mice that express a green marker protein in all of their cells. Several weeks later the grafted ovaries in the transgenic mice were found to contain hybrid follicles consisting of normal follicular cells surrounding green oocytes. These results demonstrated that transgenic (green) germ cells had migrated from the host ovary into the grafted ovarian tissue and produced green oocytes, which formed new follicles from the surrounding normal cells.

Tilly says that the concept of a fixed pool of oocytes, first asserted almost a century ago, has been so widely accepted that he is not aware of any studies over the past 50 years that have questioned its accuracy. "The ovaries visibly lose healthy follicles throughout life, while the testes continue to look the same. It was assumed that the decline in total follicles represented the gradual disappearance of a limited supply of oocytes. No one ever attempted to measure the actual rate of oocyte or follicle death before because the dogma was so persuasive," he explains.

Among many potential implications of the study is a different mechanism underlying ovarian aging. It is known that eggs released by older women are more likely to be abnormal, which has been attributed to the eggs themselves being older. But the problems could instead be the result of aging of the germline stem cells that produce the oocytes. If these stem cells could be identified and isolated, a whole new set of options for treating or preventing infertility might open up.

Additional authors of the Nature study are co-first authors Joshua Johnson, PhD, and Jacqueline Canning, along with Tomoko Kaneko, MD, PhD, and James Pru, PhD, all of the Vincent Center for Reproductive Biology. The study was supported by Vincent Memorial Research Funds and the National Institute on Aging.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School.

NASA's Mars Exploration Rovers have become eclipse watchers.

Though the Viking Landers in the 1970s observed the shadow of one Mars' two moons, Phobos, moving across the landscape, and Mars Pathfinder in 1997 observed Phobos emerge at night from the shadow of Mars, no previous mission has ever directly observed a moon pass in front of the sun from the surface of another world.

The current rovers began their eclipse-watching campaign this month. Opportunity's panoramic camera caught Mars' smaller moon, Deimos, as a speck crossing the disc of the sun on March 4. The same camera then captured an image of the larger moon, Phobos, grazing the edge of the sun's disc on March 7.

Rover controllers at NASA's Jet Propulsion Laboratory (JPL), Pasadena, Calif., are planning to use the panoramic cameras on both Opportunity and Spirit for several similar events in the next six weeks. Dr. Jim Bell of Cornell University, Ithaca, N.Y., lead scientist for those cameras, believes the most dramatic images may be the one of Phobos planned for March 10.

Depending on the orientation of Phobos as it passes between the sun and the rovers, the images might also add new information about the elongated shape of that moon.

Phobos is about 27 kilometers long by about 18 kilometers across its smallest dimension (17 miles by 11 miles). Deimos' dimensions are about half as much, but the pair's difference in size as they appear from Mars' surface is even greater, because Phobos flies in a much lower orbit.

The rovers' panoramic cameras observe the sun nearly every martian day as a way to gain information about how Mars' atmosphere affects the sunlight. The challenge for the eclipse observations is in the timing. Deimos crosses the sun's disc in only about 50 to 60 seconds. Phobos moves even more quickly, crossing the sun in only 20 to 30 seconds.

Scientists use the term "transit" for an eclipse in which the intervening body covers only a fraction of the more-distant body. For example, from Earth, the planet Venus will be seen to transit the sun on June 8, for the first time since 1882. Transits of the sun by Mercury and transits of Jupiter by Jupiter's moons are more common observations from Earth.

From Earth, our moon and the sun have the appearance of almost identically sized discs in the sky, so the moon almost exactly covers the sun during a total solar eclipse. Because Mars is farther from the sun than Earth is, the sun looks only about two-thirds as wide from Mars as it does from Earth. However, Mars' moons are so small that even Phobos covers only about half of the sun's disc during an eclipse seen from Mars.