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Issue 920 (02 October 2017)

 

Welcome to BioNews by email, published by the Progress Educational Trust, providing you with news, comment and reviews on genetics, assisted conception, embryo/stem cell research and related areas.

Visit the BioNews website at www.bionews.org.uk where you can subscribe for free to receive BioNews by email in one of three formats, and search the archive of more than 6,000 articles.

 

 

CONTENTS

Comment

News Digest

Reviews

 


 

How should we discuss genome editing in public?

02 October 2017

By Sandy Starr

Page URL: http://www.bionews.org.uk/page_891539.asp Appeared in BioNews 920

What do patients and laypeople think and know about genome editing and its implications? What are the best ways for experts and others to discuss genome editing in public, so as to improve public understanding and avoid confusion?

The charities Progress Educational Trust (PET) and Genetic Alliance UK have set out to answer these questions with a project entitled 'Basic Understanding of Genome Editing', funded by the Wellcome Trust. Throughout the first half of 2017 we conducted five day-long workshops plus additional online engagement activities with patients, practitioners, parents and carers from the (in)fertility, genetic disease and rare disease communities.

There's never been a more important time for people to get to grips with this subject, when recent headlines have been dominated by news of researchers editing the genomes of human embryos.

Such embryo research has now been carried out in the UK to study gene function (see BioNews 919), in the USA to correct a mutation that causes hypertrophic cardiomyopathy (see BioNews 912 and 916), and - most recently - in China to correct a mutation that causes beta-thalassemia (reported elsewhere in BioNews this week).

The final example is especially relevant to our project, as the Chinese researchers did not employ the CRISPR approach to genome editing that has increasingly become standard. Instead, they used an alternative approach known as 'base editing', thereby highlighting the importance of the public understanding genome editing in a way that is not confined to CRISPR.

Participants in our project - who had little or no prior knowledge of this area - explored language, imagery and ideas relating to genome editing. They examined media coverage, explanatory videos and other material. They heard from, and put questions to, experts in the science and ethics of genome editing. They even gave their own presentations on genome editing, drawing upon what they had learned.

Our eight 'Key Recommendations' summarise what we learned from our participants.

  1. Use the term 'genome editing' exclusively. Do not use potentially confusing alternatives such as 'gene editing', 'genetic editing', 'genomic editing', 'genome engineering' or 'genetic modification'.

  2. Before attempting to describe or discuss genome editing, ensure that your audience has some understanding of what a genome is. Explain this if necessary.

  3. Prioritise explaining the use(s) of genome editing over explaining the mechanism(s) via which genome editing works. Deprioritise the term 'CRISPR' - do not use the term interchangeably with genome editing (as CRISPR is just one possible approach to genome editing), and think carefully about whether and when it is necessary to refer to CRISPR at all.

  4. Explain genome editing as straightforwardly as possible, certainly in the first instance. Use simple analogies and metaphors - 'find and replace', 'copy and paste' and 'cut and paste' work well, and build on the fact that 'editing' is already something of a metaphor. Metaphors have their limitations, but they are useful in establishing basic understanding before attempting to go into greater detail.

  5. When discussing uses of genome editing, distinguish clearly between:

    • Human and other uses.
    • Current and future uses.
    • Research and treatment.
    • Uses that are currently permitted and uses which would require regulatory change.

    It may also be important to distinguish treatment from enhancement, but refrain from suggesting that there is a settled consensus on what this distinction means and where it lies (as that particular debate is ongoing).

  6. When discussing a use of genome editing that relates to humans, take particular care to address whether or not it could (intentionally or inadvertently) affect the human germline - in other words, cause a heritable change to the genome.

  7. Be prepared to have to differentiate between genome editing and genome sequencing and/or between genome editing and mitochondrial donation, as these are common areas of confusion. Having made it clear that these are different things, then bring the conversation back to genome editing.

  8. Do not expect complete retention after one explanation of genome editing, no matter how well-received the explanation is. The message will need to be repeated multiple times, in order to achieve enduring comprehension.

A full report of the findings of our project can be downloaded at www.progress.org.uk/genomeediting

Genome editing will also be a key topic of discussion at PET's upcoming Annual Conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction', taking place at in London on Friday 8 December 2017. Full details of that conference can be found here.

PET and Genetic Alliance UK would like to thank all the participants in this project for donating their invaluable time and insights. Our participants are all keen to deepen this discussion, as are both of our charities - if you are interested in collaborating on follow-up work, please email sstarr@progress.org.uk

SOURCES & REFERENCES

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

20 November 2017 - by Helen Robertson 
For the first time ever, researchers have been able to film, in real-time, the activity of the CRISPR technique on a strand of DNA...
13 November 2017 - by Dr Calum MacKellar 
On the 20th anniversary of the of the 1997 European Convention on Human Rights and Biomedicine (Oviedo Convention), the Council of Europe Committee on Bioethics organised an international conference entitled ‘Relevance and Challenges’ last month in Strasbourg, France...
30 October 2017 - by Julianna Photopoulos 
Scientists have developed the genome editing technique known as 'base editing' to turn adenine-thymine base pairs back to guanine-cytosine...
09 October 2017 - by Cara Foley 
'Would you donate your genome?' Straight to the point, the introduction immediately grabbed my attention. Genome donation wasn't something I had even considered before listening to this podcast, so I was very curious to learn more...

25 September 2017 - by Paul Waldron 
UK scientists have successfully edited the genome of human embryos to study the role of a gene key to the earliest stages of development...
21 August 2017 - by Giulia Cavaliere 
Picture this - it's the last day in the office before the summer holidays, you're looking forward to some sunshine and warmth, email auto-response set, and all ready to go. Then, all of a sudden: the news...
31 July 2017 - by Charlotte Spicer 
Scientists in the US may have successfully used genome editing in human embryos to correct disease mutations, according to a report by MIT Technology Review...
13 March 2017 - by Dr Katie Howe 
Chinese scientists have successfully used genome editing to correct mutations in viable human embryos for the first time...

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The UK courts remain unmoved on commercial surrogacy

02 October 2017

By Andrew Powell

Page URL: http://www.bionews.org.uk/page_892836.asp Appeared in BioNews 920

A recent case is noteworthy not only for clinical negligence lawyers but also those interested in surrogacy and the wider public policy debate in the UK. Much of that debate has focused on the lack of regulation provided by the current UK legal framework and the need for the law to be modernised so that it can properly afford protection to those involved in surrogacy arrangements - a view I share. 

This case was heard in June 2017 in the High Court, London, the judgment followed in September. The claimant was a woman in her late 20s, who, as a consequence of her hospital's admitted negligence in failing to detect signs of cancer from smear tests and biopsies, developed invasive cervical cancer. She required chemotherapy that, among other medical complications, led to infertility. 

As the hospital had admitted that they were responsible for causing the complications and infertility, the trial was limited to establishing how much the claimant should be awarded in damages as a result of the hospital's negligence. 

The claimant and her partner wished to enter into a commercial surrogacy arrangement in California (one of the US states where commercial surrogacy is lawful). They expressed a preference for doing it there over the UK or elsewhere, citing what they saw as advantages of the regulated and commercial model in California.

However, under the Surrogacy Arrangements Act 1985, commercial surrogacy is illegal in the UK and it is a criminal offence to advertise either for a surrogate or to be a surrogate. Surrogacy in the UK is permitted only if it is altruistic, and only reasonable expenses may be paid to the surrogate.

Although the claimant expressed misgivings about undertaking surrogacy in the UK, she and her partner said they were determined to have children and therefore prepared to use the UK system if their claim did not succeed.

But an earlier case had crucial implications: in Briody the High Court considered whether damages could be recovered to cover the costs of surrogacy in California. In this case, the claimant wished to have a genetically-related child, however expert evidence considered that there was only a one percent chance of a live birth using her own eggs. On appeal to the Court of Appeal, the High Court dismissed her claim, and on appeal she invited the Court of Appeal to allow damages for a surrogacy arrangement in California using donor eggs. 

The claim was dismissed by the Court of Appeal because they felt that it would be inappropriate to award damages to pay for what would be an unlawful contractual arrangement in the UK. The significance of using the mother's own eggs was left open.

In the present case there was legal argument as to whether use of the claimant's eggs (which had been harvested successfully prior to the chemotherapy) in a commercial surrogacy arrangement in California would be capable of attracting an award in damages, having regard to the changing attitudes towards commercial surrogacy and the number of reported cases in the Family Court where the payments in international commercial surrogacy arrangements had been authorised by High Court Judges.

Sir Robert Nelson, the judge hearing the claim, rejected this argument, observing that he was bound by the earlier decision in Briody, that the court could not award damages to enable the claimant to undertake a commercial surrogacy arrangement in California.

The judge was however minded to award damages in respect of the claimant and her partner undergoing a surrogacy arrangement in the UK using her own eggs. The judge observed he was bound by the Briody decision and that a claim for damages for a surrogacy arrangement using donor eggs would not succeed because Briody considered that it would not 'restore' the loss of a claimant having their own child, whereas in the present case the claimant's own frozen eggs were available.

Having allowed the claim in respect of the surrogacy in the UK, the court awarded the claimant £37,000 (including VAT) for each of two surrogacy arrangements in the UK. The court arrived at this amount by taking into account the reasonable expenses of the surrogate that the claimant would have to pay for the two separate surrogacy arrangements and for legal advice. 

This case obviously brings into sharp relief some of the profound reasons why individuals may wish to use surrogacy as a route to parenthood. Surrogacy is regularly in the news or often in glossy magazines concerning well known individuals; however this recent case highlights some of the difficult medical circumstances which lead to surrogacy. 

Whilst there has been growing acceptance that intended parents in the UK may enter into lawful commercial surrogacy arrangements in other countries which are then authorised by the English Family Court, the paramount concern of the court, when deciding whether to make a parental order is the welfare of the child. This case however illustrates the ambivalence of a court actively endorsing commercial surrogacy. The decision of the court is not therefore that surprising. The taboo that existed in 2002 remains 15 years later. The earlier decision of Briody made it clear that it would not be permissible to allow a claimant to pursue a contractual arrangement that would be unlawful in this country. 

The case  highlights that the availability of surrogacy in the UK is something which is not discouraged, despite the reservations of the claimant and her partner in entering into such an arrangement. The question of what amounts to 'reasonable expenses' for a surrogate in the is touched upon, the court having received expert evidence that the average payment is £10,800. Recent Family Court decisions have considered this question, but plainly there can never be a set figure because the term 'reasonable expenses' is a broad one, so taking an average figure seems the most appropriate approach. 

The distinction drawn between whether damages would be awarded for a surrogacy arrangement if it were donor eggs versus the claimant's own eggs also offers an interesting perspective on how family life is viewed in the context of trying to restore a claimant to a position that she was in prior to the hospital's negligence. 

Overall this case reinforces the reticence of the courts towards actively endorsing what is seen to be a commercial surrogacy arrangement. In some ways it is not a surprising decision – commercial surrogacy remains a taboo topic in the UK, so the decision doesn't really change matters since the decision in Briody. However it is somewhat difficult to reconcile it with the reality of the increasing number of intended parents going abroad and entering commercial surrogacy arrangements: why should the claimant in this case be treated any differently? It seems that Parliament needs to reform the law before the court would be in a position to endorse commercial surrogacy.


 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

02 October 2017 - by Melissa Elsworth 
Why would a woman choose to carry a baby for another person? Should money be involved? Does surrogacy exploit vulnerable women? And what other ethical issues are involved in the surrogacy process?...
24 July 2017 - by Natalie Gamble 
As a supporter of surrogacy, I expected the television adaptation of The Handmaid's Tale to be uncomfortable viewing. Margaret Atwood's chilling dystopian novel is well known for being the ultimate warning against surrogacy...
19 December 2016 - by Ryan Ross 
The government has welcomed a House of Lords debate on surrogacy law reform, promising to consider whether the statute needs to be updated...
31 October 2016 - by Professor Adam Balen 
There is a lack of reliable information in the public domain for patients and their families, as well as an array of misleading and confusing information, but the British Fertility Society aims to counter this with impartial advice and information...
03 June 2013 - by Antony Blackburn-Starza 
A UK High Court judge has said applications for parental orders in international surrogacy cases should be encouraged and made promptly...

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Genome editing targets beta-thalassemia in human embryos

02 October 2017

By Dr Rachel Brown

Page URL: http://www.bionews.org.uk/page_891508.asp Appeared in BioNews 920

A genome editing technique called 'base editing' has been used to correct the mutation causing the inherited blood disorder beta-thalassemia in human embryos.

Although all resulting embryos were mosaic, the researchers at Sun Yat-sen University, China say their study shows the technique could be used to correct genetic disorders caused by point mutations - a mistake in just one of the four bases of the genetic code.

'We are the first to demonstrate the feasibility of curing genetic disease in human embryos by base editor system,' said lead researcher Dr Junjiu Huang to the BBC.

Unlike the more common genome editing technology CRISPR/Cas9, base editing does not cleave DNA to make an edit, which could reduce the likelihood of off-target edits.

The study, published in Protein and Cell, follows earlier work by the same team who, in 2015, were the first to use CRISPR/Cas9 on human embryos - also in an attempt to correct the beta-thalassemia mutation (see BioNews 799).

The researchers took nuclei from skin cells taken from a patient with the disorder, and inserted them into empty donor eggs, creating human embryos carrying the mutation. They then scanned the DNA of the embryos for the point mutation, which was a guanine base in the place of an adenine, and changed it back using an enzyme.

If used clinically, the team suggest the technique could one day prevent beta-thalassemia being passed onto future generations, or even be used to treat patients. However, the resulting embryos in the current study were mosaic, with about 20 percent of cells successfully corrected, and in some cases the technique introduced other mutations instead of fixing them.

'It really isn't a rival to CRISPR/Cas9. It is a modified version with different attributes,' explained Dr Seth Shipman, a geneticist at Harvard Medical School, to online news site Gizmodo.

The edited embryos were not intended for implantation, a scenario which remains illegal in many countries, including the UK.

Professor David Liu – who was not involved in this study - developed the base editing technique at Harvard University last year. Speaking to the BBC, he explained that 'about two-thirds of known human genetic variants associated with disease are point mutations. So base editing has the potential to directly correct, or reproduce for research purposes, many pathogenic [mutations]'.

Professor Darren Griffin, a geneticist at the University of Kent, said that 'while this is undoubtedly a highly significant advance, it is important not to get carried away about its widespread utility if put into clinical practice. An embryo would still need to be diagnosed as abnormal, then the base editor applied, then re-diagnosed to make sure that it had worked. This would be an involved procedure that would be very expensive.' 

Professor Robin-Lovell-Badge at the Francis Crick Institute in London, told the BBC that this approach is unlikely to be used clinically anytime soon, adding that 'there would need to be far more debate, covering the ethics, and how these approaches should be regulated'.

'And in many countries, including China, there needs to be more robust mechanisms established for regulation, oversight, and long-term follow-up,' he said.


The latest developments in genome editing and embryo research will be discussed at the session 'What Next for Genome Editing? Politics and the Public', at the Progress Educational Trust's upcoming public conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction'.

The conference is taking place in London on Friday 8 December 2017. Full details - including sessions, speakers and how to book your place - can be found here.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

30 October 2017 - by Dr Rachel Huddart 
A new molecular tool to change individual letters in an RNA sequence may open up new possibilities for gene therapy...
30 October 2017 - by Julianna Photopoulos 
Scientists have developed the genome editing technique known as 'base editing' to turn adenine-thymine base pairs back to guanine-cytosine...

25 September 2017 - by Paul Waldron 
UK scientists have successfully edited the genome of human embryos to study the role of a gene key to the earliest stages of development...
07 August 2017 - by Charlotte Spicer 
Scientists have published their study confirming they are the first to correct a disease-causing mutation in human embryos using genome editing...
13 March 2017 - by Dr Katie Howe 
Chinese scientists have successfully used genome editing to correct mutations in viable human embryos for the first time...
27 April 2015 - by Ayala Ochert 
Chinese scientists report the first-ever genetic modification of human embryos using the CRISPR/Cas9 gene-editing technique, confirming rumours that these highly controversial experiments were underway...

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Gene linked to schizophrenia is key in early brain development

02 October 2017

By Charlott Repschlager

Page URL: http://www.bionews.org.uk/page_891524.asp Appeared in BioNews 920

A gene associated with schizophrenia influences a critical stage of early brain development in mice.

Researchers investigated a gene called ZFN804A; one of over 100 identified by a previous study as being linked to schizophrenia risk. ZFN804A is known to be significantly associated with schizophrenia, said Dr Yingwei Mao at Pennsylvania State University, and lead author of the current study.

'We provide molecular evidence showing that ZNF804A could contribute to psychiatric disorders like schizophrenia,' he said. The study supports the idea that early changes in neurodevelopment may trigger effects that are not seen till later in life. Schizophrenia usually manifests in late adolescence or early adulthood.

The researchers demonstrated that ZFN804A is necessary for the development of normal brain structure and function in mouse embryos. The gene influenced two crucial processes: proliferation, which is the replication of neuronal stem cells and migration, which is the movement of neuronal cells to specific locations within the developing brain.

'Disturbances to these processes may cause neuronal stem cells to develop into different types of cells or may cause neurons to migrate to different locations in the brain, changing neuronal circuitry and potentially leading to behavioural disorders like schizophrenia,' explained Dr Mao.

Using a yeast cell model, ZFN804A was also found to interact with at least nine genes that are involved in translating mRNA (messenger RNA) into proteins. This indicates that ZFN804A plays an important role in regulating the decoding of genes to proteins.

The researchers add that ZFN804A also interacts with other genes implicated in schizophrenia risk, highlighting the complexity of schizophrenia and the need to gain a better understanding of the underlying causes.

'Determining the role of ZNF804A is the first step in understanding how schizophrenia-associated genes contribute to abnormal brain development,' said Dr Mao. 'Understanding how these genes interact to contribute to the development of schizophrenia may allow us to identify the general pathway of the disease, potentially providing a better target for treatment.'

The study was published in Molecular Psychiatry.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

18 September 2017 - by Annabel Slater 
A 'genetic lifespan calendar' of lifelong gene expression changes has been discovered in human and mouse brains...
11 September 2017 - by Annabel Slater 
Mice deprived of two essential fatty acids during pregnancy give birth to pups with schizophrenia-like symptoms...
21 March 2016 - by Sarah Gregory 
A rare mutation in a single gene increases the risk of schizophrenia by 35 times, a new study has found...
01 February 2016 - by Helen Robertson 
A gene involved in managing the connections between brain cells appears to be associated with an increased risk of developing schizophrenia...

HAVE YOUR SAY

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Syndicate this story - click here to enquire about using this story.


 

Complaint on Irish IVF clinic's 'misleading' advert upheld

02 October 2017

By Julianna Photopoulos

Page URL: http://www.bionews.org.uk/page_891561.asp Appeared in BioNews 920

A complaint about radio and internet advertisements for a major IVF clinic in Ireland has been upheld by the Advertising Standards Authority for Ireland (ASAI).

The clinic, Sims IVF Cork, ran a radio commercial claiming 'If there's a [fertility] problem, our dedicated medical team ...will find it' through its 'his and hers' fertility tests.

Their internet advertisement described the fertility test as involving 'for the woman a simple AMH [anti-mullerian hormone] blood test that will accurately predict how fertile you are'.

However, an anonymous complainant found the radio advert 'misleading' and told the ASAI 'she did not consider that it was possible to guarantee that all fertility problems could be identified', as some patients have unexplained infertility. 

She further explained that issues caused by poor egg quality may only come to light following one or more IVF procedures.

Of the internet advert, the complainant considered it was 'irresponsible' to claim that 'AMH tests alone would accurately predict how fertile a woman was' and questioned their accuracy.

The advertisers disagreed with this and responded that 'the testing of AMH levels was accepted worldwide as an excellent method of measuring a woman's ovarian reserve and by extension her fertility potential'. They cited more than 600 articles that linked a woman's AMH levels to her fertility and mentioned that the clinic itself has written two peer-reviewed journal articles on the subject.

However, the clinic added: 'The AMH value was not taken on its own, but formed part of a diagnosis that looked at both female age and reproductive history.' Additionally, they said the test had 'a powerful prognostic value' when used together with a standard semen analysis taken from the male partner.

The ASAI committee acknowledged that 'infertility was a sensitive topic for many people' and found both Sims IVF Cork's adverts' claims to be in breach of several codes of the law. The clinic's internet description of the AMH test was considered 'likely to mislead' as the clinic had admitted that other factors would also be considered. The radio claim 'If there is a problem … we will find it' was found  to be an absolute claim which was unsubstantiated. 

'The advertising should not be used in its current format,' the ASAI concluded.

SOURCES & REFERENCES
The Daily Edge | 26 September 2017
 
Advertising Standards Agency Ireland | 
 
thejournal.ie | 23 September 2017
 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

16 October 2017 - by Shaoni Bhattacharya 
Tests which assess how many eggs a woman has in her ovaries do not accurately predict fertility, finds a new study...
09 October 2017 - by Georgia Everett 
For the first time couples in Ireland will be eligible for financial aid for fertility treatments, after the Government signed off new proposals last week...

03 April 2017 - by Antony Blackburn-Starza 
The controversial issue of IVF 'add-ons' – techniques and treatments offered to fertility patients on top of standard IVF – has been the subject of intense debate and media attention since last November's BBC Panorama's documentary, which claimed that many techniques advertised on fertility clinics websites were not backed up by good scientific evidence of success...
16 January 2017 - by Rikita Patel 
A number of IVF clinics in the UK could be misleading people with their advertised success rates, a study suggests...
21 November 2016 - by Rikita Patel 
A number of Australian IVF clinics are potentially misleading patients about their success rates, a consumer watchdog has warned...
05 September 2011 - by Rosie Beauchamp 
An Australian fertility clinic has screened what is believed to be the first TV advertisement featuring a real birth...

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Risk of developing autism is mostly caused by genetics

02 October 2017

By Shaoni Bhattacharya

Page URL: http://www.bionews.org.uk/page_891570.asp Appeared in BioNews 920

Genetic factors may explain most of the risk of developing autism spectrum disorder (ASD), suggests a new analysis.

It calculated that ASD has 83 percent heritability - this is a measure of the extent to which a particular trait is inherited within a population.

The paper, published in JAMA, is a re-analysis of a previous study by the same researchers in twins and siblings that concluded that ASD was 50 percent heritable. Many studies have attempted to quantify the contributions of genetics and environment to the risk of ASD, and estimates vary widely.

'We already know that autism has very substantial genetic contributions,' Dr Daniel Geschwind, a geneticist at the University of California, Los Angeles School of Medicine, told HealthDay News. 'The question is how much is genetic and how much is environmental?'

The authors of the new analysis put the findings into context. 'This estimate [83 percent] is slightly lower than the approximately 90 percent estimate reported in earlier twin studies and higher than the 38 percent estimate reported in a California twin study, but was estimated with higher precision,' they wrote. 'Like earlier twin studies, shared environmental factors contributed minimally to the risk of ASD.'

Dr Sven Sandin at the Icahn School of Medicine at Mount Sinai, New York, and colleagues used an alternate method to re-analyse their data from a large study of children born in Sweden between 1986 and 2006, which followed them until December 2009. This included approximately 37,600 sets of twins, 2,642,000 full sibling pairs, and about 877,800 half-sibling pairs. Of these, about 14,500 children were diagnosed with ASD.

Although the two analyses produced hugely different results for heritability, the authors of the latest analysis note: 'In both analyses, the heritability of ASD was high and the risk of ASD increased with increasing genetic relatedness.'

But Dr Sandin added: 'Even in couples who already have a child with autism, the likelihood that their next child will also develop autism is increased, but still not very high.'

The large size of the study supports the validity of the findings, said Dr Geschwind.

SOURCES & REFERENCES
The Independent | 26 September 2017
 
JAMA Network (For the Media) | 26 October 2017
 
Medical Xpress | 26 September 2017
 
HealthDay News | 26 October 2017
 
JAMA | 26 September 2017
 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

30 May 2017 - by Professor David Skuse 
In recent years, there has been an explosion in the number of children diagnosed with autism. There is seemingly one in every classroom, most of them boys; some are quiet and nerdy, others may be disruptive and aggressive. Most have normal intelligence, and can be educated in mainstream schools. Parents of such children  question why one child is affected...
06 March 2017 - by Jamie Rickman 
Researchers have discovered that genetic variants associated with Autism Spectrum Disorder (ASD) also correlate with higher intelligence...
09 March 2015 - by Sophie McLachlan 
A UK twin study estimates that between 56 and 95 percent of autism spectrum disorder cases are attributable to genetics...

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Syndicate this story - click here to enquire about using this story.


 

Child brain cancer redefined as 10 different diseases

02 October 2017

By Dr Molly Godfrey

Page URL: http://www.bionews.org.uk/page_891588.asp Appeared in BioNews 920

Deadly childhood brain tumours are highly diverse and can be divided into 10 different subtypes, according to new research.

High-grade gliomas are highly aggressive cancers and responsible for the greatest number of childhood cancer-related deaths due to a lack of effective therapies. This reclassification could lead to more personalised and successful treatments by taking into account the genetic makeup of the tumours.

Study leader Professor Chris Jones from the Institute of Cancer Research (ICR) in London, said: 'Our study uncovered a wealth of new information about children's brain cancers. We found that tumours that have historically been lumped together under one diagnosis are in fact comprised of many, remarkably different, diseases.'

Scientists from the ICR examined 1067 cases of high-grade gliomas in children and young adults and classified them according to clinical and molecular markers. These included age of onset, appearance and location of the tumours, and the number and type of genetic mutations. They found that these cancers, previously classified together, were in fact highly divergent.

'Treating cancer based only on what we see down the microscope simply isn't good enough any more. We need to start thinking about these as completely different cancers and diagnosing and treating them based on their genetic faults,' said Professor Jones.

One of the most relevant findings from the study was the genetic diversity of these cancers – for instance, some children's tumours were driven by a single genetic mutation, while a small subset had tens of thousands of genetic errors. Promisingly, some mutations were identified for which drug targets have already been developed (to treat adult cancers), and numerous new potential therapeutic targets within each subtype were also discovered.

'It's exciting that several types look like they could be clearly treatable using either existing drugs on the market or other treatments under development,' said Professor Jones.

The study was published in Cancer Cell.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

31 July 2017 - by Rikita Patel 
The IBM Watson supercomputer can analyse 160 hours' worth of genomic data in just ten minutes...
03 April 2017 - by Annabel Slater 
New genes indicating risk of ovarian and brain cancer have been identified using genome-wide association studies...
04 April 2016 - by Dr James Heather 
Hospitals around the UK are going to start examining the DNA of tumour cells from paediatric cancer patients in a pilot study starting later this year...
23 November 2015 - by Dr Molly Godfrey 
A substantial proportion of childhood cancers are caused by mutations in genes that are known to cause cancer in adults, scientists have found...

HAVE YOUR SAY

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Syndicate this story - click here to enquire about using this story.


 

CRISPR used to uncover new drug targets for cancer

02 October 2017

By Rachel Reeves

Page URL: http://www.bionews.org.uk/page_891637.asp Appeared in BioNews 920

New potential drug targets have been identified for cancers associated with KRAS gene mutations, which are thought to drive around 20-30 percent of all human cancers.

Researchers used CRISPR genome editing to identify two genesNADK and KHK, which markedly reduced the growth of human colorectal cancer cells with KRAS mutations when inactivated in a mouse model. The team also found new 'tumour suppressor' genes – those involved in keeping cancers at bay.

'One of the most surprising findings from our study is how performing this type of genetic screen directly in a mammalian microenvironment revealed not only new synthetic lethal interactions, but also new tumour suppressor genes that are dependent on KRAS mutations,' said Dr Edwin Yau of the University of California San Diego (UCSD), and first author of the study.

Cancers caused by KRAS mutations include lung, pancreatic and colorectal cancer - often the most lethal and difficult to treat.

While previous research has focused on directly targeting mutant KRAS proteins to treat cancer, with limited success, researchers at the UCSD's School of Medicine decided to search for other genes which kill KRAS-mutated cancer cells when inhibited.

The team used genome editing to systematically inactivate every gene in the genomes of two human colorectal cancer cell lines with and without the KRAS mutation.

They then investigated whether inactivating these genes affected the ability of the cancer cells to grow in mice.

Inhibiting NADK and KHK, which code for metabolic enzymes, reduced the growth of KRAS-mutant colorectal cancer cells in mice by about 50 percent. There was no effect on cells with normal KRAS.

Crucially, the team saw these results only when the cancer cells were grown in mice rather than in vitro. The mammalian system provides 'a more realistic microenvironment where the tumour has to survive' explained Dr Tariq Rana, who led the study.

The researchers also found other genes that, when inactivated, had the opposite effect of NADK and KHK. These tumour suppressor genes increased the growth of KRAS-mutant tumours, but not of normal KRAS tumours. 

The team now want to carry out further research to better understand how KRAS-mutant cancers develop.

The study was published in Cancer Research.


The latest developments in genome editing will be discussed at the session 'What Next for Genome Editing? Politics and the Public', at the Progress Educational Trust's upcoming public conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction'.

The conference is taking place in London on Friday 8 December 2017. Full details - including sessions, speakers and how to book your place - can be found here.

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Epigenetics of addiction relapse probed using rats

02 October 2017

By Annabel Slater

Page URL: http://www.bionews.org.uk/page_891670.asp Appeared in BioNews 920

Researchers have identified how the likelihood of cocaine addiction relapse is influenced by epigenetic changes in rats.

The findings could be used to understand why drug users relapse and potentially devise new therapies.

'Our goal was to discover the brain mechanisms responsible for the rewarding effects of the drug and the motivation to seek it even after long periods of abstinence,' said lead researcher Professor Christopher Cowan of the Medical University of South Carolina (MUSC).

Drug addiction alters the brain structures of addicts, and such users develop strong associations between drug effects and environmental cues. These associations can create cravings and lead to relapse in people who have quit drugs. The team of researchers investigated gene and enzyme interactions in cocaine-addicted rats to understand these associations further.

The team had previously found histone deacetylase 5 (HDAC5) enzyme can prevent rats from associating cocaine with simple cues of light and sound in the environment. HDAC5 is normally concentrated in the reward centre of the brain, which reacts strongly to cocaine, opioids and alcohol in both rats and humans.

When present in the nucleus of neurons, HDACs can block the expression of certain genes.

The researchers trained rats to press levers to receive a dose of cocaine, and to associate this with a light and sound cue. When they gave the rats HDAC5, it did not reduce the amount rats pressed the lever.

They then simulated withdrawal and abstinence in the rats by not giving them cocaine for a week, and presented them with the light and sound cue. Rats which had received HDAC5 previously did not press the lever as often as control rats. This effect continued even when researchers gave the rats a small dose of cocaine to restimulate drug-seeking behaviour.

This showed that HDAC5 prevented drug seeking and relapse behaviour in rats, even though it did not stop the initial addiction-like behaviour from forming.

The researchers then identified which genes HDAC5 binds to, finding the most significant gene was NPAS4. When the researchers reduced the amount of NPAS4 in the reward centre of the brain, rats took a longer time to associate the environmental cues with cocaine. However, they showed no difference in relapse after abstinence.

This suggested that additional genes, regulated by HDAC5, must also be affecting the strength of relapse.

Professor Cowan suggested to Newsweek that the results could potentially be used to develop therapeutic drugs to increase levels of HDAC5. '[the drug] could, in principle, help to reduce the urge to use drugs when a recovering addict encounters thing in the environment that they associate with drug use,' he said.

The researchers are now looking at additional enzymes known to be affected by drug use and which could influence relapse, and which may even be applicable to mental illnesses that use the same brain mechanisms.

'By understanding how these connects are made, we can devise therapeutic strategies to reverse these strong triggers for relapse and increase the chances of sustained recovery from addiction,' said Professor Cowan.

The study was published in Neuron.

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Video review: TED - Editing Our Evolution

02 October 2017

By Eleanor Taylor

Page URL: http://www.bionews.org.uk/page_892705.asp Appeared in BioNews 920

TED (Technology, Education and Design) are renowned for their short, engaging talks which aim to showcase powerful ideas and start a world conversation. Unsurprisingly, the recent explosion of interest surrounding the use of CRISPR/Cas9 genome editing technology has not gone unnoticed by the TED community and a plethora of talks have been created to publicise its potential.

The latest genome editing offering in the TED world comes from Dr Helen O'Neill, a molecular geneticist at University College London, UK. Dr O'Neill presented her talk 'Editing our Evolution: CRISPR/Cas9' at the 2017 TEDx Goodenough College event, which was themed '[R]evolution' and aimed to 'explore how and why the world and its inhabitants are constantly changing'. Dr O'Neill successfully delivers her talk in what I have come to know and love as the 'TED style'; she is passionate, she is concise, she uses grand statements - 'We are in the middle of a genetic revolution … one that will change everything' - and she weaves in humour to engage the audience. Indeed, her punchy statement 'when we mate, we mutate' is worthy of being printed on a t-shirt.

Dr O'Neill takes the audience through a history of how we as humans have tried to understand and manipulate our genetics, from selective breeding in agriculture from the 1700s to the present day. She describes how mutations can occur and the limitations that healthcare providers face when trying to treat disease. The thought-provoking observation that pharmaceutical products are almost exclusively tested on Caucasian males, which ignores the genetic diversity of gender and race, elegantly demonstrates that we could be doing better. It is at this point that Dr O'Neill introduces genome editing as a way of to develop personalised medical treatment based on our individual genetic make-up.

Dr O'Neill asserts that 'CRISPR is the smartphone of science'; rather than simply providing care for patients with a genetic disease, we could use this 'smartphone' to update our own technology, i.e. edit our genetic information, and potentially cure certain genetic illnesses. She acknowledges that this application will most likely be limited to the treatment of monogenic diseases, but challenges the audience to sit up and take notice because there are between 5,000-8,000 single-gene disorders that could potentially be treated.

But both the beauty and the downfall of TED talks lie in their short duration; any talk longer than 18 minutes is thought to be at risk of creating 'cognitive backlog' where audience members start to retain less of the presented material. However, in order for the talk to reach some educational depth the speaker needs to restrict the number of ideas that are presented to the audience. Dr O'Neill's talk struggles slightly with the latter, she breaks down the field of genetics to its very foundation, ensuring that all audience members can follow her narrative but as a result she only just manages to scratch the surface of what genome editing is and how it could be of benefit.

Dr O'Neill informs the audience that CRISPR could potentially be used in two ways; one, to treat individuals with a genetic illness and two, to prevent the illness from developing in the first place, however, the methodology for the latter does not receive any further attention. Yet I would argue that the potential to edit the germline and prevent the transmission of a heritable disease is worthy of discussion at a R[evolution] themed event.

An examination of the ethical dilemmas associated with genome editing's potential clinical application is also restricted by time limitations. Dr O'Neill acknowledges that 'ethics is a big problem' in the world of genome editing, however, she succinctly declares that the therapies we have at the moment are not good enough, and rather than debate the pros and cons, she urges the audience to 'move beyond caution to curiosity'.

So Dr O'Neill's talk is executed in an extremely competent, 'TED-like' manner, but the focus on breadth rather than depth of content somewhat limits its widespread appeal. Lay audience members will most likely enjoy Dr O'Neill's playful presentation style and find this talk a useful introduction to the field of genomic medicine, however, individuals that already have some familiarity with genome editing technologies may prefer to explore some of the other genome editing TED talks that are available.

From Dr O'Neill's talk you start to get a sense of the excitement building around CRISPR/Cas9 technology. However, like all good talks, it leaves you wanting more. The talk sadly ends just when the brilliant potential of genome editing starts edging into your awareness; just when you start to realise that maybe Dr O'Neill is right - we are in middle of a genetic revolution.


Dr Helen O'Neill will be chairing the session 'Creating Life in the Lab: In Vitro Gametogenesis (IVG) and Synthetic Human Entities With Embryo-Like Features (SHEEFs)', at the Progress Educational Trust's upcoming public conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction'.

The conference is taking place in London on Friday 8 December 2017. Full details - including sessions, speakers and how to book your place - can be found here.

SOURCES & REFERENCES

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Podcast Review: 'The Why Factor: Surrogacy' BBC World Service

02 October 2017

By Melissa Elsworth

Page URL: http://www.bionews.org.uk/page_892713.asp Appeared in BioNews 920

Why would a woman choose to carry a baby for another person? Should money be involved? Does surrogacy exploit vulnerable women? And what other ethical issues are involved in the surrogacy process?

In the BBC World Service's The Why Factor: Surrogacy podcast, Mary-Ann Ochota interviews individuals with a variety of connections to surrogacy: surrogates, intended parents and an anti-surrogacy activist, as well as representatives from a US fertility clinic, Families Through Surrogacy (a not-for-profit organisation), and the University of Cambridge's Centre for Family Research.

Despite the obvious limitations of a 23-minute podcast, it manages to provide important background information while also engaging (albeit superficially) with some of the ethical issues surrounding surrogacy and flagging up issues which could form the basis of future debates.

The podcast outlines the differences between traditional, gestational, altruistic, and commercial surrogacy, and explains that different countries have different laws governing surrogacy. These range from outright bans to permitting so-called 'commercial' surrogacy.

Although not discussed in depth, it also highlights other important issues, such as the impact on the surrogate's own children, the need for surrogate-born children to know their creation story, whether there should be an age-limit for intended parents (an intended mother in her mid-sixties is discussed), and who the child's true parents are.

In terms of the ethical issues involved in surrogacy, the podcast does, to a certain extent, explore the issue of the exploitation and motivation of surrogates. In my view, one of the best aspects is that it includes interviews with surrogates (rather than just industry professionals) and that these surrogates are from very different backgrounds and cultures. It was particularly valuable to be able to compare the experiences and motivations of surrogates in Canada (which permits altruistic surrogacy), Oregon, USA (which permits commercial surrogacy) and India (which permits commercial surrogacy - although no longer for foreign intended parents - see BioNews 913).

However, in my opinion, the podcast has several flaws, particularly as its main aim is to investigate the motivations, experiences and possible exploitation of surrogates.

Firstly, it does not properly explore the possibility that it is exploitative not to compensate surrogates (beyond reimbursing expenses), particularly when everyone else involved - doctors, agency, lawyers - are being paid, and surrogates are undertaking the riskiest job. These risks are highlighted by the Oregon-based surrogate, who sadly had to undergo a hysterectomy after giving birth.

Secondly, I feel that it could have investigated, to a greater extent, whether the motivations of compensation (being paid a sum over and above reasonable expenses) and altruism (wanting to help individuals who are unable to conceive and carry a child themselves) are mutually exclusive, or whether these can in fact co-exist. Although this was touched upon in the interviews with the Oregon and Indian-based surrogates, both stories were tinged by the sad though very rare outcome for the Oregon surrogate, and by the problematic practices of the clinics and agencies in India.

In my view, a more balanced presentation could include an interview with a surrogate who had not experienced a rare complication and who is based in a commercial surrogacy jurisdiction, such as California, where there is greater socioeconomic parity between the surrogate and the intended parents. In my experience, having worked alongside US surrogacy agencies and law firms (including in California), altruism and the desire to be compensated are not mutually exclusive aims.

Thirdly, the podcast failed to address the possible exploitation of intended parents, who are often so desperate to have a child (perhaps following unsuccessful IVF or repeated miscarriages) that they can be equally vulnerable and therefore are also in need of protection.

Overall, this podcast provides a good general introduction to surrogacy and is aimed predominantly at individuals who have no or little prior knowledge of this complex area. However, I would have liked to have seen the issues around exploitation explored in a more thorough and balanced way.

An interesting follow-up topic would be how to address the various risk factors involved in surrogacy and how this should be regulated, on both a domestic and international scale. After all, it is fairly straightforward to highlight the benefits and risks involved in surrogacy, but much more difficult to devise a regime whereby surrogacy arrangements can still take place with the proper protection of all parties involved. Given that the Law Commission is currently reviewing if and how surrogacy law should be reformed in England and Wales, a podcast addressing different reform proposals would be extremely valuable.

SOURCES & REFERENCES
BBC World Service | 02 October 2017
 

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Published by the Progress Educational Trust

CROSSING FRONTIERS

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Speakers include

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Professor Magdalena Zernicka-Goetz

Professor Robin Lovell-Badge

Sally Cheshire

Professor Guido Pennings

Katherine Littler

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Dr Sue Avery

Professor Richard Anderson

Dr Elizabeth Garner

Dr Andy Greenfield

Dr Anna Smajdor

Dr Henry Malter

Vivienne Parry

Dr Helen O'Neill

Dr César Palacios-González

Philippa Taylor

Fiona Fox

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