Category Archives: science

Tiger escapes from an impenetrable cage—carbon atoms show quantum effects

The likelihood of a tiger escaping from a cage using quantum effects is incredibly small. Things seem quite different for carbon. © Fotolia, Bubbers

I’ll get to the tiger reference in a moment, first, here’s a July 12, 2017 news item on Nanowerk announcing the research that inspired the tiger reference (Note A link has been removed),

Chemists at Ruhr-Universität Bochum have found evidence that carbon atoms cannot only behave like particles but also like waves. This quantum-mechanical property is well-known for light particles such as electrons or hydrogen atoms. However, researchers have only rarely observed the wave-particle duality for heavy atoms, such as carbon.

The team led by Prof Dr Wolfram Sander and Tim Schleif from the Chair for Organic Chemistry II together with Prof Dr Weston Thatcher Borden, University of North Texas, reports in the journal Angewandte Chemie (“The Cope rearrangement of 1,5-Dimethylsemibullvalene-2(4)-d1: Experimental evidence for heavy-atom tunneling”).

“Our result is one of few examples showing that carbon atoms can display quantum effects,” says Sander. Specifically, the researchers observed that carbon atoms can tunnel. They thus overcome an energetic barrier, although they do not actually possess enough energy to do that.

A July 12, 2017 Ruhr-Universität Bochum press release (also on EurekAlert), which originated the news item, expands on the theme and makes sense of the tiger analogy,

Wolfram Sander explains the paradox: “It’s as though a tiger has left his cage without jumping over the fence, which is much too high for him. But he still gets out.” This is only possible if he behaves like a wave, but not if he behaves like a particle. The probability of an object being able to tunnel depends on its mass. The phenomenon can, for instance, be observed much more easily for light electrons than for relatively heavy carbon atoms.

The researchers investigated the tunnel reaction using the Cope rearrangement, a chemical reaction that has been known for almost 80 years. The starting material for the reaction, a hydrocarbon compound, is identical to the product molecule. The same chemical compound thus exists before and after the reaction. However, the bonds between the carbon atoms change during the process.

In their experiment, the Bochum-based researchers marked one of the carbon atoms in the molecule: They replaced the hydrogen atom bonded to it with the hydrogen isotope deuterium, a heavier version of hydrogen. Molecules before and after the Cope rearrangement differed in terms of the distribution of the deuterium. Due to these different distributions, both molecular forms had slightly different energies.

Reaction shouldn’t actually take place

At room temperature, this difference has little effect; due to the plentiful supply of thermal energy in the surrounding area, both forms occur equally frequently. However, at very low temperatures under ten Kelvin, one molecule form is significantly preferred due to the energy difference. When transitioning from room temperature to extremely low temperatures, the balance has to move from an equal distribution of both forms to an uneven distribution.

This transition cannot, however, occur in the classic way – since, when rearranging from one form to the other, an energy barrier has to be overcome, although the molecule itself does not have the energy for this and the cold environment is also unable to provide it. Although the new balance should not occur in the classic way, the researchers were nevertheless able to demonstrate it in the experiment. Their conclusion: the Cope rearrangement at extremely low temperatures can only be explained by a tunnel effect. They thus provided experimental evidence for a prediction made by Weston Borden over five years ago based on theoretical studies.

Solvents influence ability to tunnel

At Ruhr-Universität, Wolfram Sander undertakes research in the cluster of excellence Ruhr Explores Solvation, where he concerns himself with the interactions of solvents and dissolved molecules. “It is known that solvents influence the ability to tunnel,” says the chemist. “However, so far it has not been understood how they do that.”

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

The Cope rearrangement of 1,5-Dimethylsemibullvalene-2(4)-d1: Experimental evidence for heavy-atom tunneling by Tim Schleif, Joel Mieres-Perez, Stefan Henkel, Melanie Ertelt, Weston Thatcher Borden, Wolfram Sander. Angewandte Chemie, 2017, DOI: 10.1002/ange.201704787, International Edition: 10.1002/anie.201704787

This paper is behind a paywall.

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

Science for the global citizen course at McMaster University in Winter 2018

It’s never too early to start planning for your course load if a June 20, 2017 McMaster University (Ontario, Canada) news release is to be believed,

In the Winter 2018 term, the School of Interdisciplinary Science is offering Science 2M03: Science for the Global Citizen, a new course designed to explore those questions and more. In this blended-learning course, students from all Faculties will examine the links between science and the larger society through live guest lecturers and evidence-based online discussions.This course is open to students enrolled in Level II or above in any program. No scientific background is needed, only an interest in becoming a more engaged and informed citizen.

The new course will cover a broad range of contemporary scientific issues with significant political, economic, social, and health implications. Topics range from artificial intelligence (AI) to genetically modified organisms (GMOs) to space exploration.

Course instructors, Dr. Kim Dej, Dr. Chad Harvey, Dr. Rosa da Silva, and Dr. Sarah Symons, all from the School of Interdisciplinary Science, will examine the basic scientific theories and concepts behind these topical issues, and highlight the application and interpretation of science in popular media and public policy.

After taking this course, students from all academic backgrounds will have a better understanding of how science is conducted, how knowledge changes, and how we can become better consumers of scientific information and more informed citizens.

3 
 63 
 1 
 68 How can science help address the key challenges in our society? How does society affect the way that science is conducted? Do citizens have a strong enough understanding of science and its methods to answer these and other similar questions? In the Winter 2018 term, the School of Interdisciplinary Science is offering Science 2M03: Science for the Global Citizen, a new course designed to explore those questions and more. In this blended-learning course, students from all Faculties will examine the links between science and the larger society through live guest lecturers and evidence-based online discussions. This course is open to students enrolled in Level II or above in any program. No scientific background is needed, only an interest in becoming a more engaged and informed citizen. The new course will cover a broad range of contemporary scientific issues with significant political, economic, social, and health implications. Topics range from artificial intelligence (AI) to genetically modified organisms (GMOs) to space exploration. Course instructors, Dr. Kim Dej, Dr. Chad Harvey, Dr. Rosa da Silva, and Dr. Sarah Symons, all from the School of Interdisciplinary Science, will examine the basic scientific theories and concepts behind these topical issues, and highlight the application and interpretation of science in popular media and public policy. After taking this course, students from all academic backgrounds will have a better understanding of how science is conducted, how knowledge changes, and how we can become better consumers of scientific information and more informed citizens.

I’m glad to see this kind of course being offered. It does seem a bit odd that none of the instructors involved with this course appear to be from the social sciences or humanities. Drs. Dej, Harvey, and da Silva all have a background in biological sciences and Dr. Symons is a physicist. Taking another look at this line from the course description, “The new course will cover a broad range of contemporary scientific issues with significant political, economic, social, and health implications,” has me wondering how these scientists are going to cover the material, especially as I couldn’t find any papers on these topics written by any of these instructors. This section puzzles me even more, “… highlight the application and interpretation of science in popular media and public policy.” Again none of these instructors seem to have published on the topic of science in popular media or science public policy.

Guest speakers can help to fill in the blanks but with four instructors (and I would imagine a tight budget) it’s hard to believe there are going to be that many guests.

I appreciate that this is more of what they used to call a ‘survey course’ meant to introduce a number of ideas rather than conveying any in depth information but I do find the instructors’ apparent lack of theoretical knowledge about anything other than their respective fields of science somewhat disconcerting.

Regardless, I wish both the instructors and the students all the best.

Upending the textbooks on Van Der Waals interactions

It’s always exciting when textbook information has to be changed due to a discovery; it’s also a reminder that science is constantly changing. From a June 29, 2017 news item on Nanowerk (Note: A link has been removed),

Van der Waals interactions between molecules are among the most important forces in biology, physics, and chemistry, as they determine the properties and physical behavior of many materials. For a long time, it was considered that these interactions between molecules are always attractive. Now, for the first time, Mainak Sadhukhan and Alexandre Tkatchenko from the Physics and Materials Science Research Unit at the University of Luxembourg found that in many rather common situations in nature the van der Waals force between two molecules becomes repulsive. This might lead to a paradigm shift in molecular interactions.

“The textbooks so far assumed that the forces are solely attractive. For us, the interesting question is whether you can also make them repulsive,” Prof Tkatchenko explains. “Until recently, there was no evidence in scientific literature that van der Waals forces could also be repelling.”

Now, the researchers have shown in their paper, published in Physical Review Letters (“Long-Range Repulsion Between Spatially Confined van der Waals Dimers”), that the forces are, in fact, repulsive when they take place under confinement.

A June 30, 2017 Université de Luxembourg press release, which originated the news item, expands on the theme,

The ubiquitous van der Waals force was first explained by the German-American physicist Fritz London in 1930. Using quantum mechanics, he proved the purely attractive nature of the van der Waals force for any two molecules interacting in free space. “However, in nature molecules in most cases interact in confined spaces, such as cells, membranes, nanotubes, etc. In is this particular situation, van der Waals forces become repulsive at large distances between molecules,” says Prof. Tkatchenko.

Mainak Sadhukhan, the co-author of the study, developed a novel quantum-mechanical method that enabled them to model van der Waals forces in confinement. “We could rationalise many previous experimental results that remained unexplained until now. Our new theory allows, for the first time, for an interpretation of many interesting phenomena observed for molecules under confinement,” Mainak Sadhukhan says.

The discovery could have many potential implications for the delivery of pharmaceutical molecules in cells, water desalination and transport, and self-assembly of molecular layers in photovoltaic devices.

Prof. Tkatchenko’s research group is working on methods that model the properties of a wide range of intermolecular interactions. Only in 2016, they found that the true nature of these van der Waals forces differs from conventional wisdom in chemistry and biology, as they have to be treated as coupling between waves rather than as mutual attraction (or repulsion) between particles.

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

Long-Range Repulsion Between Spatially Confined van der Waals Dimers by Mainak Sadhukhan and Alexandre Tkatchenko. Phys. Rev. Lett. 118, 210402 (Vol. 118, Iss. 21 — 26 May 2017) DOI:https://doi.org/10.1103/PhysRevLett.118.210402 Published 25 May 2017

This paper is behind a paywall.

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!

Refining metals more sustainably

We don’t just extract and refine metals from the earth, increasingly, we extract and refine them from consumer goods. Researchers from McGill University (Montréal, Québec, Canada) have devised a ‘greener’ technique to do this. From a June 7, 2017 McGill University news release (received via email and also on EurekAlert),

A team of chemists in Canada has developed a way to process metals without using toxic solvents and reagents.

The system, which also consumes far less energy than conventional techniques, could greatly shrink the environmental impact of producing metals from raw materials or from post-consumer electronics.

“At a time when natural deposits of metals are on the decline, there is a great deal of interest in improving the efficiency of metal refinement and recycling, but few disruptive technologies are being put forth,” says Jean-Philip Lumb, an associate professor in McGill University’s Department of Chemistry. “That’s what makes our advance so important.”

The discovery stems from a collaboration between Lumb and Tomislav Friscic at McGill in Montreal, and Kim Baines of Western University in London, Ont. In an article published recently in Science Advances, the researchers outline an approach that uses organic molecules, instead of chlorine and hydrochloric acid, to help purify germanium, a metal used widely in electronic devices. Laboratory experiments by the researchers have shown that the same technique can be used with other metals, including zinc, copper, manganese and cobalt.

The research could mark an important milestone for the “green chemistry” movement, which seeks to replace toxic reagents used in conventional industrial manufacturing with more environmentally friendly alternatives. Most advances in this area have involved organic chemistry – the synthesis of carbon-based compounds used in pharmaceuticals and plastics, for example.

“Applications of green chemistry lag far behind in the area of metals,” Lumb says. “Yet metals are just as important for sustainability as any organic compound. For example, electronic devices require numerous metals to function.”

Taking a page from biology

There is no single ore rich in germanium, so it is generally obtained from mining operations as a minor component in a mixture with many other materials. Through a series of processes, that blend of matter can be reduced to germanium and zinc.

“Currently, in order to isolate germanium from zinc, it’s a pretty nasty process,” Baines explains. The new approach developed by the McGill and Western chemists “enables you to get germanium from zinc, without those nasty processes.”

To accomplish this, the researchers took a page from biology. Lumb’s lab for years has conducted research into the chemistry of melanin, the molecule in human tissue that gives skin and hair their color. Melanin also has the ability to bind to metals. “We asked the question: ‘Here’s this biomaterial with exquisite function, would it be possible to use it as a blueprint for new, more efficient technologies?'”

The scientists teamed up to synthesize a molecule that mimics some of the qualities of melanin. In particular, this “organic co-factor” acts as a mediator that helps to extract germanium at room temperature, without using solvents.

Next step: industrial scale

The system also taps into Friscic’s expertise in mechanochemistry, an emerging branch of chemistry that relies on mechanical force – rather than solvents and heat – to promote chemical reactions. Milling jars containing stainless-steel balls are shaken at high speeds to help purify the metal.

“This shows how collaborations naturally can lead to sustainability-oriented innovation,” Friscic says. “Combining elegant new chemistry with solvent-free mechanochemical techniques led us to a process that is cleaner by virtue of circumventing chlorine-based processing, but also eliminates the generation of toxic solvent waste”

The next step in developing the technology will be to show that it can be deployed economically on industrial scales, for a range of metals.

“There’s a tremendous amount of work that needs to be done to get from where we are now to where we need to go,” Lumb says. “But the platform works on many different kinds of metals and metal oxides, and we think that it could become a technology adopted by industry. We are looking for stakeholders with whom we can partner to move this technology forward.”

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

A chlorine-free protocol for processing germanium by Martin Glavinovic, Michael Krause, Linju Yang, John A. McLeod, Lijia Liu, Kim M. Baines, Tomislav Friščić, and Jean-Philip Lumb. Science Advances 05 May 2017: Vol. 3, no. 5, e1700149 DOI: 10.1126/sciadv.1700149

This paper is open access.

ETA June 9, 2017 at 1700 hours PDT: I have to give them marks for creativity. Here’s the image being used to illustrate the work,

Caption: Strategy for reducing the environmental impact of a refining process: replace hazardous chemicals with more benign and recyclable compounds. Credit: Michael J. Krause (Western University)