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.

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The answer to the antibiotics crisis might be inside your nose

The medical weapons we have equipped ourselves with are losing their power. But scientists scent an answer. 

They say there’s a hero in everyone. It turns out that actually, it resides within only about ten percent of us. Staphylococcus lugdunensis may be the species of bacteria that we arguably don’t deserve, but it is the one that we need.

Recently, experts have cautioned that we may be on the cusp of a post-antibiotic era. In fact, less than a month ago, the US Centres for Disease Control and Prevention released a report on a woman who died from a "pan-resistant" disease – one that survived the use of all available antibiotics. Back in 1945, the discoverer of penicillin, Alexander Fleming, warned during his Nobel Prize acceptance speech against the misuse of antibiotics. More recently, Britain's Chief Medical Officer Professor Dame Sally Davies has referred to anti-microbial resistance as “the greatest future threat to our civilisation”.

However, hope has appeared in the form of "lugdunin", a compound secreted by a species of bacteria found in a rather unlikely location – the human nose.

Governments and health campaigners alike may be assisted by a discovery by researchers at the University of Tubingen in Germany. According to a study published in Nature, the researchers had been studying Staphylococcus aureus. This is the bacteria which is responsible for so-called "superbug": MRSA. A strain of MRSA bacteria is not particularly virulent, but crucially, it is not susceptible to common antibiotics. This means that MRSA spreads quickly from crowded locations where residents have weaker immune systems, such as hospitals, before becoming endemic in the wider local community. In the UK, MRSA is a factor in hundreds of deaths a year. 

The researchers in question were investigating why S. aureus is not present in the noses of some people. They discovered that another bacteria, S. lugdunensis, was especially effective at wiping out its opposition, even MRSA. The researchers named the compound created and released by the S. lugdunensis "lugdunin".

In the animal testing stage, the researchers observed that the presence of lugdunin was successful in radically reducing and sometimes purging the infection. The researchers subsequently collected nasal swabs from 187 hospital patients, and found S. aureus on roughly a third of the swabs, and S. lugdunensis on up to 10 per cent of them. In accordance with previous results, samples that contained both species saw an 80 per cent decrease of the S. aureus population, in comparison to those without lugdunin.

Most notably, the in vitro (laboratory) testing phase provided evidence that the new discovery is also useful in eliminating other kinds of superbugs, none of which seemed to develop resistance to the new compound. The authors of the study hypothesised that lugdunin had evolved  “for the purpose of bacterial elimination in the human organism, implying that it is optimised for efficacy and tolerance at its physiological site of action". How it works, though, is not fully understood. 

The discovery of lugdunin as a potential new treatment is a breakthrough on its own. But that is not the end of the story. It holds implications for “a new concept of finding antibiotics”, according to Andreas Peschel, one of the bacteriologists behind the discovery.

The development of antibiotics has drastically slowed in recent years. In the last 50 years, only two new classes of this category of medication have been released to the market. This is due to the fact almost all antibiotics in use are derived from soil bacteria. By contrast, the new findings record the first occurrence of a strain of bacteria that exists within human bodies. Some researchers now suggest that the more hostile the environment to bacterial growth, the more likely it may be for novel antibiotics to be found. This could open up a new list of potential areas in which antibiotic research may be carried out.

When it comes to beating MRSA, there is hope that lugdunin will be our next great weapon. Peschel and his fellow collaborators are in talks with various companies about developing a medical treatment that uses lugdunin.

Meanwhile, in September 2016, the United Nations committed itself to opposing the spread of antibiotic resistance. Of the many points to which the UN signatories have agreed, possibly the most significant is their commitment to “encourage innovative ways to develop new antibiotics”. 

The initiative has the scope to achieve a lot, or dissolve into box ticking exercise. The discovery of lugdunin may well be the spark that drives it forward. Nothing to sniff about that. 

Anjuli R. K. Shere is a 2016/17 Wellcome Scholar and science intern at the New Statesman