Bedbug genome sequenced for the first time, casting light on insecticide resistance

Researchers have sequenced the genome of the common bedbug for the first time, providing unprecedented insight into one of the world’s most troublesome urban pests.

The highly ambitious project, which involved 36 different institutions and over 80 scientists, used samples from both preserved and living bedbugs, known more technically as Cimex lectularius, to sequence both DNA and RNA. The oldest samples used have been held by the American Museum of Natural History (AMNH) since their acquisition in 1973.

“It’s not enough to just sequence a genome, because by itself it does not tell the full story,” said Mark Siddall, study corresponding author and curator in AMNH’s Division of Invertebrate Zoology and Sackler Institute for Comparative Genomics.

“In addition to the DNA, you want to get the RNA, or the expressed genes, and you want that not just from a single bedbug, but from both males and females at each part of the life cycle. Then you can really start asking questions about how certain genes relate to blood-feeding, insecticide resistance and other vital functions.”

Image courtesy of Benoit Guenard / North Carolina State University. Featured image courtesy of Graham Snodgrass / Armed Forces Pest Management Bureau via the University of Rochester.

Image courtesy of Benoit Guenard / North Carolina State University. Featured image courtesy of Graham Snodgrass / Armed Forces Pest Management Bureau via the University of Rochester.

Bedbugs have soared in numbers in recent years. In Australia alone bedbug infestations have risen 4,500% since 1999.

“Bedbugs all but vanished from human lives in the 1940s because of the widespread use of DDT, but, unfortunately, overuse contributed to resistance issues quite soon after that in bedbugs and other insect pests,” said Louis Sorkin, study co-author and senior scientific assistant in AMNH’s Division of Invertebrate Zoology. “Today, a very high percentage of bedbugs have genetic mutations that make them resistant to the insecticides that were commonly used to battle these urban pests.”

“Nobody was ready for this,” added Michael Scharf, the O Wayne Rollins / Orkin Chair in Molecular Physiology and Entomology at Perdue University. “It’s reached almost a crisis condition. All big cities in the US are experiencing problems. Our culture had forgotten about bedbugs, and two generations of entomologists haven’t had to deal with them.”

Image courtesy of Andrew Nuss / Purdue University.

Image courtesy of Andrew Nuss / Purdue University.

The research has produced numerous insights into bedbugs that may aid their extermination, but one finding in particular stands out: the presence of genes from the bacteria Wolbachia in the bedbug genome. The result of a process known as lateral gene transfer, the gene appears to only function in male bedbugs.

“Genomic sequences from Wolbachia are present in the bedbug genome,” said Coby Schal, project co-leader and North Carolina State University Blanton J Whitmire Distinguished Professor of Entomology. “We don’t know if the bacterium is co-opting the bedbug or if the bedbug is co-opting the bacterium. Very few of these bacterial genes are functional and we don’t know what proteins they are producing. But it would be fascinating if bacterial genes that are useful to the bedbug, such as those involved in B vitamin metabolism, were incorporated into the bedbug genome.”

“Because the inserted genes create unique genetic profiles in bedbugs, they have the potential of becoming effective targets for pest control,” added Jack Werren, professor of biology at the University of Rochester.

Image courtesy of L. Sorkin / American Museum of Natural History

Image courtesy of L Sorkin / American Museum of Natural History.

By using samples from across the bedbugs’ lifecycle, the researchers were also able to identify specific stages where they would be most resistant to insecticide.

In particular, certain genes that were only expressed after the bedbugs drank blood for the first time were found to be linked to insecticide resistance, as they provided, for example, improved detoxification or thicker skin – known as chitin.

As a result, future insecticides may be developed to target bedbugs at the first nymph stage, before they have had a chance to sample human blood.

The research was published today across two papers in the journal Nature Communications. They can be accessed here and here.

Possibly inspired by Jurassic Park, there are scientists out there exploring the realities of de-extincting dinosaurs. But is that goal achievable or are scary, deformed chicken the best that we can do? To find out whether de-extincting dinosaurs – and Elvis – is possible we spoke to author and performer Helen Pilcher

Science and fiction have always had a kind of chicken and egg relationship, so with many discoveries it can be difficult to discern what came first: did science inspire fiction or has science been developed to emulate pre-existing works of fiction? In the case of the quest to de-extinct dinosaurs, believe it or not it was technically the scientific breakthrough that came first. So for anyone who’s seen the original Jurassic Park, this anecdote told by Helen Pilcher, author of Bring Back the King: The New Science of De-extinction, might sound a little familiar.

“There was a scientist called Hendrik Poinar who was looking at insects trapped in amber and he got dreadfully excited one day because the dogma was you couldn’t get DNA from these insects,” says Pilcher. “He got really excited because he actually managed to zoom in on that insect and he saw structure inside those cells, so he saw for the first time a nucleus, which is the control centre of a cell where the DNA lives. He saw these through his microscope and he had this epiphany where he thought: ‘well oh my God, the structure is actually preserved in these cells; how big a leap is it that there could be DNA inside that nucleus?’

“At the time we didn’t really have the techniques to find out if that was the case or not, but it got people thinking,” explains Pilcher. “In fact what’s really interesting is that Michael Crichton [author and scriptwriter of Jurassic Park] actually visited Hendrik Poinar in his lab because he’d got wind of what Poinar was up to.

“It was only, I think, quite some years later when a representative from the film studios behind Jurassic Park rang Hendrik up that he put two and two together and realised that the person that had visited him was this talented author and writer with a genuine interest in the science.”

Featured image courtesy of Universal Pictures

Despite science happening first, there’s no doubt the desire to de-extinct the dinosaur has been influenced by the film Jurassic Park. Maybe not the scene where the T. Rex escapes and kills the lawyer on the toilet, but the scene where Sam Neill and Laura Dern’s characters stand drooling over a benign Brachiosaurus as it gulps down leaves from trees high above them. Who hasn’t dreamed of being there to see that?

But to de-extinct a dinosaur we’d need a sample of their DNA, and since dinosaurs became extinct around 65 million years ago that’s not exactly easy to come by, no matter how many insects in amber you find. But around three decades on from Poinar’s discoveries and Crichton’s (and Steven Spielberg’s) work, has science developed to the point where it can fulfil the vision that was ultimately realised in the fictitious Jurassic Park?

In other words, will I ever be able to walk with Brachiosaurs or run from T. rex?

The Science Behind De-Extinction

In Jurassic Park, scientists create dinosaurs from the blood of insects preserved in amber and then fill any gaps in their DNA sequence with the DNA of a frog. Unfortunately, for anyone wanting to resurrect the dinosaurs, this process is what is known in scientific fields as complete film bullshit.

To de-extinct an animal of any type you need a source of its DNA because DNA is the starting material needed to retrieve an animal’s genome. The genome is the complete set of DNA inside a cell and the full set of instructions for creating an animal. So, for example, if we wanted to create a T. rex, we’d need a copy of the T. rex’s genome, but genomes, and DNA, are very fragile. While we’re alive our DNA is constantly breaking down and getting damaged, but our cells fix that for us so we can get by. But when we die our DNA starts to decay and the long strands of DNA that exist inside our cells get broken down into smaller and smaller fragments until there comes a time when there’s nothing left.

It was the Nobel Prize winning chemist Tomas Lindahl who worked out that DNA has a half-life of 521 years. That means that after roughly 500 years half of all the links in a strand of DNA will be gone, and 500 years after that half again. DNA is a disappearing entity.

“The bad news for dinosaur fans is there comes a point when there’s no DNA left to be found,” says Pilcher. “The oldest DNA that anybody has ever retrieved from a fossil was from a horse pulled out of the permafrost in Northern Canada. The horse was 700,000 years old.

“The theoretical limit for retrieving DNA is probably 1 to 2 million years, so we might find we get DNA from something a little bit older than that horse, but probably not that much older. Dinosaurs, well the things we think of as dinosaurs, T. Rex and Stegosaurus etcetera, went extinct 65 million years ago when a massive asteroid slammed into the Earth, so their DNA is just long gone; full stop.”

Warped and Weird Looking Chicken Park

So we can’t get dinosaurs by using their DNA to clone them because we just don’t have any. But, undeterred, some scientists aren’t willing to let a little thing like the practical realities of cloning get in the way of progress; they believe, to pervert Jeff Goldblum’s monologue from Jurassic Park, “Life finds a way.”

If we are ever to see dinosaurs again then the man responsible may well be palaeontologist Jack Horner, who served as a consultant on all four Jurassic Park films.  Horner’s plan hinges on the idea that all animals share a lot of very similar genes, and what makes a human different from a chimp or a dinosaur is the way genes are switched on and off. Generally we have a common shared evolutionary path at the DNA level, so what Horner is proposing is that he take an early chicken embryo and alter which genes are turned on and which genes are turned off.

The signals needed for a chicken to sprout a dinosaur tail or to grow teeth are still there. It’s just a matter of flicking the right genetic switch

If you’ve watched Jurassic Park, you’ll know that dinosaurs had a lot in common with present day birds, and Horner believes that the signals needed for a chicken to sprout a dinosaur tail or to grow teeth are still there. It’s just a matter of flicking the right genetic switch.

As Pilcher points out, Horner’s plan isn’t without merit, but anyone imagining he could create a magnificent beast like a T. rex is going to be bitterly disappointed. Although, if a “warped and weird looking chicken” park sounds appealing to you then you just might be in luck.

“There are people out there who study the way embryos develop. These are not people who want to bring dinosaurs back to life these are people that work in human research, and they study things like how hands are formed or why a snout is different to a beak,” says Pilcher. “There are examples out there in the scientific literature where people have changed gene expression in chicken embryos and they’ve turned certain genes on or off and they have created embryonic chickens with teeth for example.

“These experiments, and this is really important to stress, were never designed to produce live freakish birds; this is about understanding the process of embryonic development and these chicks for ethical reasons were never allowed to hatch. So that kind of gives some credence to Jack Horner’s argument, but I don’t think he’s ever going to succeed in making anything that is a satisfactory dinosaur and there are lots of reasons for this. I think the best he’s going to come up with is a very warped and weird looking chicken, and I think if people out there are fans of Jurassic Park, and like me have grown up wanting to meet a T. rex, I think it’s going to be a big disappointment.”

Who Cares About Dinosaurs?

Unfortunately we can’t bring back dinosaurs, or at least we can’t bring back the dinosaurs we want like a T. rex or a Brachiosaurus, but we may have more success bringing back other animals. Consider the story of a wild mountain goat named Celia.

Image courtesy of Ivan

Celia belonged to a specific species of wild goat called the bucardo. For several reasons – including hunting – the bucardo population had been in severe decline when, in the year 2000, Celia, the last remaining animal of her kind, was killed by a falling tree in the National Park of Ordesa in north-east Spain. With Celia gone the bucardo were extinct.

Thankfully though, a year earlier researchers had taken skin samples from Ceila and frozen the tissue in liquid nitrogen. The sample was used to inject nuclei from Celia’s preserved cells into goat eggs that had been emptied of their own DNA, and in 2003 a baby bucardo was born. It was the world’s first successful de-extinction. The clone of Celia died a few minutes after birth due to a defect in one of its lungs, making the bucardo the only animal to go extinct twice, but with technology improving apace, the resurrection of the bucardo shows the power of de-extinction not to just bring back fanciful beasts but also its power to conserve the animals we’re losing right now.

“De-extinction is also about preserving ecosystems,” says Pilcher. “It’s about trying to preserve the planet that we have, which is something that we’re already trying to do, so I think de-extinction is something else in the conservation toolkit. I don’t think it’s going to be widely used. I don’t think it’s the only answer, but I think it could be part of the solution.”

Elvis World

But let’s be honest Jurassic Park wouldn’t have been the same movie if its heroes had been running from bucardo and the like. What we really want to see in fiction and in science is spectacle, and if we want spectacle then there’s really only one man we can bring back: Elvis. In her book, Pilcher details a thought experiment she explored: if all we need to de-extinct something is a source of its DNA then would it be possible to bring back anything? Including Elvis Presley?

“I’m a bit of an Elvis fan and I was interested to see how far this technology can be taken,” says Pilcher. “Instead of just bringing back a species of human could you bring back a particular person? I was interested in Elvis because in the 90s I stumbled across a website called Americans for Cloning Elvis. It suggested a couple of sources of Elvis’ DNA that could be used as a starting point for this experiment.

The Maybe Elvis Toenail is a great name for an indie-rock band, but not a good place to launch a de-extinction attempt

“There’s a lady who runs a museum in America and she has two Elvis artefacts that might be helpful. One is something that she calls The Maybe Elvis Toenail, which is a toenail that she prised out of the carpet in Graceland shortly after Elvis died, and she called it The Maybe Elvis Toenail for very obvious reasons. I think The Maybe Elvis Toenail is a great name for an indie-rock band, but not a good place to launch a de-extinction attempt.

“The second one she has is slightly less savoury. She has a wart that was removed from the back of Elvis’ wrist before he went into military service in the fifties and she has a line of evidence that suggests that this is indeed genuine. It’s been sat in a tube of formaldehyde ever since then, so its DNA would be preserved, but warts are caused by viruses so Elvis’ DNA inside this tissue sample would be cut with viral genetic material, so that’s not a great place either,” says Pilcher.

“Then I stumbled across on Ebay, you can buy samples of famous people’s hair. I actually sent off for a sample of Elvis Presley’s hair and when it arrived I was so disappointed because not only was it minuscule – it was like smaller than a single eyelash from my face – it was also ginger, so I’m slightly doubting of its authenticity, but anyway as a starting point of a thought experiment I was intrigued; can you get enough DNA from a hair to sequence a full genome in detail, and the answer is probably yes you can. I spoke to one of the world’s leading geneticists, and he tells me that yes, using the technology we have you could get a high-quality copy of Elvis Presley’s genome from a sample of his hair then what you’d do is you’d line up that DNA sequence inside a computer, next to the DNA sequence of a mere mortal, and you look for differences between the two, and there will many, there will be millions,” explains Pilcher. “Then you need a technique that lets you systematically edit these uniquely Elvis bits of DNA into a regular human cell and there is a technique, I am told, that would let someone do this. This isn’t trivial at all, but it could in theory be done.

“Now if you take the thought experiment to its logical conclusion, however, although you end up with a genetically identical copy of Elvis you end up with a completely different human being. I’m a mother of twins, mine aren’t identical, but if you look at identical twins their parents will tell you they came out with different personalities from day one and those personalities and minute physical differences that were there only become more exaggerated with time, so we’re products of nature and nurture, of DNA and our environment.

“Whereas the original Elvis grew up in poverty listening to blues and gospel music, if we did this experiment and we brought up a new Elvis today, he’d be growing up in a world surrounded by technology, by completely different music and he might be more into drum and bass than rock’n’roll, who knows. He might not even be into music at all, so you can never, ever clone the essence of an individual.”

Fortunately, we’ll never know how close to the original an Elvis clone could get because human reproductive cloning is banned, so there’ll be no theme park populated by Elvis clones anytime soon. But if science can’t or isn’t allowed to make this possibl,e then perhaps fiction can step in because I’m sure I’m not alone in saying, I wouldn’t mind seeing a movie about it.

Helen Pilcher’s book Bring Back the King: The New Science of De-extinction is available to purchase here.

Issue 36 of Factor: It’s time to engineer the environment. Out now!

It’s fair to say things aren’t looking good for the environment. As temperatures and sea levels rise, we face a dramatic transformation of the natural world, with mass extinctions and the collapse of entire ecosystems remaining a concerning prospect in the near future.

So in this, issue 36 of Factor, we’re looking at how science and the engineering of the environment could be vital to the survival of the world as we know it.

First up, technological advances in fields such as genetics are ushering in whole new approaches to conservation, and raising the possibility that even extinction might not be the end. We examine the science of de-extinction. But can we really bring back long-dead species, and even if it becomes possible, is it actually a good idea?

As part of our de-extinction triple bill, we look at how the much-lauded project to de-extinct a woolly mammoth is only a small part of a wider and more promising field, where the true value lies in modifying endangered species to survive the changing world.

We also consider the prospect of a real-life Jurassic Park. Is it possible, or are genetically modified chickens as close as we can get? And if that wasn’t enough, we’re also asking whether there would ever be a case for the de-extinction of our close cousins the Neanderthals.

At the heart of this is the gene editing technology CRISPR. We look at how the slow march of genetic engineering has led to this revolutionary technology, and discover some of the stranger projects being explored with the technology.

Of course, all of this would not be such an important topic without the spectre of climate change. At present, Donald Trump is enemy number one when it comes to refusing to take action, but with nowhere near enough being done in many parts of the world, we ask if the rest of us are any better.

Given we are unlikely to radically improve humanity’s efforts to curb climate change any time soon, we also look at how science can be used to mitigate its effects. Geoengineering could – at least in theory – be used to tackle the problem, but as we find out, it’s not without its own issues, while genetically engineered plants could at some point become a vital resource in the mission to keep our cities liveable.

And if that wasn’t enough, we also investigate the challenges of e-waste and unearth the secret history of the legendary videogame Earthbound.

As usual there’s also all of your latest news, reviews and we check out the plan to monitor our environmental impact on Mars too, in issue 36 of Factor magazine – out now on iPad and online.