Tag Archives: deoxyribonucleic acid (DNA)

Technical University of Munich: embedded ethics approach for AI (artificial intelligence) and storing a tv series in synthetic DNA

I stumbled across two news bits of interest from the Technical University of Munich in one day (Sept. 1, 2020, I think). The topics: artificial intelligence (AI) and synthetic DNA (deoxyribonucleic acid).

Embedded ethics and artificial intelligence (AI)

An August 27, 2020 Technical University of Munich (TUM) press release (also on EurekAlert but published Sept. 1, 2020) features information about a proposal to embed ethicists in with AI development teams,

The increasing use of AI (artificial intelligence) in the development of new medical technologies demands greater attention to ethical aspects. An interdisciplinary team at the Technical University of Munich (TUM) advocates the integration of ethics from the very beginning of the development process of new technologies. Alena Buyx, Professor of Ethics in Medicine and Health Technologies, explains the embedded ethics approach.

Professor Buyx, the discussions surrounding a greater emphasis on ethics in AI research have greatly intensified in recent years, to the point where one might speak of “ethics hype” …

Prof. Buyx: … and many committees in Germany and around the world such as the German Ethics Council or the EU Commission High-Level Expert Group on Artificial Intelligence have responded. They are all in agreement: We need more ethics in the development of AI-based health technologies. But how do things look in practice for engineers and designers? Concrete solutions are still few and far between. In a joint pilot project with two Integrative Research Centers at TUM, the Munich School of Robotics and Machine Intelligence (MSRM) with its director, Prof. Sami Haddadin, and the Munich Center for Technology in Society (MCTS), with Prof. Ruth Müller, we want to try out the embedded ethics approach. We published the proposal in Nature Machine Intelligence at the end of July [2020].

What exactly is meant by the “embedded ethics approach”?

Prof.Buyx: The idea is to make ethics an integral part of the research process by integrating ethicists into the AI development team from day one. For example, they attend team meetings on a regular basis and create a sort of “ethical awareness” for certain issues. They also raise and analyze specific ethical and social issues.

Is there an example of this concept in practice?

Prof. Buyx: The Geriatronics Research Center, a flagship project of the MSRM in Garmisch-Partenkirchen, is developing robot assistants to enable people to live independently in old age. The center’s initiatives will include the construction of model apartments designed to try out residential concepts where seniors share their living space with robots. At a joint meeting with the participating engineers, it was noted that the idea of using an open concept layout everywhere in the units – with few doors or individual rooms – would give the robots considerable range of motion. With the seniors, however, this living concept could prove upsetting because they are used to having private spaces. At the outset, the engineers had not given explicit consideration to this aspect.

Prof.Buyx: The approach sounds promising. But how can we avoid “embedded ethics” from turning into an “ethics washing” exercise, offering companies a comforting sense of “being on the safe side” when developing new AI technologies?

That’s not something we can be certain of avoiding. The key is mutual openness and a willingness to listen, with the goal of finding a common language – and subsequently being prepared to effectively implement the ethical aspects. At TUM we are ideally positioned to achieve this. Prof. Sami Haddadin, the director of the MSRM, is also a member of the EU High-Level Group of Artificial Intelligence. In his research, he is guided by the concept of human centered engineering. Consequently, he has supported the idea of embedded ethics from the very beginning. But one thing is certain: Embedded ethics alone will not suddenly make AI “turn ethical”. Ultimately, that will require laws, codes of conduct and possibly state incentives.

Here’s a link to and a citation for the paper espousing the embedded ethics for AI development approach,

An embedded ethics approach for AI development by Stuart McLennan, Amelia Fiske, Leo Anthony Celi, Ruth Müller, Jan Harder, Konstantin Ritt, Sami Haddadin & Alena Buyx. Nature Machine Intelligence (2020) DOI: https://doi.org/10.1038/s42256-020-0214-1 Published 31 July 2020

This paper is behind a paywall.

Religion, ethics and and AI

For some reason embedded ethics and AI got me to thinking about Pope Francis and other religious leaders.

The Roman Catholic Church and AI

There was a recent announcement that the Roman Catholic Church will be working with MicroSoft and IBM on AI and ethics (from a February 28, 2020 article by Jen Copestake for British Broadcasting Corporation (BBC) news online (Note: A link has been removed),

Leaders from the two tech giants met senior church officials in Rome, and agreed to collaborate on “human-centred” ways of designing AI.

Microsoft president Brad Smith admitted some people may “think of us as strange bedfellows” at the signing event.

“But I think the world needs people from different places to come together,” he said.

The call was supported by Pope Francis, in his first detailed remarks about the impact of artificial intelligence on humanity.

The Rome Call for Ethics [sic] was co-signed by Mr Smith, IBM executive vice-president John Kelly and president of the Pontifical Academy for Life Archbishop Vincenzo Paglia.

It puts humans at the centre of new technologies, asking for AI to be designed with a focus on the good of the environment and “our common and shared home and of its human inhabitants”.

Framing the current era as a “renAIssance”, the speakers said the invention of artificial intelligence would be as significant to human development as the invention of the printing press or combustion engine.

UN Food and Agricultural Organization director Qu Dongyu and Italy’s technology minister Paola Pisano were also co-signatories.

Hannah Brockhaus’s February 28, 2020 article for the Catholic News Agency provides some details missing from the BBC report and I found it quite helpful when trying to understand the various pieces that make up this initiative,

The Pontifical Academy for Life signed Friday [February 28, 2020], alongside presidents of IBM and Microsoft, a call for ethical and responsible use of artificial intelligence technologies.

According to the document, “the sponsors of the call express their desire to work together, in this context and at a national and international level, to promote ‘algor-ethics.’”

“Algor-ethics,” according to the text, is the ethical use of artificial intelligence according to the principles of transparency, inclusion, responsibility, impartiality, reliability, security, and privacy.

The signing of the “Rome Call for AI Ethics [PDF]” took place as part of the 2020 assembly of the Pontifical Academy for Life, which was held Feb. 26-28 [2020] on the theme of artificial intelligence.

One part of the assembly was dedicated to private meetings of the academics of the Pontifical Academy for Life. The second was a workshop on AI and ethics that drew 356 participants from 41 countries.

On the morning of Feb. 28 [2020], a public event took place called “renAIssance. For a Humanistic Artificial Intelligence” and included the signing of the AI document by Microsoft President Brad Smith, and IBM Executive Vice-president John Kelly III.

The Director General of FAO, Dongyu Qu, and politician Paola Pisano, representing the Italian government, also signed.

The president of the European Parliament, David Sassoli, was also present Feb. 28.

Pope Francis canceled his scheduled appearance at the event due to feeling unwell. His prepared remarks were read by Archbishop Vincenzo Paglia, president of the Academy for Life.

You can find Pope Francis’s comments about the document here (if you’re not comfortable reading Italian, hopefully, the English translation which follows directly afterward will be helpful). The Pope’s AI initiative has a dedicated website, Rome Call for AI ethics, and while most of the material dates from the February 2020 announcement, they are keeping up a blog. It has two entries, one dated in May 2020 and another in September 2020.

Buddhism and AI

The Dalai Lama is well known for having an interest in science and having hosted scientists for various dialogues. So, I was able to track down a November 10, 2016 article by Ariel Conn for the futureoflife.org website, which features his insights on the matter,

The question of what it means and what it takes to feel needed is an important problem for ethicists and philosophers, but it may be just as important for AI researchers to consider. The Dalai Lama argues that lack of meaning and purpose in one’s work increases frustration and dissatisfaction among even those who are gainfully employed.

“The problem,” says the Dalai Lama, “is … the growing number of people who feel they are no longer useful, no longer needed, no longer one with their societies. … Feeling superfluous is a blow to the human spirit. It leads to social isolation and emotional pain, and creates the conditions for negative emotions to take root.”

If feeling needed and feeling useful are necessary for happiness, then AI researchers may face a conundrum. Many researchers hope that job loss due to artificial intelligence and automation could, in the end, provide people with more leisure time to pursue enjoyable activities. But if the key to happiness is feeling useful and needed, then a society without work could be just as emotionally challenging as today’s career-based societies, and possibly worse.

I also found a talk on the topic by The Venerable Tenzin Priyadarshi, first here’s a description from his bio at the Dalai Lama Center for Ethics and Transformative Values webspace on the Massachusetts Institute of Technology (MIT) website,

… an innovative thinker, philosopher, educator and a polymath monk. He is Director of the Ethics Initiative at the MIT Media Lab and President & CEO of The Dalai Lama Center for Ethics and Transformative Values at the Massachusetts Institute of Technology. Venerable Tenzin’s unusual background encompasses entering a Buddhist monastery at the age of ten and receiving graduate education at Harvard University with degrees ranging from Philosophy to Physics to International Relations. He is a Tribeca Disruptive Fellow and a Fellow at the Center for Advanced Study in Behavioral Sciences at Stanford University. Venerable Tenzin serves on the boards of a number of academic, humanitarian, and religious organizations. He is the recipient of several recognitions and awards and received Harvard’s Distinguished Alumni Honors for his visionary contributions to humanity.

He gave the 2018 Roger W. Heyns Lecture in Religion and Society at Stanford University on the topic, “Religious and Ethical Dimensions of Artificial Intelligence.” The video runs over one hour but he is a sprightly speaker (in comparison to other Buddhist speakers I’ve listened to over the years).

Judaism, Islam, and other Abrahamic faiths examine AI and ethics

I was delighted to find this January 30, 2020 Artificial Intelligence: Implications for Ethics and Religion event as it brought together a range of thinkers from various faiths and disciplines,

New technologies are transforming our world every day, and the pace of change is only accelerating.  In coming years, human beings will create machines capable of out-thinking us and potentially taking on such uniquely-human traits as empathy, ethical reasoning, perhaps even consciousness.  This will have profound implications for virtually every human activity, as well as the meaning we impart to life and creation themselves.  This conference will provide an introduction for non-specialists to Artificial Intelligence (AI):

What is it?  What can it do and be used for?  And what will be its implications for choice and free will; economics and worklife; surveillance economies and surveillance states; the changing nature of facts and truth; and the comparative intelligence and capabilities of humans and machines in the future? 

Leading practitioners, ethicists and theologians will provide cross-disciplinary and cross-denominational perspectives on such challenges as technology addiction, inherent biases and resulting inequalities, the ethics of creating destructive technologies and of turning decision-making over to machines from self-driving cars to “autonomous weapons” systems in warfare, and how we should treat the suffering of “feeling” machines.  The conference ultimately will address how we think about our place in the universe and what this means for both religious thought and theological institutions themselves.

UTS [Union Theological Seminary] is the oldest independent seminary in the United States and has long been known as a bastion of progressive Christian scholarship.  JTS [Jewish Theological Seminary] is one of the academic and spiritual centers of Conservative Judaism and a major center for academic scholarship in Jewish studies. The Riverside Church is an interdenominational, interracial, international, open, welcoming, and affirming church and congregation that has served as a focal point of global and national activism for peace and social justice since its inception and continues to serve God through word and public witness. The annual Greater Good Gathering, the following week at Columbia University’s School of International & Public Affairs, focuses on how technology is changing society, politics and the economy – part of a growing nationwide effort to advance conversations promoting the “greater good.”

They have embedded a video of the event (it runs a little over seven hours) on the January 30, 2020 Artificial Intelligence: Implications for Ethics and Religion event page. For anyone who finds that a daunting amount of information, you may want to check out the speaker list for ideas about who might be writing and thinking on this topic.

As for Islam, I did track down this November 29, 2018 article by Shahino Mah Abdullah, a fellow at the Institute of Advanced Islamic Studies (IAIS) Malaysia,

As the global community continues to work together on the ethics of AI, there are still vast opportunities to offer ethical inputs, including the ethical principles based on Islamic teachings.

This is in line with Islam’s encouragement for its believers to convey beneficial messages, including to share its ethical principles with society.

In Islam, ethics or akhlak (virtuous character traits) in Arabic, is sometimes employed interchangeably in the Arabic language with adab, which means the manner, attitude, behaviour, and etiquette of putting things in their proper places. Islamic ethics cover all the legal concepts ranging from syariah (Islamic law), fiqh ( jurisprudence), qanun (ordinance), and ‘urf (customary practices).

Adopting and applying moral values based on the Islamic ethical concept or applied Islamic ethics could be a way to address various issues in today’s societies.

At the same time, this approach is in line with the higher objectives of syariah (maqasid alsyariah) that is aimed at conserving human benefit by the protection of human values, including faith (hifz al-din), life (hifz alnafs), lineage (hifz al-nasl), intellect (hifz al-‘aql), and property (hifz al-mal). This approach could be very helpful to address contemporary issues, including those related to the rise of AI and intelligent robots.


Part of the difficulty with tracking down more about AI, ethics, and various religions is linguistic. I simply don’t have the language skills to search for the commentaries and, even in English, I may not have the best or most appropriate search terms.

Television (TV) episodes stored on DNA?

According to a Sept. 1, 2020 news item on Nanowerk, the first episode of a tv series, ‘Biohackers’ has been stored on synthetic DNA (deoxyribonucleic acid) by a researcher at TUM and colleagues at another institution,

The first episode of the newly released series “Biohackers” was stored in the form of synthetic DNA. This was made possible by the research of Prof. Reinhard Heckel of the Technical University of Munich (TUM) and his colleague Prof. Robert Grass of ETH Zürich.

They have developed a method that permits the stable storage of large quantities of data on DNA for over 1000 years.

A Sept. 1, 2020 TUM press release, which originated the news item, proceeds with more detail in an interview format,

Prof. Heckel, Biohackers is about a medical student seeking revenge on a professor with a dark past – and the manipulation of DNA with biotechnology tools. You were commissioned to store the series on DNA. How does that work?

First, I should mention that what we’re talking about is artificially generated – in other words, synthetic – DNA. DNA consists of four building blocks: the nucleotides adenine (A), thymine (T), guanine (G) and cytosine (C). Computer data, meanwhile, are coded as zeros and ones. The first episode of Biohackers consists of a sequence of around 600 million zeros and ones. To code the sequence 01 01 11 00 in DNA, for example, we decide which number combinations will correspond to which letters. For example: 00 is A, 01 is C, 10 is G and 11 is T. Our example then produces the DNA sequence CCTA. Using this principle of DNA data storage, we have stored the first episode of the series on DNA.

And to view the series – is it just a matter of “reverse translation” of the letters?

In a very simplified sense, you can visualize it like that. When writing, storing and reading the DNA, however, errors occur. If these errors are not corrected, the data stored on the DNA will be lost. To solve the problem, I have developed an algorithm based on channel coding. This method involves correcting errors that take place during information transfers. The underlying idea is to add redundancy to the data. Think of language: When we read or hear a word with missing or incorrect letters, the computing power of our brain is still capable of understanding the word. The algorithm follows the same principle: It encodes the data with sufficient redundancy to ensure that even highly inaccurate data can be restored later.

Channel coding is used in many fields, including in telecommunications. What challenges did you face when developing your solution?

The first challenge was to create an algorithm specifically geared to the errors that occur in DNA. The second one was to make the algorithm so efficient that the largest possible quantities of data can be stored on the smallest possible quantity of DNA, so that only the absolutely necessary amount of redundancy is added. We demonstrated that our algorithm is optimized in that sense.

DNA data storage is very expensive because of the complexity of DNA production as well as the reading process. What makes DNA an attractive storage medium despite these challenges?

First, DNA has a very high information density. This permits the storage of enormous data volumes in a minimal space. In the case of the TV series, we stored “only” 100 megabytes on a picogram – or a billionth of a gram of DNA. Theoretically, however, it would be possible to store up to 200 exabytes on one gram of DNA. And DNA lasts a long time. By comparison: If you never turned on your PC or wrote data to the hard disk it contains, the data would disappear after a couple of years. By contrast, DNA can remain stable for many thousands of years if it is packed right.

And the method you have developed also makes the DNA strands durable – practically indestructible.

My colleague Robert Grass was the first to develop a process for the “stable packing” of DNA strands by encapsulating them in nanometer-scale spheres made of silica glass. This ensures that the DNA is protected against mechanical influences. In a joint paper in 2015, we presented the first robust DNA data storage concept with our algorithm and the encapsulation process developed by Prof. Grass. Since then we have continuously improved our method. In our most recent publication in Nature Protocols of January 2020, we passed on what we have learned.

What are your next steps? Does data storage on DNA have a future?

We’re working on a way to make DNA data storage cheaper and faster. “Biohackers” was a milestone en route to commercialization. But we still have a long way to go. If this technology proves successful, big things will be possible. Entire libraries, all movies, photos, music and knowledge of every kind – provided it can be represented in the form of data – could be stored on DNA and would thus be available to humanity for eternity.

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

Reading and writing digital data in DNA by Linda C. Meiser, Philipp L. Antkowiak, Julian Koch, Weida D. Chen, A. Xavier Kohll, Wendelin J. Stark, Reinhard Heckel & Robert N. Grass. Nature Protocols volume 15, pages86–101(2020) Issue Date: January 2020 DOI: https://doi.org/10.1038/s41596-019-0244-5 Published [online] 29 November 2019

This paper is behind a paywall.

As for ‘Biohackers’, it’s a German science fiction television series and you can find out more about it here on the Internet Movie Database.

Congratulations to winners of 2020 Nobel Prize for Chemistry: Dr. Emmanuelle Charpentier & Dr. Jennifer A. Doudna (CRISPR-cas9)

It’s possible there’s a more dramatic development in the field of contemporary gene-editing but it’s indisputable that CRISPR (clustered regularly interspaced short palindromic repeats) -cas9 (CRISPR-associated 9 [protein]) ranks very highly indeed.

The technique, first discovered (or developed) in 2012, has brought recognition in the form of the 2020 Nobel Prize for Chemistry to CRISPR’s two discoverers, Emanuelle Charpentier and Jennifer Doudna.

An October 7, 2020 news item on phys.org announces the news,

The Nobel Prize in chemistry went to two researchers Wednesday [October 7, 2020] for a gene-editing tool that has revolutionized science by providing a way to alter DNA, the code of life—technology already being used to try to cure a host of diseases and raise better crops and livestock.

Emmanuelle Charpentier of France and Jennifer A. Doudna of the United States won for developing CRISPR-cas9, a very simple technique for cutting a gene at a specific spot, allowing scientists to operate on flaws that are the root cause of many diseases.

“There is enormous power in this genetic tool,” said Claes Gustafsson, chair of the Nobel Committee for Chemistry.

More than 100 clinical trials are underway to study using CRISPR to treat diseases, and “many are very promising,” according to Victor Dzau, president of the [US] National Academy of Medicine.

“My greatest hope is that it’s used for good, to uncover new mysteries in biology and to benefit humankind,” said Doudna, who is affiliated with the University of California, Berkeley, and is paid by the Howard Hughes Medical Institute, which also supports The Associated Press’ Health and Science Department.

The prize-winning work has opened the door to some thorny ethical issues: When editing is done after birth, the alterations are confined to that person. Scientists fear CRISPR will be misused to make “designer babies” by altering eggs, embryos or sperm—changes that can be passed on to future generations.

Unusually for phys.org, this October 7, 2020 news item is not a simple press/news release reproduced in its entirety but a good overview of the researchers’ accomplishments and a discussion of some of the issues associated with CRISPR along with the press release at the end.

I have covered some CRISPR issues here including intellectual property (see my March 15, 2017 posting titled, “CRISPR patent decision: Harvard’s and MIT’s Broad Institute victorious—for now‘) and designer babies (as exemplified by the situation with Dr. He Jiankui; see my July 28, 2020 post titled, “July 2020 update on Dr. He Jiankui (the CRISPR twins) situation” for more details about it).

An October 7, 2020 article by Michael Grothaus for Fast Company provides a business perspective (Note: A link has been removed),

Needless to say, research by the two scientists awarded the Nobel Prize in Chemistry today has the potential to change the course of humanity. And with that potential comes lots of VC money and companies vying for patents on techniques and therapies derived from Charpentier’s and Doudna’s research.

One such company is Doudna’s Editas Medicine [according to my search, the only company associated with Doudna is Mammoth Biosciences, which she co-founded], while others include Caribou Biosciences, Intellia Therapeutics, and Casebia Therapeutics. Given the world-changing applications—and the amount of revenue such CRISPR therapies could bring in—it’s no wonder that such rivalry is often heated (and in some cases has led to lawsuits over the technology and its patents).

As Doudna explained in her book, A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution, cowritten by Samuel H. Sternberg …, “… —but we could also have woolly mammoths, winged lizards, and unicorns.” And as for that last part, she made clear, “No, I am not kidding.”

Everybody makes mistakes and the reference to Editas Medicine is the only error I spotted. You can find out more about Mammoth Biosciences here and while Dr. Doudna’s comment, “My greatest hope is that it’s used for good, to uncover new mysteries in biology and to benefit humankind,” is laudable it would seem she wishes to profit from the discovery. Mammoth Biosciences is a for-profit company as can be seen at the end of the Mammoth Biosciences’ October 7, 2020 congratulatory news release,

About Mammoth Biosciences

Mammoth Biosciences is harnessing the diversity of nature to power the next-generation of CRISPR products. Through the discovery and development of novel CRISPR systems, the company is enabling the full potential of its platform to read and write the code of life. By leveraging its internal research and development and exclusive licensing to patents related to Cas12, Cas13, Cas14 and Casɸ, Mammoth Biosciences can provide enhanced diagnostics and genome editing for life science research, healthcare, agriculture, biodefense and more. Based in San Francisco, Mammoth Biosciences is co-founded by CRISPR pioneer Jennifer Doudna and Trevor Martin, Janice Chen, and Lucas Harrington. The firm is backed by top institutional investors [emphasis mine] including Decheng, Mayfield, NFX, and 8VC, and leading individual investors including Brook Byers, Tim Cook, and Jeff Huber.

An October 7, 2029 Nobel Prize press release, which unleashed all this interest in Doudna and Charpentier, notes this,

Prize amount: 10 million Swedish kronor, to be shared equally between the Laureates.

In Canadian money that amount is $1,492,115.03 (as of Oct. 9, 2020 12:40 PDT when I checked a currency converter).

Ordinarily there’d be a mildly caustic comment from me about business opportunities and medical research but this is a time for congratulations to both Dr. Emanuelle Charpentier and Dr. Jennifer Doudna.

Repairing brain circuits using nanotechnology

A July 30, 2019 news item on Nanowerk announces some neuroscience research (they used animal models) that could prove helpful with neurodegenerative diseases,

Working with mouse and human tissue, Johns Hopkins Medicine researchers report new evidence that a protein pumped out of some — but not all — populations of “helper” cells in the brain, called astrocytes, plays a specific role in directing the formation of connections among neurons needed for learning and forming new memories.

Using mice genetically engineered and bred with fewer such connections, the researchers conducted proof-of-concept experiments that show they could deliver corrective proteins via nanoparticles to replace the missing protein needed for “road repairs” on the defective neural highway.

Since such connective networks are lost or damaged by neurodegenerative diseases such as Alzheimer’s or certain types of intellectual disability, such as Norrie disease, the researchers say their findings advance efforts to regrow and repair the networks and potentially restore normal brain function.

A July 30, 2019 Johns Hopkins University School of Medicine news release (also on EurekAlert) provides more detail about the work (Note: A link has been removed),

“We are looking at the fundamental biology of how astrocytes function, but perhaps have discovered a new target for someday intervening in neurodegenerative diseases with novel therapeutics,” says Jeffrey Rothstein, M.D., Ph.D., the John W. Griffin Director of the Brain Science Institute and professor of neurology at the Johns Hopkins University School of Medicine.

“Although astrocytes appear to all look alike in the brain, we had an inkling that they might have specialized roles in the brain due to regional differences in the brain’s function and because of observed changes in certain diseases,” says Rothstein. “The hope is that learning to harness the individual differences in these distinct populations of astrocytes may allow us to direct brain development or even reverse the effects of certain brain conditions, and our current studies have advanced that hope.”

In the brain, astrocytes are the support cells that act as guides to direct new cells, promote chemical signaling, and clean up byproducts of brain cell metabolism.

Rothstein’s team focused on a particular astrocyte protein, glutamate transporter-1, which previous studies suggested was lost from astrocytes in certain parts of brains with neurodegenerative diseases. Like a biological vacuum cleaner, the protein normally sucks up the chemical “messenger” glutamate from the spaces between neurons after a message is sent to another cell, a step required to end the transmission and prevent toxic levels of glutamate from building up.

When these glutamate transporters disappear from certain parts of the brain — such as the motor cortex and spinal cord in people with amyotrophic lateral sclerosis (ALS) — glutamate hangs around much too long, sending messages that overexcite and kill the cells.

To figure out how the brain decides which cells need the glutamate transporters, Rothstein and colleagues focused on the region of DNA in front of the gene that typically controls the on-off switch needed to manufacture the protein. They genetically engineered mice to glow red in every cell where the gene is activated.

Normally, the glutamate transporter is turned on in all astrocytes. But, by using between 1,000- and 7,000-bit segments of DNA code from the on-off switch for glutamate, all the cells in the brain glowed red, including the neurons. It wasn’t until the researchers tried the largest sequence of an 8,300-bit DNA code from this location that the researchers began to see some selection in red cells. These red cells were all astrocytes but only in certain layers of the brain’s cortex in mice.

Because they could identify these “8.3 red astrocytes,” the researchers thought they might have a specific function different than other astrocytes in the brain. To find out more precisely what these 8.3 red astrocytes do in the brain, the researchers used a cell-sorting machine to separate the red astrocytes from the uncolored ones in mouse brain cortical tissue, and then identified which genes were turned on to much higher than usual levels in the red compared to the uncolored cell populations. The researchers found that the 8.3 red astrocytes turn on high levels of a gene that codes for a different protein known as Norrin.

Rothstein’s team took neurons from normal mouse brains, treated them with Norrin, and found that those neurons grew more of the “branches” — or extensions — used to transmit chemical messages among brain cells. Then, Rothstein says, the researchers looked at the brains of mice engineered to lack Norrin, and saw that these neurons had fewer branches than in healthy mice that made Norrin.

In another set of experiments, the research team took the DNA code for Norrin plus the 8,300 “location” DNA and assembled them into deliverable nanoparticles. When they injected the Norrin nanoparticles into the brains of mice engineered without Norrin, the neurons in these mice began to quickly grow many more branches, a process suggesting repair to neural networks. They repeated these experiments with human neurons too.

Rothstein notes that mutations in the Norrin protein that reduce levels of the protein in people cause Norrie disease — a rare, genetic disorder that can lead to blindness in infancy and intellectual disability. Because the researchers were able to grow new branches for communication, they believe it may one day be possible to use Norrin to treat some types of intellectual disabilities such as Norrie disease.

For their next steps, the researchers are investigating if Norrin can repair connections in the brains of animal models with neurodegenerative diseases, and in preparation for potential success, Miller [sic] and Rothstein have submitted a patent for Norrin.

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

Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin by Sean J. Miller, Thomas Philips, Namho Kim, Raha Dastgheyb, Zhuoxun Chen, Yi-Chun Hsieh, J. Gavin Daigle, Malika Datta, Jeannie Chew, Svetlana Vidensky, Jacqueline T. Pham, Ethan G. Hughes, Michael B. Robinson, Rita Sattler, Raju Tomer, Jung Soo Suk, Dwight E. Bergles, Norman Haughey, Mikhail Pletnikov, Justin Hanes & Jeffrey D. Rothstein. Nature Neuroscience volume 22, pages741–752 (2019) DOI: https://doi.org/10.1038/s41593-019-0366-7 Published: 01 April 2019 Issue Date: May 2019

This paper is behind a paywall.

Frugal science: ancient toys for state-of-the-art science

A toy that’s been a plaything for 5,000 years and known as a whirligig (in English, anyway) has inspired a scientific tool for use by field biologists and students interested in creating state-of-the-art experiments. Exciting stuff, eh?

A May 23, 2019 Georgia Tech (Georgia Institute of Technology) news release (also on EurekAlert but published on May 22, 2019) announces this development in ‘frugal science’,

A 5,000-year-old toy still enjoyed by kids today has inspired an inexpensive, hand-powered scientific tool that could not only impact how field biologists conduct their research but also allow high-school students and others with limited resources to realize their own state-of-the-art experiments.

The device, a portable centrifuge for preparing scientific samples including DNA, is reported May 21 [2019] in the journal PLOS Biology. The co-first author of the paper is Gaurav Byagathvalli, a senior at Lambert High School in Georgia. His colleagues are M. Saad Bhamla, an assistant professor at the Georgia Institute of Technology; Soham Sinha, a Georgia Tech undergraduate; Janet Standeven, Byagathvalli’s biology teacher at Lambert; and Aaron F. Pomerantz, a graduate student at the University of California, Berkeley.

“I am exceptionally proud of this paper and will remember it 10, 20, 30 years from now because of the uniquely diverse team we put together,” said Bhamla, who is an assistant professor in Georgia Tech’s School of Chemical and Biomolecular Engineering.

From a Rainforest to a High School

Together the team demonstrated the device, dubbed the 3D-Fuge because it is created through 3D printing, in two separate applications. In a rainforest in Peru the 3D-Fuge was an integral part of a “lab in a backpack” used to identify four previously-unknown plants and insects by sequencing their DNA [deoxyribonucleic acid]. Back in the United States, a slightly different design enabled a new approach to creating living bacterial sensors for the potential detection of disease. That work was conducted at Lambert High School for a synthetic biology competition.

Thanks to social media and a preprint of the PLOS Biology paper on BioRxiv, the 3D-Fuge has already generated interest from around the world, including emails from high-school teachers in Zambia and Kenya. “It’s awesome to see research not just remain isolated to one location but see it spread,” said Byagathvalli. “Through this, we’ve realized how much of an impact simple yet effective tools can have, and hope this technology motivates others to continue along the same path and innovate new solutions to global issues.”

To better share the work, the team has posted the 3D-Fuge designs, videos, and photos online available to anyone.

Frugal Science

One focus of Bhamla’s lab at Georgia Tech is the development of tools for frugal science, or real research that just about anyone can afford. The tools behind state-of-the-art science often cost thousands of dollars that make them inaccessible to those without serious resources.

Centrifuges are a good example.  A small benchtop unit costs between $3,000 and $5,000; larger units cost many times that. Yet the devices are necessary to produce concentrated amounts of, say, genomic materials like DNA. By rapidly spinning samples, they separate materials of interest from biological debris.

The Bhamla team found that the 3D-Fuge works as well as its more expensive cousins, but costs less than $1.

An Ancient Toy

The 3D-Fuge is based on earlier work by Bhamla and colleagues at Stanford University on a simple centrifuge made of paper. The “paperfuge,” in turn, was inspired by a toy composed of string and a button that Bhamla played with as a child. He later discovered that these toys, known as whirligigs, have existed for some 5,000 years.

They consist of a disk – like a button – with two holes, through which is threaded a length of flexible cord whose ends are knotted to create a single loop with the disk in the middle. That simple contraption is then swung with two hands until the button is spinning and whirring at very fast speeds.

The earlier paperfuge uses a disk of paper. To that disk Bhamla glued small plastic tubes filled with a sample. He and colleagues reported that the device did indeed create high-quality samples.

In late 2017 Bhamla was separately approached by the Lambert High team and Pomerantz to see if the paperfuge could be adapted for the larger samples they needed (the paperfuge is limited to small samples of ~1 microliter—or one drop of blood).

Together they came up with the 3D-Fuge, which includes cavities for tubes that can hold some 100 times more of a sample than the paperfuge. The team developed two equally effective designs: one for field biology (led by Pomerantz) and the other for the high-school’s synthetic biology project (led by Byagathvalli).

Bhamla notes that the 3D-Fuge has some limitations. For example, it can only process a few samples at a time (some applications require thousands of samples). Further, because it’s 10 times heavier than the paperfuge, it can’t reach the same speeds or produce the same forces of that device. That said, it still weighs only 20 grams, slightly less than a AA battery.

“But it works,” said Bhamla. “All you need is an [appropriate] application and some creativity.”

Here are a couple of images showing the 3D-Fuge in action,

Using the 3D-Fuge Courtesy: Georgia Tech
Sample vial in 3D-Fuge Courtesy: Georgia Tech

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

A 3D-printed hand-powered centrifuge for molecular biology by Gaurav Byagathvalli, Aaron Pomerantz, Soham Sinha, Janet Standeven, M. Saad Bhamla. PLOS Biology DOI: https://doi.org/10.1371/journal.pbio.3000251 Published: May 21, 2019

As always with a Public Library of Science (PLOS) publication, this paper is open access.

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

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

Introduction to the Chinese CRISPR twins

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

But genetics is rarely that simple.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The ethics of not saying anything

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

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

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

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

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

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

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

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

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

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

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

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

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

CCR5 and freedom from HIV

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A big question: are genes what we thought?

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

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

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

We have reached peak gene, and passed it.

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

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

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

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

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

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

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

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

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

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

Transgenic monkeys and human intelligence

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

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

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

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

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

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

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

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

This appears to be an open access paper,

Transgenic monkeys and an ethical uproar

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

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

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

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

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

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

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

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


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

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

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

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

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

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

Global plea for moratorium on heritable genome editing

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This Comment in Nature is open access.

World Health Organization (WHO) chimes in

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

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

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

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

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

Slow science from Canada

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

Naughty (or Haughty, if you prefer) scientists

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

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

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

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

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

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

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

Parents, children, competition

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Scientists under pressure

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

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

Some thoughts

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

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

Back to the regular programme

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

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