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Hard Choices & the Conservative Mind

A brief essay on The Thoughts of Blaise Pascal
Blaise Pascal plumbs the depths of the human condition and establishes the logic of conservatism by examining…

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A brief essay on The Thoughts of Blaise Pascal

Blaise Pascal plumbs the depths of the human condition and establishes the logic of conservatism by examining hard choices in high-stakes situations. Pascal expresses his insights in brilliant pensées—fireworks of thought.

Let me focus on Pascal’s thoughts about two kinds of hard choices: (a) Who shall rule? (b) How shall I behave if God’s existence is uncertain?

Pascal’s general approach to hard choices is to clarify the limits of reason and the power of psychology, the better to chart a narrow path for rational choice: “There is nothing so conformable to reason as the disavowal of reason.” Pensée no. 272

Knowledge is incomplete. A (partial) increase in one’s knowledge tends to induce overconfidence. Wisdom consists in cognitive humility—an elusive frame of mind for intellectuals:

“The sciences have two extremes which meet. The first is that pure natural ignorance in which every man is born. The other extreme is that reached by great minds, who, having run through all that men can know, find that they know nothing, and again come round to the same ignorance from which they started; but this is a learned ignorance, conscious of itself. Those between the two, who have left their natural ignorance and not been able to reach the other, have some tincture of this vain knowledge, and assume to be wise.” Pensée no. 327

Who shall rule?

Pascal foreshadows the conservative principle, Chesterton’s fence. One should hesitate to change a rule, or to break with tradition, unless one understands the origin or function of the rule or tradition.

Pascal makes a case that traditions deserve legitimacy. Traditions have stood the test of time because they reduce conflict: Do we follow ancient laws and opinions because they are more sound? No; but because they stand alone and take from us the root of diversity [conflict].” Pensée no. 589

Pascal then illustrates the conservative principle’s function by concrete analysis of a fundamental political institution in early modern Europe: monarchy with dynastic succession by primogeniture:

The most unreasonable things in the world become most reasonable, because of the unruly lives of men. What is less reasonable than to choose the eldest son of a queen to guide a state? for we do not choose as steersman of a ship that one of the passengers who is of the best family. Such a law would be ridiculous and unjust; but since they are so themselves, and ever will be, it becomes reasonable and just. For would they choose the most virtuous and able, we at once fall to blows, since each asserts that he is the most virtuous and able. Let us then affix this quality to something which cannot be disputed. This man is the king’s eldest son. That is clear, and there is no dispute. Reason can do no better, for civil war is the worst of evils.” Pensée no. 786

Here Pascal foreshadows Nobel Laureate Thomas C. Schelling’s theory of the crucial role of salient focal points in strategic interaction and conflict resolution. Salience is psychological, not strictly logical. If there exists a clear, preferably unique, focal point, it can forestall or overcome bargaining impasses and self-serving conceptions of justice. If the focal point is recurrent—for example, primogeniture—it may readily become a tradition, a Chesterton fence.

How shall I behave if God’s existence is uncertain?

‘Pascal’s Wager,’ his most famous pensée, deploys both the logic of games of chance, and the psychology of belief-formation, to try and convince freethinkers to bet on God, and to dupe themselves

Pascal’s interlocutor is someone who does not believe in God. Their dialogue has three background empirical premises:

  • If God exists, then belief in God is a necessary condition for salvation in the afterlife.
  • One cannot prove the existence of God.
  • One cannot simply decide to believe.

Given these premises, Pascal first makes a gambler’s case that it would be prudent to believe in God. Pascal makes an appeal to interest, not evidence:

“Let us then examine this point, and say, ‘God is, or he is not.’ But to which side shall we incline? Reason can determine nothing about it. There is an infinite gulf fixed between us. A game is playing at the extremity of this infinite distance in which heads or tails may turn up. What will you wager? [… .]

Let us weigh the gain and the loss in choosing heads that God is. [… .] But there is here an infinity of an infinitely happy life to win, a chance of gain against a finite number of chances of loss, and what you stake is finite; that is decided. Wherever the infinite exists and there is not an infinity of chances of loss against that of gain, there is no room for hesitation, you must risk the whole. [… .]

Every gambler stakes a certainty to gain an uncertainty, and yet he stakes a finite certainty against a finite uncertainty without acting unreasonably. [… .] So that our argument is of infinite force, if we stake the finite in a game where there are equal chances of gain and loss, and the infinite is the winnings. This is demonstrable, and if men are capable of any truths, this is one.” Pensée no. 233

The intuition is that any positive chance at an infinite reward has infinite value, and so trumps any finite worldly pleasures here and now. 

Pascal’s wager triggered an ongoing avalanche of analysis of the logic of ‘expected utility.’ It gets complicated fast. Let me mention just a few issues for flavor. What if God exists, but punishes gamblers? What if a gambler has a high ‘discount rate’ (i.e., cares about the present, not the afterlife)? What if there are many Gods?

Howsoever that may be, Pascal is certain that he has got the gambler’s attention. A quandary—a psychological challenge—then naturally arises. If it would be prudent to believe in God, but there is no proof of God and one cannot simply decide to believe in God, then what is a non-believer to do?!

Pascal’s answer is to take steps to dupe oneself by going through the motions of religious practice: 

“I confess and admit it [that belief in God would be prudent]. Yet is there no means of seeing the hands at the game? — Yes, the Scripture and the rest, etc. — Well, but my hands are tied and my mouth is gagged: I am forced to wager and am not free, none can release me, but I am so made that I cannot believe. What then would you have me do? [… .]

Labor then to convince yourself, not by increase of the proofs of God, but by the diminution of your passions. You would fam arrive at faith, but know not the way; you would heal yourself of unbelief, and you ask remedies for it. Learn of those who have been bound as you are, but who now stake all that they possess; these are they who know the way you would follow, who are cured of a disease of which you would be cured. Follow the way by which they began, by making believe that they believed, taking the holy water, having masses said, etc. Thus you will naturally be brought to believe, and will lose your acuteness. — But that is just what I fear. — Why? what have you to lose?

The last process of reason is to recognize that there is an infinity of things which transcend it; it is but weak if it does not go so far as to know that.Pensée no. 233

The psychological thesis is that faking it is transformative. Going through the motions will eventually (a) dull one’s critical faculties, (b) erase one’s awareness of faking it, and (c) induce faith. The rational, self-interested choice is to submit to tradition as a means to psychological transformation.

Pascal’s thoughts about politics (legitimacy of dynastic succession) and about religion (prudent make-believe to achieve faith)—his thoughts about hard choices in high stakes situations—unflinchingly demonstrate the limits of reason and strategically enlist rational choice and psychology to harness traditions. The Pensées are the dawn of the modern conservative mind.

 


John Alcorn is Principal Lecturer in Formal Organizations, Shelby Cullom Davis Endowment, Trinity College, Connecticut.  Scruples about principles of historical inquiry, and a stint teaching in Columbia’s ‘great books’ core curriculum led him to explore methodological individualism and the social sciences.  As in the Dry Bones song, a concatenation of authors—Jon Elster, Diego Gambetta, Thomas C. Schelling, Robert Sugden, David Friedman, and Michael Munger—eventually brought him to discover EconTalk and EconLog.  

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Four burning questions about the future of the $16.5B Novo-Catalent deal

To build or to buy? That’s a classic question for pharma boardrooms, and Novo Nordisk is going with both.
Beyond spending billions of dollars to expand…

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To build or to buy? That’s a classic question for pharma boardrooms, and Novo Nordisk is going with both.

Beyond spending billions of dollars to expand its own production capacity for its weight loss drugs, the Danish drugmaker said Monday it will pay $11 billion to acquire three manufacturing plants from Catalent. It’s part of a broader $16.5 billion deal with Novo Holdings, the investment arm of the pharma’s parent group, which agreed to acquire the contract manufacturer and take it private.

It’s a big deal for all parties, with potential ripple effects across the biotech ecosystem. Here’s a look at some of the most pressing questions to watch after Monday’s announcement.

Why did Novo do this?

Novo Holdings isn’t the most obvious buyer for Catalent, particularly after last year’s on-and-off M&A interest from the serial acquirer Danaher. But the deal could benefit both Novo Holdings and Novo Nordisk.

Novo Nordisk’s biggest challenge has been simply making enough of the weight loss drug Wegovy and diabetes therapy Ozempic. On last week’s earnings call, Novo Nordisk CEO Lars Fruergaard Jørgensen said the company isn’t constrained by capital in its efforts to boost manufacturing. Rather, the main challenge is the limited amount of capabilities out there, he said.

“Most pharmaceutical companies in the world would be shopping among the same manufacturers,” he said. “There’s not an unlimited amount of machinery and people to build it.”

While Novo was already one of Catalent’s major customers, the manufacturer has been hamstrung by its own balance sheet. With roughly $5 billion in debt on its books, it’s had to juggle paying down debt with sufficiently investing in its facilities. That’s been particularly challenging in keeping pace with soaring demand for GLP-1 drugs.

Novo, on the other hand, has the balance sheet to funnel as much money as needed into the plants in Italy, Belgium, and Indiana. It’s also struggled to make enough of its popular GLP-1 drugs to meet their soaring demand, with documented shortages of both Ozempic and Wegovy.

The impact won’t be immediate. The parties expect the deal to close near the end of 2024. Novo Nordisk said it expects the three new sites to “gradually increase Novo Nordisk’s filling capacity from 2026 and onwards.”

As for the rest of Catalent — nearly 50 other sites employing thousands of workers — Novo Holdings will take control. The group previously acquired Altasciences in 2021 and Ritedose in 2022, so the Catalent deal builds on a core investing interest in biopharma services, Novo Holdings CEO Kasim Kutay told Endpoints News.

Kasim Kutay

When asked about possible site closures or layoffs, Kutay said the team hasn’t thought about that.

“That’s not our track record. Our track record is to invest in quality businesses and help them grow,” he said. “There’s always stuff to do with any asset you own, but we haven’t bought this company to do some of the stuff you’re talking about.”

What does it mean for Catalent’s customers? 

Until the deal closes, Catalent will operate as a standalone business. After it closes, Novo Nordisk said it will honor its customer obligations at the three sites, a spokesperson said. But they didn’t answer a question about what happens when those contracts expire.

The wrinkle is the long-term future of the three plants that Novo Nordisk is paying for. Those sites don’t exclusively pump out Wegovy, but that could be the logical long-term aim for the Danish drugmaker.

The ideal scenario is that pricing and timelines remain the same for customers, said Nicole Paulk, CEO of the gene therapy startup Siren Biotechnology.

Nicole Paulk

“The name of the group that you’re going to send your check to is now going to be Novo Holdings instead of Catalent, but otherwise everything remains the same,” Paulk told Endpoints. “That’s the best-case scenario.”

In a worst case, Paulk said she feared the new owners could wind up closing sites or laying off Catalent groups. That could create some uncertainty for customers looking for a long-term manufacturing partner.

Are shareholders and regulators happy? 

The pandemic was a wild ride for Catalent’s stock, with shares surging from about $40 to $140 and then crashing back to earth. The $63.50 share price for the takeover is a happy ending depending on the investor.

On that point, the investing giant Elliott Investment Management is satisfied. Marc Steinberg, a partner at Elliott, called the agreement “an outstanding outcome” that “clearly maximizes value for Catalent stockholders” in a statement.

Elliott helped kick off a strategic review last August that culminated in the sale agreement. Compared to Catalent’s stock price before that review started, the deal pays a nearly 40% premium.

Alessandro Maselli

But this is hardly a victory lap for CEO Alessandro Maselli, who took over in July 2022 when Catalent’s stock price was north of $100. Novo’s takeover is a tacit acknowledgment that Maselli could never fully right the ship, as operational problems plagued the company throughout 2023 while it was limited by its debt.

Additional regulatory filings in the next few weeks could give insight into just how competitive the sale process was. William Blair analysts said they don’t expect a competing bidder “given the organic investments already being pursued at other leading CDMOs and the breadth and scale of Catalent’s operations.”

The Blair analysts also noted the companies likely “expect to spend some time educating relevant government agencies” about the deal, given the lengthy closing timeline. Given Novo Nordisk’s ascent — it’s now one of Europe’s most valuable companies — paired with the limited number of large contract manufacturers, antitrust regulators could be interested in taking a close look.

Are Catalent’s problems finally a thing of the past?

Catalent ran into a mix of financial and operational problems over the past year that played no small part in attracting the interest of an activist like Elliott.

Now with a deal in place, how quickly can Novo rectify those problems? Some of the challenges were driven by the demands of being a publicly traded company, like failing to meet investors’ revenue expectations or even filing earnings reports on time.

But Catalent also struggled with its business at times, with a range of manufacturing delays, inspection reports and occasionally writing down acquisitions that didn’t pan out. Novo’s deep pockets will go a long way to a turnaround, but only the future will tell if all these issues are fixed.

Kutay said his team is excited by the opportunity and was satisfied with the due diligence it did on the company.

“We believe we’re buying a strong company with a good management team and good prospects,” Kutay said. “If that wasn’t the case, I don’t think we’d be here.”

Amber Tong and Reynald Castañeda contributed reporting.

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Petrina Kamya, Ph.D., Head of AI Platforms at Insilico Medicine, presents at BIO CEO & Investor Conference

Petrina Kamya, PhD, Head of AI Platforms and President of Insilico Medicine Canada, will present at the BIO CEO & Investor Conference happening Feb….

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Petrina Kamya, PhD, Head of AI Platforms and President of Insilico Medicine Canada, will present at the BIO CEO & Investor Conference happening Feb. 26-27 at the New York Marriott Marquis in New York City. Dr. Kamya will speak as part of the panel “AI within Biopharma: Separating Value from Hype,” on Feb. 27, 1pm ET along with Michael Nally, CEO of Generate: Biomedicines and Liz Schwarzbach, PhD, CBO of BigHat Biosciences.

Credit: Insilico Medicine

Petrina Kamya, PhD, Head of AI Platforms and President of Insilico Medicine Canada, will present at the BIO CEO & Investor Conference happening Feb. 26-27 at the New York Marriott Marquis in New York City. Dr. Kamya will speak as part of the panel “AI within Biopharma: Separating Value from Hype,” on Feb. 27, 1pm ET along with Michael Nally, CEO of Generate: Biomedicines and Liz Schwarzbach, PhD, CBO of BigHat Biosciences.

The session will look at how the latest artificial intelligence (AI) tools – including generative AI and large language models – are currently being used to advance the discovery and design of new drugs, and which technologies are still in development. 

The BIO CEO & Investor Conference brings together over 1,000 attendees and more than 700 companies across industry and institutional investment to discuss the future investment landscape of biotechnology. Sessions focus on topics such as therapeutic advancements, market outlook, and policy priorities.

Insilico Medicine is a leading, clinical stage AI-driven drug discovery company that has raised over $400m in investments since it was founded in 2014. Dr. Kamya leads the development of the Company’s end-to-end generative AI platform, Pharma.AI from Insilico’s AI R&D Center in Montreal. Using modern machine learning techniques in the context of chemistry and biology, the platform has driven the discovery and design of 30+ new therapies, with five in clinical stages – for cancer, fibrosis, inflammatory bowel disease (IBD), and COVID-19. The Company’s lead drug, for the chronic, rare lung condition idiopathic pulmonary fibrosis, is the first AI-designed drug for an AI-discovered target to reach Phase II clinical trials with patients. Nine of the top 20 pharmaceutical companies have used Insilico’s AI platform to advance their programs, and the Company has a number of major strategic licensing deals around its AI-designed therapeutic assets, including with Sanofi, Exelixis and Menarini. 

 

About Insilico Medicine

Insilico Medicine, a global clinical stage biotechnology company powered by generative AI, is connecting biology, chemistry, and clinical trials analysis using next-generation AI systems. The company has developed AI platforms that utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques for novel target discovery and the generation of novel molecular structures with desired properties. Insilico Medicine is developing breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system diseases, infectious diseases, autoimmune diseases, and aging-related diseases. www.insilico.com 


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Another country is getting ready to launch a visa for digital nomads

Early reports are saying Japan will soon have a digital nomad visa for high-earning foreigners.

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Over the last decade, the explosion of remote work that came as a result of improved technology and the pandemic has allowed an increasing number of people to become digital nomads. 

When looked at more broadly as anyone not required to come into a fixed office but instead moves between different locations such as the home and the coffee shop, the latest estimate shows that there were more than 35 million such workers in the world by the end of 2023 while over half of those come from the United States.

Related: There is a new list of cities that are best for digital nomads

While remote work has also allowed many to move to cheaper places and travel around the world while still bringing in income, working outside of one's home country requires either dual citizenship or work authorization — the global shift toward remote work has pushed many countries to launch specific digital nomad visas to boost their economies and bring in new residents.

Japan is a very popular destination for U.S. tourists. 

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This popular vacation destination will soon have a nomad visa

Spain, Portugal, Indonesia, Malaysia, Costa Rica, Brazil, Latvia and Malta are some of the countries currently offering specific visas for foreigners who want to live there while bringing in income from abroad.

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With the exception of a few, Asian countries generally have stricter immigration laws and were much slower to launch these types of visas that some of the countries with weaker economies had as far back as 2015. As first reported by the Japan Times, the country's Immigration Services Agency ended up making the leap toward a visa for those who can earn more than ¥10 million ($68,300 USD) with income from another country.

The Japanese government has not yet worked out the specifics of how long the visa will be valid for or how much it will cost — public comment on the proposal is being accepted throughout next week. 

That said, early reports say the visa will be shorter than the typical digital nomad option that allows foreigners to live in a country for several years. The visa will reportedly be valid for six months or slightly longer but still no more than a year — along with the ability to work, this allows some to stay beyond the 90-day tourist period typically afforded to those from countries with visa-free agreements.

'Not be given a residence card of residence certificate'

While one will be able to reapply for the visa after the time runs out, this can only be done by exiting the country and being away for six months before coming back again — becoming a permanent resident on the pathway to citizenship is an entirely different process with much more strict requirements.

"Those living in Japan with the digital nomad visa will not be given a residence card or a residence certificate, which provide access to certain government benefits," reports the news outlet. "The visa cannot be renewed and must be reapplied for, with this only possible six months after leaving the countr

The visa will reportedly start in March and also allow holders to bring their spouses and families with them. To start using the visa, holders will also need to purchase private health insurance from their home country while taxes on any money one earns will also need to be paid through one's home country.

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