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

Issue 914 (21 August 2017)


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

Visit the BioNews website at 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.





News Digest




We need to talk about... CRISPR

21 August 2017

By Giulia Cavaliere

Page URL: Appeared in BioNews 914

Picture this - it's the last day in the office before the summer holidays, you're already looking forward to some sunshine and warmth (if you are UK-based as I am, you’ll know both are in short supply), email auto-response set, and all ready to go. Then, all of a sudden: the news. The genome editing technique CRISPR has been used to edit human embryos in vitro (see BioNews 911) – and no, not in China, that's so 2015 – now we are talking about the USA.

That was my pre-vacation experience this summer. I clicked on my news feed and read the article in MIT Technology Review with a mixture of scepticism and curiosity – and a fleeting wish that this had not happened just as I was leaving! Intrigue soon won; this genome editing technique promises to be a game-changer in genetic engineering, with potential and actual applications for human embryos in vitro.

The scepticism, my dominant feeling at the time, was motivated by what is all too familiar to someone working in bioethics (or historians, as Professor Nathaniel Comfort at Johns Hopkins University, Maryland notes here).

There is a pattern to how such scientific 'breakthroughs' permeate society. First comes the partially reported (or leaked, as was the case with the MIT Technology Review article) news. Next come the reactions of the scientific and bioethics communities, with some celebrating the coming of a new Enlightenment and others picturing Hitler coming to town - or even appearing in dreams, as CRISPR co-inventor Professor Jennifer Doudna recently revealed (see a review in this week's BioNews). And then, as Professor Comfort says, 'technology settles into a more humdrum life as another useful tool in the biologist's kit.'

When the journal Protein and Cell published the (in)famous article in which a group of Chinese scientists reported using CRISPR on non-viable human embryos in 2015 (see BioNews 799), it sparked calls for both a worldwide moratorium on human germline editing on one hand, and a moral imperative to continue research with genome editing on the other.

Despite these reactions, with calls for a moratorium even preceding the actual publication of the article, it turned out that the 2015 experiments were not exactly what you would call a success. Out of the 86 embryos used in the experiment, the DNA of only 28 embryos was successfully spliced, and only a few contained the replaced genetic material. In addition, the embryos presented a number of 'off-target' mutations. A year later, the HFEA (Human Fertilisation and Embryology Authority) granted a licence to the Francis Crick Institute in London to use genome editing in human embryos for basic research.

But back to the latest CRISPR report. One would think that both negative and positive reactions would be more moderate, and that the latter would wait at least for the actual paper to be published, before announcing that CRISPR had been used successfully. And the definition of that being limited 'off-target' effects and avoidance of mosaicism in the embryos.

With the noteworthy exception of Hank Greely's sobering comment in Scientific American and a handful of others, once again reactions to the news were predominantly eugenics and scary super-babies versus the relief of all human miseries.

This unfolded while I was on holiday and trying to find the right balance between avoiding CRISPR-related news and being too curious to let go. A sudden thought struck me while I was swimming in the fresh water of the Adriatic Sea: maybe is for the best that I am here and not joining the conversation at this point. I have thought about genome editing a great deal in the past months, especially on the ethics of using it in the context of assisted reproduction and as a potential alternative to PGD (preimplantation genetic diagnosis) in the future, if proven safe by basic research. I have thought about it and I am adamant that I must think more, talk more, and especially listen and read more.

But why the rush? Commentaries on genome editing and other emerging biotechnologies seem to imply that there is a fight to be won here and now. That we need now to eradicate all genetic diseases since, as my dear friend and colleague Professor John Harris at Global Health and Social Medicine at King's College London likes to say, 'therapy delayed is therapy denied'. Or, on the contrary, that it is now that we need to stop, build walls, start moratoria and enact bans before it all goes back to eugenics and so-called natural reproduction becomes a thing of the past.

The problem with this rush is that the conversation becomes a fight for the best argument, the one that will win the sophist-CRISPR-prize, rather than a constructive conversation that takes into account the competing moral views that underpin those arguments, the importance of the details, the context, of listening over speaking, and reflecting over jumping the gun.

Moral psychologists have begun to show that moral judgements are formed automatically and effortlessly thanks to moral intuitions, and that only afterwards does calculating reasoning take place (Greene, Sommerville, Nystrom, Darley, & Cohen 2001; Haidt 2012; Pizarro 2000). This means that when we read about the use of CRISPR to edit human embryos, we immediately and automatically form a moral judgement, and then our calculating reasoning jumps in to find arguments to justify that initial judgement. Moral reasoning, in other words, works as a lawyer that tries to defend the initially formed judgement, rather than as a meticulous judge that collects all the available evidence first (Haidt 2012).

Not only that, we are also much better at finding evidence that supports our initial judgement than finding evidence that may contradict it (what is called 'confirmation bias', Shaw 1996). So, if like me, you think that CRISPR is not the beginning of the end at all, and that we can allow research and then wait to see what happens, you will be more likely to find the articles that support this (i.e your) view more convincing than others. This is all good as far as it goes. The risk is of constructing opposing camps rather than what research both in science and in ethics is all about: a joint effort to advance knowledge.

Luckily, all is not lost. We can change our mind, refine our intuitions, and we can try to resist the urge of camp-forming. What can help us is what moral psychologist Professor Jonathan Haidt at New York Stern Business School calls social persuasion. We can be persuaded and we can refine our initial intuitions thanks to the influence of others. But while we have to keep our ears and hearts sufficiently open, others have to present their arguments and views in such a way that does not erect walls, but builds bridges. A way that tries to engage with a (possibly different) view rather than quickly dismiss it.

As bioethicists, I believe we have a responsibility to join forces in order to favour these conversations, to present arguments that are not trying to be conclusive, but to be open. And we need to start all this right now. That's about the only rush that I feel comfortable endorsing.​

Science | 14 January 2001
Haidt, J. The Righteous Mind: Why good people are divided by religion and politics
Pantheon, New York | 2012
Journal for the Theory of Social Behaviour | 12/2000
Thinking & Reasoning | 1996


19 February 2018 - by Rikita Patel 
Researchers have found a new use for CRISPR, adapting the system to detect viral infections with high accuracy, a new study finds...
13 November 2017 - by Rachel Siden 
Members of Canada's Stem Cell Network have called for the country to re-examine its laws banning genome editing research on the human germline...
13 November 2017 - by Dr Calum MacKellar 
On the 20th anniversary of the of the 1997 European Convention on Human Rights and Biomedicine (Oviedo Convention), the Council of Europe Committee on Bioethics organised an international conference entitled ‘Relevance and Challenges’ last month in Strasbourg, France...
02 October 2017 - by Sandy Starr 
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....
04 September 2017 - by Eleanor Taylor 
As a scientist working in a fertility clinic, my normal everyday work routine is occasionally punctuated by the ripple effect that occurs when reports of a new groundbreaking reproductive technology enters the public consciousness. I am soon inundated with questions...


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Liquid DNA biopsies could be used for cancer screening

21 August 2017

By Dr Loredana Guglielmi

Page URL: Appeared in BioNews 914

US researchers have developed a new blood test to detect cancer-related DNA alterations before patients experience symptoms.

The test, known as liquid biopsy, correctly identified over half of patients with early stage cancers and produced no false positives. The diagnostic accuracy of the test increased in later disease stages. 

'This is one of the first studies to use an unbiased approach - you don't know where the mutations are going to be - and to look at the blood of early-stage cancer patients to see whether we could detect alterations,' said Professor Victor Velculescu, who led the study at the Johns Hopkins Kimmel Cancer Centre, Maryland. 

The study evaluated the presence of fragments of tumour DNA (cfDNA) in the blood of 200 patients with colorectal breast, lung, and ovarian cancers compared to a control group of 44 healthy donors.

Previous studies using liquid biopsies have been used to detect cancer relapse or to determine whether treatments are working. In those cases the specific mutation in a particular patient's cancer are known, and can be targeted.

In the new study, published in Science Translational Medicine, a panel of 58 cancer-associated genes was used to screen all the blood samples with a new technology called targeted error correction sequencing (TEC-seq) which sequences the fragments of DNA 30,000 times. The test is sensitive enough to differentiate DNA modifications which normally occur from cancer driver mutations during an individual's life.

'It's actually very hard to find these mutations in the blood, especially when you don't know what the mutations are upfront,' commented Professor Velculescu. 'There are a number of confounding errors that can come up. Besides sequencing and technical errors, you can get alterations that come from the germline and can also get mutations that come from blood cells. We developed a way in which you could distinguish tumour driver mutations from these other alterations that might be in the blood.'

Next steps for the team are to increase the number of patients and type of cancers screened, and conduct clinical trials to assess the new technology impact on clinical outcomes. Such deep sequencing analyses are currently too costly to be implemented as routine diagnostic tools.

NBC News | 17 August 2017
Science Translational Medicine | 16 August 2017
Medpage Today | 16 August 2017
Johns Hopkins Medicine | 16 August 2017


05 February 2018 - by Evelyn Jager 
'This House believes that everyone should have their whole genome sequenced at birth.' This was the motion discussed at The Great Genome Sequencing Debate at the Royal Institution on Wednesday 24 January, sponsored by Roche...
22 January 2018 - by Dr Loredana Guglielmi 
Scientists have developed a single blood test to detect eight common cancer types and their location of origin within the body...
06 November 2017 - by Isobel Steer 
Machine learning has been used to develop a promising screening test for ovarian cancer, a team of US-based researchers has said...

26 June 2017 - by Charlotte Spicer 
A new three-in-one blood test could progress personalised treatment for patients with prostate cancer...
02 May 2017 - by Dr Loredana Guglielmi 
Blood tests for tumour DNA could predict relapse of the most common type of lung cancer up to one year before clinical signs show up on patient's scans...
13 March 2017 - by Dr Loredana Guglielmi 
Researchers have developed a new blood test that can not only detect cancer at an early stage, but can also indicate where the tumour is located in the body...
09 November 2015 - by Ayala Ochert 
Scientists say it may be possible to track the progress of cancer – and cancer treatment – in real time from fragments of tumour DNA that are shed into the bloodstream...


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Sperm from stem cells could help some types of male infertility

21 August 2017

By Shaoni Bhattacharya

Page URL: Appeared in BioNews 914

Cells from genetically infertile male mice have been turned into sperm, and used to produce healthy pups.

Researchers hope the technique could one day help men with certain causes of infertility. Experts hailed the work as 'very encouraging' and 'fascinating science', while noting that the technique is experimental only, and raises ethical and legal considerations should it be developed for humans.

'Our approach allowed us to create offspring from sterile XXY and XYY mice,' says first author Dr Takayuki Hirota at the Francis Crick Institute in London. 'It would be interesting to see whether the same approach could one day be used as a fertility treatment for men with three sex chromosomes.'

Having an extra sex chromosome – three instead of two – can cause infertility in mice and men. In humans, about one in 500 men may have either an extra X chromosome (Klinefelter's syndrome) or an extra Y chromosome (Double Y) in their genomes.

British and Japanese researchers aimed to remove the extra sex chromosome in infertile male mice with this problem. They took cells from the ears of the mice and cultured them in the lab to collect fibroblast (connective tissue) cells. They then coaxed the fibroblast cells into iPS, induced pluripotent stem cells – in the process some of the cells lost their extra sex chromosome.

Using specific chemical signals, the researchers could guide these stem cells into becoming the cells which can develop into sperm. When these were transplanted into the testes of live mice, they matured into sperm, which were used in assisted reproduction to give healthy pups.

Others agree the study offers potential. 'Although a mouse study, this research is exciting, since it raises the future possibility that sperm without the extra X chromosome could be made,' said Dr Channa Jayasena, a reproductive endocrinologist at Imperial College London. 'This could offer potential hope for affected couples.'

Indeed, a preliminary experiment by the researchers turning fibroblast cells from men with Klinefelter's syndrome into stem cells in vitro managed to lose the extra X chromosome.

But, Dr Jayasena notes the new study 'raises important ethical issues'.

Professor Allan Pacey at the University of Sheffield, UK, said: 'This is very encouraging. The only fly in the ointment is that currently the use of such sperm in the UK is not lawful and it would take a change of primary legislation to allow us to use such sperm in infertility treatment.'

While praising the study, Professor Adam Balen, chair of the British Fertility Society, said its application in improving fertility in men with Klinefelter’s syndrome 'is a long way off clinical practice'.

He also noted: 'Furthermore there are possible significant risks outlined in the paper which mean that any therapeutic application is far from certain.'

The study, published in Science, found that when the cells were transplanted into the testes of mice, some of the animals developed teratomas.


06 November 2017 - by Lea Goetz 
Men with infertility experience stigmatisation and a lack of support, a first survey on the subject found...

14 November 2016 - by Dr Katie Howe 
US researchers have created functional eggs using DNA from small cells that normally form as waste products during egg development...
24 October 2016 - by Dr Katie Howe 
Scientists in Japan are the first to have created live mouse pups from eggs that were made from stem cells...
03 May 2016 - by Ayala Ochert 
Spanish scientists say they have created rudimentary sperm-like cells from skin and bone marrow cells taken from adult males...
21 March 2016 - by Dr Julia Hill 
Scientists have created human stem cells with 23 chromosomes instead of 46, the normal number in a complete genome contained in almost all cells...
06 May 2014 - by Siobhan Chan 
Skin tissue from infertile men has been converted into sperm cell precursors after their stem cells were transplanted into mice...


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


Americans becoming open to human genome editing

21 August 2017

By Dr Rachel Huddart

Page URL: Appeared in BioNews 914

A new survey suggests that Americans are becoming more accepting of the use of genome editing in humans, and there is strong support for more public involvement in discussions on the technology.

The results, published in the journal Science, come just one week after scientists successfully used genome editing to correct a disease-causing mutation in human embryos (see BioNews 912). The survey aimed to gauge the American public's attitudes toward the technology, and ascertain whether they want to be included in shaping future policy around its use.

Around two-thirds of respondents felt that 'therapeutic' genome editing to treat disease in humans was generally acceptable, an increase from previous surveys (see BioNews 862). This included treatments that would correct mutations in both somatic cells and germ cells, such as eggs and sperm. However, that support dropped when it came to using genome editing to enhance healthy humans (e.g to increase IQ or change eye colour), with only one-third of respondents feeling that this was an acceptable use.

The survey, conducted by researchers from the University of Madison-Wisconsin, the Morgridge Institute for Research, Wisconsin, and Temple University in Philadelphia, Pennsylvania, also found that a respondent's religious beliefs and level of scientific knowledge influenced their level of support.

People with religious beliefs were generally less supportive for both treatment and enhancement purposes than people who classed themselves as not religious, while respondents with a higher level of scientific knowledge were more likely to be supportive of genome editing for disease treatment than those with less. Interestingly, high-knowledge respondents had strong views both for and against human genome editing for enhancement, with about 41 per cent being supportive and a similar percentage being against it, while around half of low-knowledge respondents were neither for nor against this use of genome editing.

Despite the split in opinion on acceptable uses of genome editing, almost all respondents agreed that the public should be involved in conversations between scientists and policymakers about the role genome editing will play in society. However, it is still unclear how that process of dialogue with the public will happen.

Professor Dietram Schufele at the University of Madison-Wisconsin, who led the research, said: 'The public may be split along lines of religiosity or knowledge with regard to what they think about the technology and scientific community, but they are united in the idea that this is an issue that requires public involvement … Our findings show very nicely that the public is ready for these discussions and that the time to have the discussions is now, before the science is fully ready and while we have time to carefully think through different options regarding how we want to move forward.'


30 October 2017 - by Dr Rachel Huddart 
A new molecular tool to change individual letters in an RNA sequence may open up new possibilities for gene therapy...

07 August 2017 - by Charlotte Spicer 
Scientists have published their study confirming they are the first to correct a disease-causing mutation in human embryos using genome editing...
07 August 2017 - by Dr Greg Ball 
Research into human germline genome editing should continue, recommends an international group of 11 human genetics organisations...
20 February 2017 - by Dr Rachel Huddart 
An influential advisory group has given cautious support to the idea of making heritable changes to the human genome in order to treat or prevent disease...
28 November 2016 - by Lucas Taylor 
More than 75 percent of those with a genetic condition, and their family members, support the use of genome-editing technology, a survey has found...
01 August 2016 - by Anneesa Amjad 
A survey has found that a majority of adults in the USA are worried about the potential use of genome-editing technologies to give children a reduced risk of disease...


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


Female is not 'default sex' of embryos

21 August 2017

By Jamie Rickman

Page URL: Appeared in BioNews 914

A protein that controls removal of male reproductive tissue in female mice embryos has been discovered. 

The protein is critical to the correct growth of the female reproductive system, and overturns the longstanding theory that development of the female reproductive system is a passive process which spontaneously occurs when the male hormone androgen is not present.

'We were just shocked,' said co-author Dr Humphrey Hung-Chang Yao of the National Institute of Environmental Health Sciences (NIEHS).

The study overturns the 'female-by-default' theory, which has been held for over half a century. At the start of mammalian reproductive development, both male, sperm-carrying reproductive tracts and female, egg-delivering reproductive tracts are present. Depending on the sex of the embryo, one set of tracts usually disintegrates as development proceeds.

The team were researching how reproductive tissues communicate with early tract linings in female mouse embryos. Suspecting that a protein called COUP-TFII was involved, the team genetically modified female mice embryos to lack the gene responsible for producing it. To their surprise, the male reproductive tracts did not disintegrate in these embryos, and they were born intersex with both male and female reproductive tracts.

After ruling out the possibility that androgen was present in the mutant female mice, they concluded that COUP-TFII is required for active removal of the male tracts.

COUP-TFII is also found in many other tissues and is crucial for the survival of mice embryos. It may also be implicated in other complex disorders. While their study uses a mouse model of reproductive development, it is thought that the process is very similar in humans.

The team say the study could aid in studies of sex development disorders such as cryptorchidism (undescended testicles), Klinefelter Syndrome and Turner Syndrome.

'Individuals with [sex development disorders] may have developmental challenges due to the presence of intersex organ systems,' said Dr Kenneth Korach, head of the NIEHS Reproductive and Developmental Biological Laboratory, 'With its highly novel approach and unexpected findings, Yao's research has important implications for understanding the potential causes of these conditions.'

'This work is just the beginning and many interesting questions remain unanswered,' lead author Dr Fei Zhao said, 'We will continue to study how the embryo develops a functional reproductive system.'

Although the findings give some indication of how COUP-TFII controls disintegration of the male reproductive tracts, more research is needed. In particular the team want to investigate the interaction between COUP-TFII and male hormones such as androgen, as well as looking for other proteins involved in the process.

The study was published in the journal Science.


23 March 2015 - by Sophie McLachlan 
The nutrient-filled liquid used to grow embryos during IVF might affect the resulting male to female birth ratio, a study suggests...


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Cancer atlas leads way to personalised treatment

21 August 2017

By Marcia Costa

Page URL: Appeared in BioNews 914

Genes linked to 17 types of cancer have been mapped in a new Pathology Atlas by Swedish researchers.

The atlas links different levels of gene expression to patient survival across different cancers, and also points in the direction of new drug targets.

'We are pleased to provide a stand-alone open-access resource for cancer researchers worldwide, which we hope will help accelerate their efforts to find the biomarkers needed to develop personalised cancer treatments,' said co-author Professor Fredrik Pontén of Uppsala University.

Professor Mathias Uhlén of the Royal Institute of Technology, Sweden and his team re-analysed almost 8000 patient's tumours to compile the atlas, by using a supercomputer to analyse data collected by several public databases. They found genes involved in DNA replication, cell division and cell death tended to be expressed at higher levels in tumours.

The researchers mapped genes in the tumour samples to identify and characterise the proteins produced by these genes. They found levels of protein production varied widely across different cancers.

By identifying expression levels for each patient, it could be possible to deliver a treatment tailored for each individual. Much past research has focused on finding mutations associated with risk of cancer.

'Oncologists and pathologists are not very impressed by prognostic genes because they are only statistical,' Professor Uhlén said to GenomeWeb. 'You can have a bad gene and survive very well, and you can have a good gene and not survive.'

Furthermore, the team found 32 genes shared across more than 80 percent of the tumours, which are potential targets for drug development. The team also found several genes essential for tumour survival.

'And those could, of course, be fantastic targets for cancer therapy,' Professor Uhlén said. 'This is one reason we are saying this could be a part of personalised medicine, because we can use next-generation sequencing of these patients, put that data into the model, and then we could say these patients should be treated with this inhibitor and not this one and so on.'

The team is now analysing genetic information on other types of cancer.

Dr Nicolas Robine of the New York Genome Center, who was not involved in the research, warned MIT Technology Review that the atlas, while useful for researchers, could not provide definitive information on patient outcomes.

The atlas is part of a Swedish program started in 2003 with the aim of mapping all of the human proteins made by the body's 20,000 or more genes.

The results were published in Science.


20 November 2017 - by Marcia Costa 
A team of scientists in Germany has developed a 'sensor' that detects mutations in the key tumour suppressor gene p53 and then kills potentially cancerous cells...

14 August 2017 - by Ebtehal Moussa 
Over a 100 new genes that may be essential for cancer immunotherapy to work have been identified using a new CRISPR-based screen...
31 July 2017 - by Rikita Patel 
The IBM Watson supercomputer can analyse 160 hours' worth of genomic data in just ten minutes...
31 July 2017 - by Dr Molly Godfrey 
A comprehensive map of genes crucial to tumour cell survival has been created by researchers...
26 May 2015 - by Dr Julia Hill 
Scientists have announced a comprehensive genetic map of prostate cancer, which they say could lead to new treatments for the advanced stage of the disease...


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


Vitamin C slows leukaemia in mice by tweaking key gene

21 August 2017

By Emma Laycock

Page URL: Appeared in BioNews 914

High doses of vitamin C may help fight certain leukaemias by boosting the activity of a particular gene, suggests a new study.

Daily injections of vitamin C slowed the progression of leukaemia in mice with a faulty gene called TET2, and increased efficacy of drug treatment.

'We're excited by the prospect that high-dose vitamin C might become a safe treatment for blood diseases caused by TET2-deficient leukaemia stem cells, most likely in combination with other targeted therapies,' said corresponding study author Professor Benjamin Neel, at the Perlmutter Cancer Centre, New York University (NYU) Langone Health.

In leukaemia, cancerous cells often have mutations in gene called TET2 - its activity normally encourages blood stem cells to develop into mature white blood cells, which eventually die. Without TET2, the stem cells can multiply uncontrollably leading to leukaemia.

In the study, published in the journal Cell, the scientists genetically engineered mice such that they could reversibly lower TET2 expression, mimicking the low levels seen in patients. When researchers lowered TET2, the stem cells malfunctioned and the mice began to develop cancer. When they turned levels back up, disease progression halted.

Most patients with TET2 mutations do not have a complete loss of the protein, because they only have a mutation in one copy of the gene, first author Dr Luisa Cimmino of NYU Langone Health told The Scientist. 'And if we could only bring [its] activity back to normal levels, it would be like restoring the protein back to normal levels. That's where the vitamin C comes in.'

The team found that daily vitamin C - previously shown to stimulate the activity of TET2 - slowed the progression of leukaemia, inducing the faulty stem cells to mature and later die. In effect, giving the vitamin mimicked the effect of restoring TET2 genetically.

The researchers also found that vitamin C enhanced the sensitivity of leukaemia stem cells to a type of cancer drug, PARP inhibitors, in vitro. These drug types are known to cause cancer cell death by blocking the repair of mutations damage, and are already approved for treating certain patients with ovarian cancer, said Dr Cimmino.

'If these findings withstand clinical testing, the impact for patients with blood cancers could be significant,' Dr Eirini Papapetrou of the Icahn School of Medicine at Mount Sinai in New York City told The Scientist.

Professor Neel cautioned against eating excessive amounts of vitamin C, as humans can only get the levels required intravenously. He also added that while there are some health benefits to vitamin C, 'they're unlikely to be a general anti-cancer therapy'.

His team is moving forward with clinical trials to test the efficacy of vitamin C combined with other therapies in certain leukaemias.


27 November 2017 - by Sam Sherratt 
A new gene therapy for leukaemia is effective for a majority of patients who showed resistance to previous therapies...

19 June 2017 - by Rachel Reeves 
Cancer stem cells, thought to be the root cause of tumour recurrence, could be eradicated using vitamin C and antibiotics, suggests a new study...
17 October 2016 - by Dr Rosie Gilchrist 
Vitamins A and C help to convert adult cells into stem cells by performing a cell 'reset', erasing their epigenetic memory, a study has found...


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Book Review: A Crack in Creation - Gene Editing and the Unthinkable Power to Control Evolution

21 August 2017

By Annabel Slater

Page URL: Appeared in BioNews 914

'A crack in creation' is a beautifully dramatic name for this biography of CRISPR/Cas9, the revolutionary genome editing tool of the 21st century. Reading the prologue, I wondered if it would also be an autobiography by Professor Jennifer Doudna at the University of California (UC), Berkeley. Certainly, she begins by describing a rather grandiose, portentous dream - as our narrative heroine and real-life scientist stands on a beautiful beach from her childhood, she spies an approaching tidal wave, which she boldly paddles out to meet and dives through on a surfboard. Everything that CRISPR/Cas9 makes possible is the wave. We - the public, policymakers, and scientists - must be prepared to swim out and engage with it.

But the book is not a scientist's autobiography. I confess, I was a little disappointed. I do like reading autobiographies. By sharing childhood memories, awkward teenage years, and wryly admitted insecurities in adult life, famous scientists reassert themselves as human beings rather than icons. Still, though the book is written in the first person and describes only Professor Doudna's experiences, it is a book about herself in relation to CRISPR/Cas9, from around 2006 to 2016. Dr Samuel Sternberg, co-author of the seminal 2012 CRISPR/Cas9 paper, is listed again as co-author here.

The first half of the book is called 'The Tool'. Professor Doudna begins with an interesting account of 'natural genome editing' - spontaneous genetic rearrangements that have cured patients of genetic diseases through sheer luck - to whet our appetites for CRISPR/Cas9's potential as a tool against genetic disease. Through a brief history of alternative genome editing tools, she brings us to her meeting with Professor Jill Banfield at UC, who introduced her to 'CRISPR' - the sequence of unusual DNA repeats found in some bacteria. Professor Banfield wanted to know more about CRISPR, and based on other studies, had hypothesised that they might play some part in RNAi and bacterial immune systems. Professor Doudna, having spent much of her career studying RNA and with an interest in RNAi as a therapy, was hooked. She integrated CRISPR research into her lab and hired new postdoc researchers to carry out the work.

From here the book describes each step and set of experiments in the eventual characterisation of CRISPR, to the fusing of CRISPR with the enzyme Cas9 to create a customisable genome editing tool. This section of the book is fairly technical and requires attention to understand the significance of each step. Professor Doudna credibly describes the stepwise nature of research, how it is carried out by scientists working as part of a larger institution, occasionally derailed by researchers completing PhDs or needing to seek positions elsewhere, and draws on the published work of other groups around the world. She also emphasises the serendipitous nature of research, from meeting colleagues within the same institution or at conferences abroad, such as when she meets co-author Professor Emmanuelle Charpentier at a conference in Puerto Rico.

On the other hand, this section does describe a very neat narrative of the development of CRISPR/Cas9 - it almost seems inevitable. The inclusion of dates and names of researchers involved certainly creates a strong case for UC's claim (see BioNews 911) to the CRISPR patents.

And if this book does have any autobiographical elements, they are only assertions of Professor Doudna's persona as a scientist first, driven by a passion for research and possibilities. After the section culminates in the publication of the 2012 paper, she describes seeing the publication of other papers on CRISPR/Cas9 editing with 'elation' and 'excitement'. There is just a whisper of the patent dispute when she describes the dissection of the publication dates of these papers as 'a disheartening twist to what had begun as collegial interactions and genuine shared excitement about the implications of this research'. And then it is mentioned no more. There are no chinks in this scientist's armour regarding those matters. No acknowledgement that how scientific research is conducted, and how it is funded, also instigates many of the problems in development and regulation of genome editing technologies. In that sense, the book leaves an impression of forced gloss.

The second half of the book, 'The Task', discusses possible uses of CRISPR/Cas9 in agriculture and healthcare, referencing spots of current and past research. Although interesting and optimistic, I enjoyed the final quarter of the book more when it turned a little personal again. Our narrative heroine and scientist admits eventual caution, and then downright worry that 'public discussion was falling far behind the breakneck pace of [scientific research of CRISPR]'. Her subconscious delivers another helpfully clear and portentous dream where a pig-faced Adolf Hitler wants her to tell him the uses and implications of CRISPR/Cas9. Waking in fright, Professor Doudna draws comparisons between genome editing technology and the development of the nuclear bomb, worries over the transparency of research, and the open availability of genome editing procedures and tools. She arranges a conference to produce an advisory white paper on germline editing in human embryos, admitting such a task intimidated her and that taking a public stand on a scientific issue felt foreign and almost transgressive (see BioNews 795). The rest of the book deals with the public discussion and regulation of CRISPR.

Professor Doudna makes it clear that the book states only her opinions, and it's laudable that she is willing to make them public. She also occasionally discusses the current barriers and regulators of such applications, lifting the book slightly above general pro-science speculation and rhetorical questions. It is perhaps somewhat disappointing that the monetary side of scientific research, the patent disputes, and the distorting influence of commercialisation of technology is not discussed. The book is assiduously devoted to public debate, but the absence of these topics is both a proverbial elephant in the room and a clear message that the author does not want to step into the firing range.

I'm glad to see a scientist engaging so strongly in public debate about the use of technology, rather than speculating on the sidelines. Professor Doudna's perspective as a scientist also adds valuable insight for the public. She closes the book with a powerful call to scientists to be prepared to debate the consequences of their work, but to also communicate the nature of research.

Although the book clearly seeks to state that it was the expertise of her lab and her own specific, lifelong research interests that led to the discovery of the CRISPR/Cas9 genome editing method, she emphasises that open-ended science research was the only way to get there. It took decades of combined research and accumulated studies into the biology and chemistry of bacteria before the prospect of genome editing using CRISPR became apparent.

Professor Doudna's book delivers a positive scientist's view of a future where genome editing can deliver benefits for humankind, provided we strive for a society where everyone's rights are respected regardless of their genes. I gingerly await another author to deliver a more cynical look at whether this is possible.

Book to buy -



30 October 2017 - by Jennifer Willows 
The Broad Institute has filed arguments ahead of the upcoming CRISPR patent appeal hearing...
25 September 2017 - by Rikita Patel 
The new era of gene technology presents an exciting approach to treat deleterious, inherited genetic conditions. Presenter Jim Al-Khalili talks to Professor Jennifer Doudna, from her early life to her research into molecular biology, to the development of the CRISPR/Cas9 genome editing system...

03 July 2017 - by Annabel Slater 
'This technology really gets the imagination going. It's almost anything that you could imagine wanting to control at the level of genetics, is now in principle within reach.' And the power to control evolution raises important questions of responsibility. This is the message of Professor Jennifer Doudna...


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