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Issue 932 (08 January 2018)

 

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

 


 

ESHRE 2018: Past, present and future

08 January 2018

By Dr Roy Farquharson

ESHRE chairman

Page URL: http://www.bionews.org.uk/page_921001.asp Appeared in BioNews 932

The European Society of Human Reproduction and Embryology (ESHRE) was created by Robert Edwards and Jean Cohen in 1984. The focus, complexity and growth of ESHRE have shifted dramatically over its 34 years of work, growing to provide leadership in reproductive medicine a global setting. Here is a short history of how the society evolved and a map of where it is heading next. 

History

ESHRE was founded six years after the birth of Louise Brown in 1978 but only in the latter two of those years had IVF made any visible recorded progress. Ethical objections and biological challenges had thwarted groups in Europe and the USA who were keen to follow the precedent of Edwards and Steptoe. Some - such as Howard and Georgeanna Jones in the USA - pursued the false scent of oocyte retrieval from a natural cycle. It was the lack of state support in Britain that had forced Edwards and Steptoe into private practice at Bourn Hall near Cambridge.

France had welcomed its first IVF baby in 1982, by which time IVF in the country was in the hands of two state-supported groups, those of the biologist Jacques Testart and the gynaecologist Jean Cohen, based in Paris. By 1984, despite several live births, IVF was still faltering in France, with low implantation and high ectopic rates. Edwards, whom Cohen had met at IVF workshops at Bourn Hall, rang Cohen to ask if he might help his young biologists.

So Edwards visited Paris to take a look. During this stay in early 1984 he and Cohen recognised the need for a European society along the lines of the American Fertility Society, with its own agenda, annual meeting and - most importantly - its own journal. Reproductive medicine and science had so far been dominated by the American journals but now, Edwards would say, 'when so many of the advances in IVF were made in Europe, it occurred to me that we needed a European journal to serve as a forum for this work'.

The result of these discussions was an informal exploratory meeting at the 3rd World Congress of IVF in Helsinki and a more formal meeting in London where the Society was formally founded and the name ESHRE first recorded. Implicit in the name is the recognition and integration of both science and clinical medicine in reproduction.

As in the origins of IVF, the origins of ESHRE are essentially a story of Robert Edwards, and today one cannot exaggerate the energy he put into the society. His papers in ESHRE's archives in Belgium are testimony to his boundless energy and gentle persuasion, evident in a deluge of correspondence which one day in 1984 ran to 37 letters on ESHRE business. Thus, by the time of that September meeting in London Edwards himself had drafted by-laws which, with amendments at the time, are largely the constitutional arrangements of ESHRE today. Edwards himself wrote up the minutes and noted: 'It was felt that the scope should be restricted in general to the study of gametogenesis, conception, the first trimester of pregnancy, but with the inclusion of associated topics of relevance.'

Early days

There is much else besides the name, the core of the constitution and the scientific scope that endures from those earliest days. Of obvious lasting impact are the annual meetings and the ESHRE journals. But it was also clear from the outset that an open position on the ethical questions likely to face assisted reproduction were high on Edwards's agenda. Indeed, many of ESHRE's original members cited consensus on the ethics of IVF as their principal reason for joining. And today ESHRE's position papers on matters of ethics and law were among the most cited references. Many of the future developments after this point demonstrate a clear inheritance of what justifies the raison d'etre of ESHRE. 

Present day

The society now has over 7,000 members from 119 countries and the Annual Meeting in 2017, held over four days in Geneva, attracted over 10,000 participants. In 2017, of 1725 submitted scientific abstracts to the ESHRE meeting, 52 percent originated from outside Europe.

Training support and education, including position papers, guidelines, training events and certification programmes make up much of the everyday activities of ESHRE today. The overall aim is to set good practice standards and making improvement accessible to all. To this end, ESHRE's registries in European ART (assisted reproductive technology) and global PGD  have painstakingly documented cycles and outcomes on an annual basis. Furthermore, the registries set a benchmark of safety, access and performance against which national activity can be measured. The decline in multiple pregnancy rate in IVF seen over the past decade must surely owe much to the findings of ESHRE's data-monitoring in a sector which in Europe still represents more than half of global ART performance. Vigilance and moral alertness remain strong elements of continued ESHRE activity and have led to greater collaboration with major European authorities.

Journals

In 2017 ESHRE added a fourth title to its stable of journals, HROpen, an open-access journal designed for unrestricted readership. The Society's three other titles were each devised by Edwards, with the flagship Human Reproduction launched in January 1986. This, more than anyone could imagine, would fulfil those first pioneer ambitions of founding a journal in which European scientists and clinicians would find a welcome home for their work. Human Reproduction's sister review journal Human Reproduction Update would go on achieve record-breaking impact factors in the categories of obstetrics and gynaecology, and reproductive biology.

Political role

It's also clear from the society's history, and the 40-year history of IVF, that ESHRE has never been afraid to face political or scientific challenges, however uncomfortable that may be. ESHRE opposed introduction of the infamous Law 40 in Italy in 2004 (banning embryo freezing and embryo selection). More recently it supported open ART legislation in Poland. ESHRE has also been consistent - even if controversially so - in its position on new introductions and adjuvant treatments in ART, repeatedly calling for a strong evidence base before everyday application. This has most prominently been seen in a cautious approach to aneuploidy testing in embryos, where ESHRE has repeatedly doubted the strength of the evidence for any improvement in live birth rates. 

The challenges facing ESHRE today are reflected in the diversity of ART and its social, political and personal implications. Political representation remains an ESHRE priority, to make sure that the directives and positions of a political Europe recognise ESHRE's members and the professional sector they represent.   

Future challenges

The aim and philosophy of ESHRE is based on the underlying recognition that reproductive medicine is equally dependent on scientific and clinical knowledge that ultimately improves global reproductive health, identifies and addresses barriers to access to infertility care and provides an incremental uplift in public health benefits. ESHRE is a growing, open and inclusive community where any member or delegate can meet the world's leaders in human reproduction. It is particularly receptive to the ideas and activities of young researchers and clinicians. 

ESHRE has achieved a global profile and is the reference point in reproductive science and medicine with over 7 million babies born by IVF. We see international collaboration as the gateway to the future. Research, practice and education remain the solid foundations on which ESHRE has supported its past, present and more importantly, its future. In practical terms, ESHRE subsidises many courses, activities and workshops, several at a financial loss, to encourage educational improvement among its members and non-European delegates thereby improving the global healthcare of countries.

The ESHRE community reflects the diverse specialty interests of its members by the support provided by 14 Special Interest Groups (SIGs). These all have something in common: their passion for reproductive health and the understanding of human reproduction. In joint collaboration with our partner patient organisation, Fertility Europe, we undertook an audit that was launched in the European Parliament in March 2017, which addressed differing profiles of nine member states in relation to provision and funding of reproductive healthcare. Clear anomalies were highlighted and further collaboration with Fertility Europe is ongoing in support of European Fertility Week, which launched on 6 November 2017.

The ESHRE Executive Committee will have a more complex and growing agenda to deal with in the next two years. A comprehensive root-and-branch strategy meeting held over two days in May clearly identified areas for development and reconfiguration. As a result, a one-day meeting in September consolidated objectives and drew the roadmap for future direction of travel. Ongoing collaboration with our international partners will build on the shared areas of interest that will benefit from multiagency working. 

SOURCES & REFERENCES

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Creating life in the lab: in vitro gametogenesis (IVG) and synthetic human entities with embryo-like features (SHEEFs)

08 January 2018

By Dr Jess Buxton

Senior Lecturer in Medical Genetics, Kingston University London and Trustee, Progress Educational Trust

Page URL: http://www.bionews.org.uk/page_921077.asp Appeared in BioNews 932

What exactly are SHEEFs and IVGs? How might they shed light on the mysteries of early embryo development, and offer new hope to those affected by infertility? These questions - as well as the more philosophical issue of whether SHEEFs 'challenge what it is to be human' - were the focus of the second session at the Progress Educational Trust's annual conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction' in London on 8 December 2017.

The session featured three presentations from world-leading experts: Professors Magdalena Zernicka-Goetz, Azim Surani and Robin Lovell-Badge. These were followed by a wide-ranging discussion, deftly chaired by Dr Helen O'Neill at University College London.

The topics covered perhaps require some introduction, given the astonishing pace of recent developments. Although the term SHEEFs (synthetic human entities with embryo-like features) surfaced in early 2017, the research leading to SHEEFs builds on years of scientific work.

In 1998, a US team reported the first successful isolation of human embryonic stem (ES) cells. This major breakthrough was followed by another in 2006, when Japanese researchers found that adult body cells grown in the lab can be returned to an embryonic state – resulting in so-called IPS (induced pluripotent stem) cells. Both ES and IPS cells are described as pluripotent – that is, they have the potential to grow into almost any of the 200-plus different types of cell found in our bodies. That includes sperm and egg cells, with the term in vitro gametogenesis (IVG) being used to describe the production of artificial gametes from pluripotent stem cells.

Recent studies are now bringing together new advances in stem cell biology and tissue engineering to recapitulate embryo development in the lab. Under the right growth conditions, both human and mouse ES cells can self-organise into structures called 'gastruloids' that show some of the features seen following gastrulation - the stage of early development at which embryos change from a blob of cells to something with a front, back, top and bottom.

The first speaker in the conference session, Professor Zernicka-Goetz at the University of Cambridge, in her talk on 'Building Embryo-Like Structures In Vitro' described her team's ground-breaking work in this area. She focused on the stage of development just before implantation of the embryo into the uterine wall, often described as a 'black box', because so little is known about this process.

Implantation occurs after the cells of the embryo (at this stage called a blastocyst) have differentiated into two populations: those that will form the tissues of the actual embryo, and those (the trophectoderm) that will form the placenta and associated tissues. Professor Zernicka-Goetz explained that implantation requires 'a partnership' of these embryonic and extra-embryonic tissues, and that a failure of this process is responsible for 30-70 percent of early pregnancy loss. Studying how these cells develop and interact during this crucial developmental stage could shed light on this problem, she said.

Professor Zernicka-Goetz's team recently managed to produce an embryo-like structure in the lab, by growing mouse ES cells and extra-embryonic trophoblast stem (TS) cells together in a 3D-scaffold. The study, published in Science last year, showed that the ES and TS cells can self-assemble into structures with a shape, organisation and cell population that closely resembles that of natural post-implantation embryos. This work paves the way for further experiments that should help prise open the black box – in mice at least.

Professor Surani at the University of Cambridge, gave the next presentation on generating germ cells. He reminded the audience that we have only recently started to understand the origins of human germ cell development, even though human primordial germ cells (hPGCs - the progenitor cells that give rise to the gametes) were seen in three week-old embryos around 100 years ago. Before then, in 1892, August Weismann was the first to articulate the idea that heritable information is transmitted only by germ cells, not by somatic cells – his 'germ plasm' theory of inheritance.

Professor Surani's team has been studying how PGCs develop into egg and sperm cells. This work could eventually lead to new treatments for infertility, as well as shedding light on this fundamental yet poorly understood developmental process. He described his group's recent experiments, in which they have grown hPGCs within 'gonadal organoids';, up to the equivalent stage reached in a 4 week old human embryo. Their next goal was to reach week 7-8, he said, as this is when sperm and egg producing cells become distinct. The team have also looked at the epigenetic marks present in the DNA of the lab-grown PGCs, to check that they are being erased and reset correctly.

In a subsequent article published in the Guardian newspaper, Professor Surani said the production of artificial gametes for treating infertility was likely to be 'at least a decade away' and stressed it would first be essential to show that lab-grown egg and sperm had gone through 'all of the right stages'.

The final talk in this session, 'Do SHEEFs Challenge What It Is to Be Human?' was given by Professor Lovell-Badge at the Francis Crick Institute. 'Probably not' was his succinct answer – but could SHEEFs challenge the 14 day rule? This is the legal and regulatory limit in the UK that restricts research on human embryos to the period before the 'primitive streak'; appears at the start of gastrulation. It is the faint band of cells marking the beginning of an embryo's head-to-tail axis.

Professor Lovell-Badge explained that the acronym SHEEFs (which encompasses human gastruloids) first appeared in an article published in eLife last March. It reviewed recent and possible future developments in the field, and considered the new ethical challenges SHEEFs may pose. They concluded that limits on such research should be based on 'the appearance of features or capacities that are associated with moral status', rather than defined developmental stages such as the appearance of the primitive streak. This approach, they argued, would allow for the regulation of work on other types of possible SHEEFs, such as a 3D printed post-gastrulation embryo.

Professor Lovell-Badge went on to consider the thorny issue of how the moral status of such entities might be assessed – the beginnings of a brain? An ability to feel pain? But, he pointed out, although both neural connectivity and the presence of pathways involved in perceiving pain could potentially be detected in a SHEEF, there is no way of testing for consciousness. He also asked how SHEEFs differ from teratomas, tumours that contain several types of tissue, which can occur either naturally or following injections of IPS and ES cells.

Overall, this fascinating session on cutting edge developments in reproductive science may have thrown up more questions than answers, but the opportunity it provided to engage with the researchers carrying out this work was invaluable.

Whether its new research on SHEEFs, IVGs or the potential ethical dilemmas they pose, BioNews will be continuing to cover developments in this field and other areas of genetics, assisted conception and embryo and stem cell science throughout 2018 – if you don't already receive the weekly email roundup of this free newsletter then you can do so here.

PET would like to thank the sponsor of this session, the Edwards and Steptoe Research Trust Fund, and the other sponsors of its conference - the Anne McLaren Memorial Trust Fund, the ART Institute of Washington, Ferring Pharmaceuticals, the London Women's Clinic and Vitrolife.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

12 February 2018 - by Professor Robin Lovell-Badge 
The problem of fertility preservation for girls and women undergoing cancer treatments has been a subject of research for many decades. The recent study by McLaughlin and colleagues from Professor Evelyn Telfer's lab at the University of Edinburgh, UK, is aimed at finding a solution to this problem, with the claim that they have produced mature human egg cells in the lab for the first time...
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Is sexual reproduction still compatible with Western values? Can germline genome editing ever be considered as medicine? Can we stick to act only on serious disorders? These were some of the provocative and complex questions which were addressed during the last session of the Progress Educational Trust's annual conference...
15 January 2018 - by Eleanor Taylor 
The ever-expanding limits of human reproduction are creating complex ethical and political challenges. One topic that has generated much contention is the possibility of editing the genome of human embryos...
15 January 2018 - by Dr Danielle Griffiths 
'The Wild East and the Worried West: Pioneers or Outlaws?’ was the third session of the Progress Educational Trust's (PET) Annual Conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction'...

18 December 2017 - by Dr Avi Lerner 
The Progress Educational Trust (PET)'s Annual Conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction' discussed some of the most important ethical and scientific questions facing human reproduction. The first session, chaired by Sarah Norcross, the Director of PET, tackled the very fundamentals. What is a sperm? What is an egg? And what is an embryo?...
27 March 2017 - by Dr Rachel Huddart 
Rapid advances in stem cell and embryo research are in danger of outstripping current ethical guidelines and new regulations are urgently needed, warn scientists in a report published this week...
13 March 2017 - by Dr Dusko Ilic 
The regulatory mechanisms governing organ development are, in general, poorly defined. To recreate the complex processes involved in organ growth and maturation, scientists have started fiddling with three-dimensional (3D) cell culture...
06 March 2017 - by Anna Leida 
Stem cells from an adult mouse have been used to grow a structure resembling a mouse embryo in vitro for the first time...

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Taking paracetamol during pregnancy may reduce fertility of daughters

08 January 2018

By Ewa Zotow

Page URL: http://www.bionews.org.uk/page_920698.asp Appeared in BioNews 932

Exposure to paracetamol during pregnancy may reduce the fertility of female offspring, suggests research in rats and mice.

Dr David Kristensen at Copenhagen University Hospital in Denmark and colleagues, reviewed three recent studies on the effects of paracetamol administration during pregnancy in rats and mice. All three studies found evidence for disrupted reproductive development of female offspring, including a lower number of eggs and reduced fertility in adulthood. The review was published in Endocrine Connections.

This may be a cause for concern as paracetamol is a commonly prescribed painkiller worldwide. Previous studies have already highlighted the risks associated with exposure to chemicals during pregnancy, including a link between prenatal exposure to analgesics and reduced fertility in male offspring (see BioNews 584), however studies on females had been lacking. Females, unlike males, are born with a set number of gametes. This means that any disruption during the development may be damaging to their future fertility. 

'Although this may not be a severe impairment to fertility, it is still of real concern since data from three different labs all independently found that paracetamol may disrupt female reproductive development in this way,' said Dr Kristensen. He added that further investigation was needed to establish any effects on human fertility. 

Despite similarities between rodent and human reproductive systems, it is difficult to know to what extent these findings are relevant to human pregnancies. The dosage and length of paracetamol administration in these studies may not be representative of a typical use of painkillers in pregnant women; in two of the studies the dose was much higher than the standard recommendation, and the drugs were given for a relatively high proportion of the pregnancy duration. 

Short-term use of paracetamol is currently considered safe during pregnancy. 'Current recommendations regarding paracetamol use for the shortest duration necessary to relieve pain during pregnancy should not change on the basis of this review article,' said Dr Rod Mitchell, consultant paediatric endocrinologist at the University of Edinburgh.

However, 'further research, including laboratory experiments using human tissues or large population-based studies looking at adults exposed to paracetamol in-utero, is required to determine whether paracetamol exposure during pregnancy can adversely affect fertility in humans', he added.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

15 January 2018 - by Nina Chohan 
Men who regularly take the maximum recommended dose of ibuprofen may be at an increased risk of fertility issues...

03 July 2017 - by Emma Laycock 
The daily use of paracetamol in pregnant mice affects the brain development and behaviour of male offspring, according to researchers in Denmark...
01 February 2016 - by Fiona Ibanichuka 
Scientists have discovered that the use of painkillers during pregnancy in rats may reduce the fertility of their offspring...
15 November 2010 - by Seil Collins 
New preliminary research suggests a possible link between the use of mild painkillers during pregnancy and the birth of male children with congenital cryptorchidism, more commonly known as undescended testes, a condition which reduces male fertility. The rates of undescended testes seen in the study remained relatively low....

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German court rules that trans woman cannot be child's mother

08 January 2018

By Dr Lanay Griessner

Page URL: http://www.bionews.org.uk/page_920769.asp Appeared in BioNews 932

Germany's Federal Court of Justice (BGH) has ruled that the a trans woman must be registered as her child's legal father and not its mother.

The woman, who was assigned male at birth, froze sperm before undergoing gender reassignment and has been legally living as a woman since 2012. She is in a same-sex marriage, and in 2015 her spouse gave birth to a child conceived using the frozen sperm.

Prior to the child's birth, the couple made a written request to have both partners listed as mothers of the child in order to correspond with their gender identities. The birth registry denied this request and listed only the birth mother as the mother, and the wife who provided the sperm as the biological father. The couple unsuccessfully sued the birth registry in the Schöneberg regional court, and appealed to the BGH, which upheld the regional court's decision. 

The BGH concluded that: 'The trans person's fundamental rights aren't breached by the fact that existing ancestry law assigns her the legal status of parent according to her former sex and the specific contribution to procreation that resulted from this.'

Therefore, providing the sperm makes a person the father and the person who gives birth is always the mother, regardless of their legal genders. This was confirmed in a September 2017 case where the BGH ruled that a trans man who gave birth was considered the mother of his child, and not the father, even though he was no longer legally a woman.

Gabriela Lünsmann, board member for the Lesbian and Gay Association (LSVD) of Germany criticised the ruling for infringing a transgendered person's right to parent according to their gender identity. The LSVD is now calling for reform to the existing law to allow for more gender neutral parental assignments in the future. 

SOURCES & REFERENCES
News 24 | 04 January 2018
 
Deutsche Welle | 04 January 2018
 
Lesbian and Gay Association, Germany | 04 January 2018
 

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29 January 2018 - by Sam Sherratt 
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13 November 2017 - by Sean Byrne 
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15 August 2016 - by Dr Mary Yarwood 
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15 August 2016 - by Ryan Ross 
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15 May 2012 - by Dr Vardit Ravitsky and Professor David Heyd 
Sex reassignment is an intricate and sensitive physiological, psychological, and social process that usually entails the loss of reproductive capacity. Reproductive technology can prevent this loss, but should it be used for that purpose? A recent case in Israel raises this question...

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Sperm 'obstacle course' could improve IVF success

08 January 2018

By Dr Rachel Brown

Page URL: http://www.bionews.org.uk/page_920731.asp Appeared in BioNews 932

An 'obstacle device' has been developed by scientists in the United States which can select the fastest and healthiest sperm to use in assisted reproductive techniques.

The device - termed Spartan (Simple Periodic Array for Trapping And isolation) - was inspired by the natural filter-like capabilities of the female reproductive tract and developed by a team of researchers from Worcester Polytechnic Institute and Stanford University.

Sperm are injected into one end of the 14 millimetre long device, and must swim through numerous three-dimensional pillars to the other end. 

About 99 percent of the sperm that make it through the device are motile and the simple technique also avoids the type of damage that can occur with traditional sperm sorting methods, such high-force centrifuges. It is hoped that by selecting the healthiest sperm, patients undergoing ART will have a better chance of conceiving. 

Professor Erkan Tüzel, a biomedical engineer at the Worcester Polytechnic Institute who led the work as said: 'With Spartan, we not only get sperm with excellent motility, but also with normal morphology and better DNA integrity, helping families worldwide by reducing the stress of multiple IVF procedures, while potentially increasing pregnancy rates.'

Spartan is a simple one-step procedure and takes around 10 minutes to perform, meaning it is also easier to use in the clinic compared to current options and does not require sperm to frozen and shipped to another lab for processing.

The authors have noted, however, that the device is currently only able to recover a small number of sperm. While it is suitable for techniques such as ICSI which only need a single sperm, additional modifications will need to be made to make it suitable for other techniques that require a larger number of sperm such as intrauterine insemination.

The technology was published in the journal Advanced Science. It has since been licensed to the American company DxNow, which plans to make the product commercially available in July 2018 pending approval by the US Food and Drugs Administration.  

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

15 January 2018 - by Nina Chohan 
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18 December 2017 - by Dr Avi Lerner 
The Progress Educational Trust (PET)'s Annual Conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction' discussed some of the most important ethical and scientific questions facing human reproduction. The first session, chaired by Sarah Norcross, the Director of PET, tackled the very fundamentals. What is a sperm? What is an egg? And what is an embryo?...
27 November 2017 - by Dr Rosie Gilchrist 
Men living in areas with higher air pollution are also more likely to have a higher proportion of abnormally shaped sperm...
09 October 2017 - by Shaoni Bhattacharya 
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HAVE YOUR SAY

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


 

Professors Robin Lovell-Badge and Cathy Warwick recognised in New Year's Honours

08 January 2018

By Sandy Starr

Page URL: http://www.bionews.org.uk/page_921046.asp Appeared in BioNews 932

Leading figures in reproductive science and medicine have been recognised in the UK's New Year's Honours list 2018, including two experts who have previously written for BioNews - Professors Robin Lovell-Badge (see BioNews 781 and 799) and Cathy Warwick (see BioNews 738).

Professor Lovell-Badge - who has been awarded a CBE 'for services to genetics, stem cell research and the public understanding of science' - is group leader in stem cell biology and developmental genetics at the Francis Crick Institute in London. In 1990 his laboratory discovered Sry, one of the key genes responsible for sex determination in humans and in most other mammals. Sex determination remains a major focus of Professor Lovell-Badge's current research.

He is also active in policy, regulation and public debate concerning genetics, stem cells and human embryo research. In recent years he has played an especially prominent role in relation to genome editing, mitochondrial donation, in vitro derived gametes and synthetic human entities with embryo-like features (SHEEFs). As discussed elsewhere on BioNews this week, he gave a presentation on SHEEFs at the most recent annual conference of the Progress Educational Trust (the charity that publishes BioNews).

Professor Cathy Warwick - who has been made a dame 'for services to midwifery', having previously been awarded a CBE in 2006 'for services to healthcare' - is the outgoing chief executive of the Royal College of Midwives, and is also chair of trustees at the British Pregnancy Advisory Service.

Other honours for services to widwifery this year include an OBE for Wendy Matthews (of Barking, Havering and Redbridge University Hospitals Trust) and MBEs for Dr Tracey Cooper (of Warrington and Halton Hospitals NHS Foundation Trust) and Verena Wallace (of the Northern Ireland Executive's Department of Health).

SOURCES & REFERENCES

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

12 February 2018 - by Professor Robin Lovell-Badge 
The problem of fertility preservation for girls and women undergoing cancer treatments has been a subject of research for many decades. The recent study by McLaughlin and colleagues from Professor Evelyn Telfer's lab at the University of Edinburgh, UK, is aimed at finding a solution to this problem, with the claim that they have produced mature human egg cells in the lab for the first time...

HAVE YOUR SAY

By posting a comment you agree to abide by the BioNews terms and conditions


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


 

Gene therapy temporarily halts type 1 diabetes in mice

08 January 2018

By Isobel Steer

Page URL: http://www.bionews.org.uk/page_920707.asp Appeared in BioNews 932

A gene therapy has been used to restore normal blood sugar levels in mice with type 1 diabetes, according to a study published this month in the journal Cell Stem Cell.

In type 1 diabetes the immune system destroys beta cells, but not alpha cells, in the pancreas. A team at the University of Pittsburgh School of Medicine and the Children's Hospital of Pittsburgh attempted to turn alpha cells into beta cells, in order to produce insulin. 

'If you gave patients new insulin cells with a transplant, it will kill them off. If we use gene therapy to get the body to make new insulin-producing cells in the body, logically it should attack those cells too,' explained Dr George Gittes, a lead study author and pediatric surgeon at the University of Pittsburgh, to Gizmodo.

But their treatment was successful in mice, at least temporarily. They used an adeno-associated virus, the standard gene therapy technology, to deliver two proteins, Pdx1 and MafA, to the pancreas of a mouse. This reprogrammed alpha cells into beta cells. Normal blood sugar levels were restored in the diabetic mice. However, this effect only lasted for around four months, though this would likely translate to years in humans.

'This study is essentially the first description of a clinically translatable, simple single intervention in autoimmune diabetes that leads to normal blood sugars,' said Dr Gittes. Additionally, many treatments targeting autoimmune disorders such as diabetes depress the immune system, causing lifelong risks. This treatment doesn't – a key advantage.

The gene therapy has only been tested on mice so far, but future work will be carried out in primates, and the group hopes to gain approval from the US Food and Drugs Administration (FDA) for clinical trials in humans. It is a promising new approach to tricking the immune system and alleviating the symptoms of diabetes. 

At present, type 1 diabetes has no cure, and is managed with a lifetime of insulin injections. Insulin is a hormone produced by pancreatic beta cells, which drives glucose absorption, lowering its levels in the body. 

The finding it is the latest of a string of promising developments in gene therapy. In October, the FDA approved Spark Therapeutics's gene therapy for a rare form of inherited blindness (see BioNews 922). The month also saw successful human trials on haemophilia A (see BioNews 931) and haemophilia B (see BioNews 930). 

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05 February 2018 - by Ewa Zotow 
Animals given high doses of gene-carrying viruses in a new gene-therapy trial showed signs of severe toxicity.

11 December 2017 - by Isobel Steer 
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07 August 2017 - by Annabel Slater 
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Alcohol found to boost cancer risk by damaging stem cell DNA

08 January 2018

By Charlott Repschlager

Page URL: http://www.bionews.org.uk/page_920717.asp Appeared in BioNews 932

Drinking alcohol damages blood stem cells by altering their DNA, raising the risk of developing cancer, scientists have found.

A breakdown product of alcohol - acetaldehyde - is responsible for the damage, according to researchers at the MRC Laboratory of Molecular Biology in Cambridge. Acetaldehyde can cause irreversible DNA damage in blood stem cells, known as hematopoietic stem cells. These are the stem cells responsible for the constant production of fresh blood.

'How exactly alcohol causes damage to us is controversial,' said Professor Ketan Patel, who led the study which was published in Nature. 'This paper provides very strong evidence that an alcohol metabolite causes DNA damage [including] to the all-important stem cells that go on to make tissues.'

The link between alcohol and certain types of cancer has been known for some time, but exactly how drinking can raise cancer risk has been less clear. Acetaldehyde, a molecule produced by the breakdown of alcohol, badly damages DNA in cells, which in turn can lead to mutations and cancer, earlier studies have found. The cell has two ways of coping with the assault. 

First, acetaldehyde can be cleared away by the enzyme ALDH2 (aldehyde dehydrogenase 2). However, if more alcohol is consumed than the ALDH2 can deal with, then excess acetaldehyde can damage DNA. The second coping mechanism is to repair some of the DNA damage with an enzyme called FANCD2 (Fanconi anemia group D2 protein). 

In the study, the researchers used mice that did not possess either ALDH2 or FANCD2, or both, and gave them diluted alcohol for 10 days. They then sequenced the genome of their hematopoietic stem cells, to find that their DNA had been badly damaged. Hematopoietic stem cells from mice who had neither ALDH2 nor FANCD2 completely lost the ability to produce fresh blood.

'Our study highlights that not being able to process alcohol effectively can lead to an even higher risk of alcohol-related DNA damage and therefore certain cancers,' said Patel. 'But it's important to remember that alcohol clearance and DNA repair systems are not perfect and alcohol can still cause cancer in different ways, even in people whose defence mechanisms are intact.'

Around 8 percent of the world's population, especially people of East Asian origin, have very low levels of ALDH2. This can lead to 'flushing' after drinking. As a result, there is more pressure on FANCD2, and may lead to more missed DNA damage. This could be an explanation for the high incidence of esophageal cancer in countries such as China. 

Professor Linda Bauld, an expert on cancer prevention at Cancer Research UK, said: 'This thought-provoking research highlights the damage alcohol can do to our cells, costing some people more than just a hangover. We know that alcohol contributes to over 12,000 cancer cases in the UK each year, so it's a good idea to think about cutting down on the amount you drink.'

Cancer Research UK estimates that about 4 percent of cancers in the UK are caused by alcohol. One pint of lager or a large glass of wine a day significantly increases the risk of developing cancer.

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Offer egg freezing to all with medical need, say guidelines

08 January 2018

By Sam Sherratt

Page URL: http://www.bionews.org.uk/page_920747.asp Appeared in BioNews 932

The NHS should offer patients the chance to freeze their eggs before they receive treatments that could damage their fertility, say new guidelines published by the British Fertility Society (BFS).

Treatment for a variety of conditions, including cancer, lupus, sickle cell and gender dysphoria can leave patients unable to have children in the future. In new guidelines published in the journal Human Fertility last Wednesday, the BFS suggests that patients due to undergo these procedures should be allowed to store their eggs through the NHS to allow them a chance to have a family later.

'There are a number of situations where the preservation of fertility is needed,' said Professor Adam Balen, chair of the BFS. 'This has to happen at a time before a person is ready to start a family and can sometimes be the only hope for becoming a parent in the future.'

The NHS currently provides fertility preservation services for female cancer patients where infertility can be caused by side-effects of chemotherapy drugs or radiation. Services for patients with non-cancerous conditions that affect fertility are far patchier, and are only provided by certain Clinical Commissioning Groups (CCGs), leaving many patients uncovered.

For example, patients requiring stem cell transplants for blood diseases such as sickle cell or some types of thalassemia undergo chemotherapy to prepare their bodies for the new tissue, but although the side effects are comparable to those receiving chemotherapy for cancer, they are not necessarily given the same fertility preservation options.

Patients undergoing gender reassignment can have their fertility affected by hormone therapies and gonadal surgery, and according to Dr James Barrett, lead clinician at the Gender Identity Clinic at Tavistock and Portman NHS Foundation Trust: 'The number of people coming forward with gender dysphoria has increased rapidly over the past decade.'

Additionally, there are patients who have genetic or chromosomal conditions which will likely affect their fertility. Individuals with Turner Syndrome (monosomy X) are generally able to carry a pregnancy but can't make viable eggs. However, the BFS reports that mothers of girls with the condition may wish to donate their own eggs for freezing so their daughter can have a genetically related child later in life.

Fertility preservation technology has been available for over thirty years, and can include freezing either embryos, unfertilised oocytes or ovarian tissue. It costs around £5,000 to privately freeze eggs or embryos and around £300 a year to store them, making it unaffordable for many. Patients are then dependent on local CCGs who may or may not provide the needed services.

'Some CCGs say they will only fund for cancer,' said Dr Melanie Davies from the Department of Woman's Health, University College Hospitals London. 'What I would like to see is equity.'

NHS England responded to the publication of the new guidelines by saying that funding of fertility preservation treatment is a matter for local clinical commission groups.

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Event Review: The ethics and regulation of in vitro gametogenesis (IVG)

08 January 2018

By Sarah Carter-Walshaw

Page URL: http://www.bionews.org.uk/page_920770.asp Appeared in BioNews 932

IVG involves the use of stem cells to create sperm and egg cells in vitro, which can then be used to produce embryos. It is a technique that could provide a fertility treatment option for people who currently cannot have their own genetically related children – including infertile individuals or couples, older women, and same-sex couples. There have been some promising successes in trials with mice, and some commentators believe that within decades the intervention will be available for human use, be that for research or reproductive purposes.

A symposium on IVG on 14-15 September 2017 in London, part of the Wellcome Trust funded research programme entitled 'The Donation and Transfer of Human Reproductive Materials', generated lively debate between academics, policymakers, science communicators and scientists in the field. It was organised by Dr César Palacios-González and Professor Rosamund Scott of King's College London, and Professor Stephen Wilkinson of Lancaster University.

In addition to an enlightening session on the science and development of IVG with talks from Professors Azim Surani and Robin Lovell-Badge, there were talks on the broader ethical and legal implications by experts such as Professor John Harris (who noted questions surrounding what would be considered 'safe enough' in reproductive research), Professor I Glenn Cohen (who discussed the difficulties in regulation given the possibility of circumvention tourism), and Professor Henry Greely (who considered the ethical implications of using IVG technology). Four further talks considered more specific issues, questions and concerns raised by IVG.

Professor Sonia Suter discussed how IVG may be used to create vast numbers of embryos for the purpose of selective reproduction and the extent to which this raises concerns about choice overload for potential parents. Suter considered ways of dealing with this, including the use of algorithms, and noted the ethical concerns of the use of such technology for this purpose, such as possible abdication of decision-making, underlying biases, reduction in diversity, and commodification. 

Dr Saskia Hendriks presented her qualitative research on public, patient, and clinician perspectives. People currently unable to have their own genetically related children would be inclined to use IVG, she reported, and people would also be willing to trade-off genetic relatedness for things such as higher pregnancy rates and cheaper costs. Hendriks concluded that patients might be disinclined to pursue IVG – even at the cost of genetic relatedness – if it were risky, expensive or ineffective. Given the novelty of the technology, it was especially interesting to hear such empirical data, and this added further weight to the discussions on the value of genetic relatedness that arose several points in the symposium.

Seppe Segers explored ethical questions about 'designer babies' and IVG. He explained that while IVG may facilitate the creation of designer babies, it is neither necessary nor sufficient for this task. He concluded that even if IVG did facilitate this endeavour, it should not be grounds for undermining the development of the technology but instead should be regulated; this would be consistent with other assisted reproduction technologies and would mean that the value of genetic relatedness would be respected as well.

Dr Birgit Beck then discussed the idea that IVG technology could be used to create children who are direct descendants of early embryos and who could therefore be considered 'orphaned at conception'. She asked whether it would be wrong to bring such children into being and explored the metaphysical and moral implications of this question and of the notion of genetic orphans in general. The view as to whether (or why) it would be wrong to create children orphaned at conception would depend on one's conceptual, ontological and ethical commitments, Beck concluded. For instance, those that hold that an embryo is not an individual human being would not consider embryos to qualify as an interim generation. For these people, it would make no sense to talk of children being orphaned at conception.

The event provided much lively and stimulating debate into ethical, legal, and practical issues relating to research into IVG, and its possible use in fertility treatment. While its possible use for non-medical trait selection provides a new context in which to examine questions about selection and selective reproduction, the topic that generated the most discussion was that the intervention would allow people who are currently unable to do so, to have genetically related children. It called into question the value of genetic relatedness, the socio-ethical implications of any such value, and indeed whether there is a need or obligation to pursue interventions like IVG that would allow people to have genetically related children.

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