Conflict, consensus, crisis. Three minimum notes on the protests – OnCubaNews

Most of the opinions circulating about the July 11 protests in Cuba, particularly those that reject disorder and violence, as well as those that interpret and propose solutions to the conflict, must be right. Many reflect civic concern and commitment to issues that go beyond personal interest. Seen like this, they would be a sign of social glue, of citizen participation and consensus. At the same time, they are the mirror of a significant conflictiveness.

In this brief space, I will avoid discussing good or bad intentioned interpretations, experiences lived, read or heard, recommendations to the government, etc. I only propose to take a step back, to coldly examine some basic problems, among the many that lie ahead.

What do the protests mean?

If we were to ask mile Durkheim, one of the founders of Sociology, what is the nature of these protests, he could answer that it is a classic case of anomie. Anomie defines a situation where previously established norms and values disintegrate; a typical reaction of periods of drastic and rapid changes in the social, economic or political structures of society. Social groups that experience anomic reactions may feel disconnected, as if they do not belong to their society, and as if their society does not value their identity. Anomie can cause purposelessness, hopelessness, and encourage deviance and crime. I have intentionally underlined a few keywords in this classic definition, which is the ABCs of sociology.

In Cuba, we have been going through a transition process for more than two decades, characterized by profound changes in the social structures and in the economic life of the people, but also in the relations between civil society and political power. Among other changes, lets say, there is the very idea of socialism, which now incorporates conceptions different from those defended for half a century, as well as unprecedented policies. This transition has made visible a crisis of norms and values, widely debated in various public spaces and media. Likewise, the weakening of the sense of belonging has been pointed out; and the reproduction of marginality and its typical behaviors, within subordinate neighborhoods and social groups, but also the proliferation of crime in other social and institutional spaces, where corruption grows. As for despair, the art and literature disseminated on the island are a good mirror.

In other words, what is happening in Cuba is an anomie that should not catch us by surprise, because its factors and manifestations have not remained hidden or muzzled, as anyone can see without having to read social networks or anti-government newspapers. It has been there, in front of everyone, analyzed and discussed for too long, to ask ourselves now where the protests come from, as if they were thunder in a clear sky. Rather, one should ask why they have not happened before.

How is it that the Cuban opposition, on the island and in Miami, using the fashionable unconventional war manuals, and the CIA itself, have not managed to unleash something like this until now? And why precisely now? Durkheim would resort to another concept shared by social sciences and civil engineering: fatigue. After a year and a half of COVID-19 and six months of queues to buy basic products as Dr. Durn would say we are all more vulnerable.

What is happening to the new government?

I have pointed out before that the consensus has become more heterogeneous and contradictory in Cuba, that it has incorporated dissent, and that the Cuban government knows it. Before taking office as president, Ral recognized that the leadership of the founder of the Revolution, Fidel, was not inherited. Daz-Canel, who was already in the Political Bureau in Fidels time, was also able to know this; and in any case, he has experienced it firsthand since he took office in 2018. In fact, continuity has entailed different ways than the historical ones did before. Circumstances, which are the benchmark of politics, had already been imposed on them before they retired.

I underline what I say about a new government, because if it is postulated that this is the same Cuba as Fidel and Ral, witty literary metaphors can be constructed, but the countrys political and social process is difficult to understand. This government has sought to build its own consensus from the beginning, instead of resting on what some call the political capital of the Revolution. However, the yardstick to measure change is already another.

In effect, the new government has proposed unprecedented reforms since 1960, beginning with a new Constitution, which admits a mixed economy, with markets and the private sector, and which grants unprecedented autonomy to local powers. Its new style, learned by holding leadership positions in the provinces, emphasizes the interaction between the central and local level; and it has ministers under the age of 60 explaining problems and answering questions on television. Unlike previous periods, citizens can identify them by their names, judge them, praise them or openly mock them.

There has never been a moment like this before in terms of freedom to criticize the government, on social networks, but neither in public media, nor to access information from very diverse sources, including those of the opposition; nor is there greater freedom to enter and leave the country. Article 56 of the Constitution approved in 2019 establishes the right of association and public demonstration. In fact, a demonstration law was scheduled in the legislative calendar for October 2020 postponed, along with a dozen other bills due to the coronavirus. Regardless, the prevailing yardstick dictates that this government has done far less than it should. According to that rod, its glass would be almost empty.

As if that were not enough, after a year and a half focused on a formidable global human security crisis called a pandemic, without resources or protective alliances like those of yesteryear, this government has had to deal with the largest manifestations of discontent that occurred since 1959 Going down the streets of San Antonio de los Baos, President Daz-Canel must have remembered, like all of us who lived the summer of 1994, Fidel followed by a sea of people, going down San Lzaro street, to control that outbreak of anomie on the Malecn, without weapons or specialized forces to deal with riots. In a certain way, he did exactly the same thing as Fidel: to appear at the scene of the events, and summon the revolutionaries to take to the streets and face violence, by force, if necessary.

The same media, however, may produce different results in other circumstances. It took him a few hours to realize it. But his first slogan was carried out to the letter, not only by the police, but by the summoned organizations, first of all, the Party. Across the street, the opposition, as on November 27, 2020, capitalized on the discontent and increased the tensions. The classic escalation of violence studied by experts in conflict resolution1 was immediate.

A more complicated scenario could not be imagined to maintain the route outlined in the 8th Party Congress, just 90 days ago.

What violence and how?

In a model country for many in terms of stability, citizen respect and internal order, such as Japan, protests against police brutality against foreigners or racism are not uncommon. A group of foreign (that is, Korean) protesters can gather around them a cloud of police officers dressed as characters from Star Wars, with polycarbonate helmets and armor, armored shields and tonfas.

We are used to seeing images of violent demonstrations in other countries. Those who throw stones are part of the people, who rebel against injustice; those who shoot jets of water from riot control vehicles, tear gas, rubber bullets, or real ones, are the repressive forces. These global images do not discriminate between countries such as Chile, South Africa, Kyrgyzstan or the United States, with hundreds of wounded and dozens of deaths that are their balance.

The photos and videos that circulate in the media such as BBC Mundo above all suspicion of collusion with the Cuban regime reveal that neither the National Revolutionary Police (PNR), which here in Cuba is the only police institution, nor the special troops from the Ministry of the Interior (MININT) or the Revolutionary Armed Forces (FAR) deploy those resources. Surely the Institute of Police Sciences of the MININT teaches how to face violent scenarios. But no class or exercise is equivalent to dealing with 700 angry people marching down the street under the summer sun or doing it by force if necessary even if its instructions say to avoid injuring them or using lethal means.

This is not a technical or circumstantial detail. Among the images of the protests that went viral on social networks, a dozen protesters turned police cars upside down, and even other vehicles, jumped on them and destroyed them. Compared to any capital in Latin America, there are no forces that prevent these attacks on authority, and that repress them at that time. At the same time, some police officers and civilians, summoned to mobilize in the theater of the confrontation, incurred excesses.

Among the few data available to measure physical violence is the looting of stores, in freely convertible currency and in Cuban pesos. There were none in San Antonio de los Baos; nor in Havana until after the television appearance of President Daz-Canel (4:30 pm). Of the 28 assaults registered up to that time, 68% (19) occurred in Matanzas, the province most affected by the pandemic; almost all of them in Crdenas (13), where the combination of the drop in tourism in Varadero plus the quarantine has hit a relatively higher standard of living than in other places in the province. In that period, there was only significant looting (4) in Coln (Matanzas), and Gines (Mayabeque); and others scattered in Holgun, Bayamo, Gira (1). After the Presidents intervention, 13 stores were raided, including 4 in Havana.

The social polarization that this violence shows is inversely proportional to unity, that is, to the construction of consensus. In addition, it has a negative impact on the image of the country, which works in favor of the cornerstone of U.S. policy: isolation. Preventing the battle won at the UN from being lost in the streets of Crdenas or Paseo del Prado is also a national interest.

After having tried everything with Fidel and Ral, and 25 years after the end of the Cold War, Barack Obama and his government considered that this policy was ineffective, according to their national interest. However, although Joseph Biden, vice president of that government, supported normalization, things have changed for them. What if Daz-Canel, without the wisdom and experience of the Castros, were not able to deal, at this moment of vulnerability, with the Cuban crisis? They might reason that it is better not to lower the heat on the blockade right now, but to let it continue to simmer the island. As you would say in Cuban: whats the rush?

The protests are lessons for all who want to read them. They could teach some economists that the success of the reforms does not depend only on technically solving planning, the market, the socialist state enterprise or the private sector, but on tackling problems such as income redistribution, consumption stratification, the adjoining economically brilliant or dark spaces, the inequalities and territorial and local setbacks, the state of the productive forces called workers. They have also shown politicians that the problem of national unity is that of consensus, and that it is not solved only with summoning mobilizations of revolutionaries, but through sustained dialogue with all citizens. They have shown the Party apparatuses, once again, that the effectiveness of a public media system is not ideological, but political, and that it is measured by its credibility and capacity to convince (the unconvinced, of course). They have confirmed that law enforcement agencies can provide first aid to outbreaks of violence, but at the cost of other damage, and that it is not they who should deal with the social and political problems where dissent takes root. Finally, it has shown U.S. politicians that its alliances with this bellicose opposition reinforces the hard line on both sides, and damages the real exercise of freedom and human rights in Cuba.

The common denominator of these lessons is Cuban society, with its lights and shadows. Knowing how to decipher its present, without bipolar roadmaps, will decide what will come.

Note:

1 Violencia y solucin de conflictos, in Temas magazine # 53, January-March, 2008.

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Conflict, consensus, crisis. Three minimum notes on the protests - OnCubaNews

Who will win the battle for ‘based’? – Spectator.co.uk

Earlier this week, a pair of right-libertarian journalists announced the launch of their new site, BASEDPolitics. All hell promptly broke loose on right-wing Twitter.In the first editorial for their new site, co-founders Brad Polumbo and Hannah Cox define 'based' as 'upfront, on point, or rooted in true principles.' That fits pretty well with my understanding of the term, but it leaves something out.

That 'something' accounts for the pushback they received from the post-liberal, national conservative crowd. According to them, libertarians like Polumbo and Cox are nothing more than Koch-funded shills who fight for tax cuts and weaker antitrust laws while drag queens read to our children. They are not 'based' and have no right to refer to themselves as such.

'Our culture is not your costume,' one popular right-wing Twitter personality quipped. Sohrab Ahmari, an American Conservative editor who advocates for 'political Catholicism,'tweeted'Im never using based again, now that these corporate schmucks have appropriated it.'

Ahmari also threw in some disparaging comments about Polumbos 'gigantic' head and Coxs 'tackily overspilling dcolletage' as they appeared in the announcement graphic.

I asked Polumbo (full disclosure: he and I are both affiliated with Young Voices) whether he expected this kind of reaction. Heres what he had to say:

Oh yeah, we anticipated pushback from the very-online nationalist crowd. Im not particularly bothered by it, although some of it has been ad-hominem and juvenile, and thats pretty pathetic, fan behaviour. We wont stoop to that. But the pushback is kind of the point. The nationalists want to redefine what it means to be conservative so that it resembles big government, socially conservative Elizabeth Warren economics more than Ronald Reagan. We still believe the future of the Right should be rooted in free markets, individual liberty, the Constitution, (and)limited government.

The term 'based' originated as slang for being high on crack. Perhaps theres some connection with 'freebasing', or smoking cocaine. From there, the terms definition expanded to cover all the strange and erratic behaviours typically associated with 'crackheads'. A modern equivalent might be to say someone is 'trippin' or 'tweakin'. These dont necessarily mean the person is under the influence of psychedelics or meth, only that theyre acting like it. 'Youre crazy,' spoken either with total dismissiveness or with a hint of admiration, would convey the same meaning.

'Based' began to take on its current connotation with rapper Lil B the Based God, who released his first album, Based Boys, in 2007. According to Lil B, 'Based means being yourself. Not being scared of what people think about you. Not being afraid to do what you wanna do.'

According to one online dictionary, the term, now a 'signal of power and swagger,' became associated with the online right in the 2010s as a synonym for 'politically incorrect'. Donald Trump was 'based' because he was willing to say things that annoyed the libs and then laugh at their outrage.

'Can you believe OrangeMan said X?!' the outraged soycuck shrieks. 'Lol, based,' the gigachad responds.

It seems to me that at this point, an earlier definition of 'based' unrelated to West Coast drug culture began to influence the terms use by the new right. 'Based' retained its sense of the manic, un-self-conscious energy of Trumps Twitter, but it also took on the the sense of being 'based on' or 'based in' something older and sturdier than the endless flux of liquid modernity. ric Zemmour is based. So is Viktor Orbn. Jailing pornographers, seizing the assets of the Ford Foundation, and going to Latin Mass with your nine kids and tradwife are all based. On the darker corners of right-wing Twitter, Rhodesia, Mussolini and overt expressions of sexism are also 'based'.

The prevailing definition of 'based' sits somewhere near the intersection of troll and trad.

Polumbo told me hes fully aware that hes going against the usual meaning of the term:

'While not our only mission, a crucial part of our project is to explicitly combat the nationalist conservative movement in a substantive and ideas-based way. We are redefining what it means to be based, whether they like it or not. Freedom is based. Catholic integralism and other forms of lite-theocracy are authoritarian and un-American.'

The post-liberal response, of course, would be that right-libertarianism, like progressivism, is a dominant ideology masquerading as a scrappy resistance. They are two faces of the same beast called liberalism. They divide the world between them: freedom in the boardroom and freedom in the bedroom.

Im not nearly the libertarian Polumbo is, but Im not a fully convinced post-liberal yet either. I think wokeness is a far greater threat than socialism. At the same time, I worry that any sort of post-liberal political project could lead to tyranny. The levels of social conservatism and, frankly, religiosity it demands simply dont have enough buy-in to win national elections.

Imagine the average Joe Rogan listener. Not the alt-right white nationalist monster sketched out in thinkpiece after thinkpiece, but the representative of the American median, the 'barstool conservative'.Hes economically agnostic, an admirer of entrepreneurship who distrusts large corporations. Socially, hes slightly to the left of centre. The idea of giving puberty blockers to kids freaks him out, but he has no interest in outlawing gay marriage or no-fault divorce. Hed be more likely than Polumbo to support trade protectionism and breaking up big tech, but Ahmari would have a hard time selling him on porn bans and blue laws.

Polumbo and Cox are betting that this voting bloc will be more open to Friedrich Hayek than to Thomas Aquinas. Their plan seems to be to stan capitalism while casting wokeness as a collectivist distortion of individual liberty rather than its natural outgrowth. Its possible, they promise, to combat the excesses of progressivism to be 'based' without throwing out many of the fundamental assumptions of American politics and culture.

It might work. If their attempt to reclaim 'based' succeeds, well know it has.

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Who will win the battle for 'based'? - Spectator.co.uk

Is Ron DeSantis Shaping Up to Be Trump 2.0 in 2024? – Truthout

A common refrain in the Trump era was that despite all of Donald Trumps racist, xenophobic ambitions, he was too incompetent to carry out a wholescale remaking of U.S. society. Theres no question his four years in office had a profound, disastrous effect on the people and communities his administration targeted immigrants, Muslims and trans people, just to name a few. Plus, his openly fascist rhetoric and sometimes actions significantly emboldened the far right. However, both his legislative agenda, and to a lesser extent his exercise of executive authority, were likely hampered by his lack of experience in elected office and overall laziness, lack of discipline and inattention to detail.

Many advocates understandably fear that Trumps eventual Republican presidential successor, whoever they are, could combine the most toxic elements of Trumpism with a greater degree of technocratic skill. A more-competent Trump could do even greater damage to U.S. political infrastructure, like the refugee resettlement system that Trump dismantled, that could take decades to rebuild. A more-competent Trump could also potentially shepherd through a legislative agenda that far exceeded Trumps, which consisted primarily of a standard-fare Republican tax cut for the wealthy.

Currently, the most likely GOP successor to Trump seems to be Florida Gov. Ron DeSantis, who regularly ranks as Republicans top choice in the 2024 presidential primary if Trump declines to run. Trumps polling lead over DeSantis appears to be narrowing in recent months, though any surveys this far out should be taken with a grain of salt. Everything in DeSantiss public record suggests that he poses a serious threat to democracy, the working class and marginalized communities. DeSantis recently signed into law some of the nations most stringent anti-critical race theory legislation, and ordered a review of the states university system to determine if professors were indoctrinating students into a stale ideology, clearly a reference to ideas ranging from anti-racism to socialism. Hes also pushing a bill that would prevent teachers and private businesses from making white people feel discomfort when learning about the history of racist oppression in the United States.

DeSantis has also recently staked out his position as more anti-vaccine, anti-booster than Trump himself. In December, the Florida governor refused to say if hed gotten a COVID booster when asked by Fox Newss Maria Bartiromo. Ive done whatever I did, the normal shot, DeSantis said. DeSantis got the Johnson & Johnson single dose in April, and stonewalled in October when asked if he would get a booster.

These statements, as well as DeSantiss rising stature in the national Republican Party, seem to have rankled Trump. In comments that were widely understood to be directed at DeSantis, Trump criticized politicians who wouldnt say if they had gotten a COVID booster shot. Many Republican politicians had in fact gotten the booster, but they dont want to say it. Because theyre gutless, Trump said on the far right One America News Network. You gotta say it whether you had it or not. (At a rally in December, Trump told the crowd that hed gotten the booster. They booed him in response.)

Several days later, Axios reported Trump has been calling DeSantis a dull personality in private meetings. Also, in that report, Trump aides claimed the former president was angry that DeSantis hasnt pledged not to challenge Trump in the 2024 GOP primary, should he run again. The New York Timess Maggie Haberman tweeted that shed heard similar frustrations from those in Trump world, who said Trump thought DeSantis should be showing him more deference.

DeSantis, for his part, has taken shots at Trump as well. On the conservative Ruthless podcast, the governor said one of his biggest regrets since taking office was not being much louder in opposing Trumps calls for soft lockdowns as COVID initially spread throughout the country and world.

DeSantis also appears to be shoring up support from conservative media stars to build a parallel track of public support, separate from his standing with Trump. On the anniversary of the January 6 storming of the Capitol, the Florida governor gathered nine prominent social media stars in Tallahassee, Politico reported. Blaze TVs Sara Gonzales told Politico it would be a mistake for DeSantis not to run, and that many conservatives were hungry for someone with the guts to speak for them without fear of repercussions, but also without the obvious baggage that Trump carries.

However, despite the simmering tensions between the two men, neither appears eager to engage in an all-out attack on the other. Last week, Trump told reporters that he has a very good relationship with DeSantis. He reminded them of his early support for the Florida politician when he was a relatively unknown congressman making a longshot bid for governor. DeSantis won the [gubernatorial] election the day I announced that I was going to give him my endorsement, Trump said on the call. He made similar comments to New York Times reporter Jeremy Peters in a forthcoming book, underscoring the degree to which Trump believes hes responsible for DeSantiss success. Look, I helped Ron DeSantis at a level that nobodys ever seen before, Trump told Peters.

Despite the emerging personal rivalry between DeSantis and Trump, the two are ideologically nearly identical, and also govern in a similar manner. DeSantis reportedly rules Florida with an iron fist and demands total fealty and loyalty, just as Trump does. Ron DeSantis is essentially the speaker of the House, the president of the Senate and the chief justice of the Supreme Court right now, one Republican legislator recently told Politico. Another GOP state legislator said in the same report that its well known you cant go against him. If you cross him once, youre dead.

In another clear echo of Trumpism, DeSantis is pushing for the creation of a new, so-called election police force. The new sub-agency, whose proposed official name is the Office of Election Crimes and Security, would operate under the Department of State, which is controlled by the governor. Voting rights advocates are understandably alarmed, citing the extremely low levels of deliberate voter fraud and arguing that the goal of the new sub-agency is to depress turnout, particularly among Black voters and other groups historically targeted for harassment.

Also worrisome is a new proposed congressional district map released by DeSantiss office, an incredibly rare phenomenon. DeSantis map would cut in half the number of African American districts from four on current proposed congressional maps to two, while boosting the number of seats Donald Trump would have won in 2020 to 18 from the 16 on the map currently being considered by the GOP-led Florida Senate, Politico reported.

The 2024 primary will semi-officially start this year, after the November midterms. Trump hasnt announced whether hell run, but all signs suggest that he will. DeSantis is a young, popular, far-right politician who doesnt command the base of the party like Trump does, but comes closer than any other potential challenger at the moment. Ever since Trumps upset victory in 2016, those on both the right and the left have wondered what Trumpism without Trump might look like. In DeSantis, we could be seeing an answer.

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Is Ron DeSantis Shaping Up to Be Trump 2.0 in 2024? - Truthout

H+ 3: Radical Life Extension? Cybernetic Immortality? Or Resurrection of the Body? – Patheos

Which do you prefer: radical life extension? Cybernetic immortality? Resurrection of the body? Or, just death as endless oblivion?

Transhumanism also known as Humanity Plus or H+ plans to solve all human problems with advances in AI (Artificial Intelligence). One H+ goal is to cure death. Without the threat of death, we could elect to live forever. Either in your body or in disembodied form. Are you interested?

Here are four options. Check the box you prefer.

1 Natural death as the end of all conscious existence.

2 Radical Life Extension (RLE) in your present body.

3 Cybernetic Immortality (CI): your consciousness lives on in the computer cloud.

4 Resurrection of the body as promised in 1 Corinthians 15.

In this post the public theologian will explore the contrast between radical life extension and resurrection in light of transhumanist promises. Whether via Radical Life Extension in the body or Cybernetic Immortality in disembodied form, enhanced human intelligence and consciousness have an unending future. So we are promised. Should we trust this techno-promise? Or, should we trust Gods promise of resurrection from the body, the soma pneumatikon? What does it take for us greet the end of life with contentment?

Tracy Trothen and Calvin Mercer are the indefatigable chroniclers of the interaction between Religion and the Technological Future.

Here, in this post, I offer the third in a series of column posts tackling the religious, ethical, and social concerns raised by genetic engineering, AI (artificial intelligence), IA (intelligence amplification), transhumanism, and posthumanism. First, we asked: H+ 1: Is AI a shortcut to virtue? Or to holiness? Then, secondly, we examined varieties of religious transhumanism in the post: H+ 2: The Transhuman, the Posthuman, and the Truly Human. Here we take up one specific issue: how do we compare multiple scenarios for life extension and immortality?

Death is natural, right? Death is the irreversible cessation of the processes that keep the body working, observes physicist and theologian John Polkinghorne. Death really is the end. Its annihilation (Polkinghorne 2019, 49). With death comes oblivion.

Yet, the prospect of falling from existence into non-existence at the moment of death issues forth in anxiety. In the anxiety of having to die nonbeing is experienced from the inside, says theologian Paul Tillich. This anxiety is potentially present in every moment. It permeates the whole of mans being; it shapes soul and body and determines spiritual life; it belongs to the created character of being quite apart from estrangement and sin(Tillich 1951-1963, 1:193-194).

Is death a disease that needs to be cured? Bioethicist Gilbert Meilaender denies that aging and death belong in the disease category. Unlike disease, he says, aging is a natural stage of life that seems built in (Meilaender 2013, 2). We should live within the limits of death and aging by cultivating the virtue of patience.

If you check this first option, you elect to end your embodied consciousness and to drop from being into nonbeing. Can you be patient with this?

Transhumanists define death as a disease. Like other diseases, medical science will cure death. Then, we can live in our present bodies indefinitely.

One clarification. Lets distinguish between the aim of longevity research (LR) and radical life extension (RLE). LR is being pursued by the Buck Institute, Geron Corporation, Michael D. Wests Therapeutics, and other laboratories. Both LR and RLE belong to the prolongevity club. Note that LR is modest while H+ RLE is dramatic. Big bucks finance both. (Photo: Aubrey de Grey)

Oxford transhumanist Nick Bostrom sells stock in both LR and RLE because of the potentially enormous returns, in terms of human welfare, to investment in biogerontological research if it could lead to a further significant extension of the human health span.

Cambridge geneticist and biogerontologist Aubrey deGrey proclaims that science must triumph over what has hitherto been natures province, namely, aging and natural death. There is a good chance aging can be entirely defeated within the next few decades, de Grey writes. The speed of speed is speeding up, meaning that the relevant laboratory research is advancing at an increasingly rapid pace. The longevity escape velocity or LEV is spiraling upward(DeGrey 2009, 21).

In the race for a life of a thousand years, the runner still needs to dodge incidental death threats. Referring to RLE as practical immortality, Calvin Mercer and Tracy Trothen alert us to remain alert. Practical immortality means that one will not die from internal biological causes that have been associated with aging, but one could still die of such things as accidental causes, a new infectious disease, natural disasters, or a cosmic event(C. a. Mercer 2021, 72).

Radical life extension consists of the prolongation of terrestrial embodied living as we have known it minus the deterioration of aging and the portent of an end to life. Unless we get run over by a bus or shot in a war, we can expect over the centuries an unending number of stints on the altar guild or picnics with the PTA. Are you ready for this?

RLE is embodied immortality. Cybernetic immortality is disembodied.

The aim of the cybernetic prolongevists is to dislodge our consciousness and our intelligence from our biological substrate and upload it into a computer. As long as the computer battery remains charged, we will live in a disembodied electronic cloud virtually forever. Immortality can be attained here by uploading the information stored in our brain, a process called whole brain emulation.

How might this work? Cybernetic immortality could be attained, according to computer whiz Ray Kurzweil, because intelligence is not dependent upon our biological substrate. Kurzweil, transhumanist in mind-set even if not in name, defines intelligence as an information pattern and, as an information pattern, our intelligence could be transferred from our brain to a computer. The current substrate that houses this information pattern is our body, the eighty to ninety billion neurons in our brain. Could this neuronal information be transferred to a disembodied digital substrate? Yes, say transhumanists.

Our intelligence can live on in an enhanced form even when extricated from our bodies and placed in a computer. Uploading a human brain means scanning all of its salient details and then reinstantiating those details into a suitably powerful computational substrate. This process would capture a persons entire personality, memory, skills, and history (Kurzweil 2005, 198-199). From Kurzweils forecast of the Singularity by the year 2045, todays 2045 Initiative has begun to organize the research.

Kurzweil, like others in the H+ movement, plans to derive Homo cyberneticus from modifying Homo sapiens. Once our minds are uploaded, we will become a new species, a posthuman species. The present generation giving birth to the future posthuman species is made up of the transhumanists.

Have we seen this before? Remember Ren Descartes (1596-1650)? Descartes was a substance dualist. Our body is a physical substance while are mind or soul is a spiritual substance. By performing a soulechtomy, God could extract the soul from its physical housing, said Descartes. Now the transhumanist can do what before only God could do, allegedly.

Would you like to live indefinitely bodiless in the computer cloud?

Is it realistic to anticipate the defeat of death and unending finite life? This question must be addressed on two levels, one psychological and the other scientific.

A curious argument has broken out over the psychological acceptance of living indefinitely. Transhumanists are convinced that nobody wants to die. The transhumanists are probably right on this point.

But, does it follow that everybody wants to life forever? This, it turns out, is a matter of debate. University of Liverpool philosopher Michael Hauskeller believes the transhumanists commit the Immortality Fallacy here. If you ask people whether they want to die, most of them will indeed deny it. However, if you as, the same people whether they want to go on living forever, you may find that most will deny this too. It is quite possible that a person does not want to die and still does not want to live forever(Hauskeller 2013, 89).

In short, the question of living forever is independent of the question of death. That a person does not normally want to die does not imply that the same person does not ever want to die (i.e. in the future), adds Pablo Garca-Barranquero at Universidad de Mlaga(Garcia-Barranquero 2021, 183).

Now we ask scientifically, is RLE realistic? Probably not. LR is not likely to lead to RLE, at least according to Michael Shermer, writing in Scientific American, Radical Life Extension Is Not around the Corner(Shermer 2016, 84).

If RLE is not realistic, might cybernetic immortality be realistic? Scientifically speaking, probably not. Kurzweils presupposed theory that the human mind is an information pattern extractible from the brain does not square with what is known about mind, intelligence, and consciousness.

First, human intelligence is not limited to the brain. It is distributed throughout the body by the nervous system.

Second, all thinking includes biological stimulus and interaction, much of it with the surrounding world(Peters, Where Theres Life Theres Intelligence 2017). Intelligence is relational. dependent on the relationship of the body to the world. Our intelligent minds are inextricably embodied and relational.

Computer scientist and theologian Noreen Herzfeld, for example, emphasizes that we cannot be who we are except in relationship to others and to our natural world (Herzfeld 2002, 86-95). In short, disembodied consciousness or mental activity does not make scientific sense. (Photo: Noreen Herzfeld)

The acknowledgment of embodiment makes neuroscientists critical of the concept of cybernetic immortality. Kurzweils knowledge of neuroscience is imply inadequate to the task at hand.He mistakes the striatum for cortex and apical dendrites for axons, belies the cognitive contributions of the basal ganalia.Yet he [Kurzweil] has the unerring belief of the prophet or the fool.(Koch 2013, 760). Are transhumanists fools?

Would you be a prophet or a fool to check the cybernetic immortality box?

Caution. Some in faith communities react spasmodically: H+ should immediately be shunned! Why? Because H+ represents human hubris. Because H+ constitutes playing God like Frankenstein.

Rather than simply kicking our H+ friends, however, I recommend pausing to take a deep breath. Then allot a few moments to compare and contrast RLE and CI with the biblical promise of resurrection.

When we turn to biblical Christianity, the question of immortality does not stand alone. Standing right alongside of resurrection is the forgiveness of sin and redemption from evil. Death constitutes a cleansing, so to speak. We become washed in the blood of the lamb.

Before approaching omega, lets return for a moment to alpha. Lets return to the expulsion of Adam and Eve from the Garden of Eden in Genesis 2 and 3. Why did God expel Adam and Eve from the garden and place an angel with the fiery sword next to the No Admittance sign? Was God throwing a temper tantrum in response to the eating of the forbidden fruit? No. Adam and Eve had certainly eaten from the Tree of the Knowledge of Good and Evil, but they had not yet tasted the fruit from another important tree in the garden. That was the Tree of Life. Had they eaten from the Tree of Life, then they would live forever (Genesis 3:22). That is, we human beings would live forever in our sin, never able to escape the vicissitudes of betrayal, victimization, suffering, agony, and anxiety anticipating all of this. Evil would then have to be endured everlastingly. Here is the point: death is Gods gift. By sending Adam and Eve to their death, God was graciously bestowing escape from everlasting distress and misery.

What about sin and evil? Our transhumanist friends are as cognizant of sin as a public monument is cognizant of the pigeon excreta that adorns it. That is, they ignore it.

Here is the implication: RLE and CI would perpetuate unendingly human malevolence and victimization. New Testament historian, N.T. Wright reminds us: The kingdoms of the world rage against the kingdom of God; the problem of evil grows teeth and claws, leaping out with a snarl from the debating halls of the philosophers and on to the stage of the real world, turning gardens into deserts and human lives to dust and ashes.Evil is alive and powerful(Wright, Evil and the Justice of God 2006, 38).

It is decisive, then, in Christian theology that when we die we really die to this world. Death is total. No soulecthtomy. No mind extraction. No residuals from this life are carried on. Or, more precisely, the sins and sufferings of this life die with us.

The purpose and meaning of our individual and social lives, to be sure, come to fulfillment in our resurrection. We undergo both discontinuity and continuity as we pass through death into resurrection.

In order to convey this point, Saint Paul employs the seed analogy. A seed in the hand looks dead. Its dry. Inert. But, when we plant it in the garden with fertilizer and water, it springs up with flower or fruit, with beauty or nourishment. This describes, at least in part, what it is like for you and me to die and be raised by God.

So it is with the resurrection of the dead. What is sown is perishable (corrupt, pthora), what is raised is imperishable (incorrupt, aphtharsia).It is sown in dishonour (atimia), it is raised in glory (doxa). It is sown in weakness (astheneia), it is raised in power (dynameis).It is sown a physical body (soma psychikon), it is raised a spiritual body (soma pneumatikon). If there is a physical body, there is also a spiritual body. (I Corinthians 15:42-44).

Note Pauls term for physical body, soma psychikon. That is an ensouled body, a body with a mind. Body and soul along with our intelligence die. Kaput. Kafinished. Over. No cybernetic immortality here.

Paul stresses that what is redeemed is healed, renewed, transformed. In the resurrection we will be made ready by Gods grace for eternal life. Thats what soma pneumatikon indicates, a spiritual body.

To be spiritual does not mean to be ethereal. The resurrected body is still a body, only healed.

Let me mention again that I am editing a book with Arvin Gouw and Brian Patrick Green,Religious Transhumanism and Its Critics(Roman & Littlefield, 2022). Watch for it.

Now, which box did you check?

Our transhumanist friends will attempt to make us immortal so we can live forever in this world, this fallen world. The biblical eschatological vision, in contrast, anticipates a transformation of the world coincidental with our resurrection. Cosmic eschatology and personal eschatology coincide. Eschatology has always to be both universal and individual, says Wolfhart Pannenberg rightly (Pannenberg 1991-1998, 3:543). The consummation of Gods redemptive work for the whole of the cosmos provides the backdrop for our personal resurrection from the graves oblivion. Jesus Easter resurrection is a prolepsis of your and my resurrection.

Reformed theologian and bioethicist Ronald Cole-Turner, sets up the parallel between H+ and the biblical promise. Technology offers to give us what we want, or at least what most of us think we wantlonger life, youthful bodies, greater health, and mental ability. Christianity invites us to give up what we want, indeed to give up life itself, as the one condition for real life(Cole-Turner 2009, 58).

The New Testament message is that the God who raised Jesus from the dead on the first Easter will greet us on the other side of deaths darkness. The light beyond deaths darkness is the light of the world, the brilliance of a redeemed cosmos. This is the gospels call to trust, to trust when we cannot be in control.

Ted Peters directs traffic at the intersection of science, religion, and ethics. Peters is a professor at the Graduate Theological Union (GTU), where he co-edits the journal, Theology and Science, on behalf of the Center for Theology and the Natural Sciences (CTNS), in Berkeley, California, USA. He is author of Playing God? Genetic Determinism and Human Freedom (Routledge, 2nd ed., 2002) and editor of AI and IA: Utopia or Extinction? (ATF 2019). Watch for Teds forthcoming book, The Voice of Public Christian Theology (ATF 2022). Visit his website: TedsTimelyTake.com.

Cole-Turner, Ronald. 2009. Extreme Longevity Research: A Progressive Protestant Perspective. In Religion and the Implications of Radical Life Extension, by ed Calvin Mercer, 50-62. New York: Macmillan Palgrave.

DeGrey, Aubry. 2009. Radical Life Extension: Technological Aspects. In Religion and the Implications of Radical Life Extension, by eds. Derek F. Mather and Calvin Mercer, 13-24. New York: Macmillan Palgrave.

Garcia-Barranquero, Pablo. 2021. Transhumanist Immortality: Understanding the Dream as a Nightmare. Scientia et Fides 9:1 177-196.

Hauskeller, Michael. 2013. Better Humans? Understanding the Enchantment Project. London: Routledge.

Herzfeld, Noreen. 2002. In Our Image: Artificial Intelligence and the Human Spirit. Minneapolis MN: Fortress.

Koch, Christoph. 2013. The End of the Beginning for the Brain. Science 339:6121 759-760.

Kurzweil, Ray. 2005. The Singularity if Near: When Humans Transcend Biology. New York: Penguin.

Meilaender, Bilbert. 2013. Should We Live Forever? The Ethical Ambiguities of Aging. Grand Rapids MI: Wm B Eerdmans.

Mercer, Calvin. 2015. Whole Brain Emulation Requires Enhanced Theology, and a Handmaiden. Theology and Science 13:2 175-186.

Mercer, Calvin, and Tracy Trothen. 2021. Religion and the Technological Future: An Introduction to Biohacking, Artificial Intelligence, and Transhumanism. New York: Macmillan Palgrave.

Pannenberg, Wolfhart. 1991-1998. Systematic Theology, 3 Volumes. Grand Rapids MI: Wm B Eerdmans.

Peters, Ted. 2017. Where Theres Life Theres Intelligence. In What is Life? On Earth and Beyond, by ed Andreas Losch, 236-259. Cambridge: Cambridge University Press.

Polkinghorne, John. 2019. What can we hope for? Cambridge : Cambridge University Press.

Shermer, Michael. 2016. Radical Life Extensiion is NOT around the Corner. Scientific American 316:10 84.

Tillich, Paul. 1951-1963. Systematic Theology. 1st. 3 Volumes: Chicago: University of Chicago Press.

Wright, NT. 2007. Cosmic Future: Progress or Despair? In From Resurrection to Return: Perspectives from Theology and Science on Christian Eschatology, by Christine Ledger, and Stephen Picard, eds James Haire, 5-31. Adelaide: ATF Press.

. 2006. Evil and the Justice of God. London: SPCK.

Young, Simon. 2006. Designer Evolution: A Transhumanist Manifesto. Amherst NY: Prometheus Books.

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H+ 3: Radical Life Extension? Cybernetic Immortality? Or Resurrection of the Body? - Patheos

Tuning protein half-life in mouse using sequence-defined biopolymers functionalized with lipids – pnas.org

Significance

Functionalization of proteins and biopolymers with chemical modifications can be utilized to alter their chemical and biophysical properties. In contrast to traditional chemical functionalization strategies, the use of nonstandard amino acids enables precise positioning of functional groups. Here, we report that multisite conjugation of fatty acids, at precise sites harboring genetically encoded nonstandard amino acids with bioorthogonal chemical handles, can be employed to tune the half-life of proteins in a mouse model. This programmable approach could offer a technical foundation for the modification of protein and peptide therapeutics to improve their efficacy or pharmacokinetic profile (e.g., to prevent rapid clearance and reduce frequency of administration).

The use of biologics in the treatment of numerous diseases has increased steadily over the past decade due to their high specificities, low toxicity, and limited side effects. Despite this success, peptide- and protein-based drugs are limited by short half-lives and immunogenicity. To address these challenges, we use a genomically recoded organism to produce genetically encoded elastin-like polypeptideprotein fusions containing multiple instances of para-azidophenylalanine (pAzF). Precise lipidation of these pAzF residues generated a set of sequence-defined synthetic biopolymers with programmable binding affinity to albumin without ablating the activity of model fusion proteins, and with tunable blood serum half-lives spanning 5 to 94% of albumins half-life in a mouse model. Our findings present a proof of concept for the use of genetically encoded bioorthogonal conjugation sites for multisite lipidation to tune protein stability in mouse serum. This work establishes a programmable approach to extend and tune the half-life of protein or peptide therapeutics and a technical foundation to produce functionalized biopolymers endowed with programmable chemical and biophysical properties with broad applications in medicine, materials science, and biotechnology.

A major goal of synthetic biology is to harness biological systems to produce valuable products, such as new therapeutics, renewable chemicals, and functionalized materials. In the case of proteins, the native translation process uses information encoded in DNA to guide their template-directed production at monomeric precision, albeit limited to the chemistry of the 20 natural amino acids. Work in genetic code expansion with nonstandard amino acids (nsAAs) has expanded the chemical palette of biology through the template-directed biosynthesis of proteins with synthetic chemistries (1). To date, such work has been limited to only one or a few instances of site-specific incorporation of nsAAs per protein, constraining biopolymer synthesis to tag-and-modify approaches or simple protein decorations. Recent advances include an increase in the number and chemical diversity of nsAAs (1), the development of highly active translation machinery for efficient incorporation of nsAAs into proteins (2, 3), and engineered strains of Escherichia coli with recoded genomes possessing open coding channels that can be dedicated to the incorporation of nsAAs (46). Together, these advances enable multisite incorporation of nsAAs to endow proteins and sequence-defined biopolymers with new chemical and biophysical properties.

An active area of interest for the use of nsAAs is to enhance the functionality of protein and peptide pharmaceuticals. They represent a versatile and fast-growing class of biological therapeutics (7, 8) that are particularly attractive as potential pharmaceuticals due to their high specificity, high activity and, in the case of peptides, rapid tissue penetration (7). However, major barriers prevent the widespread clinical use of many peptide or protein-based therapeutics (7): 1) the need to administer them by injection, 2) their rapid clearance by the kidneys, and 3) their rapid proteolytic degradation. As a result, these pharmaceuticals must be frequently administered at high doses, leading to a peak-and-valley pharmacokinetic profile. These characteristics can negatively affect therapeutic efficacy, can cause undesirable side effects with reduced patient compliance (912), and can trigger an immune response, including the induction of a neutralizing antibody response (13, 14).

To address these challenges, proteins and peptides are frequently functionalized to extend their half-life and improve immunotolerance. A widely adopted strategy is the conjugation of poly(ethylene glycol) (PEG), which increases the radius of the protein and reduces proteolytic cleavage, and consequently reduces clearance (15). However, the development of alternatives to PEGylation remains important, as PEGylation does not always offer the desired effect on pharmacokinetics, and in certain cases, safety concerns about its immunogenicity and accumulation in tissues have been raised (1618). An alternative strategy is to conjugate or fuse the therapeutic protein or peptide to serum proteins with long half-lives, such as serum albumin, antibodies (e.g., full-length or fragments of IgG), or blood components, such as red blood cells (17, 18). Similarly, many approaches use chemical moieties or peptides to promote noncovalent binding interactions to the same serum proteins and complexes in order to extend half-life (1720). One effective and safe option is the use of fatty acids (FAs) to promote binding to serum albumin. For example, insulin and glucagon-like peptide-1 (GLP-1) conjugated with a single FA are clinically used to treat diabetic patients (2123).

A major hurdle to the development of functionalized therapeutics is to selectively and predictably modify the protein while maintaining bioactivity. Conventional strategies for PEGylation and functionalization with chemical moieties utilize chemistries that modify the target protein at their termini, or at residues with reactive side-chains (24). The functionalization at C or N termini can be highly selective and predictable, but it can reduce bioactivity and is thus incompatible with many proteins. In contrast, modifications at reactive side-chains (e.g., cysteine or lysine) is less restrictive, but it can be difficult (or practically impossible) to identify unique reactive sites in the peptide sequence for site-specific conjugation. To address this problem, amino acids in the protein are typically mutagenized, which can result in reduced bioactivity. Recently, nsAAs have been successfully employed for modification of proteins and peptides, offering bioorthogonal chemistries for functionalization at predetermined positions within the protein (2426). For example, human growth hormone (hGH) and fibroblast growth factor 21 (FGF21) were site-specifically PEGylated, prolonging their function through extended serum half-life in clinical trials (27, 28). In other cases, site-specific lipidation at a single nsAA was shown to extend half-life in mouse models (29, 30). Although these approaches have improved protein half-life, typically these designs are constrained to a single instance of the nsAA, which limits the versatility and tunability (e.g., customized range of half-lives) of these functionalized peptides and proteins.

In this study, we present a synthetic biology platform to biosynthesize proteinpolymer fusions with sequence-defined conjugation sites for multisite lipidation in order to extend and tailor the half-life of proteins invivo. Specifically, we encoded up to 10 instances of the nsAA para-azidophenylalanine (pAzF) in elastin-like polypeptide (ELP) fusion proteins at high yields in an engineered bacterium with a recoded genome (4), and demonstrate the ability to precisely control the position and number of FAs per biopolymer. We found that the number of FAs per protein is strongly correlated with the binding affinity to serum albumin, enabling us to tune the invivo serum half-life of proteins without accumulation in organs or eliciting an inflammatory response in mouse. These advances could be applied to extend and tune the half-life of protein or peptide therapeutics and establish a technical foundation to produce sequence-defined programmable biopolymers endowed with bespoke chemical and biophysical properties with broad applications in medicine, materials science, and biotechnology.

To enable the biosynthesis of sequence-defined synthetic biopolymers with template-directed conjugation sites, we utilized a recently described synthetic biology expression system that allows efficient incorporation of nsAAs (e.g., pAzF) at UAG codons (Fig. 1A) (2). This system possesses two unique properties. First, the expression host is the genomically recoded organism (GRO) (4), an E. coli MG1655 derivative, in which all instances of UAG stop codons were recoded to synonymous UAA codons, followed by the deletion of release factor 1 (RF1). This GRO establishes an open codon by eliminating competition between an orthogonal tRNACUA/aminoacyl tRNA synthase (aaRS) pair and termination at UAG codons by RF1. Second, aaRSs evolved for aminoacylation with nsAAs typically have significantly reduced activities compared to native enzymes, resulting in low levels of nsAA-tRNA and low yields for proteins with multiple instances of an nsAA (31). Here, we use a tRNACUA/aaRS derived from Methanocaldococcus jannaschii that was evolved for enhanced activity, enabling efficient multisite incorporation of nsAAs into proteins (2). Together, this expression system enables the biosynthesis of polypeptide polymers with multiple pAzF residues at high yields and accuracy.

Biosynthesis and functionalization of genetically encoded biopolymers for half-life extension of proteins. (A) Site-specific multisite incorporation of pAzF at UAG codons in the GRO. All 321 TAG codons in E. coli were genomically recoded to TAA. To create the GRO, RF1 was deleted. The canonical amino acids and pAzF are shown as black and red circles, respectively. The TAG codon is converted into a sense codon for multisite incorporation of pAzF. (B) Schematic of the ELP-protein with 10 pAzF residues. The chemical structure of pAzF and the sequence of a single ELP repeat are shown. (C) Functionalization of azido groups in ELPs through copper(I)-mediated click chemistry with alkynyl palmitic acid. (D) Functionalized biopolymers are characterized in mice to study impact on half-life.

To study the effect of the number of FA conjugates on the invivo serum half-life, we chose to introduce the nsAA in an ELP with 10 consecutive pentadecapeptide repeats for functionalization. ELPs have previously been fused to active therapeutic peptides for a variety of indications, including type 2 diabetes and cancer (32), and serve as a versatile module to alter their pharmacokinetics. Within each repeat of the ELP, we encoded either a tyrosine or a pAzF residue at a designated guest residue position (henceforth named the target residue) (Fig. 1B), such that the genetic template controls the number and position of pAzF residues in the ELP-GFP. In turn, the bioorthogonal copper(I)-catalyzed azide-alkyne Huisgen cycloaddition (click-chemistry) reaction between pAzF residues and palmitic acid alkynes (with an terminal alkyne, such that the carboxyl group is exposed) ensures site-specific conjugation (Fig. 1 C and D). Alkynyl palmitic acid was used for functionalization because it had previously been shown to strongly promote binding to albumin (23).

To evaluate if we could produce proteins with a genetically controlled number of FAs, we expressed ELP-GFP with 0, 1, 5, or 10 UAG codons at a yield of 70 mg/L (Fig. 2A and SI Appendix, Fig. S1). To carefully examine the fidelity and efficiency of each step in our system, we performed quantitative mass spectrometry (MS) analysis of the ELPs digested with thermolysin, which liberates each of the 10 constituent ELP units. To account for differences in ionization efficiency between the different peptide species, ion counts were quantified using a standard curve for each peptide (SI Appendix, Fig. S2). We first evaluated the efficiency of pAzF incorporation and found that the abundance of ELP units with pAzF was directly proportional to the number of UAG codons in the construct (SI Appendix, Fig. S3). Consistent with prior work (2), when all 10 ELP units contained a UAG codon, we detected minor (<5%) tyrosine misincorporation.

Analysis of the purity and bioactivity of multisite lipidated biopolymers. (A) Schematic representation of ELP-GFP reporter constructs with 1, 5, or 10 pAzF residues. Target positions for pAzF are indicated in red. (B) Relative abundance of detected nonstandard amino acids at target residues of ELP units based on quantitative MS. Treatment with ISAz selectively converts reduced pAzF residues, pAF, back into pAzF. (C) Click-chemistry with FA alkynes functionalizes all pAzF, but not pAF, residues (n = 3, error bars: mean SD). (DG) Intact MS of full-length ELP(FA)-GFP after click-chemistry with (blue) or without (black) ISAz treatment. (H) Activity of recombinant trx, trx-ELP(10pAzF), and trx-ELP(10FA) at protein quantities ranging from 25 to 150 pmol per well. (I) Effect of HSA on the activity of recombinant trx, trx-ELP(10pAzF) and trx-ELP(10FA) using 100 pmol of each protein and 500 pmol HSA. Data are normalized to the activity of each protein without HSA (n = 3, error bars: mean SEM). *P < 0.05, **P < 0.01.

While examining the fidelity of pAzF incorporation, we observed significant levels of para-aminophenylalanine (pAF) (Fig. 2B), the reduced form of pAzF, which cannot participate in click-chemistry. In our system, pAF is the result of pAzF reduction (2, 33), and causes significant impurities and heterogeneity in the final preparations if left unresolved. To overcome this impurity, we developed a method to selectively recover pAzF from pAF with the diazotransfer reagent imidazole-1-sulfonyl azide (ISAz) (Materials and Methods) (34). We previously demonstrated that this approach enabled effective conversion of pAF residues to pAzF, without introducing azides at other primary amines found in ELP-GFPs (34). Consistent with this prior work, after treatment with ISAz we observed less than 5% of pAF via quantitative MS in each of the digested ELP-GFP constructs (Fig. 2B).

We then used click-chemistry to attach alkynyl palmitic acid at the precise positions where pAzF was encoded and assessed the purity of each ELP-GFP construct. These functionalized constructs are denoted as ELP(nFA)-GFP, where n indicates the number of UAG codons encoding pAzF in the template. We observed that all pAzF residues were converted to FA conjugates and no further reduction to pAF was detected during this reaction (Fig. 2C), emphasizing the high efficiency of this conjugation strategy. To complement the quantification at the peptide level, we used MS of the intact protein to evaluate the purity of the products (Materials and Methods). We consistently observed one dominant peak at the expected mass after ISAz treatment, whereas untreated samples demonstrated heterogeneous modification of the ELP-GFP (Fig. 2 DG). For example, the ELP(10FA)-GFP without ISAz treatment showed multiple distinct peaks corresponding to an impure biopolymer with variable number of FAs. The peak profile correlates with a binomial distribution determined by the availability of pAzF residues (SI Appendix, Fig. S4) and suggests pAzF reduction is probabilistic.

Finally, we evaluated if the addition of multiple FAs per protein would impair solubility of the resulting constructs. The solubility of unmodified ELP-GFP and ISAz-treated proteins with 1, 5, or 10 FAs were determined by dynamic light scattering (DLS) analysis. All constructs, before and after FA conjugation, were soluble (>99% by volume) and did not self-assemble in solution (SI Appendix, Fig. S5). Together, these results demonstrate that the genetically controlled placement of pAzF and chemical regeneration of reduced pAF residues enable the programmable and robust functionalization of biopolymers at multiple sites.

We evaluated the effect of ELP and FA conjugation of peptide bioactivity on the activity of two proteins. We first quantified the effect of FA conjugation on GFP fluorescence, and found that it is reduced by 14 to 25% (SI Appendix, Fig. S6). In addition, to examine the effect of ELP fusion and FA conjugation on enzymatic activity, we produced and characterized thioredoxin (trx)-ELP fusion proteins. We evaluated the activity of recombinantly produced trx, trx-ELP(10pAzF), and trx-ELP(10FA), after ISAz treatment. Similar bioactivity was observed for trx and trx-ELP(10pAzF), while trx-ELP(10FA) retained greater than 50% bioactivity (Fig. 2H). In addition, we evaluated the effect of human serum albumin (HSA) binding on the activity of these proteins. To this end, we performed an activity assay in the presence of fivefold excess HSA concentration, and found that HSA binding reduced the activity of trx-ELP(10FA) by 50%, while activity of trx and trx-ELP(10pAzF) were not significantly reduced (Fig. 2I). Although FA conjugation and HSA binding may partially reduce bioactivity, these analyses demonstrate that posttranslational functionalization with FAs is compatible with bioactive proteins.

Since prior work with single FA conjugations of insulin showed that serum half-life is correlated with the binding affinity to albumin (23), we hypothesized that multisite lipidation of ELP-GFPs would significantly enhance binding affinity to mouse serum albumin (MSA), and consequently extend serum half-life, compared to a single conjugated FA. To study the impact of increasing the number of FAs, we analyzed ELP-GFP constructs (both with and without ISAz treatment) with surface plasmon resonance (SPR). The KD values of our constructs were estimated based on the steady-state binding (Table 1). There was no detectable binding between MSA and the negative control without conjugated FAs [ELP(0FA)-GFP]. For untreated biopolymers, we found that the KD with a single FA, ELP(1FA)-GFP (KD = 126 32 M), was lowered 12- to 45-fold for ELP(5FA)-GFP (KD = 10.4 4.0 M) and ELP(10FA)-GFP (KD = 2.8 0.2 M), respectively. For the ISAz-treated biopolymers, we observed much stronger binding overall: treated ELP(1FA)-GFP presented a KD of 25.9 7.1 M, and an increase to 5 and 10 FAs per protein further lowered the KD to 4.0 1.6 M and 2.22 0.03 M, respectively. These data indicate that the affinity for MSA is strongly enhanced by conjugation of multiple FAs per protein and confirm that the binding affinity is correlated with the number of FAs.

Binding affinity of ELP-GFP constructs for serum albumin

We next determined if the tighter binding affinity is translated to prolonged half-life in C57BL/6J mice. A total of 50 g of each protein variant (10 M in phosphate-buffered saline [PBS]) was injected intravenously and blood was collected after 1, 4, 8, 16, and 24 h, followed by daily collections for 7 d. The blood levels of ELP(nFA)-GFP constructs were measured using a GFP-specific ELISA, and their pharmacokinetic profiles were calculated (SI Appendix, Fig. S7 and Table S1). We observed a striking 16- to 19-fold increase in half-life from 1.7 h for ELP(0FA)-GFP to 28 to 33 h for ISAz-treated ELP(5FA)-GFP and ELP(10FA)-GFP, as well as for untreated ELP(10FA)-GFP (Fig. 3A). Notably, when the same constructs were injected subcutaneously, we observed a delayed peak concentration, but the half-lives were equivalent to intravenous injections (SI Appendix, Figs. S8 and S9). Furthermore, these data show that the half-life of tight binding ELP-GFP constructs with multiple FA conjugates approaches the half-life of MSA in mice (35 h) (35), and is similar to the half-life of 28 h reported for proteinMSA fusion proteins (36).

In vivo characterization of lipidated biopolymers in mouse. (A) Serum half-life measurements of lipidated biopolymers with or without treatment with ISAz. Measurements were collected after a single intravenous injection of 50 g biopolymer in C57BL/6J mice. ELP(0FA)-GFP after ISAz treatment was not measured (n = 4, error bars: mean SD). (B) Correlation between the KD and half-life of lipidated biopolymers with or without ISAz treatment. The horizontal, black dotted line shows the half-life of MSA, the dashed gray line shows model predictions (n = 4 to 8, error bars: mean SD, n.d. = not detected). (C) Distribution of biopolymers in mouse organs, 3 and 48 h after intravenous injection of Alexa Fluor 648labeled ELP(0FA)-GFP or ELP(10FA)-GFP. The biopolymers were treated with ISAz. The data are representative of four independent measurements. (D) Quantification of average Alexa Fluor 648 intensity for organs shown in C (n = 4, error bars: mean SEM). For each organ separately, a one-way ANOVA was used to determine whether the differences between the means of the five treatment groups were statistically significant. After multiple testing correction, *P < 0.05 and **P < 0.005. (E) Serum concentration of select inflammatory cytokines at 3 and 48 h after injection. Endotoxin (100 g) and PBS were used as positive and negative controls, respectively. Measurements below the lower limit of detection (20 pg/mL) or above the upper limit of detection (5,000 pg/mL) are plotted at their limit of detection (n = 3, error bars: mean SD).

Finally, we note that the observed KD values can be approximated by dividing the KD of ELP(1FA)-GFP (ISAz-treated) by the average number of conjugated FAs (SI Appendix, Fig. S10). This correlation has two key implications. First, biopolymers with high numbers of FA conjugates [i.e., ISAz-treated ELP(5FA)-GFP, and both treated and untreated ELP(10FA)-GFP] will have similar binding affinities to albumin, and therefore also similar half-lives. Second, tuning of the binding affinity and half-life is most pronounced at lower numbers of conjugated FAs. In the case of ISAz-treated ELP(10FA)-GFP, we found a small decrease (although not statistically significant) in half-life compared to treated ELP(5FA)-GFP and untreated ELP(10FA)-GFP. We hypothesize that denser packing of the 10 FAs does not improve, or may even reduce, the availability of FAs for albumin binding, highlighting the value of being able to precisely control the number of FAs per protein.

We computationally modeled the system to gain a deeper understanding of the correlation between the binding affinity and half-life (SI Appendix, Supplementary Information Text and Fig. S11). In brief, a set of ordinary differential equations describes the binding and release of ELP-GFP from albumin as a function of the KD, as well as the clearance of both bound and unbound ELP-GFP. Here, unbound ELP-GFP has a half-life of 1.7 h, as empirically determined, and bound ELP-GFP is cleared at the same rate as albumin (35 h for mice) (35). Importantly, the half-life of the protein is determined by three parameters in this model: 1) the half-life of unbound protein, 2) the half-life of serum albumin, and 3) the binding affinity between the protein and albumin. By simulating the kinetics over time, we were able to calculate the overall clearance rate, and predictions made by the model were in good agreement with the empirical measurements for KD and half-life (Fig. 3B and SI Appendix, Fig. S11). This suggests predictive capability for the half-life based on empirically determined KD values, or the model can provide a target KD based on the desired half-life. Together, our results confirm that titrating the number of FAs allows predictable tuning of the protein half-life by modifying the binding affinity to albumin.

To evaluate the biocompatibility of the ELP-GFP constructs, we assessed the biodistribution and inflammatory response in mouse. ELP(0FA)-GFP and ELP(10FA)-GFP labeled with Alexa Fluor 647 dye were administered intravenously, and after 3 or 48 h, the brain, lungs, heart, spleen, liver, kidneys, and blood were collected and imaged for far-red fluorescence (Fig. 3 C and D and SI Appendix, Fig. S12). In the case of ELP(0FA)-GFP, most of the reporter had cleared from the blood after 3 h, and a strong signal was observed in the kidney, whereas ELP(10FA)-GFP was clearly observed in the blood, and to a lesser extent in the kidney. For both samples, a small increase (20 to 30%) in signal was observed in the liver. After 48 h, the Alexa Fluor 647 signal was only observed in the blood of ELP(10FA)-GFPinjected mice, whereas the intensity in all other organs had returned to the basal level seen in the PBS injection control. These results are consistent with the rapid clearance of ELP(0FA)-GFP, which is likely to occur mostly through excretion from the kidneys. The blood from each of these conditions was further analyzed for signs of inflammation. We did not detect any elevation of proinflammatory cytokine levels after injection of ELP-GFP constructs compared to PBS injection, whereas injection with lipopolysaccharide (LPS) as positive control gave a clear inflammatory response at both 3 and 48 h (Fig. 3E). Together, these results show that FA conjugation enables half-life extension without long-term accumulation in organs, or eliciting an inflammatory response after intravenous injection.

Considering applications of this technology for peptide and protein drug delivery in humans, we evaluated if the use of multiple FAs per protein conveyed similar increases in binding affinity to HSA. We observed KD values of 19.3 3.9 M, 3.2 0.6 M, and 1.6 0.2 M for ELP-GFP constructs with 1, 5, and 10 FAs per protein, respectively (Table 1). These binding affinities closely mirror the values observed for MSA, suggesting that multisite lipidation of proteins could be a promising strategy to tailor protein half-life in humans.

In this study, we describe the design and production of sequenced-defined synthetic biopolymers conjugated with a programmable number of FAs to tailor the serum half-life of proteins. Specifically, the genetically encoded pAzF residues facilitate precise and programmable functionalization with FAs, which enables titration of the binding affinity to both MSA and HSA. We determined that the binding affinity to albumin was predictive of the serum half-life in mice, suggesting that the protein clearance can be tuned by controlling the number of conjugated FAs per protein. Notably, we measured serum half-lives of up to 33 h, which is 94% of the 35-h half-life of MSA. Importantly, with similar binding affinities for MSA and HSA, we hypothesize that the half-life of these same constructs will be higher in humans, given that HSA has a significantly longer half-life (19 d) (37). Furthermore, activity analysis of a trx fusion protein, trx-ELP(10FA), indicate at most a 50% activity loss (in the absence or presence of HSA), as compared with free trx. This compares favorably with other carriers reported to cause an 30- to 500-fold reduction in the activity of other peptides (3842). Although, as is true for any carrier, the effect of ELP fusion and FA conjugation on activity is expected to vary for each individual peptide, protein, or molecule, our proposed fusion partner is highly tunable, in ELP size, sequence, and FA number and position, which should enable future optimization of both pharmacokinetics and bioactivity of each drug candidate.

Lipidation is an appealing alternative to PEG, which has come under scrutiny due to concerns about immunogenicity (43, 44), and uncertainty about its degradation and clearance from the body (45). The use of FAs has clinical precedence, offers greater tunability than direct fusion to albumin, and has a well-established safety profile (46). However, the utility of current lipidation strategies is constrained by two factors. First, typically only moderate half-life extensions are achieved due to weak binding of pharmaceuticals with single FAs to albumin. Second, the ability to identify uniquely reactive residues without impacting bioactivity remains challenging with conventional labeling strategies. Our work addresses both limitations with a general methodology that enables tuning the half-life extension by titrating the number of FAs per protein, and the ability to design conjugation sites at monomeric precision enables facile screening of permissive residues to maintain bioactivity.

Unique to this work is the multisite and programmable placement of nsAAs to produce a biopolymer with tunable properties, enabled by sequence-defined insertion of multiple FAs per biopolymer for functionalization. The ELP can be placed at either of the termini, or pAzF residues can be positioned in the primary sequence of the protein, permitting the optimization of both bioactivity and half-life extension, which highlights the flexibility of this approach. Furthermore, bioorthogonal conjugation sites, such as pAzF residues, allow the attachment of a wide variety of chemical moieties to expand the palette of biological chemistry far beyond FAs at genetically encoded positions throughout the protein to enhance its functionality. This establishes a foundation for a new class of synthetic, sequence-defined biopolymers comprised of a combination of natural and synthetic monomers that unites the diversity of the chemical world with the monomeric precision of translation in biological systems. These biopolymers are uniquely enabled by recoded organisms with open coding channels dedicated to the template-directed incorporation of synthetic monomers. We envision that this work, together with further recoding efforts to open up additional coding channels dedicated for multiple distinct nsAAs (46), establishes the basis for novel and programmable biopolymers (47, 48) with broad utility in biological research, pharmaceuticals, materials science, and biotechnology.

All proteins were expressed in the GRO (E. coli C321.A, CP006698.1, GI:54981157) (4) containing a previously described OTS plasmid pAcFRS.1.t1 with a p15A origin of replication and chloramphenicol acetyltransferase selection marker (2). The ELP-GFP genes were expressed from a plasmid with colE1 origin of replication and a kanamycin resistance marker (SI Appendix, Fig. S13). Each ELP-GFP construct had 10 repetitive units of 15 amino acids (VPGAGVPGXGVPGGG), where residue X is either tyrosine or pAzF (SI Appendix, Tables S2 and S3). The gene for trx was chemically synthesized (IDT) and cloned using EcoRI and PpuMI restriction enzymes into an expression vector containing to create trx-ELP(10UAG) (SI Appendix, Table S4). The same trx gene was cloned into an empty-expression vector for expression of unfused trx.

All cultures were grown at 34C under shaking (220 rpm). Before expression, the expression strains were grown to confluence in 50 mL 2xYT media. This culture was used to inoculate 1 liter of 2xYT, containing 30 g/mL chloramphenicol, 20 g/mL kanamycin, 0.2% arabinose, and 1 mM pAzF. After 4 h, expression of ELP-GFP was induced, using a final concentration of 60 ng/mL anhydrotetracycline. Cells were harvested 24 h after inoculation by centrifugation at 4,000 g for 15 min at 4C.

The cell pellet was resuspended in PBS, pH 7.4, and lysed by sonication (12 cycles of 10-s sonication separated by 40-s intervals, 40% amplitude). Poly(ethyleneimine) was added to each lysed suspension to a final concentration of 1.25%, after which the soluble fraction was separated from the cell debris by 15 min of centrifugation at 4,000 g. ELP-GFP proteins were then purified by phase transition triggered by sodium citrate, followed by centrifugation at 15,000 g for 3 min to eliminate contaminant proteins that did not precipitate. Finally, native E. coli proteins were denatured at 75C, and removed by centrifugation. After three purification cycles, the ELP-GFP proteins to >95% purity as judged by Coomassie staining of SDS/PAGE gels.

When stated, pAF residues from ELP-GFP proteins were regenerated using ISAz, as previously described. In brief, diazotransfer reactions were performed for proteins at a concentration of 20 M using 200 equivalents of ISAz in 10 PBS (1.4 M NaCl, 0.1 M phosphate, 0.03 M KCl) pH 7.2 at room temperature. After 72 h, reactions were stopped by exchanging the buffer to PBS (1, pH7.4).

The ELP-GFP proteins were reacted with palmitic acid alkyne using copper(I)-catalyzed azide-alkyne Huisgen cycloaddition (click-chemistry). For this reaction, proteins were diluted to a final azide concentration of 30 M, 35% DMSO, 0.16 mM palmitic acid alkyne, 0.1 mM CuSO4 and 0.5 mM THPTA (premixed for 30 min), 5 mM aminoguanidine hydrochloride, and 5 mM sodium ascorbate. The click-chemistry reaction was incubated for 1 h at room temperature under constant, gentle mixing. After the reaction, the protein was buffer exchanged to PBS (pH 7.4) using Amicon filters (10 kDa molecular weight cutoff [MWCO]).

Proteins for biodistribution studies were further labeled at primary amines with an Alexa Fluor 647 succinimidyl ester. Proteins were diluted to 0.1 mg/mL, and mixed with 5 g/mL fluorophore in PBS for mild labeling. Excess dye was removed using Amicon filters (10 kDa MWCO).

Endotoxins were removed from all protein preparations used for animal experiments, using Pierce high-capacity endotoxin removal columns following the manufacturers protocol (Thermo Fisher Scientific, catalog # 88274). Prior to injection, endotoxin levels were confirmed to be under 0.1 endotoxin unit (EU) per injection using Gel-Clot LAL reagent with sensitivity of 0.06 EU/mL (Charles River, catalog #R12006).

The purity at the target residue was determined by quantitative MS. The ELP-GFP proteins were buffer exchanged and diluted to 15 M in digestion buffer (50 mM Tris, pH 8.0, and 0.5 mM CaCl2), and were digested with 1.5 M thermolysin (Promega) for 6 h at 80C. The resulting ELP-peptides were quantified using standard curves based on synthetic peptides (SI Appendix, Fig. S2). High-resolution MS data were collected using an Agilent iFunnel 6550 quadrupole time-of-flight (TOF) MS with an electrospray ionization (ESI) source, coupled to an Agilent Infinity 1290 ultrahigh-performance liquid chromatography system with an Agilent Eclipse Plus C18 1.8 m, 4.6 50-mm column. Solvents used were (solvent A) water 0.1% formic acid and (solvent B) CH3CN 0.1% formic acid. Mass spectra were gathered using Dual Agilent Jet Stream ESI in positive mode. The mass range was set from 110 to 1,700 m/z with a scan speed of three scans per second. The capillary and nozzle voltages were set to 5,500 and 2,000 V, respectively. The source parameters were set with a gas temperature of 280C and a flowrate of 11 liters/min, nebulizer at 40 psig, and sheath gas temperature at 350C at a flow of 11 liters/min. MS data were acquired with MassHunter Workstation Data Acquisition (version B.06.01, Agilent Technologies) and analyzed using MassHunterQualitative Analysis (version B.07.00, Agilent Technologies).

For MALDI-TOF analysis, 2 L of the protein samples were mixed in a ratio of 1:1:1 with 2% trifluoroacetic acid solution and then with the matrix solution (375 L of 20 mg/mL solution of 2,5-DHAP [2,5-dihydroxy acetophenone] in ethanol and 125 L of 18 mg/mL of aqueous DAC [diammonium hydrogen citrate solution]) by pipetting, until crystallization of the mixture. Then 0.5 L of the protein sample was loaded on MALDI steel target plate and analyzed after solvent evaporation.

MALDI-TOF MS spectra were acquired using an MALDI-TOF/TOF autoflex speed mass spectrometer (Bruker Daltonik), equipped with a smartbeam-II solid-state laser (modified Nd:YAG laser, = 355 nm), at the Ilse Katz Institute for Nanoscale Science and Technology (Ben-Gurion University of Negev, Beer-Sheva, Israel). The instrument was operated in positive ion, linear mode within a mass range from m/z 10 kDa to 50 kDa. Laser fluence were optimized for each sample. The laser was fired at a frequency of 1 kHz and spectra were accumulated in multiples of 500 laser shots, with 1,500 shots in total. Calibration was performed using protein calibration standard from Bruker. Spectrum analysis was performed by the Flexanalysis software.

Protein solubility and self-assembly was analyzed using a Zetasizer Nano ZS (Malvern Pananalytical). For each sample, 11 to 15 acquisitions (determined automatically by the instrument) were obtained at 25C for 10 M protein solutions in PBS. Three separately prepared samples were analyzed, and the analysis for each sample was repeated three times. Populations comprising less than 1% of the total mass (by volume) were excluded from the analysis.

Binding assays were performed on a Biacore T200 instrument. HSA (Sigma, catalog #A3782) or albumin from mouse serum (Sigma, catalog #A3139) were immobilized by amine coupling to research grade CM5 chip (GE Healthcare, catalog #BR100530) from 20 g/mL solutions in 10 mM acetate pH 5.0. High-density surfaces were created ranging from 1,300 to 12,800 RUs to minimize nonspecific binding of ELP-GFP derivatives. Binding was measured with 60-s association phase and 600-s dissociation phase with either no regeneration, or surfaces were regenerated with two 30-s pulses of 50 mM NaOH. ELP-GFP derivatives were injected in duplicates from twofold dilution series with at least six different concentrations ranging from 0.28 to 60 M (depending on the polymer and its expected Kd); PBS was used as running buffer. Data were doubly referenced against the signal collected on the reference cell and responses generated on the active cells during buffer injections. Data were analyzed using Evaluation software and fit into a steady-state affinity binding model. Each reported affinity is an average from four to eight independent measurements.

The activity of recombinant trx and trx fusion proteins were determined using the Proteostat thioredoxin-1 activity assay (Enzo). Trx catalyzed reduction of insulin and consequent aggregation of insulin in the presence of dithiothreitol (DTT) was monitored by a fluorescent dye. Trx activity was determined using a standard curve using a concentration range of bacterial trx, and the activity of samples were determined to be within the linear range of the assay. Fluorescence emission was monitored using a Biotek spectrophotometric plate reader.

All experiments were performed in C57BL/6J mice in accordance with the guidelines of the Animal Care and Use Committee of Yale University. Recommendations from the Guide for the Care and Use of Laboratory Animals (49) were followed during these experiments.

The half-lives of ELP-GFP constructs were calculated from concentrations measured from blood samples collected over the course of a week. The experiments were initiated by injecting 120 L of 10 M ELP-GFP intravenously or subcutaneously. At indicated times, 2 L blood was collected from a tail puncture, and diluted 1:25 in heparin tubes. The blood sample was vortexed briefly and cells were pelleted by centrifugation (2 min at 14,000 g). The soluble fraction was collected and frozen at 20C until analysis. ELP-GFP concentrations of the samples were determined using a GFP ELISA Kit (Abcam, catalog #ab171581). The samples were diluted in PBS as needed, to ensure that the concentration fell within the quantifiable range of the standard curve.

To study the immunogenicity and biodistribution of ELP-GFP, 120 L of 10 M Alexa Fluor 647 labeled constructs were injected, and blood and organs were collected at indicated times. As positive control for an inflammatory response, 100 g LPS was injected, and an injection of PBS was performed as negative control. Organs were imaged using Amersham Imager 600 RGB, and signal visualization and quantification were performed with FIJI (https://imagej.net/software/fiji/). For cytokine quantification, blood was allowed to coagulate, and serum was collected. Cytokines were quantified from the serum samples using the BD CBA Mouse Inflammation Kit (Fisher Scientific, catalog #BD 552364).

Data supporting the findings of this work are available within the paper and its supporting information files. The strains and plasmid (sequences) have been deposited in GenBank or Addgene: Genetically recoded organism C321.deltaA (RRID: Addgene_48998), aminoacyl tRNA synthetase (RRID: Addgene_73545), ELP-GFP reporter (Genbank: KT996142). All other study data are included in the article and/or SI Appendix.

We thank Jesse Rinehart, Michael Grome, and members of the F.J.I. laboratory for discussions and feedback on the manuscript; Terence Wu (Yale West Campus Analytical Core) for technical support; and Dr. Mark Karpasas from the Ilse Katz Institute for Nanoscale Science & Technology at Ben-Gurion University for professional help with the intact mass spectrometry experiments. We acknowledge support from the Gruber Foundation (K.V.), NIH Grant K99EB019501 (to M.A.), the Dahlia Greidinger Anti Cancer Fund (M.A.), Ben-Gurion University (M.A.), NIH Grant R01GM117230 (to F.J.I.), NSF Grant MCB-1714860 (to F.J.I.), the Arnold and Mabel Beckman Foundation (F.J.I.), DuPont Inc. (F.J.I.), and Yale University (F.J.I.) for funding.

Author contributions: K.V., P.A.-G., D.H., W.M.S., M.A., and F.J.I. designed research; K.V., P.A.-G., M.K., D.H., A.G., F.Y., E.F.-S., and M.A. performed research; K.V., P.A.-G., D.H., E.F.-S., and M.A. contributed new reagents/analytic tools; K.V., P.A.-G., M.K., D.H., E.F.-S., W.M.S., M.A., and F.J.I. analyzed data; and K.V., W.M.S., M.A., and F.J.I. wrote the paper.

Competing interest statement: K.V., P.A.-G., M.A., and F.J.I. have filed patents describing this work. F.J.I. is a cofounder of Pearl Bio, Inc.

This article is a PNAS Direct Submission.

This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2103099119/-/DCSupplemental.

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Bill extending life of VISIT FLORIDA breezes through House tourism committee – Florida Politics

A bill to extend the sunset date of VISIT FLORIDA, the state-funded nonprofit tourism marketing corporation, breezed through the House Tourism, Infrastructure & Energy Subcommittee Tuesday.

VISIT FLORIDA would cease to exist after Oct. 1, 2023, under current law. The bill, HB 489, sponsored by St. Pete Beach Republican Rep. Linda Chaney, would extend its scheduled repeal date to Oct. 1, 2028.

Chaney said VISIT FLORIDA uses a targeted approach to attract visitors into Florida.

They run their ads and they know where the consumers are that theyre going to convince to come to the state of Florida, she said. By giving them an extended horizon, theyre going to be able to do that more cost effectively. If you are somebody whos engaging a vendor and they think you may only be a customer for a year, youre not going to get the same rate as somebody whos got a longer horizon.

The bill received some pushback. Critics have accused the organization of being a form of corporate welfare and a misuse of taxpayer money.

However well intentioned some government assistance may be, the fact remains that the practice of states picking winners and losers benefits a favorite few and leaves everyone else to pay the price, said Phillip Suderman, policy director for Americans for Prosperity. Too often the winners are special interests who lobby for special favors while those who bear the cost are everyday citizens and small businesses who have to pick up the tab.

Suderman was joined by other members of Americans for Prosperity in Tuesdays meeting. They, in turn, were joined in opposition by a few small business owners. And Rep. Rick Roth said some of the points being brought up were absolutely valid. But those issues, he said, were already addressed about five years ago.

Those things were taken care of by amending Enterprise Florida and VISIT FLORIDA because of people on the board of Enterprise Florida, Roth said. These arguments were targeted mainly at Enterprise Florida because people on the board were getting benefits. So they were picking winners and losers, but thats all been changed.

About five years ago, VISIT FLORIDA saw some massive housecleaning. The organization had been criticized by both Democrats and Republicans for misspending, ineffectiveness, sketchy bonuses and a lack of accountability. The agency was put on a short leash and only given year-by-year renewals. But last year, on the heels of the COVID-19 pandemic virtually shutting down tourism in Florida, the agency reported major returns.

According to data released by Floridas Office of Economic & Demographic Research, for every $1 of taxpayer money spent on the program, it returned $3.27. And the latest projections from the state show an average of $65.4 million invested into the program over the five-year extension. VISIT FLORIDA said it helped bring a record 131.42 million visitors to Florida in 2019 when it had a budget of around $80 million. And while Rep. Randy Fine pointed out about 99% of those people wouldve likely come either way, he also said far less than that extra 1% is needed for the organization to pay for itself.

What percentage of the visitors of Florida, if they come, make that $80 million worth it? Fine asked. It turns out that if less than one-quarter of 1% of the visitors to the state of Florida wouldnt have come anyway, if one out of every 400 people who came to the state only came because we offered the program, the program pays for itself. Thats the right way to think about a program like this.

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Canadian military’s new search and rescue aircraft wont be operating this summer – Ottawa Sun

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The military cant say at this point when C-295 fixed-wing aircraft will be available for missions.

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The Canadian militarys new fleet of search-and-rescue aircraft wont be operating this summer as originally planned because of delays caused by the pandemic and other technical issues.

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The military cant say at this point when C-295 fixed-wing aircraft will be available for missions.

National Defence spokesperson Dan Le Bouthillier said the plan was to have the new aircraft reach an initial operational capability in the summer. However this timeline is shifting to allow for aircraft certification and qualification which has been running longer than anticipated as a result of the volume and complexity of the work associated with developing the CC-295 capability, and the global COVID-19 pandemic situation, he explained in an email.

A revised schedule is currently being subjected to an extensive analysis that itself will take some time to complete because of its complexity, Le Bouthillier added.

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Sources told this newspaper there are also technical concerns regarding a centre-of-gravity issue due to the cabin configuration of the CC-295, commonly referred to as C-295, as well as problems involving search-and-rescue technicians parachuting from the planes back ramp.

Were aware of the parachute and gravity issues, which is why we conduct testing and trials, Le Bouthillier confirmed. In short, these are problems that will be addressed as we work towards ensuring the fleet is safe for operational use.

Canada announced in December 2016 that it was purchasing 16 C-295 aircraft for fixed-wing search and rescue as part of a $2.2-billion project. Initial operational capability for the new fleet was supposed to be mid-2021. That was later revised to summer 2022.

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Le Bouthillier said there are currently four C-295 aircraft in Canada and five at the manufacturers facility in Spain. Aircraft qualification work was ongoing in both locations, he added.

Earlier this month, the Royal Canadian Air Force removed from service its aging Buffalo search-and-rescue planes. Until the C-295s become operational, Hercules aircraft from Winnipeg will be used for search-and-rescue response on the west coast. Some of those aircraft will be based out of Comox, B.C., during the high-tempo period in the summer and will hold response posture from their home base at 17 Wing Winnipeg during periods of low operational tempo, according to the RCAF. In addition, up to five Cormorant search-and-rescue helicopters will be available.

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But that type of interim solution is dangerous, says the United Fishermen and Allied Workers Union-Unifor, which represents those involved in the west coast fishing industry.

We are working all-year-round, union president James Lawson said. Emergencies just dont happen during the busy season.

Lawson noted that fixed-wing search and rescue aircraft were essential to any response to an emergency and were able to cover large search areas. If a Hercules has to travel from Winnipeg to get to the west coast rescue location, that puts those seeking help at risk, he added.

Lawson said the union would raise the issue with members of Parliament and hope they respond. It doesnt seem right to begin with that we have to ask MPs to make sure were treated properly, he said. We shouldnt have to argue for safety.

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The Hercules aircraft, which are already widely used in a search-and-rescue role, are capable of responding quickly to emergencies such as ships in distress in challenging weather, the RCAF says. They can be used to parachute search-and-rescue technicians, emergency gear and food, life rafts, bailing pumps, arctic survival gear and illumination flares to support rescue missions.

The interim capability involving the Hercules will be in place until the new C-295 fleet is fully operational. That could happen in 2024 or 2025.

The RCAF says it had no choice but to remove the Buffalo aircraft from service. The fleet underwent a life extension program, which ensured the planes were able to safely and effectively support search-and-rescue operations up to Jan. 15, 2022. With the life extension program now concluded, the Buffalo was no longer able to support operations, the RCAF noted.

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Lesson of the Day:In a First, Man Receives a Heart From a Genetically Altered Pig – The New York Times

Lesson Overview

Featured Article: In a First, Man Receives a Heart From a Genetically Altered Pig by Roni Caryn Rabin

On Jan. 7, doctors in Maryland successfully transplanted a pigs heart into a human. The breakthrough may lead one day to new supplies of animal organs for transplant into human patients, Roni Caryn Rabin writes.

In this lesson, you will learn about the groundbreaking procedure and consider its place within the greatest medical advancements in history. In Going Further activities, we invite you to research other recent medical breakthroughs and to speculate on how far the field of medicine might extend life.

What, in your opinion, are the greatest medical achievements of all time?

With a partner or small group, brainstorm medical innovations and advances throughout history, such as aspirin, Band-Aids, X-rays, contraceptives and the recent coronavirus vaccine. Which do you think have made the biggest impact, whether by reducing pain, suffering and disease; giving comfort; or extending human life?

Then, choose one advancement from your list and make a one-minute case to the rest of the class for why it could be the single greatest medical achievement of all time.

Read the article, then answer the following questions:

1. Why was an eight-hour surgery in Baltimore on Jan. 7 global news? In your own words, describe what happened and why you believe it is making headlines around the world.

2. Understand the importance of organ replacement by finding some numbers in this article: How many Americans received a transplanted organ last year? How many people received human donor hearts last year? How many people are waiting for kidneys and other organs? And how many people on lists waiting for organs die each day? Taken together, what do these numbers tell you about the need for organ replacements in this country?

3. Who is David Bennett Sr. and why did he decide to gamble on the experimental treatment? Would you ever consider participating in a risky and experimental trial like Mr. Bennett did?

4. The article states that xenotransplantation, the process of grafting or transplanting organs or tissues from animals to humans, has a long history. Which examples from the article did you find most fascinating or significant?

5. Why a pig heart? What advantages do pigs offer over other animals for organ procurements?

6. Dr. David Klassen, the chief medical officer of the United Network for Organ Sharing and a transplant physician, called the news of the successful transplant a watershed event. Do you agree? How significant do you think it is? Return to your list from the warm up. Where would you place this pioneering surgery, or organ transplants more generally, on your list of greatest medical achievements?

7. Do you think that the use of animal organs for human transplants will become commonplace in the next 10 or 20 years? Should they? What ethical questions and concerns, if any, does the article raise for you?

Option 1: Learn more about other medical advances.

A mechanical womb to grow mouse embryos. A drug that brings drastic weight loss to patients with obesity. An unexpected key to understanding hair loss. These are just a few of the recent medical innovations and breakthroughs covered by The Times.

Choose one of the articles below or search for one that grabs your interest on the Timess Health topic page. Then, write or discuss with a partner: What is your reaction to the article? What was the most fascinating, surprising, provocative or memorable thing you learned? What questions do you still have about the scientific breakthrough you read about?

Option 2: Share your thoughts and opinions: How long can medical advancements extend life?

Last century, the average human life expectancy doubled. Medical and social advances such as the development of antibiotics and vaccines reduced childhood deaths, mitigated diseases of old age and vastly prolonged life. In Can We Live to 200?, Nicholas St. Fleur, Chloe Williams and Charlie Wood presented 43 advances that could radically extend life spans over the next 100 years. Look at the interactive timeline, then respond to the following prompts:

Which scientific advancements and breakthroughs in the article do you most look forward to? Which do you think will most likely come to fruition?

By 2100, how long might people be able to live? Do you think humans will reach the ages of 130, 150 or even 200?

Does the possibility of radical life extension intrigue, surprise, excite or even scare you? Would you want to live to 200? How long would you want to live, if you could choose your life span?

If you are interested in joining a conversation with other students, share your thoughts in our related Student Opinion prompt.

Additional Teaching and Learning Opportunities:

Learn more about the science behind the story: Read Heres How Scientists Pulled Off the First Pig-to-Human Heart Transplant from Science.org, which details how the effort involved genetic engineering, an experimental drug and cocaine. How did the article add to or change your understanding of the first successful transplant of a pigs heart into a human? What was most interesting or surprising? What questions do you still have?

Explore bioethical issues further: The Times later reported that Mr. Bennett Sr. had a criminal record stemming from an assault 34 years ago in which he repeatedly stabbed a young man, leaving him paralyzed. The victims brother and people on social media expressed outrage and questioned the choice to select Mr. Bennett as the recipient of the pioneering transplant procedure. However, Karen J. Maschke, a research scholar at the Hastings Center and the editor of the journal Ethics & Human Research, said, Theres a longstanding standard in medical ethics that physicians dont pick and choose who they treat. Read the article and give your reaction: How should we decide who receives a lifesaving treatment? Should a patients history affect the decision? Why or why not?

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Fierce JPM Week: AstraZeneca cancer R&D head marks Imfinzi as ‘core backbone’ of oncology strategy with the right comboincluding treme – FiercePharma

In the increasingly crowded cancer immunotherapy field, AstraZenecas Imfinzi has mostly been used in stage III non-small cell lung cancer. But with the right combination strategy, the PD-L1 inhibitor has promise in other tumor types, AZs oncology R&D head said.

Imfinzi is a core backbone component of AZs overall strategy for oncology, Susan Galbraith, Ph.D., AZs executive vice president of oncology R&D, said during the Fierce JPM Week virtual conference. The drug just hit gold-standard life extension goals in two phase 3 trials when used alongside chemo in newly diagnosed biliary tract cancer and as part of a cocktail with AZs own CTLA4 inhibitor tremelimumab in first-line liver cancer.

Those trial wins fit AZs philosophy of developing treatments that can improve long-term survival and cure more patients by targeting earlier lines of treatment. But that ambition requires different components and mechanisms, such as the approach with Imfinzi and treme, Galbraith said.

In the first-line liver cancer trial dubbed Himalaya, the Imfinzi-treme pairing slashed the risk of death by 22% over Bayers aging standard-of-care Nexavar. That result marked a rare win for treme after multiple failures in non-small cell lung cancer (NSCLC), head and neck cancer and bladder cancer.

By incorporating lessons from previous trials, AZ's scientists homed in on a regimen called Stride, Galbraith said, which involves a single high dose of treme given in tandem with Imfinzi at the beginning of treatment, followed by Imfinzi alone.

That single punch of CTLA4 inhibition functions as priming the immune system. Previous research has found that with the proper priming, the bodys immune response against cancer can be very long-lasting, delivering a durability effect with an improvement particularly in the tail of the survival curve, Galbraith explained.

In the Himalaya trial, 40.5% of patients on the Stride regimen were still alive after two years, compared with 39.6% for the Imfinzi monotherapy group and 32.6% in the Nexavar arm. At three years, the survival rate stood at 30.7% for Stride, while Imfinzi monotherapy dropped faster to 24.7% and Nexavar to 20.2%.

The dose and schedule refinement, particularly with the Stride regimen, really gives us some insight into how we can improve the therapeutic index, Galbraith said.

Separately, by posting a 20% reduction in the risk of death previously untreated unresectable biliary tract cancer, Imfinzis chemo combo was the first immunotherapy regimen to improve survival in those patients.

RELATED:AstraZeneca climbs a Himalaya to find ill-fated treme a place alongside Imfinzi in liver cancer

Meanwhile, following its approach to target earlier lines of treatment with combos, AZ is running the phase 3 Emerald-1 trial to see whether adding Imfinzior Imfinzi and Roches VEGF inhibitor Avastinon top of transarterial chemoembolization could help patients with locoregional liver cancer. That data could read out later this year. A separate Emerald-2 trial is examining Imfinzi alone or the Imfinzi-Avastin pairing as a post-surgery adjuvant therapy in early liver cancer patients at high risk of recurrence.

Roche won an FDA go-ahead in 2020 for its PD-L1 inhibitor Tecentriq alongside Avastin in newly diagnosed liver cancer. Given that success, Galbraith said shes optimistic about the two Emerald trials.

Beyond treme, AZ recently turned in positive phase 2 results for Imfinzis combination with oleclumab, an anti-CD73 antibody, or monalizumab, an anti-NKG2A antibody, over solo Imfinzi in stage III non-small cell lung cancer. Now AZ is moving both new therapies into phase 3 testing.

AZ gained full rights to monalizumab from a collaboration with Innate Pharma originally signed in 2015. Last week, AZ paid Scorpion Therapeutics $75 million upfront to develop drugs against transcription factors, which have historically been hard to drug.

RELATED:AstraZeneca names Galbraith as Baselga successor in cancer R&D

The British pharma is also known for two billion-dollar licensing deals with Daiichi Sankyo featuring antibody-drug conjugates Enhertu and datopotamab deruxtecan. BTK inhibitor Calquence also came to AZ while it was in late-stage development at Acerta Pharma.

While AZ has a productive internal R&D engine, the company doesn't have a monopoly on all innovation, Galbraith said. Moving forward, AZ is very open to deals across the spectrum of drug development stages for products that can deliver value, she said.

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Fierce JPM Week: AstraZeneca cancer R&D head marks Imfinzi as 'core backbone' of oncology strategy with the right comboincluding treme - FiercePharma

Confidence is key in the expansion of BYUH, says Apostle Neil L. Andersen at Science Building dedication – Ke Alakai

Elder Neil L. Andersen, of the Quorum of the Twelve Apostles, offered a dedicatory prayer for the newly built Science Building, the first three-story building on campus on Jan. 15. He said he hopes the new building can inspire people to progress forward in confidence in fulfilling President David O. McKay's vision for BYUHawaii.

Photo by Mark Gatus

Photo by Mark Gatus

Andersen explained people must consider what can be done that is even more expansive than the schools founders imagined because the institution has grown so much. The word that came to my mind as I was sitting here was the word confidence, he added.

With the start of this new Science Building, he said BYUH community members must bring confidence in the capacities of science and confidence in [their] faith in the Lord Jesus Christ."

Confidence in a BYUH learning experience The physical construction of the Science Building, Andersen shared, is symbolic of the growth and knowledge students can experience while attending BYUH because the standards of what students should have at the University were raised.

He compared BYUH students learning experience with how the ceilings are designed to be opened. He said he prays students are not just confined to learn what their professor knows, but they will learn things even their professors never knew.

He added students must be confident there is no conflict between religion and science. "Everything is known [by] God, and if there's anything unknown, it's only a matter of time until [people] know it. And if it seems to conflict, it's only because [people] don't understand the principles behind it."

Whether knowledge comes from revelation or secular learning, both types of learning are compatible, said BYUH President John S. K. Kauwe III, during his remarks at the dedication of the new Science Building. He quoted President Russel M. Nelson's dedication of the Life Sciences building at BYU in Provo in 2014. Kauwe said, All truth is part of the everlasting gospel. There is no conflict between science and religion. Conflict arises only from an incomplete knowledge of either science or religion or both.

Andersen reminded the audience of a principle taught by President Nelson recently in General Conference. There really is such a thing as right or wrong. There really is absolute truth eternal truth."

Secondly, he shared students must be confident in themselves, so if they return to their homelands and leave a significant mark on their home countries. He added he prays people can be prayerful about this and be lifted by the building to have the confidence they need to prepare for these sacred moments in the future.

The dedication featured speeches from former BYUH President John Tanner and Vice President of Academics Isaiah Walker, as well as a musical number entitled, "All Things Denote There Is a God," in reference to the inscription on the face of the new building. The song was composed for the occasion by Erica Glenn, a visiting assistant professor of choral activities and voice in the Faculty of Culture, Language & Performing Arts.

Photo by Mark Gatus

Photo by Mark Gatus

Kathryn Palmer, a member of the Ho'olokahi Chamber Choir who sang at the ceremony, said singing in front of an apostle was really special. It always feels good when [I] can use [my] gifts or something that [Im] good at to benefit somebody else.

Palmer, a junior from Arizona majoring in business, agreed confidence was emphasized during the ceremony. To her, confidence is what she is able to accomplish despite the smaller size of her University. She emphasized confidence means understanding students here are just as meaningful and able to impact others.

Momentum to further the mission Kauwe conducted and spoke at the ceremony. He said the building represents the love and sacrifice of every member of the Church and acknowledged the faith and trust they have that makes it possible to live in Laie and learn at BYUH.

The building also represents the expectation members of the BYUH ohana will honor their covenants and commitments and strive to love others and live worthy of the Lord's blessings. He said those expectations include using the blessing of being at BYUH to spread the gospel of Jesus Christ, to serve families, communities, people of [their] homelands and the kingdom of God."

Using the words of Elder Jeffrey R. Holland from his 2021 presidential inauguration, Kauwe shared this building represents one more conspicuous step in the fulfillment of prophecy that is inextricably linked with this particular campus.

He explained, This building is going to allow for academic preparation, the exchange and discovery of knowledge, in ways that have simply not been possible on this campus before. This new capacity is going to provide students with learning and experience that will prepare them to succeed in their future endeavors, even in an increasingly challenging and changing world.

Photo by Mark Daeson Tabbilos

Photo by Mark Daeson Tabbilos

Jonah Gunter, a sophomore from Washington majoring in intercultural peacebuilding, said the event was uplifting and celebrated the growth of the campus. It wasn't just about the building, but it was about the direction that campus is taking and the momentum we have going forward to further the mission.

He shared Andersen emphasized the importance of confidence in many aspects of life. He said there must be confidence in science and faith working together to resolve any discord.

All things denote there is a God

Walker shared his awe for the building's interactive space and indoor and outdoor learning facilities. These characteristics importantly reflect and invite this spirit of inquiry, study and interaction.

The building, he said, is conducive to the natural environment surrounding the campus. He shared his admiration for the Pacific Ocean, the sacred homeland for the families of Oceania and the sacred mountain tops and forests, which will soon provide for the community.

I love how this building is situated because to me, it's an extension of, not a barrier, to the natural elements. He shared he is excited to see students being able to study the natural beauty from a new building and perspective.

Walker shared fond memories of studying and meeting his wife in the original General Classroom Building, which used to sit where the new Science Building is. I'm happy to think about the many great memories that will be made in this beautiful place, he added.

Elise Mitchell, a social media manager at University Communications and a 2020 graduate of BYUH, said she enjoyed the talks because they all centered on the student learning experience. Whether it was Isaiah Walker or [President] Kauwe, they all were able to connect the building's significance with student learning, how it's going to help further the students' education and how it's really for the students.

During the construction of the building, Tanner, who returned for the dedication for the first time since the conclusion of his presidency, shared he wanted to engrave a scripture that would describe what the building would represent.

Photo by Mark Gatus

Photo by Mark Gatus

Tanner said he and former Academic Vice President John Bell, chose Alma 30:44, which reads, All things denote there is a God; yea, even the earth, and all things that are upon the face of it. The verse embodies what he said he hopes will happen within the Science Building and on the BYUH campus generally: that students will be taught with the Spirit and come away with strengthened testimonies.

While serving as president, Tanner said he described BYUH as a "Hawaiian Zion," sharing the connection of the campus mission to several Hawaiian terms. For example, he discussed the Hawaiian word kuleana, which means having a responsibility to care for the land.

Pono, or righteousness, Tanner shared, was also in the dedication of this land through the idea that it would be a land established in righteousness. Certainly, that's part of the University's heritage, to be a Zion community, because we are embracing the idea of pono, or righteousness.

Another Hawaiian concept Tanner shared he loves is malama 'aina, or responsibility for the earth. I hope people ... will feel not only a love [for the earth], not only an understanding of it, but also a desire to take care of it. Thats a Zion responsibility."

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Confidence is key in the expansion of BYUH, says Apostle Neil L. Andersen at Science Building dedication - Ke Alakai

Can we evolve on our own terms? – Varsity

Content warning: This article discusses ableism.

What if we could cure or eliminate all diseases? What if we could live forever?

For transhumanists, these philosophical questions are simply matters of engineering and scientific innovation. Put simply, transhumanism is a belief that human beings will evolve beyond species-typical levels of physical performance, cognitive ability, and sensory perception.

According to transhumanists, we have the potential to evolve so radically that we can become posthuman, altering ourselves so successfully using technology and pharmacology that we would no longer be recognizably human. Transhumanism is a philosophy, and its adherents carry out a variety of practices to achieve their goal, including cryonics, lifestyle changes, cybernetic augmentation, neurofeedback, gene editing, and even cognitive enhancements with smart drugs.

Real research and development into transhumanism exists. The Alcor Life Extension Foundation produces leading research in cryonics. The Carboncopies Foundation accelerates neuroscience research in the hope of cracking Whole Brain Emulation simulating the human brain and its functions in order to reverse-engineer our biological brains to create artificial brains. The SENS Research Foundation is working on developing anti-aging therapies and educating people about them. Elon Musks Neuralink aims to create a way for human brains to interface with computers.

However, as fantastical and promising their pursuits may seem, transhumanist practices and innovations could lead to negative consequences to people with disabilities, going as far as suggesting that disabilities are flaws that need to be eliminated. This attitude is reminiscent of eugenics and suggests that the problem lies with people who have disabilities instead of the systemic inequities and inaccessibility that they have to deal with.

What is transhumanism?

Although its largely still a fringe belief, the internet has increased the dissemination of transhumanist thought. The World Transhumanist Association now called Humanity+ was established in 1998. Part of its stated mission is to enable humans to be better than well: that is, to be pinnacles of health.

Humans have strived to perfect ourselves for as long as we have existed. After Darwin introduced the theory of evolution, we began to imagine evolving beyond our current state. People adopt transhumanist beliefs for many different reasons; therefore, transhumanism is difficult to define because it often means something different for everyone.

Some people join the movement because they are sick and desperately want a cure. Some want to live forever. Others are frustrated by the limitations of the human body and want to use technology to fix humanity so that we can exert more control over ourselves. For some people, called biohackers, experimenting on themselves and encouraging public participation in scientific exploration is fulfilling.

Its not all fun though. Due to the cost of getting involved, most transhumanist practices are currently a largely individual pursuit, even though transhumanism was initially conceived as a way of uplifting the human species as a whole.

Science fiction or future science?

Transhumanism relies on the radical enhancement of human faculties, with the primary aim of extending human life.

In the cognitive domain, peoples expectations that cognitive enhancement drugs would work have exceeded the effects such drugs actually have. Moreover, there is little scientific evidence that smart drugs are effective or safe for long-term use by healthy people. An alternate approach, transcranial magnetic stimulation (TMS), involves stimulating the brain by passing magnetic pulses through it. TMS is used as a treatment for depression and has been proven to have cognitive benefits, including improvements in working memory, motor tasks, and some linguistic tasks. However, its long-term effects on cognition are unknown, and side effects include a minimal risk of seizures.

Meanwhile, in 2015, Chinese scientist He Jiankui edited the genes of three babies using CRISPR to make them resistant to HIV. CRISPR is a gene editing tool that can alter human DNA with a relatively high level of precision. Evaluating whether Jiankui succeeded and whether his actions could cause mutations that affect the babies biological functioning will be challenging. The long-term effects of embryonic gene-editing in humans are unknown, and it could turn out to be highly beneficial or harmful.

Some proposed transhumanist innovations, however, seem to be clearly harmful. The US Food and Drug Administration (FDA) has warned against the use of fecal transplants, which involve transferring fecal matter from the gut of a healthy person to that of an unhealthy person, to help replenish their gut bacteria after a recurrent infection. FDA guidelines state that individuals should consult a health professional before undergoing a fecal transplant.

The FDA has also condemned the idea of transfusing a young persons plasma into an older persons body to prevent aging. Although a rejuvenating effect was found when scientists stitched younger and older mice together so they shared the same circulatory system, there is no evidence that plasma transfusions are a legitimate anti-aging strategy for humans. Side effects of plasma transfusions include allergic reactions and circulatory overload.

Ethical consequences of transhumanism

There are plenty of ethical conundrums raised by transhumanism. Depending on the availability and cost of enhancement procedures across the world, a posthuman society could be even more unequal than our current one. Currently, many transhumanists are white men based in Western countries, and some of the procedures they undergo are prohibitively expensive. For instance, Silicon Valley millionaire Serge Faguet spent 250,000 USD on biohacking, including hearing implants he doesnt need, frequent biomarker tests, oestrogen blockers to boost his testosterone, and frequent consultations with Ivy League health professionals. Although the community is large and varied, to some extent being able to pursue transhumanism to move beyond mere survival to self-driven evolution reflects a level of privilege many can only dream of.

Even if large-scale augmentation was widely available at a lower cost, there is no guarantee that most people would submit to transhumanist procedures. Some of the procedures are highly invasive, and there are well-documented security risks associated when medical data is collected by electronic devices like implants. Furthermore, in a world with rising distrust in science and governments, society could perhaps be stratified into humans and posthumans, with both sides adamant that they made the right decision. Many science fiction novels have explored the perils of similar scenarios.

A slippery slope toward eugenics

A variety of devices and therapies that make the world easier to navigate for people with disabilities already exist. Some are implanted in the body, like cochlear implants, which improve hearing for those who are hard of hearing or are deaf, and have several settings for different environments. Some, like exoskeletons, are wearable devices that assist in limb movement, either for physical rehabilitation or restoring mobility. French medical device company Wandercraft recently unveiled its latest Atalante exoskeleton, which allows people with paraplegia to walk with a more natural gait. The exoskeleton is self-balancing and remote-controlled, but due to safety regulations, it must be suspended from the ceiling during use.

It can be argued that transhumanism is simply arguing for a more extensive use of such assistive devices. However, the rhetoric of transhumanists is implicitly an ableist one. It assumes that people with disabilities are in need of fixing, and that their lives would be improved by giving them the same abilities as abled people.

Take the example of Zoltan Istvan, the leader of the Transhumanist Party in the US, who caused an uproar in 2015 when he wrote an article that many considered horrifically ableist. In sum, he argued that the government does not need to spend money on making places more accessible; this money should instead go into scientific research to enhance people with disabilities. Transhumanism also advocates for genetic or embryonic screening, so that parents can choose whether to have children with disabilities.

This view is informed by a reductive focus on competition between individuals survival of the fittest as the fundamental organizing principle of society. This focus, based on how some people interpreted fitness, was the argument that was used to justify the emergence of eugenics in the nineteenth century. However, it has been argued that a crucial component of survival is social cooperation and support, which such rhetorics ignore.

Because transhumanism focuses on correcting human flaws, the movement evokes comparisons to eugenics the pseudoscientific and racist movement to improve humans through selective breeding and other physical enhancements. Some transhumanists claim that everyone has a disability, because human beings are flawed and unsuited to our environment. Others claim that no one would ever rationally choose disability, since it hampers a persons ability to live a good life.

This argument has been frequently disputed by disability activists: it is clearly possible to both have a disability and live a good life. Some people who have disabilities do experience a lower standard of living, but that is due to systemic inequities that reduce their access to things abled people take for granted. Instead of physical or mental conditions, it is societal attitudes and the resulting barriers that are disabling, because they make the world less accessible for people with certain characteristics.

The medicalization of disability turns a structural problem the problem of an inaccessible society into an individual one. Therefore, it is more prudent to remove barriers to accessibility than to try to eliminate disability itself. For instance, one of the guiding principles for the UN Convention on the Rights of Persons with Disabilities is respect for difference and acceptance of persons with disabilities as part of human diversity and humanity.

The ethical considerations of widespread human enhancement, particularly regarding disability and unequal access, are complex. For now, transhumanism is largely not viable. However, if the scientific evidence changes, we will need to have difficult conversations to move the philosophy beyond the realm of science fiction to something that will legitimately transform human existence for the better.

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Can we evolve on our own terms? - Varsity

‘Going on as we speak’ – Journalist claims Leeds are planning for life after ‘very special’ hero – MSN UK

Provided by Transfer Tavern Premier League - Leeds United v West Ham United

Leeds United are already looking at possible managerial replacements for Marcelo Bielsa this summer, according to journalist David Anderson.

The 66-year-old signed a one-year contract extension last year, so another key decision over his future is approaching for him in the coming months.

Bielsa has had a taxing season at Leeds, often having to make do without key players, and it is unknown whether or not he will continue his stay at Elland Road beyond the summer.

A fresh claim suggests that the Whites are certainly preparing for the eventuality of life after the man who Mauricio Pochettino called very special.

Speaking to GiveMeSport, Anderson claimed that Leeds are looking at possible replacements for Bielsa, eyeing up managers with a similar style of play to the incumbent boss

He revealed: Theyll be looking for somebody. This is going on as we speak, theyre looking to identify possible coaches who will be similar to him in terms of style.

In truth, it is only natural that Leeds are looking at successors to Bielsa, considering the short-term nature of most of his managerial stints and the fact that he is well into his mid-60s.

The Whites boss is a tough man to read, though, and it may be that he leaves a decision regarding his future to the last minute in order to feel sure that he is making the right call he only signed a new one-year deal on the eve of this season. He is a man of integrity and he will only stay if he believes he is still the right man for the job.

The hope is that Bielsa signs another extension despite his teams struggles, with the Argentine still a hugely influential manager who has made progress with Leeds on an annual basis since taking the reins in 2018.

In other news, Leeds reportedly turned down an approach for one player last summer. Find out who it is here.

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'Going on as we speak' - Journalist claims Leeds are planning for life after 'very special' hero - MSN UK

Wu talks about vaccination progress and pushback, on WBUR – Boston.com

COVIDBoston Mayor Michelle Wu. David L. Ryan/Globe Staff

Mayor Michelle Wu lauded the citys progress toward a vaccinated workforce, while recognizing the pushback shes received from city workers who are opposed to getting a shot, during an interview with Radio Boston host Tiziana Dearing on WBUR.

On Sunday, Wu extended the deadline for city workers to satisfy Bostons COVID-19 vaccination mandate. No employees will be placed on leave or disciplined between Jan. 25 and Jan. 30, according to a statement from the mayors office.

We did see tremendous progress in boosting our vaccination rate and closing those gaps, even over the last week, the mayor said on Radio Boston. Weve now had more than 1,600 additional city workers get vaccinated, since we announced this policy would be going into effect.

Wu said she extended the deadline to give people more time to comply with the policy. She said the city is close 94 percent of employees are vaccinated.

The goal of this was not to punish anyone for how they feel about vaccination, but to ensure our workers are safe and that anyone interacting with city workers is safe, Wu said during the interview.

Workers who oppose the policy have taken to protesting. On Monday, 100 firefighters protested the mandate outside City Hall as Wu spoke about extending the vaccination deadline. Protestors have also become a fixture outside her Roslindale home.

During the interview on WBUR, Wu said that the citys policy concerning showing proof of vaccination at public venues, such as restaurants and gyms, is going smoothly.

She also touched on a variety of other topics, from housing insecurity, the Green New Deal, and the need for more affordable public transportation.

She also noted the need to address mental health issues in the city.

There is a whole pandemic after the pandemic, of us needing to pay attention to mental health, and invest in the resources for people to feel supported and safe and feel connected to the community again, Wu said.

Stay up to date on all the latest news from Boston.com

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Wu talks about vaccination progress and pushback, on WBUR - Boston.com

MLB, players’ association plan to meet again Tuesday after sides make progress, sources say – ESPN

4:47 PM ET

Jeff PassanESPN

Major League Baseball and the MLB Players Association plan to meet again Tuesday after a Monday bargaining session led to the first sliver of progress between the sides since the league locked the players out Dec. 2, sources told ESPN on Monday.

In the face-to-face meeting, which lasted about two hours, the union offered a broad proposal in which it dropped its request for age-based free agency and significantly cut the amount of revenue sharing it asked the league to funnel away from small-market teams, according to sources.

The day before the lockout, MLB had asked the union to remove three items from its list of desires: changing the six-year reserve period before free agency, lowering arbitration eligibility to two years and adjusting revenue sharing. When the MLBPA declined to do so, negotiations ended and the league implemented the lockout, the sport's first work stoppage in more than a quarter century.

During Monday's meeting, the union rejected three MLB proposals from the first post-lockout meeting between the sides 11 days ago, sources said. MLB offered a formula-based salary system for players between two and three years of service time, a draft-pick reward for success by players who started on Opening Day rosters and a slight tweak to a draft lottery in which all non-playoff teams would be eligible to receive a top-three pick.

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The players remained steadfast in a number of their positions Monday, sources said, including raising the minimum salary from $570,500 a year to $775,000, bumping the competitive balance tax threshold from $210 million to $245 million and instituting a draft lottery among non-playoff teams for the first eight picks.

Dropping the request for age-based free agency, which would make some players eligible for free agency before the current six-year standard, helped set the stage for Tuesday's meeting. After requesting smaller-market teams receive $100 million less in revenue sharing in an earlier proposal, the union cut its ask to $30 million, according to sources.

The small meeting of four people from each party included MLB's Dan Halem and the MLBPA's Bruce Meyer, the lead negotiators, as well as longtime reliever and union leader Andrew Miller and Colorado Rockies owner Dick Monfort, who is head of the league's labor relations committee.

Time is quickly becoming a factor in the negotiations, with spring training set to start in mid-February. While a delay of spring training is unlikely to significantly change the trajectory of talks, the specter of losing regular-season games -- which begin March 31 -- is expected to play a role.

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MLB, players' association plan to meet again Tuesday after sides make progress, sources say - ESPN

Man United’s progress has been slow and painful, but it’s clear after win over West Ham – ESPN

MANCHESTER, England -- Ralf Rangnick celebrated as though he had just won the Champions League for Manchester United when Marcus Rashford tapped home Edinson Cavani's cross from 2 yards, three minutes into stoppage time, to secure a 1-0 victory against West Ham at Old Trafford on Saturday.

Man United's interim manager turned to the directors' box with both arms aloft and punched the air repeatedly as the players on the pitch raced to congratulate Rashford following his second goal in two games. Rangnick was so animated because his team had just turned a disappointing draw into a potentially crucial victory -- one that ensured United climbed above West Ham and into the top four for the first time since Oct 2.

But the man charged with stabilising the team following Ole Gunnar Solskjaer's dismissal as manager in November had another reason to celebrate Rashford's goal: For the second successive game, the former RB Leipzig and Hoffenheim coach had made a big call with his substitutions and got it right.

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At Brentford on Wednesday, Rangnick sparked an angry, even petulant, reaction from Cristiano Ronaldo when substituting the 36-year-old for Rashford. Six minutes later, Rashford scored United's third goal in a 3-1 win to make the game safe and enable Rangnick to explain to Ronaldo, in full view of the television cameras, just why he was right to make the change, regardless of the former Real Madrid forward's status as a football icon.

And as United toiled away against David Moyes's West Ham, Rangnick boldly chose to go all-out attack in a bid to find a goal in the closing stages. Having replaced Anthony Elanga with Rashford on 62 minutes, Rangnick threw on Cavani and Anthony Martial for Fred and Mason Greenwood in the 82nd minute, and instructed United to operate a 4-2-4 formation. It was win or bust, and it almost went bust when Tomas Soucek headed inches wide on 87 minutes, but Rangnick's gamble paid off when all four forwards linked together in the same move for Rashford to score the winner.

"Those are the best kind of wins, when the other team has not time to come back," Rangnick said. "We had to take some risks in the last 15 minutes, but in the end I wanted to show the players it is about winning this game, and I'm more than happy we scored the goal in the last minute."

Moments like that matter for a manager when he is trying to gain the trust of a new group of players. If you take a risk and it backfires, the players question your judgment, but if it comes off, it certainly helps to dilute any doubt that may have taken hold in the dressing room.

Rangnick still has plenty to do at Old Trafford to secure the full, unequivocal support of his players and, considering he is only likely to be in charge until a permanent manager is appointed this summer, he might never get close to universal backing. But in a slow, painstaking manner, the 63-year-old is gradually steadying the ship at United, even if it can still be hard to watch at times.

Under Rangnick, United have lost just once in 10 in all competitions -- a 1-0 defeat at home to Wolves earlier this month. Yet, they have managed to score just seven goals in six home games -- and three of those came against Burnley, the Premier League's bottom team. Man United have conceded just seven goals in 10 games under Rangnick, too, and tightening up at the back was crucial with Solskjaer's side conceding a staggering 25 goals during his final 10 games in charge.

Rangnick has turned off his side's dripping tap in defence, but the downside is that it has created a drought of chances and goals at the other end of the pitch. Against West Ham, Manchester United had 18 efforts on goal, but only three hit the target -- with such a poor conversion rate, it is no surprise that they are finding it difficult to beat teams comfortably.

Dan Thomas is joined by Craig Burley, Shaka Hislop and others to bring you the latest highlights and debate the biggest storylines. Stream on ESPN+ (U.S. only).

Ronaldo, for instance, has scored just two goals in seven appearances under Rangnick and one of those was a penalty. He played in a central role against West Ham and did little to affect the game. His main contribution was heading the ball at the near post when defending corners, and as important as that is, it is not why Ronaldo was brought back to the club last summer.

The key to any successful football team, however, is a solid defence. Once those foundations are in place, a team can break forward and attack with the confidence that they are safe to leave gaps at the back. Man United aren't at that stage yet, but progress is being made, and Rangnick is able to look ahead to the international break having seen his team win back-to-back games for the first time since he took charge in December.

The race for fourth is intense, with Man United, West Ham, Arsenal, Spurs and Wolves separated by just four points, but Man United have a run of fixtures in February that give them the opportunity to pull clear of some of their rivals. They face Burnley, Southampton, Leeds and Watford next month before a daunting March against Manchester City, Tottenham and Liverpool, but Man United are in a better place than they were when Rangnick arrived, so there are positives to focus on.

And everything looks better after a stoppage-time victory, no matter how uninspiring the performance may have been.

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Man United's progress has been slow and painful, but it's clear after win over West Ham - ESPN

The Progress Parade continues in the City of Sullivan – a new addition is coming to The Sully – WTHITV.com

SULLIVAN, Ind. (WTHI) - Over in the City of Sullivan, the progress parade continues.

On Monday, community members broke out the golden shovels to break ground on an exciting addition to the Sullivan Greenway System.

It's called the "Lover's Lane Loop."

This was made possible thanks to over $1 million in funding provided by the Indiana Department of Transportation. This money allows for the expansion of the Sullivan Greenway system to the historic Lover's Lane.

The Greenway System or "The Sully" is an outdoor trail system. It promotes connectivity throughout the community.

Mayor Clint Lamb says that the connection of The Sully to Lover's Lane is the next step in the revitalization of the city.

"There is no silver bullet to revitalize rural Indiana or rural America. It's a combination of bringing folks together, and getting them excited -- caring about the emotional well-being of the citizens of the community. This is more than just fancy sidewalks and a tangible project. It gets people out and moving again. It gets people exploring their community," Lamb said.

Lover's Lane pays homage to a historical sidewalk that cuts down the middle of a block.

The project is scheduled to be completed this coming April or May.

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The Progress Parade continues in the City of Sullivan - a new addition is coming to The Sully - WTHITV.com

Firefighters making progress on winter wildfire burning in Big Sur, but evacuation orders remain – KCBX

Firefighters are gaining control of a brush fire called the Colorado Fire that erupted Friday along the Big Sur coast, with the blaze now 35 percent contained and about 700 acres still burning.

While evacuation orders remain in place, the emergency shelter in Carmel closed Monday morning.

About 500 people live within the Colorado Fire evacuation zone, but Maia Carroll with Monterey County Office of Emergency Services said only a couple of people stayed at the emergency shelter set up at Carmel Middle School this weekend.

Big Sur residents are pretty resilient and are used to fires," Carroll said. "When they have to evacuate, they dont always use the evacuation centers and shelters.

Carroll said because they know many people decided not to evacuate, there is a boil your own water notice for those in the evacuation zone who are not California American Water company customers and power outages are expected to continue.

There is a dumpster at the north bound shoulder of Highway 1 and Pfeiffer Ridge Road for people to bring spoiled food.

Cari Dighton with the Red Cross said although theyve closed the emergency shelter due to lack of use, people in the evacuation zone can still seek help by calling 2-1-1.

2-1-1 will be a great resource for people looking for hotel accommodations," Dighton said. " I know there are some area hotels that have made some special accommodations for those that have been affected.

As firefighters continue battling the blaze, Highway 1 continues to stay closed from Garrapata Creek to Point Sur.

Carroll with Monterey County Emergency Services said she understands people may be frustrated by the road closures, since they cant go back into their homes yet.

As frustrating as it may be, respect the closures, take a breath," Carroll said. "We are looking at some really good progress on the fire, according to Cal Fire. So hopefully those road blocks will be done away with soon.

Dighton with the Red Cross said although a blaze like this in winter is unusual, it's becoming more common, and she urges people in fire risk zones to have to-go bags ready all year around.

Over the last couple years, weve seen an increase in the number of major disasters that happen across the nation and in our own state," Dighton said. "They are more frequent, they are more impactful and a lot of people are at risk of facing a disaster of this nature.

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Firefighters making progress on winter wildfire burning in Big Sur, but evacuation orders remain - KCBX

Progress on St. Pete Beachs $90M Corey Landing project – St Pete Catalyst

A developers proposed $90 million mixed-use development in St. Pete Beach is inching closer to breaking ground.

Earlier this month, the St. Pete Beach city commissioners unanimously approved the allocation of 150 dwelling units from the citys residential pool reserve, which allows developer Ram Realty Advisors to create 243 luxury residential units for its Corey Landing project.

The entire vision for Corey Landing entails building 243 Class-A residential units, along with 12,000 square feet of retail and commercial space, and 5,000 square feet of restaurant space on four acres at the east end of Corey Avenue.

The property is adjacent to The Blue Parrot and includes the site of the former Leverocks restaurant.

The city commission also approved conditional use approval for commercial docks and plans for the waterfront, dock-up restaurant.

The approval is one of several steps needed toward making the waterfront development a reality. South Florida-based real estate firm Ram Realty Advisors is the group behind the project.

Corey Landing would be seven stories high and would wrap around the parking garage, shielding the garage from view.

Weve been working it for over a year already to get to where we are today, said Travis Williams, vice president for development with Ram Realty Advisors.

Williams added how Ram Realty Advisors specializes in high-end luxury developments and has funds earmarked for this project.

A major component of Corey Landing is a 0.7-acre linear public park, which would turn the vacant site deemed as an eyesore into a vibrant meeting place and connect to the proposed docks that would surround the waterfront property. The city would retain the entitlements to the park while the developer would be responsible for redeveloping it. The park would feature bike racks and a waterfront overlook.

Site maps presented to the city show the project would be broken up into two main areas.

Area one includes the proposed dock-up restaurant that would have 3,500 square feet of indoor dining space and 1,500 square feet of outdoor space. Its the same area where the public docks would be located.

The second area includes the 243 residential units and the 12,000 square feet of commercial and retail space, which encompasses 8,264 square feet of retail and 3,959 square feet of co-working/commercial space adjacent to the planned public park. The retail would be located on the corner of Bay Street and Corey Avenue.

Attorney Elise Batsel, with the law firm of Sterns, Weaver and Miller, reiterated how the clients proposed project aligns with the citys 2015 Corey Avenue Vision Plan, which outlines goals for Corey Avenue such as creating housing, a public space, and overall an east-end anchor to spur economic activity.

The site is currently zoned TC-2, which permits residential and commercial use.

The team also noted how the property currently takes in $94,000 in tax revenue, but the development would bring in $1.3 million of annual revenue for the city.

However, city commissioners discussed how residents have expressed concerns for the project, such as the density with the number of units and scale of the project, and the vehicular traffic it may bring.

We want a pretty city, not just a pretty area. They [the developers] are trying to make the math work for an amenity-rich project, commissioner Melinda Pletcher said, explaining the need for balance in the city as well as the citys goals to help raise the Corey Avenue corridor. When you come over that bridge, it [Corey Landing] sets the vibrancy and the bar a lot higher.

As far as the concern with the flow of traffic, a traffic study was completed and it was determined the roads can handle the increased activity, City Manager Alex Rey said.

Ram Realty Advisors is known for other sophisticated projects, such as Curv in Fort Lauderdale, which Williams had previously compared to the Corey Landing site. The urban infill mixed-use Curv development was completed last year. It is on three acres of land and includes an eight-story luxury apartment complex with Whole Foods as the anchor.

The team is working with North Carolina-based design consultant Kimley-Horn and Florida-based LRK (Looney Ricks Kiss) Architects.

The next step is for the city to review the conditional use permit, on Feb. 2.

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Progress on St. Pete Beachs $90M Corey Landing project - St Pete Catalyst

What progress? Women still far behind men in elite university power positions | – University Business

New report shows the incredible disparities not just in president positions but also among deans and provosts.

It doesnt take a Ph.D. to see just how wide the gaps are between women and men in power positions in higher education. They are, and have been, easily recognizable.

Just 22% of Research I institutions have women leading as presidents, and only 26% of their boards have women in chair positions. The division among academic deans and provosts is an alarming 20% or more. Those data come from a national report from the Womens Power Gap Initiative at the Eos Foundation and the American Association of University Women (AAUW) that highlighted the pervasive differences at 131 of the top universities.

Its alarming to see that women are still so vastly underrepresented at the top levels of academic leadership, said Gloria Blackwell, AAUW CEO. Historically, universities have been catalysts for social and economic progress in America and AAUW has supported pathways for women in academia for over a century. Its extremely disappointing that most institutions are still failing to give womenespecially women of colorequal opportunities to rise in their careers. We need immediate action to eliminate the barriers against women and people of color whose perspectives, brilliance, and leadership we need to move us all forward.

Women might be the dominant gender on campuses across the U.S.they have been since the 1970sbut when it comes to earning some of the most significant roles, those by and large still go to men. They havent even been able to get past 39% and 38%, respectively, in provost and dean positions, let alone get to the 50% threshold.

Its time for new approaches. Lets stop trying to fix the women and instead fix the system. The lack of women presidents is not a pipeline issuewomen serve as nearly 40% of all provosts. What we are seeing is systemic bias, said Andrea Silbert, President of Eos. Change must start with governing boardsonly 38% of universities were willing to share board diversity data. If boards dont provide transparency, what message does that send?

The AAUW and Eos noted in their report that of those that did, only 8% of boards have gender equity. One of the most significant findings was just how few women of color are in power positions nationwide at these institutions. There were two Asian, two Black and two Hispanic presidents among all of them. Meanwhile, Black male presidents have doubled in less than two years while women of color still lag.

Ive experienced firsthand gender bias and would have never ascended to university president had it not been for the support of two women board members who supported my leadership, said Juliet Garcia, former president of The University of Texas at Brownsville and first Latina to serve as president of a college or university in the U.S. The UT system once required reporting on race and gender among leadership positions; however, once the path-breaking women were replaced on the board, the disclosure structure was eliminated.

Speaking of states, it might be surprising to learn that of the eight Massachusetts R1 universities, only three have ever installed women as presidents. None currently occupy those positions. Meanwhile, California has been far more progressive, with 8 of 11 having women in that leadership post. Six institutions have had at least three women presidentsCUNY graduate school, the University of Colorado at Boulder, the University of Wisconsin-Madison, the University of New Hampshire, the University of Iowa and the University of California-Santa Cruz. But 60 institutions have never had a woman as president.

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What progress? Women still far behind men in elite university power positions | - University Business

Seagate Highlights Positive Progress Towards Global Diversity, Equity, and Inclusion Initiatives – Business Wire

FREMONT, Calif.--(BUSINESS WIRE)--Seagate Technology Holdings plc (NASDAQ: STX) (the Company or Seagate) today announces publication of its third annual Diversity, Equity, and Inclusion (DEI) Report: Crafting an Inclusive Datasphere, covering fiscal year 2021.

The Report highlights global workforce initiatives and positive progress towards our DEI initiatives. Technology leadership underpins Seagates success, and it is our employees who bring that technology to life. Innovation thrives in a culture that embraces different voices, where employees are equal contributors and are empowered to express themselves authentically. Building this culture takes constant work and willingness to be transparent about progress.

At Seagate, inclusion is so much more than just a core valueits how we lead and do business all over the world, says Dave Mosley, Seagates chief executive officer. When we lead with inclusion, we create a space for diverse voices to be heard, valued and elevated, which in turn inspires greater innovation throughout our products, technologies, partnerships and communities.

Seagate is proud of its FY21 accomplishments, including growth in our female representation across several leadership levels, growth in our employee resource groups and external brand recognition as a best employer for women, military and LGBTQ+ equality, to name a few, says Heather Howell, Seagates director of diversity, equity and inclusion.

Learn more about inclusion at Seagate, and read the Report, here: https://www.seagate.com/jobs/diversity-and-inclusion/.

About Seagate

Seagate Technology crafts the datasphere, helping to maximize humanitys potential by innovating world-class, precision-engineered data storage and management solutions with a focus on sustainable partnerships. A global technology leader for more than 40 years, the company has shipped over three billion terabytes of data capacity. Learn more about Seagate by visiting http://www.seagate.com or following us on Twitter, Facebook, LinkedIn, YouTube, and subscribing to our blog.

2022 Seagate Technology LLC. All rights reserved. Seagate, Seagate Technology, and the Spiral logo are registered trademarks of Seagate Technology LLC in the United States and/or other countries.

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Seagate Highlights Positive Progress Towards Global Diversity, Equity, and Inclusion Initiatives - Business Wire