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The Fertility Show, Manchester Central, 24-25 March 2018

Issue 938 (19 February 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

 


 

We need progress in French ART law

19 February 2018

By Catherine Rongieres

Coordinator of ART centre, Strasbourg University Hospital, France

Page URL: http://www.bionews.org.uk/page_933236.asp Appeared in BioNews 938

The first law on Assisted Reproductive Technology (ART) was passed in France in 1994 as part of the so-called 'bioethics legislation' that followed other European countries' legislation, such as the UK's 1990 Human Fertilisation and Embryology act. France's law which placed much tighter constraints on individuals access to ARTs than the UK.

More European countries followed suit. Germany already possessed the strictest and the most binding legislation in the world regarding ART, with a few recent legal challenges notably on PGD (preimplantation genetic diagnosis). Conversely, Spain, still traumatised by the interference of the dictator Francisco Franco into the private life of citizens, considered ART a matter for the individual, resulting in a relatively non-restrictive 2006 law.

For a long time, Belgium had no legal framework for ART excepting a 2003 law relating to research on in-vitro embryos. Thus, apart from some recommendations relating to the age either of gamete donors, or of the recipient woman, and the prohibition of certain eugenic or commercial practices, there was no other limit or condition. When legislation was brought in, the goal is was to clarify rather than restrict practices: to set the procedures for a more uniform ART, increasing transparency and protecting the patients by reducing multiple embryo transfers. There is no legal limitation for the use of ART as the centres develop their own access criteria.

Thus the law from our neighbouring countries allow for quick and easy access to any new technology.

The French bioethics law of 1994 was revised in 2004 and 2011, as the intention was always to be able to modify it in the face of evolution of practices, and also of opinion and societal changes. In any case, this law was attractive because of the reflection it induced. However, contrary to common law, anything that is not explicitly authorised in this law is forbidden. Thus, any new technology or societal change which had not been anticipated is therefore impossible to access until the next revision.

Furthermore, although these revisions were planned every five years, they took place instead every seven years, and the publication of the necessary administrative permission (known as decrees of application) was sometimes delayed further. For example, while the law authorising women without children to donate eggs was passed in 2011, the necessary decrees were issued only in 2015.

This situation has led to our patients leaving for nearby countries (such as Spain, Belgium and England) to access what is forbidden to them in France. The French law, which claim to protect against commercial, eugenic or other abuses, does not fulfil their aims and undermines the principles on which the French pride themselves. Equitable access to healthcare instead becomes a two-tier system, where those who have the financial resources to go abroad can avail themselves of the techniques forbidden at home.

So yes, the stakes in this new revision of the law are major.

'What kind of world do we want for tomorrow?' It is a question that opened one of the 'états généraux' (or public discussions) on bioethics on 18 January. Such public meetings will continue to be held over six months and inform the new bioethics law, which will include ART access, expected at the end of the year.

The National Advisory Board of Ethics (CCNE) will collect opinions through their website and organise about 60 debates across France open to the public, and stakeholders such as patient groups, professional and academic societies and religious organisations. They will also consult experts from ethics committees of the main research institutes, and the regional education authorities.

It is not acceptable to integrate new technologies only when they have been validated by our neighbours. We shall not recover from the delay in some techniques which today are forbidden in France, such as (PGS (preimplantation genetic screening)), research on embryos or gene therapy. The expertise acquired, the spirit of innovation and criticism that develops whilst enacting a new practice is not transmissible, so we continue to lag behind.

One may well wonder whether the law should rule on any technique and in detail. For example, to be able to use the technique of freezing by vitrification, it was necessary to wait for the revision of the law in 2011. The efficiency of this technique was demonstrated in numerous scientific articles and it was adopted by our international counterparts. As soon as we were able to use it, our results very clearly improved.

But societal changes are also in question. Currently same-sex couples and single women may not access ART. Other forbidden practices include: surrogacy, egg freezing for non-medical reasons (except non-mothers who may preserve five oocytes for themselves when donating), double donation (where both eggs and sperm come from donors) and posthumous embryo transfer to a woman after her husband's death. Donor-conceived offspring have no right to know their genetic origins.

In June 2017, the CCNE recommended against widening access to egg freezing. The arguments put forward are of medical rather than ethical nature: stressing the dangerousness of the stimulation treatments and oocyte retrieval, as well as the lack of certainty of success. But if the CCNE considers the treatments of ART in this light, it should not only prohibit IVF in general but oocyte donation in particular that uses 'dangerous' treatments on women trying to help other women. This argument is totally inconsistent.

It is fundamental that ART professionals, as well as sociologists and lawyers concerned by these questions – as well as the concerned population – mobilise to bring back the debates to the concept of the individual's autonomy. This should be possible with an open and flexible law, which can still forbid eugenic or commercial practices and set limits to avoid dangerous practices. It should also enable access and appropriate research, but not get lost into the details which need purely a scientific peer review. I am afraid that France is not ready for it: we are still too paternalistic.

SOURCES & REFERENCES

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Short-acting asthma inhalers affect women's fertility

19 February 2018

By Dr Lanay Griessner

Page URL: http://www.bionews.org.uk/page_932717.asp Appeared in BioNews 938

Women using short-acting asthma inhalers took longer to become pregnant than women using long-acting inhaled asthma medications and those without asthma, researchers from the University of Adelaide in Australia, have found.

The study, published in the European Respiratory Journal, used data from the Screening for Pregnancy Endpoints (SCOPE) study, which included 5600 woman from Australia, New Zealand, the UK and Ireland. The women were all in the early stages of pregnancy with their first child.

Around 10 percent of participants in the study reported that they had asthma. Women treating their asthma with short-acting beta-agonists took on average 20 percent longer to conceive than women without asthma, or those using long-acting inhaled corticosteroids. Short-acting medication takers were also 30 percent more likely to take more than a year to conceive.

'Several studies have identified a link between asthma and female infertility, but the impact of asthma treatments on fertility has been unclear,' said Dr Luke Grzeskowiak from University of Adelaide who led the study.

Asthma is one of the most common conditions affecting women of reproductive age. Today, an estimated 5.4 million people in the UK are receiving asthma treatment, according to Asthma UK.

The relationship between asthma and fertility is not well understood. Both women and healthcare professionals have expressed concerns in the past about the safety of using medication to control asthma during pregnancy.

'This large study provides reassurance that using preventers, which include inhaled corticosteroids and long-acting bronchodilators, to prevent asthma symptoms helps asthmatic women be as fertile as non-asthmatic women, while intermittent treatment with short acting relievers is associated with reduced fertility,' said Professor Mina Gaga, president of the European Respiratory Society and medical director of the respiratory department of Athens Chest Hospital.

However, researchers have expressed concern about the interpretation of the results. Professor Kevin McConway, a statistician at the Open University who was not involved in the study, said in a statement: 'Though the researchers found that the women taking only short-term relievers were more likely to take over a year to get pregnant, this effect was not big enough to rule out the possibility that it was simply due to chance.'

Professor Tony Fox, a pharmaceutical medicine researcher at King's College London added: 'The investigators should consider whether patients using symptomatic short-acting bronchodilators are actually treating their asthma less well than those patients using inhaled corticosteroids to prevent asthma attacks from happening in the first place.'

Further studies are planned for women undergoing fertility treatments to see if improving asthma control is able to improve fertility outcomes. 

SOURCES & REFERENCES
University of Adelaide | 16 February 2018
 
European Respiratory Journal | 15 February 2018
 
The Independent | 15 February 2018
 

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Fathers may pass ovarian cancer risk to daughters

19 February 2018

By Dr Rosie Gilchrist

Page URL: http://www.bionews.org.uk/page_932904.asp Appeared in BioNews 938

Scientists have identified a new gene for ovarian cancer risk that may be passed down from fathers to their daughters.

The risk of a woman getting ovarian cancer has been known to be linked to whether or not her mother had the disease, through mutations in the BRCA genes. However not all cases can be explained this way.

By examining ovarian cancer risk in 189 women and their grandmothers from the Familial Ovarian Cancer Registry at the Roswell Park Cancer Institute in Buffalo, New York, researchers found that the risk of some cases of ovarian cancer was passed down via the X chromosome from the father's side. The study was published in PLOS Genetics.

'Our study may explain why we find families with multiple affected daughters: because a dad's chromosomes determine the sex of his children, all of his daughters have to carry the same X chromosome genes,' said Dr Kevin Eng, first author of the study.

'It's an all-or-none kind of pattern: a family with three daughters who all have ovarian cancer is more likely to be driven by inherited X mutations than by BRCA mutations,' he said.

The researchers then looked for which genes might be causing this association. They searched for changes in the genetic sequence of the X chromosomes of women with ovarian cancer but without a BRCA mutation, and found mutations in a gene called MAGEC3.

'What we have to do next, is make sure we have the right gene by sequencing more families,' said Dr Eng. 'This finding has sparked a lot of discussion within our group about how to find these X-linked families.'

These results could have implications for improving the screening and early detection of ovarian cancer. Dr Catherine Pickworth from Cancer Research UK told the BBC: 'This research suggests that some women's risk of ovarian cancer could be passed down through their father's family, as well as their mother's, due to newly discovered faulty genes. In future, this could help women with a family history of ovarian cancer better understand their risk of developing the disease. This is important because ovarian cancer is often diagnosed at a late stage when it's harder to treat.'

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Huntington's protein is 'super assassin' for cancer cells

19 February 2018

By Hannah Somers

Page URL: http://www.bionews.org.uk/page_932880.asp Appeared in BioNews 938

Researchers have discovered that the protein responsible for the development of Huntington's disease is highly toxic to cancer cells. While the molecule has been understood in the context of Huntington's disease for years, it has only recently been found to have treatment implications for other diseases.

'This molecule is a super assassin against all tumour cells,' said senior author Dr Marcus Peter at Northwestern University Feinberg School of Medicine in Chicago, Illinois. 'We've never seen anything this powerful.' The study was published in EMBO Reports.

Huntington's disease is a fatal genetic condition currently affecting over 30,000 people in the USA, with a further 200,000 at risk of development later in life. The disease causes deterioration of physical and mental capabilities of patients over several years and is incurable.

Researchers began to investigate the effects of Huntington's on cancer after finding that Huntington's patients have significantly lower rates of cancer development than the general population, with 80 percent fewer cases.

Huntington's disease is caused by the over-abundance of a repeating sequence 'CAG' in the DNA of a protein called huntingtin. When transcribed, this repeating sequence forms several small interfering RNA molecules (siRNAs) which attack other genes essential for cell survival. The more CAG repeats present in a patient's gene, the faster they will develop the associated disease.

While previously observed that nerve cells are susceptible to cell death via the activity of huntingtin, the researchers have now identified that cancer cells are also highly susceptible to destruction by siRNA.

In order to test the hypothesis in a treatment scenario, Dr Peter worked alongside Dr Shad Thaxton, also at Feinberg to use nanoparticles to deliver huntingtin to mice with human ovarian cancer. The treatment significantly reduced tumour growth with no associated toxicity in the mice.

Their colleague Dr Andrea Murmann, also at Feinberg, used huntingtin to treat a range of cancers found in humans and mice, including brain, lung, skin and breast cancers. The protein was toxic to all tested cancers in both species.

'We believe a short-term treatment cancer therapy for a few weeks might be possible, where we could treat a patient to kill the cancer cells without causing the neurological issues that Huntington's patients suffer from,' said Dr Peter.

The group is now working to refine the delivery mechanism,  aiming to improve the efficacy of this molecule reaching tumour sites. They are also working on stabilising and creating effective storage methods for the nanoparticles involved in protein delivery.

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Woman uses dead son's sperm for IVF grandchildren

19 February 2018

By Georgia Everett

Page URL: http://www.bionews.org.uk/page_932881.asp Appeared in BioNews 938

A woman in India has used the frozen sperm of her dead son in order to have grandchildren via a surrogate.

Prathamesh Patil died from a brain tumour in 2016 but made the decision to preserve his sperm before undergoing chemotherapy and radiotherapy procedures. Mr Patil was unmarried, so he authorised his mother and his sister to use it in the event of his death.

His mother, Rajashree Patil, procured the sperm following his death and doctors at Pune's Sahyadri Hospital used it to fertilise eggs from an anonymous donor. The resultant embryos were implanted into Mrs Patil's cousin, who acted as surrogate after it was deemed that she was not medically fit to carry the baby herself. The twin babies – a boy called Prathmesh and a girl called Preesha – were born on February 12. Mrs Patil intends to raise the twins as her own children.

Mr Patil was diagnosed with cancer in 2010 whilst he was in Germany studying for a master's degree in engineering. Mrs Patel described her son as the 'ideal man'.

'He was a bright student and excelled in academics. Even when he was diagnosed with a brain tumour and later lost his vision after the chemotherapy, he did not lose spirit. He fought valiantly until the last breath. He always tried to regale us with his stories and humour. That's why, when we lost him, I wanted to have grandchildren using the cryopreserved semen.' 

Dr Supriya Puranik, the head of the IVF department in Sahyadri Hospital, said that Mrs Patil's case was unique compared to other women delivering babies through assisted conception.

'Being an IVF specialist, I am happy that science and new technologies are adding cheerful moments in people's lives… But here, in this case, it was about a grief-stricken mother whose son was away for studies when he faced health issues,' Dr Puranik noted.

Whilst it is a heart-warming story, many are concerned about the ethics of such a procedure. Hari Ramasubramanian, founder of the Indian Surrogacy Law Centre, described the ethical issues in the case: 'There are four issues here. First, did the son give consent that his semen be used for procreation after his death? Second, how are the grandparents going to secure the future of the newborns in all aspects of life and living? Third, while a person has the right to become a parent, the right to become grandparents is completely outside the ambit of fundamental rights. Fourth, and most importantly, what about the rights of the child to have normal parenting?'

Ramasubramanian also noted that there is currently no specific legislation governing this area of reproduction, as India's Surrogacy Regulation Bill 2016 is still pending.

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CRISPR pioneer's lab develops system to target infections and cancer

19 February 2018

By Rikita Patel

Page URL: http://www.bionews.org.uk/page_932842.asp Appeared in BioNews 938

Researchers have developed a new application for CRISPR, adapting the system to detect viral infections with high accuracy, a new study finds.

When CRISPR was coupled with the enzyme Cas12a, researchers at the University of California, Berkeley, found that the system could detect the human papillomavirus (HPV) subtypes with high accuracy in human samples. The team named this mechanism DETECTR (DNA Endonuclease Targeted CRISPR Trans Reporter) mechanism. Early detection of viral infections such as HPV is crucial to prevent or treat conditions linked to the virus, including cervical cancer in women.

'We found something absolutely surprising,' said study author and CRISPR pioneer Professor Jennifer Doudna of the University of California, Berkeley, speaking to STAT news. In the study, published in Science, she and her team programmed CRISPR-Cas12a with a reporter molecule and specific RNA guide to detect and snip the double-stranded DNA sequence of HPV. The reporter molecule gave off a fluorescent signal when cut by CRISPR, revealing that Cas12a induced cuts in double-stranded as well as single strands of DNA.

DETECTR could also be used to identify tumour cells and fetal cells in pregnant women, the authors suggest. The technology could be useful in a diagnostic setting in under-resourced areas and countries to provide faster results. Current virus diagnostic-kits and DNA sequencing technology require more time to analyse data and offer a diagnosis.

'[DETECTR] remains active and able to cut any single-stranded DNA that comes by,' said Professor Doudna. While the mechanism offers new opportunities for medical use, at the same time it may be problematic if it induces unintended mutations and 'triggers undesired gene edits', she acknowledged.

In a second paper published in Science, Professor Doudna's team and researchers at the McGovern Institute in Boston, Massachusetts, showed that the diagnostic tool SHERLOCK (Specific High Sensitivity Reporter unLOCKing) could be adapted to accurately detect viruses such as Zika and dengue in human samples. Like DETECTR, SHERLOCK detects specific DNA and RNA sequences of viruses, including Zika or dengue, with high accuracy rates using CRISPR enzymes.

Together, these diagnostic tools have 'real potential to make an impact on human health and society', study co-author Omar Abudayyeh, a PhD student in the McGovern Institute lab, told the Verge.

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Stem cell vaccine works against multiple cancers in mice

19 February 2018

By Charlott Repschlager

Page URL: http://www.bionews.org.uk/page_932745.asp Appeared in BioNews 938

Researchers successfully used inactivated induced pluripotent stem cells (iPSCs) to elicit an immune response against different cancers in mice.

The team at Stanford University confirmed that iPSCs from mice and humans have similar expression levels of antigens to those found in different cancers.

Previous cancer vaccines have had limited success because only one antigen has generally been targeted, results have initially been promising but then resistance develops as cancer cells without the target antigen proliferate. The idea that stem cells and cancer cells have similar antigen profiles is not new and has the advantage that several known and unknown antigens can be presented to the immune system at the same time, allowing for a more effective immune response.

Studies have established that embryonic stem cells can protect mice from transplanted tumour but using inactivated iPSCs as an immunotherapy against cancer has the advantage that while embryonic stem cell rely on the availability of embryonic tissue and therefore have ethical and feasibility issues, iPSCs can be derived from adult cells.

'What surprised us most was the effectiveness of the iPSC vaccine in re-activating the immune system to target cancer,' said Dr Joseph Wu, lead author of the study. 'This approach may have clinical potential to prevent tumour recurrence or target distant metastases.'

The group used iPSCs created from mouse fibroblasts, in addition to an immune-boosting bacterial DNA fragment, to vaccinate mice before transplanting them with either breast, skin or lung cancer. While the control animals developed considerable tumours, the treated mice presented with smaller tumours or with tumour regression. These results highlight a potential prophylactic application of the vaccine, for example in the elderly or other groups who are prone to the development of cancers.

To confirm that the immune response is specific to cancer, the researchers transferred T cells from vaccinated animals into non-vaccinated animals with breast cancer and found that the tumours in the non-vaccinated animals also showed signs of regression. This approach did not work in mice with skin cancer, however, it was found to prevent regrowth of skin tumours after partial surgery, indicating a possible usefulness in real life skin cancer scenarios.

While the scientists note that there were no signs of an autoimmune reaction or other serious adverse effects, they caution that this therapeutic approach is far from being proven in humans. Professor Daniel Davis, Professor of Immunology at the University of Manchester, who was not involved in the study, added: 'As the authors say themselves, we have no idea if something like this could work in humans. If it does, this type of cancer treatment is most likely to be useful in combination with other therapies. In the meantime, as scientists often quip, this is good news for mice.'

SOURCES & REFERENCES
Elsevier | 15 February 2018
 
EurekAlert | 15 February 2018
 
The Scientist | 15 February 2018
 

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DNA nanorobots help shrink tumours in mice

19 February 2018

By Dr Molly Godfrey

Page URL: http://www.bionews.org.uk/page_932814.asp Appeared in BioNews 938

Nanorobots made of DNA, that can target and kill tumours in mouse cancer models, have been developed by scientists.

Researchers from the Biodesign Institute at Arizona State University (ASU) in the USA and from the National Centre for Nanoscience and Technology (NCNST) in China, collaborated to develop DNA nanorobots which travel the bloodstream and find tumours. Once tumours are located, the nanorobots are programmed to deliver a protein which causes the blood supply of the tumours to be blocked, thus leading to their 'starvation' and shrinkage.

'These nanorobots can be programmed to transport molecular payloads and cause on-site tumour blood supply blockages, which can lead to tissue death and shrink the tumour,' said Professor Baoquan Ding from the NCNST, one of four lead authors of the study.

The research, published in Nature Biotechnology, found that DNA nanorobot treatment successfully led to shrinkage of a variety of different tumour types in mouse cancer models, as well as preventing cancers from spreading. Treated mice were also found to survive 1.5-2 times longer than untreated ones.

The nanorobots are designed as flat sheets of DNA, which can be loaded with a blood-clotting enzyme known as thrombin. The DNA sheets are folded into tubes, hiding thrombin in the centre. On the outside of the tubes are 'DNA aptamers' - structures which recognise and bind to specific tumour proteins (not found of the surface of healthy cells). Once tumours are located by the DNA aptamer binding, the tube unfolds, leading to the release of thrombin, triggering blood clotting and tissue death.

This strategy could have advantages over traditional treatments such as chemotherapy or radiotherapy, as the killing activity is very specifically restricted to tumours – no other cell types or tissues were affected in the mouse models. This could lead to a reduction in side effects.

The authors tested their DNA nanorobots for safety in Bama miniature pigs, closer to humans in physiology than mice, checking that they did not induce an immune response or cause random blood clotting events. 'The nanorobot proved to be safe and immunologically inert for use in normal mice and, also in Bama miniature pigs,' said Professor Yuliang Zhao from the NCNST.

Although the research is still far from clinically relevant, it represents a significant advance in the field of nanomedicine. 'I think we are much closer to real, practical medical applications of the technology,' said Professor Hao Yan from ASU, a lead author on the study. 'Combinations of different rationally designed nanorobots carrying various agents may help to accomplish the ultimate goal of cancer research: the eradication of solid tumours and vascularised metastases.'

SOURCES & REFERENCES
Nature Biotechnology | 12 February 2018
 
Science Daily | 12 February 2018
 
The Independent | 12 February 2018
 
The Scientist | 12 February 2018
 

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Board Game Review: The Genomics Game

19 February 2018

By Jean Bvumbe

Page URL: http://www.bionews.org.uk/page_933139.asp Appeared in BioNews 938

It's not often you get to play board games at work. Recently at Guy's Hospital in London, the research nurse team were delighted to try out The Genomics Game, released by the NHS's Genomics Education Programme.

The first challenge with any new game is getting to grips with the rules. Luckily the instruction manual and introduction were clear and very straightforward to follow. This is an added bonus – when you are playing a board game you do not want difficult explanations and complicated rules as this can be off putting, especially if, like us, you don't have too much time.

The game is played with a maximum of two teams and takes approximately 45 minutes. The aim of the game is to land on as many 'double helix spaces' as you can, and win five tokens so that you can spell the word 'genes'. During the game, teams take it in turns to answer a series of questions as quickly as possible, monitored by a timer that is provided with the game.

We liked the look of the board. It was a clever design all fitting with the DNA and genetics theme. It was very easy to follow the pattern and know where to go. I have to admit that we were a bit confused initially as we thought each team was to follow the colour of their piece on the board but it soon became clear that everyone followed the same direction.

We were a little confused with the letters on the board ACA, TGT, CAG and CTG as they did not mean anything to us and they had not been explained in the manual. This would have been helpful.

The questions on the cards were fantastic, challenging and informative at the same time. Everyone felt as if they came away with something that they learned, but at the same time did not feel too discouraged by the difficulty of the questions. We all felt that we also knew the answers to some of the questions that were being asked of other players. The explanations to the answers were also a very good idea and gave us a bit of background to understand the correct answer.

The questions varied significantly in difficulty. As an example:

Question G-004: What is DNA?

  • An explosive
  • A molecule that contains genetic information
  • A molecule that carries oxygen

There were two answers here that could be plausible given that they are both clinical. To make the game more accessible for less scientifically knowledgeable players, we thought it could instead be structured like the following question, which has only one obvious answer:

Question G-005: In genetics and genomics what does DNA stand for?

  • Did Not Attend
  • Doesn't Need an Ambulance
  • Deoxyribonucleic Acid

We especially liked the way that the questions also relate to day-to-day medical treatments. For example, we appreciated one question about MRSA and how the genome of MRSA bacteria can be sequenced during an outbreak in order to find a root cause.

The game as a whole was very informative. It challenged our perceptions of what is said in the media or by other healthcare professionals, and was easy to follow, which makes it less taxing.

It would be a great tool to give our nurses, new and existing, that extra knowledge when it comes to something like genomics, which sounds very complicated but when simplified like this seems much easier. We loved the game brought out the competitive nature in us, making it a great game to add to a study day.

Enquiries to receive a copy of the game can be made on the Genomics Education Programme website.

SOURCES & REFERENCES

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