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Jennifer Doudna: I have to be true to who I am as a scientist

Crispr inventor Jennifer Doudna talks about discovering the gene-editing tool, the split with her collaborator and the complex ethics of genetic manipulation.

Jennifer Doudna, 53, is an American biochemist based at the University of California, Berkeley. Together with the French microbiologist Emmanuelle Charpentier, she led the discovery of the revolutionary gene-editing tool, Crispr. The technology has the potential to eradicate previously incurable diseases, but also poses ethical questions about the possible unintended consequences of overwriting the human genome.

Were you nerdy as a child? What got you hooked on science?
Yes, I was nerdy. My father was a professor of American literature in Hawaii and he loved books. One day I came home from school and he haddropped a copy of The Double Helix on the bed, by Jim Watson. One rainy afternoon I read it and I was just stunned. I was blown away that you could do experiments about what a molecule looks like. I was probably 12 or 13. I think that was the beginning of starting to think,Wow, that could be an amazing thing to work on.

You’ve spent most of your career uncovering the structure of RNA and never set out to create a tool to copy andpaste human genes. How did you end up working on Crispr?
I think you can put scientists into two buckets. One is the type who dives very deeply into one topic for their whole career and they know it better than anybody else in the world. Then there’s the other bucket, where I would put myself, where it’s like you’re at a buffet table and you see an interesting thing here and do it for a while, and that connects you to another interesting thing and you take a bit of that. That’s how I came to be working on Crispr it was a total side-project.

But when you first started your collaboration with Emmanuelle Charpentier, did you have a hunch you were on to something special?
We met at a conference in San Juan, Puerto Rico, and took a walk around the old town together. She was so passionate, her excitement was very infectious. I still remember walking down this street with her and she said: “Well I’m really glad you want to work with us on the mysterious [Cas9 the enzyme that snips DNA at the chosen location in the editing process].” It was this kind of electrifying moment. Even then I just had this gut feeling that this was something really interesting.

How important is personal chemistry in science collaborations?
It’s essential. Working in a lab is analogous to being in a high-school play: you’re rehearsing long hours, it’s crowded, there are stressful things that come up. It’s the same thing in science. Things never work as you think they will, experiments fail and so to have people around that really get along with each other is super important. Many collaborations dont work out, usually just because people’s interests aren’t aligned or people don’t really like working together.

The real frenzy around your work started in 2012, when you showed that Crispr-Cas9 could be used to slice up DNA at any site [of the DNA molecule] you wanted. Did you realise this was abig deal gradually or immediately?
It wasn’t a gradual realisation, it was one of those OMG moments where you look at each other and say holy moly. This was something we hadn’t thought about before, but now we could see how it worked, we could see it would be such a fantastic way to do gene editing.

After you demonstrated Crispr could edit bacterial DNA, two rival labs (Harvard and the Broad Institute) got there first in human cells. How come they beat you to it?
They were absolutely set up to do that kind of experiment. They had all the tools, the cells growing, everything was there. For us, they were hard experiments to do because its not the kind of science we do. What speaks to the ease of the system was that a lab like mine could even do it.

The Broad Institute won the latest round of an ongoing legal battle over patent rights they claim that it wasn’t obvious that Crispr could be used to edit human cells too. Where do you stand?
People have asked me over and over again: Did you know it was going to work? But until you do an experiment you don’t know that’s science. I’ve been lambasted for this in the media, but I have to be true to who I am as a scientist. We certainly had a hypothesis and it certainly seemed likea very good guess that it would.

There’s the patent dispute and you and Emmanuelle Charpentier also ended up pursuing rival projects to commercialise the technology. Are you all still friends?
If there’s a sadness to me about all of this and a lot of it’s been wonderful and really exciting it’s that I would’ve loved to continue working with Emmanuelle, scientifically. For multiple reasons that wasn’t desirable to her. I’m not blaming her at all she had her reasons and I respect her a lot.

The media loves to drive wedges, but we are very cordial. I was just with her in Spain and she was telling me about the challenges [of building her new lab in Berlin]. I hope on her side, certainly on my side, we respect each other’s work and in the end were all in it together.

In your book you describe a nightmare youhad involving Hitler wearing a pig mask, asking to learn more about your amazing technology. Do you still have anxiety dreams about where Crispr might leave the human race?
I had the Hitler dream and I’ve had a couple of other very scary dreams, almost like nightmares, which is quite unusual for an adult. Not so much lately, but in the first couple of years after I published my work, the field was moving so fast. I had this incredible feeling that the science was getting out way ahead of any considerations about ethics, societal implications and whether we should be worrying about random people in various parts of the world using this for nefarious purposes.

In 2015, you called for a moratorium on the clinical use of gene editing. Where do you stand on using Crispr to edit embryos these days?
It shouldn’t be used clinically today, but in the future possibly. That’s a big change for me. At first, I just thought why would you ever do it? Then I started to hear from people with genetic diseases in their family this is now happening every day for me. A lot of them send me pictures of their children. There was one that I can’t stop thinking about, just sent to me in the last 10 days or so. A mother who told me that her infant son was diagnosed with a neurodegenerative disease, caused by a sporadic rare mutation. She sent me a picture of this little boy. He was this adorable little baby, he was bald, in his little carrier and so cute. I have a son and my heart just broke.

What would you do as a mother? You see your child and he’s beautiful, he’s perfect and you know he’s going to suffer from this horrible disease and theres nothing you can do about it. Its horrible. Getting exposed to that, getting to know some of these people, it’s not abstract any more, it’s very personal. And you think, if there were away to help these people, we should do it. It would be wrong not to.

What about the spectre of designer babies?
A lot of it will come down to whether the technology is safe and effective, are there alternatives that would be equally effective that we should consider, and what are the broader societal implications of allowing gene editing? Are people going to start saying I want a child that’s 6ft 5in and has blue eyes and so on? Do we really want to go there? Would you do things that are not medically necessary but are just nice-to-haves, for some people? It’s a hard question. There are a lot of grey areas.

Are you worried about cuts to science funding, including to the National Institutes of Health (NIH) budget?
I am very concerned. Science funding is not a political football but in fact a down payment on discovery, the seed money to fund a critical step toward ending Alzheimers or curing cancer.

Researchers currently working on projects aimed at improving numerous aspects of our agriculture, environment and health may be forced to abandon their work. The outcome is that people will not receive the medical treatments they need, our struggle to feed our exploding population will deepen, and our efforts to manage climate change will collapse.

Over the long term, the very role of fundamental science as a means to better our society may come into question. History and all evidence points to the fact that when we inspire and support our scientific community we advance our way of life and thrive.

Were you disturbed when Trump tweeted, If U.C. Berkeley does not allow free speech and practices violence on innocent people with a different point of view NO FEDERAL FUNDS? in response to a planned alt-right speaker being cancelled due to violent protests on campus?
Yes. It was a confusing tweet since the university was clearly committed to ensuring that the event would proceed safely and first amendment rights were supported. Few expected the awful actions of a few to be met with a willingness from the highest office to deprive more than 38,000 students access to an education.

You’ve spoken at Davos, shared the $3m 2015 Breakthrough prize, been listed among the 100 most influential people in the world by Time magazine. Are you still motivated about heading into the lab these days?
Yesterday I was getting ready to go to a fancy dinner. I was in a cocktail gown and had my makeup on and my hair done, but I wanted to talk to a postdoc in my lab about an experiment he was doing, so I texted him saying can we Skype? It was 8am in California, I was over here [in the UK] in my full evening gown, talking about the experiment. That’s how nerdy I am.

A Crack in Creation: The New Power to Control Evolution by Jennifer Doudna and Sam Sternberg is published by The Bodley Head (20). To order a copy for 17 go to bookshop.theguardian.com or call 0330 333 6846. Free UK p&p over 10, online orders only. Phone orders min p&p of 1.99

Read more: https://www.theguardian.com/science/2017/jul/02/jennifer-doudna-crispr-i-have-to-be-true-to-who-i-am-as-a-scientist-interview-crack-in-creation

Can you judge a book by its odour?

Cocoa, wood, rusks every book has a distinctive smell. And each smell says something about how and when it was made, and where it has been.

What does it mean to experience a book? To a bibliophile such as Alberto Manguel, smell plays an important part. In a talk at the British Library this week, the one-time protege of Jorge Luis Borges and director of the National Library of Argentina said he was particularly partial to old Penguin paperbacks, which he loved for their odour of fresh rusk biscuits.

Audience members responded with their own sense impressions. Peter, a pensioner, said he experienced books as smelling of salt and pepper that dryness when you open the cupboard with a touch of the sea, while 46-year-old Donna confessed that she had recently bought a book for her young son partly because it smelled of the rain.

To conservators and historians, smell has always played an important role in assessing the origin and condition of historic books, and in working out how to look after them. I have no vocabulary to define this, but there is a curious warm leathery smell to English parchment, unlike the sharper, cooler scent of Italian skins, wrote the Cambridge University don and librarian Christopher de Hamel in his bestselling Meetings with Remarkable Manuscripts.

But that lack of vocabulary could be about to change, thanks to a groundbreaking project by researchers at UCL Institute for Sustainable Heritage, who have devised a way of relating such apparently subjective descriptions directly to the chemical composition of books. In a paper published this week in the journal Heritage Science, Cecilia Bembibre and Matija Strli describe how they analysed samples from an old book, picked up in a second-hand shop, and developed a historic book odour wheel, which connects identifiable chemicals with peoples reactions to them.

Using fibres from the novel, they produced an extract of historic book, which was presented to 79 visitors to Birmingham Museum and Art Gallery. Chocolate, cocoa or chocolatey were the most frequent words used to describe the smell of a copy of French writer Bernard Gassets 1928 novel Les Chardons du Baragan, followed by coffee, old, wood and burnt.

From the analytical perspective, and given that coffee and chocolate come from fermented/roasted natural lignin and cellulose-containing product, they share many VOCs (volatile organic compounds) with decaying paper, wrote the researchers, who combined the results with those of earlier research projects, such as studies of a 1940s visitors book at the National Trusts Knole House in Kent. Their study also took them beyond books themselves, to the places in which many of them are read: libraries. In another experiment, they asked visitors to the Wren Library in St Pauls cathedral to describe what the library smelled like to them. Everyone described its smell as woody, while 86% also experienced it as smoky, 71% as earthy and just under half (41%) reported the scent of vanilla all smells associated with particular chemicals in old books.

researcher
The smell of heritage researcher Matija Strli with his nose in a book Photograph: Supplied

The project originated in Strlis observation of the importance of smell to conservators and librarians. Librarians have told us that its the smell that hits readers first. Its the way libraries communicate, before people even get to the books; but what the books communicate through smell is also interesting. The idea is to propose a large theoretical framework of which smells hold cultural value for us as a society, he says.

Strli, a professor of heritage science at UCL, is a chemist by training. We know very well how to analyse the chemicals, but what they mean, and the emotions they trigger, is a completely different matter. For that, you need a multi-disciplinary study, he says. It wasnt until the arrival of Bembibre a PhD student with a background in communications that the project began to acquire an anthropological and cultural breadth.

Libraries such as St Paul’s, dedicated to historic books, smell different to those housing more recent literature,” says Strli. “We know that books produced before approximately 1850 have a different smell to those produced between 1850 and 1990, and that’s because late 19th- and most 20th-century printing was dominated by acid sizing the process to which pulp was subjected to reduce the water-absorbancy of paper, so that it could then be written on.”

The life of individual books also affects their smell: how far they have travelled; whether they have been kept in damp or dry environments. As De Hamel points out, some manuscripts have hardly stirred from their original shelves since the day they were completed; others have zig-zagged across the known world in wooden chests or saddle bags, swaying on the backs of horses or over the oceans in little sailing ships, or as aircraft freight.

The medieval manuscripts De Hamel was dealing with were created by hand on long-lasting parchment made from animal skins which also have their own distinctive smell. Industrialised publishing from the mid 19th-century created less-hardy books, prone to a fate that every secondhand book collector fears: foxing, the brown blotches that appear on so many old volumes. Foxing happens when small impurities left by the metal beaters used to process the paper pulp combine with fungal growth on the ageing paper.

Many people assume the blotches themselves give old books their familiar musty pong. “In fact,” says Strli, “the smell is due to the release of chemicals such as furfural and hexanol as the paper itself decays.” Hexanol is often described as smelling farmlike or of old clothing or old room, which the odour wheel consigns to a category labelled earthy/musty/mouldy.

Bembibre
Bembibre investigating the science of book smells in the lab. Photograph: National Trust/James Dobson

But foxing itself is likely to be less prevalent as manufacturing changes. In the 1980’s, the technology changed because of environmental concerns about the chlorinated chemicals emitted through the manufacture process. The happy consequence of that was that the paper became more stable again, says Strli.

The researchers believe the historic book odour wheel could become a useful diagnostic tool for conservators across a wide range of areas, helping them to assess the condition of objects through their olfactory profile. If a book smells chocolatey, its likely that it is releasing vanillin, benzaldehyde and furfural three chemicals associated with the degradation of the cellulose and lignin in paper. But the study also has wider implications, as the heritage industry grapples with a new interest in the historical importance of smell. By documenting the words used to describe a heritage smell, our study opens a discussion about developing a vocabulary to identify aromas that have cultural meaning and significance, says Bembibre.

So what can the odour wheel tell us about Manguels description of Penguin books as smelling like fresh rusk biscuits? Biscuits is a word that often comes up when describing books. Two compounds in particular: furfural (smelling of sweetness or bread) and vanillin (smelling of vanilla) could be responsible, says Bembibre. His words might indicate that the books themselves are deteriorating, but they also reveal his pleasure in them. The gift industry has long wised up to this. The British Library shop, a few metres from the theatre where Manguel was speaking, sells a candle that purports to smell of library.

“This is not just about the composition of smell itself, but about human sensibility,” Bembibre says. “By reconstructing the smell and assessing the human reaction to it, we will be able to work out what it is that we want to preserve.”

Read more: https://www.theguardian.com/books/2017/apr/07/the-smell-of-old-books-science-libraries

Scientists create 3D-printed objects that can change shape after they’re printed

3D printed plastics tend to remain pretty stable over time. For example, your 3D-printed Yoda wont turn into a Chewbacca head without some severe plastic trauma until now. Scientists at MIT have created a 3D printing technique that allows you to change the polymers in an object after printing. This means you can grow or shrink and object, change its color, and even change its shape completely.

The idea is that you could print a material and subsequently take that material and, using light, morph the material into something else, or grow the material further, said Jeremiah Johnson, Associate Professor of Chemistry at MIT. Postdoc Mao Chen and graduate student Yuwei Gu led the research and wrote a paper on the findings.

The technique is called living polymerization and it creates materials whose growth can be halted and then restarted later on, according to the release.

The team first used a technique that involved a 3D printed object inside a solution. When you shined a UV light on the object while it was inside a solution the resulting chemical reaction released free radicals. These free radicals then bound to other monomers inside the solution, adding them to the original object. This was too reactive, however, and damaged the object.

The new technique uses polymers with chemical groups that act like a folded up accordion. When light hits the new materials they stretch out and change the material.

This let them create objects that changed stiffness in UV light and could grow and shrink when heated or cooled. They could even fuse two objects with just UV light.

Sadly you won’t be able to use this technology to morph a Millennium Falcon into the Death Star yet. However, the technology should make for some interesting materials experiments at MIT.

Read more: https://techcrunch.com/2017/01/16/scientists-create-3d-printed-objects-that-can-change-shape-after-theyre-printed/

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