"Moonshot", ("Little, Big")

[fiefoe]

Dr Albert Bourla shows a bit more personality in this than other CEO books I can remember. One now knows he let his high school age son listen in on his phone calls with heads of state.

• We always start with a very small dose and put the subjects under close medical supervision. We are doing tests and looking for any signals that could create any safety concerns. If everything is approved to go forward, we move to a higher dose and repeat the same process. At the same time, we measure the biological effect that each dose has on humans. We cannot estimate efficacy at this stage; instead we are looking for surrogate endpoints, possible measures of effect, like stimulation of the immune system with antibody and T-cell responses. We progressively increase the dose until we reach a level that is safe and satisfies our surrogate criteria for efficacy. If this is not possible, we go back to the molecular scientists to reengineer the candidates, and once again we will start new Phase 1 studies with new vaccine candidates.
  If our Phase 1 studies are successful, we move the best candidates into Phase 2 studies. In the Phase 2 studies, we try the vaccine candidates in different regimens—one or two doses, three or six weeks apart, in young or old adults, etc. We are trying many combinations, and we constantly measure safety and efficacy surrogate endpoints until we decide that we have one that is optimal. A Phase 2 study usually has very high standards for determining success because it green-lights the initiation of the final and most important study: Phase 3. The learnings from these earlier phases inform the refined focus necessary to initiate a Phase 3 study.
• They decided to target 120 sites so they could recruit these participants faster (later we increased this number to 153). But the most critical factor was to select research sites in areas where there would be a heavy COVID-19 disease burden, so the attack rates (percentage of participants who contract the disease naturally during the study period) would be higher. If you have low attack rates, and as a result fewer people getting sick, you cannot be sure if your vaccine provides protection... The problem was that the attack rates for different locations were changing over time. When a city or county had a lot of infections, they would usually take policy measures, and the attack rates would drop after a period of time.
• “Where are you going to find that much dry ice?”
  “We calculated that we would need one to two percent of the US dry ice supply. The problem is more logistical, but we have a solution. We will start manufacturing dry ice in our facilities and use it on-site.”
• The key ingredient in our COVID-19 vaccine would prove to be lipids. Remember that our vaccine uses lipid nanoparticles to transport mRNA to instruct cells to make the SARS-CoV-2 spike protein. Lipids, which are chemically synthesized, became the most important constraint to solve for. They were a new ingredient, not used at scale in other vaccines.
  To make matters even more complex, there are four different lipids needed. Two are proprietary and two are commodity.
• Things were progressing, but there were a lot of ups and downs. And I was relentless in keeping the pressure up. I am very good at remembering numbers. When a projection was presented one week and then lowered without explanation the following week or month, I was livid.
  “The timelines on the schedules of slide number seven don’t match the dates at the executive summary slide. Your numbers at slide eleven are lower than what you showed me last time. You should have these changes up front and highlighted, not buried on a slide in the middle of the presentation deck. Please don’t do this again. You know how well I remember the numbers.”
• Shipping a vaccine at this temperature at scale had never been done before. There was simply no infrastructure to support it. Imagine having a rocket—the vaccine—with no place to land it. Our global supply chain team came up with a brilliant solution.
• 
  Setting up test sites early in the pandemic prepared CVS well for the vaccination phase. They hired nurses and technicians to ensure adequate capacity. And thanks to CVS’s digital and human outreach, 94 percent of patients returned for their second dose of vaccine on the day of their appointment. If patients had trouble getting to the store, CVS had an arrangement with the ride-share company Lyft to get them there.
• There are many different types and brands of syringes that are commercially available, and each one has a different dead volume. Typically, the issue can be resolved by overfilling the vials to cover all options. But in the case of a COVID-19 vaccine in the middle of a pandemic, every single drop saved could mean additional lives saved. To be accurate, each dose is 0.3 ml, so with any excess ml per vial we had potential to save an additional life. We didn’t have the luxury of wasting any doses.
• We needed syringe and needle matches that would extract and dispense six doses consistently. We discovered a very large number of syringe and needle combinations that could achieve that, and by using the right combination of low-dead-volume syringes and needles, we discovered it was possible to reduce the waste and get safely at least 20 percent more vaccine out of each vial.
• “Be my guest, Jared,” I replied. “I prefer to have Japan’s prime minister complaining to you about the cancellation of the Olympics rather than to me.”
  Thankfully, our manufacturing team continued to work miracles, and I received an improved manufacturing schedule that would allow us to provide the additional doses to the US from April to July without cutting the supply to the other countries.
• When on the morning of May 5, 2021, I read the statement of Ambassador Tai—that the US would support the TRIPS waiver, which would undercut intellectual property protections—I was, frankly, pissed. I was truly angry that at the same time that the US government was blocking us from exporting COVID-19 doses to other countries, their trade representative was supporting a proposal that would directly harm the intellectual property rights of an American company.
• The proposed waiver for COVID-19 vaccines, threatens to disrupt the flow of raw materials. It will unleash a scramble for the critical inputs we require in order to make a safe and effective vaccine. Entities with little or no experience in manufacturing vaccines are likely to chase the very raw materials we require to scale our production, putting the safety and security of all at risk.
• Israel had a small number of doses that were approaching their expiry date, and he wanted us to facilitate moving these doses to another country so they could be used immediately. The plan was to give these doses to the Palestinian National Authority, but at the last moment the Palestinians refused to accept them, and now there was an urgent need to resolve this. There were a lot of challenges, but I agreed with him that it would be terrible if we let lifesaving doses expire because of technical or bureaucratic issues. In the days that followed, we started texting each other and talking on the phone daily about this issue, until eventually a deal was made between Israel and South Korea, and Pfizer facilitated the transfer.
• AdAge wrote that “Pfizer has been, far and away, the big winner in vaccine brand popularity.” The paper’s five strategies for brands to succeed in a crowded market emphasized our visibility and transparency, and our inclusion of consumers in the product itself.

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Try as I might, I just couldn't get a handle on the book, a John Crowley fantasy on my to-read list for a long time. It seems way heavier on atmosphere than on plot -- but maybe I'm mistaken here, but I wouldn't really know.

• he wondered about their lives in these places, which to him seemed gloomily peripheral, though the kids were cheerful enough.
• (Later on, it was Smoky’s habit to try to sort out his half-siblings and their houses and assign them to their proper cities and states while he sat on the toilet. Maybe that was because it was in their toilets that he had felt most anonymous, anonymous to the point of invisibility; anyway, he would pass the time there shuffling his brothers and sisters and their children like a pack of cards, trying to match faces to porches to lawns, until late in life he could deal out the whole of it. It gave him the same bleak satisfaction he got from solving crossword puzzles, and the same doubt
• The more he looked at her the stronger it grew, the more she looked at him the more he felt… what? In a moment of silence they simply looked at each other, and understanding hummed, thundered within Smoky as he realized what had happened: not only had he fallen in love with her, and at first sight, but she at first sight had fallen in love with him, and the two circumstances had this effect: his anonymity was being cured. Not disguised, as George Mouse had tried to do, but cured, from the inside out. That was the feeling. It was as though she stirred him with cornstarch. He had begun to thicken.
• “No. It’s not like that. Outside, you see colors inside it; so, inside it—”
  “You see colors outside it.”
  “Yes. The whole world colored, as though it were made of candy—no, like it was made of a rainbow. A whole colored world as soft as light all around as far as you can see.
• The Things that Make us Happy / Make us Wise.
• “Then it all got mixed up. It seemed there wasn’t any time that wasn’t being broken flat and put away, that I wasn’t doing it any more, that it was happening by itself; and that all that was left was awful time, walking down halls time, waking up in the night time, nothing doing time…”
• First she wanted to taste the sweat that shone on his throat and fragile clavicle; then he chose to undo the tails of her shirt, that she had tied up beneath her breasts; then, but then impatient they forgot about taking turns and quarreled silently, eagerly over each other, like pirates dividing treasure long sought, long imagined, long withheld.
• Sophie saw them coupling. She felt with intense certainty what moods Smoky made come and go in her sister, though they were not the moods she had known Daily Alice to feel before. She saw clearly what it was to make her sister’s brown eyes grow dense and inward, or leap to light: saw it all. It was as though Daily Alice were made of some dark glass which had always been partly opaque, but now, held up before the bright lamp of Smoky’s love, became wholly transparent, so that no detail of Alice could be hidden from her as she watched them.
• At the thought a sudden picture, a colored engraving, was projected before him on the water: a bewigged fish in a high-collared coat, a huge letter under his arm, his mouth gaping open. In air. At this nightmare image (from where?) his gills gasped and he awoke momentarily;
• In those days, as he never tired of saying, photography was like a religion. A perfect image was like a gift of grace, but sin would always be swiftly punished. A sort of Calvinist dogma, where you never knew when you were right, but must be constantly vigilant against error.
• “You mustn’t look at them, though,” Nora said to him, “because, well,” dancing from foot to foot, “in some of them we were—Stark Naked!” And he had promised, thinking of the Muslim letter-readers who must cover their ears when they read letters for their clients, so as not to overhear the contents.
• He knew light had its gifts and its surprises; could not these be among them? No, they could not. Nora and Timmie Willie had caught, by accident or design, creatures that seemed on the point of metamorphosis from natural to outlandish. A bird’s face here and yet that claw which gripped the branch was a hand, a hand in a sleeve. There wasn’t any doubt about it when you studied it long enough. This cobweb was no cobweb but the trailing skirt of a lady whose pale face was collared in these dark leaves.
• Suppose a branch of our old family tree—a branch that seemed doomed to wither—had in fact not died out but survived, survived by learning arts just as new to the world but utterly different from the tool-making and fire-building of its grosser cousins, us. Suppose that instead they had learned concealment, smallification, disappearance, and some way to blind the eyes of beholders.
  Suppose they had learned to leave no trace; no barrow, flint, glyph; no bone, no tooth.
  Except that now Man’s arts had caught up with them, had discovered an eye dull enough to see them and record the fact, a retina of celluloid and silver-salts less forgetful, less confusable; an eye that couldn’t deny what it had seen.
• It occurred to him that seeing a woman’s child is like seeing a woman naked, in the way it changes how her face looks to you, how her face becomes less the whole story.