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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

Ancient Roman teaching methods for maths education?

I find this delightful (from a July 7,2017 news item on phys.org),

Schoolchildren from across the region have been learning different ways to engage with maths, as part of a series of ancient Roman classroom days held at the University of Reading [UK].

Organised by the University’s Department of Classics, the Reading Ancient Schoolroom event saw pupils undertake a series of ancient-style school exercises, including doing multiplication, division, and calculating compound interest with Roman numerals. A key difference between how maths was taught then and now is that sums were not written down in ancient Roman times – instead an abacus or a counting board with dried beans was used.

In addition, school children in antiquity were taught individually by the teacher and worked on their own assignments, rather than being taught as a whole class. This meant pupils were able to work at their own rate of ability.

A July 6, 2017 University of Reading press release, which originated the news item, expands on the theme,

Professor Eleanor Dickey, who organised the series of events, said: ‘We’ve been running these ancient schoolroom days for a few years now and what we’ve learnt during that time is that the children really engage with the ancient teaching methods, especially when it comes to maths. We’ve found that children who aren’t naturally gifted at maths actually enjoy using the abacus and counting boards and this helps to stimulate their interest and learning of the subject.

“As follow up to the day we provide teachers with a pack of teaching materials they can take back to their own classroom and this includes instructions on how to make a counting board, as well as other maths-related and non-maths-related activities. It is my hope that some of these ancient methods can help to further modern teaching practice.”

Other activities on the day included reading poetry written without word division or punctuation, learning to write with a stylus on a wax tablet and reading from papyrus scrolls. Wearing Roman costumes, students also got to sample some authentic Roman food and handle objects from the University of Reading’s Ure Museum of Greek Archaeology.

Professor Dickey continued: “Ancient education methods, by being very different from our own, help us better appreciate both the advantages and the disadvantages of our own system, and show that doing things our way is neither natural nor inevitable.

“The ancient Roman school days are also a great way to get children interested in history more generally.”

The research which helped determine what a day in an ancient Roman classroom was like came from Professor Dickey’s discovery and translation of a set of ancient textbooks describing what children did in school. Parts of these historical records were published last year in a book by Professor Dickey: Learning Latin the Ancient Way: Latin Textbooks in the Ancient World, published by Cambridge University Press.

In hindsight it seems obvious. Of course an abacus helps with learning as it’s more engaging. You get to make a range of gestures and you make sounds (the clicking of the abacus beads) neither of which are  typically part of the maths experience. Then, there’s the individualized attention and your own special maths problems.

Training drugs

This summarizes some of what’s happening in nanomedicine and provides a plug (boost) for the  University of Cambridge’s nanotechnology programmes (from a June 26, 2017 news item on Nanowerk),

Nanotechnology is creating new opportunities for fighting disease – from delivering drugs in smart packaging to nanobots powered by the world’s tiniest engines.

Chemotherapy benefits a great many patients but the side effects can be brutal.
When a patient is injected with an anti-cancer drug, the idea is that the molecules will seek out and destroy rogue tumour cells. However, relatively large amounts need to be administered to reach the target in high enough concentrations to be effective. As a result of this high drug concentration, healthy cells may be killed as well as cancer cells, leaving many patients weak, nauseated and vulnerable to infection.

One way that researchers are attempting to improve the safety and efficacy of drugs is to use a relatively new area of research known as nanothrapeutics to target drug delivery just to the cells that need it.

Professor Sir Mark Welland is Head of the Electrical Engineering Division at Cambridge. In recent years, his research has focused on nanotherapeutics, working in collaboration with clinicians and industry to develop better, safer drugs. He and his colleagues don’t design new drugs; instead, they design and build smart packaging for existing drugs.

The University of Cambridge has produced a video interview (referencing a 1966 movie ‘Fantastic Voyage‘ in its title)  with Sir Mark Welland,

A June 23, 2017 University of Cambridge press release, which originated the news item, delves further into the topic of nanotherapeutics (nanomedicine) and nanomachines,

Nanotherapeutics come in many different configurations, but the easiest way to think about them is as small, benign particles filled with a drug. They can be injected in the same way as a normal drug, and are carried through the bloodstream to the target organ, tissue or cell. At this point, a change in the local environment, such as pH, or the use of light or ultrasound, causes the nanoparticles to release their cargo.

Nano-sized tools are increasingly being looked at for diagnosis, drug delivery and therapy. “There are a huge number of possibilities right now, and probably more to come, which is why there’s been so much interest,” says Welland. Using clever chemistry and engineering at the nanoscale, drugs can be ‘taught’ to behave like a Trojan horse, or to hold their fire until just the right moment, or to recognise the target they’re looking for.

“We always try to use techniques that can be scaled up – we avoid using expensive chemistries or expensive equipment, and we’ve been reasonably successful in that,” he adds. “By keeping costs down and using scalable techniques, we’ve got a far better chance of making a successful treatment for patients.”

In 2014, he and collaborators demonstrated that gold nanoparticles could be used to ‘smuggle’ chemotherapy drugs into cancer cells in glioblastoma multiforme, the most common and aggressive type of brain cancer in adults, which is notoriously difficult to treat. The team engineered nanostructures containing gold and cisplatin, a conventional chemotherapy drug. A coating on the particles made them attracted to tumour cells from glioblastoma patients, so that the nanostructures bound and were absorbed into the cancer cells.

Once inside, these nanostructures were exposed to radiotherapy. This caused the gold to release electrons that damaged the cancer cell’s DNA and its overall structure, enhancing the impact of the chemotherapy drug. The process was so effective that 20 days later, the cell culture showed no evidence of any revival, suggesting that the tumour cells had been destroyed.

While the technique is still several years away from use in humans, tests have begun in mice. Welland’s group is working with MedImmune, the biologics R&D arm of pharmaceutical company AstraZeneca, to study the stability of drugs and to design ways to deliver them more effectively using nanotechnology.

“One of the great advantages of working with MedImmune is they understand precisely what the requirements are for a drug to be approved. We would shut down lines of research where we thought it was never going to get to the point of approval by the regulators,” says Welland. “It’s important to be pragmatic about it so that only the approaches with the best chance of working in patients are taken forward.”

The researchers are also targeting diseases like tuberculosis (TB). With funding from the Rosetrees Trust, Welland and postdoctoral researcher Dr Íris da luz Batalha are working with Professor Andres Floto in the Department of Medicine to improve the efficacy of TB drugs.

Their solution has been to design and develop nontoxic, biodegradable polymers that can be ‘fused’ with TB drug molecules. As polymer molecules have a long, chain-like shape, drugs can be attached along the length of the polymer backbone, meaning that very large amounts of the drug can be loaded onto each polymer molecule. The polymers are stable in the bloodstream and release the drugs they carry when they reach the target cell. Inside the cell, the pH drops, which causes the polymer to release the drug.

In fact, the polymers worked so well for TB drugs that another of Welland’s postdoctoral researchers, Dr Myriam Ouberaï, has formed a start-up company, Spirea, which is raising funding to develop the polymers for use with oncology drugs. Ouberaï is hoping to establish a collaboration with a pharma company in the next two years.

“Designing these particles, loading them with drugs and making them clever so that they release their cargo in a controlled and precise way: it’s quite a technical challenge,” adds Welland. “The main reason I’m interested in the challenge is I want to see something working in the clinic – I want to see something working in patients.”

Could nanotechnology move beyond therapeutics to a time when nanomachines keep us healthy by patrolling, monitoring and repairing the body?

Nanomachines have long been a dream of scientists and public alike. But working out how to make them move has meant they’ve remained in the realm of science fiction.

But last year, Professor Jeremy Baumberg and colleagues in Cambridge and the University of Bath developed the world’s tiniest engine – just a few billionths of a metre [nanometre] in size. It’s biocompatible, cost-effective to manufacture, fast to respond and energy efficient.

The forces exerted by these ‘ANTs’ (for ‘actuating nano-transducers’) are nearly a hundred times larger than those for any known device, motor or muscle. To make them, tiny charged particles of gold, bound together with a temperature-responsive polymer gel, are heated with a laser. As the polymer coatings expel water from the gel and collapse, a large amount of elastic energy is stored in a fraction of a second. On cooling, the particles spring apart and release energy.

The researchers hope to use this ability of ANTs to produce very large forces relative to their weight to develop three-dimensional machines that swim, have pumps that take on fluid to sense the environment and are small enough to move around our bloodstream.

Working with Cambridge Enterprise, the University’s commercialisation arm, the team in Cambridge’s Nanophotonics Centre hopes to commercialise the technology for microfluidics bio-applications. The work is funded by the Engineering and Physical Sciences Research Council and the European Research Council.

“There’s a revolution happening in personalised healthcare, and for that we need sensors not just on the outside but on the inside,” explains Baumberg, who leads an interdisciplinary Strategic Research Network and Doctoral Training Centre focused on nanoscience and nanotechnology.

“Nanoscience is driving this. We are now building technology that allows us to even imagine these futures.”

I have featured Welland and his work here before and noted his penchant for wanting to insert nanodevices into humans as per this excerpt from an April 30, 2010 posting,
Getting back to the Cambridge University video, do go and watch it on the Nanowerk site. It is fun and very informative and approximately 17 mins. I noticed that they reused part of their Nokia morph animation (last mentioned on this blog here) and offered some thoughts from Professor Mark Welland, the team leader on that project. Interestingly, Welland was talking about yet another possibility. (Sometimes I think nano goes too far!) He was suggesting that we could have chips/devices in our brains that would allow us to think about phoning someone and an immediate connection would be made to that person. Bluntly—no. Just think what would happen if the marketers got access and I don’t even want to think what a person who suffers psychotic breaks (i.e., hearing voices) would do with even more input. Welland starts to talk at the 11 minute mark (I think). For an alternative take on the video and more details, visit Dexter Johnson’s blog, Nanoclast, for this posting. Hint, he likes the idea of a phone in the brain much better than I do.

I’m not sure what could have occasioned this latest press release and related video featuring Welland and nanotherapeutics other than guessing that it was a slow news period.

Robot artists—should they get copyright protection

Clearly a lawyer wrote this June 26, 2017 essay on theconversation.com (Note: A link has been removed),

When a group of museums and researchers in the Netherlands unveiled a portrait entitled The Next Rembrandt, it was something of a tease to the art world. It wasn’t a long lost painting but a new artwork generated by a computer that had analysed thousands of works by the 17th-century Dutch artist Rembrandt Harmenszoon van Rijn.

The computer used something called machine learning [emphasis mine] to analyse and reproduce technical and aesthetic elements in Rembrandt’s works, including lighting, colour, brush-strokes and geometric patterns. The result is a portrait produced based on the styles and motifs found in Rembrandt’s art but produced by algorithms.

But who owns creative works generated by artificial intelligence? This isn’t just an academic question. AI is already being used to generate works in music, journalism and gaming, and these works could in theory be deemed free of copyright because they are not created by a human author.

This would mean they could be freely used and reused by anyone and that would be bad news for the companies selling them. Imagine you invest millions in a system that generates music for video games, only to find that music isn’t protected by law and can be used without payment by anyone in the world.

Unlike with earlier computer-generated works of art, machine learning software generates truly creative works without human input or intervention. AI is not just a tool. While humans program the algorithms, the decision making – the creative spark – comes almost entirely from the machine.

It could have been someone involved in the technology but nobody with that background would write “… something called machine learning … .”  Andres Guadamuz, lecturer in Intellectual Property Law at the University of Sussex, goes on to say (Note: Links have been removed),

Unlike with earlier computer-generated works of art, machine learning software generates truly creative works without human input or intervention. AI is not just a tool. While humans program the algorithms, the decision making – the creative spark – comes almost entirely from the machine.

That doesn’t mean that copyright should be awarded to the computer, however. Machines don’t (yet) have the rights and status of people under the law. But that doesn’t necessarily mean there shouldn’t be any copyright either. Not all copyright is owned by individuals, after all.

Companies are recognised as legal people and are often awarded copyright for works they don’t directly create. This occurs, for example, when a film studio hires a team to make a movie, or a website commissions a journalist to write an article. So it’s possible copyright could be awarded to the person (company or human) that has effectively commissioned the AI to produce work for it.

 

Things are likely to become yet more complex as AI tools are more commonly used by artists and as the machines get better at reproducing creativity, making it harder to discern if an artwork is made by a human or a computer. Monumental advances in computing and the sheer amount of computational power becoming available may well make the distinction moot. At that point, we will have to decide what type of protection, if any, we should give to emergent works created by intelligent algorithms with little or no human intervention.

The most sensible move seems to follow those countries that grant copyright to the person who made the AI’s operation possible, with the UK’s model looking like the most efficient. This will ensure companies keep investing in the technology, safe in the knowledge they will reap the benefits. What happens when we start seriously debating whether computers should be given the status and rights of people is a whole other story.

The team that developed a ‘new’ Rembrandt produced a video about the process,

Mark Brown’s April 5, 2016 article abut this project (which was unveiled on April 5, 2017 in Amsterdam, Netherlands) for the Guardian newspaper provides more detail such as this,

It [Next Rembrandt project] is the result of an 18-month project which asks whether new technology and data can bring back to life one of the greatest, most innovative painters of all time.

Advertising executive [Bas] Korsten, whose brainchild the project was, admitted that there were many doubters. “The idea was greeted with a lot of disbelief and scepticism,” he said. “Also coming up with the idea is one thing, bringing it to life is another.”

The project has involved data scientists, developers, engineers and art historians from organisations including Microsoft, Delft University of Technology, the Mauritshuis in The Hague and the Rembrandt House Museum in Amsterdam.

The final 3D printed painting consists of more than 148 million pixels and is based on 168,263 Rembrandt painting fragments.

Some of the challenges have been in designing a software system that could understand Rembrandt based on his use of geometry, composition and painting materials. A facial recognition algorithm was then used to identify and classify the most typical geometric patterns used to paint human features.

It sounds like it was a fascinating project but I don’t believe ‘The Next Rembrandt’ is an example of AI creativity or an example of the ‘creative spark’ Guadamuz discusses. This seems more like the kind of work  that could be done by a talented forger or fraudster. As I understand it, even when a human creates this type of artwork (a newly discovered and unknown xxx masterpiece), the piece is not considered a creative work in its own right. Some pieces are outright fraudulent and others which are described as “in the manner of xxx.”

Taking a somewhat different approach to mine, Timothy Geigner at Techdirt has also commented on the question of copyright and AI in relation to Guadamuz’s essay in a July 7, 2017 posting,

Unlike with earlier computer-generated works of art, machine learning software generates truly creative works without human input or intervention. AI is not just a tool. While humans program the algorithms, the decision making – the creative spark – comes almost entirely from the machine.

Let’s get the easy part out of the way: the culminating sentence in the quote above is not true. The creative spark is not the artistic output. Rather, the creative spark has always been known as the need to create in the first place. This isn’t a trivial quibble, either, as it factors into the simple but important reasoning for why AI and machines should certainly not receive copyright rights on their output.

That reasoning is the purpose of copyright law itself. Far too many see copyright as a reward system for those that create art rather than what it actually was meant to be: a boon to an artist to compensate for that artist to create more art for the benefit of the public as a whole. Artificial intelligence, however far progressed, desires only what it is programmed to desire. In whatever hierarchy of needs an AI might have, profit via copyright would factor either laughably low or not at all into its future actions. Future actions of the artist, conversely, are the only item on the agenda for copyright’s purpose. If receiving a copyright wouldn’t spur AI to create more art beneficial to the public, then copyright ought not to be granted.

Geigner goes on (July 7, 2017 posting) to elucidate other issues with the ideas expressed in the general debates of AI and ‘rights’ and the EU’s solution.

Robots and a new perspective on disability

I’ve long wondered about how disabilities would be viewed in a future (h/t May 4, 2017 news item on phys.org) where technology could render them largely irrelevant. A May 4, 2017 essay by Thusha (Gnanthusharan) Rajendran of Heriot-Watt University on TheConversation.com provides a perspective on the possibilities (Note: Links have been removed),

When dealing with the otherness of disability, the Victorians in their shame built huge out-of-sight asylums, and their legacy of “them” and “us” continues to this day. Two hundred years later, technologies offer us an alternative view. The digital age is shattering barriers, and what used to the norm is now being challenged.

What if we could change the environment, rather than the person? What if a virtual assistant could help a visually impaired person with their online shopping? And what if a robot “buddy” could help a person with autism navigate the nuances of workplace politics? These are just some of the questions that are being asked and which need answers as the digital age challenges our perceptions of normality.

The treatment of people with developmental conditions has a chequered history. In towns and cities across Britain, you will still see large Victorian buildings that were once places to “look after” people with disabilities, that is, remove them from society. Things became worse still during the time of the Nazis with an idealisation of the perfect and rejection of Darwin’s idea of natural diversity.

Today we face similar challenges about differences versus abnormalities. Arguably, current diagnostic systems do not help, because they diagnose the person and not “the system”. So, a child has challenging behaviour, rather than being in distress; the person with autism has a communication disorder rather than simply not being understood.

Natural-born cyborgs

In contrast, the digital world is all about systems. The field of human-computer interaction is about how things work between humans and computers or robots. Philosopher Andy Clark argues that humans have always been natural-born cyborgs – that is, we have always used technology (in its broadest sense) to improve ourselves.

The most obvious example is language itself. In the digital age we can become truly digitally enhanced. How many of us Google something rather than remembering it? How do you feel when you have no access to wi-fi? How much do we favour texting, tweeting and Facebook over face-to-face conversations? How much do we love and need our smartphones?

In the new field of social robotics, my colleagues and I are developing a robot buddy to help adults with autism to understand, for example, if their boss is pleased or displeased with their work. For many adults with autism, it is not the work itself that stops from them from having successful careers, it is the social environment surrounding work. From the stress-inducing interview to workplace politics, the modern world of work is a social minefield. It is not easy, at times, for us neurotypticals, but for a person with autism it is a world full contradictions and implied meaning.

Rajendra goes on to highlight efforts with autistic individuals; he also includes this video of his December 14, 2016 TEDx Heriot-Watt University talk, which largely focuses on his work with robots and autism  (Note: This runs approximately 15 mins.),

The talk reminded me of a Feb. 6, 2017 posting (scroll down about 33% of the way) where I discussed a recent book about science communication and its failure to recognize the importance of pop culture in that endeavour. As an example, I used a then recent announcement from MIT (Massachusetts Institute of Technology) about their emotion detection wireless application and the almost simultaneous appearance of that application in a Feb. 2, 2017 episode of The Big Bang Theory (a popular US television comedy) featuring a character who could be seen as autistic making use of the emotion detection device.

In any event, the work described in the MIT news release is very similar to Rajendra’s albeit the communication is delivered to the public through entirely different channels: TEDx Talk and TheConversation.com (channels aimed at academics and those with academic interests) and a pop culture television comedy with broad appeal.

A question of consciousness: Facebotlish (a new language); a July 5, 2017 rap guide performance in Vancouver, Canada; Tom Stoppard’s play; and a little more

This would usually be a simple event announcement but with the advent of a new, related (in my mind if no one else’s) development on Facebook, this has become a roundup of sorts.

Facebotlish (Facebook’s chatbots create their own language)

The language created by Facebook’s chatbots, Facebotlish, was an unintended consequence—that’s right Facebook’s developers did not design a language for the chatbots or anticipate its independent development, apparently.  Adrienne LaFrance’s June 20, 2017 article for theatlantic.com explores the development and the question further,

Something unexpected happened recently at the Facebook Artificial Intelligence Research lab. Researchers who had been training bots to negotiate with one another realized that the bots, left to their own devices, started communicating in a non-human language.

In order to actually follow what the bots were saying, the researchers had to tweak their model, limiting the machines to a conversation humans could understand. (They want bots to stick to human languages because eventually they want those bots to be able to converse with human Facebook users.) …

Here’s what the language looks like (from LaFrance article),

Here’s an example of one of the bot negotiations that Facebook observed:Bob: i can i i everything else . . . . . . . . . . . . . .
Alice: balls have zero to me to me to me to me to me to me to me to me to
Bob: you i everything else . . . . . . . . . . . . . .
Alice: balls have a ball to me to me to me to me to me to me to me
Bob: i i can i i i everything else . . . . . . . . . . . . . .
Alice: balls have a ball to me to me to me to me to me to me to me
Bob: i . . . . . . . . . . . . . . . . . . .
Alice: balls have zero to me to me to me to me to me to me to me to me to
Bob: you i i i i i everything else . . . . . . . . . . . . . .
Alice: balls have 0 to me to me to me to me to me to me to me to me to
Bob: you i i i everything else . . . . . . . . . . . . . .
Alice: balls have zero to me to me to me to me to me to me to me to me to

It is incomprehensible to humans even after being tweaked, even so, some successful negotiations can ensue.

Facebook’s researchers aren’t the only one to come across the phenomenon (from LaFrance’s article; Note: Links have been removed),

Other AI researchers, too, say they’ve observed machines that can develop their own languages, including languages with a coherent structure, and defined vocabulary and syntax—though not always actual meaningful, by human standards.

In one preprint paper added earlier this year [2017] to the research repository arXiv, a pair of computer scientists from the non-profit AI research firm OpenAI wrote about how bots learned to communicate in an abstract language—and how those bots turned to non-verbal communication, the equivalent of human gesturing or pointing, when language communication was unavailable. (Bots don’t need to have corporeal form to engage in non-verbal communication; they just engage with what’s called a visual sensory modality.) Another recent preprint paper, from researchers at the Georgia Institute of Technology, Carnegie Mellon, and Virginia Tech, describes an experiment in which two bots invent their own communication protocol by discussing and assigning values to colors and shapes—in other words, the researchers write, they witnessed the “automatic emergence of grounded language and communication … no human supervision!”

The implications of this kind of work are dizzying. Not only are researchers beginning to see how bots could communicate with one another, they may be scratching the surface of how syntax and compositional structure emerged among humans in the first place.

LaFrance’s article is well worth reading in its entirety especially since the speculation is focused on whether or not the chatbots’ creation is in fact language. There is no mention of consciousness and perhaps this is just a crazy idea but is it possible that these chatbots have consciousness? The question is particularly intriguing in light of some of philosopher David Chalmers’ work (see his 2014 TED talk in Vancouver, Canada: https://www.ted.com/talks/david_chalmers_how_do_you_explain_consciousness/transcript?language=en runs roughly 18 mins.); a text transcript is also featured. There’s a condensed version of Chalmers’ TED talk offered in a roughly 9 minute NPR (US National Public Radio) interview by Gus Raz. Here are some highlights from the text transcript,

So we’ve been hearing from brain scientists who are asking how a bunch of neurons and synaptic connections in the brain add up to us, to who we are. But it’s consciousness, the subjective experience of the mind, that allows us to ask the question in the first place. And where consciousness comes from – that is an entirely separate question.

DAVID CHALMERS: Well, I like to distinguish between the easy problems of consciousness and the hard problem.

RAZ: This is David Chalmers. He’s a philosopher who coined this term, the hard problem of consciousness.

CHALMERS: Well, the easy problems are ultimately a matter of explaining behavior – things we do. And I think brain science is great at problems like that. It can isolate a neural circuit and show how it enables you to see a red object, to respondent and say, that’s red. But the hard problem of consciousness is subjective experience. Why, when all that happens in this circuit, does it feel like something? How does a bunch of – 86 billion neurons interacting inside the brain, coming together – how does that produce the subjective experience of a mind and of the world?

RAZ: Here’s how David Chalmers begins his TED Talk.

(SOUNDBITE OF TED TALK)

CHALMERS: Right now, you have a movie playing inside your head. It has 3-D vision and surround sound for what you’re seeing and hearing right now. Your movie has smell and taste and touch. It has a sense of your body, pain, hunger, orgasms. It has emotions, anger and happiness. It has memories, like scenes from your childhood, playing before you. This movie is your stream of consciousness. If we weren’t conscious, nothing in our lives would have meaning or value. But at the same time, it’s the most mysterious phenomenon in the universe. Why are we conscious?

RAZ: Why is consciousness more than just the sum of the brain’s parts?

CHALMERS: Well, the question is, you know, what is the brain? It’s this giant complex computer, a bunch of interacting parts with great complexity. What does all that explain? That explains objective mechanism. Consciousness is subjective by its nature. It’s a matter of subjective experience. And it seems that we can imagine all of that stuff going on in the brain without consciousness. And the question is, where is the consciousness from there? It’s like, if someone could do that, they’d get a Nobel Prize, you know?

RAZ: Right.

CHALMERS: So here’s the mapping from this circuit to this state of consciousness. But underneath that is always going be the question, why and how does the brain give you consciousness in the first place?

(SOUNDBITE OF TED TALK)

CHALMERS: Right now, nobody knows the answers to those questions. So we may need one or two ideas that initially seem crazy before we can come to grips with consciousness, scientifically. The first crazy idea is that consciousness is fundamental. Physicists sometimes take some aspects of the universe as fundamental building blocks – space and time and mass – and you build up the world from there. Well, I think that’s the situation we’re in. If you can’t explain consciousness in terms of the existing fundamentals – space, time – the natural thing to do is to postulate consciousness itself as something fundamental – a fundamental building block of nature. The second crazy idea is that consciousness might be universal. This view is sometimes called panpsychism – pan, for all – psych, for mind. Every system is conscious. Not just humans, dogs, mice, flies, but even microbes. Even a photon has some degree of consciousness. The idea is not that photons are intelligent or thinking. You know, it’s not that a photon is wracked with angst because it’s thinking, oh, I’m always buzzing around near the speed of light. I never get to slow down and smell the roses. No, not like that. But the thought is, maybe photons might have some element of raw subjective feeling, some primitive precursor to consciousness.

RAZ: So this is a pretty big idea – right? – like, that not just flies, but microbes or photons all have consciousness. And I mean we, like, as humans, we want to believe that our consciousness is what makes us special, right – like, different from anything else.

CHALMERS: Well, I would say yes and no. I’d say the fact of consciousness does not make us special. But maybe we’ve a special type of consciousness ’cause you know, consciousness is not on and off. It comes in all these rich and amazing varieties. There’s vision. There’s hearing. There’s thinking. There’s emotion and so on. So our consciousness is far richer, I think, than the consciousness, say, of a mouse or a fly. But if you want to look for what makes us distinct, don’t look for just our being conscious, look for the kind of consciousness we have. …

Intriguing, non?

Vancouver premiere of Baba Brinkman’s Rap Guide to Consciousness

Baba Brinkman, former Vancouverite and current denizen of New York City, is back in town offering a new performance at the Rio Theatre (1680 E. Broadway, near Commercial Drive). From a July 5, 2017 Rio Theatre event page and ticket portal,

Baba Brinkman’s Rap Guide to Consciousness

Wednesday, July 5 [2017] at 6:30pm PDT

Baba Brinkman’s new hip-hop theatre show “Rap Guide to Consciousness” is all about the neuroscience of consciousness. See it in Vancouver at the Rio Theatre before it goes to the Edinburgh Fringe Festival in August [2017].

This event also features a performance of “Off the Top” with Dr. Heather Berlin (cognitive neuroscientist, TV host, and Baba’s wife), which is also going to Edinburgh.

Wednesday, July 5
Doors 6:00 pm | Show 6:30 pm

Advance tickets $12 | $15 at the door

*All ages welcome!
*Sorry, Groupons and passes not accepted for this event.

“Utterly unique… both brilliantly entertaining and hugely informative” ★ ★ ★ ★ ★ – Broadway Baby

“An education, inspiring, and wonderfully entertaining show from beginning to end” ★ ★ ★ ★ ★ – Mumble Comedy

There’s quite the poster for this rap guide performance,

In addition to  the Vancouver and Edinburgh performance (the show was premiered at the Brighton Fringe Festival in May 2017; see Simon Topping’s very brief review in this May 10, 2017 posting on the reviewshub.com), Brinkman is raising money (goal is $12,000US; he has raised a little over $3,000 with approximately one month before the deadline) to produce a CD. Here’s more from the Rap Guide to Consciousness campaign page on Indiegogo,

Brinkman has been working with neuroscientists, Dr. Anil Seth (professor and co-director of Sackler Centre for Consciousness Science) and Dr. Heather Berlin (Brinkman’s wife as noted earlier; see her Wikipedia entry or her website).

There’s a bit more information about the rap project and Anil Seth in a May 3, 2017 news item by James Hakner for the University of Sussex,

The research frontiers of consciousness science find an unusual outlet in an exciting new Rap Guide to Consciousness, premiering at this year’s Brighton Fringe Festival.

Professor Anil Seth, Co-Director of the Sackler Centre for Consciousness Science at the University of Sussex, has teamed up with New York-based ‘peer-reviewed rapper’ Baba Brinkman, to explore the latest findings from the neuroscience and cognitive psychology of subjective experience.

What is it like to be a baby? We might have to take LSD to find out. What is it like to be an octopus? Imagine most of your brain was actually built into your fingertips. What is it like to be a rapper kicking some of the world’s most complex lyrics for amused fringe audiences? Surreal.

In this new production, Baba brings his signature mix of rap comedy storytelling to the how and why behind your thoughts and perceptions. Mixing cutting-edge research with lyrical performance and projected visuals, Baba takes you through the twists and turns of the only organ it’s better to donate than receive: the human brain. Discover how the various subsystems of your brain come together to create your own rich experience of the world, including the sights and sounds of a scientifically peer-reviewed rapper dropping knowledge.

The result is a truly mind-blowing multimedia hip-hop theatre performance – the perfect meta-medium through which to communicate the dazzling science of consciousness.

Baba comments: “This topic is endlessly fascinating because it underlies everything we do pretty much all the time, which is probably why it remains one of the toughest ideas to get your head around. The first challenge with this show is just to get people to accept the (scientifically uncontroversial) idea that their brains and minds are actually the same thing viewed from different angles. But that’s just the starting point, after that the details get truly amazing.”

Baba Brinkman is a Canadian rap artist and award-winning playwright, best known for his “Rap Guide” series of plays and albums. Baba has toured the world and enjoyed successful runs at the Edinburgh Fringe Festival and off-Broadway in New York. The Rap Guide to Religion was nominated for a 2015 Drama Desk Award for “Unique Theatrical Experience” and The Rap Guide to Evolution (“Astonishing and brilliant” NY Times), won a Scotsman Fringe First Award and a Drama Desk Award nomination for “Outstanding Solo Performance”. The Rap Guide to Climate Chaos premiered in Edinburgh in 2015, followed by a six-month off-Broadway run in 2016.

Baba is also a pioneer in the genre of “lit-hop” or literary hip-hop, known for his adaptations of The Canterbury Tales, Beowulf, and Gilgamesh. He is a recent recipient of the National Center for Science Education’s “Friend of Darwin Award” for his efforts to improve the public understanding of evolutionary biology.

Anil Seth is an internationally renowned researcher into the biological basis of consciousness, with more than 100 (peer-reviewed!) academic journal papers on the subject. Alongside science he is equally committed to innovative public communication. A Wellcome Trust Engagement Fellow (from 2016) and the 2017 British Science Association President (Psychology), Professor Seth has co-conceived and consulted on many science-art projects including drama (Donmar Warehouse), dance (Siobhan Davies dance company), and the visual arts (with artist Lindsay Seers). He has also given popular public talks on consciousness at the Royal Institution (Friday Discourse) and at the main TED conference in Vancouver. He is a regular presence in print and on the radio and is the recipient of awards including the BBC Audio Award for Best Single Drama (for ‘The Sky is Wider’) and the Royal Society Young People’s Book Prize (for EyeBenders). This is his first venture into rap.

Professor Seth said: “There is nothing more familiar, and at the same time more mysterious than consciousness, but research is finally starting to shed light on this most central aspect of human existence. Modern neuroscience can be incredibly arcane and complex, posing challenges to us as public communicators.

“It’s been a real pleasure and privilege to work with Baba on this project over the last year. I never thought I’d get involved with a rap artist – but hearing Baba perform his ‘peer reviewed’ breakdowns of other scientific topics I realized here was an opportunity not to be missed.”

Interestingly, Seth has another Canadian connection; he’s a Senior Fellow of the Azrieli Program in Brain, Mind & Consciousness at the Canadian Institute for Advanced Research (CIFAR; Wikipedia entry). By the way, the institute  was promised $93.7M in the 2017 Canadian federal government budget for the establishment of a Pan-Canadian Artificial Intelligence Strategy (see my March 24, 2017 posting; scroll down about 25% of the way and look for the highlighted dollar amount). You can find out more about the Azrieli programme here and about CIFAR on its website.

The Hard Problem (a Tom Stoppard play)

Brinkman isn’t the only performance-based artist to be querying the concept of consciousness, Tom Stoppard has written a play about consciousness titled ‘The Hard Problem’, which debuted at the National Theatre (UK) in January 2015 (see BBC [British Broadcasting Corporation] news online’s Jan. 29, 2015 roundup of reviews). A May 25, 2017 commentary by Andrew Brown for the Guardian offers some insight into the play and the issues (Note: Links have been removed),

There is a lovely exchange in Tom Stoppard’s play about consciousness, The Hard Problem, when an atheist has been sneering at his girlfriend for praying. It is, he says, an utterly meaningless activity. Right, she says, then do one thing for me: pray! I can’t do that, he replies. It would betray all I believe in.

So prayer can have meanings, and enormously important ones, even for people who are certain that it doesn’t have the meaning it is meant to have. In that sense, your really convinced atheist is much more religious than someone who goes along with all the prayers just because that’s what everyone does, without for a moment supposing the action means anything more than asking about the weather.

The Hard Problem of the play’s title is a phrase coined by the Australian philosopher David Chalmers to describe the way in which consciousness arises from a physical world. What makes it hard is that we don’t understand it. What makes it a problem is slightly different. It isn’t the fact of consciousness, but our representations of consciousness, that give rise to most of the difficulties. We don’t know how to fit the first-person perspective into the third-person world that science describes and explores. But this isn’t because they don’t fit: it’s because we don’t understand how they fit. For some people, this becomes a question of consuming interest.

There are also a couple of video of Tom Stoppard, the playwright, discussing his play with various interested parties, the first being the director at the National Theatre who tackled the debut run, Nicolas Hytner: https://www.youtube.com/watch?v=s7J8rWu6HJg (it runs approximately 40 mins.). Then, there’s the chat Stoppard has with previously mentioned philosopher, David Chalmers: https://www.youtube.com/watch?v=4BPY2c_CiwA (this runs approximately 1 hr. 32 mins.).

I gather ‘consciousness’ is a hot topic these days and, in the venacular of the 1960s, I guess you could describe all of this as ‘expanding our consciousness’. Have a nice weekend!

‘Hunting’ pharmaceuticals and removing them from water

Pharmaceuticals are not the first pollutants people think of when discussing water pollution but, for those who don’t know, it’s a big issue and scientists at the University of Surrey (UK) have developed a technology they believe will help to relieve the contamination. From an April 10, 2017 University of Surrey press release (also on EurekAlert),

The research involves the detection and removal of pharmaceuticals in or from water, as contamination from pharmaceuticals can enter the aquatic environment as a result of their use for the treatment of humans and animals. This contamination can be excreted unchanged, as metabolites, as unused discharge or by drug manufacturers.

The research has found that a new type of ‘supermolecule’, calix[4], actively seeks certain pharmaceuticals and removes them from water.

Contamination of water is a serious concern for environmental scientists around the world, as substances include hormones from the contraceptive pill, and pesticides and herbicides from allotments. Contamination can also include toxic metals such as mercury, arsenic, or cadmium, which was previously used in paint, or substances that endanger vital species such as bees.

Professor Danil de Namor, University of Surrey Emeritus Professor and leader of the research, said: “Preliminary extraction data are encouraging as far as the use of this receptor for the selective removal of these drugs from water and the possibility of constructing a calix[4]-based sensing devices.

“From here, we can design receptors so that they can bind selectively with pollutants in the water so the pollutants can be effectively removed. This research will allow us to know exactly what is in the water, and from here it will be tested in industrial water supplies, so there will be cleaner water for everyone.

“The research also creates the possibility of using these materials for on-site monitoring of water, without having to transport samples to the laboratory.”

Dr Brendan Howlin, University of Surrey co-investigator, said: “This study allows us to visualise the specific receptor-drug interactions leading to the selective behaviour of the receptor. As well as the health benefits of this research, molecular simulation is a powerful technique that is applicable to a wide range of materials.

“We were very proud that the work was carried out with PhD students and a final year project student, and research activities are already taking place with the Department of Chemical and Processing Engineering (CPI) and the Advanced Technology Institute (ATI).

“We are also very pleased to see that as soon as the paper was published online by the European Journal of Pharmaceutical Sciences, we received invitations to give keynote lectures at two international conferences on pharmaceuticals in Europe later this year.”

That last paragraph is intriguing and it marks the first time I’ve seen that claim in a press release announcing the publication of a piece of research.

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

A calix[4]arene derivative and its selective interaction with drugs (clofibric acid, diclofenac and aspirin) by Angela F Danil de Namor, Maan Al Nuaim, Jose A Villanueva Salas, Sophie Bryant, Brendan Howlin. European Journal of Pharmaceutical Sciences Volume 100, 30 March 2017, Pages 1–8 https://doi.org/10.1016/j.ejps.2016.12.027

This paper is behind a paywall.