That was then, this is now

In 1957, when flu swept through Hong Kong, Mr [Maurice] Hilleman identified the virus as a new form to which people had no natural immunity and passed on his findings to vaccine-makers. When the virus reached the United States a few months later 40m doses of vaccine were ready to limit its damage.

Here is more from The Economist, circa 2005, via Brian LaRocca.  How many of you have heard of Maurice Hilleman? He has other accomplishments, and according to Wikipedia “He is credited with saving more lives than any other medical scientist of the 20th century.”  I say he is underrated!

Comments

Wait a second. I’ve been told it takes much longer to develop and approve a vaccine. How was this possible over 60 years ago, with relatively primitive technology?

That's the flu (influenza A). Just a new strain of an old species. There's a tried-and-true method to make vaccine using eggs.

For COVID-19 you have to do it all from scratch. No vaccines have ever been created for any coronavirus.

That's not true. There are very widely utilized vaccines for Canine Coronavirus and Feline Coronavirus.

There's nothing impossible about Coronavirus vaccines. We don't have one because other than SARS1 the 4 Coronaviruses were some of the 200 or so viruses causing common cold, and so it'd be spectacularly hard to test efficacy, and well, it's just a cold.

Meanwhile SARS1 went away too fast, only lasted a few months.

I'd put odds of a successful vaccine for SARS2-Covid-19 by year-end having been given to over 10k people at probably 50%, and probably 80%+ by next year.

We have animal vaccines for coronavirus but no human ones.

https://en.wikipedia.org/wiki/Avian_coronavirus#Vaccines
https://en.wikipedia.org/wiki/Bovine_coronavirus
https://en.wikipedia.org/wiki/Canine_coronavirus

Moderna had created a vaccine for MERS. And they had a vaccine for Covid-19 in January.

Their use of messenger RNA as a vaccine is exponentially less risky than older generations of vaccines.

The FDA needs to serously consider allowing Phase 2 testing on front line responders.

The risk posed to them by this untested vaccine, is significantly lower than the risk of actually getting Covid-19.

https://www.mercatus.org/publications/covid-19/accelerating-availability-vaccine-candidates-covid-19
People can expect that by the end of summer, going into a possible fall peak, there will be several vaccine candidates for COVID-19, and that researchers will have partial and preliminary data on those candidates’ safety and effectiveness based on a few months of clinical trials. Even if clinical trials are not complete, there should be enough data that informed patients may reasonably desire to get vaccinated. Congress should not let the traditional FDA approval process stop them from doing so.

oh, yes they should! Bad things can happen with vaccines as with other drugs. We don’t want the cure to be worse than the disease!

Full disclosure: I’ve never worked in vaccine development

And, on the margin, we do not want the disease to be worse than the cure. We want to pursue cures up to the margin where marginal cost = marginal benefit. This principle doe not negate realizing that some cures CAN be worse than the disease.

The estimated 18-month time frame to develop a vaccine has nothing to do with technology. It's all safety testing. They've already dosed some humans with vaccines, and now they have to watch them 14 months to see if there are any long-term negative effects.

The idea is that if you're going to administer a vaccine to billions of people, you'd better make sure it's safe. This seems reasonable, but the trade-off is that we have no vaccine for a year and a half.

How was 14 established as the optimal waiting period? Were the cost and benefits evaluations that established it the same as what we now believe to be those of Covid-19?

No fda

FDA established in 1908.

Ok, more specifically, the FDA typically did not require demonstration of safety and effectiveness of so-called ethical preparations until after the thalidomide scandal of the early 60s. Before then, with the exception of penicillin preparations, the agency focussed very much on the F part of its remit: food

Thalidomide was never approved for use in the US. There were pills imported and used for experimental testing. The Europeans tightened their regulation of pharmaceuticals after thalidomide. Back then, the US was a world leader.

There’s no way Tyler isn’t cognizant of the greater message of his post- that vaccines have been successfully developed and employed in the US in a much shorter time frame than 12-18 months.

"Finally, Hilleman took a step that seems unbelievable in the bureaucratically hardened, litigious society of today. He bypassed the Department of Health, Education and Welfare's (HEW) Division of Biologic Standards and contacted the heads of the six U.S. vaccine manufacturers directly. His message was simple. "Don't kill your roosters." As a farm boy growing up in Montana, Hilleman had learned that farmers sell their roosters for stewing pots at the end of the spring hatching season. Because of his years working with the influenza virus, he knew that vaccine manufacturers produce their vaccine in fertilized chicken eggs. To produce vaccine on the scale Hilleman was envisioning would require a massive amount of fertilized chicken eggs. Manufacturers would need every rooster they could get. Recognizing that time was of the essence, Hilleman followed up his phone calls by shipping samples of this new strain to each of the six manufacturers for vaccine production on 22 May 1957. Initially dubbed "Far East influenza," the virus was later named the Asian Flu."

*Influenza* by George Dehner.

The rooster is the perfect symbol for toxic masculinity. I weep for those poor hens, especially the trans hens of color on the lowest rung of the pecking order.

still over a million deaths worldwide....116,000 American

NYC has over ~15,000 infected, ~2,000 hospitalized, and 114 dead. So begins the war on the virus.

In 1957 both corporate taxes and upper-bracket income taxes were MUCH lower than today, therefore encouraging private sector innovation. Also the FDA was not around in 1957 and drug regulation was basically non-existent.

The top tax rate in the US was much *higher* in 1957 than it is today:

https://www.taxpolicycenter.org/statistics/historical-highest-marginal-income-tax-rates

Doubt it, seems unlikely a vaccine could have been developed quickly under those conditions.

Please tell me you are being sarcastic

Yes it's his hilarious troll joke

More than Salk? Polio and flu.

The middle of the 20th Century was an age of medical heroes, most of whom are forgotten today except for Salk and a few others. For example, I've been reading Jared Diamond's books for 25 years, but I only learned this year that his father Louis Diamond invented in the 1940s a procedure that is said to have saved the lives of hundreds of thousands of babies.

As far as I can tell, there were dozens of guys like this.

Much lower taxes and regulation at mid-century was a massive boost to innovation in the medical sphere.

I know you are trolling, but there's truth in your trolling . When Salk'so team at U of M wanted to test their flu vaccine, the first of its kind , they just drove down to the local mental hospital and started poking the patients .

That's because there was still lots of low-hanging fruit to be picked. It was the very beginning of molecular biology. One man COULD do something revolutionary.

Computer science showed exactly the same pattern 50 years later. In a hundred years people will be saying exactly the same thing about people like Dijkstra and Knuth, or Page and Brin. "Wow, back then there men who could develop revolutionary algorithms *all by themselves*."

According to Wikipedia, the 1957 Asian flu killed 69,800 people in the US and 1-4 million worldwide. https://en.m.wikipedia.org/wiki/Influenza_A_virus_subtype_H2N2#Asian_flu

The 1968 Hong Kong flu killed 100,000 Americans and 1 million worldwide: https://en.m.wikipedia.org/wiki/1968_flu_pandemic

I bet the death toll is lower this time.

The down stream impacts our response will case far more deaths than the Hong Kong flu.

I agree, and perhaps people would be less willing to support extreme corrective measures if they realized that this is not the first big pandemic we’ve had in modern times, which a lot of people seem to think it is.

Why would it be lower?

With an R0 of 2, we're looking at 50% infection with 1% death rate

Using a simple ratio of 1 reported case = 10 unreported cases, and using Italy as a current example, it is pretty easy to figure out the result of reported cases x 10 divided by country population to get an extremely rough estimate of how many people in Italy have been infected till now.

59,138 x 10 / 60,000,000 = less than 1%

Change the ratio to 1 to 100 (a number for which there is absolutely no evidence in places with much better testing such as South Korea or Germany), and less than 10% of all Italians have been infected.

For Italy as a whole, sure, less than 1%.

For Lombardy... Lombardy has about 50% Italy's counted cases, and population is 10,060,574. 59,138*10/2 = 295,690/10,060,574 = about 3%.

10% in Lombardy is not so impossible if there are 30 unknown cases for every 1 people know about. Apparent C:F ratio of 12% in Lombardy vs 0.7-0.8% in SK suggests about 15x ratio in recording. You'd need SK to be undercounting by half again to get to 30x.

The death might be lower if only because we have better breathing machines than in 1957 and a lot more people trained in how to use them. Iron lungs, as they called them, were big, bulky, expensive and more complicated to operate than modern ventilators. I'm not going to say "modern times win", but we have learned some useful stuff.

Our HOPE is that it’s lower! We are taking extreme measures to this end. So yes, we hope that our measures leading to a recession are not wasted!

In this specific case, Hilleman delivered samples to vaccine manufacturers on May 22 1957 and the first deliveries went to the military on September 1st, with the full order of 60 million out by February 2nd 1958. While they dramatically got it out much faster than predicted (53 million by mid November) it was considered a bungled failure by the public, who accused the government of conspiring with pharmaceutical companies to produce expensive vaccines bought mostly by corporations for their own employees. It appears we just got lucky, however, as the pandemic disappeared before WHO or the CDC could get on top of it, and only by the grace of God lacked the Spanish Flu's mortality

Nobody suggested locking down the country in 57 and 68. They probably would have thought the idea preposterous.

There wasn't social media, an enormous number of people who have a desire to reduce/eliminate humanity, and the media (as it stands today) in 57 and 68.

I think the difference between then and now boiled down to this: ventilators were not widely available in 1957, so if you get the flu, and it was a severe case where you had difficulty breathing, you would probably die (so that's why this pandemic and especially the one in 1919 were so deadly). In 2020 we can save far more people than in 1957 if we put patients in a ventilator, but unfortunately we don't have enough of them. So the lockdown is a way of slowing down the pandemic so more people have access to ventilators. This is a failure of planning, of thinking the era of these pandemics were a thing of the past.

cove77: "still over a million deaths worldwide....116,000 American"

,

...and the Great Chinese Famine (1958-1961) killed about 40 Million

life is risky

Yes he does seem to be massively underrated.

"Robert Gallo described him as "the most successful vaccinologist in history". It's a pity they didn't cite praise from someone more respectable than Gallo.

What is the shade toward gallo based on? Hopefully more than having read "the band played on" and accepting it as unbiased fact....

Are you perhaps too young to remember Gallo's attempt to claim credit for "discovering" a virus that had, in fact, been sent to him by Montagnier?

I can remember biological science acquaintances fuming about the man's behaviour.

I am too young, but fortunately books exist. There is nuance here: See wikipedia,
"Montagnier's group in France isolated HIV almost one and a half years before Gallo,[25] while Gallo's group demonstrated that the virus causes AIDS and generated much of the science that made the discovery possible, including a technique previously developed by Gallo's lab for growing T cells in the laboratory.[3] When Montagnier's group first published their discovery, they said HIV's role in causing AIDS "remains to be determined."[26]"

It really depends on how one determines primacy for these things, or in some sense what it means to "discover" HIV. In my opinion, isolating a virus and then doing nothing afterwards is less important than figuring out how it actually relates to the disease at hand.

And if you read yet further, the story you reference is pretty murky:

"In 1989, the investigative journalist John Crewdson[27] suggested that Gallo's lab might have misappropriated a sample of HIV isolated at the Pasteur Institute by Montagnier's group.[28] Investigations by the National Institutes of Health (NIH) and the HHS ultimately cleared Gallo's group of any wrongdoing[26][29] and demonstrated that they had numerous isolates of HIV of their own. As part of these investigations, the United States Office of Research Integrity at the National Institutes of Health commissioned Hoffmann–La Roche scientists to analyze archival samples established at the Pasteur Institute and the Laboratory of Tumor Cell Biology (LTCB) of the National Cancer Institute between 1983 and 1985. They concluded that the virus used in Gallo's lab had come from Montagnier's lab; it was a virus from a patient that had contaminated a virus sample from another patient."

WKPD can whitewash as much as it likes. I was around at the time. I remember bioscience acquaintances and their view of Gallo. I remember their delight later when the Nobel committee rewarded Montagnier and not Gallo.

Indeed, he wasn't well liked, and that was likely why he didn't get the nobel. On the science, there is little doubt that he deserved the prize, as Montagnier himself acknowledged.

Anyway, I have argued with facts, you have argued via "I was alive at the time" and "my friends didn't like him," so this seems pointless.

Unrelated to this post but I know someone that takes plaquenil (brand name of Hydroxychloroquine) for rheumatoid arthritis and is having trouble getting their prescription refilled right now for obvious reasons.

I am no health industry person but this got me thinking about the people that die from coronavirus.

Perhaps the people that die are the type that have some overactive response to the virus kind of like how rheumatoid arthritis is an overactive immune response.

Is anyone collecting data on who is dying and whether or not there is a relationship between those who die and those that have immune system responses like people with rheumatoid? This would seem to imply that those with certain allergies or those with immune systems that geek out might be more at risk.

Perhaps just like rheumatoid, these things are more common in older people. Even asthma might be like that.

yes, most of the elderly who died have this hyperactive immune response called a cytokine storm. Not sure if it is similar to the rheumatoid arthritis case
just one of many papers
https://www.medrxiv.org/content/10.1101/2020.03.01.20029769v2

That's good insight. They call it the cytokine storm nowadays, where the inflammation response goes out of control. There was some talk about this on various pharmaceutical blogs. (We have chloroquine in the house because we were in Ethiopia and lucked out with good weather meaning no mosquitoes. No, we aren't going to dose ourselves.)

More evidence that Nobels are BS.

A hero; Joseph Goldberger is another that is not a household name.

I remember having the 1957 flu. I was in 6th grade. My class size was about 25. The first week, about ten missed school. Week two, I got sick and missed. When I returned the class size was about a dozen, and my recollection is that most were recouped like me, but there were two or three who never got sick. Recollection obviously affected by the degradation of my memory over that time.

That was back when countries cared about America, before the Borkian "nothing but shareholder returns matter" philosophy spread through our leadership. America has paid the price for failing to understand that efficient allocation of capital and strategic strength are not the same things.

Lol in 1957 the general consensus was that the whole vaccine was just a boondoggle cooked up to goose drug company profits. In other words if you were old enough to remember 1957 (I’m assuming you were alive but not cognizant) you’d have been one of those people grumbling about drug companies.

A friend noted: " D. A. Henderson, who led the effort to eradicate the world of smallpox, once said, “Nobody thanks me that they haven’t died of smallpox.”

Once this is over,
Some will claim it was an overreaction
Because
It was successful.

When fumbling Covid-19 might sink the Trump presidency, media tells us the virus will kill millions. If Covid-19 is contained and Trump takes credit, media will tell us the pandemic was never anything to worry about anyway. When Gavin Newsome runs for the presidency in 2024, media will remind us how he was single-handedly responsible for saving the country with his brave shelter-in-place order.

When covid is contained but the economy is in recession, Trump will say all the restriction measures were unnecessary and a result of the media out to get him.

Nah, Trump will blame all those people who got sick. Using much the same tone as when sending his wishes for Sen. Paul to get better.

Yep and it’s gonna work too. Market isn’t my fault it’s China’s fault is going to let him coast to a 40 state victory and spend the next four years making Beijing squirm. Good news is you are probably old AF so just run out and get the China virus and end it.

yup! When this is over, MR commentators will say “ what’s the big deal” and the rest of us will say “we just avoided disaster”.

Like your friend in high school who said “uh... you’re the least drunk person... you should drive”. And you said no. Enough said...

Wow- no I never heard of him before. Thanks!

Okay, so Mnuchin wants $4 trillion to handle certain financial and economic outcomes of shutting down the economy to fight a virus that primarily afflicts the elderly with co-morbidities. $4 trillion for business.

We are talking $4 trillion, and I sense we are in the first inning of economic costs of the shut-down policy.

For those of you schooled in monetary policy and macroeconomics: So what means $4 trillion in additional government outlays, I assume financed by a combination of borrowing and money-printing (within a one- or two-year period)?

How about $8 trillion?

$12 trillion? (I think this number is possible).

So…who is in denial?

The libertarians have become statist-martinets, and printing money no longer inevitably leads to the Weimar Republic....you know, making predictions is hard, especially about the future.

Who would have predicted this?

Ok. A counterfactual. Assume that there is a tiny death rate but a hige hospitalization rate. What happens then?

(For those of you not following the news, this is true of New York)

There is a time lag between hospitalization and death. Less clear is the amount of people being kept alive ion ventilators who will never breath normally, as noted by this article from March 21 concerning New Orleans.

“It’s called acute respiratory distress syndrome, ARDS. That means the lungs are filled with fluid. And it’s notable for the way the X-ray looks: The entire lung is basically whited out from fluid. Patients with ARDS are extremely difficult to oxygenate. It has a really high mortality rate, about 40%. The way to manage it is to put a patient on a ventilator. The additional pressure helps the oxygen go into the bloodstream.

“Normally, ARDS is something that happens over time as the lungs get more and more inflamed. But with this virus, it seems like it happens overnight. When you’re healthy, your lung is made up of little balloons. Like a tree is made out of a bunch of little leaves, the lung is made of little air sacs that are called the alveoli. When you breathe in, all of those little air sacs inflate, and they have capillaries in the walls, little blood vessels. The oxygen gets from the air in the lung into the blood so it can be carried around the body.

“Typically with ARDS, the lungs become inflamed. It’s like inflammation anywhere: If you have a burn on your arm, the skin around it turns red from additional blood flow. The body is sending it additional nutrients to heal. The problem is, when that happens in your lungs, fluid and extra blood starts going to the lungs. Viruses can injure cells in the walls of the alveoli, so the fluid leaks into the alveoli. A telltale sign of ARDS in an X-ray is what’s called ‘ground glass opacity,’ like an old-fashioned ground glass privacy window in a shower. And lungs look that way because fluid is white on an X-ray, so the lung looks like white ground glass, or sometimes pure white, because the lung is filled with so much fluid, displacing where the air would normally be.”

“With our coronavirus patients, once they’re on ventilators, most need about the highest settings that we can do. About 90% oxygen, and 16 of PEEP, positive end-expiratory pressure, which keeps the lung inflated. This is nearly as high as I’ve ever seen. The level we’re at means we are running out of options.

“In my experience, this severity of ARDS is usually more typical of someone who has a near drowning experience — they have a bunch of dirty water in their lungs — or people who inhale caustic gas. Especially for it to have such an acute onset like that. I’ve never seen a microorganism or an infectious process cause such acute damage to the lungs so rapidly. That was what really shocked me.”
...
"But we are trying to wean down the settings on the ventilator as much as possible, because you don’t want someone to be on the ventilator longer than they need to be. Your risk of mortality increases every day that you spend on a ventilator. The high pressures from high vent settings is pushing air into the lung and can overinflate those little balloons. They can pop. It can destroy the alveoli. Even if you survive ARDS, although some damage can heal, it can also do long-lasting damage to the lungs. They can get filled up with scar tissue. ARDS can lead to cognitive decline. Some people’s muscles waste away, and it takes them a long time to recover once they come off the ventilator. www.propublica.org/article/a-medical-worker-describes--terrifying-lung-failure-from-covid19-even-in-his-young-patients

It depends on what the expenditures go toward. Anything expended on activities with NPV's >0 have no cost at all. Loans to FOD (friends of Donald) that eventually go bust anyway do not fall into the NPV>0 category

Nah, he's a White Man, and Taylor Swift has already made it clear we have too many of those.

Notwithstanding his obvious merits, he had an advantage in comparison with these days: in 1957, when the Jet age was just starting but mass tourism was still decades away (especially to Asia), this sort of illnesses traveled more slowly between the continents

https://www.theguardian.com/world/2020/mar/18/japanese-flu-drug-clearly-effective-in-treating-coronavirus-says-china

Medical authorities in China have said a drug used in Japan to treat new strains of influenza appeared to be effective in coronavirus patients, Japanese media said on Wednesday.

Zhang Xinmin, an official at China’s science and technology ministry, said favipiravir, developed by a subsidiary of Fujifilm, had produced encouraging outcomes in clinical trials in Wuhan and Shenzhen involving 340 patients.

“It has a high degree of safety and is clearly effective in treatment,” Zhang told reporters on Tuesday.

Patients who were given the medicine in Shenzhen turned negative for the virus after a median of four days after becoming positive, compared with a median of 11 days for those who were not treated with the drug, public broadcaster NHK said.
----
Great news, the carriers can be cleaned in a few days instead of weeks.

WHO is launching a megatrial with 4 promising drugs but favipiravir,is not on the list
1- Remdesivir : developed for Ebola. didn't work for it shuts down RNA polymerase.
2-Chloroquine and hydroxychloroquine: anti malarial drugs, Highly touted by this French Professor: Raoult, an infection disease specialist but needs more verification. Now used pre-emptively by some health workers, cheap and side effects are well known
3- Ritonavir/lopinavir a drug combinmation used as a protease inhibitor for HIV, showed some effectiveness against MERS
4-Ritonavir/lopinavir + interferon beta same drugs with an added inflammation regulator

This is now:

"WE CANNOT LET THE CURE BE WORSE THAN THE PROBLEM ITSELF. AT THE END OF THE 15 DAY PERIOD, WE WILL MAKE A DECISION AS TO WHICH WAY WE WANT TO GO!"

A clear and calming message from our president.

Enjoy Monday morning's opening in the markets.

I say give that man a prize!

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