…what ails [DOT 11/12/22]

…sometimes it sounds like we’re living in the future

Over the past decade, thousands of people have agreed to be genetically engineered in experimental trials to develop these treatments — and to save their lives. Famously proposed 50 years ago, such fixes, or ‌gene therapies, began earnest development in 1989. After fits and starts, the first real cures for children born with no functioning immune system arrived in the early 2000s.

Several approved gene therapy medicines now exist. All involve taking a virus, replacing its harmful contents with a disease-treating gene, and injecting it into a person (or exposing the person’s cells to that virus in a dish and putting them back). Though effective, these treatments remain cumbersome to build and jaw-droppingly expensive: One recently approved gene therapy for people with an inherited bleeding disorder costs a record-breaking $3.5 million for a single-use vial, making it the most expensive drug in the world.

Gene editing is much newer technology and builds on the gains of gene therapy. Instead of using a virus, however, gene editing relies on a molecular machine called CRISPR, which can be instructed to repair a mutation in a gene in nearly any organism, right where that “typo” occurs. Impressively versatile, potential applications for CRISPR range from basic science to agriculture and climate change. In medicine, CRISPR gene editing allows physicians to directly fix typos in the patients’ DNA. And so much substantive progress has been made in the field of genetic medicine that it’s clear scientists have now delivered on a remarkable dream: word-processor-like control over DNA.

…it goes on to describe a scenario in which a tailored gene-editing therapy could go from a sample of the prospective patient’s DNA to a CRISPR-tailored medication in a month & leave the patient cured within two…which in light of the actual experience of many trying to access healthcare sounds the wrong kind of fantastic

Just as CRISPR once seemed to be something out of science fiction, so might everything in the preceding paragraphs — but every step of that process is technically feasible today.

…well, feasible in some senses, at least…not including economically or in terms of broad accessibility, though

There are up to 400 million people worldwide affected by one of the 7,000 diseases caused by mutations in single genes. ‌Scientists owe them and their families honesty about the ‌‌chasm between a test tube in a lab and an IV line in a hospital. The greatest obstacles are not technical but legal, financial and organizational.

…so…that whole test-to-treatment-in-a-month deal…which fyodor urnov here reckons could (once the whole system is appropriately scaled up to an on-demand partially-automated process) get shaved down to as little as a three day turnaround…in practice…even if the option is on the table in a given case…it’s…less timely

However, from more than 15 years of experience building such gene-editing medicines and advancing them to clinical trials, I know this process is only the first step in a four-year journey likely to cost at least $8 million to $10 million.

…&…some of why doesn’t sound entirely crazy

‌‌According to U.S. and European law, a detailed process is in place to ensure safety and efficacy of the experimental medicine. It starts with meticulous studies using human cells in a dish and in animals. This takes at least two years, and if everything checks out, scientists embark on the most expensive leg of the trip: making the CRISPR medicine, which has to be synthesized to comply with a regulatory standard known as good manufacturing practice. Designed to protect patients from faulty medicines, this U.S. federal requirement stretches out the making of clinic-grade CRISPR to a year and over $1 million, followed by over a year of animal testing. All of this happens before you can use it to treat a human being.

…but…when you think about what the tailored element of this stuff means…it does sort of defeat the whole point of the exercise

Who will invest $10 million to build a medicine to correct a specific mutation ‌that can then be used to treat only one person? Even if the money were available, people with such rare diseases would be likely to die by the time the necessary experiments are complete — infuriatingly rendering my ability to engineer the CRISPR medicine of zero help to the‌‌ people who write to me and millions more in similar predicaments.

…except…& I am a long way from understanding the hows & whys that determine this stuff…so I’m taking fyodor’s word for it…it’s isn’t always a just-the-one cure

A case study from gene therapy with viruses highlights the problem. Dr. Donald Kohn at U.C.L.A. built a therapy for a devastating genetic disease called severe combined immune deficiency. Partnering with clinicians at University College London, he used this therapy to treat 50 children doomed to die. Forty-eight were cured by the therapy; the other two survived after receiving a bone-marrow transplant.

…sometimes…it’s not even one, though…which…seems unbelievable…or too believable

But public universities are not in the business of commercializing medicines they build. For this reason, U.C.L.A. licensed this miracle drug to a for-profit biotechnology company. After the company failed to make a profit on it, U.C.L.A. took back the license and obtained funding from the State of California to treat a small number of children in an academic setting. No children were treated in the four years it was under for-profit purview.

…unsurprisingly…that for-profit part has a lot to do with it…because the post-natal sanctity of human life continues to appear on precious few balance sheets…&…the needs of the few aren’t on a par with the needs of the select few

For diseases with fewer than 100 patients, such prices are still not enough for these efforts to make commercial sense, as demonstrated by a biotechnology company, bluebird bio. After 20 years of engineering such gene therapies and significant success in the clinic, bluebird bio now struggles to remain solvent — even as it priced its most recent approved medicine at $3 million. Another gene-editing biotechnology company recently halted clinical trials for a rare disease with 300 patients in the United States, saying it couldn’t make the economic case to continue the experiments. For a disease that affects one person, the current for-profit system thus makes building a gene therapy or a gene editing cure a daunting challenge.
[…]
Streamlining regulation won’t be enough, though. Where will the funding for developing cures for single patients come from? Biotechnology companies are unlikely to voluntarily take this on, given the financial cost, though the for-profit sector could make a significant contribution by sharing technologies and resources that would accelerate this effort. Tapping into federal and state funding could provide a path forward. Recently, the F.D.A. greenlighted a clinical trial collaboration between experts at U.C.S.F. and U.C.L.A. and my colleagues at U.C. Berkeley’s Innovative Genomics Institute, for a gene editing approach to sickle cell disease. My sense of pride in this achievement is diluted by the realization that ours is the only such all-academic trial in the entirety of the gene editing space. To truly realize the potential of this technology, there should be dozens of such efforts underway.
[…]
But for the next few years, devastating genetic ailments and cancer are where CRISPR clinical trials must remain; ethical considerations over the safety of patients being exposed to new technology dictate that. Today’s tools are also the cognate of the first iPod — at the time, an exhilarating advance but still low tech compared with present-day smartphones. Everything we learn about how to gene-edit people from this work, coupled with continued CRISPR innovation in the academic and for-profit sector, will provide a foundation for more deeply understanding how to safely edit DNA to treat and potentially prevent dire common diseases.
https://www.nytimes.com/2022/12/09/opinion/crispr-gene-editing-cures.html

…it’s not that we can’t do the thing…it’s that we can’t do the thing we can do…seems like that ought to make a lot less sense than it does…& sound a damn sight less familiar

As many as a million different species are threatened with extinction. Is there anything we can do to stop them from vanishing forever?
[…]
There is a lot on the line. Just life on Earth as we know it. Without some sort of intervention, scientists fear a mass extinction will occur, with dire implications for human beings.

…I know…it sounds hyperbolic…& maybe even is…except there’s that whole tipping point/exponential curve thing that comes with the “objects in the near-view mirror may be closer than they appear” warning

The summit’s headline goal is codifying a commitment from countries to preserve 30 percent of their land and water by 2030. That target has a pithy name: “30 by 30.”
[…]
But there are plenty of other issues to hash out, and much of the agreement’s text still needs to be negotiated by representatives of about 190 countries.
[…]
And how much should rich nations — ones that have already gained by harnessing natural resources — help out poor ones that are still developing?

…so…that’ll be going gangbusters, I’m sure

It’s complicated. For one, the United States isn’t an official party to the negotiations.

In 1993, Bill Clinton signed the Convention on Biological Diversity, the international treaty underlying this month’s negotiations. But the pact has never been able to garner the elusive 67-votes supermajority in the Senate needed for ratification.

…yeah…we kinda know the answer to that…& it’s not confined to the senate

Yet the Biden administration has its own “30 by 30” goal of preserving nearly a third of the nation’s land and water by the end of the decade, dubbed “America the Beautiful.”

…but…talk about making an example

In 2010, for instance, nations set 20 goals for conserving the world’s biodiversity. The targets included minimizing the impacts of ocean acidification on coral reefs and maintaining the genetic diversity of cultivated plants.

More than a decade later, none of those goals set at the conference in Japan have been fully achieved, according to a recent assessment.

…so…you know that thing about repeating actions (or lack of taking them) while expecting things to go differently being a functional definition of insanity?

Farmers rely on dwindling numbers of bees and other insects to pollinate their crops. Fishers depend on healthy oceans for their food and livelihoods.

The loss of wildlife isn’t just bad for the plants and animal themselves. Extinctions threaten to degrade ecosystems that people rely on for safe water, protein and other vital resources.

“With a bottomless appetite for unchecked and unequal economic growth, humanity has become a weapon of mass extinction,” Guterres said.
https://www.washingtonpost.com/climate-environment/2022/12/09/cop15-biodiversity-nature-montreal-climate/

…hyperbole?

In malignant conflicts, the kind that leave everyone worse off, there is the thing we argue about endlessly, to the point of stupefaction.
[…]
Then there is the issue that the conflict is really about, the thing no one discusses. That understory is the most interesting part — and talking about it is the only way to escape our state of perpetual misery.
[…]
“People really think that the majority of the other party is just cuckoo on this stuff,” says Stephen Hawkins, More in Common’s director of research. “Regardless of whether you’re left, right or center, people tend to get it wrong by a significant margin.”
[…]
The new data does not mean we agree; we do not. But it does mean we are not having the right fight, the one we most need to have as a country, because we are so preoccupied with what the report calls “imagined enemies.”
[…]
For my job, I interview a lot of Americans who disagree on many things. Most Americans I meet can handle much more complexity than our news coverage and political debates assume. Most of us recognize that our country is about more than one legacy. “American history is longer, larger, more various, more beautiful, and more terrible than anything anyone has ever said about it,” James Baldwin wrote.
[…]
Many of our disagreements are manufactured. We are being played by conflict entrepreneurs — people and companies who exploit conflict for their own dysfunctional ends, and it is getting harder and harder to avoid their phantom traps and have the right debate.

Three years ago, More in Common did another report on the gap between Americans’ actual beliefs and our perception of each other. That study found that partisan Americans who watched a lot of news or had fewer friends across the aisle were the ones who were most ignorant about their opponents. They wildly misunderstood the other side. The rest of the country, which consumed less news, was much more accurate about who really thought what.

…or understatement?

This report shows something new. Nearly all Americans, including the less politically engaged and more moderate among us, are seeing a distorted reality, and are worrying more than they ought to about a threat that is not really a threat. That perceived threat is what leads to violence throughout human history. When people feel desperate and afraid, when they feel they cannot trust the institutions to protect them, they tend to take matters into their own hands.

What if we started recognizing this manipulation — and refused to be played? What if journalists covered the next “education war” with the goal of getting the story right — resisting fake binaries and elevating the stories of people who do not fit the false caricature? In the months and years to come, we have got to find ways to know one another again. To listen and speak our minds, with dignity and courage.

Otherwise, we will simply move from one wrong fight to another, from critical race theory to social-emotional learning to whatever imaginary schism comes next.
https://www.washingtonpost.com/opinions/2022/12/08/american-polarization-crt-more-in-common-report/

…after all…when it comes to who’s trying to bring which fight to who while staying ignorant about what…shit’s complicated

The US is a rogue state leading the world towards ecological collapse [per monbiot in the guardian, any road]

…if also frequently all kinds of fucking obvious

Anderson Lee Aldrich, 22, allegedly entered Club Q in Colorado Springs just before midnight on Nov. 19 and opened fire, killing five people and injuring 17 others. Four days later, in one of several court documents filed by the public defenders representing Aldrich, a footnote stated that Aldrich is nonbinary and uses they/them pronouns.

Aldrich was charged Tuesday with 305 criminal counts, including first-degree murder and bias-motivated crimes. In court appearances this week, Aldrich’s lawyers and District Attorney Michael Allen used he/him pronouns for Aldrich, but Aldrich’s attorneys referred to their client as “Mx. Aldrich,” using a gender-neutral honorific.
[…]
Online extremism experts say the suspect could be trolling — which is when someone makes an inflammatory or disingenuous remark meant to provoke — and that the discord and confusion created among the queer community and right-wing pundits could be intentional. Xavier Kraus, who said he lived next door to the suspect and the suspect’s mother from August 2021 to September 2022, said he believes the claim that Aldrich is nonbinary is “a total troll on the community, and a total troll on the system.” Aldrich, he said, never used they/them pronouns with him or mentioned being nonbinary.

…could be? …we’re going with “could be”?

Jared Holt, senior research manager at the Institute for Strategic Dialogue, a global nonprofit combating online extremism and disinformation, said he was “immediately skeptical” of the Colorado suspect’s assertion.

That skepticism only grew this week after NBC News reported that the FBI is looking into two websites connected to the suspect. One of the websites, which Kraus said Aldrich created in the spring or early summer, is a forum-type “free speech” site where people have anonymously posted racist and antisemitic memes, language and videos.
[…]
There is also an offensive article about Aldrich on Encyclopedia Dramatica, an extremist, racist and homophobic version of Wikipedia that describes itself as a “troll archive.” The article has been on the site since 2015 and is laced with personal attacks against Aldrich.
[…]
A moderator for the site — which has been tied to at least two terror attacks over the last five years — told NBC News that Aldrich has been a contributor since 2015. While the moderator declined to comment on the Club Q shooting, the entry about Aldrich was updated on Nov. 22, just days after the shooting, with the sentence, “It wasn’t our fault, we swear!”
[…]
[Alejandra] Caraballo [a clinical instructor at Harvard Law School’s Cyberlaw Clinic] described the different potential effects of the suspect’s identity as a Kobayashi Maru, which is a training simulation in “Star Trek” where there are no winning outcomes. 

Regardless of whether the suspect is being sincere, Caraballo said, the suspect’s claim could allow anti-LGBTQ activists and pundits to spread the false idea that nonbinary and trans people are unstable and dangerous. And if Aldrich is lying, those pundits could also use it as a reason to refuse to recognize self-identification in other contexts, such as in prisons, when trans women request to be housed with women.
https://www.nbcnews.com/nbc-out/out-news/extremism-experts-say-discussing-colorado-shooting-suspects-pronouns

Why Conservatives Invented a ‘Right to Post’ [The Atlantic]

…just how obvious does bad faith have to be before we recognize it as such?

https://www.theguardian.com/environment/2022/dec/10/cop15-what-are-the-key-targets-for-the-biodiversity-agreement

Some of the world’s largest oil and gas companies have internally dismissed the need to swiftly move to renewable energy and cut planet-heating emissions, despite publicly portraying themselves as concerned about the climate crisis, a US House of Representatives committee has found.

Documents obtained from companies including Exxon, Shell, BP and Chevron show that the fossil fuel industry “has no real plans to clean up its act and is barreling ahead with plans to pump more dirty fuels for decades to come”, said Carolyn Maloney, the chair of the House oversight committee, which has investigated the sector for the past year.
[…]
In reality, executives, the documents show, were derisive of the need to cut emissions, disparaged climate activists and worked to secure US government tax credits for carbon capture projects that would allow them to continue business as usual. Maloney, a Democrat, said that “these companies know their climate pledges are inadequate, but are prioritizing big oil’s record profits over the human costs of climate change”.
[…]
[Ro] Khanna rejected allegations from Republicans that the Democrat-led committee had engaged in a sort of corporate witch-hunt. “The industry was the one out there continuing to make false statements about climate change and climate legislation,” he said. “Our goal is to get them to stop engaging in climate misinformation.”

Several of the company executives appeared before the committee, where they faced accusations their companies knew of the dangers of the climate crisis for decades, only to hide this from the public. Darren Woods, chief executive of Exxon, said last year that his company’s claims over climate change were “consistent with science” at the time.
[…]
Privately, however, these companies downplayed any need to scale down their fossil fuel activity and even to ramp it up, the committee found.
[…]
One BP executive subsequently asserted in an internal email that the company had “no obligation to minimize GHG [greenhouse gas] emissions”, while another admitted that any of its divestments of fossil fuels “may not directly lead to a reduction in absolute global emissions”.
[…]
“The key revelation in this report is that big oil has no intention of actually following through on its climate commitments,” said Jamie Henn, director of Fossil Free Media.

“It isn’t transitioning to clean energy, it’s doubling down on methane gas, and it’s actively lobbying against renewable energy solutions. This is the big tobacco playbook all over again: pretend you care about a problem, but continue your deadly business as usual.”
https://www.theguardian.com/business/2022/dec/09/oil-gas-companies-fossil-fuel-industry-house-committee

The committee said it found Shell, Chevron, BP and the American Petroleum Institute all made major investments in projects that would “protect and entrench the use of fossil fuels, long past the timeline scientists say would be safe to prevent catastrophic climate change” despite making climate pledges.

“They’re basically saying, ‘we’re going to increase production, we’re going to increase emissions, but we’re also going to be able to claim being this clean tech company, this green company, because we can take some symbolic actions that make it look like we’re in the climate fight,’” said Rep. Ro Khanna, D-Calif., a member of the committee.

“The cynicism was breathtaking, and unfortunately, it was quite successful,” he said, “It’s been a successful PR strategy.”

…same old, same old?

The committee’s Democratic members all signed on to the report, but no Republicans put their name on it.

When reached for comment, a press representative for the Republicans on the committee pointed to statements Rep. James Comer, R-Ky., made during a hearing in October in which he said the investigation was “to deliver partisan theater for prime-time news.”

…trolling was hardly invented on the internet

“These documents demonstrate how the fossil fuel industry ‘greenwashed’ its public image with promises and actions that oil and gas executives knew would not meaningfully reduce emissions, even as the industry moved aggressively to lock in continued fossil fuel production for decades to come — actions that could doom global efforts to prevent catastrophic climate change,” the committee wrote in the report.
[…]
The report went further to say that the big oil companies have avoided accountability and obstructed the committee’s investigation, which was originally launched in September 2021, after not complying with subpoenas for documents issued by Rep. Carolyn Maloney, D-N.Y, the chair of the committee.

…but…if members of congress aren’t in a position to force industry’s hand…I might not be entirely clear who is…outside of the traditional pitchforks&torches sort of a mob…&…well…that many torches is probably going to undermine the point in this kind of case?

“That’s the only way we’re going to have accountability,” he said. “You can’t expect a House subcommittee to go up against oil companies that have been misleading American public for 40 years and all of a sudden have accountability.
https://www.nbcnews.com/science/environment/oil-companies-doom-global-efforts-climate-change-house-committee-finds

…with elected officials like these

Sinema – “She answers to billionaires” [Guardian]

The Panhellenic Socialist Movement (PASOK), one of Greece’s main opposition parties, said in a statement Friday: “Following the latest developments and the investigation by Belgian authorities into corruption of European officials, MEP Eva Kaili is expelled from PASOK-Movement of change by decision of President Nikos Androulakis.”

Kaili’s political group within the European Parliament, the Progressive Alliance of Socialists and Democrats, also announced on Friday they were suspending Kaili from the group with immediate effect “in response to the ongoing investigations.”

This comes as Belgium’s federal prosecutor confirmed to Belgian public service broadcaster RTBF on Friday that one of the parliament’s 14 vice presidents had been taken in for questioning as part of a probe into corruption involving the European Parliament and a country from the Persian Gulf.

In a statement, the prosecutor said that for two years, Belgian federal police inspectors “suspected a country from the Persian Gulf of influencing economic and political decisions of the European parliament,” according to RTBF.
https://edition.cnn.com/2022/12/09/europe/eva-kaili-european-parliament-greece-expelled-intl-hnk/index.html

https://www.theguardian.com/world/2022/dec/08/qatar-gas-output-increase-catastrophic-global-heating-report

…who needs…well…looking out for?

https://www.theguardian.com/environment/2022/dec/09/marine-life-threatened-perfect-storm-red-list-reveals-species-on-brink-extinction-aoe

…& who’s got their eye on the clock?

The resulting shift in my sense of time had a range of effects. I found it harder to pay attention to other events and processes that took longer or played out less sensationally even if I cared about them — like the local effects of climate change, grass-roots housing campaigns or even just the details of friends’ lives. I felt like my thoughts were running on shorter loops or never getting completed. Even my breaths were short, as though a full inhale couldn’t fit into such tiny intervals, and my joints would ache from a state of constant anticipation. It was the feeling of a furrowed brow, applied to my entire body. Most haunting was a sense that I had no substance, and that the physical world, with all its minute fluctuations and gradual changes, was somehow losing its color and texture.

In the past few years, in part because of how frayed my mind felt, I started avoiding my Twitter and Instagram feeds altogether. From this remove, I sat down and wrote out on paper what it was that I really wanted from these platforms. The answer ended up being a sense of recognition among peers, connection to people with shared interests and whose work I admire and the ability to encounter new, unexpected ideas. As opposed to algorithms, I wanted these new things to be recommended by individuals who had reasons to like them, like the weekly set on my local college radio station by a D.J. whose wide-ranging taste I’m at pains to describe, but reliably enjoy. Really, I think I just wanted everything to have a little more context.
What Twitter Does to Our Sense of Time [NYT]

…& who’s looking out for whose interests?

Weisselberg was a Trump loyalist for over 50 years, a virtual family “apprentice.” He wouldn’t have turned state’s evidence unless the Manhattan District Attorney’s office had him dead to rights.

Loyal to the end, Weisselberg never fingered Trump personally at trial and even cooperated with defense lawyers by forswearing Trump’s involvement in the fraud. Still, Weisselberg’s testimony was the centerpiece of the Trump Organization’s conviction because he laid out how he saved the company taxes.
[…]
Of course, the jury didn’t have to guess who was the primary beneficiary. Although Trump was not a named defendant, the prosecution went out of its way to insert Trump into the jurors’ minds, arguing in closing arguments that Trump explicitly sanctioned tax fraud and that “this whole narrative that Donald Trump is blissfully ignorant is just not real.”
[…]
Prior to the convictions, DA Bragg had already seemed to be reviving his stalled criminal investigation into Trump personally by hiring Matthew Colangelo, a highly experienced Justice Department lawyer and complex white-collar fraud investigator. Before joining the top tier at DOJ, Colangelo led New York Attorney General Letitia James’ inquiry into Trump.

Trump could be forgiven just now for secretly wondering why he ever ran for president, even as he runs again, motivated partly, it appears, by its cherished immunity from prosecution. He got away with questionable financial conduct for years in New York before he took his misconduct to Washington and multiplied it several hundred times over.

By thrusting himself into the national spotlight, there is no way that his misconduct wouldn’t catch stellar prosecutors’ careful attention.
https://www.nbcnews.com/think/opinion/trump-org-verdict-shows-best-tool-prosecutors-have-former-president

…or talking out the side of their mouth

Speaking to members of his personal human rights council on Wednesday, Putin claimed that Russia would not use nuclear weapons first in any conflict, denied that Russian troops were deserting en masse from the field of battle, and claimed he would not need to mobilise more troops, a process that has caused considerable upheaval in Russia.

But mainly the Russian president defended the “special military operation” – his preferred term for what he openly admitted was a Russian war of conquest that he compared with the territorial ambitions of former Russian tsars.

“As for the slow process of the special military operation, then, of course, it can be a long-term process,” Putin said. “But then you mentioned that new territories had appeared. This is such a significant result for Russia … The Azov Sea has become an internal Russian sea. Even Peter I had fought for access to the Azov Sea.”
https://www.theguardian.com/world/2022/dec/07/vladimir-putin-says-russias-war-on-ukraine-could-be-long-term-process

“The settlement process as a whole, yes, it will probably be difficult and will take some time. But one way or another, all participants in this process will have to agree with the realities that are taking shape on the ground,” the Russia president said during remarks at a press-conference in Bishkek, Kyrgyzstan.
[…]
Despite all evidence to the contrary, Putin claimed that his military operation was going to plan. “Everything is stable. There are no questions or problems there,” he said, adding that information was being given to the public transparently.
[…]
Speaking after an awards ceremony for “Heroes of Russia” at the Kremlin on Thursday, the president addressed a group of soldiers. Acknowledging the targeted attacks by Russia, Putin blamed Ukraine for initiating a trend of attacking civilian infrastructure, pointing to a blast on a key bridge between the Russian mainland and the annexed Crimean peninsula.

“Yes, we do that,” Putin said, of the strikes on the Ukraine grid. “But who started it? There’s a lot of noise about our strikes on the energy infrastructure of a neighbouring country. This will not interfere with our combat missions.”
https://www.theguardian.com/world/2022/dec/09/putin-shelling-ukraine-power-grid-russia-president-strikes-energy-infrastructure

…who started it? …who fucking started it? …fuck that for a game of soldiers

…damn it…I was going to make this about something altogether different…but…best laid plans & all that…oh, well…maybe someone else will get to that stuff…or…I dunno…it’ll keep until tomorrow…assuming tomorrow ever comes?