DARK MATTER


“Researchers capture first ‘image’ of a dark matter web that connects galaxies. Dark matter filaments bridge the space between galaxies in this false colour map. The locations of bright galaxies are shown by the white regions and the presence of a dark matter filament bridging the galaxies is shown in red.”

ELECTRICALLY CHARGED DUST STORMS
https://www.scientificamerican.com/article/electric-sand-how-titans-dunes-got-their-weird-shapes/
https://www.nytimes.com/2017/03/10/science/space-dust-on-earth.html
Flecks of Extraterrestrial Dust, All Over the Roof
by William J. Broad  /  March 10, 2017

“His book, “In Search of Stardust: Amazing Micro-Meteorites and Their Terrestrial Imposters,” due out in August, details the secret of his extraordinarily successful hunts. Its 150 pages and 1,500 photomicrographs, or photos taken through a microscope, tell how Mr. Larsen taught himself to distinguish cosmic dust from the minuscule contaminants that arise from roads, shingles, factories, roof tiles, construction sites, home insulation and holiday fireworks. As his book puts it, “To pick out one extraterrestrial particle among billions of others requires knowledge both about what to look for and what to disregard.”

The diminutive flecks to which Mr. Larsen, 58, has devoted himself represent the smallest parts of a cosmic downpour that has lashed the Earth for billions of years. Careful observers of the night sky are familiar with shooting stars — speeding bits of extraterrestrial rock that plunge through the Earth’s atmosphere, often burning up completely. The biggest can strike the ground, some forcefully enough to dig craters. In 2013, a relatively small rock exploded over the Russian city Chelyabinsk, releasing a shock wave that injured hundreds of people, mainly as windows shattered into flying glass.

But all that represents a tiny fraction of the downpour. Scientists say most of the cosmic material is remarkably small — barely the width of a human hair. Known as micrometeorites, they rain down on the planet more or less continuously but have proved remarkably hard to find. Some bits are so small and lightweight that they drift down to the Earth’s surface without melting. The dust consists of tiny remnants from the solar system’s birth, including debris from comets and from ages of smashups among planets and the big rocks known as asteroids. While most of the particles are interplanetary in nature, some contain grains of matter from outside the solar system, or true stardust. Their diversity makes them excellent windows on the cosmos.


These examples of space dust found on Earth are collected in a new book, “In Search of Stardust: Amazing Micro-Meteorites and Their Terrestrial Imposters,” and were found on buildings, parking lots, sidewalks and park benches.”

Scientists have found micrometeorites mainly in the Antarctic, remote deserts and other places far from civilization’s haze. Starting in the 1940s and 1950s, investigators tried to find them in urban areas but eventually gave up because of the riot of human contaminants. Significantly, it turns out that specialists trying to establish the cosmic origins of the tiny specks have tended to examine their chemical signatures rather than their overall appearance. That left a large opening for Mr. Larsen. Matthew J. Genge, one of the Geology paper’s four authors and a senior lecturer in earth and planetary science at Imperial College, London, used an electron microprobe at the Natural History Museum in London to determine the chemical makeup of Mr. Larsen’s finds and confirm their cosmic origin.

In an interview, he said that, over all, the grains that survive the atmospheric plunge and land on the Earth’s surface add up to more than 4,000 tons annually, or more than 10 tons a day. “He’s done a valuable thing in classifying the contaminants,” Dr. Genge said of Mr. Larsen’s work. “It has wide-reaching implications.” Donald E. Brownlee, an astronomer at the University of Washington who helped establish the field, called Mr. Larsen a true citizen scientist whose work will aid the global hunt for the tiny specks. “Your car is covered with cosmic dust,” Dr. Brownlee said. “We inhale this stuff. We eat it every time we eat lettuce. But normally, it’s incredibly difficult to find.”


“Jon Larsen looking for micrometeorites on a roof. He was an enthusiastic rock collector as a child in Norway but became a professional musician. His quest for space dust began in 2009.”

Mr. Larsen came to what he calls Project Stardust as a jazz guitarist in Norway, perhaps known best as the founder of Hot Club de Norvège, a string quartet. His group helped spur the global revival of gypsy jazz. As Mr. Larsen tells the story, he was an enthusiastic rock collector as a child but did so well as a musician that he set aside his early scientific ambitions. Then, in 2009, at a country house outside Oslo, he was cleaning an outdoor table when a bright speck caught his eye. “It was blinking in the sunlight,” he recalled. He touched the fleck. “It was angular in some way, kind of metallic but so small — a tiny dot.”

Intrigued, Mr. Larsen suspected it was a cosmic visitor and began to look for more. He collected dust samples from Oslo and cities around the globe, moonlighting as a scientist while vacationing or touring with his jazz group. He took samples from roads, roofs, parking lots and industrial areas Put indelicately, he collected hundreds of pounds of dreck — sludge from drains, gutters and downspouts, the dregs of civilization that most people try to avoid. “Still, I didn’t find a single micrometeorite,” he recalled. “It was very frustrating.” Mr. Larsen then changed tactics. Rather than looking exclusively for cosmic dust, he taught himself how to classify the dozens of different kinds of earthly contaminants, starting a process of elimination that slowly narrowed the candidates and raised the chances that some tiny fraction of the urban debris might turn out to belong to the cosmos. The breakthrough came two years ago. In London, Dr. Genge studied one of the gathered particles — from Norway, not Timbuktu — and confirmed that it was indeed a traveler from outer space. Mr. Larsen quickly identified hundreds more. “Once I knew what to look for, I found them everywhere,” he said.

In the Geology paper, the scientific team reports the discovery of about 500 micrometeorites — collected mainly from roof gutters in Norway — and tells of the detailed analysis of 48 of the extraterrestrial specks. The team includes two of Dr. Genge’s students, Martin D. Suttle of Imperial College and Matthias Van Ginneken of the Université Libre in Brussels. The team described the cosmic dust as the youngest collected to date, because gutters tend to get cleaned fairly regularly. Also, urban surfaces are recent arrivals in the global landscape compared to polar ice and ancient deserts.


“Varieties of space dust, barely the width of a human hair. These photomicrographs were made with a special camera setup that magnifies the dust grains nearly 3,000 times”

In his travels, Mr. Larsen recently visited with Michael E. Zolensky, an extraterrestrial materials scientist in Houston at the Johnson Space Center of the National Aeronautics and Space Administration. They not only talked shop but also went up to the roof of the large building that houses rocks from the Apollo moon program. “It was pretty cool,” Dr. Zolensky said. “The curation building is now a collector of cosmic dust.”

In an interview, Mr. Larsen described his method — sorting through the contaminants in a process of elimination — as “something that anybody can do. It could and should become part of teachings in schools, an aspect of citizen science.” Dr. Brownlee of the University of Washington agreed. He said that, while many schools try to find cosmic dust particles in programs meant to make science classes more inviting and accessible, few if any succeed. “It could help a lot,” he said of Mr. Larsen’s method. “For education, it’s pretty cool.” Dr. Genge of Imperial College said Mr. Larsen’s techniques, if adopted widely, might also open a new lens on the cosmos.

The gravitational pull of the planets, he noted, appear to tug on the dust clouds of the solar system and slowly change their orbits. He said a wave of new terrestrial finds could help scientists better map the clouds, raising more questions for science about the structure of the universe. “I consider my microscope a telescope,” Dr. Genge said. “It can give you a pretty big picture.”

Yale-led team puts dark matter on the map
“A 3-D visualization of reconstructed dark matter clump distributions in a distant galaxy cluster, obtained from the Hubble Space Telescope Frontier Fields data. The unseen matter in this map is comprised of a smooth heap of dark matter on which clumps form.”

GRAVITATIONAL LENSING
https://blogs.scientificamerican.com/cross-check/astrophysicist-says-experiments-might-soon-reveal-dark-matters-true-nature/
https://phys.org/news/2017-03-team-dark.html
Team puts dark matter on the map  /  March 1, 2017

“A Yale-led team has produced one of the highest-resolution maps of dark matter ever created, offering a detailed case for the existence of cold dark matter—sluggish particles that comprise the bulk of matter in the universe. The dark matter map is derived from Hubble Space Telescope Frontier Fields data of a trio of galaxy clusters that act as cosmic magnifying glasses to peer into older, more distant parts of the universe, a phenomenon known as gravitational lensing.

Yale astrophysicist Priyamvada Natarajan led an international team of researchers that analyzed the Hubble images. “With the data of these three lensing clusters we have successfully mapped the granularity of dark matter within the clusters in exquisite detail,” Natarajan said. “We have mapped all of the clumps of dark matter that the data permit us to detect, and have produced the most detailed topological map of the dark matter landscape to date.” Scientists believe dark matter—theorized, unseen particles that neither reflect nor absorb light, but are able to exert gravity—may comprise 80% of the matter in the universe. Dark matter may explain the very nature of how galaxies form and how the universe is structured. Experiments at Yale and elsewhere are attempting to identify the dark matter particle; the leading candidates include axions and neutralinos.

“While we now have a precise cosmic inventory for the amount of dark matter and how it is distributed in the universe, the particle itself remains elusive,” Natarajan said. Dark matter particles are thought to provide the unseen mass that is responsible for gravitational lensing, by bending light from distant galaxies. This light bending produces systematic distortions in the shapes of galaxies viewed through the lens. Natarajan’s group decoded the distortions to create the new dark matter map.

Significantly, the map closely matches computer simulations of dark matter theoretically predicted by the cold dark matter model; cold dark matter moves slowly compared to the speed of light, while hot dark matter moves faster. This agreement with the standard model is notable given that all of the evidence for dark matter thus far is indirect.”

ELECTRIC SAND DUNES
http://www.news.gatech.edu/2017/03/27/electric-sands-titan
http://gizmodo.com/saturns-weirdest-moon-is-full-of-electric-sand-1793728449
Saturn’s Weirdest Moon Is Full of Electric Sand
by Rae Paoletta   /  3/29/17

“A new study from Georgia Tech, published on March 27th in Nature Geoscience, sought to shed light on the massive and mysterious sand dunes engulfing Titan. Through laboratory experiments, the researchers found that under Titan-like atmospheric conditions, sand grains collide and become electrically charged, clumping together and remaining clumped for an incredibly long time. While wind-blown sand on Earth can also become electrically charged, the electrostatic forces are typically ephemeral and much weaker. The team compared the adhesive quality of the sand on Titan to packing peanuts and cats. “If you grabbed piles of grains and built a sand castle on Titan, it would perhaps stay together for weeks due to their electrostatic properties,” Josef Dufek, the Georgia Tech professor who co-led the study, said in a statement. “Any spacecraft that lands in regions of granular material on Titan is going to have a tough time staying clean. Think of putting a cat in a box of packing peanuts.”

To reach this conclusion, the team created a modified pressure vessel and inserted naphthalene and biphenyl grains—hydrocarbon compounds similar in composition to what the sand is probably like on Titan. On Earth, naphthalene and biphenyl are considered toxic and are used moth balls and citrus fruit wrappings, respectively.  The team then added Titan-like “wind” by rotating the tube for 20 minutes in pure nitrogen environment, since that’s what the moon’s atmosphere is almost entirely composed of. Overwhelmingly, the sand stuck together, which doesn’t happen on Earth unless you add water to the mix. Speaking of Earth, our sand is mostly silica-based, and didn’t have the same sticky quality when the researchers used it to repeat their experiments.


“Radar imaging from NASA’s Cassini spacecraft shows dunes stretching across the Shangri-La Sand Sea of Saturn’s largest moon, Titan. Research suggests the dunes’ shape and orientation are influenced by powerful electrostatic charges.”

“These non-silicate, granular materials can hold their electrostatic charges for days, weeks, or months at a time under low-gravity conditions,” study co-author George McDonald, said in a statement. The new study offers the latest indication that although Titan looks astonishingly similar to Earth—it’s the only other world in the solar system with surface oceans, for one—many of the processes shaping its surface are truly alien. “Titan’s extreme physical environment requires scientists to think differently about what we’ve learned of Earth’s granular dynamics,” Dufek said. “Landforms are influenced by forces that aren’t intuitive to us because those forces aren’t so important on Earth. Titan is a strange, electrostatically sticky world.”

SEE ALSO


(@38m)

GENETICALLY ENHANCED ASTRONAUTS

RADIATION-PROOF PROTOTROPHIC HUMAN CELLS
http://www.spacegenes.com/
http://www.popsci.com/9-body-hacks-superhuman-powers
http://lifeonmars.pub/articles/mars-thermonuclear-explosion/
https://www.gizmodo.com.au/2017/04/darpa-wants-to-hack-your-brain-to-make-you-learn-faster/
http://mentalfloss.com/article/84570/scientists-say-greenland-sharks-may-live-400-years
http://blogs.discovermagazine.com/d-brief/2017/04/20/naked-mole-rats-oxygen/
https://www.theatlantic.com/science/archive/2017/04/octopuses-do-something-really-strange-to-their-genes/522024/
https://www.wsj.com/articles/elon-musk-lays-out-plans-to-meld-brains-and-computers-1492738741
https://www.technologyreview.com/s/604142/engineering-the-perfect-astronaut/
Engineering the Perfect Astronaut
by Antonio Regalado / April 15, 2017

“At the International Astronautical Congress last September, in Guadalajara, Mexico, Elon Musk convinced many die-hard space engineers he could get a fleet of private rockets filled with thousands of people to Mars. Musk’s speech was long on orbits, flight plans, and fuel costs. But it was short on how any of those colonists would survive. Bathed in radiation and with nothing growing on it, the Red Planet is basically a graveyard.

Recently, a few scientists have started to explore whether we might be able to do a little better if we created new types of humans more fit for the travails of space travel. Some far-out ideas once relegated to science fiction and TED Talks (here and here) have recently started to take concrete form. Experiments have begun to alter human cells in the lab. Can they be made radiation-proof? Can they be rejiggered to produce their own vitamins and amino acids?

One person looking at the idea is Christopher Mason, a member of the Department of Physiology and Biophysics at Weill Cornell Medicine. In 2011, Mason came up with what he called a “500-year plan” to get humans off Earth. In it, genetic modification plays a big role. “I think we have to consider it for people that we send to other planets,” he says. “We don’t know if it’s a slight nudge to existing gene expression, or a whole new chromosome, or finally a complete rewriting of the genetic code.” Mason says there’s a decade or two of work left just to find out what effect space travel has on your genes, and which ones might be okay to change and which should be on a “do not disturb” list. His lab participates in NASA’s Twins Study, which is tracking physiological changes to an astronaut who was sent to the International Space Station for a year while his twin brother stayed on Earth. So far, that’s about as close as NASA has gotten to the subject of GM astronauts—one that still hasn’t been broached in any official agency document.

Yet Mason says his lab is ready to take an initial step. Space is full of rays and fast-moving particles that damage DNA. So he’s working on radiation-proofing human cells. His students are taking cells and adding extra copies of p53, a gene involved in preventing cancer that’s known as the “protector of the genome.” Elephants have many extra copies of p53 and hardly ever get cancer, so maybe astronauts should have them too. Mason says he recently submitted a proposal to NASA to send the modified cells to the space station. “There is not a genetic engineering astronaut’s consortium or anything, but maybe we should start one,” he says.

All this has become easier to think about because it has become easier to do. In 2015 we published an article, “Engineering the Perfect Baby,” about the fact that gene editing, especially with a technology called CRISPR, had suddenly made it possible to easily change the genes in a human embryo. For the first time, we faced the real possibility of genetically modified people. Since then, scientists in China and Europe have begun editing embryos to see how it works. Would it be ethical to then actually make a gene-fixed baby? The U.S. National Academy of Sciences this year said yes, heritable genetic changes could be considered to avoid disease, but only in a few situations and under very strict supervision. The organization opined that under certain rare circumstances in which a couple could not otherwise have a healthy child, it would be acceptable to create a GM human being.

Mason thinks that space travel will offer a second, very powerful argument in favor of genetically modifying people. “You can’t send someone to another planet without genetically protecting them if you are able to,” he says. “That would also be unethical.” But putting astronauts in the mix might also open the door to “enhancement.” For now, the experts remain dead set against using gene editing to make a child who is smarter or endowed with perfect eyesight. But let’s face it: NASA already “selects” people according to just such criteria, accepting only 14 of 18,300 applicants to its latest class of astronauts. Maybe you have seen the movie Gattaca? Only supermen with topped-off genomes are allowed to travel to Titan, while the genetic losers, called “invalids,” stare up in envy as the rockets lift off. Like most good science fiction, the 1997 film is not so far from reality.

To think about surviving in space, a term from the science of genetics—“fitness”—will come in handy. In genetics, the fitness of an organism is how well it can thrive and reproduce in a given environment. The fitness of a human in space or on Mars is extremely low. Just picture an astronaut encased in a space suit with the right amount of oxygen, the right amount of nitrogen, and the right temperature. The purpose of that suit is to bring along the environment for which the astronaut’s genes make him or her fit.

Some scientists have already prepared a catalogue of genes that might help. A Boston company called Veritas Genetics is offering to sequence anyone’s genome for $999. And one of the things that Veritas will give you is a report on your “space genes.” Do you have the specific variant of EPAS1, common to Tibetans, that lets you get by with less oxygen? How about the natural mutation that results in huge, extra-lean muscles, which might counter atrophy? Another DNA variant is associated with good problem-solving skills and low anxiety.

You’d be unusual if you had any one of these mutations. And the chances are billions to one that you have all of them. That’s why to get them all into one astronaut—the perfect astronaut—we might want to add them, probably before birth, and maybe using a technology like CRISPR. George Church, the big-bearded Harvard University genetics powerhouse and all-in futurist who founded Veritas, circulates a similar list of “rare protective gene variants relevant to an extraterrestrial environment.” Call it a wish list.

What other kind of adaptations could we install into our race of astronauts? If you leave some large elephants on an island and come back 10,000 years later, what you’ll find is a bunch of small elephants. They’ll have adapted to the lack of surface area and shortage of food. The phenomenon is called “island dwarfism.” Under the Mars domes, smaller might be better too. There’s probably not that much space, and every pound of provisions NASA takes into Earth orbit costs $10,000. That means the perfect astronaut probably isn’t just twice as strong as the average person but half as big. (Church, who is 6’5″, notes that he was once told by NASA not to bother applying because he was too tall.)

Let’s take the modifications even further, as some scientists say we might need to. If you ate breakfast cereal this morning, you might have looked at the side of the box, where it says things like “Vitamin C—10% Daily Value.” The “essential” nutrients and vitamins listed on the box are so called because the human body can’t make them. Instead, we have to eat organisms that do, like plants, fungi, or bacteria. These organisms are classified as “prototrophs,” meaning they synthesize everything they need from minimal starting ingredients like simple sugars or what’s in the soil.

In 2016, Harris Wang of Columbia University gave a talk titled “Synthesizing a Prototrophic Human” at a large off-the-record meeting of synthetic biologists organized by Church at Harvard Medical School. It could be pretty interesting for space travel, Wang told the group, if humans could subsist on sugar water.

Despite the title of his talk, when I reached Wang by phone he wanted everyone to know he’s not actually synthesizing humans or astronauts and doesn’t have plans to. That’s still many, many years away, if ever. “I am suggesting that if you want to do intergalactic travel, you need to solve the problem of being totally self-sufficient,” he says. “We are putting humans in very extreme conditions, and from that perspective this seems to be one idea for a long-term plan.”

Wang says it’s not certain if the concept can even work. In his lab, researchers are trying to get human kidney cells to synthesize the nine amino acids our bodies don’t normally make, starting with the simplest one, methionine, manufactured by adding a single gene. If that works, he’ll move on to tryptophan, phenylalanine, and vitamins D, C, and B. Altogether, creating a prototrophic human cell would require around 250 new genes.

Creating astronauts able to make their own essential nutrients would obviously be immensely complicated. Yet as complex as it is, it might be less challenging than the alternatives, such as terraforming a planet or bringing along a space ring complete with an atmosphere, plants, and livestock grazing overhead. Wang told me it would also be interesting if space travelers could perform their own photosynthesis, turning light into food. But any human able to do so would hardly be human, he admits.”

PREVIOUSLY on #SPECTRE

RECREATIONAL GENETICS
http://spectrevision.net/2015/05/08/recreational-genetics/
PART PIG?
http://spectrevision.net/2013/12/06/part-pig/
SIGHTS UNSEEN
http://spectrevision.net/2014/03/21/sights-unseen/
BIRDS CAN “SEE” EARTH’S MAGNETIC FIELD
http://spectrevision.net/2007/10/06/birds-can-see-earths-magnetic-field/
EXOLINGUISTICS
http://spectrevision.net/2016/04/08/exolinguistics/

REPROGRAMMED STEM CELLS


“In a medical first, a donor’s iPS cells were transformed into retinal cells and transplanted into a patient”

INDUCED PLURIPOTENT STEM (iPS) CELL BANKS
http://www.nature.com/news/how-ips-cells-changed-the-world-1.20079
http://www.nature.com/news/stem-cells-cruise-to-clinic-1.12511
http://www.nature.com/news/stem-cells-reprogrammed-using-chemicals-alone-1.13416
http://www.nature.com/news/japanese-man-is-first-to-receive-reprogrammed-stem-cells-from-another-person-1.21730
Japanese man is first to receive ‘reprogrammed’ stem cells from another person
by David Cyranoski /  28 March 2017

“On March 28, a Japanese man in his 60s became the first person to receive cells derived from induced pluripotent stem (iPS) cells that had been donated by another person. The surgery is expected to set the path for more applications of iPS cell technology, which offers the versatility of embryonic stem cells without the latter’s ethical taint. Banks of iPS cells from diverse donors could make stem cell transplants more convenient to perform, while slashing costs.

iPS cells are created by removing mature cells from an individual (from their skin, for example), reprogramming these cells back to an embryonic state, and then coaxing them to become a cell type useful for treating a disease. In the recent procedure, performed on a man from Hyogo prefecture, skin cells from an anonymous donor were reprogrammed and then turned into a type of retinal cell that was transplanted onto the retina of the patient who suffers from age-related macular degeneration. Doctors hope the cells will stop progression of the disease, which can lead to blindness.

In a procedure performed in September 2014 at the Kobe City Medical Center General Hospital, a Japanese woman received retinal cells derived from iPS cells. They were taken from her own skin, though, and then reprogrammed. Such cells prepared for a second patient were found to contain genetic abnormalities and never implanted. The team decided to redesign the study based on new regulations, and no other participants were recruited to the clinical study. In February 2017, the team reported that the one patient had fared well. The introduced cells remained intact and vision had not declined as would usually be expected with macular degeneration. In today’s procedure — performed at the same hospital and by the same surgeon Yasuo Kurimoto — doctors used iPS cells that had been taken from a donor’s skin cells, reprogrammed and banked. Japan’s health ministry approved the study, which plans to enroll 5 patients, on 1 February.

Using a donor’s iPS cells does not offer an exact genetic match, raising the prospect of immune rejection. But Shinya Yamanaka, the Nobel Prize-winning stem-cell scientist who pioneered iPS cells, has contended that banked cells should be a close enough match for most applications. Yamanaka is establishing an iPS cell bank, which depends on matching donors to recipients via three genes that code for human leukocyte antigens (HLAs) — proteins on the cell surface that are involved in triggering immune reactions. His iPS Cell Stock for Regenerative Medicine currently has cell lines from just one donor. But by March 2018, they hope to create 5-10 HLA-characterized iPS cell lines, which should match 30%-50% of Japan’s population.

Use of these ready-made cells has advantages for offering stem cell transplants across an entire population, says Masayo Takahashi, an ophthalmologist at the RIKEN Center for Developmental Biology who devised the iPS cell protocol deployed in today’s transplant. The cells are available immediately — versus several months’ wait for a patient’s own cells — and are much cheaper. Cells from patients, who tend to be elderly, might have also accumulated genetic defects that could increase the risk of the procedure.

At a press conference after the procedure, Takahashi said the surgery had gone well but that success could not be declared without monitoring the fate of the introduced cells. She plans to make no further announcements about patient progress until all five procedures are finished. “We are at the beginning,” she says.”


“A microscopic view of brain cells generated from induced pluripotent stem cells”

STEM CELL SUPER DONORS
https://www.newscientist.com/article/mg19225723-400-organs-on-demand-no-embryo-needed/
https://www.newscientist.com/article/dn22348-cloning-and-stem-cell-nobel-for-gurdon-and-yamanaka/
https://www.newscientist.com/article/mg23331113-900-clinic-claims-it-has-used-stem-cells-to-treat-downs-syndrome/
http://blogs.discovermagazine.com/crux/2016/10/24/wanted-stem-cell-super-donors/
Wanted: Stem Cell Super Donors
By Kim Smuga-Otto | October 24, 2016

“Our bodies’ cells didn’t evolve to flourish in a petri dish. Even fast-growing skin cells stop dividing and turn thin and ragged after a few weeks outside the body. This natural obstacle limited the therapeutic potential of lab-grown cells – if you can’t grow the cells, you can’t use them to heal damaged tissue. Then, a decade ago, Nobel Prize winner Shinya Yamanaka identified a cocktail of genes that, when added to mouse skin cells, transformed them into a new kind of cell that grew happily in ever expanding colonies. More importantly, these cells, dubbed “induced pluripotent stem cells” (iPSC), had their internal clocks set back to an earlier stem cell-like state, giving them the ability to grow into any other cell type found in the body.

When Yamanaka, along with other teams of scientists, repeated this feat with human cells, the press seized on the clinical implications of using a person’s own cells to regenerate damaged tissues or even entire organs. But even as scientists devise new ways to grow heart muscle or neurons from iPSCs and other stem cells, financial constraints could put a personal stock of iPSCs out of reach for all but the wealthiest patients.

Luckily for the rest of us, there are people whose DNA enables their cells to coexist within the immune systems of people not closely related to them, making them, if not universal donors, at least super donors. These donors’ skin cells would be used to create off-the-shelf iPSC banks for use in future clinical trials and, potentially, stem cell therapy, said Yamanaka in a presentation at a recent stem cell symposium in Berkeley, California. Yamanaka discussed the success and setbacks of the first, and to date only, iPSC clinical trial that he and a team of scientists conducted in 2014. Retinal cells were grown from patients’ own skin cells and transplanted into their eyes with the hope of restoring vision.

The health and purity of the iPSCs and the final retinal cells was a primary concern for Yamanaka. During the lengthy and involved growth and selection process, the cells can acquire mutations that can turn cancerous. So before the surgery, the team sequenced the genomes of the retinal cells they grew, looking for any unexpected changes to their genes. The first patient’s cells had no serious mutations and were successfully transplanted into her eye. Because they were her cells, immune suppression drugs weren’t necessary. While there was no measurable improvement to her vision, it hasn’t deteriorated further.

Genome sequencing of the second patient’s iPSCs, however, revealed mutations in two genes. They weren’t linked to cancers, in fact Yamanaka had never heard of these particular genes before. One mutation was located on the male patient’s single X chromosome, so there wasn’t a healthy backup copy. And to be safe, they decided to halt the trial in 2015. Given the eight months spent preparing the cells, and the hopes of the patient and medical team, Yamanaka said he “still wonders whether my judgment was appropriate.”

On the positive side, Yamanaka’s experiment revealed practical limitations of using a patient’s own cells for therapy. To make iPSCs suitable for lab research, explained Yamanaka, “you just need one hard-working grad student for three months.” To make a clinical-grade cell line, by contrast, it takes a team of 50 people working two years. Every step of the procedure needs to be standardized and documented. For some potential iPSC therapies, like adding neurons after spinal cord injuries, cells may be needed within a few months of the injuries.

Seeing how difficult it is to make iPSCs for clinical uses, it would be ideal to have a bank of generic stem cells stocked and ready to go. Creating such a bank is one of the goals of Japan’s Center for iPS Cell Research and Application (CiRA), a joint private-public venture that aims to have such cells available when the retinal cell clinical trial resumes in late 2017.


“Illustration of how one stem cell “super donor” could benefit numerous people”

The problem with using cells and tissues grown from generic iPSCs is the same one plaguing organ transplant medicine, namely, immune system rejection. Human cells have two sets of markers, one inherited from each parent, that tell immune cells to ignore one’s own cells. The chance of transplant rejection shrinks with a perfect or close match to these markers. Unfortunately, finding a good tissue match can take years, as witnessed by the long waiting periods on organ donation lists.

As a way around this problem, Yamanaka describes an individual who inherits two identical copies of these immune system-coding markers — a super donor of sorts. Similar to the way someone with type A blood can donate to people with either A or AB blood types, a super donor’s iPSC cells could serve a greater segment of the population. Yamanaka points to a particular set of markers that would allow a super donor’s cells to match as much as 13 percent of the Japanese population. In fact, because the Japanese population contains fewer genetic variations, just 140 super donors could cover 90 percent of the population. And once an iPSC donor’s cell line is stored in the cell bank, it can serve a nearly unlimited number of people.

To find these super donors, CiRA is cooperating with the Japanese Red Cross. Not only are they looking for compatible cell markers, they also need to scrutinize the donor’s and their family’s health history. And it’s critical that the donors understand how extensively their cells might be used. CiRA has already developed their first super donor cell line, and hope to be able to cover 50 percent of Japan’s population in the next five years.

A similar endeavor is underway in the United States. The wider genetic diversity of markers within the U.S. population would require a larger team of super donors; it is estimated that 200 donors could cover 95 percent of people in the U.S. A company called Cellular Dynamics International has developed 11 such lines so far, enough to cover 35 percent of the U.S. population. And best of all, once an iPSC line has been certified mutation free, it can be used to generate all sorts of cells and tissues. So in addition to the blindness trial, Japanese scientists are planning to start a spinal cord damage clinical trial in 2017. Once these stem cell tissue banks are in place, the supply will no longer be a barrier to clinical iPSC trials.”

PREVIOUSLY on SPECTREVISION

REGROWING BONES
http://spectrevision.net/2015/07/17/regrowing-bones/
3-D PRINTING CUSTOMIZED KIDNEYS
http://spectrevision.net/2011/03/04/printing-replacement-kidneys/