Tag: Sanger Life

Chernobyl Dogs
Sanger LifeSanger Science

Chernobyl: chasing a ‘catching’ cancer

By: Alison Cranage, Science Writer at the Wellcome Sanger Institute
Date: 06.12.18

Chernobyl_placement_Holek_WikimediaCommons_300On 24th April 1986, a reactor at the Chernobyl power plant in the Ukraine exploded. It was the worst nuclear accident the world has ever seen.

Radioactive material plumed, contaminating the air, soil and water. Effects are still seen today, 32 years later and hundreds of miles away, where land in parts of Europe is deemed unsafe for farming.

The number of people who died as a result of the disaster may never be known. It is thought that thousands of lives have been lost. Some died from acute radiation sickness immediately after the blast; others, later, from thyroid cancer caused by exposure to radiation.

After the explosion, over 90,000 people were evacuated from hundreds of towns and communities in the vicinity of the plant. They had to leave everything behind, including their pets. The area lay barren for many years as high radiation levels meant nothing could grow.

Chernobyl’s Exclusion Zone

Today, a 200 km chain-link metal fence surrounds the plant – creating an ‘exclusion zone’ stretching for 30km in every direction. Radiation levels have returned to near normal in most places, though certain ‘hot spots’ remain. Forests have re-established themselves, swallowing the abandoned towns and villages.

People have returned to the zone too – some 3,500 work there, as security guards or in offices that, remarkably, still surround the power plant. Animals have also returned, including bears, wolves and smaller mammals. Some animals never left, including the descendants of the pet dogs that people had to leave behind when they fled.

The dogs, resembling German Shepherds, are fed by visitors, workers and the security guards. Despite this kindness, the animals face many challenges. During the harsh winters, they seek shelter in the abandoned buildings. They are hunted by wolves in the forests and exposed to rabies by wild animals. Though puppies seem to thrive, it is hard to find a dog more than a few years old.

Alex Cagan, post-doctoral researcher at the Wellcome Sanger Institute, joined a trip to Chernobyl in June 2018. Run by the Clean Futures Fund (CFF), he travelled with a team of vets to visit the abandoned dogs. He was looking for an unusual type of cancer.

Catching cancer

Transmissible cancer is a strange form of the disease. Unlike any other type of cancer it is not caused by an individual’s own cells growing uncontrollably. It’s an infectious cancer – it’s a cancer dogs can catch.

It first arose in an animal who lived about 8,000 years ago. Cells from this animal, termed the ‘founder dog’, were passed on to other dogs. The cells somehow survive, evading the immune system of new animals, continuing to grow and form tumours.

The tumours are contagious, sexually transmitted, and have spread around the world. Genomic analysis has shown that wherever there are populations of stray dogs – from the deserts of Africa to the Himalayas to the Australian Outback – there are these tumours. Each one carries descendants of the cells from the founder dog.

In essence, the tumour is a parasite, being passed from host to host. Little is understood about its biology – for example no-one knows exactly how it escapes the immune system. Alex is working with Elizabeth Murchison, a group leader at the University of Cambridge who studies transmissible cancers. The aim was to collect samples for genomic analysis – to see if the radiation has any effects on the cancers.

Caring for the dogs of Chernobyl

Clean Futures Fund make several trips a year to care for the animals. The vets check the dogs, treat any injuries and neuter them, to help control the population. Researchers from around the world, studying the unique environment and the effects of radiation on animal populations, join them.

Alex joined the team in the town of Slavutych, just outside the exclusion zone. Travelling by train, and then in an old Soviet truck, they entered the exclusion zone every day, setting up makeshift clinics in old barracks or buildings.

Despite the 30 degree summer heat, everyone entering the zone is required to wear long sleeves and trousers to cover as much skin as possible, as a precaution. All visitors are given a small Geiger-counter to wear around their neck – constantly monitoring the radiation levels. There’s no eating or drinking allowed out in the open, to minimise the risk of radiation exposure. People are screened on the way out of the zone to check radiation levels on their body. If they’re too high, the advice is to take a shower.

“I was worried at first,” said Alex. “But I was with radiation experts and they weren’t, so my mind was put at ease. The amount of background radiation there now, in most places, is the same as you’d get taking a trans-Atlantic flight. The risks are really low.”

“You do see the odd anomaly. There was a sink in one of the buildings with a mirror above it. Someone had written ‘Danger: Do not touch sink bowls. Handles ok’. If you pointed your Geiger counter at it, the readings were massive.”

Each person in the team had a clear job. While the dog catchers set off to find the strays, the vets set up the clinics. Alex took tissue samples from the testes of the neutered animals.

The curious case of the contagious cancer

In the 200 dogs he saw over two weeks, Alex didn’t find a single case of transmissible cancer. Elizabeth was surprised to hear the news. “We see transmissible cancer in dogs all around the world. We find it almost everywhere there are free roaming dog populations. We don’t know why the dogs in Chernobyl don’t have it.”

“There are several theories. Most likely it is probably by chance. They are an isolated population, so perhaps they’ve never come across it, or maybe the disease used to be in the population but has now disappeared. This is really just speculation, but it might be something unique about this dog population, perhaps their immune systems are more able to fight it off somehow. But as far as we know there is nothing different about them compared to other Ukrainian dog populations.”

“We know the cancers are very sensitive to radiotherapy – and so the wildest theory is that maybe the exposure to radiation over the years have been protective.”

“The wildest theory is that maybe the exposure to radiation over the years have been protective”

The dog transmissible cancer normally doesn’t grow if its DNA is broken, or exposed to DNA damaging agents. This is good news for any dogs who do have it – it is easily treated with chemotherapy and the vets had doses ready.

“We will probably never know why it’s not there.” Elizabeth is going to keep in touch with CFF, in case the vets do spot any cases.

If they find it, her team is particularly interested in the ‘mutational signature’ of the DNA in the tumour cells. These are patterns of change in a DNA sequence. Anything that causes damage to DNA, like tobacco smoke, or radiation, causes a unique pattern of change. Radiation causes a particular kind of damage to DNA – double stranded breaks.

The team were particularly keen to study cancers that might have been exposed to radiation. Would they be able to spot tell-tale signs of the Chernobyl explosion in the DNA? It would tell them how the cancer responds to DNA damage and different levels of radiation.

From Chernobyl to Tasmania (via Cambridge)

Elizabeth’s research into transmissible cancers continues back in Cambridge. Her goal is to look at the genomic diversity of transmissible cancers around the world. As well as being affected by external agents, the transmissible cancer genome evolves over time, accumulating changes. By tracking these changes, her team is able to construct an evolutionary tree – showing how related each cancer is to another, and when it was passed on.

1024px-Tasdevil_largeHer team are also studying the effects of another infectious cancer – Tasmania Devil Facial Tumour Disease. Spread in the animals’ saliva when they bite each other’s faces, the cancer is a huge threat to the devils. It has decimated their numbers, affecting up to 65 per cent of the population in Tasmania, Australia.

When Elizabeth was based at the Sanger Institute, she sequenced the genome of the Tasmanian devil transmissible cancer. She found that, again, the disease first arose from the cells of a single animal – in this case, a female Tasmanian devil. The animal has been dubbed ‘The Immortal Devil’, because although she died over 20 years ago, her DNA lives on in the contagious cancer cells she spawned. Elizabeth’s aim is to eliminate the disease.

Mutational DNA Signatures

Alex’s visit was driven by curiosity and he hopes it will deliver some useful insights. He took 20 DNA samples from the dogs for his group’s cancer work back at the Sanger Institute. Their team is interested in mutational signatures – although they will be looking for DNA damage in healthy, non-cancerous cells. DNA analysis of the healthy dogs will also give information about the population as a whole. For example, it may reveal if the dogs have mated with the wolf population. And it may give clues as to why the dogs only live for a few years.

Chernobyl is a unique location for tragic reasons. But it might be able to help Alex’s team find out more about the impact of radiation on the genome. A huge amount is unknown, said Alex. “It is the first time that complete genomes have been sequenced from any animals living in the exclusion zone. We don’t know what we will find.”

Find out more

Alex Cagan is speaking about his work at the next ‘Genome Lates’ event on Friday 7th December at the Wellcome Genome Campus in Cambridge.

About the Author

Alison Cranage is the Science Writer at the Wellcome Trust Sanger Institute

Human Embryo Editing: science fiction or science fact?
Influencing PolicySanger Life

Human Embryo Editing: science fiction or science fact?

By: Anna Middleton, Head of the Society and Ethics research group at the Wellcome Genome Campus Connecting Science
Date: 29.11.18

“As scientific knowledge advances and societal views evolve, the clinical use of germline editing should be revisited on a regular basis”

2015 Organizing Committee of the First International Summit on Human Genome Editing

And here we are at the end of 2018, ‘revisiting’ this for real. I’m writing this while sitting in the audience in Hong Kong at the Second International Summit on Human Genome Editing, funded by the Royal Society, National Academy of Sciences, National Academy of Medicine and the University of Hong Kong. As an invited presenter on the public responses to genomics I’m excited to be sitting amongst global representatives from science, medicine and ethics.

The first thing that strikes me is the overwhelming presence of media in the auditorium, all excited by the announcement yesterday of the ‘first’ edited embryos to have been born, apparently delivered a few weeks ago.  The veracity of this is still very much a topic of debate across the media and scientific establishment.  There are many gaps and unusual elements to the announcement that call for caution and further detail.  But in the busy coffee breaks, the chat focuses on the ‘disbelief and horror’, and ‘how did he manage to do this without ethical regulation?’ There is concern in the air about the ‘ease’ with which the scientist could persuade a series of patients undergoing IVF to allow him to edit their healthy embryos. Prof He Jiankui, an associate professor at a Shenzhen university (https://theconversation.com/rogue-science-strikes-again-the-case-of-the-first-gene-edited-babies-107684) claims to have edited a single gene that may offer some level of protection against future HIV infection.

The editing of embryos with intention of implantation and pregnancy, is illegal in many countries including the UK, all of the EU and the US.  A change in the law is not going to happen any time soon, but I guess that may give time for the scientific research and ethical enquiry to reach some level of consensus on what could and should be offered.

What seems to be generally agreed amongst the audience of delegates at this Summit is that the science just isn’t there yet to guarantee that there would be no downstream effects of editing one gene and either inadvertently editing another at the same time, or causing a disruption of an unexpected pathway leading to the creation of disease. So, what cannot be guaranteed is that these newly edited children won’t be susceptible to other serious health problems. We are reassured by Prof He that he will cover the medical bills for these children up to the age of 18.

Such reassurance on medical bills doesn’t really cover all of the implications and issues that Prof He’s announcement presents. The Nuffield Council on Bioethics previously reported in ‘Genome Editing and human reproduction report’ (July 2018): ‘We can, indeed, envisage circumstances in which heritable genome editing interventions SHOULD be permitted’. But the caveat was that such a possibility would only come after appropriate public debate.

At the Summit, one of the leaders in the field,  Prof George Daley, from Harvard Medical School reassured his audience that the current ‘mishap’ should not put us off striving for delivering the best science together with ethical frameworks to offer oversight of embryo editing. He asserts: ‘we need a well-defined translational pathway’ so that in the future we could offer embryo editing clinically for those that need it.

The science and the ethics of these issues have a long way to go. But already Prof He’s claim is opening up another level of debate.

Prof Daley was also asked about  ‘other clinical pathways that could be used instead of embryo editing, what about pre-implantation genetic diagnosis?’ He replied that he envisions in the future that embryo editing will be easier than PGD; and editing of gametes before fertilisation will become a reality, thus both of these may become the treatment of choice.

So there we have it. At this Summit on Genome Editing, we appear to be heading towards a future where editing of embryos in clinical practice to patients and families is technically possible. At the Summit we hear impassioned calls from patient groups, for example, the Sickle Cell Disease Community who are embracing genome editing, primarily in somatic testing, but they were not ruling out work in embryos.

There are repeated calls from the audience for ‘consensus’ and ‘acceptability’ from the public. These calls are fleetingly mentioned without real thought or understanding of just how hard this is to do. With an average reading age of 10 in the UK and 85 per cent of people having never heard of the word ‘genome’ before, we have a long way to go to socialise this enough to enable meaningful debate.  That’s not to say we shouldn’t do it, we absolutely should, but instead of just imagining this happens by osmosis, we should adequately value, resource and support the communication research to enable this to happen appropriately.

The summit organisers have put out a statement on the issue, which concludes that, currently “the scientific understanding and technical requirements for clinical practice remain too uncertain and the risks too great to permit clinical trials of germline editing.”

The question of if this is fact or fiction will become clear in coming days and weeks. What is clear is that there is an urgent need for the community to reach some conclusions on the issues raised. And the clock is ticking.

About the Author

Anna Middleton is Head of the Society and Ethics research group at the Wellcome Genome Campus Connecting Science

Dr Cordelia Langford wins BioBeat award
Sanger Life

Dr Cordelia Langford wins BioBeat award

By: Alison Cranage, Science Writer at the Wellcome Sanger Institute
Date: 14.11.18

Cordelia’s love of science started early, as she visited her father at work in his research laboratory.

“From a very young age I went into his lab – and I was intrigued by the science happening there. He was an electron microscopist and I was fascinated with the inner functioning of cells. That’s something that’s stayed with me.

The Medical Research Council - Laboratory of Molecular Biology (known as the MRC-LMB) as it was until it was rebuilt in 2013. Image credit: Jynto, Wikmedia Commons

The Medical Research Council – Laboratory of Molecular Biology (known as the MRC-LMB) as it was until it was rebuilt in 2013. It was here that Cordelia’s love of science was sparked. Image credit: Jynto, Wikmedia Commons

“My mother was head of science at a senior school in Cambridge. Between them they fostered this interest in science. When I was 16 I had the opportunity of a holiday job at the MRC Laboratory of Molecular Biology. I realised I had a talent for technical work – everything started from there. I wanted to become qualified, but I didn’t follow the traditional route. All of my post A-level qualifications were done whilst I continued working. I joined the Sanger Centre as an undergraduate research assistant in 1994, when the Sanger was less than a year old, working on the human genome project.”

Since then, the science and the technology to deliver cutting edge genomic research have been constantly evolving. That first human genome sequence took 13 years to complete. Now, the Sanger Institute sequences the equivalent of a human genome every 24 minutes.

“I am so inspired by the mission of the Sanger Institute. Part of what drives me is wanting to move our science forwards in the delivery of what does truly feel like research that is changing the lives of people. Having an understanding of the Sanger’s ambitious scientific goals, and knowing everything that’s going on in terms of technical development, then being able to translate that into new pipelines and new platforms is very satisfying.

“And I get to work with some extraordinary, talented people.”

Cordelia now leads a team of 300 scientists and the delivery of all the scientific operations at the Sanger Institute. This includes all the data production pipelines – from the animal facility, to the production and maintenance of cells and tissues used in research, and all of the DNA and RNA sequencing facilities.

She described some of the support she’s had throughout her career.

“In the main it’s been training. Technical skills, but more importantly skills that you need to become a manager of people and operations. I still reflect on a training course I went on for presentation skills, very early on in my PhD. I still use those techniques for presentations today. I feel as though there has been a sustained investment in helping me to hone my skills and I feel like I’ve never stopped learning.”

The UK Biobank vanguard project (to sequence the genomes of the first 50,000 UK Biobank volunteers) is being overseen by the Sanger Institute's Cordelia Langford after successfully led the Sanger's bid to carry out the work

The UK Biobank Vanguard project (to sequence the genomes of the first 50,000 UK Biobank volunteers) is being overseen by the Sanger Institute’s Cordelia Langford after successfully she led the Sanger’s bid

Cordelia described one of the most exciting areas of her work at the moment – UK Biobank. The project is following the health and well-being of 500,000 volunteer participants, providing health information to researchers from around the world. She recently led the Institutes successful bid to sequence 50,000 whole genomes as part of the project.

“It’s the end point that’s the main excitement. It’s a mind blowing resource that’s been built up. The gathering of the information, the consent of the participants and the richness of the dataset – it’s really only recently sunk in how impactful this is around the world. It’s openly available for researchers to access. The fact that my teams are able to generate the icing on the cake with full genome sequence data to add to that is very rewarding.”

biobeat18_moversCordelia was recognised in the collaboration category of the BioBeat award. Much of her work spans across different teams within the institute, as well as between institutes around the world. She also co-ordinates partnerships with commercial companies – those that supply the DNA sequencing machines and associated technologies, for example. Recently she brought together thought leaders, suppliers and partners in DNA sequencing for a unique meeting to describe the future strategy for genomic technology. The aim was to enable the research community to work together with technology suppliers to shape a road map for the future.

“I believe that revolutionary collaborative exchange – breaking the boundaries between researchers, innovators and suppliers – is key. It will enable us to deliver transformative science and tackle global challenges.” says Cordelia.

The BioBeat award celebrates women in science and bio-business. We discussed some of the issues that face women in science today.

Dr Cordelia Langford, Head of Scientific Operations at the Wellcome Sanger Institute, was named as one of Biobeat18's top movers and shakers

Dr Cordelia Langford, Head of Scientific Operations at the Wellcome Sanger Institute, was named as one of BioBeat18’s top movers and shakers

“I feel as though I’ve experienced a lot of what is often spoken about as challenges faced by women. A perception of glass ceilings, of being treated differently. People have not always encouraged my growth, or supported positive outcomes in certain situations.

“I think some of those experiences, or unintentional comments, have made me feel inhibited at times, and perhaps hindered me. I’ve sometimes had a feeling of imposter syndrome, and I’ve realised it’s not all from within. Getting through that barrier is tough, psychologically. But when it’s not there it’s such an amazing and empowering feeling. I feel less inhibited now, more able to play to my strengths as a leader, and to be me.

“There is a gender imbalance in science, as elsewhere in society. I believe there is more work to do to change the perception that appointing women to senior positions is tokenism. Women should be truly and equally recognised for their skills and achievements and should have every opportunity to reach their potential.

“I want to be part of the solution, clearing the way for junior staff so they feel there aren’t so many ceilings to smash. My past experiences, and my leadership skills, can help me to do .”

“I’m delighted to be taking over the chair of the Athena SWAN working group here at the Sanger Institute from 2019. We are committed to advancing gender equality in terms of representation, progression and success for all.”

With such a broad level of experience, it’s interesting to hear what advice she’d give for young researchers.

Cordelia_advice“Something that has been a golden thread for me is that I’ve been really clear about what I think I can achieve. I’ve thought about how I might travel towards my career goals. I’ve always kept that in mind. I’ve been patient, gathered my experience and taken job opportunities.

“Something I advise people is to have an open mind about opportunities. Don’t always feel you have to climb the ladder. Sometimes a sideways move might actually be building experience and knowledge that may be a spring board to a more senior role, if that’s what people are after.

“A solid group of mentors is invaluable. And something I’ve learnt more recently is the importance of balancing work with life. I know that I’m much more effective if I have time clear to be able to think, to reflect on what’s important here at work, and make sure I focus on the priorities.”

Finally, we talked about winning the BioBeat award. “I was privileged to be approached and to be included among such an outstanding group of leaders -it’s so gratifying and I feel very proud.” Cordelia said.

She also acknowledged all of the staff in her teams. “They are hugely inspiring, with diverse experiences and views. Everyone comes together to work towards joint goals.”

Her teams remain at the forefront of genome science. They have embraced and developed new technologies – for example in sequencing RNA from single cells, to allow the discovery of its activities. They are also enabling the high throughput sequencing and analysis needed for so many of the research projects at Sanger.

Golden Eagle - the first UK species to have its DNA read by the Sanger Institute as part of its 25 genomes for 25 years project. Image credit: Martin Mecnarowski, Wikimedia Commons.

Golden Eagle – the first UK species to have its DNA read by the Sanger Institute as part of its 25 genomes for 25 years project. Image credit: Martin Mecnarowski, Wikimedia Commons.

The next big challenge for Cordelia’s teams is the Darwin Tree of Life Project, where the Institute will be sequencing all animal, plant, fungi and protozoan life in the UK – some 66,000 species. The project brings huge technical challenges, in sample collection, DNA extraction and preparation, sequencing new genomes and assembling them – and doing all that at scale. The project has captured her imagination.

“It was fantastic to be able to sequence the golden eagle – it’s such an iconic bird. And the genome we published was very good quality. There are undoubtedly going to be a lot of surprises as we sequence thousands of new species, we’re going to learn a lot, and it’s going to be an exhilarating and impactful project.”

About the Author

Alison Cranage is the Science Writer at the Wellcome Sanger Institute