Public Health, Pandemics, and the Government

 In a recent article by the former head of the NIH, in the NY Times, the author notes:

 Future historians will judge the development of safe and effective mRNA vaccines for Covid in 11 months as one of the greatest medical achievements in human history. We felt that at last we were on a path to conquering this disease and stopping the terrible death toll. And to a major extent, that came true: Current estimates by the Commonwealth Fund, a nonprofit foundation supporting research on health care, are that more than three million lives were saved in the United States between December 2020 and November 2022 by Covid vaccines. If you were vaccinated, you might be one of them. I might be also. Yet ultimately more than 50 million adult Americans declined vaccination — even after the shots were made widely available at no cost. Though medicine and public health make poor bedfellows with politics, one’s political party was a strong predictor of resistance. So was religion, with white evangelical Christians (my own group) the most resistant of all. Public distrust, driven by social media, cable news and even some politicians, reflected a host of concerns: whether Covid-19 was real, whether it was really all that serious, whether the vaccines were rushed, whether there were common and serious side effects that had been hidden, whether the mRNA would alter the recipient’s DNA, and whether companies had skirted the rules about safety. More outlandish conspiracies also circulated on social media: that the vaccines contained microchips or cells from recently aborted fetuses, for example. People of faith were particularly hard hit by misinformation.

 The author then presents his “philosophical” version of “truth”. He states:

 What do we mean by truth anyway?

 Let’s consider a set of concentric circles that represent various levels of truth. At the center is what could be called the zone of necessary truth. Items in this zone consist of statements about a concrete reality that just has to be the way that it is. Those items would have to be true in any imaginable universe, and they don’t care how we feel. In this rather narrow zone, the main entries are from mathematics and possibly from the nature of time. ….

 Unfortunately this alleged layer of truth has been buffeted by the minds of mathematicians over the centuries. Non-Euclidian geometry just a simple example. He continues:

 The next circle out, which is the home for a much wider range of reality claims, is firmly established facts. These are conclusions that are overwhelmingly supported by evidence, but discerning them has required human observation. We can safely place here most scientific conclusions about objective reality that have been supported by multiple experimental approaches and sustained over many decades…

 The author asserts DNA as such an example. However how we perceive DNA today as compared to how it was perceived in 1953 is dramatically different. Science at this level is a continual battle of ideas. It is one of “on the one hand and then on the other” For example, what is cancer? In 1964 I read Watson’s book on the Gene. Now when I read the literature it is dramatically more complex.

 As we move further out from the center, we reach claims that are potentially true, but the evidence is currently insufficient to move them into the circle of firmly established facts. We can call this the zone of uncertainty. Here’s an example: Did mask mandates provide benefit to a community in reducing Covid transmission? One careful study in Bangladesh said yes, but other large-scale studies in the West have had difficulty documenting that — with a major reason being that compliance has been so uneven. On the other hand, many studies have shown personal benefit from consistent mask-wearing in reducing risk to individuals and their close contacts.

 This statement can be an example of how “politicians” mess things up. To answer the mask issue we must first understand how the disease is transmitted. Since COVID is a single stranded RNA virus, which attached to cells via an ACE2 membrane receptor, it may be just nano particle like. No one knows. If nano then masks of the typical variety are useless. Furthermore, viruses can enter the surface of the eye, go down the gland to the nose then from there anywhere. So must we wear eye protection as well. Nano masks and nano eye protection are not readily available. Level 2 bio-hazard facilities may have them but never saw them on the E train. This issue is still not resolved and the author unfortunately seems clueless and balmes the public for even raising the question.

 Going even farther out, we get into territory where facts and evidence are frankly scanty or just irrelevant. This is the zone of subjective opinion. Some examples: Tattoos are cool. Dogs make better pets than cats. Shoes with brown leather tops and thick white soles look really good on men (on this last one, opinions at my house do not match). Disagreements about topics in this zone do not threaten the order of things. In fact, they make our society richer and more interesting because people have different tastes.

 The above are opinions, not facts. I like blue not orange. Perhaps it is the genetic makeup of my limbic system.

 When disagreements arise about what is true, it is really important to assess which zone we are working in. Looking at our concentric circles, I think we can all accept that claims in the outermost zone are subjective, so it’s fine to disagree about those. But here’s the point I really want to emphasize: As you move inward to zones where there is more and more actual evidence, it becomes more and more important to track down that evidence, and not just say that everything is a matter of opinion. When you get to the solid foundation in the innermost two circles, these are matters of currently established truth that have to be true for everybody. Those facts don’t care how you feel, and they can’t be — and are not — a matter of opinion.

 Opinions are available to all. Truth may be very difficult to determine. COVID was a challenge. What was shown was that the arrogance of “experts” and politicians isolated the public in a lack of trust. In my opinion and my experience the political experts exuded gross arrogance and talked down to the public. The author is a physician and a scientist. That duplex lends itself to a certain mindset. In contrast I studied medicine and see myself fundamentally as an engineer. When using my engineering expertise to raise capital in a venture world, I could only succeed by understanding how to communicate with the investors, I had to get to their level of understanding, I had to convince them with facts, and avoided truths. For in a venture environment today’s truth may be tomorrow’s falsity. Think dotcom bust.

 For a scientist, however, especially one under the rubric of the Government, they speak ex Cathedra. The arrogance of the scientist isolated the citizens and led to islands of disbelief. This article has no self doubt, just a continuation of the attitude of “truth” is theirs and if you fail to accept it you are anathema!

The author talks of efficacy. He alleges that the mRNA vaccine has high efficacy. In reality we face moving targets. Namely the virus mutates continuously. Secondly, the mRNA vaccine does NOT prevent infection, frankly no vaccine does. It just primes the immune system through B cells antibodies, T cells and the rest of the adaptive immune response. It does not prevent transmission. It takes days to get the primed immune system to react, and during that time we have the possibility to transmit.  These are complex issues, dealing with an moderate understanding of the immune system. Political science types seem to fail to understand that 99.999% of the people are clueless! Thus when they make dicta to be obeyed, and find out that the extreme dicta are not TRUTH, they lose all confidence. Once lost never regained!

Quality

 Quality is important. The Japanese learned that exceptional well. From tin toys to high quality photographic equipment and highly reliable cars. If it is made in Japan it would be the best.

Now for Chinese goods, the same is not there. They are cheap, but as the saying goes you get what you pay for. I have been observing this over the past few years with Amazon purchases. The latest was a clock. Looked good on line but when delivered it was a disaster, and in this case an expensive one. The numbers on the face were wrong to start with, the clock face was askew, and the ability to adjust the time required medical instruments to get to the change control! 

Now the list goes on. Buy batteries from a Chinese source and you have no idea if they are knock off. I have another clock, looks great but burns through batteries every 3 weeks. 

Does the American consumer want quality or just to be able to buy more junk. I suspect quality will become a real issue. Think Yugos.

Polyspecific Antibodies

 Five years ago I wrote a Technical Note on Poly-sspecific antibodies. Simply stated these complex antibodies could bind to multiple surface markers on a cancer cell as well as attaching to an immune cell, thus facilitating an aggressive immunotherapeutic response targeted specifically to the cancer cell. 

A recent paper in Nature Cancer,  details how these PSAb have been developed and are being used in multiple myeloma. The author notes:

To create the components of the new trispecific antibody, ISB 2001, the authors selected high-affinity antibody Fab fragments (the region of an antibody that gives antigen specificity) directed against both CD38 and BCMA, two well-validated targets in the MM therapeutics landscape3,5. The two anti-tumor Fab fragments were combined into a single trispecific antibody molecule with a Fab fragment directed against the T cell activation antigen CD3. A Fab fragment with medium-low affinity for CD3 was used because this was previously shown to help improve the balance between TCE efficacy and safety6,7. The anti-CD38 Fab fragment was additionally selected to recognize an epitope distinct from that recognized by daratumumab. This was done to avoid potential dampening of the activity of ISB 2001 in patients with r/r MM who have been recently treated with a daratumumab-based regimen. In addition, Carretero-Iglesia et al.4 generated an array of monospecific and bispecific control molecules. Together, these make for exceptionally well-controlled experiments from which the reader and fellow scientists can easily draw conclusions. The CD3, CD38 and BCMA Fab fragments were combined with an antibody Fc fragment that was mutated to retain its ability to extend the antibody in vivo half-life while preventing it from  interacting with IgG Fc receptors, thereby minimizing target-binding-independent T cell activation. Here, the spatial configuration of the Fab fragments was found to be crucial for optimal activity. Placing either of the tumor-targeting Fab fragments close to the CD3 Fab (meaning on the same antibody heavy chain) resulted in greater potency than did distal positioning (on the other heavy chain). In the trispecific setting, having the BCMA tumor-binding Fab positioned between the Fc fragment and the CD3 Fab was optimal for cytotoxicity (Fig. 1). As CD38 has a broader expression profile than BMCA (CD38 is more often expressed on non-tumor cells), placing the CD38 Fab in the less-active distal position resulted in reduced on-target off-tumor T cell activation, with the promise of maximizing the therapeutic window. Avidity (the combined binding strength in antibody–antigen complexes) is fundamental to antibody functional responses8. By mixing antibodies directed against multiple epitopes on a given antigen, high-avidity immune complexes may be formed that are characterized by tightened binding and increased activity toward cells expressing the antigen. In engineered antibodies, a covalent linkage between Fab fragments directed against distinct epitopes and/or distinct antigens may be used to generate bi- or multispecific antibodies with novel functions9. These ‘obligate bi- or multispecific antibodies’ may also benefit from higher activity due to avidity binding, an effect we might therefore call ‘obligate avidity’. 

 Namely the techniques we explored half a decade ago are making an entry into a significant malignancy with some hope of establishing a total remission.

 

Happy Friday the 13th!

 Somehow this day has always had its problems. So lie low and wait till the 14th!

Excellent Discussion on Free Speech; A Threatened Right

 The Indispensible Right by Turley is an exceptionally well written and structured presentation of the position of the First Amendment right to free speech since the founding of the country. Although the Amendment states that free speech shall not be abridged, over the nearly 250 years of this country group after group, Administration after Administration have found ways and means to go around the right of free speech. The use of the less well defined assertion of sedition has been used to attack those not in power by those in power.

My view of many of these issues is somewhat nuanced and reflects personal contact with those whose free speech was encumbered by Presidents. As Turley opens with Ms Whitney, an alleged communist in the early part of the twentieth century, it was my grandmother, Hattie Kruger, who was arrested by Wilson and thrown in the Occoquan prison with six other women for protesting outside the White House with suffragists. Imprisoned for sign holding outside the White House, by direct order of Wilson, the seven women were dragged to the prison, hosed down in frigid November weather, force fed by hose, and allowed no counsel. Occoquan was the Guantanamo of Wilson’s time. Women were the Al Qaeda of his period as well. But the crime of the women was just their right to free speech.

Turley takes the reader from one act of free speech suppression to another over 250 years. From Adams, to Jefferson, to Jackson, Lincoln, yet somehow missing Wilson. On p 153 Turley seems to glorify Wilson as a defender of rage rhetoric. In my opinion and in my experience such could not be farther from the truth. Wilson made propaganda a key element of his Administration (see Bernays, Propaganda. Bernays was one of Wilson’s chief propagandists and his work made it to Madison Avenue for decades), he made it the driver for the entry into WW I. Wilson was a manipulative southerner and Turley’s reference to Wilson’s work on Constitutional Government was far from the interpretation of many. Wilson saw a Parliamentary system as a better one and he rejected many elements of the Constitution.

Overall the book is easy to read for those not fully engaged in the topic for a period of time. It is an excellent overview of how free speech has been curtailed historically.

The book begins with an attempt to address the question of what is a “right” and what is the basis for these rights. In this context there is the concept of natural rights, those rights that are assumed to have some universality. The origin of this rights is debatable, as from God, or as a fundamental part of the human psyche. The author examines many of these dimensions. Locke has been the alleged basis for property rights for example. Namely property rights result from the act of human work on unencumbered land for example. Then there is the concept that rights are a result of the human brains function. In my view it is a limbic system functionality. The classic example is a two year old and their toy. Try taking it away and the child screams “mine!”. Parents then attempt to mollify this limbic response to a right to property by saying the child should “share” and this does not always work. Natural Rights lead to Natural Law. In Ockham’s case he sees a distinction between God given Natural Rights and the rights mandated by law. Thus one can question that Freedom of Speech is either a Natural Right, a legal right, or both.

The book proceeds through various examples of Freedom of Speech and the suppression of it by Government. In this context we use one assumes the legal right of Free Speech. The most compelling violation of Free Speech in my opinion is the Bebs case. The author focuses on weaknesses of the Court and especially Holmes in deciding this case. However Deb, a Socialist, was arguing against the War, WW I. The Congress had passed an Act prohibiting any speech against the War, a clear violation of the First Amendment. The Court in the Debs case blatantly followed the Congress and denied the Constitution. Silencing a political adversary via the law and the Court had become a common practice. Debs was subsequently pardoned. This is in contrast to the Goldman case, a foreign born national and communist, not a socialist. Goldman gets set back from whence she came because the communists fundamentally argued for an overthrow of the Government, not a Free Speech issue. The Debs decision really needs more depth. It is in my opinion a key landmark in a poor Court. The details behind Debs, its context, the Socialists etc need to be placed in context. For example, the counterpoint of Ema Goldman and the communists set an alter example. Goldman was not a natural born citizen, thus there was a place to return her to. Also the communists desired to truly overthrow the Government and replace it with communism. Socialists in extreme wanted public utilities so that water and sewers worked.

Finally the author deals with the current Trump issues. Here things, in my opinion, get a bit muddy, mainly due to the timeliness of the case. Did Trump incite to riot, or was it just free speech? Will the Court be Holmesian or extend the First Amendment accordingly? Is there a clear line between Free Speech and the limits thereto?

Exceptional and Prescient

 Vertigo by Jahner is undoubtedly the best work on Weimar I have read over decades. The author addresses all elements of what led up to, and operated during, and led to the Nazi takeover. The author covers social, economic, political and intellectual areas.

 Germany was in chaos after the defeat for a variety of reasons. The author presents the Spartacists and Rosa Luxemburg with great clarity. I recall in the 60s when the local SDS chapter at MIT was called the Rosa Luxemburg chapter. For years I had no idea who she was until I spent time with a business partner and close friend, Pietr Mroczk, a Solidarity member and their voice in the US. Over drinks in Warsaw I got to understand Rosa. As the author describes her accurately, she could be a Socialist, Marxist, Communist all in one day. Her true goal appeared to be an anarchist, using the rubric of her left wing ideas as the battering ram. She and her colleagues led to the early battles between left and right and the death of many as a result, including her own.

 The author presents an excellent overview of the political leadership, its vacillations and collapses. Ending with old man Hindenburg and leading to Hitler. The author presents an excellent overview of the vacuous architects and their followers. Bauhaus et al led to blank and bland society as well.

 The author presents the life of young women drawn into the work world and the libertine life styles all too well known in Weimar.

 What is a bit missing is what we Germany before the War that allowed for this type of seismic change. Unlike the US, for example, Germany was a class society, not like the UK but more in the serf like Middle Ages. How that effected the social change is unknown in this work.

 Also missing is the explosion of academic excellence. Germany was the bastion of such things as Chemistry, especially Organic Chemistry. As any student of Organic Chemistry in the US feels, the reactions developed in Germany were done just to force others to memorized hundreds of reactions which frankly would best be left on paper. Yet Germany was also the home of Quantum mechanics as well as early constructs of nuclear theory. This part of the Weimar period would have been of interest.

 Overall this book is a sine qua non, other works delight in the hedonism of the period failing to ply together all elements that resulted in the Nazi era.

More importantly this work may give us a glimpse of what can happen to society is massive internal dissension and economic strife.

Heresy vs Disinformation

 Back in the 14th century, the then Popes, located in Avignon, assigned to the Dominicans the task of seeking out heretics, and having the local authorities dispatch them accordingly. Now just what was heresy? It was what the Pope and/or the Dominicans assigned to the process decided it to be. 

A classic case was that of the Franciscans who believed in poverty. And they further believed that Jesus had no property and was reliant upon the kindness of strangers. For the Franciscans they vowed poverty, chastity and obedience. The latter could according to Francis be excused at times if one's belief was contrary to the commands. Whereas poverty and chastity were difficult to exempt from. This caused a problem with the Pope, especially, since he lived in extreme elegance surrounded by excessive riches.

The Franciscans were considered heretics by the Dominicans in accord with the ten Pope John XXII, legal scholar, not a theologian, and one consumed by riches. 

Along comes Ockham, and argues the case for his order. Then along comes the Pope and accuses Ockham of heresy, punishable by death. Ockham escapes and hides out in Munich under the protection of the local King,

Segue to now. Disinformation is changed from heresy and the Dominicans and Popes are found in select groups reporting to political pontiffs. It was Ockham who set the ball rolling but it would take 200 years for Luther and his political allies to get it full speed.

One wonders if there will be a 21st century Ockham and a 23rd century Luther. Just a thought.

Tree Collecting

 The NY Times had an interesting article about those who collect trees. The author recounts the tales of those who collect trees. Tree collecting is unlike flower collecting. You plant a flower and year after year if lucky it blooms. Like my day lilies. However tree collecting is not cyclical like flowers. It is linear in time, trees just keep growing and from year to year they are different. I am a tree collector, yes on my 15,000 sq ft of New Jersey clay.

I started with ginkgos. I have dozens and hundreds of seedlings. My Ag Agent got a 5' one this year, she has quite a few now. I got seeds from the NY Botanical Garden back in 1990, and now have dozens. Then I got metasequoia, an assumed extinct Chinese tree rediscovered in 1947. They grow 4"+ a year. I have the largest collection on the East Coast. Of course the locals in town are clueless and I am called "the tree man". I kind of like it. Some neighbors are former city types, the cut down all the trees and planted grass. My tree however make up for the callous grass lovers and reduce run-off. I have more than 50 tree species. Such as catalpas, 30' pea plants. I have pinus rigida, from Island beach, trees which grown from Florida to the high mountains in Canada. They have no fear of any climate change. 

My taxodium, or swamp cypress enjoy the run off from those with just grass, it helps prevent flooding. Then there are cunninghamia, many pines, magnolias, maples, oaks, chamacypirus, and the list goes on. 

I realize that being in New Jersey when I sell the house the new owner will likely cut every tree down and plant grass! It must be some mental defect, on them or me, but I prefer to believe it is not me. To prevent this I have spread ginkgo nuts across the country. Despite the professionals the ginkgo does naturalize, especially with squirrels around. 

Tree growers like myself look at the long term. Each year I can see the trees expanding, growing taller, enriching their shape. 

I am not a grass lover, have little of it. But I can sit on my deck and enjoy the pallet of green from the variety of trees, then the fall change, winter clarity of branches and Spring budding.

So yes, I am a tree collector. I hope the next owner has at least a bit of the same delight. But it is New Jersey, so I fear they will not.

Classroom Etiquette

 Back in the Dark Ages, say 1960, there were no mobile phones and no laptops or pads. There were spiral bound notebooks, pens and pencils. That's it. In fact I still have notebooks from classes in college and grad school. Why? I took great notes and annotated them neatly. I used sized spiral bound note books with a Parker 51 pen and black ink. My writing was clear block letters, organized neatly by topic. Also I dated each lecture. I then annotated them for exams.

Finally schools are ridding the interference of electronic devices. As the Harvard Crimson notes: As middle and high school students descended upon Cambridge for their first day of classes on Tuesday, one thing was missing from their pockets: cell phones. Beginning this fall, cell phone use during instructional time will not be permitted for all students grades six through twelve, Cambridge interim Superintendent David Murphy said in an interview Tuesday. “We just want to make sure that our learning environments are as free of distractions as possible so that the focus can be on the teaching and learning,” Murphy said. According to Cambridge Public Schools spokesperson Sujata Wycoff, though how phones are confiscated may vary across schools, expectations remain the same: cell phones will be collected at the beginning of each period and returned at the end, but students can use their phone during lunch time, in between classes, and before or after school.

Phones and pads detract and do not add. Paper has been useful for centuries and before that even wax tablets. Phones are distractions. I see many walkers in the AM while biking on their phones texting or whatever as they purportedly are getting exercise. Who can really waste so much time.

Congrats to Cambridge.