Tasmanian devils look set to conquer their own pandemic



Alecia Carter, Author provided

Hamish McCallum, Griffith University and Austin H. Patton, University of California, Berkeley

In the midst of a human pandemic, we have some good news about a wildlife one: our new research, published today in Science, shows Tasmanian devils are likely to survive despite the infectious cancer that has ravaged their populations.

Tasmanian devils have been devastated by a bizarre transmissible cancer. Devil facial tumour disease, or DFTD for short, was first detected in 1996 in northeast Tasmania. Transmitted via biting, DFTD has spread over almost the entire state, reaching the west coast in the past two or three years. It has led to a decline of at least 80% in the total devil population.

Tasmanian devil with facial tumour
The infectious tumours are spread by biting.
CREDIT, Author provided

Ten years ago, we thought there was a real chance DFTD would drive the Tasmanian devil to extinction. Our concern arose not just because the cancer was almost inevitably lethal, but also because the transmission rate did not appear to slow down, even as devils became very rare.

Our new research has some good news: by pioneering application of genomic analysis typically used for viruses, we have discovered the curve has flattened and the rate of increase of infections has slowed. This means while the disease is probably not going away, neither are Tasmanian devils.

Genomics is a relatively new field of science that uses the vast amounts of data available from modern genetic sequencing techniques to answer some of the most difficult and important questions in biology.




Read more:
We developed tools to study cancer in Tasmanian devils. They could help fight disease in humans


The genomic approach we used is called phylodynamics. It uses sophisticated mathematical analysis of small changes in DNA to reconstruct the evolution and spread of the tumour through devil populations. This is the same method used to track the COVID-19 pandemic, and it was first developed to study the influenza virus. Viruses have small genomes and evolve rapidly. This is the first time the method has been used for a pathogen with a much more complex and slowly evolving genome.

Screening more than 11,000 genes, we found the R number (the average number of secondary cases for each primary case, now familiar from COVID-19) has fallen from about 3.5 at the peak of the epidemic to about one now. This suggests some sort of steady state has been reached, and the disease and devils are now coexisting.

Reproduction number RE of DFTD from 1990 to the present.
Reproduction number RE of DFTD from 1990 to the present.
CREDIT, Author provided

This discovery backs up a paper we published last year, in which we reached a similar conclusion using mathematical models based on marking and recapturing Tasmanian devils at a single study site, without taking genetics into account.

Our new study is based on samples collected across Tasmania since the early 2000s. Given the very different nature of the two methods, the agreement between the results lends us increased confidence in our conclusions.

This paper, in addition to several we have published recently, shows there have been rapid evolutionary changes in Tasmanian devils and in the tumours themselves since the emergence of this transmissible cancer. Already, frequencies of gene variants known to be associated with immune function in humans have increased in Tasmanian devil populations, suggesting the devils are evolving and adapting to the threat.

We also now know a relatively small number of genes has a large influence on whether devils become infected, and whether they survive if they do.

Finally, and perhaps most encouragingly of all, we have now seen tumours shrink and disappear — something that was unheard of when the disease first emerged. What’s more, we also know this has a strong genetic basis, again suggesting the devils are genetically adapting to their foe.

Together, all of these discoveries show wild Tasmanian devils can evolve very rapidly — over just five generations or so — in response to this disease. This has profoundly encouraging implications for their likely future survival.

Baby Tasmanian devil
Tasmanian devils now have much better genetic defences against the disease.
Rodrigo Hamede, Author provided

There is still much more to learn about the evolution of the devils and their tumours. But meanwhile, our results provide a warning that a strategy of reintroducing captive-reared animals to supplement diseased wild devil populations is likely to be counterproductive.

When devils from populations that have never been exposed to the disease interbreed with wild animals in diseased populations, the evolution we have seen in wild populations is likely to slow down or even reverse, endangering those populations.

What’s more, the slowing rate of disease transmission may be partly a consequence of reduced devil population densities, resulting in fewer bites. Artificially boosting population densities might accelerate disease transmission, the opposite of the intended effect.




Read more:
Sexual aggression key to spread of deadly tumours in Tasmanian devils


With the growing body of evidence showing extinction of devils is quite unlikely even over the next 100 years, we have time for careful consideration of management strategies. Specifically, models can be developed to assess the evolutionary and epidemiological consequences of reintroductions or translocations.

One possibility would be to captively breed devils that have the right genes to boost their chance of surviving the disease. More broadly, our research underlines the vital importance of taking evolutionary considerations into account when managing endangered species. We now have the genomic tools to do so.


Many thanks to Andrew Storfer at Washington State University, Menna Jones and Rodrigo Hamede at the University of Tasmania, and Paul Hohenlohe at the University of Idaho for their contributions to this article and the research it describes.The Conversation

Hamish McCallum, Professor, Griffith School of Environment and Science, Griffith University and Austin H. Patton, Postdoctoral Associate, University of California, Berkeley

This article is republished from The Conversation under a Creative Commons license. Read the original article.

We developed tools to study cancer in Tasmanian devils. They could help fight disease in humans



Shutterstock

Andrew S. Flies, University of Tasmania; Amanda L. Patchett, University of Tasmania; Bruce Lyons, University of Tasmania, and Greg Woods, University of Tasmania

Emerging infectious diseases, including COVID-19, usually come from non-human animals. However our understanding of most animals’ immune systems is sadly lacking as there’s a shortfall in research tools for species other than humans and mice.

Our research published today in Science Advances details cutting edge immunology tools we developed to understand cancer in Tasmanian devils. Importantly, these tools can be rapidly modified for use on any animal species.

Our work will help future wildlife conservation efforts, as well as preparedness against potential new diseases in humans.

The fall of the devil

Tasmanian devil populations have undergone a steep decline in recent decades, due to a lethal cancer called devil facial tumour disease (DFTD) first detected in 1996.

A decade after it was discovered, genetic analysis revealed DFT cells are transmitted between devils, usually when they bite each other during mating. A second type of transmissible devil facial tumour (DFT2) was detected in 2014, suggesting devils are prone to developing contagious cancers.

A Tasmanian devil with devil facial tumour disease.
Save the Tasmanian Devil Program

In 2016, researchers reported some wild devils had natural immune responses against DFT1 cancers. A year later an experimental vaccine for the original devil facial tumour (DFT1) was tested in devils artificially inoculated with cancer cells.

While the vaccine didn’t protect them, in some cases subsequent treatments were able to induce tumour regression.

But despite the promising results, and other good news from the field, DFT1 continues to suppress devil populations across most of Tasmania. And DFT2 poses an additional threat.




Read more:
Deadly disease can ‘hide’ from a Tasmanian devil’s immune system


Following a blueprint requires tools

In humans, there has been incredible progress in treatments targeting protein that regulate our immune system. These treatments work by stimulating the immune system to kill cancer cells.

Our team’s analyses of devil DNA showed these immune genes are also present in devils, meaning we may be able to develop similar treatments to stimulate the devil immune system.

But studying the DNA blueprint for devils takes us only so far. To build a strong house, you need to understand the blueprint and have the right tools. Proteins are the building blocks of life. So to build effective treatments and vaccines for devils we have to study the proteins in their immune system.

Until recently, there were few research tools available for this. And this problem was all too familiar to researchers studying immunology and disease in species other than humans, mice or rats.

Into the FAST lane

You could build a house with just a saw, hammer and nails – but a better and faster build requires a larger, more versatile toolbox.

In our new research, we’ve added more than a dozen tools to the toolbox for understanding tumours in Tasmanian devils. These are Fluorescent Adaptable Simple Theranostic proteins – or simply, FAST proteins.

The term “theranostic” merges therapeutic and diagnostic. FAST proteins can be used as a therapeutic drug to treat a disease, or as a diagnostic tool to determine its cause and better understand it.

A key feature of FAST proteins is they can be tagged with a fluorescent protein marker, and can be released from the cells that we engineered in the lab to make them.

This way, we can collect and observe how the proteins attach and interact with other proteins without needing to add a tag later in the process.

To understand this, imagine trying to use a tiny key in a tiny lock in the dark. It would be difficult, but much easier if both were tagged with a coloured light. In the context of the immune system, it’s easier to understand what we need to turn on or off if we can see where the proteins are.

By mapping how proteins within the devil’s immune system interact, we can find better ways to stimulate the immune system.

An overview of the FAST protein system. Fluorescent proteins and immune system proteins from different species can be rapidly swapped to make new FAST proteins.
Andrew S. Flies/WildImmunity

The FAST system is also adaptable, meaning new targets can be cut-and-pasted into the system as they’re identified, like changing the bits on a drill. Therefore, it’s useful for studying the immune systems of other animals too, including humans.

Also, the system is simple enough that most people with basic cell culture and molecular biology experience could use it.




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Needle in a haystack

Cancer cells in humans and animals can travel via the bloodstream to spread, or “metastasise”, throughout the body. Identifying single tumour cells in blood can shed light on how cancer invades devils’ organs and kills them.

Using FAST tools, we discovered CD200 – a protein that inhibits anti-cancer responses in humans – is highly expressed in devils. With FAST tools, we were able to mix DFT2 cancer cells into devil blood and pick them out, despite there being about one cancer cell for every 1,000 blood cells.

CD200 is a powerful “off switch” for the immune system, so identifying this off switch allows us it can help us produce a vaccine that disables the switch.

A devil facial tumour 2 (DFT2) cell, with the cell nucleus shown in blue.
Andrew S. Flies/WildImmunity

By rapidly sifting out the best ways to stimulate the devil’s immune system, FAST tools are accelerating our research into developing a preventative vaccine to protect devils from DFT.

Why study animal immune systems?

COVID-19 has once again brought emerging infectious diseases onto the global stage. The ability to rapidly develop immunology tools for new species means we can jump into action when a new virus jumps into humans.

Additionally, species are going extinct at an alarming rate, and wildlife disease is increasingly threatening conservation efforts.

Understanding how the immune systems of other animals fight diseases could provide a blueprint for developing vaccines and therapeutics to help them.The Conversation

Andrew S. Flies, Senior Research Fellow in Immunology, University of Tasmania; Amanda L. Patchett, , University of Tasmania; Bruce Lyons, , University of Tasmania, and Greg Woods, Professional Research Fellow, University of Tasmania

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Tasmanian devils are evolving rapidly to fight their deadly cancer


Menna Elizabeth Jones, University of Tasmania; Andrew Storfer, Washington State University; Hamish McCallum, Griffith University; Paul Hohenlohe, University of Idaho, and Rodrigo Hamede, University of Tasmania

For the past 20 years, an infectious cancer has been killing wild Tasmanian devils, creating a massive challenge for conservationists. But new research, published today in Nature Communications, suggests that devils are evolving rapidly in response to their highly lethal transmissible cancer and that they could ultimately save themselves.

Cancer is usually a disease that arises and dies with its host. In vertebrates, only two known types – Canine Transmissible Venereal Cancer in dogs and Devil Facial Tumour Disease (DFTD) – have taken the extraordinary evolutionary step of becoming transmissible. These cancers can grow not just within their host but can spread to other individuals. Because the cancer cells are all descendants of one mutant cell, the cancer is effectively immortal.

To grow in the new host, the tumour cell must evade detection and rejection by the immune system. Both the devil and dog transmissible cancers have sophisticated mechanisms for hiding from the host’s immune system. Our research suggests that the devil is nevertheless evolving resistance to the disease.

Ecological disaster

The Tasmanian devil is too important to lose – and this would seem careless following the extinction of the thylacine, the world’s largest marsupial predator, in the 1930s. Since the thylacine’s extinction, devils have stepped up to the role of top marsupial predator, keeping numbers of destructive feral cats at bay in Tasmania. With the decline of the devils, invasive species have become more active.

Since it was first detected in northeastern Tasmania in the mid-1990s, DFTD has spread slowly southward and westward. It will reach all parts of Tasmania within a few years; only the far northwest coast and parts of the southwest are still disease-free.

Devil Facial Tumour Disease has spread across the island over two decades.
Menna Jones

Devil populations have declined by at least 80%, and by more than 90% in some areas within six years of local disease outbreak.

DFTD kills most devils at sexual maturity. Before the disease arrived, most devils produced three litters over their lifetime. Most now raise only one.

The cascading effects of the loss of Tasmania’s top predator on the rest of the ecosystem could lead to loss of further species. Already, feral cats have increased activity and small mammals on which cats prey have declined.

Cats may also be preventing recovery of the eastern quoll. Brushtail possums behave as if devils were already extinct, grazing freely on pasture in the open.

Evolution in action

Our research has been a truly international effort. We used data collected by Menna Jones at the University of Tasmania since 1999. This archive of tissue samples now represents one of the best resources globally for studying evolution of an emerging infectious disease in wildlife.

Andrew Storfer at Washington State University and Paul Hohenlohe at the University of Idaho compared the frequency of genes in devils in regions before DFTD arrived to devils 8-16 years after DFTD arrived.

We identified significant changes in two small regions in the DNA samples of devils from regions with DFTD. Five of seven genes in the two regions were related to cancer or immune function in other mammals, suggesting that Tasmanian devils are indeed evolving resistance to DFTD. Evolution is often thought of as a slow process, but these changes have occurred in as few as 4–8 generations of devils since disease outbreak.

Devils are surviving at our long-term sites, despite models that predicted extinction. Previously, studies have shown that devils with lower rates of DFTD showed specific changes in their immune response. Our genetic results might explain why.

New infectious diseases put strong pressure on their hosts to evolve, leading to rapid changes in resistance or tolerance. Rapid evolution requires pre-existing genetic variation. Our results are surprising because Tasmanian devils have low levels of genetic diversity.

Evolution doesn’t just act on the devils; it also also acts on the disease. The disease evolves to not kill the host before it can spread to another host, but also to overcome the host’s defences. Over the long term, pathogen (the cause of the disease) and host usually evolve to live together as rabbits and Myxoma virus have evolved together.

Our results suggest that devils in the wild may save themselves through evolution. However, it is essential for managers to develop strategies that help the devils do so. For example, releasing fully susceptible devils that have had no exposure to the disease into populations where resistance is developing is likely to be counterproductive.

DFTD presents a unique opportunity to study the early stages of the evolution of a new disease and transmissible cancer with its animal host. Ultimately, through future research, we may understand how cancers can become transmissible and how their hosts respond.

The Conversation

Menna Elizabeth Jones, Associate professor, University of Tasmania; Andrew Storfer, Professor & Associate Director, School of Biological Sciences, Washington State University; Hamish McCallum, Professor, Griffith School of Environment and Acting Dean of Research, Griffith Sciences, Griffith University; Paul Hohenlohe, , University of Idaho, and Rodrigo Hamede, Post Doctoral Research Fellow, Conservation Biology and Wildlife Management, University of Tasmania

This article was originally published on The Conversation. Read the original article.