Category Archives: Social issues ( be civil ! )

Finally, an article in the press that’s not a hit piece on Cassava

Cassava Biosciences has had the worst press imaginable with hit pieces in the Wall Street Journal, Science magazine, the New Yorker and the New York Times.  Finally Nature News has a balanced article showing how the shorts have been attacking the company and its drug — https://www.nature.com/articles/d41586-023-00050-z.

I’d written about this before and that post can be found after the ***

The Nature article discusses concerns by Elizabeth McNally editor of the Journal of Clinical Investigation, that journals are being manipulated by short sellers claiming that an article is fraudulent.

“Typically, when a whistle-blower contacts a journal about concerns over manipulated images or otherwise questionable data, the allegations are taken on good faith, McNally told Nature. The idea that whistle-blowers could be doing this for their own financial gain “was very eye-opening to me”, she says.”

One particular criticism of Cassava found in the Nature article is rather amusing. “Amid the allegations about Cassava’s data, researchers have expressed concern over how Simufilam works. Aside from the preliminary studies by Cassava and its collaborators, the strategy of stablilizing filamin-A to tackle Alzheimer’s hasn’t been on anyone’s radar, says George Perry, an Alzheimer’s researcher at the University of Texas at San Antonio. “The fact that it hasn’t been widely studied means that it hasn’t been confirmed.”

The fact that filamin-A hasn’t been on anyone’s radar is actually in its favor, since aBeta, the great white whale of Alzheimer’s research has been impaled with multiple expensive harpoons, with minimal benefit to patients.

The Nature article notes that some of the FDA petitioners wanted the Simulfilam studies stopped, something any drug company with a competing product for Alzheimer’s might wish, but should never ask for.

****

The copy of this post was changed to respond to the valid criticisms of Dr. Elizabeth Bik.

 

Cassava shorts should be worried

Yesterday, 1 November ’22, a blockbuster  article was published in the Journal of Clinical Investigation (JCI) written by its editor Elizabeth McNally — https://www.jci.org/articles/view/166176.

It is just over a year ago since the first of the articles attacking Cassava Sciences appeared.  The first was in the New Yorker which profiled Jordan Thomas as the second coming of Christ for exposing supposed fraudulent data published by Cassava principals —

Radden Keefe P. The Bounty Hunter. The New Yorker. Updated January 17, 2022. Accessed October 11, 2022. https://www.newyorker.com/magazine/2022/01/24/jordan-thomas-army-of-whistle-blowers.

There were similar articles in Science — 2022;377(6604):358–363

and the New York Times https://www.nytimes.com/2022/04/18/health/alzheimers-cassava-simufilam.html.

They relied on the same assertions given to the FDA asking that the clinical trials be stopped because of ‘danger’ to the patients.

It’s worth reading McNally’s article completely.  It isn’t very long.

A few highlights (“the Journal” refers to the JCI)

“Throughout 2022, the Journal has been repeatedly contacted to comment on the 2012 JCI paper. Although we cannot be certain, there now appear to be new “short and distorters.” A recent round of emails was sent simultaneously to multiple journals and editors, identifying 25 articles with potential problems and providing recommendations on how the journals should respond. Importantly, these accusatory emails do not identify any financial conflicts of interest on the part of the whistleblowers. The emails insist that an investigation begin within 24 hours and request that the journals update them on investigative progress. As an editor, I am expressing concern because this represents a new means of manipulating the scientific publishing industry.”

So journal editors are like docs. They talk to each other to find out what’s really going on.  It is likely that McNally called up other journal editors to find out if her experience was common.

Here is why those sending the eMails should not sleep well of a night.

“Last, if the Journal uncovers allegations made for the purposes of stock manipulation, with evidence of misinformation, the JCI may elect to express its concern to the US Securities and Exchange Commission or the Department of Justice.”

It’s about time.

Whether the ‘whistle-blowers’ are guilty of anything will be determined by the suits (from investors losing money on Cassava, or perhaps Cassava itself) which are almost sure to follow.

As some of you know, I think Cassava’s data is even better than they realize. Be warned the following link is long, detailed and will require your concentration  — https://luysii.wordpress.com/2021/08/25/cassava-sciences-9-month-data-is-probably-better-than-they-realize/

New Year’s Wish

My wife and I are staying up until midnight to make sure that 2022 really comes to an end.

 

Orwell does Stanford, Stanford does Newspeak

At the end of 1984, Orwell adds a non-novelistic appendix — “The Principles of Newspeak”

” Newspeak was the official language of Oceania (what England and Europe had become).    . . ..  The purpose of Newspeak was not only to provide a medium of expression for the world-view and mental habits proper to the devotees of Ingsoc or English Socialism, but to make all other modes of thought impossible.”  …

“This was done partly by the invention of new words, but chiefly by eliminating undesirable words … ”

“It was intended that when Newspeak had been adopted once and for all and Oldspeak forgotten …  a thought diverging from the principles of Ingsoc — should be literally unthinkable, at least so far as thought is dependent on words.”

Which brings us to 20 December ’22 and an editorial in the Wall Street Journal titled “The Stanford Guide to Acceptable Words” — unfortunately behind a paywall.   Stanford administrators apparently published an index of forbidden words to be eliminated from the school’s websites and computer codes, with inclusive replacements.   Somehow it came to light this month, and Stanford has hidden it because of the hilarity it induced, so we can’t enjoy it.

Fortunately, the WSJ editorial does provide a few examples

American is to be replaced by U. S. Citizen

Immigrant is to be replaced with person who has immigrated

Master (as in mastering a subject) is out because of its slavery connocations

Not to beat a dead horse is gone because it “normalizes violence against animals”

The list was prefaced with a trigger warning (a phrase no  longer to be used) “This website contains language that is offensive or harmnful. Please engage with this website at your own pace.

The editorial concludes by noting that ‘stupid’ is on the list.

How prescient Orwell was

The previous post in the series shows how his idea of doublethink encapsulates what chemists must do to use quantum mechanics to understand atoms.  — https://luysii.wordpress.com/2022/12/27/orwell-does-quantum-mechanics/

The one before that anticipates the 180 degree reversal of COVID advice in China — https://luysii.wordpress.com/2022/12/26/orwell-does-china/

 

Orwell does quantum mechanics

I can find no evidence that George Orwell knew or cared about quantum mechanics when he wrote 1984 in 1948.

He invented the term doublethink to describe the thought control of the totalitarian society in the novel.

“Doublethink means the power of holding two contradictory beliefs in one’s mind simultaneously, and accepting both of them.”

For chemists to think about the quantum mechanics of the atom, doublethink is necessary as this old post will show.

Here are a few examples from the Novel

War is Peace

Love is Hate

Ignorance is Strength

Freedom is Slavery

Here are a few doublethinks from Quantum Mechanics as applied to the atoms loved by chemists everywhere

Atomic orbitals in atoms have angular momentum as do curved trajectories. Trajectories don’t exist in atoms (or anywhere in the quantum world)

Relativistic corrections must be made for rapidly moving electrons in heavy elements close to the nucleus.  They may move but they don’t have trajectories.

The two s atomic orbital has a node where electrons are never found.

Electrons are found on both sides of the node.  How do they get there?

A moving charge creates a magnetic field, and a magnetic field affects a moving charge, so placing a moving charge in a magnetic field should alter its energy. This accounts for the Zeeman effect (the splitting of spectral lines in a magnetic field). Trajectories help you understand this (even if they can’t really exist in the confines of the atom).

Here is an old post on the subject.

Be warned, it’s technical

Doublethink and angular momentum — why chemists must be adept at it

Chemists really should know lots and lots about angular momentum which is intimately involved in 3 of the 4 quantum numbers needed to describe atomic electronic structure. Despite this, I never really understood what was going until taking the QM course, and digging into chapters 10 and 11 of Giancoli’s physics book (pp. 248 -310 4th Edition).

Quick, what is the angular momemtum of a single particle (say a planet) moving around a central object (say the sun)? Well, its magnitude is the current speed of the particle times its mass, but what is its direction? There must be a direction since angular momentum is a vector. The (unintuitive to me) answer is that the angular momemtum vector points upward (resp. downward) from the plane of motion of the planet around the center of mass of the sun planet system, if the planet is moving counterclockwise (resp. clockwise) according to the right hand rule. On the other hand, the momentum of a particle moving in a straight line is just its mass times its velocity vector (e.g. in the same direction).

Why the difference? This unintuitive answer makes sense if, instead of a single point mass, you consider the rotation of a solid (e.g. rigid) object around an axis. All the velocity vectors of the object at a given time either point in different directions, or if they point in the same direction have different magnitudes. Since the object is solid, points farther away from the axis are moving faster. The only sensible thing to do is point the angular momentum vector along the axis of rotation (it’s the only thing which has a constant direction).

Mathematically, this is fairly simple to do (but only in 3 dimensions). The vector from the axis of rotation to the planet (call it r), and the vector of instantaneous linear velocity of the planet (call it v) do not point in the same direction, so they define a plane (if they do point in the same direction the planet is either hurtling into the sun or speeding directly away, hence not rotating). In 3 dimensions, there is a unique direction at 90 degrees to the plane. The vector cross product of r and v gives a vector pointing in this direction (to get a unique vector, you must use the right or the left hand rule). Nicely, the larger r and v, the larger the angular momentum vector (which makes sense). In more than 3 dimensions there isn’t a unique direction away from a plane, which is why the cross product doesn’t work there (although there are mathematical analogies to it).

This also explains why I never understood momentum (angular or otherwise) till now. It’s very easy to conflate linear momentum with force and I did. Get hit by a speeding bullet and you feel a force in the same direction as the bullet — actually the force you feel is what you’ve done to the bullet to change its momentum (force is basically defined as anything that changes momentum).

So the angular momentum of an object is never in the direction of its instantaneous linear velocity. But why should chemists care about angular momentum? Solid state physicists, particle physicists etc. etc. get along just fine without it pretty much, although quantum mechanics is just as crucial for them. The answer is simply because the electrons in a stable atom hang around the nucleus and do not wander off to infinity. This means that their trajectories must continually bend around the nucleus, giving each trajectory an angular momentum.

Did I say trajectory? This is where the doublethink comes in. Trajectory is a notion of the classical world we experience. Consider any atomic orbital containing a node (e.g. everything but a 1 s orbital). Zeno would have had a field day with them. Nodes are surfaces in space where the electron is never to be found. They separate the various lobes of the orbital from each other. How does the electron get from one lobe to the other by a trajectory? We do know that the electron is in all the lobes because a series of measurements will find the electron in each lobe of the orbital (but only in one lobe per measurement). The electron can’t make the trip, because there is no trip possible. Goodbye to the classical notion of trajectory, and with it the classical notion of angular momentum.

But the classical notions of trajectory and angular momentum still help you think about what’s going on (assuming anything IS in fact going on down there between measurements). We know quite a lot about angular momentum in atoms. Why? Because the angular momentum operators of QM commute with the Hamiltonian operator of QM, meaning that they have a common set of eigenfunctions, hence a common set of eigenvalues (e.g. energies). We can measure these energies (really the differences between them — that’s what a spectrum really is) and quantum mechanics predicts this better than anything else.

Tomorrow:  Orwell does Stanford

Yesterday: Orwell does China  — https://luysii.wordpress.com/2022/12/26/orwell-does-china/

Orwell does China

1984 continues to remain incredibly prescient.  Orwell’s 1984 world was divided into 3 large states Oceania (originating from England and the USA), Eurasia (originating from the Soviet union) and Eastasia (originating from China and Japan).  Currently Oceania where the protagonist Winston Smith lives is at war with Eurasia and we’re in the middle of Hate Week.

“After the processions, the speeches, the shouting the singing, the bannersm, the posters … the tramp of marching feet, the grinding of the caterpillars of tanks .. after 6 days of this it was announced that Oceania was not at war with Eurasia. Oceania was at war with Eastasia.  Eurasia was an ally.”

“Winston was taking part in a demonstration in one of the London squares at the moment when it happened….  On a scarlet draped platform an orator of the Inner Party, a small lean man … was haranguing the crowd.  At every few moments the fury of the crowd boiled over and the voice of the epaker was drowned by a wild beastlike roraring that rose uncontrollably from thousands of throats. …

“The speech had been proceeding for perhaps twenty minutes when a   messenger hurried onto the platform and a slip of paper was slipped into the speaker’s hand.  He unrolled and read it without pausing in his speech.  Nothing altered in his voice or manner, or in the content of what he was saying, but suddenly the names were different.,  Without words said, a wave of understanding rippled through the crowd.  Oceania was at war with Eastasia.”

Winston immediately goes back to the Ministry of Truth.

“Oceania was at war with Eastasia: Oceania had always been at war with Eastasia.  A large part of the political literature of five years was no completely obsolete.  Reports and records of all kinds, newspapers, books, pamphlets, films, sound tracks, photographs–all had to be rectified at lightning speed.”

Addendum 27 December 22 – from a family member whose veracity is unquestionable

“In  July of 1971 Chairman Mao and Chou en Lai called for a gathering in Tiananmen Square for a major announcement. The Argentine ambassador, a friend of my father, attended the pronouncement in The Great Hall of the People. In the Fall of 72, my Dad and I were in Beijing (then still called Peking) and we had dinner with the ambassador. He told us about his experience that evening.

 The square was packed with several hundred thousand people who greeted the diplomats as they passed through the square on the way to the Great Hall with fevered shouts and banners calling for death to the Americans, their running dogs, and all capitalists imperialist.
In the Hall Mao announced that Nixon was coming to China.
When the diplomats left, the crowd in the square had new banners and were shouting welcome President Nixon and the Americans.
He said it was the most terrifying demonstration of power he had ever witnessed. “

Well, Orwell wrote the above in  “1984”, but he could have written the following about the Party’s volte face re Zero Covid

 

I called the current state in China in March of this year

https://www.cnn.com/2022/12/14/china/beijing-zero-covid-easing-streets-impact-intl-hnk-mic/index.html?utm_term=16710088517904a0e1f78c2ad&utm_source=cnn_Meanwhile+in+China+-+12.14.2022&utm_medium=email&bt_ee=UJOa6AAdoMdpv8zVd3R8kqP0vvKzTdQEV38THfAQNCVnL8dBJWuzcCiELZKliS9c&bt_ts=1671008851894 of

Back on March 15  2022,  I wrote a post about what was likely to happen in China.  It included older posts along the same line.   The basic argument was that the Chinese populace is a bunch of immunologic virgins to the pandemic virus due to several factors (1) the zero covid policy (2) the low rate of vaccination in the most susceptible –e.g. the elderly (3) the ineffectiveness of the vaccines they’ve been given.   Fortunately the newer variants don’t appear as malignant as the original SARS-CoV-2

Here’s the old post

China will be near collapse due to COVID19 — here’s why

Here is why I think China will be near collapse due to COVID19 in the next few months.

Due to a strict containment policy, the only experience the Chinese population (excepting Wuhan) has had with the pandemic virus has been by vaccination, mostly with Sinopharm and Coronavac.  These are known to be less effective against the Omicron variant than the western mRNA vaccines (Pfizer, etc.) which themselves are not terribly effective against infection.  So most Chinese are immunologic virgins for exposure to the variants of the pandemic virus and the omicron variant of the virus is incredibly infectious.

In contrast, western populations have been exposed to variant after variant of the pandemic virus, building up immunity to coronaviruses.  The vast majority of cases are mild not requiring hospitalization, and many are completely asymptomatic.

One small piece of evidence for this — there are many more —

The following is from a post July/2020.

https://www.nytimes.com/2020/07/09/nyregion/nyc-coronavirus-antibodies.html–https://www.cnbc.com/2020/04/23/new-york-antibody-study-estimates-13point9percent-of-residents-have-had-the-coronavirus-cuomo-says.html.

New York State  randomly tested 3,000 people at grocery stores and shopping locations across 19 counties in 40 localities to see if they had the antibodies to fight the coronavirus, indicating they have had the virus and recovered from it. With more than 19.4 million people residents, according to U.S. Census data, the preliminary results imply that at least 2.7 million New Yorkers have been infected with Covid-19.They weren’t all hospitalized.

If you’re into authoritative statements, here is Dr. Fauci 3 months ago –Source — https://nypost.com/2021/12/12/omicron-appears-to-evade-some-protection-from-covid-vaccines/

“We’re getting anecdotal information … not necessarily confirmed yet, that the level of severity appears to be maybe a bit less than in the Delta. But there are a lot of confounding issues that it may be due to the underlying protection in the community due to prior infections,”

Omicron spreads like wildfire.  For example, we had to call our plumber a week ago.  He has trained his teenage daughter to enter the trade.  We talked about the pandemic.  Teenagers love crowded parties (well I did, and so did our kids). His daughter  told us that apparently one irresponsible kid came to a party while sick in the early stages of what turned out to COVID19 and transmitted the virus to NINETEEN people.

Here is the Hong Kong experience.  It began with an aircrew member from Cathay Pacific Airways Ltd., who was subsequently found to be infected with omicron.  He ate lunch at a restaurant 27 December ’21 with his family. . Five other customers later tested positive.   By the first week in March there were over 50,000 new cases each day.  Fortunately Hong Kong appears to have passed the peak with ‘only’ 20 – 30 thousand new cases each day.

The South China Morning Post of 16 March notes that 90% of Hong Kong residents have received one dose of a vaccine.  This hardly speaks well for the efficacy of whatever they received.

The Hong Kong experience has been rationalized by several reasons perhaps peculiar to Hong Kong:

l. A very low vaccination rate among the most vulnerable (e.g. over 80)

2. Very high population density — 50% of the population in Hong Kong live in public housing which is mostly very tall, very skinny high rises, due to the lack of buildable land in Hong Kong.  The elevators are a perfect way to transmit the virus.

I can’t speak to how common this is elsewhere in China.

5 days ago the number of cases in China was 1,000.  Today (16 March) I read that there were 5,100 on 15 March — https://www.scmp.com/news/china/science/article/3170631/china-reports-another-3000-covid-19-cases-latest-surge-continues?module=lead_hero_story&pgtype=homepage

So the elevator pitch is — a highly infectious virus is loose in a huge, previously uninfected population with minimal vaccine protection.

I was very worried that something like this could happen all over China in posts  written 2 and 3months ago, long before the number of cases in Hong Kong took off.  You can find my reasoning in the following post — https://luysii.wordpress.com/2022/01/15/i-hope-to-hell-i-was-wrong-about-china/   It was published 15 January ’22, and can be found below and it contains the 12 December ’21 post:

Addendum 16 Marchhttps://www.shine.cn/news/nation/2203163160/–Mainland China now has 1,860 locally transmitted cases — with most in the province next to North, but in 20 other locations all over China including Shanghai and Beijing. This is is not good news given how infectious Omicron is.

 

I hope to Hell I was wrong about China

From the South China Morning Post — 9:52pm, 15 Jan, 2022

“The Chinese capital reported its first community case of the Omicron coronavirus variant on Saturday, with local and imported infections of the strain now detected in about half of the country’s provinces and municipalities.”

https://www.scmp.com/news/china/politics/article/3163525/china-braces-omicron-variant-extends-its-reach-and-lunar-new-

If true, containment, quarantine, lockdowns and isolation are hopeless.  The quote implies that they’ve already failed.

I find this very worrisome for reasons listed in a post 12 December 2021, a copy of which is below.

The short answer is that the mainland Chinese are immunologic virgins to exposure to the variants of the pandemic virus.  Hopefully their vaccines will work better against omicron than those of the west, but there is no reason to think they will.

Is China following a Smokey the Bear policy on the pandemic?

China is following a prevent pandemic virus infection policy, just as Smokey the Bear followed a prevent forrest fires policy.  The latter didn’t work out well, as although fires were prevented for a while. However, when fires did occur, they were much much worse than the smaller ones Smokey prevented.  There was much more tinder and stuff to burn.

Actually Smokey has changed his tune slightly.

https://en.wikipedia.org/wiki/Smokey_Bear  SmokeyBear.com’s current site has a section on “Benefits of Fire” that includes this information: “Fire managers can reintroduce fire into fire-dependent ecosystems with prescribed fire. Under specific, controlled conditions, the beneficial effects of natural fire can be recreated, fuel buildup can be reduced, and we can prevent the catastrophic losses of uncontrolled, unwanted wildfire.”

Revision 14 December 2021 — China’s policy of prevention has resulted in a Chinese population which has been vaccinated using two killed virus vaccines (Sinopharm, Coronavac).  They have not had any natural infections with the virus (aside from the original cases) as far as we know given what China has allowed out.

Infection with the virus itself exposes you to all its proteins, with your immune system responding to all of them.   Western vaccines are just to the spike protein.

It tends to be forgotten that moist cases of pandemic viral infection are asymptomatic.

Given 800K deaths  from COVID19  in the USA, how can I possibly say this is good. Here’s how :>

If you had an infection with the virus, you develop antibodies.  Nowadays, everyone who is vaccinated has antibodies so there is no point in testing for them, but what were things like in the days before vaccines?

The following is from a post July/2020.

https://www.nytimes.com/2020/07/09/nyregion/nyc-coronavirus-antibodies.html–https://www.cnbc.com/2020/04/23/new-york-antibody-study-estimates-13point9percent-of-residents-have-had-the-coronavirus-cuomo-says.html.

New York State  randomly tested 3,000 people at grocery stores and shopping locations across 19 counties in 40 localities to see if they had the antibodies to fight the coronavirus, indicating they have had the virus and recovered from it. With more than 19.4 million people residents, according to U.S. Census data, the preliminary results imply that at least 2.7 million New Yorkers have been infected with Covid-19.They weren’t all hospitalized.

Here’s some work the same month from Queens — https://www.nytimes.com/2020/07/09/nyregion/nyc-coronavirus-antibodies.html

At a clinic in Corona, a working-class neighborhood in Queens, more than 68 percent of people tested positive for antibodies to the new coronavirus. At another clinic in Jackson Heights, Queens, that number was 56 percent. But at a clinic in Cobble Hill, a mostly white and wealthy neighborhood in Brooklyn, only 13 percent of people tested positive for antibodies.

So the disease has already to spread to half the population in some neighborhoods in Queens. If even 10% of them were sick that would have been 140,000 hospitalizations.  They didn’t happen.

OK, so a lot more people were infected than got sick.  Why is this good?

Enter the omicron variant of the pandemic virus.  It can evade the antibodies produced by all the current vaccines (in the West — protection against the Chinese killed viral vaccines CoronaVac and Sinopharm isn’t known yet).   Yet omicron doesn’t appear to produce severe disease. Thus far…

 

The CDC in the past week said of the 40+ omicron cases it knows about (there certainly are more out there, and more to come), there was one hospitalization (for two days) and no deaths.

Here is Dr. Fauci 12 December 2021 — “We’re getting anecdotal information … not necessarily confirmed yet, that the level of severity appears to be maybe a bit less than in the Delta. But there are a lot of confounding issues that it may be due to the underlying protection in the community due to prior infections,”

Source — https://nypost.com/2021/12/12/omicron-appears-to-evade-some-protection-from-covid-vaccines/

So the Chinese population may be sitting ducks for omicron having been given vaccines (Sinopharm, Coronavac) of unknown potency against omicron.  If their statistics are true there has been little or no natural infection with the pandemic virus in the Chinese population (which Fauci has just implicated is protective),.  Given that I have a son, daughter in law and two grandkids living in Hong Kong, I find this extremely disconcerting.

A few Thanksgiving thankyou’s

The following was published 5 years ago, but with time and ever more research our organization seems even more miraculous (see last paragraph).  It’s amazing that it lasts as long as it does, and for that we should be thankful.   Call this prayer if you wish.

As CEO of a very large organization, it’s time to thank those unsung divisions that make it all possible.  Fellow CEOs should take note and act appropriately regardless of the year it’s been for them.

First: thanks to the guys in shipping and receiving.  Kinesin moves the stuff out and Dynein brings it back home.  Think of how far they have to go.  The head office sits in area 4 of the cerebral cortex and K & D have to travel about 3 feet down to the motorneurons in the first sacral segment of the spinal cord controlling the gastrocnemius and soleus, so the boss can press the pedal on his piano when he wants. Like all good truckers, they travel on the highway.  But instead of rolling they jump.  The highway is pretty lumpy being made of 13 rows of tubulin dimers.

Now chemists are very detail oriented and think in terms of Angstroms (10^-10 meters) about the size of a hydrogen atom. As CEO and typical of cell biologists, I have to think in terms of the big picture, so I think in terms of nanoMeters (10^-9 meters).  Each tubulin dimer is 80 nanoMeters long, and K & D essentially jump from one to the other in 80 nanoMeter steps.  Now the boss is shrinking as he gets older, but my brothers working for players in the NBA have to go more than a meter to contract the gastrocnemius and soleus (among other muscles) to help their bosses jump.  So split the distance and call the distance they have to go one Meter.  How many jumps do Kinesin and Dynein have to make to get there? Just 10^9/80 — call it 10,000,000. The boys also have to jump from one microtubule to another, as the longest microtubule in our division is at most 100 microns (.1 milliMeter).  So even in the best of cases they have to make at least 10,000 transfers between microtubules.  It’s a miracle they get the job done at all.

To put this in perspective, consider a tractor trailer (not a truck — the part with the motor is the tractor, and the part pulled is the trailer — the distinction can be important, just like the difference between rifle and gun as anyone who’s been through basic training knows quite well).  Say the trailer is 48 feet long, and let that be comparable to the 80 nanoMeters K and D have to jump. That’s 10,000,000 jumps of 48 feet or 90,909 miles.  It’s amazing they get the job done.

Second: Thanks to probably the smallest member of the team.  The electron.  Its brain has to be tiny, yet it has mastered quantum mechanics because it knows how to tunnel through a potential barrier.   In order to produce the fuel for K and D it has to tunnel some 20 Angstroms from the di-copper center (CuA) to heme a in cytochrome C oxidase (COX).  Is the electron conscious? Who knows?  I don’t tell it what to do.   Now COX is just a part of one of our larger divisions, the power plant (the mitochondrion).

Third: The power plant.  Amazing to think that it was once (a billion years or more ago) a free living bacterium.  Somehow back in the mists of time one of our predecessors captured it.  The power plant produces gas (ATP) for the motors to work.  It’s really rather remarkable when you think of it.   Instead of carrying a tank of ATP, kinesin and dynein literally swim in the stuff, picking it up from the surroundings as they move down the microtubule.  Amazingly the entire division doesn’t burn up, but just uses the ATP when and where needed.  No spontaneous combustion.

There are some other unsung divisions to talk about (I haven’t forgotten you ladies in the steno pool, and your incredible accuracy — 1 mistake per 100,000,000 letters [ Science vol. 328 pp. 636 – 639 ’10 ]).  But that’s for next time.

To think that our organization arose by chance, working by finding a slightly better solution to problems it face boggles this CEO’s mind (but that’s the current faith — so good to see such faith in an increasingly secular world).

Call the thankfulness of the CEO prayer if you wish.

Addendum 29 November ’22 — from a friend “We also have to thank all the tau molecules that stabilize the microtubules— until the misbehavior of ERK and JNK1 overdecorate them with holiday lighting (phosphates) and they fall apart. So after Thanksgiving, be careful not to overcommercialize the holiday season.”

The cryoEM work of the last 5 years has shown us the structure of large molecular machines made of multiple proteins, DNAs and RNAs which are even more impressive (to me) than single protein structure.   One example [ Nature vol. 609 pp. 630 – 639 ’22 ] shows the Holliday junction which allows strand migration between the strands of two DNA duplexes.   Pictured is the complex from bacteria which is confined in a rectangle with sides 220 and 120 Angstroms (not sure how thick it is).  The complex contains a molecular motor which slides the junction.  You could spend your life just studying this one structure.  It’s hard for me to see how it arose.

Why affirmative action was necessary

It is likely that the  Supreme Court will strike down Affirmative Action.  Since I’m far older than most of the readership, I’m republishing part of an old post which describes just how necessary affirmative action was.  That’s not to say it is necessary now (about which more in a future post).

Fall 1956:  Enter Princeton along with 725+ others.  The cast of characters included about 5 Asians, 1 Indian Asian, no hispanics and/or latinos as I recall, and all of 2 blacks.  I was the first to attend from a small (212 kids in 4 grades) NJ High School. I’d never been west of Philly, and immediately appreciated what passed for diversity back then — a roommate from Florida, and 2 guys next door from Wisconsin and Tennessee, the four of us packed like sardines into two miniscule rooms (each of which is now a single).

Although my High School was above the Mason Dixon line, there was only 1 black student in all 4 classes when I was there.  A 2nd cousin who graduated 6 years before I entered, noted that there were NO blacks when she was there and asked why, and was told “we don’t encourage them to attend”.   To be fair, there were very few black families in the area.

So, because we were musicians, and in the marching band, I got to know one of the blacks.  At away games there were postgame parties  (what’s the point of having games after all?).  Girls would come up to Harvey and tell him that he must meet Virginia, she’s wonderful. etc. etc.  Virginia being the black girl at their school, as Harvey was the black boy at ours.  There was no condescension involved, and I never saw anyone at Princeton give Harvey a hard time, and we had plenty of southerners.  It was the way things were, and we had no idea that things could be different.

Sad addendum 19 November:  A classmate responded to the above paragraph — “We did have two Black students in our class, who were openly harassed on the campus; one  left early. The second was in Bicker and was offered a bid to Elm club, which according to reports led to the Elm club president punching out one of the Bicker committee members.

Spring 1958: Back at the H. S.  The one black girl in the class 2 years behind me was very smart.  She graduated as the Salutatorian.  However, she should have been the Valedictorian, the powers that be having decided that it wouldn’t do to have a black in that position.  That didn’t stop her of course. The high school was so small that it was folded into a regional H. S. the next year.  So our little high school has reunions every 5 years or so for anyone who ever went there, and I saw her 40 – 50 years later.  She’d become a very high powered R. N. with a very responsible position.

Fall 1960: Harvard Chemistry department.  Not a black, not a latino, not an Asian to be found in the grad school (there was one Sikh).  I don’t recall seeing any as undergraduates.  There were a fair number of Japanese, and Asian Indian postdocs however.  Fast forward to the present for what it looks like now — https://luysii.wordpress.com/2012/04/19/the-harvard-chemistry-department-reunion-part-i/.

Fall 1962: Entering Penn Med school — 125 students, one black (a Nigerian) no latinos/hispanics, no asians of any sort, under 10 women.  They really can’t be blamed for this, the pipeline was empty.

Summer 1963: Visiting my wife to be at her home in Alexandria Virginia.  A drive perhaps 10 – 20 miles south toward Richmond finds restaurants with Colored entrances.

2008:  My wife has a cardiac problem, and the cardiologists want her to be on coumadin forever, to prevent stroke.  As a neurologist having seen the disasters that coumadin and heparin could cause when given for the flimsiest of indications (TIAs etc. etc.), I was extremely resistant to the idea, and started reading the literature references the cardiologist gave me, along with where the references led.   The definitive study on her condition had been done by a black cardiologist from Kentucky.  We had a long and very helpful talk about what to do.

Diversity is not an end in itself, although some would like it to be.  I’ve certainly benefitted from knowing people from all over.  That’s not the point.  Like it or not, intelligence is hereditary to some extent (people argue about just how much, but few think that intelligence is entirely environmental).  The parents (and grandparents) of today’s blacks , are likely just intelligent as their MD, Attorney, teacher etc. etc. offspring today.  This country certainly pissed away an awful lot of brains of these generations.   So clearly, I’m all for letting the best into our elite institutions whatever they look like.

Cassava shorts should be worried

Yesterday, 1 November ’22, a blockbuster  article was published in the Journal of Clinical Investigation (JCI) written by its editor Elizabeth McNally — https://www.jci.org/articles/view/166176.

It is just over a year ago since the first of the articles attacking Cassava Sciences appeared.  The first was in the New Yorker which profiled Jordan Thomas as the second coming of Christ for exposing supposed fraudulent data published by Cassava principals —

Radden Keefe P. The Bounty Hunter. The New Yorker. Updated January 17, 2022. Accessed October 11, 2022. https://www.newyorker.com/magazine/2022/01/24/jordan-thomas-army-of-whistle-blowers.

Nowhere in the article was it mentioned that the ‘whistle-blowers’ stood to gain financially because they had shorted the stock.

 

Addendum 2 Nov— see comment by Elizabeth Bik at the end — this is incorrect.  It was mentioned that the whistleblowers had short positions in the stock.

There were similar articles in Science — 2022;377(6604):358–363

and the New York Times https://www.nytimes.com/2022/04/18/health/alzheimers-cassava-simufilam.html.

They relied on the same assertions given to the FDA asking that the clinical trials be stopped because of ‘danger’ to the patients.

In none of these articles was it mentioned that those claiming fraud by the Cassava investigators were short the stock.

Addendum 2 Nov— see comment by Elizabeth Bik at the end — this is incorrect.  It was mentioned that the whistleblowers had short positions in the stock.

It’s worth reading McNally’s article completely.  It isn’t very long.

A few highlights (“the Journal” refers to the JCI)

“Throughout 2022, the Journal has been repeatedly contacted to comment on the 2012 JCI paper. Although we cannot be certain, there now appear to be new “short and distorters.” A recent round of emails was sent simultaneously to multiple journals and editors, identifying 25 articles with potential problems and providing recommendations on how the journals should respond. Importantly, these accusatory emails do not identify any financial conflicts of interest on the part of the whistleblowers. The emails insist that an investigation begin within 24 hours and request that the journals update them on investigative progress. As an editor, I am expressing concern because this represents a new means of manipulating the scientific publishing industry.”

So journal editors are like docs. They talk to each other to find out what’s really going on.  It is likely that McNally called up other journal editors to find out if her experience was common.

Here is why those sending the eMails should not sleep well of a night.

“Last, if the Journal uncovers allegations made for the purposes of stock manipulation, with evidence of misinformation, the JCI may elect to express its concern to the US Securities and Exchange Commission or the Department of Justice.”

It’s about time.

Science, The New Yorker, and the New York Times are guilty of very sloppy reporting.

Whether the ‘whistle-blowers’ are guilty of anything will be determined by the suits (from investors losing money on Cassava, or perhaps Cassava itself) which are almost sure to follow.

As some of you know, I think Cassava’s data is even better than they realize. Be warned the following link is long, detailed and will require your concentration  —

Cassava Sciences 9 month data is probably better than they realize