I did an interview with my old friend Chris Mooney for Point of Inquiry, and it’s now live. We talk about the end of the Earth, punching Buzz Aldrin, Hollywood science, and other topics astronomical and hysterical. Enjoy!

Imagine trying to rewind the clock and start your life anew, perhaps by moving to a new country or starting a new career. You would still be constrained by your past experiences and your existing biases, skills and knowledge. History is difficult to shake off, and lost potential is not easily regained. This is a lesson that applies not just to our life choices, but to stem cell research too.

Over the last four years, scientists have made great advances in reprogramming specialised adult cells into stem-like ones, giving them the potential to produce any of the various cells in the human body. It’s the equivalent of erasing a person’s past and having them start life again.

But a large group of American scientists led by Kitai Kim have found a big catch. Working in mice, they showed that these reprogrammed cells, formally known as “induced pluripotent stem cells” or iPSCs, still retain a memory of their past specialities. A blood cell, for example, can be reverted back into a stem cell, but it carries a record of its history that constrains its future. It would be easier to turn this converted stem cell back into a blood cell than, say, a brain cell.

The history of iPSCs is written in molecular marks that annotate its DNA. These ‘epigenetic’ changes can alter the way a gene behaves even though its DNA sequence is still the same. It’s the equivalent of sticking Post-It notes in a book to tell a reader which parts to read or ignore, without actually editing the underlying text. Epigenetic marks separate different types of cells from one another, influencing which genes are switched on and which are inactivated. And according to Kim, they’re not easy to remove, even when the cell has apparently been reprogrammed into a stem-like state.

But reprogramming adult cells is just one of two ways of making stem cells tailored to a person’s genetic make-up. The other is known as nuclear transfer. It involves transplanting a nucleus (and the DNA inside it) from one person’s cell into an empty egg. The egg becomes an embryo, which yields stem cells containing the donor’s genome. Kim has found that these cells (known as nuclear transfer embryonic stem cells or ntESCs) are much more like genuine embryonic stem cells than the reprogrammed iPSCs. They’re ‘stemmier’, for lack of a better word.

Kim’s research tells us that creating stem cells through nuclear transfer is not a technique that’s easily disregarded. It certainly steers into trickier ethical territory since harvesting ntESCs destroys the embryo. And it is still trailing behind technically; so far, it has only been successfully done in monkeys and other non-human mammals, and it has been mired in scientific scandal.

Meanwhile, work on iPSCs has raced ahead. The starting pistol was fired in 2006, when a group of Japanese scientists first showed that it was possible to create these cells in mice. The race intensified in 2007, when two research groups independently managed to do the same for human cells. In 2009, mouse iPSCs were used to produce live animals, passing the ultimate test of their stem-like status. Various groups have made the technique more efficient, sped it up, found ways of sorting out the most promising cells, and changed the details so that it doesn’t use viruses (or uses only viruses).

But all along, scientists have realised that there are subtle differences between iPSCs and genuine embryonic stem cells and, indeed, between iPSCs produced from different tissues. For a start, some types of cell are easier to reprogram than others – skin, stomach or liver cells, for example, are easier to convert than cells from connective tissues. And the older or more specialised the cells are, the harder the task becomes.

Kim’s team found that once the cells are converted, there are further issues. They found it easier to produce blood cells from iPSCs that themselves came from blood cells, rather than those derived from connective tissue or brain cells. By contrast, iPSCs made from connective tissue were the better choice for producing bone cells.

Kim thinks that this is because the widely used reprogramming techniques fail to strip away a cell’s epigenetic markers. He focused on one such marker – the presence of methyl groups on DNA, which typically serve to switch off genes, like Post-it notes that say “Ignore this”. Kim found that the methylation patterns of iPSCs are very different depending on the cells they came from. Those that come from brain or connective cells, for example, have methyl groups at places that are needed to produce blood cells, and vice versa. Even iPSCs that come from slightly different lineages of blood cells carry distinctive patterns of methyl marks.

In all of these tests, ntESCs (those produced by nuclear transfer) were far more similar to genuine embryonic stem cells than any of the iPSCs. Their patterns of methylation were a closer match and they were easier to convert into any type of adult cell. This certainly makes sense – when the nucleus is transferred into an empty shell, it its DNA is rapidly and actively stripped of its methyl groups. Its history is erased with far greater efficiency than the reprogrammed iPSCs.

This seems like a clear win for the nuclear transfer method, but Kim thinks there are ways of improving the reprogramming technique to get around this problem. For a start, you can efficiently convert iPSCs derived from one type of cell into another via another round of programming and reprogramming. For example, you could reprogram a brain cell into an iPSC, convert it into a blood cell, reprogram it back into an iPSC again, and get a stock that’s very good at creating blood cells. This does, however, seem like a very roundabout strategy – why not start with blood cells in the first place?

A better solution is to try and strip away the epigenetic marks more directly. Some chemicals can do that, and after treating the iPSCs with such substances for a few days, Kim improved their ability to produce tissues regardless of their origins.

Another group led by Jose Polo found the same epigenetic problem, but they discovered a simpler solution – grow the cells for a long time. When cells are grown in culture, they need to be frequently ‘passaged’. That is, they need to be split among fresh containers so that they don’t run out of room and nutrients. Polo found that continuous passaging solves the epigenetic problem, reprogramming the iPSCs into a far more stem-like state, free from the constraints of their origins. It seems that when iPSCs are created, their epigenetic marks are eventually removed even though the process is gradual and slow.

And after all, the epigenetic memory of reprogrammed cells isn’t necessarily a bad thing. If you want to produce blood in bulk, why not start with iPSCs that are very good at making blood cells but not other types? Indeed, it’s still very difficult to nudge stem cells into becoming specific tissues, and starting off with cells that naturally gravitate towards certain fates could well be a blessing in disguise.

Reference: Nature http://dx.doi.org/10.1038/nature09342 and Nature Biotechnology http://dx.doi.org/10.1038/nbt1667

More on epigenetics:

• Shutting off a single gene could improve fertility by activating dormant egg-producing cells
• Crickets forewarn their offspring about predators before they’re born
• Alcohol tastes and smells better to those who get their first sips in the womb
• Child abuse permanently modifies stress genes in brains of suicide victims
• Obesity amplifies across generations; can folate-rich diets stop it?

If the citation link isn’t working, read why here

To seal more car deals, Chevrolet UK looked to arm its salesmen with the perfect weapon of confidence: an unstoppable handshake. Here’s the secret they received from Geoffrey Beattie, Head of Psychological Sciences at the University of Manchester:

PH (Perfect Handshake)= ? (e^2 + ve^2)(d^2) + (cg + dr)^2 + ?{(4<s>^2)(4<p>^2)}^2 + (vi + t + te)^2 + {(4<c>^2 )(4<du>^2)}^2

We hope (and suspect) the training posters and equation, supposedly meant for Chevrolet-sellers, are meant for publicity and are not a real attempt to improve customer relations.

The variables, as outlined in a Chevrolet press release:

(e) is eye contact (1=none; 5=direct) 5; (ve) is verbal greeting (1=totally inappropriate; 5=totally appropriate) 5; (d) is Duchenne smile – smiling in eyes and mouth, plus symmetry on both sides of face, and slower offset (1=totally non-Duchenne smile (false smile); 5=totally Duchenne) 5; (cg) completeness of grip (1=very incomplete; 5=full) 5; (dr) is dryness of hand (1=damp; 5=dry) 4; (s) is strength (1= weak; 5=strong) 3; (p) is position of hand (1=back towards own body; 5=other person’s bodily zone) 3; (vi) is vigour (1=too low/too high; 5=mid) 3; (t) is temperature of hands (1=too cold/too hot; 5=mid) 3; (te) is texture of hands (5=mid; 1=too rough/too smooth) 3; (c) is control (1=low; 5=high) 3; (du) is duration (1= brief; 5=long) 3.

The press release details some pretty common sense advice: avoid sweaty palms; don’t squeeze too hard or hold on too long; make eye contact. But putting the formula into action might be tough; if actually meant to inspire confidence (which the release says 70 percent of hand-shakers are lacking), doing the math before every hand-to-hand may instead lead to more perfect head scratching.

Related content:
Discoblog: Alien Math Shows Why Grad Student Doesn’t Have a Girlfriend
Discoblog: How to Make People Believe in ESP: Tell Them Scientists Think It’s Bogus
Discoblog: New Study: If a Dude Sounds Strong, He Probably Is
Discoblog: Can a Brain Scan Predict Your Behavior Better Than You Can?
80beats: Want Someone to Take a Decision Seriously? Hand Them Something Heavy

Image: flickr / Aidan Jones

Schemes to hack the planet and save us from global warming have two layers of obstacles to overcome. First, is it technologically and physically possible to do what’s proposed? And then there’s the second: Is it politically possible to tinker with the planet?

Those who would argue “absolutely not” to the latter got a boost by a new study out in Nature Geoscience. Katharine Ricke and her team modeled the effects of one of the most popular geoengineering plans: seeding the atmosphere with aerosols to reflect away some of the sun’s rays, mimicking the way a massive volcanic eruption can cool the Earth. Ricke found that the effects on rainfall and temperature could vary wildly by region—and that what’s best for one country could spell disaster for another.

For example, Ricke says, her study found that levels of sulphate that kept China closest to its baseline climate were so high that they made India cold and wet. Those that were best for India caused China to overheat. She notes, however, that both countries fared better either way than under a no-geoengineering policy [Nature].

Given the complex connectivity of the climate system, it’s not possible to fix everything to everybody’s liking. While the team’s study shows that geoengineers could control either temperature or precipitation pretty well by fine-tuning their atmospheric seeding, they couldn’t control both at once.

“People won’t agree on what level of geoengineering is desirable,” says Myles Allen of the University of Oxford, who was involved in the study. “It works, but it won’t work the same way for everyone” [New Scientist].

Nevertheless, the drumbeat for geoengineering isn’t quieting. Two books that came out this spring, Jeff Goodell’s “How To Cool the Planet” and Eli Kintisch’s “Hack the Planet”, delved into the idea. Several more out this year try to predict what the Earth will be like in the warmer future, and whether you should go ahead and buy that summer vacation property in Canada. Last September Britain’s Royal Society issued a report calling for investment in geoengineering as a backup plan in case nations fail to constrain their emissions. And that was before the failure of the Copenhagen climate summit.

But, as climate models improve, scientists could get a better picture of the fallout from such a dramatic action as seeding the atmosphere with aerosols, according to climate guru Ken Caldeira.

“I don’t think climate modelling is at the point where we should trust one single model at that scale,” Caldeira says. “But I think the results are robust in the sense that it’s the kind of issue that people will need to face. The qualitative idea is that you’re going to have differential results in different regions, and that’s going to cause people to want different amounts of this stuff up there, if they want any of it up there at all” [Nature].

Related Content:
80beats: Bill Gates Funds Seawater Cloud Seeding, “The Most Benign Form of Geoengineering”
80beats: Iron-Dumping Experiment Is a Bust: It Feeds Crustaceans, Doesn’t Trap Carbon
80beats: If We Can’t Stop Emitting CO2, What’s Our Plan B?
DISCOVER: 5 Most Radical Ways to Squelch a Climate Crisis (photo gallery)
DISCOVER: It’s Gettin’ Hot in Here: The Big Battle Over Climate Science

Image: iStockphoto

The force of blog nature known as BORA! has decided he does not like the Pepsi aftertaste and is leaving Scienceblogs. I’m just back from a wonderfully rain-soaked vacation in Ireland, so I’m scrambling to get back up to speed. I won’t update my post on the scienceblogs diaspora till this afternoon. But in the meantime, read the epic farewell from BORA!

Science fiction is often associated with depictions of technology which, to quote Arther Clarke’s third law, is “so advanced that it seems like magic to us.” But science fiction’s other side is less about techno-gizmology and more about pushing us to think about what it is to be human. It asks what it would be like to live with different social norms (think of the group family structure in Caprica, or the androgynous society of Ursula Le Guin’s Left Hand of Darkness), different notions of identity (think of Star Trek’s “The Borg”, Avatar), and of reality itself (The Matrix).

The examples I’ve mentioned are from literature, movies, and TV. What about theater? Science fiction rarely shows up on the stage. But there are exceptions. This past week I was a guest instructor in a class called “Theater for Nerds” in Northwestern University’s summer program in theatre arts for high school seniors. It’s a class created by JC Aevaliotis for in-depth readings of plays that work at the intersection of art and another discipline (history, philosophy, science)–nerdy stuff indeed. I was invited to help discuss a play called On Ego, a collaboration between playwright Mick Gordon and neuropsychologist Paul Broks. The play is an exploration of different ideas about how we can go from what David Foster Wallace called the “2.8 pounds of electrified pate” that is our brain to something so vaunted as a sense of self. One idea, called “ego theory,” holds that there is an inner essence, denoted by “I”; the other idea, called “bundle theory” holds that there is no inner essence, but instead we are long series or bundle of interconnected sensations and thoughts. The underlying brain processes such as memories, feelings, thoughts, are sprinkled across diverse regions of the brain with no special point of convergence. Instead, we “come together in a work of fiction” – our brain is a story-telling machine, and the “self” is a story.

The play uses a thought experiment rooted in science fiction, and originally posed by philosopher Derek Parfit. You get beamed by a teleporter to a different location. But, a malfunction occurs and your original version is not destroyed. Which one is your “true” self? An ego theorist, who believes there must be a persistence of an inner “I” to maintain identity, would say the original; a bundle theorist, who thinks that the self is just the bundle of memories and experience, all faithfully copied by the teleporter, would say the copy is no less “you” than the original.

A beautiful ambiguity is introduced through Alice, the wife of the protagonist of the play, Alex. Alice has Capgras Syndrome. In Capgras there is a disconnection between the part of our brain that does facial recognition and the part of the brain that gives you an emotional response when you see someone familiar. Facial recognition occurs, but not the emotional reaction. This isn’t noticeable for strangers, but when your wife or husband appears, the strangeness of not feeling any emotional reaction causes people with Capgras to claim that the person before them is an imposter. Alex has a teleporter accident, where his “original” is not destroyed, but his copy goes on to visit Alice. But Alice refuses to believe that Alex is her husband. Is this the Capgras talking, or is she someone who believes in the “I” as persisting inner essence and has detected that Alex is, in fact, a “fake”?

The play manages to pack in all of these deep questions into a tight and dramatic story. It’s a great role model for how scientists might collaborate with story makers in a deeper way than increasing the plausibility of a far-out plot point or helping to fact check dialog. What makes this collaboration between science and art so successful is that the science fiction of the teleporter and science fact of Capgras are needed for the story to work as a piece of theater. They serve to dramatically present open questions about what it is to be human in a way that will leave the audience with a lot to think about.

In a future (pun intended) post, I’ll look at what some recent sci-fi movies and TV series (Avatar, Surrogates, Caprica) say about the nature of the self.