The event also launched a new phase of the Genomics Conversation, a programme of activities led by Genomics England which involves the public and stakeholders in discussions about key issues in genomic medicine.
(If you cannot see the film below, click here to view it.)
The Chief Medical Officer's Annual Report Generation Genome provides a comprehensive and considered focus on the potential of genomic technologies – coupled with clinical and phenotypic data – to transform the lives of patients...
Genome sequencing in Scotland has received a major cash boost, following a £6 million investment into the Scottish Genomes Partnership (SGP), which will begin working with Genomics England on the 100,000 Genomes Project...
Sperm counts of men in developed nations have fallen by 52 percent in the last 40 years.
An analysis, which combined the results of 185 studies carried out between 1973 and 2011, also showed that the average sperm concentration had dropped by nearly 60 percent. The reasons for this decline remain unclear.
'This study is an urgent wake-up call for researchers and health authorities around the world,' said Dr Hagai Levine, the study’s lead author and researcher at the Hadassah Braun School of Public Health and Community Medicine, part of the Hebrew University of Jerusalem.
The research, which was published in the journal Human Reproduction Update, analysed studies encompassing over 42,000 men. After taking account of other influencing factors such as age and time since last ejaculation, the team found that in men from Western countries including Europe, North America and Oceania, average sperm concentration fell from 99 million per ml in 1973 to 47.1 million per ml in 2011, which is below the threshold for fertility. While the study did not examine sperm quality, Dr Levine called this 'particularly concerning'.
The decline in sperm count was not seen for men in other countries, leading some to speculate that environmental factors might be responsible. However the researchers did not look at the causes of the decline, and they also caution that far fewer sperm count studies have been carried out in developing countries.
Male fertility experts have welcomed the study for addressing many concerns regarding previous studies of sperm quality, such as only including studies that counted sperm using modern equipment, and excluding studies that recruited men from fertility clinics. Professor Richard Sharpe of the University of Edinburgh said the study 'is about as close as we are going to get' to being sure that sperm counts are declining.
The research also showed that the rate of decline in sperm counts has continued beyond 1995, indicating that the drop is ongoing. 'The continuous nature of the decline is of as much concern as the decline itself, given that we still do not know what lifestyle, dietary or chemical exposures might have caused this decrease,' added Professor Sharpe.
Experts agreed that more research is needed in this area to identify the underlying cause of the decline. Professor Daniel Brison, scientific director of the Department of Reproductive Medicine, University of Manchester, said 'this has major implications not just for fertility but for male health and wider public health. This study should act as a wake-up call to prompt active research in this area.'
Twenty-five years ago, I recall sitting in a journal club in which the collective minds tore apart the then recently published (and still much quoted) meta-analysis by Elizabeth Carlsen, 'Evidence for decreasing quality of semen during past 50 years'. This BMJ paper made the headlines in 1992...
While media reports regularly remind us of women's biological clocks and warn of the dangers of women leaving it 'too late' to have children, until recently little attention has been paid to the role of men in timing when to have children, and the effect of age on male fertility...
The finding comes from the first study to report cumulative live birth rates for women undergoing assisted reproductive treatment (ART), including up to eight cycles of IVF.
'What this shows is that women going into IVF today have a very reasonable chance of getting pregnant,' said lead author Professor Michael Chapman of University of New South Wales (UNSW), Australia.
Researchers at UNSW followed 56,652 women who had begun ART in Australia and New Zealand from 2009 – 2012, either until 2014 or until their first treatment-dependent live birth. Women who used donated eggs or embryos were excluded.
They then calculated the cumulative cycle-specific live birth rate against the age of the women, for up to eight cycles of treatment.
The results showed that the overall chances of successful IVF increased with each cycle. However, this was strongly influenced by age. Women under 35 showed the highest rate of success following the first cycle, at around 44 percent. This rate increased to 77 percent by the eighth cycle.
Yet women aged 40 – 44 showed a rate of 10 percent for the first cycle, rising to approximately 40 percent by the seventh cycle.
Professor Chapman said that until now, data on multiple cycles had not been made available.
'These estimates can be used when counselling prospective parents about the likelihood of treatment success, as well as for educating the public and informing policy on ART treatments,' the authors said.
Dr Georgina Chambers of UNSW, and co-author of the study, told The Conversation that around 30 percent of women drop out of treatment after an unsuccessful IVF cycle, due to the physical and emotional demands of treatment, a poor chance of success, and the cost.
'We hope providing success rates in this more meaningful way is reassuring for women and couples,' Dr Chambers said.
However, she added that the study did not take into account individual factors that would affect likelihood of conception, such as ovarian reserve or body mass index.
'Whether women should start IVF treatment or continue it should ultimately be a decision for the fertility doctor and patient, taking into account all medical and non-medical factors,' she said.
The cumulative chances of a woman getting pregnant following IVF increase with each treatment cycle until the sixth cycle, after which the increases are minimal, show study results from Australia and New Zealand....
The gene therapy significantly increased the muscle strength of dogs naturally affected by DMD, improving their ability to walk, run and jump.
'This is very encouraging, as current treatments for muscular dystrophy are merely palliative and patients are under constant medical care throughout their life,' said Dr John Counsell, who was not involved in the study but works at the Gene Transfer Technology Group at University College London.
DMD is a rare, progressive disease affecting all muscles of the body, including the heart and diaphragm. It is caused by mutations in the dystrophin gene, which leads to a deficiency of dystrophin protein. Dystrophin is important in supporting the muscle fibres during contraction; without it, the muscle fibres become damaged and eventually die.
As it is one of the largest human genes, it is technically challenging to insert the entire dystrophin gene into a viralvector, as is usually done for gene therapy. For this reason, the researchers in this study developed a gene therapy that delivers a smaller but functional version of the dystrophin gene (called micro-dystrophin). This was packaged into a non-pathogenic virus called an adeno-associated virus (AAV).
Twelve dogs with DMD received a single dose of the micro-dystrophin gene therapy and were monitored for up to two years. The researchers observed an increased amount of dystrophin protein in the dogs' muscles and a stabilisation of clinical symptoms in most of the dogs. There were no serious immune reactions to the gene therapy.
'The studies in dogs have been spectacular and exceeded our expectations,' said Professor George Dickson, who led the research at Royal Holloway University of London. My team has worked for many years to optimise a gene therapy medicine for DMD, and now the quite outstanding work of colleagues in France, in Genethon, in Nantes and in Paris has taken us close to clinical trials in DMD patients.'
In a separate study, a group of researchers from the US developed a micro-dystrophin gene therapy using a different type of AAV vector. They tested this in a recently established, severe DMD mouse model that is thought to be more like the human condition than the commonly used mdx mouse.
15 weeks after AAV injection, the researchers detected an increased amount of dystrophin protein in the mouse muscles. There were also improvements in muscle function and a reduction in muscle scarring and inflammation.
Whilst evaluating cardiac function, the researchers unexpectedly found pathological changes in the hearts of control mice, which meant that they were similar to the DMD hearts. For this reason, they could not evaluate the effect of the micro-dystrophin gene therapy on cardiac function and concluded that the mouse was not a good model for DMD-associated cardiomyopathy.
The results of the study are yet to be published, but the work – led by Professor Shoukhrat Mitalipov at the Oregon Health and Science University, Portland – is believed to include the largest number of successfully modified embryos produced using CRISPR technology.
Professor Mitalipov declined to comment on the study, but stated the results are pending publication next month. However, Dr Jun Wu, a collaborator at the Salk Institute, California told MIT Technology Review, 'So far as I know this will be the first study reported in the US.'
Three published attempts of genome editing in human embryos have been carried out in China to date, the first in 2015 (see BioNews 799). Professor Shirley Hodgson, a specialist in genetics at St George's, University of London, said the 2015 study had shown CRISPR to be 'a technique with significant errors in human embryos with regard to accuracy, resulting in "off-target" mutations in other genes, and mosaicism in the developing embryo, since usually the "repair" has only occurred in a proportion of embryonic cells.'
However, sources claim that the US study overcomes these two hurdles. Professor Mitalipov's group are believed to have injected eggs with CRISPR at the same time as they were fertilised with donorsperm, as opposed to after. The donor sperm contained inherited disease-related mutations, though it is not known which disease genes these were. It is reported that the majority of cells in the resulting embryos were successfully edited so that the disease genes were replaced with healthy genes, with few errors.
The successfully edited embryos of 'clinical quality' were discarded after a few days. The team had no intention of implanting them.
A scientist familiar with the project told MIT Technology Review, 'It is proof of principle that it can work. They significantly reduced mosaicism. I don't think it's the start of clinical trials yet, but it does take it further than anyone has before.'
Scientists are reluctant to comment on the results until they have been confirmed in a published scientific paper, yet some caution that there is still a long way to go until it would be possible to implant any edited embryos.
'While it might be tempting to consider a technology that potentially offers the prospect of curing serious genetic diseases at such an early stage of development, there are major risks, both of technical failure and unanticipated adverse consequences, which could affect generations to come,' said Professor Frances Flinter, a clinical geneticist at Guy's & St Thomas' NHS Foundation Trust, London, who was not involved in the study.
Besides the safety issues, the study also raises important ethical questions about how the technology could or should be used. Research involving human embryo editing is barred from federal funding in the US. Careful regulation is in place in the UK, with scientists granted permission from the Human Fertilisation and Embryology Authority (see BioNews 837) to genetically modify human embryos for research use only.
Dr Simon Waddington of University College London, who was not involved in the study, concluded, 'If what has been reported in the media is backed up by a paper published in a peer-reviewed journal, it would be a valuable increment but we still have a long way to go.'
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 Progress Educational Trust has set out to answer these questions, with its 'Basic Understanding of Genome Editing' project....
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...
The IBM Watson supercomputer can analyse 160 hours' worth of genomic data in just ten minutes.
In a proof-of-concept study, researchers at New York Genome Centre have demonstrated this speed of analysis could prove life-saving in finding drug targets and even clinical trials for some fast-progressing cancers.
'This study is an important step forward promoting human-machine interface as a way to address a key bottleneck in cancer genomics,' claim the authors.
In the study, published in Neurology Genetics, researchers used data obtained from a patient who had died of glioblastoma – an aggressive form of brain cancer. DNA and RNA had been extracted from the tumour tissue, in addition to the patient's healthy DNA extracted from normal blood. These samples had been sequenced for comparison.
The researchers compared the supercomputer's ability to interpret whole genome sequencing (WGS) data with the work of a team of experts, which had taken them over six days. Through the use of artificial intelligence (see BioNews 747), the beta version of the automated system IBM Watson Genomic Analytics rapidly analysed this sequenced genomic data and cross-referenced findings with biomedical literature on PubMed in ten minutes.
The results quickly revealed genemutations that could have acted as drug targets, and potential therapeutic options for the patient. The supercomputer was also able to identify a potentially relevant clinical trial.
'We identified a potentially relevant National Institutes of Health-sponsored clinical trial with targeted therapies that matched the mutations/pathways seen with WGS and RNA sequencing that were not otherwise visible,' Principal investigator Dr Robert Darnell of the The Rockerfeller University, told Medscape Medical News. While this trial had been identified and recommended to the patient, the tumour growth had progressed too rapidly for him to be eligible.
'Time was a big variable in [the patient 's] outcome... This case therefore illustrates the potential and the challenge of where high-end cancer genomics is at and where it is headed,' said Dr Darnell.
'The study documents the strong potential of Watson for Genomics to help clinicians scale precision oncology more broadly,' commented Vanessa Michelini, Watson for Genomics Innovation Leader at IBM Watson Health. 'Clinical and research leaders in cancer genomics are making tremendous progress towards bringing precision medicine to cancer patients, but genomic data interpretation is a significant obstacle, and that's where Watson can help.'
A computer-based platform which looks to greatly speed up genetic analysis of tumours has been unveiled in the USA. Currently such analysis can take up to eight weeks, the new platform promises to deliver results in just 47 seconds...
A comprehensive map of over 760 genes crucial to tumourcell survival has been created by researchers.
A team from the Broad Institute of MIT and Harvard, and the Dana-Farber Cancer Institute, Massachusetts identified these so-called 'cancer dependencies' in a study published in Cell.
Professor Paul Workman from the Institute of Cancer Research, who was not involved in the study, said: 'This important study sheds light on how human cancer cells are dependent on particular genes. The genes identified could be targets for drug discovery efforts to find new targeted treatments.'
'Much of what has been and continues to be done to characterise cancer has been based on genetics and sequencing. That's given us the parts list,' said study co-senior author Dr William Hahn, a member of both the Broad and Dana-Farber Institutes, and a leader in the Cancer Dependency Map initiative. 'Mapping dependencies ascribes function to the parts and shows you how to reverse engineer the processes that underlie cancer.'
The researchers inactivated thousands of different genes in more than 500 different human cancer cell lines (representing more than 20 different types of cancer), and then monitored cell growth and survival, to investigate which genes the cancers were dependent on. They used RNAi to inactivate the genes, a method of gene silencing which uses small pieces of RNA (siRNAs).
'The simplest thing one can do with perturbed cells is allow them to keep growing over time and see which ones thrive,' said study co-senior author Dr David Root, from the Broad Institute. 'If cells with a certain gene silenced disappear, for example, it means that gene is essential for proliferation.'
After exposing the cells to pools of these siRNAs, and following them for 40 days, the researchers analysed the results using a novel computational tool (DEMETER). This tool allowed researchers to differentiate true dependencies from false positives – a common problem in RNAi-based studies.
Many of the 'dependencies' identified are specific to certain cancer types. However, around 10 percent of them – 76 genes – are common to multiple cancers. This suggests that a relatively small number of therapies targeting these core dependencies might be used to treat a wide range of cancers. Furthermore, around 20 percent of the dependencies link back to genes previously identified as potential drug targets.
'Our results provide a starting point for therapeutic projects to decide where to focus their efforts,' said study co-first author Dr Francisca Vazquez.
However, the dependencies map is not yet all-inclusive. 'These estimates are hard to make, but we are probably 15 to 20 percent away from being complete,' said Dr Hahn.
The University of California has moved to appeal a decision of the US Patent Trial and Appeal Board (PTAB) over the use of CRISPR in eukaryotic cells.
This latest appeal is part of an ongoing dispute over the US patent for CRISPR/Cas9 between the University of California (UC), and the University of Vienna and Professor Emmanuelle Charpentier, against both the Broad Institute of MIT and Harvard University (Broad/MIT) regarding who has the right to a patent on the eukaryotic application of CRISPR/Cas9 technology.
'Ultimately, we expect to establish definitively that the team led by Jennifer Doudna and Emmanuelle Charpentier was the first to engineer CRISPR/Cas9 for use in all cell types including eukaryotic cells,' statedEdward Penhoet, a special adviser on CRISPR to UC.
In 2012, researchers at UC - including Professor Jennifer Doudna and Professor Emmanuelle Charpentier – first filed a patent for their discovery of CRISPR/Cas9 and its ability to edit purified DNAin vitro. Later in 2012, a team of researchers at the Broad Institute used CRISPR/Cas9 to edit the genome of eukaryotic cells, and therefore filed for a patent based on this use.
In 2014, the US Patent and Trademark Office (USPTO) granted the patent for use in eukaryotic cells to the Broad/MIT group. Despite the UC team filing their patent claim first, the Broad group asked for 'accelerated examination' and so their application was considered first.
As a result, UC Berkeley asked for an 'interference proceeding' to reassess and determine who was the first to invent the genome editing tool.
However, in February 2017, the PTAB again ruled that the Broad/MIT group could keep its patents on using CRISPR/Cas9 in eukaryotic cells, stating that there is no interference between the two groups' patent claims – that is, the one issued to the Broad/MIT group is sufficiently different from that filed by the UC team.
The UC team are now appealing this decision, stating that the work initially performed by Professor Doudna and Professor Charpentier – although it involved characterising a purified enzyme in a test tube – provided obvious evidence that genome editing could be made to work in living mammalian cells. Thus they contend that the patent held by the Broad/MIT for this application is not novel.
The UC brief – which was issued on 25 July this year – also states that the PTAB 'ignored key evidence' and 'made multiple errors' when assessing whether CRISPR/Cas9 genome editing in eukaryotes was an obvious extension of the UC invention.
However, Jacob Sherkow, an intellectual property attorney at the New York Law School has cautioned that the UC group's brief 'overplays these mistakes relative to the PTAB's analysis.' He has added that 'while there are some interesting chestnuts in its brief - such as UC pointing out that the PTAB virtually ignored some important patents pending at the time the Broad patent was filed – I don't think that's going to be enough to win the day for UC.'
This brief will be heard by the US Court of Appeals for the Federal Circuit on 25 October 2017.
The Broad Institute of Massachusetts Institute of Technology and Harvard will take part in an initiative to simplify licensing CRISPR genome editing technology to other organisations and institutions...
The European Patent Office has declared that it intends to grant a broad patent for the use of CRISPR technologies to the University of California, the University of Vienna and Dr Emmanuelle Charpentier of the Max-Planck Institute in Berlin...
When I first listened to this radio programme, I was convinced that I was listening to the wrong thing: Sputnik does not fall under BioNews' usual remit. I persevered to find that, yes, this show was actually about genome editing and not – much to my relief – on the Soviet satellites (on which I have approximately zero opinions).
Thankfully, smooth-voiced host James Fletcher was on hand to provide some context; both Sputnik and genome editing have sparked global scientific races, apparently. The launch of Sputnik in 1955 heralded the start of the space race between the Soviet Union and the USA, and now scientists are racing to edit genes in adults and in viable human embryos. A bit of a tenuous link to be honest, which led to a shaky opener.
The broadcast by BBC World Service is split into four parts, each with an assigned 'expert witness'. The first chapter tackles 'The Language of Life', aiming to elucidate exactly what DNA, genes and genome editing are. A wise place to start.
'I just think of DNA being a Word document', says Carl Zimmer, a science journalist for the New York Times. Fletcher expands the analogy to suggest that genes should be viewed as short chapters within this Word document, and genome editing as correcting a spelling mistake.
I felt that this was a very slick analogy and one that I intend to use myself in the future. The Word analogy even proves useful with the introduction of CRISPR as like 'the search and replace' function.
While Zimmer does not offer his own opinion on whether genome editing is out of control, he does illustrate the concern with a tale about one of the unnamed discoverers of CRISPR. Following her initial elation, she began to worry that she had 'unleashed a power that humanity might not be able to control and that might lead to terrible things'.
A pretty ominous end to the first part.
Part two, the cleverly named 'The Cutting and Pasting Edge', is a rather enlightening discussion, despite sprinklings of unnecessary scientific jargon. Professor Robin Lovell-Badge of the Francis Crick Institute, London, presents a fascinating depiction of how CRISPR is actually being used in research and why. This cutting edge work could have the 'potential to avoid serious genetic disease in children' by using CRISPR to 'correct a mutation in an early embryo', according to Professor Lovell-Badge.
The research is framed as being incredibly promising, suggesting that attempts to recreate it will happen globally. This leads to a discussion detailing how the regulation of embryo research varies internationally, which is a significant point when considering whether genome editing has got out of hand, or if it will do so in the future.
Part three, 'Unknown Unknowns', sees the arrival of Dr Marcy Darnovsky of the Centre for Genetics and Society, a non-profit organisation in California.
'What used to be seen as a science-fiction hypothetical really is an urgent social justice issue,' she warns. Dr Darnovsky has a slightly more apocalyptic view on genome editing than the previous contributors.
Here talk turns to editing the germline. This is always the most controversial issue in genome editing. It's all well and good altering your own DNA because it only affects you. But altering it when you know it's going to be passed on into future generations? Risky, to say the least.
Fletcher and Dr Darnovsky continue by discussing the grey area between fixing genetic diseases and creating designer babies. 'Are stronger bones or better eyesight medically justified, or designer tweaks?' asks Fletcher. This opened up the programme to examining the commercial and social implications of genome editing, which I think can often get overlooked. It also led to Dr Darnovsky giving a damning but justified answer to the titular question.
The narrator rather darkly announces the arrival of the final chapter: 'The Creator'.
'Evolution has created wondrous forms most beautiful and I think it is our responsibility to understand how that is done and to see if we can do it at least as well,' says Dr Kevin Esvelt of the Massachusetts Institute of Technology in Cambridge, Massachusetts.
I still cannot quite get over the audaciousness of this statement. Surely scientists do not have a right to create anything better than evolution, let alone have a responsibility to do so?
Dr Esvelt considered the creation of 'gene drives' which are intended to skew genetic inheritance; here cells are engineered such that they have their own CRISPR system in order to pass on altered DNA. This would guarantee that the edited genes would be passed on to future generations. Recall that this was a big no-no according to Dr Darnovsky (and myself).
By this point, my eyebrow was twitching with relative outrage at Dr Esvelt's comments, so I was exceedingly grateful when his contribution became decidedly less inflammatory. He began to raise some important moral issues surrounding genome editing concluding that: 'No one person is wise enough to make these decisions.'
Fletcher rounds off the discussion by summing up some of the ideas presented throughout. No unambiguous answer to the titular question is offered, but despite this, I myself have now formed an opinion on whether I think genome editing is out of control currently (it's a no).
I've already complained about the bizarre Sputnik introduction, but I have a few other bones to pick. It’s a seemingly minor point, but the unnecessarily menacing music peppered throughout was very distracting. It was straight out of Scooby Doo and I am fairly certain this was not the desired effect.
Overall, the show was illuminating and informative and does very well to convey the extraordinary power of the technology. The diversity of the panel enabled them to address a comprehensive range of thought-provoking topics – if not opinions.
In fact all the guests agreed that (spoiler alert!) genome editing is either out of control, or it could be if caution is not exercised. Although this rings true for me, I am going to play Devil's advocate. Why not include the voice of someone who completely disagreed? The programme was an inoffensive listen and the panel's conclusions justifiable, if not exciting.
By including radically different voices it would have been raised to the provocative, but engrossing, and would have served to reignite my eyebrow twitch.
Genomics may herald a bright future - for those who understand it. But what about those who do not? Dr Kat Arney's new book 'How to Code a Human' is a beautiful example of how complicated genetic topics can be simplified and clarified to make them understandable and enjoyable for the least-scientific of readers....
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