Gretchen Vogel

A Seismic Shift for Stem Cell Research

The development of pluripotent cells from individual skin cells has opened up a new world of research, but scientists say they still need to work with embryonic stem cells.

Breakthrough of the year. Reprogramming Cells.

REPROGRAMMING CELLS. The riddle of Dolly the Sheep has puzzled biologists for more than a decade: What is it about the oocyte that rejuvenates the nucleus of a differentiated cell, prompting the genome to return to the embryonic state and form a new individual? This year, scientists came closer to solving that riddle. In a series of papers, researchers showed that by adding just a handful of genes to skin cells, they could reprogram those cells to look and act like embryonic stem (ES) cells. ES cells are famous for their potential to become any kind of cell in the body. But because researchers derive them from early embryos, they are also infamous for the political and ethical debates that they have sparked. The new work is both a scientific and a political breakthrough, shedding light on the molecular basis of reprogramming and, perhaps, promising a way out of the political storm that has surrounded the stem cell field. The work grows out of a breakthrough a decade ago. In 1997, Dolly, the first mammal cloned from an adult cell, demonstrated that unknown factors in the oocyte can turn back the developmental clock in a differentiated cell, allowing the genome to go back to its embryonic state. Various experiments have shown how readily this talent is evoked. A few years ago, researchers discovered that fusing ES cells with differentiated cells could also reprogram the nucleus, producing ES-like cells but with twice the normal number of chromosomes. Recently, they also showed that a fertilized mouse egg, or zygote, with its nucleus removed could also reprogram a somatic cell. Meanwhile, the identity of the reprogramming factors continued to puzzle and tantalize biologists. In 2006, Japanese researchers announced that they were close to at least part of the answer. By adding just four genes to mouse tail cells, they produced what they call induced pluripotent stem (iPS) cells: cells that looked and acted like ES cells. This year, in two announcements that electrified the stem cell field, scientists closed the deal. In a series of papers in June, the same Japanese group, along with two American groups, showed that the iPS cells made from mouse skin could, like ES cells, contribute to chimeric embryos and produce all the body’s cells, including eggs and sperm. The work convinced most observers that iPS cells were indeed equivalent to ES cells, at least in mice. Then in November came a triumph no one had expected this soon: Not one, but two teams repeated the feat in human cells. The Japanese team showed that their mouse recipe could work in human cells, and an American team found that a slightly different recipe would do the job as well. The advance seems set to transform both the science and the politics of stem cell research. Scientists say the work demonstrates that the riddle of Dolly may be simpler than they had dared to hope: Just four genes can make all the difference. Now they can get down to the business of understanding how to guide the development of these highpotential cells in the laboratory. In December, scientists reported that 2

The Inner Lives of Sponges

Symbiotic ties, bioactive compounds, and mysterious distributions of bacteria characterize these ancient invertebrates.

Trachea transplants test the limits.

June 2008 was the first time a patient received a trachea transplant that made use of her own stem cells, in what was then the most advanced example of tissue engineering. Since then, 14 other patients have received bioengineered tracheas. Some observers wonder if the surgeries are really examples of successful tissue engineering that utilize the special abilities of stem cells or an elaborate temporary fix that is destined to fail. Two surgeons are trying to address the doubts of their approach with clinical trials, but others contend that, before pushing ahead, the trachea pioneers should focus on understanding what happens to the grafts over the long term.

For More Protein, Filet of Cricket

Could an African caterpillar be the new beefsteak? As the world diverts more of its grain harvests into producing meat, some scientists are pushing policymakers to take a closer look at insects as an environmentally friendlier source of protein. Whereas a cow needs to eat roughly 8 grams of food to gain a gram in weight, for instance, insects need less than two. The U.N. Food and Agriculture Organization is currently developing policy guidelines that will encourage countries to include insects in their food-security plans.

Mending the Youngest Hearts

Tissue EngineeringThis month, after an arduous approval process, surgeons are testing tissue-engineered cardiac blood vessels in the first U.S. patients. The implants, which are used to connect a major cardiac vein and the artery that carries blood to the lungs, are made of a synthetic scaffold seeded with cells from the patients own bone marrow. In the body, the graft develops into a living blood vessel that grows with the patient. But new experiments suggest that inflammation, long seen as an enemy of transplants and artificial implants alike, seems to play a key role in the transformation of the cell-filled scaffold into a healthy blood vessel. And stem cells, which have been seen as the stars of tissue engineering, play a less significant role than expected. The results are prompting tissue engineers to rethink the role of inflammation and stem cells.

To Scientists' Dismay, Mixed-Up Cell Lines Strike Again

Over the past 5 years, a handful of research teams have raised concerns about ongoing attempts to transplant mesenchymal stem cells (MSCs), stem cells found in bone marrow and muscle, into people with heart disease and other conditions. The groups had found that MSCs could become cancerlike after growing for months in the lab. But three of these research teams have now discovered that the cancerlike cells they spotted are unrelated to the original MSCs. In each case, tumor cells that the researchers were using for other projects had contaminated the MSCs and, because they grow faster than the stem cells, ultimately took over the cell culture.

Testing new Ebola tests

As Ebola continues to rage in three West African countries—and projections for the epidemic9s growth look increasingly dire—health officials are hoping they will soon have an additional tool to fight the disease: an easy-to-use, fast, and inexpensive diagnostic test for the responsible virus. Several teams are working on prototype kits—small disposable devices resembling home pregnancy tests—that use just a few drops of blood from a fingertip jab and can be carried easily to remote villages or on door-to-door screening campaigns. At least two of the potential diagnostics will undergo their first field trials in Guinea and Sierra Leone in the coming weeks.

The 'do unto others' malaria vaccine.

Progress is accelerating on transmission-blocking vaccines (TBVs), which would use humans to generate antibodies and deliver them to mosquitoes, with the aim of preventing the insects from spreading the disease. A half-dozen TBVs could have a shot at clinical trials sometime in the next 5 years, researchers say. Even so, the scientific and social hurdles remain daunting. Key among them is whether people can be persuaded to get a vaccination that doesn9t prevent them from getting sick but instead protects family and neighbors from getting infected. That also raises the bar for an extremely safe vaccine.

How Do Organs Know When They Have Reached the Right Size

Developmental biologists have found dozens of proteins and genes that play a role in the growth of plants and animals. But how growing organs and organisms can sense their size and know when to stop is still a mystery. Developmental biologists continue to explore that mystery, and the current objects of their attention are imaginal discs, flattened sacs of cells that grow during fruit flies9 larval stages. Scientists can also change the rate at which imaginal disc cells divide, prompting either too many or not enough cells to form, but the cell size adjusts so that organ size remains the same. How does a developing organ somehow senses the mechanical forces on its growing and dividing cells?