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Losing just one night sleep can cause the brain to experience ‘power failures’ according to research

Being deprived of sleep even for one night makes the brain unstable and prone to sudden shutdowns akin to a power failure – brief lapses that hover between sleep and wakefulness, according to researchers.

“It’s as though it is both asleep and awake and they are switching between each other very rapidly,” said David Dinges of the University of Pennsylvania School of Medicine, whose study appears in the Journal of Neuroscience.

“Imagine you are sitting in a room watching a movie with the lights on. In a stable brain, the lights stay on all the time. In a sleepy brain, the lights suddenly go off,” Dinges said.

The findings suggest that people who are sleep-deprived alternate between periods of near-normal brain function and dramatic lapses in attention and visual processing.

“This involves more structures changing than we’ve ever seen before, but changing just during these lapses,” Dinges said.

He and colleagues did brain imaging studies on 24 adults who performed simple tasks involving visual attention when they were well rested and when they had missed a night’s sleep.

The researchers used a type of brain imaging known as functional magnetic resonance imaging, or fMRI, which measures blood flow in the brain.

They found significant, momentary lapses in several areas of the brain, which seemed to frequently falter when the people were deprived of sleep, but not when these same people were well rested.

“These people are not lying in bed. They are sitting up doing a task they learned and they are working very hard at doing their best,” Dinges said.

He said the lapses seem to suggest that loss of sleep renders the brain incapable of fully fending off the involuntary drive to sleep.

He said the study makes it clear how dangerous sleep deprivation can be while driving on the highway, when even a four-second lapse could lead to a major accident.

“These are not just academic interests,” he said.

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The Journal of Neuroscience

May 21, 2008, 28(21):5519-5528; doi:10.1523/JNEUROSCI.0733-08.2008

Behavioral/Systems/Cognitive
Lapsing during Sleep Deprivation Is Associated with Distributed Changes in Brain Activation

Michael W. L. Chee,1 Jiat Chow Tan,1 Hui Zheng,1 Sarayu Parimal,1 Daniel H. Weissman,2 Vitali Zagorodnov,3 and David F. Dinges4

1Cognitive Neuroscience Laboratory, Duke–National University of Singapore Graduate Medical School, Singapore 169611, Singapore, 2Department of Psychology, University of Michigan, Ann Arbor, Michigan 48109, 3School of Computer Engineering, Nanyang Technological University, Singapore 639798, Singapore, and 4Division of Sleep and Chronobiology, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Correspondence should be addressed to Dr. Michael Chee, Cognitive Neuroscience Laboratory, Duke–National University of Singapore Graduate Medical School, 7 Hospital Drive, #01-11, Block B, Singapore 169611, Singapore. Email: mchee@pacific.net.sg

Abstract

Lapses of attention manifest as delayed behavioral responses to salient stimuli. Although they can occur even after a normal night’s sleep, they are longer in duration and more frequent after sleep deprivation (SD). To identify changes in task-associated brain activation associated with lapses during SD, we performed functional magnetic resonance imaging during a visual, selective attention task and analyzed the correct responses in a trial-by-trial manner modeling the effects of response time. Separately, we compared the fastest 10% and slowest 10% of correct responses in each state. Both analyses concurred in finding that SD-related lapses differ from lapses of equivalent duration after a normal night’s sleep by (1) reduced ability of frontal and parietal control regions to raise activation in response to lapses, (2) dramatically reduced visual sensory cortex activation, and (3) reduced thalamic activation during lapses that contrasted with elevated thalamic activation during nonlapse periods. Despite these differences, the fastest responses after normal sleep and after SD elicited comparable frontoparietal activation, suggesting that performing a task while sleep deprived involves periods of apparently normal neural activation interleaved with periods of depressed cognitive control, visual perceptual functions, and arousal. These findings reveal for the first time some of the neural consequences of the interaction between efforts to maintain wakefulness and processes that initiate involuntary sleep in sleep-deprived persons.

Key words: lapses; visual cortex; functional neuroimaging; cognitive control; attention; sleep deprivation

Being deprived of sleep even for one night makes the brain unstable and prone to sudden shutdowns akin to a power failure – brief lapses that hover between sleep and wakefulness, according to researchers.”It’s as though it is both asleep and awake and they are switching between each other very rapidly,” said David Dinges of the University of Pennsylvania School of Medicine, whose study appears in the Journal of Neuroscience.”Imagine you are sitting in a room watching a movie with the lights on. In a stable brain, the lights stay on all the time. In a sleepy brain, the lights suddenly go off,” Dinges said

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May 28, 2008, Forbes.com – Dr. Francis Collins, who became the public face for a watershed science project – unraveling the human genetic code – is resigning as the government’s gene guru.

Collins, arguably the nation’s most influential geneticist, announced Wednesday that he will leave the National Institutes of Health this summer to explore other opportunities.

The folksy geneticist helped translate the complexities of DNA into everyday vernacular, once famously calling the human genome or genetic code the “book of human life.” He became a leading advocate for the privacy of genetic information.

But Collins may be better known to laymen for his 2007 best-selling book about his belief in both God and science.

By Henry Fountain, May 27, 2008, The New York Times – Down below the ocean, there are some things that are very real — namely, bacteria and archaea. By some estimates, sub-seafloor prokaryotes may account for two-thirds of the biomass of these types of organisms on Earth.

The latest evidence for such a huge undersea biosphere, and a depth record of sorts, is reported in Science by R. John Parkes of Cardiff University and colleagues. They have found living prokaryotes 5,335 feet below the ocean floor off Newfoundland, about twice as deep as the previous record.

Intact cells were found in cores drilled through sediments up to 111 million years old, although the age of the prokaryotes themselves is an open question. The researchers were able to amplify genetic material, which strongly suggests that the cells are living, feeding on trapped methane, other hydrocarbons and organic carbon. Prokaryotes are simple organisms without a nucleus; they are an organism whose DNA is not contained within a nucleus, e.g. a bacterium.

Temperatures of the deepest core samples were estimated from 140 to 212 degrees Fahrenheit, so the cells qualify as extremophiles, able to withstand harsh conditions like those found around deep-sea hydrothermal vents. Some of the genetic sequences found match those from known heat-loving bacterial strains like Pyrococcus.

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Pyrococcus

Living cells have been found at greater depths under land, but the concentration of cells in the undersea cores (about a million per milliliter) is much higher. The finding is another that stretches the boundaries of where life can flourish — with all that implies about the situation on worlds other than Earth.

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Prokaryotes include the archaebacteria and bacteria. Shown here are two types of bacteria. On the left is a cyanobacteria, called an autotroph, or self-feeder, because it carries out photosynthesis and produces its own food. On the right is a species of Salmonella, which must ingest organic compounds and so is called a heterotroph, or other feeder. The numerous flagella seen here enable Salmonella to move through the intestinal tracts of animals, where they can cause the food-borne illness salmonellosis.

Prokaryote, is a relatively simple unicellular organism, such as a bacterium, characterized by the absence of a nucleus and other specialized cell structures. Scientists distinguish prokaryotes from eukaryotes, which are more complex organisms with cells that contain a nucleus, such as plants and animals.

Scientists classify prokaryotes in different ways, depending on the classification system used. In 1938 American biologist Herbert Copeland proposed that unicellular organisms lacking nuclei be classified in their own kingdom called Kingdom Monera, now called Kingdom Prokaryotae. All bacteria were categorized in this new kingdom. This scheme was the first to establish separate kingdoms for prokaryotes (organisms without nuclei) and eukaryotes (organisms with nuclei). In the 1970s scientists determined that cyanobacteria, formerly known as blue-green algae, have physical features that make them more closely related to bacteria than to algae. Although the exact classification of cyanobacteria is still under debate, some scientists now classify cyanobacteria in the Kingdom Prokaryotae, while algae remains classified in the Kingdom Protista.

In 1990 American microbiologist Carl Woese proposed that bacteria be divided into two groups, archaebacteria and bacteria, based on their structural and physiological differences. Archaebacteria consist of a small group of primitive anaerobes (organisms that do not require oxygen). They are found in a narrow range of habitats—often in extreme environments such as hydrothermal vents on the deep ocean floor. In contrast, bacteria live in a wide range of environments with or without oxygen, at various temperatures, and at various levels of acidity. In some classification systems, the archaebacteria are considered prokaryotes; in other systems they are classified in a category known as the Domain Archaea.

Prokaryotic cells are relatively small, ranging in size from 0.0001 to 0.003 mm (0.000004 to 0.0001 in) in diameter. With the exception of a few species, prokaryotic cells are surrounded by a protective cell wall. The cell walls of archaebacteria and bacteria contain forms of peptidoglycan, a protein-sugar molecule not present in the cell walls of fungi, plants, and certain other eukaryotes. The archaebacteria cell wall has a more diverse chemical composition than the cell wall of bacteria.

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Extremophiles

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Sea Vents

Life exists not just around vents, but inside them too. Unlike the life forms that crawl or swim around the vents, those inside are invisible. These microscopic bacteria (one-celled organisms) not only survive but even thrive in the dark and hot environment of the vent. In the absence of sunlight, specially adapted bacteria and similar organisms called Archaea convert the vent chemicals to usable bioenergy, in a process analogous to plants’ ability to use sunlight.

Yellowstone Hotsprings

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Researchers have discovered a bizarre group of microbes that live inside rocks in the inhospitable geothermal environment at Wyoming’s Yellowstone National Park. One scientist describes the life–form, found in the pores of rocks in a highly acidic environment, as “pretty weird,” and resembling a lichen. Scientists believe similar kinds of geothermal environments may have once existed on Mars. The Yellowstone discovery may help steer the hunt for evidence of life on Mars.

Antarctica – Subglacial Lakes

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In addition to the super-hot environment of sea vents and hot springs, bacterial life may also exist in the cold, dark environment beneath the Antarctic ice sheet. Scientists aren’t yet sure, but the suggestions are strong. Two separate research teams have drilled into Lake Vostok, a suspected body of water below the Antarctic ice sheet. (It is still “suspected,” and not proven, because scientists are reluctant to explore further until they know their actions will not contaminate a potentially unique environment.) Both teams found bacteria inside ice that is believed to be created from lake water. DNA analysis indicates that although the bacteria have been isolated for millions of years, they are biologically similar to known organisms.

Atacama Desert

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Scientists now know that life exists not only in very hot and very cold liquid environments, but in a very dry environment as well. Environmental microbiologists have discovered evidence of microbial life about a foot below the rough terrain of Chile’s Atacama desert, one of the driest places on Earth. Their finding contradicts previous beliefs that the desert is too dry to support life, and may influence how scientists look for life in the similarly dry environment of Mars.

Europa

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Europa ?

Some scientists speculate that if life does exist beyond Earth, it might be the form of vent bacteria. Because these microscopic life forms have already proven their ability to survive in the extreme environment of Earth’s hydrothermal vents, they might also survive in similar environments elsewhere – for example, on Europa. Europa is one of Jupiter’s moons, and is covered in ice. Scientists have recently uncovered strong evidence of liquid water beneath Europa’s ice, which may be due to hydrothermal vents, which may in turn host bacteria. Alternatively, scientists who have found evidence of bacteria living inside Antarctic ice speculate that they may also live inside Europa’s ice. The questions exceed the answers, but the clues are tantalizing.

Extremophiles act like alien organisms
By Bjorn Carey
LiveScience

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NASA / Univ. of Alabama
A fluorescent stain renders adds a green tinge to the corkscrew-shaped Spirochaeta americana from California’s Mono Lake. Green spots are spheroplasts. Reddish areas are dead cells.

Extremophilic microbes are a wild bunch. They can be found thriving in some of the most hostile environments imaginable — swimming in near-boiling water, eating rocks, lounging in subzero temperatures and hanging out where radiation levels rival nuclear reactors.

They’re tougher than duct tape, boldly going where humans dare not and cannot.

Extremophiles are also a multimillion-dollar-a-year business — some of them are employed to eat oil and help clean up spills. Others have important applications in medical research. But for many scientists, these hardy microbes are interesting because they suggest the potential for life on other planets.

Recent discoveries have greatly expanded the range of these wild things. Here’s a census of small creatures living in some of the worst conditions imaginable.

Microbial extremophiles have recently been discovered thriving in the extremely hostile environments in the depths of the Mediterranean Sea.

At nearly 2.5 miles (4 kilometers) below sea level, with salt concentrations 10 times higher than seawater, pressure 400 times greater than atmospheric pressure, and a lack of oxygen to boot, the conditions in which these microbes thrive are some of the most hostile environments on Earth.

In the Jan. 7 issue of the journal Science, researchers working on the European Biodeep project reported the discovery of new microbes in the anoxic basins, or “brine lakes,” located off the coast of Sicily.

It is these types of conditions, particularly the high concentrations of magnesium chloride, that have scientists imagining what the environments of other planets might consist of, and whether they contain life.

“Ascertaining the nature of the subsurface on other planets is tricky, but there is growing evidence for hypersaline environments on Mars and Jupiter’s moon, Europa. Indeed, Europa is believed to have a subsurface ocean rich in magnesium salts,” Terry McGenity, the lead scientist of the University of Essex group working on the Biodeep project, told LiveScience.

Since light cannot penetrate water of this depth, there are no photosynthetic bacteria in the basins. Most of the organisms the Biodeep workers have found reduce sulfates to run their metabolism.

Some of the microbes McGenity’s group found were completely unknown, including a new group of Archaea they have named MSBL-1. McGenity speculates that these microbes are methanogens because they are related to methane-producing Archaea, and no other methane-producing microbes were found in the basins, which are abundant with methane.

The European Mars Express mission detected hints of methane in Mars’ atmosphere last year, and some astrobiologists have speculated that the methane could be a by-product of extremophilic methanogens or some other form of microbial life.

Life fueled by hydrogen
Another recent extremophile study discovered microbes in the hot springs of Yellowstone National Park using hydrogen as their primary fuel source, refuting the popular conception that sulfur is the main source of energy for microbes living in thermal features.

The research was designed to find the main source of energy of microbes living in hot springs with temperatures over 158 degrees Fahrenheit (70 Celsius), a temperature too high for photosynthesis.

“It was a surprise to find hydrogen was the main energy source for microbes in hot springs,” said University of Colorado researcher Norman Pace, who led the team.

Pace’s colleague John Spear, lead author of the study published in January’s online edition of the Proceedings of the National Academy of Sciences, speculated about what the discovery of hydrogen-fueled microbes means for life on other planets.

“Hydrogen is the most abundant element in the universe,” Spear points out. “If there is life elsewhere, it could be that hydrogen is its fuel.”

Life in cold climates:

Hiding beneath sheets of ice in Siberia and Antarctica are microbes called psychrophiles or psychrotrophs. They consist mostly of bacteria, fungi and algae that thrive in freezing temperatures ranging from 23 to 59 degrees Fahrenheit (-5 to 20 Celsius).

In addition to being cold, the environments that these microbes are found in are sometimes at tremendous depths — more than 2 miles (3.2 kilometers) below the surface.

Psychrophiles help us clean up arctic oil spills. They also turn our milk sour. There is a good chance, scientists say, that extraterrestrial life could be similar to this class of microbes. In a solar system where many of the planets — including Mars — have large ice deposits and colder temperatures in general, psychrophiles might thrive.

Undersea hot spots
Rising as high as 15 stories off the ocean floor at depths of 7,000 feet (2,100 meters), hydrothermal vents that spew acidic, mineral-rich water are the places to be — if you can stand the heat. The water coming out of the vents can reach temperatures as high as 750 degrees Fahrenheit (400 degrees Celsius), but that’s just fine for undersea thermophiles.

The mineral-munching microbes living around these volcanic “chimneys,” which are so deep no sunlight can reach them, give yet another view of what life could be like on another planet, where lack of sunlight would hinder organisms relying on photosynthesis as their energy producing mechanism.

A number of the planets and moons in our solar system are covered in ice, but scientists speculate that below some of that ice are liquid oceans. If there is also volcanic activity on those ocean floors, it is possible that similar hydrothermal vents could be growing there as well. Although it is nearly impossible to know whether there is life in those oceans, such worlds would at least contain an environment in which we know organisms could live.

Life in the deep ocean, in rocks … and in space?
A sediment sample recently dredged up from Challenger Deep, the deepest part of the Pacific Ocean, was abundant in single-celled protists called foraminifera. Researchers were surprised to find these soft-shelled critters at depths of nearly 7 miles (11.2 kilometers), where the pressure is 1,100 times greater than at the surface.

“I am very surprised that so many very simple, soft-shelled foraminifera are dwelling at the deepest part of the ocean,” said Hiroshi Kitazato, of the Institute for Research on Earth Evolution at the Japan Agency for Marine-Earth Science and Technology.

Kitazato suggests that the deep trenches, where the creatures can feed on bits of sunken organic matter, may provide a refuge for the foraminifera.

The fossil record of foraminifera is more than 550 million years old. In last week’s issue of the journal Science, Kitazato suggested that these new creatures probably represent the remnants of a deep-dwelling group that was able to adapt to high pressures.

The rest of the wild bunch

· Endoliths and hypoliths are two types of extremophiles that live inside rocks or between the mineral grains. Endoliths have been found more than 2 miles below Earth’s surface, and if they can stand the heat, they could dwell much deeper. Early observations show that they feed on surrounding iron, potassium or sulfur. Water is scarce at these depths, and this slows down the procreation cycle of the organisms — some reproduce only once every 100 years! Hypoliths are photosynthetic organisms, so the rocks they live in must be translucent, like quartz. Hypoliths are commonly found in extreme deserts in cold climates, such as Antarctica on the Canadian Arctic’s Cornwallis Island. Their translucent homes provide them with many comforts, such as trapped moisture and protection from ultraviolet rays and harsh winds.

· Hyperthermophiles are organisms that prefer temperatures above 140 degrees F, some even as high as 250 degrees F (121 degrees C), although those have trouble reproducing. The hardiest of the 50 known species are those living near hydrothermal vents — these require temperatures of over 194 degrees F (90 degrees C) to live. In addition to being heat-resistant, many hyperthermophiles can withstand other environment stresses, such as high acidity and radiation. One thermophile, Thermus aquaticus, produces a DNA polymerase enzyme that is widely used in molecular biology research for use in high-temperature polymerase chain reactions used to replicate DNA.

· Toxitolerant organisms can withstand high levels of damaging agents. They can be found swimming around in benzene-saturated water or in the core of a nuclear reactor. One species of bacteria, Deinococcus radiodurans, can withstand a 15,000-gray dose of radiation – 10 grays would kill a human, and it takes over 1,000 grays to kill a cockroach. Extraterrestrial life forms would most likely need to possess similar tolerances to radiation, because the atmosphere on other planets, or lack thereof, filters out much less radiation than Earth’s.

· Oligotrophic bacteria survive in, and in some cases prefer, environments that are low in nutrients. They have evolved metabolic processes that allow them to produce their own sulfur and phosphorus, and they feed on their own organic waste.

While there is no evidence for life beyond Earth, information about extraterrestrial environments combined with the discoveries of life in places on our planet thought to be inhabitable keeps scientists optimistic.

“If it works this way on Earth, it’s likely to happen elsewhere,” says Spear, the University of Colorado scientist. “When you look up at the stars, there is a lot of hydrogen in the universe.”

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Eukaryotes have areas inside the cell separated off from the rest of the cell by membranes, like the cell membrane (see below). These areas include the nucleus, numerous mitochondria and other organelles such as the golgi body, and or chloroplasts within each of their cells. These areas are made distinct from the main mass of the cells cytoplasm by their own membrane in order to allow them to be more specialised. You can think of them as separate rooms within your house. The nucleus contains all the cell’s DNA, the Mitochondria are where energy is generated, chloroplasts are where plants trap the suns energy in photosynthesis. There are exceptions to every rule of course, and in this case the most obvious two are the red blood cells of animals and the sieve tube elements of plants, which, though living, have no nucleus and no DNA, normally these cells to do not live very long.

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Prokaryotes do not have a nucleus, mitochondria or any other membrane bound organelles. In other words neither their DNA nor any other of their metabolic functions are collected together in a discrete membrane enclosed area. Instead everything is openly accessible within the cell, though some bacteria have internal membranes as sites of metabolic activity these membranes do not enclose a separate area of the cytoplasm. See Cells: The Basis of Life

SAN ANTONIO, Texas (CNN) — Last week in an operating room in Texas, a wounded American soldier underwent a history-making procedure that could help him regrow the finger that was lost to a bomb attack in Baghdad last year.

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Army Sgt. Shiloh Harris is wheeled into surgery to undergo the experimental treatment to regrow what’s left of his finger.

Army Sgt. Shiloh Harris’ doctors applied specially formulated powder to what’s left of the finger in an effort to do for wounded soldiers what salamanders can do naturally: replace missing body parts.

If it sounds like science fiction, the lead surgeon agreed.

“It is. But science fiction eventually becomes true, doesn’t it?” said Dr. Steven Wolf of Brooke Army Medical Center.

Harris’ surgery is part of a major new medical study of “regenerative medicine” being pursued by the Pentagon and several of the nation’s top medical facilities, including the University of Pittsburgh Medical Center and the Cleveland Clinic. So far nearly $250 million has been dedicated to the research.

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A powder derived from pig tissue may coax human stem cells back to work growing new body parts.

Air Force Technical Sgt. Israel Del Toro is one of the wounded vets who might one day benefit from this research. He was injured by a bomb in Afghanistan. Both his hands were badly burned. On his left hand, what was left of his fingers fused together. “You know in the beginning when I first got hurt, I told them just cut it off. So I can get some function,” Del Toro said. His doctors did not cut off his injured left arm. And since that injury, advancements in burn and amputation treatment mean he may one day be able to use his fingers again.

A key to the research dedicated to regrowing fingers and other body parts is a powder, nicknamed “pixie dust” by some of the people at Brooke. It’s made from tissue extracted from pigs.

The pixie dust powder itself doesn’t regrow the missing tissue, it tricks the patient’s body into doing that itself. All bodies have stem cells. As we are developing in our mothers’ wombs, those stem cells grow our fingers, toes, organs — essentially our whole body. The stem cells stop doing that around birth, but they don’t go away. The researchers believe the “pixie dust” can put those stem cells back to work growing new body parts.

The powder forms a microscopic “scaffold” that attracts stem cells and convinces them to grow into the tissue that used to be there. “If it is next to the skin, it will start making skin. If it’s next to a tendon, it will start making a tendon, and so that’s the hope, at least in this particular project, that we can grow a finger,” Wolf said.

It has worked in earlier experiments. “They have taken a uterus out of a dog, made one in the lab, put it back in, and had puppies,” said Wolf. Researchers have also regrown a human bladder, implanted it in a person and it is working as nature intended.

While the technique has incredible promise, doctors will be watching for unexpected side effects as they follow Harris’ recovery. “It could grow a cancer,” Wolf said. “We will be closely monitoring for that to make sure that doesn’t happen.”

If the military’s most badly wounded start benefiting, so will civilians. “If we can pull this off in missing parts the next step is, ‘OK, can we grow a pancreas? Can we grow and replace that in a diabetic?’ And can we do the same thing with a kidney and can we do the same thing with a heart?”

One day, he hopes, people with heart trouble will be told, “That’s OK. We will just grow you another one.

“That is something that is real science fiction.”

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Doctors hope the powder they applied to Sgt. Shiloh Harris’ amputation site will help his finger regrow.
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Caption: Microscopic view of a colony of original human embryonic stem cell lines from the James Thomson lab at the University of Wisconsin-Madison. These cells, which arise at the earliest stages of development, are blank slate cells capable of differentiating into any of the 220 types of cells in the human body. They can provide access to cells for basic research and potential therapies for many types of disease. Thomson, a developmental biologist and professor of anatomy, directed the research group that reported the first isolation of embryonic stem cell lines from a nonhuman primate in 1995, work that led his group to the first successful isolation of human embryonic stem cell lines in 1998. In 2007, Thomson and his colleagues, and a group in Japan, successfully reprogrammed adult skin cells to create the world’s first induced pluripotent stem cells, cells that have all the qualities of embryonic stem cells.
Date: 2005
Photo credit: Jeff Miller/University of Wisconsin-Madison

The Mayo Clinic – Researchers believe stem cells offer great promise for new medical treatments. Learn about stem cell types, current and possible uses, ethical issues and the state of research.

You’ve heard about stem cells in the news, and perhaps you’ve wondered if they might help you or a loved one with a serious disease. You may struggle with understanding what stem cells are, how they’re being used to treat disease and injury, and why they’re the subject of such vigorous debate.

Here, you can sort through the hype and the hope and get answers to frequently asked questions about stem cells.

Why is there high interest in stem cells?

Researchers are interested in stem cells for two main reasons:

* Knowledge. By studying how stem cells mature into cells that eventually become bones, heart muscles, other organs and tissue, researchers hope to learn more about the function of stem cells and what can go wrong in development. This knowledge may shed new light on how a variety of diseases and conditions develop, such as heart disease, cancer or birth defects.
* Therapy. Researchers hope they can manipulate stem cells into becoming specific types of cells. If this is done successfully, stem cells may be used to regenerate and repair tissues and organs to treat diseases and conditions such as diabetes, heart failure, Parkinson’s disease, inherited genetic diseases or spinal cord injuries. Stem cells could also be grown to become organs to use in transplants, since donor organs are often in short supply. Stem cells may also one day be useful in testing experimental medications before human clinical trials.

What exactly are stem cells?

Stem cells are master cells of the body — cells from which all other cells with specialized functions are created. Under the right conditions in the body or a laboratory, stem cells divide to form more cells, called daughter cells. These daughter cells either become new stem cells (self-renewal) or become specialized cells (differentiation) with a more specific function, such as blood cells, brain cells, heart muscle or bone. Stem cells are unique — no other cell in the body has the ability to self-renew or to differentiate.

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Caption: This microscopic image shows a large sphere of neural stem cells in culture, surrounded by stem cells that are “leaving home,” migrating away from the sphere. To better address the public issues raised by new neuroscience research, two University of Wisconsin-Madison faculty, professor of neuroscience Ronald Kalil and professor of science and technology policy Clark Miller, have created a new dual-degree graduate program in neuroscience and public policy.

Researchers have discovered several sources of stem cells:

* Embryonic stem cells. These stem cells come from embryos that are four to five days old. At this stage, an embryo is called a blastocyst and has about 50 to 150 cells. These are pluripotent (ploo-RIP-o-tunt) stem cells, meaning they can divide into more stem cells or they can specialize and become any type of body cell. In this way, embryonic stem cells have the highest potential for use to regenerate or repair diseased tissue and organs in people.
* Adult stem cells. These stem cells are found in small numbers in most adult tissues, such as bone marrow. Adult stem cells are also found in children and in placentas and umbilical cords. Because of that, a more precise term for these cells is somatic stem cell, meaning “of the body.” Until recently, it was felt that adult stem cells could only create similar types of cells. For instance, it was thought that stem cells residing in the bone marrow could give rise only to blood cells. However, a controversial new theory suggests that adult stem cells may be more versatile than previously thought and able to create unrelated types of cells after all. For instance, bone marrow stem cells may be able to create muscle cells. This research is in the very early stages.
* Adult cells altered to have properties of embryonic stem cells. In late 2007 two groups of researchers reported they had created stem cells from skin cells in laboratory studies. By altering the genes in the skin cells, researchers were able to reprogram the cells to act similarly to embryonic stem cells. While this new technique may help researchers avoid the controversies that come with embryonic stem cells, more research is needed. The technique of altering adult cells involves processes that may not be safe for use in people. And whether this new type of stem cells can be as useful as embryonic stem cells remains to be seen.
* Embryonic germ cells. These are stem cells that come from areas within an embryo or fetus that are destined to become either the testicles or ovaries. Like embryonic stem cells, embryonic germ cells can become any type of cell. Less research has been done on embryonic germ cells because the embryos used to obtain them must be aborted. In addition, these cells tend to differentiate spontaneously, so they may be more difficult to use in a controlled manner.
* Amniotic fluid stem cells. Researchers have also discovered stem cells in amniotic fluid. Amniotic fluid fills the sac that surrounds and protects a developing fetus in the uterus. Researchers identified stem cells in samples of amniotic fluid drawn from pregnant women during a procedure called amniocentesis. During this test, a doctor inserts a long, thin needle into a pregnant woman’s abdomen to collect amniotic fluid. The fluid can be tested for abnormalities, such as Down syndrome, and is generally considered safe for the developing fetus and the mother. Researchers were able to use amniocentesis fluid to identify stem cells that could develop into several other types of cells. More study of amniotic fluid stem cells is needed to understand their potential.

Embryonic stem cells are obtained from early-stage embryos — a group of cells that forms when a woman’s egg is fertilized with a man’s sperm. Extracting stem cells from the embryos destroys the embryos. Some people view this as taking a human life, which raises moral and ethical considerations.

The embryos being used in embryonic stem cell research come from eggs that were fertilized at in vitro fertilization clinics but never implanted in a woman’s uterus because they were no longer wanted or needed. The excess embryos were frozen and later voluntarily donated for research purposes. The stem cells can live and grow in special solutions in test tubes or petri dishes in laboratories.

Researchers believe that adult stem cells may not be as versatile and durable as embryonic stem cells are. Adult stem cells may not be able to be manipulated to produce all cell types, which limits how they can be used to treat diseases, and they don’t seem to have the same ability to multiply that embryonic stem cells do. They’re also more likely to contain abnormalities due to environmental hazards, such as toxins, or from errors acquired by the cells during replication.

What is a stem cell line and why do researchers want to use them?

A stem cell line is a group of cells that all descend from a single original stem cell. Cells in a stem cell line keep dividing but don’t differentiate into specialized cells. Ideally, they remain free of genetic defects and continue to create more stem cells. Clusters of cells can be taken from a stem cell line and frozen for storage or shared with other researchers. This way, researchers don’t have to get stem cells from an embryo itself.

Why do researchers want to create more embryonic stem cell lines?

Researchers who receive federal funding to support their experiments — as most academic researchers do — are limited by law to working with about 20 stem cell lines. Those who want to experiment using other stem cell lines must find private funding for separate laboratory space and private funding must also be used to buy separate equipment for research.

The 20 or so stem cell lines approved for research date back to the late 1990s, and some researchers contend that they pose several problems:

* The limited number of stem cell lines limits the genetic diversity available, so cells may be useful only for certain diseases or people.
* The lines are old, so cells don’t grow as well as new ones.
* The lines may have been contaminated by nonhuman cells in the growth cultures, compromising their safety.
* The DNA in some of the cells may subtly change over time, causing genetic flaws that could be passed along to daughter cells or to humans.

How can additional stem cell lines be made available more quickly to U.S. researchers?

It will take a presidential order or an act of Congress signed by the president to make federal funding available for research on other stem cell lines. This would speed the development of embryonic stem cell research in the United States.

Some researchers have turned to private funding to finance their embryonic stem cell studies and have created their own stem cell lines. Also, individual states can pass their own laws allowing funding of embryonic stem cell research with state money.

What is stem cell therapy and how does it work?

Stem cell therapy is the replacement of diseased, dysfunctional or injured cells with either adult or embryonic stem cells. It’s somewhat similar to the organ transplant process but uses cells instead of organs. Stem cell therapy is sometimes called regenerative medicine.

Researchers grow stem cells in the lab. These stem cells are manipulated to make them specialize into specific types of cells, such as heart muscle cells, blood cells or nerve cells. This manipulation may involve changing the material in which the stem cells are grown or even injecting genes into the cells. The specialized cells are then implanted into a person. If the person has heart disease, the cells would be injected into the heart muscle. The normally functioning implanted heart cells, in theory, could replace the defective heart cells.

Have stem cells already been used to treat diseases?

Yes, stem cell transplants, also known as bone marrow transplants, have been performed in the United States since the late 1960s. These transplants have proved highly successful in treating a number of cancerous diseases, such as leukemia, and noncancerous diseases, such as aplastic anemia.

Stem cell transplants use cells harvested from a donor’s or person’s own bone marrow, circulating blood or umbilical cord blood. These are all adult stem cells. In addition, adult stem cells have been used in human experiments testing the potential treatment of diabetes, heart disease and other conditions.

Embryonic stem cell treatment is just beginning to be tested in people. Clinical trials using stem cells to treat neurological diseases are the first to begin recruiting participants.

To be useful in people, researchers must be certain that embryonic stem cells will differentiate into the specific cell types desired. Researchers, for instance, don’t want to transplant a stem cell into a person hoping it’ll become a heart cell only to learn that it’s become a bone cell, with potentially dangerous consequences. Researchers have found ways to direct stem cells to become specific types of cells, and research into this area continues.

Embryonic stem cells could also become tumor cells — something that’s happened in animal experiments — or travel to a part of the body where they’re not intended to go. They also might trigger an immune response in which the recipient’s body attacks the stem cells as foreign invaders, or simply fail to function normally, with unknown consequences. Researchers have found ways to avoid these complications and continue studying ways to control stem cells.

What is therapeutic cloning and what benefits might it offer?

Therapeutic cloning is a technique to create embryonic stem cells without using fertilized eggs. In this technique, the nucleus is removed from a woman’s unfertilized egg. The nucleus is also removed from a somatic cell of a donor — a person with a disease or injury, such as type 1 diabetes. This donor nucleus is then injected into the egg, replacing the nucleus that was removed, a process called nuclear transfer. The egg is allowed to divide and soon forms a blastocyst. This creates a line of embryonic stem cells that is genetically identical to the donor’s — in essence, a clone. This technique is also called somatic cell nuclear transfer.

Some researchers believe that embryonic stem cells derived from therapeutic cloning may offer benefits over those from fertilized eggs because they’re less likely to be rejected once transplanted back into the donor, and they may allow researchers to see exactly how a disease develops.

In addition, some researchers consider therapeutic cloning a good alternative to creating embryonic stem cell lines from fertility treatments, since they come from cells that were never fertilized. However, this technique is not without opponents. Critics contend therapeutic cloning can also be perceived as destruction of a human life or potential human life.

Has therapeutic cloning in people been successful?

Researchers haven’t been able to successfully perform therapeutic cloning of humans. In 2005, South Korean researchers reported creation of human embryonic stem cells this way, but their claims were ultimately not substantiated.

What does the future hold for stem cell therapy?

Researchers say the field has great promise. Stem cell transplants using adult stem cells continue to be refined and improved. And researchers are discovering that adult stem cells may be somewhat more versatile than originally thought, which means they may be able to treat a wider variety of diseases. Studies using embryonic stem cells to regenerate tissue and organs in people are just getting started. Researchers are enthusiastic about the potential for these treatments.

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Caption: Red blood cell colony derived from human embryonic stem cells by scientists at the University of Wisconsin-Madison. These are the first specialized human cells coaxed down a specific developmental pathway to be reported in the scientific literature. The ability to make human blood in the lab may one day augment human blood supplies for purposes of transfusion and transplantation.
Date: 2001
Photo credit: UW-Madison University Communications 608/262-0067
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Caption: Derived from human embryonic stem cells, precursor neural cells grow in a lab dish and generate mature neurons (red) and glial cells (green), in the lab of University of Wisconsin-Madison stem cell researcher and neurodevelopmental biologist Su-Chun Zhang.
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Montage. DNA is a protein-building code library.
A protein is like a word built of letters (amino acids) which are spelled out along the length of the DNA “page.”

May 26, 2008 – Geneticists of Leiden University Medical Centre (LUMC) are the first to determine the DNA sequence of a woman. She is also the first European whose DNA sequence has been determined. This has been announced by the researchers this morning, during a special press conference at ‘Bessensap’, a yearly meeting of scientists and the press in the Netherlands.

Following in-depth analysis, the sequence will be made public, except incidental privacy-sensitive findings. The results will contribute to insights into human genetic diversity.

DNA of geneticist Marjolein Kriek

The DNA is that of dr Marjolein Kriek, a clinical geneticist at LUMC. “If anyone could properly consider the ramifications of knowing his or her sequence, it is a clinical geneticist,” says professor Gert-Jan B van Ommen, leader of the LUMC team and director of the ‘Center for Medical Systems Biology’ (CMSB), a center of the Netherlands Genomics Initiative.

Van Ommen continues: “Moreover, while women don’t have a Y-chromosome, they have two X-chromosomes. As the X-chromosome is present as a single copy in half the population, the males, it has undergone a harsher selection in human evolution. This has made it less variable. We considered that sequencing only males, for ‘completeness’, slows insight into X-chromosome varialibity. So it was time, after sequencing four males, to balance the genders a bit”. He smiles: “And after Watson we also felt that it was okay to do Kriek”.

Eight times coverage

The DNA sequencing was done with the Illumina 1G equipment. This has been installed in January 2007 in the Leiden Genome Technology Center, the genomics facility of LUMC and CMSB. In total, approx. 22 billion base pairs (the ‘letters’ of the DNA language) were read. That is almost eight times the size of the human genome.’

Dr. Johan den Dunnen, project leader at the Leiden Genome Technology Center: ‘This high coverage is needed to prevent mistakes, connect the separate reads and reduces the chance of occasional uncovered gaps.

Johan den Dunnen: ‘The sequencing itself took about six months. Partly since it was run as a ‘side operation’ filling the empty positions on the machine while running other projects. Would such a job be done in one go, it would take just ten weeks”.

The cost of the project was approximately €40.000.- This does not include further in-depth bioinformatics analysis. This is estimated to take another six months.

History

In 2001, the DNA sequence was published of a combination of persons. The DNA sequences of Jim Watson, discoverer of the DNA’s double helix structure, followed in 2007, and later the DNA of gene hunter Craig Venter. Recently the completion of the sequences of two Yoruba-Africans was announced.

Source: Leiden University

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A remarkably short scientific paper, known officially as a letter, was published on 25 April 1953 in Nature, by James Watson and Francis Crick.

It was perhaps the most momentous paper of the modern era, proposing a structure for the chemical, DNA (Deoxyribose Nucleic Acid), which composes the hereditary material of all living cellular organisms.

The proposed structure – a double helix – rapidly became an icon, aesthetically beautiful, and stunning in its capacity to explain how DNA is replicated in order to transmit the genetic material to the next generation.

The insight that the discovery provided, into how human characteristics arise from our individual genes, created a veritable super-highway of research, ushering in gene therapy for inherited diseases and culminating in the sequencing of the human genome.

The discovery of DNA paved the way for a whole new arena of human endeavour, the biotechnology industry. Now, DNA technology affects everyday lives. Medical and scientific experiments, based on the discovery of DNA, are having a colossal impact on the future.

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