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“Find and Replace” Across An Entire Genome

It couldn’t be easier to make sweeping edits on a computer document. If I were so inclined, I could find every instance of the word “genome” in this article and replace it with the word “cake”.

Now, a team of scientists from Yale and Harvard Medical School have done a similar trick for DNA. Geneticists have long been able to edit individual genes, but this group has developed a way of rewriting DNA en masse. And they’ve used it to recode the entire cake genome of a bacterium.

Their success was possible because the same genetic code underlies all life. It’s written in the four letters (nucleotides) that chain together to form DNA: A, C, G and T. Every set of three letters (or ‘codon’) corresponds to a different amino acid, the building blocks of proteins. For example, GCA codes for alanine; TGT means cysteine. The chain of letters is translated into a chain of amino acids until you get to a stop codon. These special triplets act as full stops that indicate when a protein is finished.

This code is virtually the same in every gene on the planet. In every human, tree and bacterium, the same codons correspond to the same amino acids, with only minor variations. The code also includes a lot of redundancy. Four DNA letters can be arranged into 64 possible triplets, which are assigned to only 20 amino acids or a stop codon. So for example, GCT, GCA, GCC and GCG all code for alanine. And these surplus codons provide some wiggle room for geneticists to play around with.

The Harvard and Yale team, led by Farren Isaacs and George Church, started TAG with TAA throughout the entire cake genome of the common gut bacterium Escherichia coli. Both are stop codons, so there’s no noticeable difference to the bacterium – it’s like replacing every full stop in this post with… a slightly different full stop. But to the team, the cake- genome-wide swap freed up the TAA codon, so that they could reassign it to other amino acids, beyond the usual 20.  And that opens up many possible applications for what they’re calling a “genomically recoded organism” or GRO.


The team is pursuing three applications. First, by assigning codons to new amino acids, they can create a wider range of proteins than the ones living things currently use. These, in turn, could produce new types of drugs or substances, from polymers that can deliver drugs to specific parts of the body to coated surfaces that can prevent the growth of microbes. The idea is that new amino acids will provide chemists and engineers with more options for achieving these goals, just like adding new colours to an artist’s palette changes the range of things they can paint. “You can imagine converting these recoded organisms into factories for producing materials with new and exciting properties,” says Isaacs.

Second, the team could use the tweaked genetic codes to make living things resistant to viruses. Viruses make copies of themselves by hijacking the protein-making factories of their hosts. They depend on the fact that their proteins are encoded by the same triplets as those of their hosts. If their hosts stray from this universal genetic code, their factories will mangle the virus’s instructions, creating distorted and useless proteins. That would be useful for industry as well as medicine. The biotechnology company Genzyme had to shut down a manufacturing plant for several months after it was hit by a contaminating virus. Millions of dollars were lost.

And sure enough, the team’s recoded microbes were less susceptible to at least one type of phage—a virus that kills bacteria. They weren’t invincible by any means, but the colonies did take longer to die. The effect was small, but not unexpectedly so. The TAG codon is rare (which is why the team started with it) and only found at the end of genes. Reassigning it shouldn’t have done that much to hamper a virus. But it did, which suggests that bigger changes might be even lead to complete protection.

Third, and for similar reasons, the altered codes could be used to contain genetically modified organisms, preventing them from breeding with wild populations. It’s the geneticist’s version of the Tower of Babel story – modified creatures would be imprisoned by their own genetic tweaks, unable to productively exchange genes with natural counterparts.


The recoding relied on two complementary technologies, invented by the team – MAGE, which substitutes TAA for TAG in separate pieces of bacterial DNA, and CAGE, which knits the pieces together into a whole genome.

MAGE, the older of the two techniques, made its debut two years ago. It stands for “multiplex automated genome engineering”, a fancy way of saying that it can easily change a genome many times over. It was originally used to create millions of small variants of bacterial genomes, producing a multitude of strains that can be tested for new abilities. As Jo Marchant puts it in her excellent feature, it’s an “evolution machine”. In its debut, within a matter of days, it had evolved a strain of E.coli that would produce large amounts of lycopene, a pigment that makes tomatoes red.

MAGE is a versatile editor. Not only can it create many diverse changes in a group of cells, it can also create many specific changes in a single cell. That’s what the team have now done. TAG appears in 321 places throughout the E.coli genome. For each one, the team created a small stretch of DNA that had TAA instead of TAG, surrounded by exactly the same letters. They fed these edited fragments into bacteria, which used them to build new copies of their own DNA. The result: daughter bacteria with edited genomes.

In this way, they created 32 strains of E.coli that, between them, had every possible substitution of TAG to TAA. This might seem overly complicated, but replacing every TAG with TAA in a single step would be inefficient, slow, and error-prone. A single mistake could be lethal for the microbes. By taking things slowly, and spreading the substitutions among 32 strains, the team could better troubleshoot any tricky snags.

To combine the 32 strains into one, the team developed CAGE (or “conjugative assembly genome engineering”). The technique relies on the bacterial equivalent of sex – a process called conjugation where two cells sidle up, form a physical link between one another, and swap DNA.

The team matched their 32 strains up in pairs, in a league that looked like a knock-out sports tournament. One strain of each pair would deliver its edited genes into its partner, and the incoming genes were designed to merge with those of the recipient in specific ways. Thirty-two strains with 10 edits each became sixteen strains with 20 edits each. Sixteen turned into eight and eight into four.

When I first wrote about this in 2011, the team reached this “semi-final” stage. They had four strains of E.coli, each with a quarter of its genome stripped of TAG codons. Now, they’ve gone all the way, producing a single strain where every TAG is now a TAA. They also managed to get rid of release factor 1 (RF1), a protein that recognises TAG as a stop signal and halts the production of whatever protein’s being made.

The recoded microbe picked up 355 mutations along the way, but it seemed outwardly normal and  reproduced at a healthy pace. With TAG free from its duties as a punctuation mark, the team could reassign it to new amino acids, just as they planned. “In a plug and play manner, you can start to pop in new amino acids with new chemistries,” says Isaacs.

And as the team hoped, the new strain was more resistant to viruses than normal ones… but not completely resistant. To realise the ultimate goal of making virus-proof or genetically-contained organisms, they’ll have to do much more than replace one stop codon.

What next?

Next, the team need to start recoding the “sense codons”—the ones that actually correspond to amino acids.  And that is a lot harder. If you alter these sequences, you could screw up how genes are switched on or off, how efficiently or accurately they’re used to make proteins, how well those proteins work once they’re made, and more. And since bacterial genes overlap a lot, if you change a single instance of a single codon, you could be messing up three different genes at once. “There are a lot of things that can go wrong, and that’s not even an exhaustive list,” says Marc Lajoie, the lead author of the new research. “It’s just the stuff we know about.”

Also, sense codons are far more common than stop codons. E.coli has 321 instances of TAG in its genome. Add the next rarest codons—AGA and AGG—and you have upwards of 5,000 changes to make. If you want to recode just the 13 rarest ones (which the team calls the “forbidden codons”), you’d have to make 155,000 changes. Things get difficult fast.

To start with, Lajoie and Siriam Kosuri tried to recode the forbidden codons—completely substituting them for replacements that code for the same amino acid. And rather than doing it across the entire E.coli genome, they focused on recoding just 42 essential genes, one at a time. That makes for a manageable total of 405 changes rather than 155,000. Still, this is the sort of experiment where you imagine scientists interlacing their fingers, stretching their arms out to crack all of their knuckles, and then getting down to it.

“Changing TAG throughout the entire genome was a way of getting our feet wet. That project was intended to succeed,” says Lajoie. “In this one, we were actually looking to fail.” They wanted to see what would work and what wouldn’t.

They found that 26 of the 42 recoded genes were successful—that is, bacteria that carried them survived and, on average, grew just 20 percent slower than their normal kin. And perhaps more importantly, every single one of 405 forbidden codons could be recoded either individually or in small groups. None of them in itself was a deal-breaker. All of them could be replaced to an extent.

“That was a surprise and very encouraging to us,” says Lajoie. It means that all of these are “amenable to genome-wide removal”. The circumstances that determine success or failure will lie in the quirks of each specific gene, and can potentially be dealt with.

“Through this tour de force of genome engineering, they’ve essentially shown that there are no large fundamental barriers to codon reassignment,” says Chang Liu, a biomedical engineer from the University of California, Irvine. “Rather, it is an exercise in overcoming an array of small hurdles, each of which we already have the technology to address.”

The team is now building on this pilot, and start replacing sense codons across the entire E.coli genome. That will allow them to take their technique from the world of impressive demos into actual applications. But more than that, it will help them to probe the very nature of our genetic code. How did it evolve? Why is it structured the way it is, with three letters to a codon? And how malleable is it? “Only now do we have the ability to start making fundamental changes to the code and seeing the consequences,” says Isaacs.

Lajoie adds, “We’re only starting to see all of the tangled constraints that determine how genomes work. Nobody understands the full complexity – that’s why it’s so difficult.”

Reference: Lajoie, Rovner, Goodman, Aerni, Haimovich, Kuznetsov, Mercer, Wang, Carr, Mosberg, Rohland, Schultz, Jacobson, Rinehart, Church & Isaacs. 2013 Genomically Recoded Organisms Expand Biological Functions. Science http://dx.doi.org/10.1126/science.1241459

Lajoie, Kosuri, Mosberg, Gregg, Zhang & Church. 2013. Probing the Limits of Genetic Recoding in Essential Genes. Science  http://dx.doi.org/10.1126/science.1241460

Note: This post builds upon an earlier one published in 2011. A bit like science, then.

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So Science…Might Have Gotten It Wrong. Now What?

Last week, I wrote about a scientific paper that was published in the elite journal Nature in 1995. Within a couple of years, the findings of said paper were called into question by several other papers in different journals. As of today, nearly two decades since the original came out, nobody has replicated it. And yet, it’s still sitting there in the literature, still influencing others. It’s been cited nearly 1,000 times.

Some readers were angry with my post, arguing, for example, that “science’s self-correcting paradigm works over decades”. Indeed, that was my point. Science’s self-correction is generally very slow — perhaps, as many argue, too slow.

This week I learned about an unfolding scientific debate that’s got me thinking again about the challenge — the impossibility? — of swift and sure scientific correction. What does it mean when one group of researchers, or even two or three groups, can’t replicate a particular scientific finding? Does that necessarily mean it’s wrong? At what point should a scientist give up on a new idea for lack of supporting evidence?

That unfolding debate started in late 2011, when Chen-Yu Zhang’s team from Nanjing University in China found something pretty wild: bits of rice RNA floating in the bloodstreams of Chinese men and women. That might not seem so strange; rice was a primary ingredient of their diets, after all. But RNA molecules are pretty fragile. So the discovery shocked and intrigued many biologists.

“It’s just a very neat new physiologic mechanism,” says Ken Witwer, a molecular biologist at Johns Hopkins University in Baltimore. “How is it that a small RNA, or any RNA, could survive this trip from the mouth, with all these enzymes in saliva, down into the stomach, with the acidic environment there, and make it all the way into the gut, to the point that it could cross over into the blood? What form would this RNA have to be in to make that journey?”

Even more provocative: Zhang’s study also showed that in mice, those same tiny pieces of plant RNA — dubbed microRNA or miRNA, and made up of just two-dozen nucleotides, or letters of code — can shut down a gene involved in cholesterol uptake.

The study had big implications for medicine and our food supply. For instance, it suggested that researchers might be able to design oral RNA drugs for a host of diseases, “one of the holy grails” of the field, Witwer says. The data also provided evidence, at least according to a press release issued by Zhang, that miRNAs are “essential functional molecules” in Chinese herbal remedies. Finally, some people — like the author of a controversial* column published in The Atlantic — used the study to argue that genetically modified organisms (GMOs) are harmful to eat (despite loads of evidence to the contrary). (Update 7/9:  See below a response from the author of that column.)

Andres Rodriguez, via Flickr
Andres Rodriguez, via Flickr

So the paper made its media splash. And in the 21 months since its publication, the work has been cited in 42 other papers, according to Web of Knowledge.

A few of those could be considered replication studies. In one, David Galas of the Pacific Northwest Diabetes Research Institute, in Seattle, performed genetic sequencing of human blood samples and found low levels of miRNA from many species, including bacteria, fungi, insects, and plants. Galas’s team detected the same specific rice miRNA that Zhang had — dubbed miR-168 — albeit at far lower levels than Zhang had.

Two other follow-up studies were bankrolled by agricultural giant Monsanto (which, it must be said, sells GMOs and thus has a big stake in claims that they’re dangerous). The Monsanto researchers combed through large datasets of genetic sequences obtained from mammals, chickens, and insects, looking for any trace of plant miRNAs. They found them in some of the datasets, but again, at very low levels. And sometimes the data didn’t make sense — they found miR-168, for example, in animals that had never eaten food containing miR-168, suggesting that it could have been the result of a contamination, Witwer says. “We know that pollen has miRNAs in it, and depending on the time of the year, maybe we have more pollen contamination, even in our best labs, than at other times.”

The July issue of RNA Biology adds two more skeptical papers to the mix. In one of them, Witwer’s team fed monkeys a Silk fruit and protein shake, which happens to contain high levels of miR-168 and other plant miRNAs. The researchers tested the animals’ blood for miRNAs before the feeding and 1, 4, and 12 hours after the feeding.

The scientists used the same method that Zhang’s group had: polymerase chain reaction, or PCR, which allows researchers to identify specific segments of DNA or RNA by copying them over and over again, and then fluorescing the copies. When Witwer’s team used PCR to find miRNAs in the smoothies, the results were sensitive and consistent. But when looking at the monkeys’ blood, the PCR data were much more variable. “We weren’t completely confident in the accuracy of the method,” Witwer says.

So his team repeated the experiment using a newer and more precise type of PCR, called droplet digital PCR. This time, they again saw a lot of variability in the blood data, and no consistent differences between the samples taken before and after the animals ate the shakes. Witwer’s conclusion: Plant miRNAs probably don’t transfer into our blood after digesting it, at least not in quantities anywhere near what Zhang’s group had reported.

In the other new paper, Stephen Chan of the Brigham and Women’s Hospital in Boston found that healthy athletes did not carry detectable levels of plant miRNAs in their blood after eating fruit chock-full of those molecules. The scientists also couldn’t find this kind of transfer in experiments with mice and bees. “We conclude,” the paper states, “that horizontal delivery of microRNAs via typical dietary ingestion is neither a robust nor a frequent mechanism.”

Forest Wander, via Flickr
Forest Wander, via Flickr

So what do all of these studies say about this particular finding, and more generally, about science’s self-correcting process?

Less than two years after the original paper came out, at least five studies have followed it up. And in my (utterly non-expert) judgment, it seems like none of them meaningfully replicate Zhang’s paper. (Zhang has not responded to my request for comment; I will update the post if/when he does. Update, 7/8: Zhang has responded to my request for comment; see his full response at the bottom of this post.)

The studies are consistent in finding very low levels of plant miRNAs in people and a variety of other species. Witwer says that’s enough evidence of a non-result to move on from the whole idea. “I’m willing to help out if someone’s organizing an attempt to replicate something, but I’m probably not going to devote my lab to answering more questions on this issue,” he says. “We’ve convinced ourslves that we’re not seeing anything here.”

Others, though, aren’t ready to drop it. Galas, whose paper found miR-168 in low levels in human blood, says the only thing we know for sure is how difficult the question is to study. “The major result is that miRs are difficult to measure accurately,” he says. What’s more, he says, Witwer’s feeding experiments aren’t necessarily damning because their specifics differ from the original Zhang paper.

For Galas, the current data only makes the question more worthy of study by the RNA community, not less. “This is a an important topic to get pinned down — the potential for new biological phenomena is significant.”

This story helps explain why science’s self-correction process can’t be super-quick. It takes time for evidence to accumulate and show clear trends. That said, scientists could be better at making that correction process more efficient. One step, Witwer says, is transferring published data into public repositories that can be easily shared with the scientific community.

As Witwer reported in February, less than 40 percent of studies reporting microRNA sequencing data submitted that data to public databases. More interesting: The scientists who did share were more likely to have high-quality papers. The only paper in the analysis to be retracted, by the way, was one that did not share its raw data.

“I think that science can be self-correcting,” Witwer says, “but it requires people to do that correcting.”

*That column was rightfully struck down by science bloggers Emily Willingham and Christie Wilcox, and because of their posts, the author eventually amended it. The self-correction of the blogosphere is just a tad faster than the self-correction of science, eh? (UPDATE 7/9: The author of the column says his re-write had nothing to do with the bloggers; see his full comment here.)

UPDATE #1 (7/4): Also, just noticed that the incomparable Willingham beat me to this story a couple of weeks ago! Go check out her post at Forbes.

UPDATE #2 (7/8): Dr. Zhang sent me a lengthy letter in response to my request for comment about Dr. Witwer’s new study. You can read that (in .pdf form) by clicking here.

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Engineering mosquito gut bacteria to fight malaria

A malarial mosquito is a flying factory for Plasmodium – a parasite that fills its guts, and storms the blood of every person it bites. By hosting and spreading these parasites, mosquitoes kill 1.2 million people every year.

But Plasmodium isn’t the only thing living inside a mosquito’s guts. Just as our bowels are home to trillions of bacteria, mosquitoes also carry their own microscopic menageries. Now, Sibao Wang from Johns Hopkins Bloomberg School of Public Health has transformed one of these bacterial associates into the latest recruit in our war against malaria. By loading it with genes that destroy malarial parasites, Wang has turned the friend of our enemy into our friend.

Many groups of scientists have tried to beat malaria by genetically modifying the species of mosquito that carries it – Anopheles gambiae. Marcelo Jacobs-Lorena, who led Wang’s new study, has been at the forefront of these efforts. In 2002, his team loaded mosquitoes with a modified gene so that their guts produce a substance that kills off Plasmodium.


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Genetically engineered silkworms with spider genes spin super-strong silk

In a lab at the University of Wyoming, some silkworms are spinning cocoons of silk, just as every silkworm has done for millions of years. But these insects are special. They have been genetically engineered to spin a hybrid material that’s partly their own silk, and partly that of a spider. With spider DNA at their disposal, they can weave fibres that are unusually strong and tough. It’s the latest step in a decades-long quest to produce artificial spider silk.

Spider silk is a remarkable material, wonderfully adapted for trapping, crushing, climbing and more. It is extraordinarily strong and tough, while still being elastic enough to stretch several times its original length. Indeed, the toughest biological material ever found is the record-breaking silk of the Darwin’s bark spider. It’s 10 times tougher than Kevlar, and the basis of webs that can span rivers.


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Without some basic science, GM mosquitoes won’t bite

There have been several stories recently about genetically modified mosquitoes, bred for the purpose of fighting diseases like malaria and dengue fever. These are exciting, sophisticated techniques, but in a new piece for Slate, I argue that they’re being let down by the fact that we still don’t know a lot about basic mosquito biology, like thier mating behaviour. Ecology may not be as sexy as tinkering with genes, but history teaches us that it’s vital if these approaches are to work.

Here’s a taster; head to Slate for more.

But all of these recent attempts to turn mosquitoes into malaria- and dengue-killing machines have something in common: The modified mosquitoes need to have lots of sex to spread their altered genes through the wild population. They must live long enough to become sexually active, and they have to compete successfully for mates with their wild peers. And that is a problem, because we still know surprisingly little about the behavior and ecology of mosquitoes, especially the males. How far do they travel? What separates the Casanovas from the sexual failures. What affects their odds of survival in the wild? How should you breed the growing mosquitoes to make them sexier? Big question marks hang over these seemingly straightforward questions.

Heather Ferguson from the University of Glasgow studies mosquito ecology. She views the knowledge gap in this field as a significant obstacle that stands in the way of the GM-mosquito initiatives. History tells us how dismally such initiatives can fare if they are not constructed on solid ecological foundations. In the 1970s and 1980s, several groups tried to control the mosquito population by releasing sterile males that would engage females in fruitless sex. The vast majority of the experiments failed.

Their poor performance is often blamed on the fact that the males were sterilized with damaging doses of radiation. But they had many other disadvantages. Lab-bred mosquitoes are frequently reared in large, dense groups, which produces smaller, less competitive individuals. The artificial lights of a lab could also entrain their body clocks to the wrong daily rhythms, driving them to search for mates at the wrong time of the day. And in several cases, the modified males ignored the wild mosquitoes and preferred to mate with their lab-reared kin instead. These problems went unnoticed in lab tests, where the modified mosquitoes were compared with unaltered ones that had been raised in the same conditions. They seemed to be perfectly competitive, but they proved to be feeble challengers to their wild peers.

Picture by James Gathany

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Hacking the genome with a MAGE and a CAGE

It couldn’t be easier to make sweeping edits on a computer document. If I were so inclined, I could find every instance of the word “genome” in this article and replace it with the word “cake”. Now, a team of scientists from Harvard Medical School and MIT have found a way to do similar trick with DNA. Geneticists have long been able to edit individual genes, but this group has developed a way of rewriting DNA en masse, turning the entire genome of a bacterium into an “editable and evolvable template”.

Their success was possible because the same genetic code underlies all life. The code is written in the four letters (nucleotides) that chain together to form DNA: A, C, G and T. Every set of three letters (or ‘codon’) corresponds to a different amino acid, the building blocks of proteins. For example, GCA codes for alanine; TGT means cysteine. The chain of letters is translated into a chain of amino acids until you get to a ‘stop codon’. These special triplets act as full stops that indicate when a protein is finished.

This code is virtually the same in every gene on the planet. In every human, tree and bacterium, the same codons correspond to the same amino acids, with only minor variations. The code also includes a lot of redundancy. Four DNA letters can be arranged into 64 possible triplets, which are assigned to only 20 amino acids and one stop codon. So for example, GCT, GCA, GCC and GCG all code for alanine. And these surplus codons provide enough wiggle room for geneticists to play around with.

Farren Isaacs, Peter Carr and Harris Wang have started to replace every instance of TAG with TAA in the genome of the common gut bacterium Escherichia coli. Both are stop codons, so there’s no noticeable difference to the bacterium – it’s like replacing every word in a document with a synonym. But to the team, the genome-wide swap will eventually free up one of the 64 triplets in the genetic code. And that opens up many possible applications.


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Gene therapy saves patient from lifetime of blood transfusions

Gene_therapyThe patient known as P2 is just 18 years old, but he has been receiving monthly blood transfusions since the age of 3. P2 has a genetic disorder called beta-thalassaemia. Thanks to a double whammy of faulty genes, he can’t produce working versions of haemoglobin, the protein that allows red blood cells to carry oxygen around the body. Regular transfusions were the only things that kept him alive but for the last 21 months, he hasn’t needed them.

An international team of scientists have managed to partially correct his genetic faults, granting him his independence. It’s a major victory for gene therapy, the act of editing faulty genes within living cells in order to treat diseases.


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Genes from Arctic bacteria used to create new vaccines


Walk among the Arctic ice and you’ll sometimes encounter distinctive patches of red snow. They’re caused by a species of bacteria called Colwellia psycherythraea. It’s a cold specialist – a cryophile – that can swim and grow in extreme subzero temperatures where most other bacteria would struggle to survive. Colwellia’s cold-tolerating genes allow it to thrive in the Arctic, but Barry Duplantis from the University of Victoria wants to use them in human medicine, as the basis of the next generation of anti-bacterial vaccines.

Colwellia’s fondness for cold comes at a price – it dies at temperatures that most other bacteria cope with easily. By shoving Colwellia genes into bacteria that cause human diseases, Duplantis managed to transfer this temperature sensitivity, creating strains that died at human body temperature. When he injected these heat-sensitive bacteria into mice, they perished, but not before alerting the immune system and triggering a defensive response that protected the mice against later assaults. The Colwellia genes transformed another species of bacteria from a cause of disease into a vaccine against it.


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Unintentional genetic engineering – grafted plants trade genes

Blogging on Peer-Reviewed ResearchFor centuries, farmers have been genetically modifying their plants without even knowing it. That’s the message from German scientists who found that grafting, a common technique used to fuse parts of two plants together, causes the two halves to swap genes with each other.

Grafting can involve fusing the stem of one plant (the scion) to the roots of another (the stock), or a dormant bud to another stem. There are many reasons for this – sometimes it’s the most cost-effective way of cultivating the scion, sometimes the stock has properties that the scion lacks including hardiness or sturdiness. The vessels of the two halves eventually merge but people have long believed that they keep their genetic material to themselves. It turns out they were wrong.

Sandra Stegemann and Ralph Bock from the Max-Planck Institute tested the theory by grafting two strains of genetically engineered tobacco plant. A Samsun NN strain had its main genome loaded with a gene that produced a glowing yellow protein, and another that made the plant resistant to the antibiotic kanamycin. The second Petit Havana strain was engineered to produce a glowing green protein, and be resistant to spectinomycin, another antibiotic. These genes were shoved into the genome of its chloroplast, the small structures that allow plant cells to photosynthesise and that contain their own separate genetic material.

Once the plants had merged, Stegemann and Bock found that the point of fusion was rife with cells that produced both glowing proteins and shrugged off both antibiotics. They cut slices from the plant and grew them in liquid that contained both kanamycin and spectinomycin for a month. While chunks that were taken from other parts of the plant fared poorly under these conditions, many of those from the graft site thrived, even producing fresh shoots.


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The effect of GM crops on local insect life


Blogging on Peer-Reviewed ResearchA large study weighs up the existing evidence on the impact of GM crops on local insect life, providing some much-needed scientific rigour to the GM debate.

In Europe, the ‘GM debate‘ about the merits and dangers of genetically-modified (GM) crops is a particularly heated one. There is a sense of unease about the power of modern genetic technology, and a gut feeling that scientists are ‘playing God‘. These discontents are stoked by the anti-GM camp, who describe GM crops with laden and fear-mongering bits of unspeak like ‘Frankenstein foods‘ and ‘unnatural’.

Bt cotton is better for non-targeted insects than non-resistant crops sprayed with insecticdes.In a debate so fuelled by emotion and personal values, scientific research and a critical analysis of the evidence rarely gets a look-in. But science has to grudgingly admit some blame in this, because there is actually precious little research on the safety of GM crops. And many of the studies that have been done were short-term and poorly replicated.

A lack of research is dangerous. It provides opening for people on either side of the debate to quote single, small studies as canon and brushing aside any research that contrasts with their stances.

Michelle Marvier and colleagues from Santa Clara University, California, are trying to change all that. They have analysed over 42 field experiments on GM crops to get an overall picture about their safety. The technique they used is called meta-analysis, a statistical tool that asks “What does everyone think?” It works on the basis that individual small studies may be far from conclusive, but pooling their results together can lead to stronger and more accurate results.


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Genetically-modified mosquitoes fight malaria by outcompeting normal ones


Blogging on Peer-Reviewed ResearchFighting malaria with mosquitoes seems like an bizarrely ironic strategy but it’s exactly what many scientists are trying to do. Malaria kills one to three million people every year, most of whom are children. Many strategies for controlling it naturally focus on ways of killing the mosquitoes that spread it, stopping them from biting humans, or getting rid of their breeding grounds.

anophelesgambiaemosquito.jpgBut the mosquitoes themselves are not the real problem. They are merely carriers for the true cause of malaria – a parasite called Plasmodium. It suits neither mosquitoes nor humans to be infected with Plasmodium, and by helping them resist it, we may inadvertently help ourselves. With the power of modern genetics and molecular biology, scientists have produced strains of genetically engineered mosquitoes that cannot transmit the malarial parasite.

These ‘GM-mosquitoes’ carry a modified gene – a transgene – that produces chemicals which interfere with Plasmodium‘s development. Rather than being suitable carriers, the bodies of the modified mosquitoes spell death for any invading Plasmodium.

But scientists can’t very well change the genes of every mosquito in the tropics. To actually reduce the burden of malaria, the genetic changes that induce malaria resistance need to be spread throughout the mosquito population. The easiest way to do this is, of course, to let the insects do it themselves. And Mauro Marrelli and colleagues from the Johns Hopkins University have found that they are more than up to the task.


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How to turn cotton into a food crop


Blogging on Peer-Reviewed ResearchThe world is currently home to 6.5 billion people and over the next 50 years, this number is set to grow by 50%. With this massive planetary overcrowding, Band Aid’s plea to feed the world seems increasingly unlikely. Current food crops seem unequal to the task, but scientists at Texas University may have developed a solution, a secret ace up our sleeves – cotton.

Cotton.JPGCotton is famed for its use in clothes-making and has been grown for this purpose for over seven millennia. We do not think of it as a potential source of food, and for good reason. The seeds of the cotton plant are rife with a potent poison called gossypol that attacks both the heart and liver. Only the multi-chambered stomachs of cattle and other hooved animals can cope with this poison, relegating cottonseed to a role as animal feed.

Getting rid of gossypol could contribute towards reducing the world’s hunger crisis. A fifth of a cottonseed’s weight is made up of oil, and a quarter of high-quality protein, and for every kilogram of fibre, each cotton plant produces 1.65 kg of seed. The plant is a worldwide crop, grown in over 80 countries by some 20 million farmers, the majority of whom live in the poorest parts of the world where starvation is an ever-looming threat. If only the seeds could be made edible.


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Genetically modified cotton protects surrounding crops from moth

Blogging on Peer-Reviewed ResearchGenetically modified crops have received a frosty welcome in the UK, and more widely in Europe. Those opposed to such crops worry (among other things) that they could affect the flora around them by outcompeting them or by spreading their altered genes in a round of genetic pass-the-parcel. Now, a new study shows that genetically-modified crops does affect surrounding plants – but in a positive way. 

Bollworm1.jpgKong-Ming Wu from the Chinese Academy of Agricultural Sciences found that genetically modified cotton designed to kill an insect pest can also protect other species plants from its jaws. In doing so, this “Bt cotton” could help to reduce the need and demand for other sprayed insecticides. 

Bt cotton has been loaded with insect-killing genes taken from a bacterium called Bacillus thuringiensis (hence “Bt”). This species lives in soil and the surface of plants, and it produces crystals of proteins that are toxic to hungry insects. If they are swallowed, they stick to molecules in the pest’s gut, breaking down its lining and allowing both B.thuringiensis spores and colonies of normal gut bacteria to invade. It’s this wanton spread of bacteria that kills the animal.