Tag Archives: eugenics

Genes, intelligence, Chinese CRISPR (clustered regularly interspaced short palindromic repeats) babies, and other children

This started out as an update and now it’s something else. What follows is a brief introduction to the Chinese CRISPR twins; a brief examination of parents, children, and competitiveness; and, finally, a suggestion that genes may not be what we thought. I also include a discussion about how some think scientists should respond when they know beforehand that one of their kin is crossing an ethical line. Basically, this is a complex topic and I am attempting to interweave a number of competing lines of query into one narrative about human nature and the latest genetics obsession.

Introduction to the Chinese CRISPR twins

Back in November 2018 I covered the story about the Chinese scientist, He Jiankui , who had used CRISPR technology to edit genes in embryos that were subsequently implanted in a waiting mother (apparently there could be as many as eight mothers) with the babies being brought to term despite an international agreement (of sorts) not to do that kind of work. At this time, we know of the twins, Lulu and Nana but, by now, there may be more babies. (I have much more detail about the initial controversies in my November 28, 2018 posting.)

It seems the drama has yet to finish unfolding. There may be another consequence of He’s genetic tinkering.

Could the CRISPR babies, Lulu and Nana, have enhanced cognitive abilities?

Yes, according to Antonio Regalado’s February 21, 2019 article (behind a paywall) for MIT’s (Massachusetts Institute of Technology) Technology Review, those engineered babies may have enhanced abilities for learning and remembering.

For those of us who can’t get beyond the paywall, others have been successful. Josh Gabbatiss in his February 22, 2019 article for independent.co.uk provides some detail,

The world’s first gene edited babies may have had their brains unintentionally altered – and perhaps cognitively enhanced – as a result of the controversial treatment undertaken by a team of Chinese scientists.

Dr He Jiankui and his team allegedly deleted a gene from a number of human embryos before implanting them in their mothers, a move greeted with horror by the global scientific community. The only known successful birth so far is the case of twin girls Nana and Lulu.

The now disgraced scientist claimed that he removed a gene called CCR5 [emphasis mine] from their embroyos in an effort to make the twins resistant to infection by HIV.

But another twist in the saga has now emerged after a new paper provided more evidence that the impact of CCR5 deletion reaches far beyond protection against dangerous viruses – people who naturally lack this gene appear to recover more quickly from strokes, and even go further in school. [emphasis mine]

Dr Alcino Silva, a neurobiologist at the University of California, Los Angeles, who helped identify this role for CCR5 said the work undertaken by Dr Jiankui likely did change the girls’ brains.

“The simplest interpretation is that those mutations will probably have an impact on cognitive function in the twins,” he told the MIT Technology Review.

The connection immediately raised concerns that the gene was targeted due to its known links with intelligence, which Dr Silva said was his immediate response when he heard the news.

… there is no evidence that this was Dr Jiankui’s goal and at a press conference organised after the initial news broke, he said he was aware of the work but was “against using genome editing for enhancement”.

..

Claire Maldarelli’s February 22, 2019 article for Popular Science provides more information about the CCR5 gene/protein (Note: Links have been removed),

CCR5 is a protein that sits on the surface of white blood cells, a major component of the human immune system. There, it allows HIV to enter and infect a cell. A chunk of the human population naturally carries a mutation that makes CCR5 nonfunctional (one study found that 10 percent of Europeans have this mutation), which often results in a smaller protein size and one that isn’t located on the outside of the cell, preventing HIV from ever entering and infecting the human immune system.

The goal of the Chinese researchers’ work, led by He Jiankui of the Southern University of Science and Technology located in Shenzhen, was to tweak the embryos’ genome to lack CCR5, ensuring the babies would be immune to HIV.

But genetics is rarely that simple.

In recent years, the CCR5 gene has been a target of ongoing research, and not just for its relationship to HIV. In an attempt to understand what influences memory formation and learning in the brain, a group of researchers at UCLA found that lowering the levels of CCR5 production enhanced both learning and memory formation. This connection led those researchers to think that CCR5 could be a good drug target for helping stroke victims recover: Relearning how to move, walk, and talk is a key component to stroke rehabilitation.

… promising research, but it begs the question: What does that mean for the babies who had their CCR5 genes edited via CRISPR prior to their birth? Researchers speculate that the alternation will have effects on the children’s cognitive functioning. …

John Loeffler’s February 22, 2019 article for interestingengineering.com notes that there are still many questions about He’s (scientist’s name) research including, did he (pronoun) do what he claimed? (Note: Links have been removed),

Considering that no one knows for sure whether He has actually done as he and his team claim, the swiftness of the condemnation of his work—unproven as it is—shows the sensitivity around this issue.

Whether He did in fact edit Lulu and Nana’s genes, it appears he didn’t intend to impact their cognitive capacities. According to MIT Technology Review, not a single researcher studying CCR5’s role in intelligence was contacted by He, even as other doctors and scientists were sought out for advice about his project.

This further adds to the alarm as there is every expectation that He should have known about the connection between CCR5 and cognition.

At a gathering of gene-editing researchers in Hong Kong two days after the birth of the potentially genetically-altered twins was announced, He was asked about the potential impact of erasing CCR5 from the twins DNA on their mental capacity.

He responded that he knew about the potential cognitive link shown in Silva’s 2016 research. “I saw that paper, it needs more independent verification,” He said, before adding that “I am against using genome editing for enhancement.”

The problem, as Silva sees it, is that He may be blazing the trail for exactly that outcome, whether He intends to or not. Silva says that after his 2016 research was published, he received an uncomfortable amount of attention from some unnamed, elite Silicon Valley leaders who seem to be expressing serious interest in using CRISPR to give their children’s brains a boost through gene editing. [emphasis mine]

As such, Silva can be forgiven for not quite believing He’s claims that he wasn’t intending to alter the human genome for enhancement. …

The idea of designer babies isn’t new. As far back as Plato, the thought of using science to “engineer” a better human has been tossed about, but other than selective breeding, there really hasn’t been a path forward.

In the late 1800s, early 1900s, Eugenics made a real push to accomplish something along these lines, and the results were horrifying, even before Nazism. After eugenics mid-wifed the Holocaust in World War II, the concept of designer children has largely been left as fodder for science fiction since few reputable scientists would openly declare their intention to dabble in something once championed and pioneered by the greatest monsters of the 20th century.

Memories have faded though, and CRISPR significantly changes this decades-old calculus. CRISPR makes it easier than ever to target specific traits in order to add or subtract them from an embryos genetic code. Embryonic research is also a diverse enough field that some scientist could see pioneering designer babies as a way to establish their star power in academia while getting their names in the history books, [emphasis mine] all while working in relative isolation. They only need to reveal their results after the fact and there is little the scientific community can do to stop them, unfortunately.

When He revealed his research and data two days after announcing the births of Lulu and Nana, the gene-scientists at the Hong Kong conference were not all that impressed with the quality of He’s work. He has not provided access for fellow researchers to either his data on Lulu, Nana, and their family’s genetic data so that others can verify that Lulu and Nana’s CCR5 genes were in fact eliminated.

This almost rudimentary verification and validation would normally accompany a major announcement such as this. Neither has He’s work undergone a peer-review process and it hasn’t been formally published in any scientific journal—possibly for good reason.

Researchers such as Eric Topol, a geneticist at the Scripps Research Institute, have been finding several troubling signs in what little data He has released. Topol says that the editing itself was not precise and show “all kinds of glitches.”

Gaetan Burgio, a geneticist at the Australian National University, is likewise unimpressed with the quality of He’s work. Speaking of the slides He showed at the conference to support his claim, Burgio calls it amateurish, “I can believe that he did it because it’s so bad.”

Worse of all, its entirely possible that He actually succeeded in editing Lulu and Nana’s genetic code in an ad hoc, unethical, and medically substandard way. Sadly, there is no shortage of families with means who would be willing to spend a lot of money to design their idea of a perfect child, so there is certainly demand for such a “service.”

It’s nice to know (sarcasm icon) that the ‘Silicon Valley elite’ are willing to volunteer their babies for scientific experimentation in a bid to enhance intelligence.

The ethics of not saying anything

Natalie Kofler, a molecular biologist, wrote a February 26, 2019 Nature opinion piece and call to action on the subject of why scientists who were ‘in the know’ remained silent about He’s work prior to his announcements,

Millions [?] were shocked to learn of the birth of gene-edited babies last year, but apparently several scientists were already in the know. Chinese researcher He Jiankui had spoken with them about his plans to genetically modify human embryos intended for pregnancy. His work was done before adequate animal studies and in direct violation of the international scientific consensus that CRISPR–Cas9 gene-editing technology is not ready or appropriate for making changes to humans that could be passed on through generations.

Scholars who have spoken publicly about their discussions with He described feeling unease. They have defended their silence by pointing to uncertainty over He’s intentions (or reassurance that he had been dissuaded), a sense of obligation to preserve confidentiality and, perhaps most consistently, the absence of a global oversight body. Others who have not come forward probably had similar rationales. But He’s experiments put human health at risk; anyone with enough knowledge and concern could have posted to blogs or reached out to their deans, the US National Institutes of Health or relevant scientific societies, such as the Association for Responsible Research and Innovation in Genome Editing (see page 440). Unfortunately, I think that few highly established scientists would have recognized an obligation to speak up.

I am convinced that this silence is a symptom of a broader scientific cultural crisis: a growing divide between the values upheld by the scientific community and the mission of science itself.

A fundamental goal of the scientific endeavour is to advance society through knowledge and innovation. As scientists, we strive to cure disease, improve environmental health and understand our place in the Universe. And yet the dominant values ingrained in scientists centre on the virtues of independence, ambition and objectivity. That is a grossly inadequate set of skills with which to support a mission of advancing society.

Editing the genes of embryos could change our species’ evolutionary trajectory. Perhaps one day, the technology will eliminate heritable diseases such as sickle-cell anaemia and cystic fibrosis. But it might also eliminate deafness or even brown eyes. In this quest to improve the human race, the strengths of our diversity could be lost, and the rights of already vulnerable populations could be jeopardized.

Decisions about how and whether this technology should be used will require an expanded set of scientific virtues: compassion to ensure its applications are designed to be just, humility to ensure its risks are heeded and altruism to ensure its benefits are equitably distributed.

Calls for improved global oversight and robust ethical frameworks are being heeded. Some researchers who apparently knew of He’s experiments are under review by their universities. Chinese investigators have said He skirted regulations and will be punished. But punishment is an imperfect motivator. We must foster researchers’ sense of societal values.

Fortunately, initiatives popping up throughout the scientific community are cultivating a scientific culture informed by a broader set of values and considerations. The Scientific Citizenship Initiative at Harvard University in Cambridge, Massachusetts, trains scientists to align their research with societal needs. The Summer Internship for Indigenous Peoples in Genomics offers genomics training that also focuses on integrating indigenous cultural perspectives into gene studies. The AI Now Institute at New York University has initiated a holistic approach to artificial-intelligence research that incorporates inclusion, bias and justice. And Editing Nature, a programme that I founded, provides platforms that integrate scientific knowledge with diverse cultural world views to foster the responsible development of environmental genetic technologies.

Initiatives such as these are proof [emphasis mine] that science is becoming more socially aware, equitable and just. …

I’m glad to see there’s work being done on introducing a broader set of values into the scientific endeavour. That said, these programmes seem to be voluntary, i.e., people self-select, and those most likely to participate in these programmes are the ones who might be inclined to integrate social values into their work in the first place.

This doesn’t address the issue of how to deal with unscrupulous governments pressuring scientists to create designer babies along with hypercompetitive and possibly unscrupulous individuals such as the members of the ‘Silicon Valley insiders mentioned in Loeffler’s article, teaming up with scientists who will stop at nothing to get their place in the history books.

Like Kofler, I’m encouraged to see these programmes but I’m a little less convinced that they will be enough. What form it might take I don’t know but I think something a little more punitive is also called for.

CCR5 and freedom from HIV

I’ve added this piece about the Berlin and London patients because, back in November 2018, I failed to realize how compelling the idea of eradicating susceptibility to AIDS/HIV might be. Reading about some real life remissions helped me to understand some of He’s stated motivations a bit better. Unfortunately, there’s a major drawback described here in a March 5, 2019 news item on CBC (Canadian Broadcasting Corporation) online news attributed to Reuters,

An HIV-positive man in Britain has become the second known adult worldwide to be cleared of the virus that causes AIDS after he received a bone marrow transplant from an HIV-resistant donor, his doctors said.

The therapy had an early success with a man known as “the Berlin patient,” Timothy Ray Brown, a U.S. man treated in Germany who is 12 years post-transplant and still free of HIV. Until now, Brown was the only person thought to have been cured of infection with HIV, the virus that causes AIDS.

Such transplants are dangerous and have failed in other patients. They’re also impractical to try to cure the millions already infected.

In the latest case, the man known as “the London patient” has no trace of HIV infection, almost three years after he received bone marrow stem cells from a donor with a rare genetic mutation that resists HIV infection — and more than 18 months after he came off antiretroviral drugs.

“There is no virus there that we can measure. We can’t detect anything,” said Ravindra Gupta, a professor and HIV biologist who co-led a team of doctors treating the man.

Gupta described his patient as “functionally cured” and “in remission,” but cautioned: “It’s too early to say he’s cured.”

Gupta, now at Cambridge University, treated the London patient when he was working at University College London. The man, who has asked to remain anonymous, had contracted HIV in 2003, Gupta said, and in 2012 was also diagnosed with a type of blood cancer called Hodgkin’s lymphoma.

In 2016, when he was very sick with cancer, doctors decided to seek a transplant match for him.

“This was really his last chance of survival,” Gupta told Reuters.

Doctors found a donor with a gene mutation known as CCR5 delta 32, which confers resistance to HIV. About one per cent of people descended from northern Europeans have inherited the mutation from both parents and are immune to most HIV. The donor had this double copy of the mutation.

That was “an improbable event,” Gupta said. “That’s why this has not been observed more frequently.”

Most experts say it is inconceivable such treatments could be a way of curing all patients. The procedure is expensive, complex and risky. To do this in others, exact match donors would have to be found in the tiny proportion of people who have the CCR5 mutation.

Specialists said it is also not yet clear whether the CCR5 resistance is the only key [emphasis mine] — or whether the graft-versus-host disease may have been just as important. Both the Berlin and London patients had this complication, which may have played a role in the loss of HIV-infected cells, Gupta said.

Not only is there some question as to what role the CCR5 gene plays, there’s also a question as to whether or not we know what role genes play.

A big question: are genes what we thought?

Ken Richardson’s January 3, 2019 article for Nautilus (I stumbled across it on May 14, 2019 so I’m late to the party) makes and supports a startling statement, It’s the End of the Gene As We Know It We are not nearly as determined by our genes as once thought (Note: A link has been removed),

We’ve all seen the stark headlines: “Being Rich and Successful Is in Your DNA” (Guardian, July 12); “A New Genetic Test Could Help Determine Children’s Success” (Newsweek, July 10); “Our Fortunetelling Genes” make us (Wall Street Journal, Nov. 16); and so on.

The problem is, many of these headlines are not discussing real genes at all, but a crude statistical model of them, involving dozens of unlikely assumptions. Now, slowly but surely, that whole conceptual model of the gene is being challenged.

We have reached peak gene, and passed it.

The preferred dogma started to appear in different versions in the 1920s. It was aptly summarized by renowned physicist Erwin Schrödinger in a famous lecture in Dublin in 1943. He told his audience that chromosomes “contain, in some kind of code-script, the entire pattern of the individual’s future development and of its functioning in the mature state.”

Around that image of the code a whole world order of rank and privilege soon became reinforced. These genes, we were told, come in different “strengths,” different permutations forming ranks that determine the worth of different “races” and of different classes in a class-structured society. A whole intelligence testing movement was built around that preconception, with the tests constructed accordingly.

The image fostered the eugenics and Nazi movements of the 1930s, with tragic consequences. Governments followed a famous 1938 United Kingdom education commission in decreeing that, “The facts of genetic inequality are something that we cannot escape,” and that, “different children … require types of education varying in certain important respects.”

Today, 1930s-style policy implications are being drawn once again. Proposals include gene-testing at birth for educational intervention, embryo selection for desired traits, identifying which classes or “races” are fitter than others, and so on. And clever marketizing now sees millions of people scampering to learn their genetic horoscopes in DNA self-testing kits.[emphasis mine]

So the hype now pouring out of the mass media is popularizing what has been lurking in the science all along: a gene-god as an entity with almost supernatural powers. Today it’s the gene that, in the words of the Anglican hymn, “makes us high and lowly and orders our estate.”

… at the same time, a counter-narrative is building, not from the media but from inside science itself.

So it has been dawning on us is that there is no prior plan or blueprint for development: Instructions are created on the hoof, far more intelligently than is possible from dumb DNA. That is why today’s molecular biologists are reporting “cognitive resources” in cells; “bio-information intelligence”; “cell intelligence”; “metabolic memory”; and “cell knowledge”—all terms appearing in recent literature.1,2 “Do cells think?” is the title of a 2007 paper in the journal Cellular and Molecular Life Sciences.3 On the other hand the assumed developmental “program” coded in a genotype has never been described.


It is such discoveries that are turning our ideas of genetic causation inside out. We have traditionally thought of cell contents as servants to the DNA instructions. But, as the British biologist Denis Noble insists in an interview with the writer Suzan Mazur,1 “The modern synthesis has got causality in biology wrong … DNA on its own does absolutely nothing [ emphasis mine] until activated by the rest of the system … DNA is not a cause in an active sense. I think it is better described as a passive data base which is used by the organism to enable it to make the proteins that it requires.”

I highly recommend reading Richardson’s article in its entirety. As well, you may want to read his book, ” Genes, Brains and Human Potential: The Science and Ideology of Intelligence .”

As for “DNA on its own doing absolutely nothing,” that might be a bit of a eye-opener for the Silicon Valley elite types investigating cognitive advantages attributed to the lack of a CCR5 gene. Meanwhile, there are scientists inserting a human gene associated with brain development into monkeys,

Transgenic monkeys and human intelligence

An April 2, 2019 news item on chinadaily.com describes research into transgenic monkeys,

Researchers from China and the United States have created transgenic monkeys carrying a human gene that is important for brain development, and the monkeys showed human-like brain development.

Scientists have identified several genes that are linked to primate brain size. MCPH1 is a gene that is expressed during fetal brain development. Mutations in MCPH1 can lead to microcephaly, a developmental disorder characterized by a small brain.

In the study published in the Beijing-based National Science Review, researchers from the Kunming Institute of Zoology, Chinese Academy of Sciences, the University of North Carolina in the United States and other research institutions reported that they successfully created 11 transgenic rhesus monkeys (eight first-generation and three second-generation) carrying human copies of MCPH1.

According to the research article, brain imaging and tissue section analysis showed an altered pattern of neuron differentiation and a delayed maturation of the neural system, which is similar to the developmental delay (neoteny) in humans.

Neoteny in humans is the retention of juvenile features into adulthood. One key difference between humans and nonhuman primates is that humans require a much longer time to shape their neuro-networks during development, greatly elongating childhood, which is the so-called “neoteny.”

Here’s a link to and a citation for the paper,

Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development by Lei Shi, Xin Luo, Jin Jiang, Yongchang Chen, Cirong Liu, Ting Hu, Min Li, Qiang Lin, Yanjiao Li, Jun Huang Hong Wang, Yuyu Niu, Yundi Shi, Martin Styner, Jianhong Wang, Yi Lu, Xuejin Sun, Hualin Yu, Weizhi Ji, Bing Su. National Science Review, nwz043, https://doi.org/10.1093/nsr/nwz043 Published: 27 March 2019

This appears to be an open access paper,

Transgenic monkeys and an ethical uproar

Predictably, this research set off alarms as Sharon Kirkey’s April 12, 2019 article for the National Post describes in detail (Note: A link has been removed)l,

Their brains may not be bigger than normal, but monkeys created with human brain genes are exhibiting cognitive changes that suggest they might be smarter — and the experiments have ethicists shuddering.

In the wake of the genetically modified human babies scandal, Chinese scientists [as a scientist from the US] are drawing fresh condemnation from philosophers and ethicists, this time over the announcement they’ve created transgenic monkeys with elements of a human brain.

Six of the monkeys died, however the five survivors “exhibited better short-term memory and shorter reaction time” compared to their wild-type controls, the researchers report in the journa.

According to the researchers, the experiments represent the first attempt to study the genetic basis of human brain origin using transgenic monkeys. The findings, they insist, “have the potential to provide important — and potentially unique — insights into basic questions of what actually makes humans unique.”

For others, the work provokes a profoundly moral and visceral uneasiness. Even one of the collaborators — University of North Carolina computer scientist Martin Styner — told MIT Technology Review he considered removing his name from the paper, which he said was unable to find a publisher in the West.

“Now we have created this animal which is different than it is supposed to be,” Styner said. “When we do experiments, we have to have a good understanding of what we are trying to learn, to help society, and that is not the case here.” l

In an email to the National Post, Styner said he has an expertise in medical image analysis and was approached by the researchers back in 2011. He said he had no input on the science in the project, beyond how to best do the analysis of their MRI data. “At the time, I did not think deeply enough about the ethical consideration.”

….

When it comes to the scientific use of nonhuman primates, ethicists say the moral compass is skewed in cases like this.

Given the kind of beings monkeys are, “I certainly would have thought you would have had to have a reasonable expectation of high benefit to human beings to justify the harms that you are going to have for intensely social, cognitively complex, emotional animals like monkeys,” said Letitia Meynell, an associate professor in the department of philosophy at Dalhousie University in Halifax.

“It’s not clear that this kind of research has any reasonable expectation of having any useful application for human beings,” she said.

The science itself is also highly dubious and fundamentally flawed in its logic, she said.
“If you took Einstein as a baby and you raised him in the lab he wouldn’t turn out to be Einstein,” Meynell said. “If you’re actually interested in studying the cognitive complexity of these animals, you’re not going to get a good representation of that by raising them in labs, because they can’t develop the kind of cognitive and social skills they would in their normal environment.”

The Chinese said the MCPH1 gene is one of the strongest candidates for human brain evolution. But looking at a single gene is just bad genetics, Meynell said. Multiple genes and their interactions affect the vast majority of traits.

My point is that there’s a lot of research focused on intelligence and genes when we don’t really know what role genes actually play and when there doesn’t seem to be any serious oversight.

Global plea for moratorium on heritable genome editing

A March 13, 2019 University of Otago (New Zealand) press release (also on EurekAlert) describes a global plea for a moratorium,

A University of Otago bioethicist has added his voice to a global plea for a moratorium on heritable genome editing from a group of international scientists and ethicists in the wake of the recent Chinese experiment aiming to produce HIV immune children.

In an article in the latest issue of international scientific journal Nature, Professor Jing-Bao Nie together with another 16 [17] academics from seven countries, call for a global moratorium on all clinical uses of human germline editing to make genetically modified children.

They would like an international governance framework – in which nations voluntarily commit to not approve any use of clinical germline editing unless certain conditions are met – to be created potentially for a five-year period.

Professor Nie says the scientific scandal of the experiment that led to the world’s first genetically modified babies raises many intriguing ethical, social and transcultural/transglobal issues. His main personal concerns include what he describes as the “inadequacy” of the Chinese and international responses to the experiment.

“The Chinese authorities have conducted a preliminary investigation into the scientist’s genetic misadventure and issued a draft new regulation on the related biotechnologies. These are welcome moves. Yet, by putting blame completely on the rogue scientist individually, the institutional failings are overlooked,” Professor Nie explains.

“In the international discourse, partly due to the mentality of dichotomising China and the West, a tendency exists to characterise the scandal as just a Chinese problem. As a result, the global context of the experiment and Chinese science schemes have been far from sufficiently examined.”

The group of 17 [18] scientists and bioethicists say it is imperative that extensive public discussions about the technical, scientific, medical, societal, ethical and moral issues must be considered before germline editing is permitted. A moratorium would provide time to establish broad societal consensus and an international framework.

“For germline editing to even be considered for a clinical application, its safety and efficacy must be sufficient – taking into account the unmet medical need, the risks and potential benefits and the existence of alternative approaches,” the opinion article states.

Although techniques have improved in recent years, germline editing is not yet safe or effective enough to justify any use in the clinic with the risk of failing to make the desired change or of introducing unintended mutations still unacceptably high, the scientists and ethicists say.

“No clinical application of germline editing should be considered unless its long-term biological consequences are sufficiently understood – both for individuals and for the human species.”

The proposed moratorium does not however, apply to germline editing for research uses or in human somatic (non-reproductive) cells to treat diseases.

Professor Nie considers it significant that current presidents of the UK Royal Society, the US National Academy of Medicine and the Director and Associate Director of the US National Institute of Health have expressed their strong support for such a proposed global moratorium in two correspondences published in the same issue of Nature. The editorial in the issue also argues that the right decision can be reached “only through engaging more communities in the debate”.

“The most challenging questions are whether international organisations and different countries will adopt a moratorium and if yes, whether it will be effective at all,” Professor Nie says.

A March 14, 2019 news item on phys.org provides a précis of the Comment in Nature. Or, you ,can access the Comment with this link

Adopt a moratorium on heritable genome editing; Eric Lander, Françoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg and specialists from seven countries call for an international governance framework.signed by: Eric S. Lander, Françoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg, Catherine Bourgain, Bärbel Friedrich, J. Keith Joung, Jinsong Li, David Liu, Luigi Naldini, Jing-Bao Nie, Renzong Qiu, Bettina Schoene-Seifert, Feng Shao, Sharon Terry, Wensheng Wei, & Ernst-Ludwig Winnacker. Nature 567, 165-168 (2019) doi: 10.1038/d41586-019-00726-5

This Comment in Nature is open access.

World Health Organization (WHO) chimes in

Better late than never, eh? The World Health Organization has called heritable gene editing of humans ‘irresponsible’ and made recommendations. From a March 19, 2019 news item on the Canadian Broadcasting Corporation’s Online news webpage,

A panel convened by the World Health Organization said it would be “irresponsible” for scientists to use gene editing for reproductive purposes, but stopped short of calling for a ban.

The experts also called for the U.N. health agency to create a database of scientists working on gene editing. The recommendation was announced Tuesday after a two-day meeting in Geneva to examine the scientific, ethical, social and legal challenges of such research.

“At this time, it is irresponsible for anyone to proceed” with making gene-edited babies since DNA changes could be passed down to future generations, the experts said in a statement.

Germline editing has been on my radar since 2015 (see my May 14, 2015 posting) and the probability that someone would experiment with viable embryos and bring them to term shouldn’t be that much of a surprise.

Slow science from Canada

Canada has banned germline editing but there is pressure to lift that ban. (I touched on the specifics of the campaign in an April 26, 2019 posting.) This March 17, 2019 essay on The Conversation by Landon J Getz and Graham Dellaire, both of Dalhousie University (Nova Scotia, Canada) elucidates some of the discussion about whether research into germline editing should be slowed down.

Naughty (or Haughty, if you prefer) scientists

There was scoffing from some, if not all, members of the scientific community about the potential for ‘designer babies’ that can be seen in an excerpt from an article by Ed Yong for The Atlantic (originally published in my ,August 15, 2017 posting titled: CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?),

Ed Yong in an Aug. 2, 2017 article for The Atlantic offered a comprehensive overview of the research and its implications (unusually for Yong, there seems to be mildly condescending note but it’s worth ignoring for the wealth of information in the article; Note: Links have been removed),

” … the full details of the experiment, which are released today, show that the study is scientifically important but much less of a social inflection point than has been suggested. “This has been widely reported as the dawn of the era of the designer baby, making it probably the fifth or sixth time people have reported that dawn,” says Alta Charo, an expert on law and bioethics at the University of Wisconsin-Madison. “And it’s not.”

Then about 15 months later, the possibility seemed to be realized.

Interesting that scientists scoffed at the public’s concerns (you can find similar arguments about robots and artificial intelligence not being a potentially catastrophic problem), yes? Often, nonscientists’ concerns are dismissed as being founded in science fiction.

To be fair, there are times when concerns are overblown, the difficulty is that it seems the scientific community’s default position is to uniformly dismiss concerns rather than approaching them in a nuanced fashion. If the scoffers had taken the time to think about it, germline editing on viable embryos seems like an obvious and inevitable next step (as I’ve noted previously).

At this point, no one seems to know if He actually succeeded at removing CCR5 from Lulu’s and Nana’s genomes. In November 2018, scientists were guessing that at least one of the twins was a ‘mosaic’. In other words, some of her cells did not include CCR5 while others did.

Parents, children, competition

A recent college admissions scandal in the US has highlighted the intense competition to get into high profile educational institutions. (This scandal brought to mind the Silicon Valey elite who wanted to know more about gene editing that might result in improved cognitive skills.)

Since it can be easy to point the finger at people in other countries, I’d like to note that there was a Canadian parent among these wealthy US parents attempting to give their children advantages by any means, legal or not. (Note: These are alleged illegalities.) From a March 12, 2019 news article by Scott Brown, Kevin Griffin, and Keith Fraser for the Vancouver Sun,

Vancouver businessman and former CFL [Canadian Football League] player David Sidoo has been charged with conspiracy to commit mail and wire fraud in connection with a far-reaching FBI investigation into a criminal conspiracy that sought to help privileged kids with middling grades gain admission to elite U.S. universities.

In a 12-page indictment filed March 5 [2019] in the U.S. District Court of Massachusetts, Sidoo is accused of making two separate US$100,000 payments to have others take college entrance exams in place of his two sons.

Sidoo is also accused of providing documents for the purpose of creating falsified identification cards for the people taking the tests.

In what is being called the biggest college-admissions scam ever prosecuted by the U.S. Justice Department, Sidoo has been charged with nearly 50 other people. Nine athletic coaches and 33 parents including Hollywood actresses Felicity Huffman and Lori Loughlin. are among those charged in the investigation, dubbed Operation Varsity Blues.

According to the indictment, an unidentified person flew from Tampa, Fla., to Vancouver in 2011 to take the Scholastic Aptitude Test (SAT) in place of Sidoo’s older son and was directed not to obtain too high a score since the older son had previously taken the exam, obtaining a score of 1460 out of a possible 2400.

A copy of the resulting SAT score — 1670 out of 2400 — was mailed to Chapman University, a private university in Orange, Calif., on behalf of the older son, who was admitted to and ultimately enrolled in the university in January 2012, according to the indictment.

It’s also alleged that Sidoo arranged to have someone secretly take the older boy’s Canadian high school graduation exam, with the person posing as the boy taking the exam in June 2012.

The Vancouver businessman is also alleged to have paid another $100,000 to have someone take the SAT in place of his younger son.

Sidoo, an investment banker currently serving as CEO of Advantage Lithium, was awarded the Order of B.C. in 2016 for his philanthropic efforts.

He is a former star with the UBC [University of British Columbia] Thunderbirds football team and helped the school win its first Vanier Cup in 1982. He went on to play five seasons in the CFL with the Saskatchewan Roughriders and B.C. Lions.

Sidoo is a prominent donor to UBC and is credited with spearheading an alumni fundraising campaign, 13th Man Foundation, that resuscitated the school’s once struggling football team. He reportedly donated $2 million of his own money to support the program.

Sidoo Field at UBC’s Thunderbird Stadium is named in his honour.

In 2016, he received the B.C. [British Columbia] Sports Hall of Fame’s W.A.C. Bennett Award for his contributions to the sporting life of the province.

The question of whether or not these people like the ‘Silicon Valley elite’ (mentioned in John Loeffler’s February 22, 2019 article) would choose to tinker with their children’s genome if it gave them an advantage, is still hypothetical but it’s easy to believe that at least some might seriously consider the possibility especially if the researcher or doctor didn’t fully explain just how little is known about the impact of tinkering with the genome. For example, there’s a big question about whether those parents in China fully understood what they signed up for.

By the way, cheating scandals aren’t new (see Vanity Fair’s Schools For Scandal; The Inside Dramas at 16 of America’s Most Elite Campuses—Plus Oxford! Edited by Graydon Carter, published in August 2018 and covering 25 years of the magazine’s reporting). On a similar line, there’s this March13, 2019 essay which picks apart some of the hierarchical and power issues at play in the US higher educational system which led to this latest (but likely not last) scandal.

Scientists under pressure

While Kofler’s February 26, 2019 Nature opinion piece and call to action seems to address the concerns regarding germline editing by advocating that scientists become more conscious of how their choices impact society, as I noted earlier, the ideas expressed seem a little ungrounded in harsh realities. Perhaps it’s time to give some recognition to the various pressures put on scientists from their own governments and from an academic environment that fosters ‘success’ at any cost to peer pressure, etc. (For more about the costs of a science culture focused on success, read this March 2, 2019 blog posting by Jon Tennant on digital-science.com for a breakdown.)

One other thing I should mention, for some scientists getting into the history books, winning Nobel prizes, etc. is a very important goal. Scientists are people too.

Some thoughts

There seems to be a great disjunction between what Richardson presents as an alternative narrative to the ‘gene-god’ and how genetic research is being performed and reported on. What is clear to me is that no one really understands genetics and this business of inserting and deleting genes is essentially research designed to satisfy curiosity and/or allay fears about being left behind in a great scientific race to a an unknown destination.

I’d like to see some better reporting and a more agile response by the scientific community, the various governments, and international agencies. What shape or form a more agile response might take, I don’t know but I’d like to see some efforts.

Back to the regular programme

There’s a lot about CRISPR here on this blog. A simple search of ‘CRISPR ‘in the blog’s search engine should get you more than enough information about the technology and the various issues ranging from intellectual property to risks and more.

The three part series (CRISPR and editing the germline in the US …), mentioned previously, was occasioned by the publication of a study on germline editing research with nonviable embryos in the US. The 2017 research was done at the Oregon Health and Science University by Shoukhrat Mitalipov following similar research published by Chinese scientists in 2015. The series gives relatively complete coverage of the issues along with an introduction to CRISPR and embedded video describing the technique. Here’s part 1 to get you started..

CRISPR and editing the germline in the US (part 3 of 3): public discussions and pop culture

After giving a basic explanation of the technology and some of the controversies in part 1 and offering more detail about the technology and about the possibility of designer babies in part 2; this part covers public discussion, a call for one and the suggestion that one is taking place in popular culture.

But a discussion does need to happen

In a move that is either an exquisite coincidence or has been carefully orchestrated (I vote for the latter), researchers from the University of Wisconsin-Madison have released a study about attitudes in the US to human genome editing. From an Aug. 11, 2017 University of Wisconsin-Madison news release (also on EurekAllert),

In early August 2017, an international team of scientists announced they had successfully edited the DNA of human embryos. As people process the political, moral and regulatory issues of the technology — which nudges us closer to nonfiction than science fiction — researchers at the University of Wisconsin-Madison and Temple University show the time is now to involve the American public in discussions about human genome editing.

In a study published Aug. 11 in the journal Science, the researchers assessed what people in the United States think about the uses of human genome editing and how their attitudes may drive public discussion. They found a public divided on its uses but united in the importance of moving conversations forward.

“There are several pathways we can go down with gene editing,” says UW-Madison’s Dietram Scheufele, lead author of the study and member of a National Academy of Sciences committee that compiled a report focused on human gene editing earlier this year. “Our study takes an exhaustive look at all of those possible pathways forward and asks where the public stands on each one of them.”

Compared to previous studies on public attitudes about the technology, the new study takes a more nuanced approach, examining public opinion about the use of gene editing for disease therapy versus for human enhancement, and about editing that becomes hereditary versus editing that does not.

The research team, which included Scheufele and Dominique Brossard — both professors of life sciences communication — along with Michael Xenos, professor of communication arts, first surveyed study participants about the use of editing to treat disease (therapy) versus for enhancement (creating so-called “designer babies”). While about two-thirds of respondents expressed at least some support for therapeutic editing, only one-third expressed support for using the technology for enhancement.

Diving even deeper, researchers looked into public attitudes about gene editing on specific cell types — somatic or germline — either for therapy or enhancement. Somatic cells are non-reproductive, so edits made in those cells do not affect future generations. Germline cells, however, are heritable, and changes made in these cells would be passed on to children.

Public support of therapeutic editing was high both in cells that would be inherited and those that would not, with 65 percent of respondents supporting therapy in germline cells and 64 percent supporting therapy in somatic cells. When considering enhancement editing, however, support depended more upon whether the changes would affect future generations. Only 26 percent of people surveyed supported enhancement editing in heritable germline cells and 39 percent supported enhancement of somatic cells that would not be passed on to children.

“A majority of people are saying that germline enhancement is where the technology crosses that invisible line and becomes unacceptable,” says Scheufele. “When it comes to therapy, the public is more open, and that may partly be reflective of how severe some of those genetically inherited diseases are. The potential treatments for those diseases are something the public at least is willing to consider.”

Beyond questions of support, researchers also wanted to understand what was driving public opinions. They found that two factors were related to respondents’ attitudes toward gene editing as well as their attitudes toward the public’s role in its emergence: the level of religious guidance in their lives, and factual knowledge about the technology.

Those with a high level of religious guidance in their daily lives had lower support for human genome editing than those with low religious guidance. Additionally, those with high knowledge of the technology were more supportive of it than those with less knowledge.

While respondents with high religious guidance and those with high knowledge differed on their support for the technology, both groups highly supported public engagement in its development and use. These results suggest broad agreement that the public should be involved in questions of political, regulatory and moral aspects of human genome editing.

“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,” says Scheufele. “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.”

Here’s a  link to and a citation for the paper,

U.S. attitudes on human genome editing by Dietram A. Scheufele, Michael A. Xenos, Emily L. Howell, Kathleen M. Rose, Dominique Brossard1, and Bruce W. Hardy. Science 11 Aug 2017: Vol. 357, Issue 6351, pp. 553-554 DOI: 10.1126/science.aan3708

This paper is behind a paywall.

A couple of final comments

Briefly, I notice that there’s no mention of the ethics of patenting this technology in the news release about the study.

Moving on, it seems surprising that the first team to engage in germline editing in the US is in Oregon; I would have expected the work to come from Massachusetts, California, or Illinois where a lot of bleeding edge medical research is performed. However, given the dearth of financial support from federal funding institutions, it seems likely that only an outsider would dare to engage i the research. Given the timing, Mitalipov’s work was already well underway before the recent about-face from the US National Academy of Sciences (Note: Kaiser’s Feb. 14, 2017 article does note that for some the recent recommendations do not represent any change).

As for discussion on issues such as editing of the germline, I’ve often noted here that popular culture (including advertising with the science fiction and other dramas laid in various media) often provides an informal forum for discussion. Joelle Renstrom in an Aug. 13, 2017 article for slate.com writes that Orphan Black (a BBC America series featuring clones) opened up a series of questions about science and ethics in the guise of a thriller about clones. She offers a précis of the first four seasons (Note: A link has been removed),

If you stopped watching a few seasons back, here’s a brief synopsis of how the mysteries wrap up. Neolution, an organization that seeks to control human evolution through genetic modification, began Project Leda, the cloning program, for two primary reasons: to see whether they could and to experiment with mutations that might allow people (i.e., themselves) to live longer. Neolution partnered with biotech companies such as Dyad, using its big pharma reach and deep pockets to harvest people’s genetic information and to conduct individual and germline (that is, genetic alterations passed down through generations) experiments, including infertility treatments that result in horrifying birth defects and body modification, such as tail-growing.

She then provides the article’s thesis (Note: Links have been removed),

Orphan Black demonstrates Carl Sagan’s warning of a time when “awesome technological powers are in the hands of a very few.” Neolutionists do whatever they want, pausing only to consider whether they’re missing an opportunity to exploit. Their hubris is straight out of Victor Frankenstein’s playbook. Frankenstein wonders whether he ought to first reanimate something “of simpler organisation” than a human, but starting small means waiting for glory. Orphan Black’s evil scientists embody this belief: if they’re going to play God, then they’ll control not just their own destinies, but the clones’ and, ultimately, all of humanity’s. Any sacrifices along the way are for the greater good—reasoning that culminates in Westmoreland’s eugenics fantasy to genetically sterilize 99 percent of the population he doesn’t enhance.

Orphan Black uses sci-fi tropes to explore real-world plausibility. Neolution shares similarities with transhumanism, the belief that humans should use science and technology to take control of their own evolution. While some transhumanists dabble in body modifications, such as microchip implants or night-vision eye drops, others seek to end suffering by curing human illness and aging. But even these goals can be seen as selfish, as access to disease-eradicating or life-extending technologies would be limited to the wealthy. Westmoreland’s goal to “sell Neolution to the 1 percent” seems frighteningly plausible—transhumanists, who statistically tend to be white, well-educated, and male, and their associated organizations raise and spend massive sums of money to help fulfill their goals. …

On Orphan Black, denial of choice is tantamount to imprisonment. That the clones have to earn autonomy underscores the need for ethics in science, especially when it comes to genetics. The show’s message here is timely given the rise of gene-editing techniques such as CRISPR. Recently, the National Academy of Sciences gave germline gene editing the green light, just one year after academy scientists from around the world argued it would be “irresponsible to proceed” without further exploring the implications. Scientists in the United Kingdom and China have already begun human genetic engineering and American scientists recently genetically engineered a human embryo for the first time. The possibility of Project Leda isn’t farfetched. Orphan Black warns us that money, power, and fear of death can corrupt both people and science. Once that happens, loss of humanity—of both the scientists and the subjects—is inevitable.

In Carl Sagan’s dark vision of the future, “people have lost the ability to set their own agendas or knowledgeably question those in authority.” This describes the plight of the clones at the outset of Orphan Black, but as the series continues, they challenge this paradigm by approaching science and scientists with skepticism, ingenuity, and grit. …

I hope there are discussions such as those Scheufele and Brossard are advocating but it might be worth considering that there is already some discussion underway, as informal as it is.

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Part 1: CRISPR and editing the germline in the US (part 1 of 3): In the beginning

Part 2: CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?

CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?

Having included an explanation of CRISPR-CAS9 technology along with the news about the first US team to edit the germline and bits and pieces about ethics and a patent fight (part 1), this part hones in on the details of the work and worries about ‘designer babies’.

The interest flurry

I found three articles addressing the research and all three concur that despite some of the early reporting, this is not the beginning of a ‘designer baby’ generation.

First up was Nick Thieme in a July 28, 2017 article for Slate,

MIT Technology Review reported Thursday that a team of researchers from Portland, Oregon were the first team of U.S.-based scientists to successfully create a genetically modified human embryo. The researchers, led by Shoukhrat Mitalipov of Oregon Health and Science University, changed the DNA of—in MIT Technology Review’s words—“many tens” of genetically-diseased embryos by injecting the host egg with CRISPR, a DNA-based gene editing tool first discovered in bacteria, at the time of fertilization. CRISPR-Cas9, as the full editing system is called, allows scientists to change genes accurately and efficiently. As has happened with research elsewhere, the CRISPR-edited embryos weren’t implanted—they were kept sustained for only a couple of days.

In addition to being the first American team to complete this feat, the researchers also improved upon the work of the three Chinese research teams that beat them to editing embryos with CRISPR: Mitalipov’s team increased the proportion of embryonic cells that received the intended genetic changes, addressing an issue called “mosaicism,” which is when an embryo is comprised of cells with different genetic makeups. Increasing that proportion is essential to CRISPR work in eliminating inherited diseases, to ensure that the CRISPR therapy has the intended result. The Oregon team also reduced the number of genetic errors introduced by CRISPR, reducing the likelihood that a patient would develop cancer elsewhere in the body.

Separate from the scientific advancements, it’s a big deal that this work happened in a country with such intense politicization of embryo research. …

But there are a great number of obstacles between the current research and the future of genetically editing all children to be 12-foot-tall Einsteins.

Ed Yong in an Aug. 2, 2017 article for The Atlantic offered a comprehensive overview of the research and its implications (unusually for Yong, there seems to be mildly condescending note but it’s worth ignoring for the wealth of information in the article; Note: Links have been removed),

… the full details of the experiment, which are released today, show that the study is scientifically important but much less of a social inflection point than has been suggested. “This has been widely reported as the dawn of the era of the designer baby, making it probably the fifth or sixth time people have reported that dawn,” says Alta Charo, an expert on law and bioethics at the University of Wisconsin-Madison. “And it’s not.”

Given the persistent confusion around CRISPR and its implications, I’ve laid out exactly what the team did, and what it means.

Who did the experiments?

Shoukhrat Mitalipov is a Kazakhstani-born cell biologist with a history of breakthroughs—and controversy—in the stem cell field. He was the scientist to clone monkeys. He was the first to create human embryos by cloning adult cells—a move that could provide patients with an easy supply of personalized stem cells. He also pioneered a technique for creating embryos with genetic material from three biological parents, as a way of preventing a group of debilitating inherited diseases.

Although MIT Tech Review name-checked Mitalipov alone, the paper splits credit for the research between five collaborating teams—four based in the United States, and one in South Korea.

What did they actually do?

The project effectively began with an elevator conversation between Mitalipov and his colleague Sanjiv Kaul. Mitalipov explained that he wanted to use CRISPR to correct a disease-causing gene in human embryos, and was trying to figure out which disease to focus on. Kaul, a cardiologist, told him about hypertrophic cardiomyopathy (HCM)—an inherited heart disease that’s commonly caused by mutations in a gene called MYBPC3. HCM is surprisingly common, affecting 1 in 500 adults. Many of them lead normal lives, but in some, the walls of their hearts can thicken and suddenly fail. For that reason, HCM is the commonest cause of sudden death in athletes. “There really is no treatment,” says Kaul. “A number of drugs are being evaluated but they are all experimental,” and they merely treat the symptoms. The team wanted to prevent HCM entirely by removing the underlying mutation.

They collected sperm from a man with HCM and used CRISPR to change his mutant gene into its normal healthy version, while simultaneously using the sperm to fertilize eggs that had been donated by female volunteers. In this way, they created embryos that were completely free of the mutation. The procedure was effective, and avoided some of the critical problems that have plagued past attempts to use CRISPR in human embryos.

Wait, other human embryos have been edited before?

There have been three attempts in China. The first two—in 2015 and 2016—used non-viable embryos that could never have resulted in a live birth. The third—announced this March—was the first to use viable embryos that could theoretically have been implanted in a womb. All of these studies showed that CRISPR gene-editing, for all its hype, is still in its infancy.

The editing was imprecise. CRISPR is heralded for its precision, allowing scientists to edit particular genes of choice. But in practice, some of the Chinese researchers found worrying levels of off-target mutations, where CRISPR mistakenly cut other parts of the genome.

The editing was inefficient. The first Chinese team only managed to successfully edit a disease gene in 4 out of 86 embryos, and the second team fared even worse.

The editing was incomplete. Even in the successful cases, each embryo had a mix of modified and unmodified cells. This pattern, known as mosaicism, poses serious safety problems if gene-editing were ever to be used in practice. Doctors could end up implanting women with embryos that they thought were free of a disease-causing mutation, but were only partially free. The resulting person would still have many tissues and organs that carry those mutations, and might go on to develop symptoms.

What did the American team do differently?

The Chinese teams all used CRISPR to edit embryos at early stages of their development. By contrast, the Oregon researchers delivered the CRISPR components at the earliest possible point—minutes before fertilization. That neatly avoids the problem of mosaicism by ensuring that an embryo is edited from the very moment it is created. The team did this with 54 embryos and successfully edited the mutant MYBPC3 gene in 72 percent of them. In the other 28 percent, the editing didn’t work—a high failure rate, but far lower than in previous attempts. Better still, the team found no evidence of off-target mutations.

This is a big deal. Many scientists assumed that they’d have to do something more convoluted to avoid mosaicism. They’d have to collect a patient’s cells, which they’d revert into stem cells, which they’d use to make sperm or eggs, which they’d edit using CRISPR. “That’s a lot of extra steps, with more risks,” says Alta Charo. “If it’s possible to edit the embryo itself, that’s a real advance.” Perhaps for that reason, this is the first study to edit human embryos that was published in a top-tier scientific journal—Nature, which rejected some of the earlier Chinese papers.

Is this kind of research even legal?

Yes. In Western Europe, 15 countries out of 22 ban any attempts to change the human germ line—a term referring to sperm, eggs, and other cells that can transmit genetic information to future generations. No such stance exists in the United States but Congress has banned the Food and Drug Administration from considering research applications that make such modifications. Separately, federal agencies like the National Institutes of Health are banned from funding research that ultimately destroys human embryos. But the Oregon team used non-federal money from their institutions, and donations from several small non-profits. No taxpayer money went into their work. [emphasis mine]

Why would you want to edit embryos at all?

Partly to learn more about ourselves. By using CRISPR to manipulate the genes of embryos, scientists can learn more about the earliest stages of human development, and about problems like infertility and miscarriages. That’s why biologist Kathy Niakan from the Crick Institute in London recently secured a license from a British regulator to use CRISPR on human embryos.

Isn’t this a slippery slope toward making designer babies?

In terms of avoiding genetic diseases, it’s not conceptually different from PGD, which is already widely used. The bigger worry is that gene-editing could be used to make people stronger, smarter, or taller, paving the way for a new eugenics, and widening the already substantial gaps between the wealthy and poor. But many geneticists believe that such a future is fundamentally unlikely because complex traits like height and intelligence are the work of hundreds or thousands of genes, each of which have a tiny effect. The prospect of editing them all is implausible. And since genes are so thoroughly interconnected, it may be impossible to edit one particular trait without also affecting many others.

“There’s the worry that this could be used for enhancement, so society has to draw a line,” says Mitalipov. “But this is pretty complex technology and it wouldn’t be hard to regulate it.”

Does this discovery have any social importance at all?

“It’s not so much about designer babies as it is about geographical location,” says Charo. “It’s happening in the United States, and everything here around embryo research has high sensitivity.” She and others worry that the early report about the study, before the actual details were available for scrutiny, could lead to unnecessary panic. “Panic reactions often lead to panic-driven policy … which is usually bad policy,” wrote Greely [bioethicist Hank Greely].

As I understand it, despite the change in stance, there is no federal funding available for the research performed by Mitalipov and his team.

Finally, University College London (UCL) scientists Joyce Harper and Helen O’Neill wrote about CRISPR, the Oregon team’s work, and the possibilities in an Aug. 3, 2017 essay for The Conversation (Note: Links have been removed),

The genome editing tool used, CRISPR-Cas9, has transformed the field of biology in the short time since its discovery in that it not only promises, but delivers. CRISPR has surpassed all previous efforts to engineer cells and alter genomes at a fraction of the time and cost.

The technology, which works like molecular scissors to cut and paste DNA, is a natural defence system that bacteria use to fend off harmful infections. This system has the ability to recognise invading virus DNA, cut it and integrate this cut sequence into its own genome – allowing the bacterium to render itself immune to future infections of viruses with similar DNA. It is this ability to recognise and cut DNA that has allowed scientists to use it to target and edit specific DNA regions.

When this technology is applied to “germ cells” – the sperm and eggs – or embryos, it changes the germline. That means that any alterations made would be permanent and passed down to future generations. This makes it more ethically complex, but there are strict regulations around human germline genome editing, which is predominantly illegal. The UK received a licence in 2016 to carry out CRISPR on human embryos for research into early development. But edited embryos are not allowed to be inserted into the uterus and develop into a fetus in any country.

Germline genome editing came into the global spotlight when Chinese scientists announced in 2015 that they had used CRISPR to edit non-viable human embryos – cells that could never result in a live birth. They did this to modify the gene responsible for the blood disorder β-thalassaemia. While it was met with some success, it received a lot of criticism because of the premature use of this technology in human embryos. The results showed a high number of potentially dangerous, off-target mutations created in the procedure.

Impressive results

The new study, published in Nature, is different because it deals with viable human embryos and shows that the genome editing can be carried out safely – without creating harmful mutations. The team used CRISPR to correct a mutation in the gene MYBPC3, which accounts for approximately 40% of the myocardial disease hypertrophic cardiomyopathy. This is a dominant disease, so an affected individual only needs one abnormal copy of the gene to be affected.

The researchers used sperm from a patient carrying one copy of the MYBPC3 mutation to create 54 embryos. They edited them using CRISPR-Cas9 to correct the mutation. Without genome editing, approximately 50% of the embryos would carry the patients’ normal gene and 50% would carry his abnormal gene.

After genome editing, the aim would be for 100% of embryos to be normal. In the first round of the experiments, they found that 66.7% of embryos – 36 out of 54 – were normal after being injected with CRIPSR. Of the remaining 18 embryos, five had remained unchanged, suggesting editing had not worked. In 13 embryos, only a portion of cells had been edited.

The level of efficiency is affected by the type of CRISPR machinery used and, critically, the timing in which it is put into the embryo. The researchers therefore also tried injecting the sperm and the CRISPR-Cas9 complex into the egg at the same time, which resulted in more promising results. This was done for 75 mature donated human eggs using a common IVF technique called intracytoplasmic sperm injection. This time, impressively, 72.4% of embryos were normal as a result. The approach also lowered the number of embryos containing a mixture of edited and unedited cells (these embryos are called mosaics).

Finally, the team injected a further 22 embryos which were grown into blastocyst – a later stage of embryo development. These were sequenced and the researchers found that the editing had indeed worked. Importantly, they could show that the level of off-target mutations was low.

A brave new world?

So does this mean we finally have a cure for debilitating, heritable diseases? It’s important to remember that the study did not achieve a 100% success rate. Even the researchers themselves stress that further research is needed in order to fully understand the potential and limitations of the technique.

In our view, it is unlikely that genome editing would be used to treat the majority of inherited conditions anytime soon. We still can’t be sure how a child with a genetically altered genome will develop over a lifetime, so it seems unlikely that couples carrying a genetic disease would embark on gene editing rather than undergoing already available tests – such as preimplantation genetic diagnosis or prenatal diagnosis – where the embryos or fetus are tested for genetic faults.

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As might be expected there is now a call for public discussion about the ethics about this kind of work. See Part 3.

For anyone who started in the middle of this series, here’s Part 1 featuring an introduction to the technology and some of the issues.

CRISPR and editing the germline in the US (part 1 of 3): In the beginning

There’s been a minor flurry of interest in CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats; also known as CRISPR-CAS9), a gene-editing technique, since a team in Oregon announced a paper describing their work editing the germline. Since I’ve been following the CRISPR-CAS9 story for a while this seems like a good juncture for a more in-depth look at the topic. In this first part I’m including an introduction to CRISPR, some information about the latest US work, and some previous writing about ethics issues raised when Chinese scientists first announced their work editing germlines in 2015 and during the patent dispute between the University of California at Berkeley and Harvard University’s Broad Institute.

Introduction to CRISPR

I’ve been searching for a good description of CRISPR and this helped to clear up some questions for me (Thank you to MIT Review),

For anyone who’s been reading about science for a while, this upbeat approach to explaining how a particular technology will solve all sorts of problems will seem quite familiar. It’s not the most hyperbolic piece I’ve seen but it barely mentions any problems associated with research (for some of the problems see: ‘The interest flurry’ later in part 2).

Oregon team

Steve Connor’s July 26, 2017 article for the MIT (Massachusetts Institute of Technology) Technology Review breaks the news (Note: Links have been removed),

The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon, MIT Technology Review has learned.

The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR, according to people familiar with the scientific results.

Until now, American scientists have watched with a combination of awe, envy, and some alarm as scientists elsewhere were first to explore the controversial practice. To date, three previous reports of editing human embryos were all published by scientists in China.

Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.

Although none of the embryos were allowed to develop for more than a few days—and there was never any intention of implanting them into a womb—the experiments are a milestone on what may prove to be an inevitable journey toward the birth of the first genetically modified humans.

In altering the DNA code of human embryos, the objective of scientists is to show that they can eradicate or correct genes that cause inherited disease, like the blood condition beta-thalassemia. The process is termed “germline engineering” because any genetically modified child would then pass the changes on to subsequent generations via their own germ cells—the egg and sperm.

Some critics say germline experiments could open the floodgates to a brave new world of “designer babies” engineered with genetic enhancements—a prospect bitterly opposed by a range of religious organizations, civil society groups, and biotech companies.

The U.S. intelligence community last year called CRISPR a potential “weapon of mass destruction.”

Here’s a link to a citation for the groundbreaking paper,

Correction of a pathogenic gene mutation in human embryos by Hong Ma, Nuria Marti-Gutierrez, Sang-Wook Park, Jun Wu, Yeonmi Lee, Keiichiro Suzuki, Amy Koski, Dongmei Ji, Tomonari Hayama, Riffat Ahmed, Hayley Darby, Crystal Van Dyken, Ying Li, Eunju Kang, A.-Reum Park, Daesik Kim, Sang-Tae Kim, Jianhui Gong, Ying Gu, Xun Xu, David Battaglia, Sacha A. Krieg, David M. Lee, Diana H. Wu, Don P. Wolf, Stephen B. Heitner, Juan Carlos Izpisua Belmonte, Paula Amato, Jin-Soo Kim, Sanjiv Kaul, & Shoukhrat Mitalipov. Nature (2017) doi:10.1038/nature23305 Published online 02 August 2017

This paper appears to be open access.

CRISPR Issues: ethics and patents

In my May 14, 2015 posting I mentioned a ‘moratorium’ on germline research, the Chinese research paper, and the stance taken by the US National Institutes of Health (NIH),

The CRISPR technology has reignited a discussion about ethical and moral issues of human genetic engineering some of which is reviewed in an April 7, 2015 posting about a moratorium by Sheila Jasanoff, J. Benjamin Hurlbut and Krishanu Saha for the Guardian science blogs (Note: A link has been removed),

On April 3, 2015, a group of prominent biologists and ethicists writing in Science called for a moratorium on germline gene engineering; modifications to the human genome that will be passed on to future generations. The moratorium would apply to a technology called CRISPR/Cas9, which enables the removal of undesirable genes, insertion of desirable ones, and the broad recoding of nearly any DNA sequence.

Such modifications could affect every cell in an adult human being, including germ cells, and therefore be passed down through the generations. Many organisms across the range of biological complexity have already been edited in this way to generate designer bacteria, plants and primates. There is little reason to believe the same could not be done with human eggs, sperm and embryos. Now that the technology to engineer human germlines is here, the advocates for a moratorium declared, it is time to chart a prudent path forward. They recommend four actions: a hold on clinical applications; creation of expert forums; transparent research; and a globally representative group to recommend policy approaches.

The authors go on to review precedents and reasons for the moratorium while suggesting we need better ways for citizens to engage with and debate these issues,

An effective moratorium must be grounded in the principle that the power to modify the human genome demands serious engagement not only from scientists and ethicists but from all citizens. We need a more complex architecture for public deliberation, built on the recognition that we, as citizens, have a duty to participate in shaping our biotechnological futures, just as governments have a duty to empower us to participate in that process. Decisions such as whether or not to edit human genes should not be left to elite and invisible experts, whether in universities, ad hoc commissions, or parliamentary advisory committees. Nor should public deliberation be temporally limited by the span of a moratorium or narrowed to topics that experts deem reasonable to debate.

I recommend reading the post in its entirety as there are nuances that are best appreciated in the entirety of the piece.

Shortly after this essay was published, Chinese scientists announced they had genetically modified (nonviable) human embryos. From an April 22, 2015 article by David Cyranoski and Sara Reardon in Nature where the research and some of the ethical issues discussed,

In a world first, Chinese scientists have reported editing the genomes of human embryos. The results are published1 in the online journal Protein & Cell and confirm widespread rumours that such experiments had been conducted — rumours that sparked a high-profile debate last month2, 3 about the ethical implications of such work.

In the paper, researchers led by Junjiu Huang, a gene-function researcher at Sun Yat-sen University in Guangzhou, tried to head off such concerns by using ‘non-viable’ embryos, which cannot result in a live birth, that were obtained from local fertility clinics. The team attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9. The researchers say that their results reveal serious obstacles to using the method in medical applications.

“I believe this is the first report of CRISPR/Cas9 applied to human pre-implantation embryos and as such the study is a landmark, as well as a cautionary tale,” says George Daley, a stem-cell biologist at Harvard Medical School in Boston, Massachusetts. “Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes.”

….

Huang says that the paper was rejected by Nature and Science, in part because of ethical objections; both journals declined to comment on the claim. (Nature’s news team is editorially independent of its research editorial team.)

He adds that critics of the paper have noted that the low efficiencies and high number of off-target mutations could be specific to the abnormal embryos used in the study. Huang acknowledges the critique, but because there are no examples of gene editing in normal embryos he says that there is no way to know if the technique operates differently in them.

Still, he maintains that the embryos allow for a more meaningful model — and one closer to a normal human embryo — than an animal model or one using adult human cells. “We wanted to show our data to the world so people know what really happened with this model, rather than just talking about what would happen without data,” he says.

This, too, is a good and thoughtful read.

There was an official response in the US to the publication of this research, from an April 29, 2015 post by David Bruggeman on his Pasco Phronesis blog (Note: Links have been removed),

In light of Chinese researchers reporting their efforts to edit the genes of ‘non-viable’ human embryos, the National Institutes of Health (NIH) Director Francis Collins issued a statement (H/T Carl Zimmer).

“NIH will not fund any use of gene-editing technologies in human embryos. The concept of altering the human germline in embryos for clinical purposes has been debated over many years from many different perspectives, and has been viewed almost universally as a line that should not be crossed. Advances in technology have given us an elegant new way of carrying out genome editing, but the strong arguments against engaging in this activity remain. These include the serious and unquantifiable safety issues, ethical issues presented by altering the germline in a way that affects the next generation without their consent, and a current lack of compelling medical applications justifying the use of CRISPR/Cas9 in embryos.” …

The US has modified its stance according to a February 14, 2017 article by Jocelyn Kaiser for Science Magazine (Note: Links have been removed),

Editing the DNA of a human embryo to prevent a disease in a baby could be ethically allowable one day—but only in rare circumstances and with safeguards in place, says a widely anticipated report released today.

The report from an international committee convened by the U.S. National Academy of Sciences (NAS) and the National Academy of Medicine in Washington, D.C., concludes that such a clinical trial “might be permitted, but only following much more research” on risks and benefits, and “only for compelling reasons and under strict oversight.” Those situations could be limited to couples who both have a serious genetic disease and for whom embryo editing is “really the last reasonable option” if they want to have a healthy biological child, says committee co-chair Alta Charo, a bioethicist at the University of Wisconsin in Madison.

Some researchers are pleased with the report, saying it is consistent with previous conclusions that safely altering the DNA of human eggs, sperm, or early embryos—known as germline editing—to create a baby could be possible eventually. “They have closed the door to the vast majority of germline applications and left it open for a very small, well-defined subset. That’s not unreasonable in my opinion,” says genome researcher Eric Lander of the Broad Institute in Cambridge, Massachusetts. Lander was among the organizers of an international summit at NAS in December 2015 who called for more discussion before proceeding with embryo editing.

But others see the report as lowering the bar for such experiments because it does not explicitly say they should be prohibited for now. “It changes the tone to an affirmative position in the absence of the broad public debate this report calls for,” says Edward Lanphier, chairman of the DNA editing company Sangamo Therapeutics in Richmond, California. Two years ago, he co-authored a Nature commentary calling for a moratorium on clinical embryo editing.

One advocacy group opposed to embryo editing goes further. “We’re very disappointed with the report. It’s really a pretty dramatic shift from the existing and widespread agreement globally that human germline editing should be prohibited,” says Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, California.

Interestingly, this change of stance occurred just prior to a CRISPR patent decision (from my March 15, 2017 posting),

I have written about the CRISPR patent tussle (Harvard & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley) previously in a Jan. 6, 2015 posting and in a more detailed May 14, 2015 posting. I also mentioned (in a Jan. 17, 2017 posting) CRISPR and its patent issues in the context of a posting about a Slate.com series on Frankenstein and the novel’s applicability to our own time. This patent fight is being bitterly fought as fortunes are at stake.

It seems a decision has been made regarding the CRISPR patent claims. From a Feb. 17, 2017 article by Charmaine Distor for The Science Times,

After an intense court battle, the US Patent and Trademark Office (USPTO) released its ruling on February 15 [2017]. The rights for the CRISPR-Cas9 gene editing technology was handed over to the Broad Institute of Harvard University and the Massachusetts Institute of Technology (MIT).

According to an article in Nature, the said court battle was between the Broad Institute and the University of California. The two institutions are fighting over the intellectual property right for the CRISPR patent. The case between the two started when the patent was first awarded to the Broad Institute despite having the University of California apply first for the CRISPR patent.

Heidi Ledford’s Feb. 17, 2017 article for Nature provides more insight into the situation (Note: Links have been removed),

It [USPTO] ruled that the Broad Institute of Harvard and MIT in Cambridge could keep its patents on using CRISPR–Cas9 in eukaryotic cells. That was a blow to the University of California in Berkeley, which had filed its own patents and had hoped to have the Broad’s thrown out.

The fight goes back to 2012, when Jennifer Doudna at Berkeley, Emmanuelle Charpentier, then at the University of Vienna, and their colleagues outlined how CRISPR–Cas9 could be used to precisely cut isolated DNA1. In 2013, Feng Zhang at the Broad and his colleagues — and other teams — showed2 how it could be adapted to edit DNA in eukaryotic cells such as plants, livestock and humans.

Berkeley filed for a patent earlier, but the USPTO granted the Broad’s patents first — and this week upheld them. There are high stakes involved in the ruling. The holder of key patents could make millions of dollars from CRISPR–Cas9’s applications in industry: already, the technique has sped up genetic research, and scientists are using it to develop disease-resistant livestock and treatments for human diseases.

….

I also noted this eyebrow-lifting statistic,  “As for Ledford’s 3rd point, there are an estimated 763 patent families (groups of related patents) claiming CAS9 leading to the distinct possibility that the Broad Institute will be fighting many patent claims in the future.)

-30-

Part 2 covers three critical responses to the reporting and between them describe the technology in more detail and the possibility of ‘designer babies’.  CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?

Part 3 is all about public discussion or, rather, the lack of and need for according to a couple of social scientists. Informally, there is some discussion via pop culture and Joelle Renstrom notes although she is focused on the larger issues touched on by the television series, Orphan Black and as I touch on in my final comments. CRISPR and editing the germline in the US (part 3 of 3): public discussions and pop culture

Maths gallery at the UK’s Science Museum takes flight

Mathematics: The Winton Gallery at the Science Museum, Zaha Hadid Architects’ only permanent public museum exhibition design. London. Photograph: Nicholas Guttridge/NIck Guttridge

This exhibition looks great in the picture, I wonder what the experience is like. Alex Bellos is certainly enthusiastic in his Dec. 7, 2016 posting on the Guardian’s website,

Mathematics underlies all science, so for a science museum to be worthy of the name, maths needs to included somewhere. Yet maths, which deals mainly in abstract objects, is [a] challenge for museums, which necessarily contain physical ones. The Science Museum’s approach in its new gallery is to tell historical stories about the influence of mathematics in the real world, rather than actually focussing directly on the mathematical ideas involved. The result is a stunning gallery, with fascinating objects beautifully laid out, yet which eschews explaining any maths. (If you want to learn simple mathematical ideas, you can always head to the museum’s new interactive gallery, Wonderlab).

Much of the attention on Mathematics: The Winton Gallery – the main funders are David Harding, founder and CEO of investment firm Winton, and his wife Claudia – has been on Zaha Hadid’s design. The gallery is the first UK project by Zaha Hadid Architects to open since her unexpected death in March [2016], and the only permanent public museum exhibition she designed. Her first degree was in maths, before she turned to architecture.

Hanging from the ceiling is an aeroplane – the Handley Page ‘Gugnunc’, built in 1929 for a competition to build safe aircraft – and surrounding it is a swirly ceiling sculpture that represents the mathematical equations that describe airflow. In fact, the entire gallery follows the contours of the flow, providing the positions of the cabinets below.

The Science Museum’s previous maths gallery, which had not been updated in decades, contained about 600 objects, including cabinets crammed with geometrical objects and many examples of the same thing, such as medieval slide rules or Victorian curve-drawing machines. The new gallery has less than a quarter of that number of objects in the same space.

Every object now is in its own cabinet, and the extra space means you can walk around them from all angles, as well as making the gallery feel more manageable. Rather than being bombarded with stuff, you are given a single object to contemplate that tells part of a wider story.

In a section on “form and beauty”, there is a modern replica of a 1920s chair based on French architect’s Le Corbusier’s Modulor system of proportions, and two J W Turner sketches from his Royal Academy lectures on perspective.

The section “trade and travel” has a 3-metre long replica of the 1973 Globtik Tokyo oil tanker, then the largest ship in the world. In its massive cabinet it looks as terrifying as a Damien Hirst shark. The maths link? Because British mathematician William Froode a century before had worked out that bulbous bows were better than sharp bows at the fronts of boats and ships.

The new maths gallery is a wonderfully attractive space, full of interesting and thought-provoking objects, and a very welcome addition [geddit?] to London’s museums. Go!

A Dec. 8 (?), 2016 [London, UK] Science Museum press release is the first example I’ve seen of the funders being highlighted quite so prominently, i.e., before the press release proper,

Mathematics: The Winton Gallery designed by Zaha Hadid Architects opens at the Science Museum

  • A stunning new permanent gallery that reveals the importance of mathematics in all our lives through remarkable historical artefacts, stories and design
  • Free to visit and open daily from 8 December 2016
  • The only permanent public museum exhibition designed by Zaha Hadid anywhere in the world

Principal Funder: David and Claudia Harding
Principal Sponsor: Samsung
Major Sponsor: MathWorks

On 8 December 2016 the Science Museum will open an inspirational new mathematics gallery, designed by Zaha Hadid Architects.

Mathematics: The Winton Gallery brings together remarkable stories, historical artefacts and design to highlight the central role of mathematical practice in all our lives, and explores how mathematicians, their tools and ideas have helped build the modern world over the past four centuries.

More than 100 treasures from the Science Museum’s world-class science, technology, engineering and mathematics collections have been selected to tell powerful stories about how mathematics has shaped, and been shaped by, some of our most fundamental human concerns – from trade and travel to war, peace, life, death, form and beauty.

Curator Dr David Rooney said, ‘At its heart this gallery reveals a rich cultural story of human endeavour that has helped transform the world over the last four hundred years. Mathematical practice underpins so many aspects of our lives and work, and we hope that bringing together these remarkable stories, people and exhibits will inspire visitors to think about the role of mathematics in a new light.’

Positioned at the centre of the gallery is the Handley Page ‘Gugnunc’ aeroplane, built in 1929 for a competition to construct safe aircraft. Ground-breaking aerodynamic research influenced the wing design of this experimental aeroplane, helping to shift public opinion about the safety of flying and to secure the future of the aviation industry. This aeroplane encapsulates the gallery’s overarching theme, illustrating how mathematical practice has helped solve real-world problems and in this instance paved the way for the safe passenger flights that we rely on today.

Mathematics also defines Zaha Hadid Architects’ enlightening design for the gallery. Inspired by the Handley Page aircraft, the design is driven by equations of airflow used in the aviation industry. The layout and lines of the gallery represent the air that would have flowed around this historic aircraft in flight, from the positioning of the showcases and benches to the three-dimensional curved surfaces of the central pod structure.

Mathematics: The Winton Gallery is the first permanent public museum exhibition designed by Zaha Hadid Architects anywhere in the world. The gallery is also the first of Zaha Hadid Architects’ projects to open in the UK since Dame Zaha Hadid’s sudden death in March 2016. The late Dame Zaha first became interested in geometry while studying mathematics at university. Mathematics and geometry have a strong connection with architecture and she continued to examine these relationships throughout each of her projects; with mathematics always central to her work. As Dame Zaha said, ‘When I was growing up in Iraq, math was an everyday part of life. We would play with math problems just as we would play with pens and paper to draw – math was like sketching.’

Ian Blatchford, Director of the Science Museum Group, said, ‘We were hugely impressed by the ideas and vision of the late Dame Zaha Hadid and Patrik Schumacher when they first presented their design for the new mathematics gallery over two years ago. It was a terrible shock for us all when Dame Zaha died suddenly in March this year, but I am sure that this gallery will be a lasting tribute to this world-changing architect and provide inspiration for our millions of visitors for many years to come.’

From a beautiful 17th century Islamic astrolabe that uses ancient mathematical techniques to map the night sky, to an early example of the famous Enigma machine, designed to resist even the most advanced mathematical techniques for code breaking during the Second World War, each historic object within the gallery has an important story to tell. Archive photography and film helps to capture these stories, and introduces the wide range of people who made, used or were impacted by each mathematical device or idea.

Some instruments and objects within the gallery clearly reference their mathematical origin. Others may surprise visitors and appear rooted in other disciplines, from classical architecture to furniture design. Visitors will see a box of glass eyes used by Francis Galton in his 1884 Anthropometric Laboratory to help measure the physical characteristics of the British public and develop statistics to support a wider social and political movement he termed ‘eugenics’. On the other side of the gallery is the pioneering Wisard pattern-recognition machine built in 1981 to attempt to re-create the ‘neural networks’ of the brain. This early Artificial Intelligence machine worked, until 1995, on a variety of projects, from banknote recognition to voice analysis, and from foetal growth monitoring in hospitals to covert surveillance for the Home Office.

A richly illustrated book has been published by Scala to accompany the new gallery. Mathematics: How it Shaped Our World, written by David Rooney, expands on the themes and stories that are celebrated in the gallery itself and includes a series of newly commissioned essays written by world-leading experts in the history and modern practice of mathematics.

David Harding, Principal Funder of the gallery and Founder and CEO of Winton said, ‘Mathematics, whilst difficult for many, is incredibly useful. To those with an aptitude for it, it is also beautiful. I’m delighted that this gallery will be both useful and beautiful.’

Mathematics: The Winton Gallery is free to visit and open daily from 8 December 2016. The gallery has been made possible through an unprecedented donation from long-standing supporters of science, David and Claudia Harding. It has also received generous support from Samsung as Principal Sponsor, MathWorks as Major Sponsor, with additional support from Adrian and Jacqui Beecroft, Iain and Jane Bratchie, the Keniston-Cooper Charitable Trust, Dr Martin Schoernig, Steve Mobbs and Pauline Thomas.

After the press release, there is the most extensive list of ‘Abouts’ I’ve seen yet (Note: This includes links to the Science Museum and other agencies),

About the Science Museum
The Science Museum’s world-class collection forms an enduring record of scientific, technological and medical achievements from across the globe. Welcoming over 3 million visitors a year, the Museum aims to make sense of the science that shapes our lives, inspiring visitors with iconic objects, award-winning exhibitions and incredible stories of scientific achievement. More information can be found at sciencemuseum.org.uk

About Curator David Rooney
Mathematics: The Winton Gallery has been curated by Dr David Rooney, who was responsible for the award-winning 2012 Science Museum exhibition Codebreaker: Alan Turing’s Life and Legacy as well as developing galleries on time and navigation at the National Maritime Museum, Greenwich. David writes and speaks widely on the history of technology and engineering. His critically acclaimed first book, Ruth Belville: The Greenwich Time Lady, was described by Jonathan Meades as ‘an engrossing and eccentric slice of London history’, and by the Daily Telegraph as ‘a gem of a book’. He has recently authored Mathematics: How It Shaped Our World, to accompany the new mathematics gallery, and is currently writing a political history of traffic.

About David and Claudia Harding
David and Claudia Harding are associated with Winton, one of the world’s leading quantitative investment management firms which David founded in 1997. Winton uses mathematical and scientific methods to devise, evaluate and execute investment ideas on behalf of clients all over the world. A British-based company, Winton and David and Claudia Harding have donated to numerous scientific and mathematical causes in the UK and internationally, including Cambridge University, the Crick Institute, the Max Planck Institute, and the Science Museum. The main themes of their philanthropy have been supporting basic scientific research and the communication of scientific ideas. David and Claudia reside in London.

About Samsung’s Citizenship Programmes
Samsung is committed to help close the digital divide and skills gap in the UK. Samsung Digital Classrooms in schools, charities/non-profit organisations and cultural partners provide access to the latest technology. Samsung is also providing the training and maintenance support necessary to help make the transition and integration of the new technology as smooth as possible. Samsung also offers qualifications and training in technology for young people and teachers through its Digital Academies. These initiatives will inspire young people, staff and teachers to learn and teach in new exciting ways and to help encourage young people into careers using technology. Find out more

About MathWorks
MathWorks is the leading developer of mathematical computing software. MATLAB, the language of technical computing, is a programming environment for algorithm development, data analysis, visualisation, and numeric computation. Simulink is a graphical environment for simulation and Model-Based Design for multidomain dynamic and embedded systems. Engineers and scientists worldwide rely on these product families to accelerate the pace of discovery, innovation, and development in automotive, aerospace, electronics, financial services, biotech-pharmaceutical, and other industries. MATLAB and Simulink are also fundamental teaching and research tools in the world’s universities and learning institutions. Founded in 1984, MathWorks employs more than 3000 people in 15 countries, with headquarters in Natick, Massachusetts, USA. For additional information, visit mathworks.com

About Zaha Hadid Architects
Zaha Hadid founded Zaha Hadid Architects (ZHA) in 1979. Each of ZHA’s projects builds on over thirty years of exploration and research in the interrelated fields of urbanism, architecture and design. Hadid’s pioneering vision redefined architecture for the 21st century and captured imaginations across the globe. Her legacy is embedded within the DNA of the design studio she created as ZHA’s projects combine the unwavering belief in the power of invention with concepts of connectivity and fluidity.

ZHA is currently working on a diversity of projects worldwide including the new Beijing Airport Terminal Building in Daxing, China, the Sleuk Rith Institute in Phnom Penh, Cambodia and 520 West 28th Street in New York City, USA. The practice’s portfolio includes cultural, academic, sporting, residential, and transportation projects across six continents.

About Discover South Kensington
Discover South Kensington brings together the Science Museum and other leading cultural and educational organisations to promote innovation and learning. South Kensington is the home of science, arts and inspiration. Discovery is at the core of what happens here and there is so much to explore every day. discoversouthken.com

About Zaha Hadid: Early Paintings and Drawings at the Serpentine Sackler Gallery
This week an exhibition of paintings and drawings by Zaha Hadid will open at the Serpentine Galleries that will reveal her as an artist with drawing at the very heart of her work. It will include calligraphic drawings and rarely seen private notebooks, showing her complex thoughts about architecture’s forms and relationship to the world we live in. Zaha Hadid: Early Paintings and Drawings at the Serpentine Sackler Gallery is free to visit and runs from 8th December 2016 – 12th February 2017.

I found the mentions of Zaha Hadid fascinating and so I looked her up on Wikipedia, where I found this (Note: Links have been removed),

Dame Zaha Mohammad Hadid, DBE (Arabic: زها حديد‎‎ Zahā Ḥadīd; 31 October 1950 – 31 March 2016) was an Iraqi-born British architect. She was the first woman to receive the Pritzker Architecture Prize, in 2004.[1] She received the UK’s most prestigious architectural award, the Stirling Prize, in 2010 and 2011. In 2012, she was made a Dame by Elizabeth II for services to architecture, and in 2015 she became the first woman to be awarded the Royal Gold Medal from the Royal Institute of British Architects.[2]

She was dubbed by The Guardian as the ‘Queen of the curve’.[3] She liberated architectural geometry[4] with the creation of highly expressive, sweeping fluid forms of multiple perspective points and fragmented geometry that evoke the chaos and flux of modern life.[5] A pioneer of parametricism, and an icon of neo-futurism, with a formidable personality, her acclaimed work and ground-breaking forms include the aquatic centre for the London 2012 Olympics, the Broad Art Museum in the US, and the Guangzhou Opera House in China.[6] At the time of her death in 2016, Zaha Hadid Architects in London was the fastest growing British architectural firm.[7] Many of her designs are to be released posthumously, ranging in variation from the 2017 Brit Awards statuette to a 2022 FIFA World Cup stadium.[8][9]

Dubbed ‘Queen of the curve’, Hadid has a reputation as the world’s top female architect,[3][62][63][64][65] although her reputation is not without criticism. She is considered an architect of unconventional thinking, whose buildings are organic, dynamic and sculptural.[66][67] Stanton and others also compliment her on her unique organic designs: “One of the main characteristics of her work is that however clearly recognizable, it can never be pigeonholed into a stylistic signature. Digital knowledge, technology-driven mutations, shapes inspired by the organic and biological world, as well as geometrical interpretation of the landscape are constant elements of her practice. Yet, the multiplicity and variety of the combination among these facets prevent the risk of self-referential solutions and repetitions.”[68] Allison Lee Palmer considers Hadid a leader of Deconstructivism in architecture, writing that, “Almost all of Hadid’s buildings appear to melt, bend, and curve into a new architectural language that defies description. Her completed buildings span the globe and include the Jockey Club Innovation Tower on the north side of the Hong Kong Polytechnic University in Hong Kong, completed in 2013, that provides Hong Kong an entry into the world stage of cutting-edge architecture by revealing a design that dissolved traditional architecture, the so called modernist “glass box,” into a shattering of windows and melting of walls to form organic structures with halls and stairways that flow through the building, pooling open into rooms and foyers.”[69]

Hadid’s architectural language has been described by some as “famously extravagant” with many of her projects sponsored by “dictator states”. [emphasis mine] [70] Rowan Moore described Hadid’s Heydar Aliyev Center as “not so different from the colossal cultural palaces long beloved of Soviet and similar regimes”. Architect Sean Griffiths characterised Hadid’s work as “an empty vessel that sucks in whatever ideology might be in proximity to it”.[71] Art historian Maike Aden criticises in particular the foreclosure of Zaha Hadid’s architecture of the MAXXI in Rome towards the public and the urban life that undermines even the most impressive program to open the museum.[72]

If you think about it, most of the world’s great monuments were built by dictators or omnipotent rulers of one country or another. Getting the money and commitment can present an ethical/moral issue for any artist or architect who has a ‘grand design’.