The ironically quiet threat plaguing organizations

Noise: A Flaw in Human Judgment: Kahneman, Daniel, Sibony, Olivier,  Sunstein, Cass R.: 9780316451406: Amazon.com: Books

“Noise” is unwanted variability in judgments that should be identical, and most senior executives underestimate just how loud it is within their organizations.

The term comes from three prominent professors: Nobel Prize-winning psychologist Daniel Kahneman, PhD, with Princeton University; Olivier Sibony, PhD, with HEC Paris and Oxford’s Saïd Business School; and Cass Sunstein, founder and director of the Program on Behavioral Economics and Public Policy at Harvard Law School. The premise is the thesis of their new 400-page book aptly titled, Noise: A Flaw in Human Judgment.

One example of noise the authors put forth is turning to three different physicians for consults and receiving three different opinions.

“So your three physicians made judgments about the same case, and we would expect them to give identical answers. The fact that they’re variable is an indication that something is wrong with the system,” Dr. Kahneman told WBUR

Noise differs from bias. Dr. Sibony illustrates bias with an analogy of stepping on the scale each morning to receive a weight that is one pound lighter than you actually are, on average, every day. Noise is stepping on scale three times in rapid succession and receiving a different number each time — random variability of something that should be the same. 

Ironically, noise is usually quiet and undetected in systems. When the professorial trio asked 828 senior executives in a variety of industries how much variation they expected to find in expert judgments, the median answer was 10 percent. In reality, the variation in expert judgments can be four to five times that. 

The reason noise is easy to underestimate? We don’t anticipate people seeing the world differently from how we do.

“And therefore we can’t imagine that there is as much noise as there is,” Dr. Sibony told WBUR.

Furthermore, noise can only be identified in statistics, making it more difficult to think about and more likely to go undiscussed, Dr. Kahneman told nonprofit media outlet network, The Conversation

Physicians and medicine are hardly the only profession with risk for noise. A noise audit for an insurance company found the median difference in the pricing determined by its underwriters for identical policies was 55 percent. The median difference in the payouts determined by its claims adjusters for identical claims was 43 percent. A senior executive estimated that the annual cost of this unwanted variability totaled hundreds of millions of dollars, according to strategy+business magazine. Noise exists in criminal sentencing, job interviewing, fingerprint examinations and employee performance reviews, among other fields and functions.

Human complexity and our cognitive flaws mean there is no straightforward way to eliminate noise, although the authors offer advice for curbing it in decision-making. Their recommendations include conducting noise audits to better understand the level of noise within organizations and practice decision-making hygiene in singular decisions, which involves sequencing information, resisting “premature intuition” (the feeling you “know” something even if you are not sure why) and dividing complex judgments into more digestible components.

Find the book here

Kati Kariko Helped Shield the World From the Coronavirus

Katalin Kariko at her home in Jenkintown, Pa., in February. Dr. Kariko’s early research into mRNA eventually led to development of the Moderna and Pfizer-BioNTech vaccines.Credit.

She grew up in Hungary, daughter of a butcher. She decided she wanted to be a scientist, although she had never met one. She moved to the United States in her 20s, but for decades never found a permanent position, instead clinging to the fringes of academia.

Now Katalin Kariko, 66, known to colleagues as Kati, has emerged as one of the heroes of Covid-19 vaccine development. Her work, with her close collaborator, Dr. Drew Weissman of the University of Pennsylvania, laid the foundation for the stunningly successful vaccines made by Pfizer-BioNTech and Moderna.

For her entire career, Dr. Kariko has focused on messenger RNA, or mRNA — the genetic script that carries DNA instructions to each cell’s protein-making machinery. She was convinced mRNA could be used to instruct cells to make their own medicines, including vaccines.

But for many years her career at the University of Pennsylvania was fragile. She migrated from lab to lab, relying on one senior scientist after another to take her in. She never made more than $60,000 a year.

By all accounts intense and single-minded, Dr. Kariko lives for “the bench” — the spot in the lab where she works. She cares little for fame. “The bench is there, the science is good,” she shrugged in a recent interview. “Who cares?”

Dr. Anthony Fauci, director of the National Institutes of Allergy and infectious Diseases, knows Dr. Kariko’s work. “She was, in a positive sense, kind of obsessed with the concept of messenger RNA,” he said.

Dr. Kariko’s struggles to stay afloat in academia have a familiar ring to scientists. She needed grants to pursue ideas that seemed wild and fanciful. She did not get them, even as more mundane research was rewarded.

“When your idea is against the conventional wisdom that makes sense to the star chamber, it is very hard to break out,” said Dr. David Langer, a neurosurgeon who has worked with Dr. Kariko.

Dr. Kariko’s ideas about mRNA were definitely unorthodox. Increasingly, they also seem to have been prescient.

“It’s going to be transforming,” Dr. Fauci said of mRNA research. “It is already transforming for Covid-19, but also for other vaccines. H.I.V. — people in the field are already excited. Influenza, malaria.”

For Dr. Kariko, most every day was a day in the lab. “You are not going to work — you are going to have fun,” her husband, Bela Francia, manager of an apartment complex, used to tell her as she dashed back to the office on evenings and weekends. He once calculated that her endless workdays meant she was earning about a dollar an hour.

For many scientists, a new discovery is followed by a plan to make money, to form a company and get a patent. But not for Dr. Kariko. “That’s the furthest thing from Kate’s mind,” Dr. Langer said.

She grew up in the small Hungarian town of Kisujszallas. She earned a Ph.D. at the University of Szeged and worked as a postdoctoral fellow at its Biological Research Center.

In 1985, when the university’s research program ran out of money, Dr. Kariko, her husband, and 2-year-old daughter, Susan, moved to Philadelphia for a job as a postdoctoral student at Temple University. Because the Hungarian government only allowed them to take $100 out of the country, she and her husband sewed £900 (roughly $1,246 today) into Susan’s teddy bear. (Susan grew up to be a two-time Olympic gold medal winner in rowing.)

When Dr. Kariko started, it was early days in the mRNA field. Even the most basic tasks were difficult, if not impossible. How do you make RNA molecules in a lab? How do you get mRNA into cells of the body?

In 1989, she landed a job with Dr. Elliot Barnathan, then a cardiologist at the University of Pennsylvania. It was a low-level position, research assistant professor, and never meant to lead to a permanent tenured position. She was supposed to be supported by grant money, but none came in.

She and Dr. Barnathan planned to insert mRNA into cells, inducing them to make new proteins. In one of the first experiments, they hoped to use the strategy to instruct cells to make a protein called the urokinase receptor. If the experiment worked, they would detect the new protein with a radioactive molecule that would be drawn to the receptor.

“Most people laughed at us,” Dr. Barnathan said.

One fateful day, the two scientists hovered over a dot-matrix printer in a narrow room at the end of a long hall. A gamma counter, needed to track the radioactive molecule, was attached to a printer. It began to spew data.

Their detector had found new proteins produced by cells that were never supposed to make them — suggesting that mRNA could be used to direct any cell to make any protein, at will.

“I felt like a god,” Dr. Kariko recalled.

She and Dr. Barnathan were on fire with ideas. Maybe they could use mRNA to improve blood vessels for heart bypass surgery. Perhaps they could even use the procedure to extend the life span of human cells.

Dr. Barnathan, though, soon left the university, accepting a position at a biotech firm, and Dr. Kariko was left without a lab or financial support. She could stay at Penn only if she found another lab to take her on. “They expected I would quit,” she said.

Universities only support low-level Ph.D.s for a limited amount of time, Dr. Langer said: “If they don’t get a grant, they will let them go.” Dr. Kariko “was not a great grant writer,” and at that point “mRNA was more of an idea,” he said.

But Dr. Langer knew Dr. Kariko from his days as a medical resident, when he had worked in Dr. Barnathan’s lab. Dr. Langer urged the head of the neurosurgery department to give Dr. Kariko’s research a chance. “He saved me,” she said.

Dr. Langer thinks it was Dr. Kariko who saved him — from the kind of thinking that dooms so many scientists.

Working with her, he realized that one key to real scientific understanding is to design experiments that always tell you something, even if it is something you don’t want to hear. The crucial data often come from the control, he learned — the part of the experiment that involves a dummy substance for comparison.

“There’s a tendency when scientists are looking at data to try to validate their own idea,” Dr. Langer said. “The best scientists try to prove themselves wrong. Kate’s genius was a willingness to accept failure and keep trying, and her ability to answer questions people were not smart enough to ask.”

Dr. Langer hoped to use mRNA to treat patients who developed blood clots following brain surgery, often resulting in strokes. His idea was to get cells in blood vessels to make nitric oxide, a substance that dilates blood vessels, but has a half-life of milliseconds. Doctors can’t just inject patients with it.

He and Dr. Kariko tried their mRNA on isolated blood vessels used to study strokes. It failed. They trudged through snow in Buffalo, N.Y., to try it in a laboratory with rabbits prone to strokes. Failure again.

And then Dr. Langer left the university, and the department chairman said he was leaving as well. Dr. Kariko again was without a lab and without funds for research.

A meeting at a photocopying machine changed that. Dr. Weissman happened by, and she struck up a conversation. “I said, ‘I am an RNA scientist — I can make anything with mRNA,’” Dr. Kariko recalled.

Dr. Weissman told her he wanted to make a vaccine against H.I.V. “I said, ‘Yeah, yeah, I can do it,’” Dr. Kariko said.

Despite her bravado, her research on mRNA had stalled. She could make mRNA molecules that instructed cells in petri dishes to make the protein of her choice. But the mRNA did not work in living mice.

“Nobody knew why,” Dr. Weissman said. “All we knew was that the mice got sick. Their fur got ruffled, they hunched up, they stopped eating, they stopped running.”

It turned out that the immune system recognizes invading microbes by detecting their mRNA and responding with inflammation. The scientists’ mRNA injections looked to the immune system like an invasion of pathogens.

But with that answer came another puzzle. Every cell in every person’s body makes mRNA, and the immune system turns a blind eye. “Why is the mRNA I made different?Dr. Kariko wondered.

A control in an experiment finally provided a clue. Dr. Kariko and Dr. Weissman noticed their mRNA caused an immune overreaction. But the control molecules, another form of RNA in the human body — so-called transfer RNA, or tRNA — did not.

A molecule called pseudouridine in tRNA allowed it to evade the immune response. As it turned out, naturally occurring human mRNA also contains the molecule.

Added to the mRNA made by Dr. Kariko and Dr. Weissman, the molecule did the same — and also made the mRNA much more powerful, directing the synthesis of 10 times as much protein in each cell.

The idea that adding pseudouridine to mRNA protected it from the body’s immune system was a basic scientific discovery with a wide range of thrilling applications. It meant that mRNA could be used to alter the functions of cells without prompting an immune system attack.

“We both started writing grants,” Dr. Weissman said. “We didn’t get most of them. People were not interested in mRNA. The people who reviewed the grants said mRNA will not be a good therapeutic, so don’t bother.’”

Leading scientific journals rejected their work. When the research finally was published, in Immunity, it got little attention.

Dr. Weissman and Dr. Kariko then showed they could induce an animal — a monkey — to make a protein they had selected. In this case, they injected monkeys with mRNA for erythropoietin, a protein that stimulates the body to make red blood cells. The animals’ red blood cell counts soared.

The scientists thought the same method could be used to prompt the body to make any protein drug, like insulin or other hormones or some of the new diabetes drugs. Crucially, mRNA also could be used to make vaccines unlike any seen before.

Instead of injecting a piece of a virus into the body, doctors could inject mRNA that would instruct cells to briefly make that part of the virus.

“We talked to pharmaceutical companies and venture capitalists. No one cared,” Dr. Weissman said. “We were screaming a lot, but no one would listen.”

Eventually, though, two biotech companies took notice of the work: Moderna, in the United States, and BioNTech, in Germany. Pfizer partnered with BioNTech, and the two now help fund Dr. Weissman’s lab.

Soon clinical trials of an mRNA flu vaccine were underway, and there were efforts to build new vaccines against cytomegalovirus and the Zika virus, among others. Then came the coronavirus.

Researchers had known for 20 years that the crucial feature of any coronavirus is the spike protein sitting on its surface, which allows the virus to inject itself into human cells. It was a fat target for an mRNA vaccine.

Chinese scientists posted the genetic sequence of the virus ravaging Wuhan in January 2020, and researchers everywhere went to work. BioNTech designed its mRNA vaccine in hours; Moderna designed its in two days.

The idea for both vaccines was to introduce mRNA into the body that would briefly instruct human cells to produce the coronavirus’s spike protein. The immune system would see the protein, recognize it as alien, and learn to attack the coronavirus if it ever appeared in the body.

The vaccines, though, needed a lipid bubble to encase the mRNA and carry it to the cells that it would enter. The vehicle came quickly, based on 25 years of work by multiple scientists, including Pieter Cullis of the University of British Columbia.

Scientists also needed to isolate the virus’s spike protein from the bounty of genetic data provided by Chinese researchers. Dr. Barney Graham, of the National Institutes of Health, and Jason McClellan, of the University of Texas at Austin, solved that problem in short order.

Testing the quickly designed vaccines required a monumental effort by companies and the National Institutes of Health. But Dr. Kariko had no doubts.

On Nov. 8, the first results of the Pfizer-BioNTech study came in, showing that the mRNA vaccine offered powerful immunity to the new virus. Dr. Kariko turned to her husband. “Oh, it works,” she said. “I thought so.”

To celebrate, she ate an entire box of Goobers chocolate-covered peanuts. By herself.

Dr. Weissman celebrated with his family, ordering takeout dinner from an Italian restaurant, “with wine,” he said. Deep down, he was awed.

“My dream was always that we develop something in the lab that helps people,” Dr. Weissman said. “I’ve satisfied my life’s dream.”

Dr. Kariko and Dr. Weissman were vaccinated on Dec. 18 at the University of Pennsylvania. Their inoculations turned into a press event, and as the cameras flashed, she began to feel uncharacteristically overwhelmed.

A senior administrator told the doctors and nurses rolling up their sleeves for shots that the scientists whose research made the vaccine possible were present, and they all clapped. Dr. Kariko wept.

Things could have gone so differently, for the scientists and for the world, Dr. Langer said. “There are probably many people like her who failed,” he said.

“I got the vaccine…now what can I do?”

https://mailchi.mp/85f08f5211a4/the-weekly-gist-february-5-2021?e=d1e747d2d8

Image result for after the vaccine covid

A family member in her 70s called with the great news that she received her first dose of the COVID vaccine this week. She mentioned that she was hoping to plan a vacation in the spring with a friend who had also been vaccinated, but her doctor told her it would still be safest to hold off booking travel for now: “I was surprised she wasn’t more positive about it. It’s the one thing I’ve been looking forward to for months, if I was lucky enough to get the shot.” 

It’s not easy to find concrete expert guidance for what it is safe (or safer?) to do after receiving the COVID vaccine. Of course, patients need to wait a minimum of two weeks after receiving their second shot of the Pfizer or Moderna vaccines to develop full immunity.

But then what? Yes, we all need to continue to wear masks in public, since vaccines haven’t been proven to reduce or eliminate COVID transmission—and new viral variants up the risk of transmission. But should vaccinated individuals feel comfortable flying on a plane? Visiting family? Dining indoors? Finally going to the dentist?
 
It struck us that the tone of much of the available guidance speaks to public health implications, rather than individual decision-making. Take this tweet from CDC director Dr. Rochelle Walensky. A person over 65 asked her if she could drive to visit her grandchildren, whom she hasn’t seen for a year, two months after receiving her second shot. Walensky replied, “Even if you’ve been vaccinated, we still recommend against traveling until we have more data to suggest vaccination limits the spread of COVID-19.” 

From a public health perspective, this may be correct, but for an individual, it falls flat. This senior has followed all the rules—if the vaccine doesn’t enable her to safely see her grandchild, what will? It’s easy to see how the expert guidance could be interpreted as “nothing will change, even after you’ve been vaccinated.”

Debates about masking showed us that in our individualistic society, public health messaging about slowing transmission and protecting others sadly failed to make many mask up.

The same goes for vaccines: most Americans are motivated to get their vaccine so that they personally don’t die, and so they can resume a more normal life, not by the altruistic desire to slow the spread of COVID in the community and achieve “herd immunity”. 

In addition to focusing on continued risk, educating Americans on how the vaccinated can make smart decisions will motivate as many people as possible to get their shots.

Turning the tide in the battle against the virus

https://mailchi.mp/85f08f5211a4/the-weekly-gist-february-5-2021?e=d1e747d2d8

Image result for Turning the tide

The national COVID indicators all continued to move in the right direction this week, with new cases down 16 percent, hospitalizations down 26 percent, and deaths (while still alarmingly high at more than 3,000 per day) down 6 percent from the week prior.

More good news: both nationally and globallythe number of people vaccinated against COVID now exceeds the total number of people infected with the virus, at least according to official statistics—the actual number of coronavirus infections is likely several times higher.

On the vaccine front, Johnson & Johnson filed with the Food and Drug Administration (FDA) for an Emergency Use Authorization for its single-dose COVID vaccine, which could become the third vaccine approved for use in the US following government review later this month. The J&J vaccine is reportedly 85 percent effective at preventing severe COVID disease, although it is less effective at preventing infection than the Pfizer and Moderna shots.

Elsewhere, TheLancet reported interim Phase III results for Russia’s Sputnik V vaccine trials, showing it to be 91 percent effective at preventing infection, and a new study found the Oxford-AstraZeneca vaccine to be 75 percent effective against the more-contagious UK virus variant.

Amid the positive vaccine news, the Biden administration moved to accelerate the vaccination campaigninvoking the Defense Production Act to boost production and initiating shipments directly to retail pharmacies. With the House and Senate starting the budget reconciliation process that could eventually lead to as much as $1.9T in stimulus funding, including billions more for vaccines and testing, it feels as though the tide may be finally turning in the battle against coronavirus.

While the key indicators are still worrisome—we’re only back to Thanksgiving-week levels of new cases—and emerging variants are cause for concern, it’s worth celebrating a week that brought more good news than bad.

Best to follow Dr. Fauci’s advice for this Super Bowl weekend, however: “Just lay low and cool it.”

Deborah Birx says Trump received a “parallel set of data” on the coronavirus

https://www.washingtonpost.com/politics/2021/01/25/health-202-hospitals-drag-feet-new-regulations-disclose-costs-medical-services/

The former White House coronavirus response coordinator told CBS News’s “Face The Nation” that she saw Trump presenting graphs about the coronavirus that she did not help make. Someone inside or outside of the administration, she said, “was creating a parallel set of data and graphics that were shown to the president.”

Birx also said that there were people in the White House who believed the coronavirus was a hoax and that she was one of only two people in the White House who routinely wore masks.

Birx was often caught between criticism from Trump, who at one point called her “pathetic” on Twitter when she contradicted his more optimistic predictions for the virus, and critics in the scientific community who thought she did not do enough to combat false information about the virus from TrumpThe Post’s Meryl Kornfield reports.

“Colleagues of mine that I’d known for decades — decades — in that one experience, because I was in the White House, decided that I had become this political person, even though they had known me forever,” she told CBS. “I had to ask myself every morning, ‘Is there something that I think I can do that would be helpful in responding to this pandemic?’ And it’s something I asked myself every night.”

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told the New York Times that Trump repeatedly tried to minimize the severity of the virus and would often chide him for not being positive enough in his statements about the virus. 

Fauci also described facing death threats as he was increasingly vilified by the president’s supporters. “One day I got a letter in the mail, I opened it up and a puff of powder came all over my face and my chest,” he said. The powder turned out to be benign.

Fauci: Lack of facts ‘likely did’ cost lives in coronavirus fight

Fauci: Lack of facts 'likely did' cost lives in coronavirus fight | TheHill

Anthony Fauci on Friday said that a lack of facts “likely did” cost lives over the last year in the nation’s efforts to fight the coronavirus pandemic.

In an appearance on CNN, the nation’s leading infectious diseases expert was directly asked whether a “lack of candor or facts” contributed to the number of lives lost during the coronavirus pandemic over the past year.

“You know it very likely did,” Fauci said. “You know I don’t want that … to be a sound bite, but I think if you just look at that, you can see that when you’re starting to go down paths that are not based on any science at all, that is not helpful at all, and particularly when you’re in a situation of almost being in a crisis with the number of cases and hospitalizations and deaths that we have.”

“When you start talking about things that make no sense medically and no sense scientifically, that clearly is not helpful,” he continued.

President Biden on Thursday unveiled a new national coronavirus strategy that is, in part, aimed at “restoring trust in the American people.”

When asked why that was important, Fauci recognized that the past year of dealing with the pandemic had been filled with divisiveness.

“There’s no secret. We’ve had a lot of divisiveness, we’ve had facts that were very, very clear that were questioned. People were not trusting what health officials were saying, there was great divisiveness, masks became a political issue,” Fauci said.

“So what the president was saying right from the get-go was, ‘Let’s reset this. Let everybody get on the same page, trust each other, let the science speak.’”

Fauci, who was thrust into the national spotlight last year as part of former President Trump‘s coronavirus task force, often found himself at odds with the former president. Trump frequently downplayed the severity of the virus and clashed publicly with Fauci.

Speaking during a White House press briefing on Thursday, Fauci said it was “liberating” to be working in the Biden administration.

There have been more than 24,600,000 coronavirus infections in the U.S. since the pandemic began, according to a count from Johns Hopkins University. More than 410,000 people have died.

Cartoon – History Repeating Itself (Covid-19)

Editorial Cartoon: COVID-19 returns | Opinion | dailyastorian.com

Cartoon – Less “I” and more “US.”

Trump's coronavirus press conference less than inspiring - The San Diego  Union-Tribune