Biologists reconstruct genome of 11,000-year-old “almost immortal” sexually-transmitted dog cancer

Canine transmissible venereal tumours (CTVT) is one of only two natural transmissible cancers, and could hold the key to better organ transplants in humans.

Veterinary biologists have discovered that a sexually-transmitted cancer found in dogs around the world first originated 11,000 years ago, making it potentially the oldest living mammalian creature.

The study from the Wellcome Trust’s Sanger Institute, published in Science, analysed the genome of canine transmissable venereal tumours (CTVT), a disease that is one of only two known cancers of its type to have been observed in the natural world (the other, transferred via bites, affecting Tasmanian devils). It’s not a cancer caused by the transfer of a virus, like with cervical cancer and the HPV virus in humans - it’s the transfer of actual cancerous dog cells from dog to dog.

“They are actually a parasite, they need to have their host in order to survive, but they’re actually derived from the same species as their host,” Dr Elizabeth Murchison, the study’s lead author, explained to me. “They’re quite a strange disease. They are an infectious disease, but they’re originally from the same species as their host, which makes them a kind of very tricky to combat.”

“It’s the oldest continually surviving mammalian lifeform that we know of,” she said. “It is almost immortal.”

Genome analysis of samples from a dog in Brazil and another Australia found that the cancer had undergone a huge number of mutations, in the order of two million, since it first began metastasising within the first dog to contract it.

Murchison said: “Between humans we each have about three million mutations, the natural variance that makes us different to other people. Similarly dogs have about three million natural variants that make one dog different to another dog. But cancers themselves, in humans, don’t tend to differ from their host very much. They usually have between 1,000 and 5,000 mutations in the genome that makes the cancer different to the host. Whereas this dog cancer has acquired about two million, which is almost making it like a different individual to the original host that gave rise to it.”

Relying on recent research which found that, within cancer patients, the number of mutations within a cancer correlates both to the type of cancer and the age of the patient, the study team were able to trace back in time to the point at which mutations must have started - giving the age of CTVT at 11,000 years.

Yet CTVT stayed within the small population where it first emerged for roughly 10,500 years, until suddenly spreading elsewhere around the globe - a time that coincides with the beginnings of the European age of exploration. While there’s no way to know where in the world the cancer first appear (yet), the earliest known historical mention of it is by a London doctor in 1810.

With the information from the origin dog’s genome, the team was able to create an image of what it probably looked like. Here's a video from the team further explaining their work:

What’s more, the cancer appears to have been caused by in-breeding.

“It was a relatively inbred individual,” explains Murchison. “Similarly, the Tasmanian devils are relatively inbred population - they live on an island, and they have a small population. The cancer might have originated in a dog that lived in an in-bred population, but from there it managed to adapt into all sorts of out-bred dogs. It can even survive in other species of canids, including jackals and coyotes and foxes. It’s pretty remarkable.”

Theoretically, this type of cancer could emerge at any time in any species, Murchison pointed out, but the experience of the dog and Tasmanian devil transmissible cancers - and from a third variant, which emerged briefly in a population of laboratory hamsters in the 1960s - seems to indicate that in-bred populations are more at risk. There are human populations which suffer from low genetic diversity around the world, and this research could be important in understanding transmissible cancers in the case of a variant appearing.

“These cancers have to overcome one of the most fundamental immunological barriers, and how they do it is still a mystery,” Murchison said. “It’s incredibly important to understand how they do it, as it has implications for how cancers evade the immune system, but also potentially how other infectious diseases might work, and have implications for how to design better methods for helping transplant recipient patients not to reject their graft transplant organs.”

Murchison is also keen to see if further research could help the endangered Tasmanian devil, whose variant is much more aggressive than CTVT and which can kill its host in a matter of months.

What the first dog to get CTVT may have looked like. (Image: Sanger Institute)

Ian Steadman is a staff science and technology writer at the New Statesman. He is on Twitter as @iansteadman.

Yu Ji/University of Cambridge NanoPhotonics
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Nanoengine evolution: researchers have built the world’s smallest machine

The engine could form the basis of futuristic tiny robots with real-world applications.

Richard P Feynman, winner of the Nobel Prize in Physics in 1965, once remarked in a now-seminal lecture that a time would come where we would “swallow the doctor”. What he meant, of course, was the actualisation of a science-fiction dream – not one in which a universal cure-all prescriptive drug would be available, but one in which society would flourish through the uses of tiny devices, or more specifically, nanotechnology. 

First, a quick primer on the field is necessary. Nanoscience involves the study and application of technologies at an extremely tiny scale. How tiny, you ask? Given that one nanometre is a billionth of a metre, the scale of work taking place in the field is atomic in nature, far beyond the observational powers of the naked human eye.

Techno-optimists have long promoted potential uses of nano-sized objects, promising increases in efficiency and capabilities of processes across the board as a result. The quintessential “swallow the doctor” example is one which suggests that the fully-realised potential of nanotechnology could be applied to medicine. The idea is that nanobots could circulate our bodily systems in order to reverse-engineer the vast array of health problems that threaten us.

It’s natural to be sceptical of such wild aspirations from a relatively young field of study (nanoscience unofficially began in 1959 following Feynman’s lecture “There’s Plenty of Room at the Bottom”), but associated research seems to be gaining widespread endorsement among prominent scientists and enthusiasts. Ray Kurzweil, Director of Engineering at Google, thinks a booming nanotechnology industry is crucial in the creation of a technological singularity, while futurist and viral video philosopher Jason Silva believes the technology will help us cure ageing.

The high-profile intrigue surrounding nanotechnology means that word of any significant developments is certain to stimulate heightened interest – which is why researchers’ achievement in building the world’s tiniest engine this month is so significant.

Reporting their results in the journal Proceedings of the National Academy of Sciences, the University of Cambridge researchers explained how the nanoengine was formed and why it represented a key step forward in the transition of the technology from theory to practice.

The prototype nanoengine is essentially composed of charged particles of gold, bound by polymers responsive to temperature in the form of a gel. The engine is then exposed to a laser which beams and heats the device, causing it to expel all water from the polymeric gel. The consequence of this is a collapsing of the gold particles into an amalgamated, tightened cluster. Following a period of cooling, the polymer then begins to reabsorb the water molecules it lost in the heating process, resulting in a spring-like expansion that pushes apart the gold particles from their clustered state.

"It's like an explosion," said Dr Tao Ding from Cambridge's Cavendish Laboratory. "We have hundreds of gold balls flying apart in a millionth of a second when water molecules inflate the polymers around them."

The process involved takes advantage of the phenomenon of Van der Waals forces – the attraction between atoms and molecules. The energy from these forces is converted into elastic energy, which in turn is rapidly released from the polymer. "The whole process is like a nano-spring," said Professor Jeremy Baumberg, who led the research.

Scientists have been tirelessly working towards the creation of a functional nanomachine – one which can effortlessly swim through water, gauge its surroundings and communicate. Prior to the research, there was a difficulty in generating powerful forces at a nanometre scale. These newly devised engines, however, generate forces far larger than any previously produced.

They have been named “ANTs”, or actuating nano-transducers. "Like real ants, they produce large forces for their weight. The challenge we now face is how to control that force for nano-machinery applications," said Baumberg.

In an email exchange with New Statesman about the short-term and long-term goals in bringing this engine closer to a practical reality, Baumberg said: “It allows us for the first time, the prospect of making nano-machines and nanobots. The earliest stage applications we can see are to make pumps and valves in microfluidic systems. Microfluidic chips are really interesting for synthesising pharmaceuticals, biomedical sensing and separation, as well as many other biochemical processes.

“But all pumps and valves currently need to be made with hydraulics, so you need a pipe onto the chip for each one, limiting strongly the complexity of anything you do with them. We believe we can now make pumps and valves from the ANTs which are each controlled by a beam of light, and we can have thousands on a single chip. Beyond this, we are looking at making tiny nanomachines that can walk around, controlled by beams of light.”

The embedding of nanobots into all facets of culture is still a long way off, and researchers will need to find a way of harnessing the energy of nanoengines. However, the prospect of one day seeing the fruition of nanorobotics is worth all the patience you can get. The tiniest robot revolution has just begun.