The science behind RHCs liver thread

I didn't, but about ten years ago the BBC did a series called Space Race, which was fantastic. The Soviets, whilst brilliant engineers, were bedevilled by politics and budgets. I was due to meet Leonov in May, but he pulled out due to ill health. Great pity.

 

It was on BBC4, I think, so you could probably get it on iplayer.
I knew the broad outlines of course, but some of the details were fascinating. The risks they took, because they were desperate to beat the Yanks, were outrageous at times. Incredibly brave.
Leonov tells the story of the first space walk. Nobody anticipated that the internal pressure of his suit would make it inflate in space. As it blew up his hands were slipping back out of the gloves so he couldn't reel himself in. He decided to let some of the air out of his suit! Almost snuffed it through hypoxia, but managed to get back in.
Crazy.

 

I was due to meet Gene Cernan in May of last year, but he pulled out due to ill health, and his skipper on Gemini IX and Apollo X, Tom Stafford, was there instead. Pushing ninety, but he was bloody brilliant - the body is old and frail, but the mind is as sharp as ever.

Anyway, Stafford was telling of Cernan's walk on Gemini that nearly ended in total disaster, and when he co-commanded the Apollo-Soluz mission with Leonov in 1975, he told him the struggles Cernan had. 'Oh yes', replied Leonov, 'We could have told you how difficult it would be, but our propaganda tried to portray it as an easy success for Soviet Russia!'. They remain good friends to this day, and both have grandchildren named after the other astronaut/cosmonaut.

As a postscript, it's one of the things the very underrated-but-brilliant engineer Buzz Aldrin never gets the credit for: he, more than any other astronaut, worked his bollocks and his big ****ing brain off overcoming what could have been a terminal problem for the programme, to result in totally successful EVA's on Gemini XII with his commander Jim Lovell in charge of the mission. The Right ****ing Stuff indeed.

(Now advertising porridge - we all have to make a living!)

 

No. I bloody well missed that. It looked really good as well

 

https://www.bbc.co.uk/iplayer/episode/b04lcxms/cosmonauts-how-russia-won-the-space-race

Well that's Eastenders ****ed for tonight.

 

The unit's out at the lesbians on Saturday so I'll get it watched then

 

Talk about being brought back down to Earth.

 

Very good

 

This star cheated death, exploding again and again
The weirdest supernova ever has lasted more than three years, and may be the third outburst from the same star
BY
LISA GROSSMAN
1:00PM, NOVEMBER 8, 2017

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GHOST IN THE SHELL What looked like an ordinary supernova, shown in this artist’s illustration, might be the result of a single star exploding at least three times, blowing off expanding shells of gas each time.

NASA, ESA, G. BACON/STSCI

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  This exploding star, named iPTF14hls, has erupted continuously for the last three years, and it may have had two other outbursts in the past, astronomers report in the Nov. 9 Nature. Such a tireless supernova could be the first example of a proposed explosion that involves burning antimatter in a stellar core — or it could be something new altogether.

“A supernova is supposed to be a one-time thing — the star explodes, it’s dead, it’s done, it can’t explode again,” says astrophysicist Iair Arcavi of the University of California, Santa Barbara. “It’s the weirdest supernova we’ve ever seen … It’s like the star that keeps on dying.”

When iPTF14hls was discovered in September 2014 by the Intermediate Palomar Transient Factory, which scans the sky regularly with a telescope at the Palomar Observatory near San Diego, it looked like an ordinary type 2 supernova in a galaxy about 500 million light-years away. These explosions mark the death throes of a star between eight and about 50 times the mass of the sun (SN: 2/18/17, p. 24), and typically glow for about 100 days before starting to dim.

The first sign that iPTF14hls was unusual came a few weeks after its discovery, when it started growing brighter. That turned out to be one of five irregular cycles of brightening and dimming.

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Nevertheless, it persisted
The star iPTF14hls continued its eruption for more than 600 days, and fluctuated in brightness at least five times (yellow). Typical supernovas (blue) fade after about 100 days.

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S. WILKINSON/LCO


Even stranger, data collected from September 2014 to June 2016 show that the supernova remained bright for more than 600 days, Arcavi and colleagues report. The eruption, which is just showing signs of winding down now, may have already been in progress when it was discovered, so it could have persisted even longer.

“That’s just unheard of,” says theoretical physicist Stanford Woosley of the University of California, Santa Cruz, who was not involved in the discovery. “Ordinary supernovae don’t do that.”

Normally, layers of gas kicked out of an exploding star slow and cool as they expand. But iPTF14hls maintained a toasty temperature — about 5,700° Celsius — for the entire time it was observed, and its outer gas layers did not slow down as they should have. That means that this gas may have already cooled and slowed, suggesting it had been expelled in an earlier, superpowerful eruption that occurred unseen between 2010 and 2014, the team suggests.

Historical data on photographic plates from the Palomar Observatory showed yet another bright burst in the same part of the sky in 1954. One theory suggests that stars between 95 and 130 times the mass of the sun can explode several times, although these cyclic deaths have never been seen before. Such stars get so hot that they convert gamma rays, whose high energy helped keep the star from collapsing under its own gravity, into electrons and their antimatter counterparts, positrons. Without that internal energy, the star’s core collapses and gets even hotter. That collapse can trigger a partial explosion, in which the star blows off a large amount of mass. But after the explosion, the electrons and positrons can recombine into gamma rays and hold up the remaining stellar core.

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An eerie echo
Historical data from the Palomar Observatory showed a bright burst in 1954 at the same point in the sky as iPTF14hls (left). In 1993, the explosion had faded (right).

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S. WILKINSON/LCO, DSS, POSS


The star can blow off steam several times, the idea goes, before finally dying in a supernova. Eventually, the remains of such a supernova would collapse into a black hole with about 40 times the mass of the sun.

But this theory also predicts that the star would blow off all its hydrogen in the first explosion. That doesn’t fit here: iPTF14hls expelled 50 times the mass of the sun in hydrogen in 2014. The amount of energy in the most recent explosion is also greater than it should be.

Woosley thinks that a magnetar (SN Online: 11/3/10), a highly magnetized rapidly rotating stellar corpse, could glow continuously for around two years, although that wouldn’t explain the 1954 eruption. He hopes the most recent data will help determine which theory is right, or if physicists need to come up with something new.

The show may be ending. The latest data shows that iPTF14hls is finally fading, Arcavi says. As the outer layers of gas cool and become transparent, they could reveal whatever is at the explosion’s core. The team plans to just keep watching.

“I am not making any more predictions about this thing,” Arcavi says. “It surprised us every time.”

 

watched it last night (not eastenders). It's been on before, but it was well worth a second watch. Had to laugh though at the bit towards the end when the commentator said the US had overtaken the Soviets by advancing docking, rendezvous AND EVA's with ease: er, not that last bit they didn't. The Eva's on Gemini IX (Cernan), X (Collins) and XI (the above-mentioned Gordon) were near disasters. As said, it was primarily the work leading up to and during XII by Aldrin on EVA's that saved the programme.

Otherwise great watching. Korolev was every bit the rocket-scientist as Von Braun. His death was a tragedy for human exploration. He was absolutely hated by the KGB and had spent years in in labour camps under Stalin. If you get a chance to watch the series Space Race try it out: not just space geeks like me love it.

 

https://www.livescience.com/50718-weekend-reading.html?utm_source=notification

 

Ditto

 

Simulating the universe using Einstein’s theory of gravity may solve cosmic puzzles
Until recently, simulations of the universe haven’t given its lumps their due
BY
EMILY CONOVER
3:30PM, NOVEMBER 14, 2017

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UNEVEN TERRAIN Universe simulations that consider general relativity (one shown) may shift knowledge of the cosmos.

JAMES MERTENS

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If the universe were a soup, it would be more of a chunky minestrone than a silky-smooth tomato bisque.

Sprinkled with matter that clumps together due to the insatiable pull of gravity, the universe is a network of dense galaxy clusters and filaments — the hearty beans and vegetables of the cosmic stew. Meanwhile, relatively desolate pockets of the cosmos, known as voids, make up a thin, watery broth in between.

Until recently, simulations of the cosmos’s history haven’t given the lumps their due. The physics of those lumps is described by general relativity, Albert Einstein’s theory of gravity. But that theory’s equations are devilishly complicated to solve. To simulate how the universe’s clumps grow and change, scientists have fallen back on approximations, such as the simpler but less accurate theory of gravity devised by Isaac Newton.

Relying on such approximations, some physicists suggest, could be mucking with measurements, resulting in a not-quite-right inventory of the cosmos’s contents. A rogue band of physicists suggests that a proper accounting of the universe’s clumps could explain one of the deepest mysteries in physics: Why is the universe expanding at an increasingly rapid rate?

The accepted explanation for that accelerating expansion is an invisible pressure called dark energy. In the standard theory of the universe, dark energy makes up about 70 percent of the universe’s “stuff” — its matter and energy. Yet scientists still aren’t sure what dark energy is, and finding its source is one of the most vexing problems of cosmology.

Perhaps, the dark energy doubters suggest, the speeding up of the expansion has nothing to do with dark energy. Instead, the universe’s clumpiness may be mimicking the presence of such an ethereal phenomenon.

Most physicists, however, feel that proper accounting for the clumps won’t have such a drastic impact. Robert Wald of the University of Chicago, an expert in general relativity, says that lumpiness is “never going to contribute anything that looks like dark energy.” So far, observations of the universe have been remarkably consistent with predictions based on simulations that rely on approximations.

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Growing a lumpy universe
The universe has gradually grown lumpier throughout its history. During inflation, rapid expansion magnified tiny quantum fluctuations into minute density variations. Over time, additional matter glommed on to dense spots due to the stronger gravitational pull from the extra mass. After 380,000 years, those blips were imprinted as hot and cold spots in the cosmic microwave background, the oldest light in the universe. Lumps continued growing for billions of years, forming stars, planets, galaxies and galaxy clusters.

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C. CARREAU/ESA


As observations become more detailed, though, even slight inaccuracies in simulations could become troublesome. Already, astronomers are charting wide swaths of the sky in great detail, and planning more extensive surveys. To translate telescope images of starry skies into estimates of properties such as the amount of matter in the universe, scientists need accurate simulations of the cosmos’s history. If the detailed physics of clumps is important, then simulations could go slightly astray, sending estimates off-kilter. Some scientists already suggest that the lumpiness is behind a puzzling mismatch of two estimates of how fast the universe is expanding.

Researchers are attempting to clear up the debate by conquering the complexities of general relativity and simulating the cosmos in its full, lumpy glory. “That is really the new frontier,” says cosmologist Sabino Matarrese of the University of Padua in Italy, “something that until a few years ago was considered to be science fiction.” In the past, he says, scientists didn’t have the tools to complete such simulations. Now researchers are sorting out the implications of the first published results of the new simulations. So far, dark energy hasn’t been explained away, but some simulations suggest that certain especially sensitive measurements of how light is bent by matter in the universe might be off by as much as 10 percent.

Soon, simulations may finally answer the question: How much do lumps matter? The idea that cosmologists might have been missing a simple answer to a central problem of cosmology incessantly nags some skeptics. For them, results of the improved simulations can’t come soon enough. “It haunts me. I can’t let it go,” says cosmologist Rocky Kolb of the University of Chicago.

Smooth universe
By observing light from different eras in the history of the cosmos, cosmologists can compute the properties of the universe, such as its age and expansion rate. But to do this, researchers need a model, or framework, that describes the universe’s contents and how those ingredients evolve over time. Using this framework, cosmologists can perform computer simulations of the universe to make predictions that can be compared with actual observations.

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COSMIC WEB Clumps and filaments of matter thread through a simulated universe 2 billion light years across. This simulation incorporates some aspects of Einstein’s theory of general relativity, allowing for detailed results while avoiding the difficulties of the full-fledged theory.
JULIAN ADAMEK
After Einstein introduced his theory in 1915, physicists set about figuring out how to use it to explain the universe. It wasn’t easy, thanks to general relativity’s unwieldy, difficult-to-solve suite of equations. Meanwhile, observations made in the 1920s indicated that the universe wasn’t static as previously expected; it was expanding. Eventually, researchers converged on a solution to Einstein’s equations known as the Friedmann-Lemaître-Robertson-Walker metric. Named after its discoverers, the FLRW metric describes a simplified universe that is homogeneous and isotropic, meaning that it appears identical at every point in the universe and in every direction. In this idealized cosmos, matter would be evenly distributed, no clumps. Such a smooth universe would expand or contract over time.


A smooth-universe approximation is sensible, because when we look at the big picture, averaging over the structures of galaxy clusters and voids, the universe is remarkably uniform. It’s similar to the way that a single spoonful of minestrone soup might be mostly broth or mostly beans, but from bowl to bowl, the overall bean-to-broth ratios match.

In 1998, cosmologists revealed that not only was the universe expanding, but its expansion was also accelerating (SN: 2/2/08, p. 74). Observations of distant exploding stars, or supernovas, indicated that the space between us and them was expanding at an increasing clip. But gravity should slow the expansion of a universe evenly filled with matter. To account for the observed acceleration, scientists needed another ingredient, one that would speed up the expansion. So they added dark energy to their smooth-universe framework.

Now, many cosmologists follow a basic recipe to simulate the universe — treating the cosmos as if it has been run through an imaginary blender to smooth out its lumps, adding dark energy and calculating the expansion via general relativity. On top of the expanding slurry, scientists add clumps and track their growth using approximations, such as Newtonian gravity, which simplifies the calculations.

In most situations, Newtonian gravity and general relativity are near-twins. Throw a ball while standing on the surface of the Earth, and it doesn’t matter whether you use general relativity or Newtonian mechanics to calculate where the ball will land — you’ll get the same answer. But there are subtle differences. In Newtonian gravity, matter directly attracts other matter. In general relativity, gravity is the result of matter and energy warping spacetime, creating curves that alter the motion of objects (SN: 10/17/15, p. 16). The two theories diverge in extreme gravitational environments. In general relativity, for example, hulking black holes produce inescapable pits that reel in light and matter (SN: 5/31/14, p. 16). The question, then, is whether the difference between the two theories has any impact in lumpy-universe simulations.

Most cosmologists are comfortable with the status quo simulations because observations of the heavens seem to fit neatly together like interlocking jigsaw puzzle pieces. Predictions based on the standard framework agree remarkably well with observations of the cosmic microwave background — ancient light released when the universe was just 380,000 years old (SN: 3/21/15, p. 7). And measurements of cosmological parameters — the fraction of dark energy and matter, for example — are generally consistent, whether they are made using the light from galaxies or the cosmic microwave background.

However, the reliance on Newton’s outdated theory irks some cosmologists, creating a lingering suspicion that the approximation is causing unrecognized problems. And some cosmological question marks remain. Physicists still puzzle over what makes up dark energy, along with another unexplained cosmic constituent, dark matter, an additional kind of mass that must exist to explain observations of how galaxies and galaxy clusters rotate. “Both dark energy and dark matter are a bit of an embarrassment to cosmologists, because they have no idea what they are,” says cosmologist Nick Kaiser of École Normale Supérieure in Paris.

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An image from the Two-Micron All Sky Survey of 1.6 million galaxies in infrared light reveals how matter clumps into galaxy clusters and filaments. Future large-scale surveys may require improved simulations that use general relativity to track the evolution of lumps over time.
T.H. JARRETT, J. CARPENTER & R. HURT, OBTAINED AS PART OF 2MASS, A JOINT PROJECT OF UNIV. OF MASSACHUSETTS AND THE INFRARED PROCESSING AND ANALYSIS CENTER/CALTECH, FUNDED BY NASA AND NSF
Dethroning dark energy
Some cosmologists hope to explain the universe’s accelerating expansion by fully accounting for the universe’s lumpiness, with no need for the mysterious dark energy.

These researchers argue that clumps of matter can alter how the universe expands, when the clumps’ influence is tallied up over wide swaths of the cosmos. That’s because, in general relativity, the expansion of each local region of space depends on how much matter is within. Voids expand faster than average; dense regions expand more slowly. Because the universe is mostly made up of voids, this effect could produce an overall expansion and potentially an acceleration. Known as backreaction, this idea has lingered in obscure corners of physics departments for decades, despite many claims that backreaction’s effect is small or nonexistent.

Backreaction continues to appeal to some researchers because they don’t have to invent new laws of physics to explain the acceleration of the universe. “If there is an alternative which is based only upon traditional physics, why throw that away completely?” Matarrese asks.

Most cosmologists, however, think explaining away dark energy just based on the universe’s lumps is unlikely. Previous calculations have indicated any effect would be too small to account for dark energy, and would produce an acceleration that changes in time in a way that disagrees with observations.

“My personal view is that it’s a much smaller effect,” says astrophysicist Hayley Macpherson of Monash University in Melbourne, Australia. “That’s just basically a gut feeling.” Theories that include dark energy explain the universe extremely well, she points out. How could that be if the whole approach is flawed?

New simulations by Macpherson and others that model how lumps evolve in general relativity may be able to gauge the importance of backreaction once and for all. “Up until now, it’s just been too hard,” says cosmologist Tom Giblin of Kenyon College in Gambier, Ohio.

To perform the simulations, researchers needed to get their hands on supercomputers capable of grinding through the equations of general relativity as the simulated universe evolves over time. Because general relativity is so complex, such simulations are much more challenging than those that use approximations, such as Newtonian gravity. But, a seemingly distinct topic helped lay some of the groundwork: gravitational waves, or ripples in the fabric of spacetime.

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SPECKLED SPACETIME A lumpy universe, recently simulated using general relativity, shows clumps of matter (pink and yellow) that beget stars and galaxies.
H. MACPHERSON, PAUL LASKY, DANIEL PRICE


The Advanced Laser Interferometer Gravitational-Wave Observatory, LIGO, searches for the tremors of cosmic dustups such as colliding black holes (SN: 10/28/17, p. 8). In preparation for this search, physicists honed their general relativity skills on simulations of the spacetime storm kicked up by black holes, predicting what LIGO might see and building up the computational machinery to solve the equations of general relativity. Now, cosmologists have adapted those techniques and unleashed them on entire, lumpy universes.

The first lumpy universe simulations to use full general relativity were unveiled in the June 2016 Physical Review Letters. Giblin and colleagues reported their results simultaneously with Eloisa Bentivegna of the University of Catania in Italy and Marco Bruni of the University of Portsmouth in England.

So far, the simulations have not been able to account for the universe’s acceleration. “Nearly everybody is convinced [the effect] is too small to explain away the need for dark energy,” says cosmologist Martin Kunz of the University of Geneva. Kunz and colleagues reached the same conclusion in their lumpy-universe simulations, which have one foot in general relativity and one in Newtonian gravity. They reported their first results in Nature Physics in March 2016.

Backreaction aficionados still aren’t dissuaded. “Before saying the effect is too small to be relevant, I would, frankly, wait a little bit more,” Matarrese says. And the new simulations have potential caveats. For example, some simulated universes behave like an old arcade game — if you walk to one edge of the universe, you cross back over to the other side, like Pac-Man exiting the right side of the screen and reappearing on the left. That geometry would suppress the effects of backreaction in the simulation, says Thomas Buchert of the University of Lyon in France. “This is a good beginning,” he says, but there is more work to do on the simulations. “We are in infancy.”

Different assumptions in a simulation can lead to disparate results, Bentivegna says. As a result, she doesn’t think that her lumpy, general-relativistic simulations have fully closed the door on efforts to dethrone dark energy. For example, tricks of light might be making it seem like the universe’s expansion is accelerating, when in fact it isn’t.

When astronomers observe far-away sources like supernovas, the light has to travel past all of the lumps of matter between the source and Earth. That journey could make it look like there’s an acceleration when none exists. “It’s an optical illusion,” Bentivegna says. She and colleagues see such an effect in a simulation reported in March in the Journal of Cosmology and Astroparticle Physics. But, she notes, this work simulated an unusual universe, in which matter sits on a grid — not a particularly realistic scenario.

For most other simulations, the effect of optical illusions remains small. That leaves many cosmologists, including Giblin, even more skeptical of the possibility of explaining away dark energy: “I feel a little like a downer,” he admits.

Light paths
Lumps (gray) within this simulated universe change the path light takes (yellow lines), potentially affecting observations. Matter bends space, slightly altering the light’s trajectory from that in a smooth universe.

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JAMES MERTENS


Surveying the skies
Subtle effects of lumps could still be important. In Hans Christian Andersen’s “The Princess and the Pea,” the princess felt a tiny pea beneath an impossibly tall stack of mattresses. Likewise, cosmologists’ surveys are now so sensitive that even if the universe’s lumps have a small impact, estimates could be thrown out of whack.

The Dark Energy Survey, for example, has charted 26 million galaxies using the Victor M. Blanco Telescope in Chile, measuring how the light from those galaxies is distorted by the intervening matter on the journey to Earth. In a set of papers posted online August 4 at arXiv.org, scientists with the Dark Energy Survey reported new measurements of the universe’s properties, including the amount of matter (both dark and normal) and how clumpy that matter is (SN: 9/2/17, p. 32). The results are consistent with those from the cosmic microwave background — light emitted billions of years earlier.

To make the comparison, cosmologists took the measurements from the cosmic microwave background, early in the universe, and used simulations to extrapolate to what galaxies should look like later in the universe’s history. It’s like taking a baby’s photograph, precisely computing the number and size of wrinkles that should emerge as the child ages and finding that your picture agrees with a snapshot taken decades later. The matching results so far confirm cosmologists’ standard picture of the universe — dark energy and all.

“So far, it has not yet been important for the measurements that we’ve made to actually include general relativity in those simulations,” says Risa Wechsler, a cosmologist at Stanford University and a founding member of the Dark Energy Survey. But, she says, for future measurements, “these effects could become more important.” Cosmologists are edging closer to Princess and the Pea territory.

Those future surveys include the Dark Energy Spectroscopic Instrument, DESI, set to kick off in 2019 at Kitt Peak National Observatory near Tucson; the European Space Agency’s Euclid satellite, launching in 2021; and the Large Synoptic Survey Telescope in Chile, which is set to begin collecting data in 2023.

If cosmologists keep relying on simulations that don’t use general relativity to account for lumps, certain kinds of measurements of weak lensing — the bending of light due to matter acting like a lens — could be off by up to 10 percent, Giblin and colleagues reported at arXiv.org in July. “There is something that we’ve been ignoring by making approximations,” he says.

That 10 percent could screw up all kinds of estimates, from how dark energy changes over the universe’s history to how fast the universe is currently expanding, to the calculations of the masses of ethereal particles known as neutrinos. “You have to be extremely certain that you don’t get some subtle effect that gets you the wrong answers,” Geneva’s Kunz says, “otherwise the particle physicists are going to be very angry with the cosmologists.”

Some estimates may already be showing problem signs, such as the conflicting estimates of the cosmic expansion rate (SN: 8/6/16, p. 10). Using the cosmic microwave background, cosmologists find a slower expansion rate than they do from measurements of supernovas. If this discrepancy is real, it could indicate that dark energy changes over time. But before jumping to that conclusion, there are other possible causes to rule out, including the universe’s lumps.

Until the issue of lumps is smoothed out, scientists won’t know how much lumpiness matters to the cosmos at large. “I think it’s rather likely that it will turn out to be an important effect,” Kolb says. Whether it explains away dark energy is less certain. “I want to know the answer so I can get on with my life.”

 

Scientists make first ever attempt at gene editing inside the body
New therapy will permanently alter DNA, with no way to alter mistakes editing may cause – but offers chance to tackle currently incurable metabolic diseases

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Brian Madeux, 44, sits with his girlfriend Marcie Humphrey, waiting to receive the first human gene editing therapy. Photograph: Eric Risberg/AP

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• Wednesday 15 November 2017 12.33 GMT

Scientists have tried editing a gene inside the body for the first time, in a bold attempt to tackle an incurable a disease by permanently changing a patient’s DNA.

On Monday in California, 44-year-old Brian Madeux intravenously received billions of copies of a corrective gene and a genetic tool to cut his DNA in a precise spot.

“It’s kind of humbling to be the first to test this,” said Madeux, who has a metabolic disease called Hunter syndrome. “I’m willing to take that risk. Hopefully it will help me and other people.”

Signs of whether it is working may come in a month; tests will confirm in three months.

If successful, the new technique could give a major boost to the fledgling field of gene therapy. Scientists have edited people’s genes before, altering cells in the lab that are then returned to patients. There also are gene therapies that do not involve editing DNA.

But these methods can only be used for a few types of diseases. Some give results that may not last. Some others supply a new gene like a spare part, but can’t control where it inserts in the DNA, possibly causing a new problem, such as cancer.

This time, the genetic tinkering is happening in a precise way inside the body – like sending a miniature surgeon along to place the new gene in exactly the right location.

“We cut your DNA, open it up, insert a gene, stitch it back up. Invisible mending,” said Dr Sandy Macrae, president of Sangamo Therapeutics, the California company testing the therapy for two metabolic diseases and haemophilia. “It becomes part of your DNA and is there for the rest of your life.”


That also means there is no way to erase any mistakes the editing might cause.

The risks can’t be fully known, but because these are incurable diseases the studies should move forward, said one independent expert, Dr Eric Topol of the Scripps Translational Science Institute in San Diego.

Protections are in place to help ensure safety, and animal tests were very encouraging, according to Dr Howard Kaufman, a Boston scientist on the National Institutes of Health panel that approved the studies.

He said gene editing’s promise is too great to ignore. “So far there’s been no evidence that this is going to be dangerous,” he said. “Now is not the time to get scared.”

Fewer than 10,000 people worldwide have these metabolic diseases, partly because many die very young. Those with Madeux’s condition lack a gene that makes an enzyme that breaks down certain carbohydrates. These build up in cells and cause havoc throughout the body.

Patients may have frequent colds and ear infections, distorted facial features, hearing loss, heart problems, breathing trouble, skin and eye problems, bone and joint flaws, bowel issues and brain and cognitive problems.

“Many are in wheelchairs … dependent on their parents until they die,” said Dr. Chester Whitley, a University of Minnesota genetics expert who plans to enrol patients in the studies.

Currently, weekly doses of the missing enzyme can ease some symptoms, but cost $100,000 to $400,000 a year and do not prevent brain damage.

Madeux, who now lives near Phoenix, Arizona, is engaged to a nurse, Marcie Humphrey, who he met 15 years ago in a study that tested the enzyme therapy at UCSF Benioff Children’s Hospital Oakland, where the gene editing experiment also took place.

He has had 26 operations for hernias, bunions, bones pinching his spinal column, and ear, eye and gall bladder problems.

“It seems like I had a surgery every other year of my life,” he said. Last year he nearly died from an attack of bronchitis and pneumonia. The disease had warped his airway: “I was drowning in my secretions, I couldn’t cough it out.”

Gene editing will not fix damage he’s already suffered, but he hopes it will end the need for weekly enzyme treatments.

Initial studies will involve up to 30 adults to test safety, but the ultimate goal is to treat children very young, before much damage occurs.

The gene-editing tool Crispr-Cas9 has had a lot of recent attention, but this study used a different tool called zinc finger nucleases. They work like molecular scissors that seek and cut a specific piece of DNA.

The therapy has three parts: the new gene and two zinc finger proteins. DNA instructions for each part are placed in a virus that has been altered to not cause infection but instead to ferry them into cells. Billions of copies of these are given to the patient intravenously.

They travel to the liver, where cells use the instructions to make the zinc fingers and prepare the corrective gene. The fingers cut the DNA, allowing the new gene to slip in. The new gene then directs the cell to make the enzyme the patient lacked.


Only 1% of liver cells would have to be corrected to successfully treat the disease, said Madeux’s physician and study leader, Dr Paul Harmatz.

Safety worries plagued some earlier gene therapies. One potential problem is that the virus might provoke an immune system attack, which caused the death of 18-year-old Jesse Gelsinger during a gene therapy study in 1999. However, the new studies use a different virus that has proved much safer in other experiments.

Another worry is that inserting a new gene might have unforeseen effects on other genes. That was the case during a gene therapy trial attempting to cure a rare immune system disorder known as “bubble boy disease”. Several patients later developed leukaemia because the new gene entered a place in the native DNA where it unintentionally activated a cancer gene.

“When you stick a chunk of DNA in randomly, sometimes it works well, sometimes it does nothing and sometimes it causes harm,” said Hank Greely, a Stanford University bioethicist. “The advantage with gene editing is you can put the gene in where you want it.”

Finally, some fear that the virus could get into other places like the heart, or eggs and sperm where it could affect future generations. Doctors say built-in genetic safeguards prevent the therapy from working anywhere but the liver, like a seed that only germinates in certain conditions.

Meanwhile, Madeaux remains optimistic. “I’m nervous and excited,” he said. “I’ve been waiting for this my whole life: something that can potentially cure me.

 

How dad’s stress changes his sperm
RNA-packed vesicles that glom onto the germ cells can be altered by a stress hormone, a mouse study suggests
BY
LAURA SANDERS
3:30PM, NOVEMBER 15, 2017

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NOT BUNDLES OF JOY Stress may change the genetic contents of sperm by tweaking small packets of RNA in seminal fluid, a study in mice suggests.

WASHINGTON, D.C. — Sperm from stressed-out dads can carry that stress from one generation to another. “But one question that really hasn’t been addressed is, ‘How do dad’s experiences actually change his germ cell?’” said Jennifer Chan, a neuroendocrinologist at the University of Pennsylvania, on November 13 at the annual meeting of the Society for Neuroscience.

Now, from a study in mice, Chan and her colleagues have some answers, and even hints at ways to stop this stress inheritance.

The researchers focused on the part of the male reproductive tract called the caput epididymis, a place where sperm cells mature. Getting rid of a stress-hormone sensor there called the glucocorticoid receptor stopped the transmission of stress, the researchers found. When faced with an alarming predator odor, offspring of chronically stressed mice dads overproduce the stress hormone corticosterone. But mice dads that lacked this receptor in the epididymis had offspring with normal hormonal responses.

Earlier work has shown that epididymis cells release small packets filled with RNA that can fuse to sperm and change their genetic payload. Experiments on cells in dishes revealed that chronic exposure to corticosterone changed the RNA in these vesicles. The results offer an explanation of how stress can change sperm: By activating the glucocorticoid receptor, stress tweaks the RNA in epididymis vesicles. Then, those vesicles deliver their altered contents to sperm, passing stress to the next generation.

Similar vesicles are present in human seminal fluid, even after ejaculation. Chan and colleagues are testing whether humans carry similar signs of stress in these RNA-loaded vesicles by studying college students’ semen samples. Exam schedules will be used as a stress indicator, she said.

That whole piece has stressed me out

 

Precision Oncology seeks to identify and target the mutation that drives a tumor. Despite its straightforward rationale, concerns about its effectiveness are mounting. What is the biological explanation for the “imprecision?” First, Precision Oncology relies on indiscriminate sequencing of genomes in biopsies that barely represent the heterogeneous mix of tumor cells. Second, findings that defy the orthodoxy of oncogenic “driver mutations” are now accumulating: the ubiquitous presence of oncogenic mutations in silent premalignancies or the dynamic switching without mutations between various cell phenotypes that promote progression. Most troublesome is the observation that cancer cells that survive treatment still will have suffered cytotoxic stress and thereby enter a stem cell–like state, the seeds for recurrence. The benefit of “precision targeting” of mutations is inherently limited by this counterproductive effect. These findings confirm that there is no precise linear causal relationship between tumor genotype and phenotype, a reminder of logician Carveth Read's caution that being vaguely right may be preferable to being precisely wrong. An open-minded embrace of the latest inconvenient findings indicating nongenetic and “imprecise” phenotype dynamics of tumors as summarized in this review will be paramount if Precision Oncology is ultimately to lead to clinical benefits. Cancer Res; 77(23); 1–7. ©2017 AACR.

 

very interesting.

the action of a normal cell verses a cancer cell in terms of replication is very different. finding why they become voracious and replicate madly is really key but the genetically engineered custom treatments are IMO the game changer to target just the cancer and not this kill everything approach we have now.

 

Immuno-oncology

 

I've been studying and attending a uni course on the engineering side of manufacturing biotech products.