Everyday Erinyes #350

Posted by Joanne Dixon at 2:29 pm Open Thread, Politics

Dec 252022

Experts in autocracies have pointed out that it is, unfortunately, easy to slip into normalizing the tyrant, hence it is important to hang on to outrage. These incidents which seem to call for the efforts of the Greek Furies (Erinyes) to come and deal with them will, I hope, help with that. As a reminder, though no one really knows how many there were supposed to be, the three names we have are Alecto, Megaera, and Tisiphone. These roughly translate as “unceasing,” “grudging,” and “vengeful destruction.”

It’s still the holiday season, and I am still – sort of – on break. Not on break from posting the blog, but on break from the kind of news that warns us and may scare us into some kind of action. This story may scare us, but only because a development so major can open up so many possibilities for noth good and evil. Still, it’s exciting, and it’s inspiring to think about the good which can be done.

And for sure this technology is going to be used. By humans. Who can and do make mistakes (as the article makes very clear.) But innocent mistakes – even when catastrophic – are a different matter from deliberate misuse, generally done for money or power. That absolutely must be reckoned with.
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Did He Jiankui ‘Make People Better’? Documentary spurs a new look at the case of the first gene-edited babies

He Jiankui seemed unprepared for the furor set off by his bombshell announcement.
The He Lab/Wikimedia Commons, CC BY

G. Owen Schaefer, National University of Singapore

In the four years since an experiment by disgraced scientist He Jiankui resulted in the birth of the first babies with edited genes, numerous articles, books and international commissions have reflected on whether and how heritable genome editing – that is, modifying genes that will be passed on to the next generation – should proceed. They’ve reinforced an international consensus that it’s premature to proceed with heritable genome editing. Yet, concern remains that some individuals might buck that consensus and recklessly forge ahead – just as He Jiankui did.

Some observers – myself included – have characterized He as a rogue. However, the new documentary “Make People Better,” directed by filmmaker Cody Sheehy, leans toward a different narrative. In its telling, He was a misguided centerpiece of a broader ecosystem that subtly and implicitly supported rapid advancement in gene editing and reproductive technologies. That same system threw He under the bus – and into prison – when it became evident that the global community strongly rejected his experiments.

Creation of the ‘CRISPR babies’

“Make People Better” outlines an already well-documented saga, tracing the path of He from a promising young scientist at Rice and Stanford to a driven researcher establishing a laboratory in China that secretly worked to make heritable genome editing a reality.

He’s experiment involved using the CRISPR-Cas9 technique. Sometimes compared to “molecular scissors,” this precision tool allows scientists to make very specific edits to DNA in living cells. He used CRISPR to alter the CCR5 gene in human embryos with the goal of conferring immunity to HIV. These embryos were brought to term, resulting in the birth of at least three children with altered DNA.

The revelation of the births of the first gene-edited babies in November 2018 resulted in an international uproar. A laundry list of ethical failings in He’s experiment quickly became evident. There was insufficient proof that editing embryos with CRISPR was safe enough to be done in humans. Appropriate regulatory approval had not been obtained. The parents’ consent was grossly inadequate. And the whole endeavor was shrouded in secrecy.

Trailer for the documentary ‘Make People Better.’

New context, same story

Three figures play a central role in “Make People Better”‘s study of He Jiankui. There’s Antonio Regalado, the reporter from MIT Technology Review who broke the original story. There’s Ben Hurlbut, an ethicist and confidante of He. And there’s Ryan (the documentary withholds his full identity), a public relations representative who worked with He to make gene editing palatable to the world. He Jiankui himself was not interviewed, though his voice permeates the documentary in previously unreleased recordings by Hurlbut.

Regalado and Hurlbut have already written a considerable amount on this saga, so the documentary’s most novel contribution comes from Ryan’s discussion of his public relations work with He. Ryan appears to be a true believer in He’s vision to literally “make people better” by using gene editing to prevent dreadful diseases.

But Ryan is aware that public backlash could torpedo this promising work. His reference point is the initial public hostility to GMO foods, and Ryan strove to avoid that outcome by gradually easing the public in to the heritable gene editing experiment.

This strategy turned out to be badly mistaken for a variety of reasons. He Jiankui was himself eager to publicize his work. Meanwhile, Regalado’s tenacious journalism led him to a clinical trials registry where He had quietly posted about the study.

But ultimately, those factors just affected the timing of revelation. Both Ryan and He failed to appreciate that they had very little ability to influence how the experiment would be received, nor how much condemnation would result.

Blind spots

While some documentaries strive to be flies on the wall, objectivity is elusive. Tone, framing, editing and choice of interview subjects all coalesce into a narrative with a perspective on the subject matter. A point of view is not itself objectionable, but it opens the documentary to critiques of its implicit stance.

An uncomfortable tension lies at the center of “Make People Better.”

On the one hand, the documentary gives substantial attention to Hurlbut and Ryan, who emphasize that He did not act alone. He discussed his plans with dozens of people in China and around the world, whose implicit support was essential to both the experiment and his confidence that he was doing nothing wrong.

On the other hand, the documentary focuses on understanding He’s background, motives and ultimate fate. Other figures who might have influenced He to take a different path fade into the background – sometimes quite literally, appearing for only seconds before the documentary moves on.

Indeed, as a biomedical ethicist, I believe there is good reason to put responsibility for the debacle squarely on He’s shoulders. Before the news broke in 2018, international panels of experts had already issued advisory statements that heritable gene editing was premature. Individuals like Hurlbut personally advised He as much. The secrecy of the experiment itself is a testament: He must have suspected the international community would reject the experiment if they knew what was going on.

If He had gone through proper, transparent channels – preregistering the trial and consulting publicly with international experts on his plans before he began – the whole saga could have been averted. He chose a different, more dangerous and secretive path from the vast majority of researchers working in reproductive biotechnology, which I suggest must be acknowledged.

The documentary does not reflect critically on its own title. The origin of the phrase “make people better” is surprising and the film’s most clever narrative moment, so I won’t spoil it. But does heritable gene editing really make people better? Perhaps instead, it makes better people.

The gene-edited babies were created via in vitro fertilization specifically as a part of He’s experiment. They would not have existed if He had never gotten involved in gene editing. So, some would argue, He did not save any individual from contracting HIV. Rather, he created new people potentially less likely to contract HIV than the general population.

I contend that this doesn’t mean gene editing is pointless. From a population health perspective, gene editing could save lives by reducing the incidence of certain diseases. But this perspective does change the moral tenor of gene editing, perhaps reducing its urgency.

What’s more, editing CCR5 is a dubious means to improve human well-being, since there are already effective ways to prevent HIV infection that are far less risky and uncertain than heritable gene editing. Scientific consensus suggests that the best first-in-human candidates for heritable gene editing are instead devastating genetic disorders that cannot be ameliorated in other ways.

The future for He Jiankui

Perhaps due to the timing of its filming, the documentary does not dwell on He being sentenced to three years in Chinese prison as a result of the experiment, nor mention that he was released early in 2022.

Evidently, He is not content to fade quietly into obscurity. He says he is slated in March 2023 to give a talk at the University of Oxford that may shed more light on his motives and actions. In the meantime, he has established a new biotech start-up focused on developing gene therapies. To be clear, this work does not involve editing embryos.

Still, it appears prison has not diminished He’s ambition. He claims that he could develop a cure for the degenerative genetic disease Duchenne muscular dystrophy – if he receives funding in excess of US$100 million.

To me, this ambition reflects a curious symmetry between Regalado and He in “Make People Better.” Both are driven to be first, to be at the forefront of their respective fields. Sometimes, as with Regalado, this initiative can be good – his intrepid reporting and instinct to publish quickly brought He’s unethical experiment to a rapid close. But in other cases, like He’s, that drive can lead to dangerous science that runs roughshod over ethics and good governance.

Perhaps, then, the best lesson a viewer can take from “Make People Better” is that ambition is a double-edged sword. In the years to come, it will be up to the international community to keep such ambition in check and ensure proper restrictions and oversight on heritable genome editing.

G. Owen Schaefer, Assistant Professor in Biomedical Ethics, National University of Singapore

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Alecto, Megaera, and Tisiphone, may I ask that you keep looking over the shoulders of the scientists develop and using this echnology, and keep them on the strait and narrow? Or at the very lest, nudge their associates to blow the whistle when they stray off of the path. And help our legislators understand how best to regulate this technology – and us understand how best to advise them.

The Furies and I will be back.

Open Thread November 28, 2022

Posted by Joanne Dixon at 6:48 am Open Thread, Personal, Politics

Nov 282022

Yesterday, I finished knitting a sweater, finished knitting a collar extention onto a sweatshirt, started a new sweater – and took a fairly deep dive into Joyce Vance’s newsletter, which was in the category of “The Week Ahead” – she doesn’t do one of those every weekend, but she often does. For this coming eeek, she is anticipating the circus (not her term, my interpretatin only) than can be expected in the Eleventh Circuit Court of Appeals pursuant to Jack Smith’s demolition of Judge Cannon. It’s long and nerdy (she says so herself), and I’ll not try to boil it down further here, but I do provide a link. I do hope she is 100% correct – and I feel there is a good chance of it. ALso, I did a few December cartoons – just enough to take me several days past my next visit to Virgil (this Sunday).

Cartoon – 28 Blackbeard loaded

Short Takes –

Democratic Underground (multigraincracker) – Her mother was also her uncle, DNA test.
Quote – The mother had XY chromosomes in her blood and saliva, but her hair and cheek cells had XX chromosomes. Parts of the daughter’s genome matched each kind of her mother’s mismatched DNA. The daughter had inherited some DNA from her mother which originally belonged to her mother’s fraternal twin brother, who was never born. That makes the mother a chimera, the result of an embryo that had absorbed and incorporated cells from a twin who had vanished before anyone knew he had existed.
Click through for article, and don’t neglest the comments, which include more links to other anomalies. We are constantly learning so much more about genetics – and all of it makes the arrogance of people who insist there are two sexes, period, more outrageous.

Mother Jones – Hundreds of New York Women Are About to Sue Alleged Rapists (and Enablers) Under a Revolutionary New Law
Quote – Now, Carroll and thousands of other sexual assault survivors in New York state are getting a new chance to seek legal accountability against people who harmed them years or decades ago. Under the Adult Survivors Act, New Yorkers who were sexually assaulted as adults but who have run out of time to seek accountability in court will have a one-year “lookback window” to sue their abusers, as well as institutions that were negligent in responding to the assault.
Click through for details. To me, in a kind of rarefied way, this is analogous to the Federal statute of limitations’ exception for availability. But here, its society’s contempt for and distrust of women which conctitutes the unavailability.

DNYUX (also the NY Times, which is paywalled) – At Protests, Guns Are Doing the Talking
Quote – Across the country, openly carrying a gun in public is no longer just an exercise in self-defense — increasingly it is a soapbox for elevating one’s voice and, just as often, quieting someone else’s…. Whether at the local library, in a park or on Main Street, most of these incidents happen where Republicans have fought to expand the ability to bear arms in public, a movement bolstered by a recent Supreme Court ruling on the right to carry firearms outside the home. The loosening of limits has occurred as violent political rhetoric rises and the police in some places fear bloodshed among an armed populace on a hair trigger.
Click through for more – examples and analysis. This is what happens when people (I’m looking at you, SCOTUS) are allowed to conflate speech with something which isn’t speech at all.

Food For Thought

(Just till after the runoff)

Everyday Erinyes #298

Posted by Joanne Dixon at 1:51 pm Politics

Dec 262021

This article was posted before the heads-up from Walter Reed (which sent Mother Jones off to investigate, which led to an article included among today’s short takes), but that diesn’t mean it’s “old news.” I doubt that anyoe here has been up close and personal with gene sequencing. If you are into genealogy, or if you have any kind of hereditary medical condition, you may have in some obscure way used the results of the process, but of course that doesn’t make an expert, any more than drinking milk makes one an expert on cattle – much less a cow. As always, The Conversation has taken pains to make what’s in the article clear, and, hopefully, interesting.
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Genomic sequencing: Here’s how researchers identify omicron and other COVID-19 variants

Sequencing the genome of a virus gives researchers information on how mutations can affect its transmissibility and virulence.
catalinr/iStock via Getty Images Plus

Andre Hudson, Rochester Institute of Technology and Crista Wadsworth, Rochester Institute of Technology

How do scientists detect new variants of the virus that causes COVID-19? The answer is a process called DNA sequencing.

Researchers sequence DNA to determine the order of the four chemical building blocks, or nucleotides, that make it up: adenine, thymine, cytosine and guanine. The millions to billions of these building blocks paired up together collectively make up a genome that contains all the genetic information an organism needs to survive.

When an organism replicates, it makes a copy of its entire genome to pass on to its offspring. Sometimes errors in the copying process can lead to mutations in which one or more building blocks are swapped, deleted or inserted. This may alter genes, the instruction sheets for the proteins that allow an organism to function, and can ultimately affect the physical characteristics of that organism. In humans, for example, eye and hair color are the result of genetic variations that can arise from mutations. In the case of the virus that causes COVID-19, SARS-CoV-2, mutations can change its ability to spread, cause infection or even evade the immune system.

We are both biochemists and microbiologists who teach about and study the genomes of bacteria. We both use DNA sequencing in our research to understand how mutations affect antibiotic resistance. The tools we use to sequence DNA in our work are the same ones scientists are using right now to study the SARS-CoV-2 virus.

The first human genome took two decades to sequence. With advances in technology, scientists are now able to sequence DNA in a matter of hours.

How are genomes sequenced?

One of the earliest methods scientists used in the 1970s and 1980s was Sanger sequencing, which involves cutting up DNA into short fragments and adding radioactive or fluorescent tags to identify each nucleotide. The fragments are then put through an electric sieve that sorts them by size. Compared with newer methods, Sanger sequencing is slow and can process only relatively short stretches of DNA. Despite these limitations, it provides highly accurate data, and some researchers are still actively using this method to sequence SARS-CoV-2 samples.

Since the late 1990s, next-generation sequencing has revolutionized how researchers collect data on and understand genomes. Known as NGS, these technologies are able to process much higher volumes of DNA at the same time, significantly reducing the amount of time it takes to sequence a genome.

There are two main types of NGS platforms: second-generation and third-generation sequencers.

Second-generation sequencing marks each nucleotide with a specific color.

Second-generation technologies are able to read DNA directly. After DNA is cut up into fragments, short stretches of genetic material called adapters are added to give each nucleotide a different color. For example, adenine is colored blue and cytosine is colored red. Finally, these DNA fragments are fed into a computer and reassembled into the entire genomic sequence.

Third-generation technologies like the Nanopore MinIon directly sequence DNA by passing the entire DNA molecule through an electrical pore in the sequencer. Because each pair of nucleotides disrupts the electrical current in a particular way, the sequencer can read these changes and upload them directly to a computer. This allows clinicians to sequence samples at point-of-care clinical and treatment facilities. However, Nanopore sequences smaller volumes of DNA compared with other NGS platforms.

Third-generation sequencing detects changes in an electrical current to identify nucleotides.

Though each class of sequencer processes DNA in a different way, they can all report the millions or billions of building blocks that make up genomes in a short time – from a few hours to a few days. For example, the Illumina NovaSeq can sequence roughly 150 billion nucleotides, the equivalent of 48 human genomes, in just three days.

Using sequencing data to fight coronavirus

So why is genomic sequencing such an important tool in combating the spread of SARS-CoV-2?

Rapid public health responses to SARS-CoV-2 require intimate knowledge of how the virus is changing over time. Scientists have been using genome sequencing to track SARS-CoV-2 almost in real time since the start of the pandemic. Millions of individual SARS-CoV-2 genomes have been sequenced and housed in various public repositories like the Global Initiative on Sharing Avian Influenza Data and the National Center for Biotechnology Information.

Genomic surveillance has guided public health decisions as each new variant has emerged. For example, sequencing the genome of the omicron variant allowed researchers to detect over 30 mutations in the spike protein that allows the virus to bind to cells in the human body. This makes omicron a variant of concern, as these mutations are known to contribute to the virus’s ability to spread. Researchers are still learning about how these mutations might affect the severity of the infections omicron causes, and how well it’s able to evade current vaccines.

A screen showing sequences of the letters T, C, A and G. — This image shows a DNA readout of the alpha variant of SARS-CoV-2. A mutation is marked by dotted lines.
Sebastian Gollnow/picture alliance via Getty Images

Sequencing also has helped researchers identify variants that spread to new regions. Upon receiving a SARS-CoV-2 sample collected from a traveler who returned from South Africa on Nov. 22, 2021, researchers at the University of California, San Francisco, were able to detect omicron’s presence in five hours and had nearly the entire genome sequenced in eight. Since then, the Centers for Disease Control and Prevention has been monitoring omicron’s spread and advising the government on ways to prevent widespread community transmission.

The rapid detection of omicron worldwide emphasizes the power of robust genomic surveillance and the value of sharing genomic data across the globe. Understanding the genetic makeup of the virus and its variants gives researchers and public health officials insights into how to best update public health guidelines and maximize resource allocation for vaccine and drug development. By providing essential information on how to curb the spread of new variants, genomic sequencing has saved and will continue to save countless lives over the course of the pandemic.

[Get the best of The Conversation, every weekend. Sign up for our weekly newsletter.]

Andre Hudson, Professor and Head of the Thomas H. Gosnell School of Life Sciences, Rochester Institute of Technology and Crista Wadsworth, Assistant Professor in the Thomas H. Gosnell School of Life Sciences, Rochester Institute of Technology

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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AMT, Genomic sequencing is certainly not something I am an expert on. All I ever knew about it was that in the book “Gödel, Escher, Bach: an Eternal Golden Braid,” Douglas Hofstadter used “dialogues” based on Achilles and the Tortoise because their first latters matched adenine and thymine (he also snuck in a Crab for cytosine and occassionally referred to G for guaritine. Once I believe it was a guitar.) Pretty sophisticated for short pieceswhich were intended to bu humorous (but also to make readers think.)

Thank heaven we don’t need to be experts – that’s what real experts are for. But it’s nice to be a little familiar with a process, and its results, which are going to be dominating medical fields (and not just epidemiology) for decades to come.

The Furies and I will be back.