Map of life expectancy at birth from Global Education Project.

Sunday, February 28, 2021

What is conservatism?

 As the Conservative Political Action Conference is happening, it seems a good time to ask what conservatism actually means. The dictionary definition is:

1. commitment to traditional values and ideas with opposition to change or innovation

2. the holding of political views that favor free enterprise, private ownership, and socially traditional ideas

Is that really what it means? Hardly anybody in the U.S. is opposed to private ownership in general, or to "free enterprise," whatever that means. And what ideas are considered "socially traditional" depends on your tradition.  I'll grant you that conservative politicians use rhetoric that corresponds to number 2, although getting to the world they espouse would require a great deal of change and innovation. However, the entire program at CPAC is about idolization of a serial adulterer and con artist whose socially traditional ideas consist mostly of racism. 


Philip E. Agre was a highly accomplished and prolific scholar of information theory and linguistics, who wrote the famous essay "What is Conservatism" in 2004. Shortly thereafter, for unknown reasons, he dropped out of academia and out of public life entirely. He let it be known (by way of his sister if I remember correctly) that he was well and his choice was voluntary. Whether he painted his mailbox blue I do not know. In any case, here is his definition:

Q: What is conservatism?
A: Conservatism is the domination of society by an aristocracy.

Q: What is wrong with conservatism?
A: Conservatism is incompatible with democracy, prosperity, and civilization in general. It is a destructive system of inequality and prejudice that is founded on deception and has no place in the modern world.

He uses the word aristocracy loosely. For sociologists and historians, it refers to a particular kind of ruling caste, with titles of rank, usually associated with landholdings. But he is referring generally to a ruling class of one kind or another. "From the pharaohs of ancient Egypt to the self-regarding thugs of ancient Rome to the glorified warlords of medieval and absolutist Europe, in nearly every urbanized society throughout human history, there have been people who have tried to constitute themselves as an aristocracy. These people and their allies are the conservatives."


To maintain their privilege, they need to convince people that it is right and proper. Hence the defense of "tradition." We are your overlords, that is traditional, therefore it is right. But most people, if they had the chance to think about it and act on their conclusions, might well decide it isn't right after all. So as Agre goes on to say:

Conservatism in every place and time is founded on deception. The deceptions of conservatism today are especially sophisticated, simply because culture today is sufficiently democratic that the myths of earlier times will no longer suffice.  . . . American culture still being comparatively healthy, overt arguments for aristocracy (for example, that the children of aristocrats learn by osmosis the profound arts of government and thereby acquire a wisdom that mere experts cannot match) are still relatively unusual. Instead, conservatism must proceed through complicated indirection, and the next few sections of this article will explain in some detail how this works. The issue is not that rich people are bad, or that hierarchical types of organization have no place in a democracy. Nor are the descendents of aristocrats necessarily bad people if they do not try to perpetuate conservative types of domination over society. The issue is both narrow and enormous: no aristocracy should be allowed to trick the rest of society into deferring to it.. . . Conservatism has opposed rational thought for thousands of years. What most people know nowadays as conservatism is basically a public relations campaign aimed at persuading them to lay down their capacity for rational thought.

He goes on to describe specific strategies and rhetorical tricks that we think of as being largely innovations of the Trump years, but remember he was writing in 2004 during the reign of George Bush II. I recommend you read the whole thing. I'll discuss it in more detail anon.  

Yes Woodie, 74 million voters are against Democracy. Donald Trump is a fascist.


Sunday Sermonette: A problematic passage

I don't know for sure, but I have to think that Deuteronomy 30 has been an inspiration, and perhaps cited as a justification, for Zionism. It explicitly predicts the return of the Israelites from diaspora to the promised land. 

However, in historical fact the diaspora did not happen because of apostasy, as the previous curses predicted. On the contrary, it resulted from a failed result against Roman rule in 67 CE, that culminated in the sack of Jerusalem and destruction of the temple in 70. This is remembered as a heroic collective act with a tragic outcome, the central symbol being the mass suicide at Masada, although that is likely an invention by Josephus. These events happened long after the conclusion of the Tanakh, so how they relate to scripture is a matter for interpretation. At the end is a passage that is frequently quoted out of context by some Christians. I'll comment on that.

30 “And when all these things come upon you, the blessing and the curse, which I have set before you, and you call them to mind among all the nations where the Lord your God has driven you, and return to the Lord your God, you and your children, and obey his voice in all that I command you this day, with all your heart and with all your soul; then the Lord your God will restore your fortunes, and have compassion upon you, and he will gather you again from all the peoples where the Lord your God has scattered you. If your outcasts are in the uttermost parts of heaven, from there the Lord your God will gather you, and from there he will fetch you; and the Lord your God will bring you into the land which your fathers possessed, that you may possess it; and he will make you more prosperous and numerous than your fathers. And the Lord your God will circumcise your heart and the heart of your offspring, so that you will love the Lord your God with all your heart and with all your soul, that you may live. 7

The idea of circumcising your heart is pretty weird, I must say.

And the Lord your God will put all these curses upon your foes and enemies who persecuted you. And you shall again obey the voice of the Lord, and keep all his commandments which I command you this day. The Lord your God will make you abundantly prosperous in all the work of your hand, in the fruit of your body, and in the fruit of your cattle, and in the fruit of your ground; for the Lord will again take delight in prospering you, as he took delight in your fathers, 10 if you obey the voice of the Lord your God, to keep his commandments and his statutes which are written in this book of the law, if you turn to the Lord your God with all your heart and with all your soul.

11 “For this commandment which I command you this day is not too hard for you, neither is it far off. 12 It is not in heaven, that you should say, ‘Who will go up for us to heaven, and bring it to us, that we may hear it and do it?’ 13 Neither is it beyond the sea, that you should say, ‘Who will go over the sea for us, and bring it to us, that we may hear it and do it?’ 14 But the word is very near you; it is in your mouth and in your heart, so that you can do it.

15 “See, I have set before you this day life and good, death and evil. 16 If you obey the commandments of the Lord your God[a] which I command you this day, by loving the Lord your God, by walking in his ways, and by keeping his commandments and his statutes and his ordinances, then you shall live and multiply, and the Lord your God will bless you in the land which you are entering to take possession of it. 17 But if your heart turns away, and you will not hear, but are drawn away to worship other gods and serve them, 18 I declare to you this day, that you shall perish; you shall not live long in the land which you are going over the Jordan to enter and possess. 19 I call heaven and earth to witness against you this day, that I have set before you life and death, blessing and curse; therefore choose life, that you and your descendants may live, 20 

You will see bumper stickers saying "therefore choose life, that you and your children may live," in connection with an anti-abortion message. This passage obviously has nothing to do with abortion. There is nothing in the Bible, anywhere, Old Testament or New, that condemns abortion. Therefore they have to make something up.


loving the Lord your God, obeying his voice, and cleaving to him; for that means life to you and length of days, that you may dwell in the land which the Lord swore to your fathers, to Abraham, to Isaac, and to Jacob, to give them.”


  1. Deuteronomy 30:16 Gk: Heb lacks If you obey the commandments of the Lord your God

Saturday, February 27, 2021

Vaccine disinformation

I wrote a background piece on the mRNA vaccine recently. Since then I've come across some weird false claims about it, so I figured I'd take a minute to set things straight.

A very quick review


I won't  take up a lot of time with the basics of the cellular machinery, but as you ought to know if you don't already DNA, which resides in the cellular nucleus, contains the instructions for making proteins. A "gene," basically, means the instructions for making a specific protein. Proteins are long chains of smaller chemicals called amino acids. There are 20 different amino acids encoded by DNA. (Some others occur biologically but that's a complication we can ignore for now.) 

DNA consists of two strands, each consisting of a sequence of four different "bases," designated A, G, T and C. A always bonds with T, and G with C. Three letter sequences of A, G, T and C are the "words" that specify amino acids. One of the DNA strands, called the 'sense' strand, contains the codes. The other is a template that allows the DNA to reproduce when the cell divides. When it's time to make a protein, the DNA unzips to present the sense strand, and the cellular machinery makes a corresponding messenger RNA strand to carry the information out into the cell. Little cellular machines called ribosomes attach to the mRNA and move along it assembling the proteins. Once the proteins are made, the cell destroys the mRNA. 

Of course, the vaccine introduces the mRNA into your cells directly, it doesn't affect your DNA at all.


So, to debunk a totally false claim that seems to be going around, mRNA does not and cannot replicate. The total amount of mRNA that's in the vaccine is the total amount that will ever be in your body, and it won't be there for long. Even if the cell tried to replicate it, which it doesn't, you'd end up with an anti-sense strand that doesn't do anything. The only permanent effect will be that the cell will display the proteins specified by the mRNA on its surface, and your immune system will make antibodies to them.

Second, the proteins specified by the the mRNA vaccine are part of the so-called viral "spike" that binds to the ACE2 receptor, but the vaccine does not create functional spikes. Just to review, the ACE2 receptor is a protein complex displayed on the surface of many cells, which regulates the balance between two signalling molecules called angiotensin II and angiotensin, thereby regulating your blood pressure and inflammatory response. The coronavirus spike fits in the receptor like a lock into a key, and uses it to get its genetic material into the cell. However, again, the proteins made by the mRNA vaccine do not create a functional spike and even if they did, there are so few of them that even if they did bind to some ACE2 receptors, it wouldn't be enough to raise your blood pressure or cause inflammation. The multiple millions of viral particles if you get an actual infection, however, could indeed wreak havoc in that way. That's why you want to get the vaccine, to make sue that doesn't happen. 
The reason I make these geeky explanations is because I am very puzzled why people who don't have the least idea what they are talking about are getting onto public platforms and spewing bullshit that endangers people's lives. They say all this complicated stuff that makes it seem like they know what they are talking about for people who don't know the basic biology, but it's unmitigated nonsense. I don't know if they're trying to develop a following of dupes who will give them money, or they just like to make people  think they're smart since they know they really aren't. But I'm going to carry on with this theme of bullshit artists in the next post.

Wednesday, February 24, 2021

Wednesday Bible Study: Recapitulation

Deuteronomy 29 is just repetition, and it's getting very tedious. D really needed an editor. I don't really have anything to say about it. Verse 11 refers to slaves. Note that this is the chapter division in the Pentateuch. The Torah attaches verse 1 to the previous chapter.

29 [a] These are the words of the covenant which the Lord commanded Moses to make with the people of Israel in the land of Moab, besides the covenant which he had made with them at Horeb.

[b] And Moses summoned all Israel and said to them: “You have seen all that the Lord did before your eyes in the land of Egypt, to Pharaoh and to all his servants and to all his land, the great trials which your eyes saw, the signs, and those great wonders; but to this day the Lord has not given you a mind to understand, or eyes to see, or ears to hear. I have led you forty years in the wilderness; your clothes have not worn out upon you, and your sandals have not worn off your feet; you have not eaten bread, and you have not drunk wine or strong drink; that you may know that I am the Lord your God. And when you came to this place, Sihon the king of Heshbon and Og the king of Bashan came out against us to battle, but we defeated them; we took their land, and gave it for an inheritance to the Reubenites, the Gadites, and the half-tribe of the Manas′sites. Therefore be careful to do the words of this covenant, that you may prosper[c] in all that you do.

10 “You stand this day all of you before the Lord your God; the heads of your tribes,[d] your elders, and your officers, all the men of Israel, 11 your little ones, your wives, and the sojourner who is in your camp, both he who hews your wood and he who draws your water, 12 that you may enter into the sworn covenant of the Lord your God, which the Lord your God makes with you this day; 13 that he may establish you this day as his people, and that he may be your God, as he promised you, and as he swore to your fathers, to Abraham, to Isaac, and to Jacob. 14 Nor is it with you only that I make this sworn covenant, 15 but with him who is not here with us this day as well as with him who stands here with us this day before the Lord our God.

16 “You know how we dwelt in the land of Egypt, and how we came through the midst of the nations through which you passed; 17 and you have seen their detestable things, their idols of wood and stone, of silver and gold, which were among them. 18 Beware lest there be among you a man or woman or family or tribe, whose heart turns away this day from the Lord our God to go and serve the gods of those nations; lest there be among you a root bearing poisonous and bitter fruit, 19 one who, when he hears the words of this sworn covenant, blesses himself in his heart, saying, ‘I shall be safe, though I walk in the stubbornness of my heart.’ This would lead to the sweeping away of moist and dry alike. 20 The Lord would not pardon him, but rather the anger of the Lord and his jealousy would smoke against that man, and the curses written in this book would settle upon him, and the Lord would blot out his name from under heaven. 21 And the Lord would single him out from all the tribes of Israel for calamity, in accordance with all the curses of the covenant written in this book of the law. 22 And the generation to come, your children who rise up after you, and the foreigner who comes from a far land, would say, when they see the afflictions of that land and the sicknesses with which the Lord has made it sick— 23 the whole land brimstone and salt, and a burnt-out waste, unsown, and growing nothing, where no grass can sprout, an overthrow like that of Sodom and Gomor′rah, Admah and Zeboi′im, which the Lord overthrew in his anger and wrath— 24 yea, all the nations would say, ‘Why has the Lord done thus to this land? What means the heat of this great anger?’ 25 Then men would say, ‘It is because they forsook the covenant of the Lord, the God of their fathers, which he made with them when he brought them out of the land of Egypt, 26 and went and served other gods and worshiped them, gods whom they had not known and whom he had not allotted to them; 27 therefore the anger of the Lord was kindled against this land, bringing upon it all the curses written in this book; 28 and the Lord uprooted them from their land in anger and fury and great wrath, and cast them into another land, as at this day.’

29 “The secret things belong to the Lord our God; but the things that are revealed belong to us and to our children for ever, that we may do all the words of this law.


  1. Deuteronomy 29:1 Ch 28.69 in Heb
  2. Deuteronomy 29:2 Ch 29.1 in Heb
  3. Deuteronomy 29:9 Or deal wisely
  4. Deuteronomy 29:10 Gk Syr: Heb your heads, your tribes

Tuesday, February 23, 2021

Science III

While I have been defending the honor of the scientific enterprise, don't think for a nanosecond that I'm uncritical. I did feel the need to point out that the descriptions of certain funded studies by a right wing web site are ridiculous caricatures, or really just lies. A complicated study of the hunting behavior and associated metabolic burden of panthers is turned into "The National Science Foundation received $856,000 in funding from the Federal Government to conduct a study to see if it is possible to train Lions to walk on a treadmill. It took the Lions eight months."  That description is a lie. You must understand that all right wing media consists mostly of disinformation. 

Now, once you know what the study was actually investigated and what methods it used, you may or may not feel that particular study is the best possible use of taxpayer dollars. That's a highly subjective question. As I have said, there's no formula that can tell us what investigations are most worth doing. We don't know where basic research will lead in the long run. You can't put every grant proposal up for a national referendum, so there has to be a mechanism to evaluate them that relies on a limited number of experts. Review panels do have specific criteria they are supposed to use, and each of the National Institutes of Health has what's called a National Advisory Council that has the final sign-off on awards. It includes lay advocates as well as scientific experts. The broad funding priorities for NIH, NSF and the other agencies that fund science are set by congress, and you get to vote for your representative and senators. I don't know what more you could ask for.

That said, science is certainly not a self-contained, self-justifying, politically and morally pure enterprise. It is done by humans, and embedded in society. It is subject to fraud, error, and various kinds of biases. Outright fraud, fortunately, seems to be uncommon, and it is fairly well-policed. If you're interested in the policing process, check out Retraction Watch.) Every human enterprise is subject to fraud, the business corporation probably more than any other. (Viz. Wells Fargo, Worldcom, and Enron.) 

Outright fraud, however, sort of blurs into error, given the nature of the enterprise. Investigators often -- actually most of the time -- want to get certain results. Whether it's because they are defending their own theories, certain dramatic findings will boost their careers, a positive finding can be the basis for the next grant, or just because positive findings are more likely to be published, they have a favored conclusion. And the rules of inference are complicated, and rather easy to manipulate, consciously or unconsciously. This is a complicated subject and I won't take time to go into it in depth right now, but the replication crisis in social psychology is a good case study. But the good thing about science is that in the long run, it's self-repairing. Spurious beliefs can hang around for a long time -- the opioid epidemic is a good example of the harm they can do -- but we catch up to them eventually.

Other biases, however, are hard to correct. The choice of what questions to ask, even if entrusted to initiating investigators, congress, expert review committees, and National Advisory Councils, is still subject to all of the cultural and power biases in society. Whether we are asking the questions that matter most to people with least power has a pretty obvious answer: probably not so much. Furthermore, the implications of scientific findings depend on your values, interests and prior beliefs. Given a finding about the public health harm done by a pollutant, what standards exactly should we set to regulate it? Given the tradeoffs among effectiveness, safety and cost of a given drug, should it be approved? To whom should it be prescribed? And racism, sexism and other biases often lead entire programs of research down rabbit holes. 

So by all means be critical. But get your facts straight.

Monday, February 22, 2021

More on Science

I alluded previously to much of what I'm going to say here but I want to unpack it a bit. As I noted, at the time Benjamin Franklin experimented with electricity, it wasn't obvious that his investigations had any economic value. And indeed they didn't for another hundred years or so. But as people came to understand more about electricity, it completely transformed the world. Einstein's general theory of relativity had no evident value either, until the Global Positioning System came along, and now it's essential. Same with quantum theory - it's essential to the engineering of the device you are reading this on, among other technological achievements.

Same with the life sciences. When Leeuwenhoek looked through the microscope and saw his "animalcules," it wasn't obvious that the discovery was important, but now we know it is absolutely essential to public health, medicine, and how the world works including agriculture. By studying non-human animals we gain insight into our own nature. And science works by putting together findings and methods from disparate sources. 

Chimpanzees (not monkeys) are our closest living relatives. Well, about as close as bonobos anyway. Studying their behavior has taught us a lot about ourselves. One of their behaviors that was mysterious for a long time is that they like to throw things. Like Clayton Kershaw - well, not quite like him, but like me anyway - they can throw pretty hard and pretty accurately. No other primate does this. Sometimes they might do it to ward off a rival or protect themselves, but they often do it for no obvious reason. The reason chimp in the zoo throw feces, by the way, is because they usually don't have anything else handy. In the wild, they throw rocks and vegetation.


Some scientists studied this, partly with funding from NIH, and they published their results in the Philosophical Transactions of the Royal Society.  Pretty prestigious! That's where Leeuwenhoek published his observations, in 1677, and that's where Franklin published his kite experiment. It turns out to be interesting for several reasons. Here's the abstract:

It has been hypothesized that neurological adaptations associated with evolutionary selection for throwing may have served as a precursor for the emergence of language and speech in early hominins. Although there are reports of individual differences in aimed throwing in wild and captive apes, to date there has not been a single study that has examined the potential neuroanatomical correlates of this very unique tool-use behaviour in non-human primates. In this study, we examined whether differences in the ratio of white (WM) to grey matter (GM) were evident in the homologue to Broca's area as well as the motor-hand area of the precentral gyrus (termed the KNOB) in chimpanzees that reliably throw compared with those that do not. We found that the proportion of WM in Broca's homologue and the KNOB was significantly higher in subjects that reliably throw compared with those that do not. We further found that asymmetries in WM within both brain regions were larger in the hemisphere contralateral to the chimpanzee's preferred throwing hand. We also found that chimpanzees that reliably throw show significantly better communication abilities than chimpanzees that do not. These results suggest that chimpanzees that have learned to throw have developed greater cortical connectivity between primary motor cortex and the Broca's area homologue. It is suggested that during hominin evolution, after the split between the lines leading to chimpanzees and humans, there was intense selection on increased motor skills associated with throwing and that this potentially formed the foundation for left hemisphere specialization associated with language and speech found in modern humans.


There's a good deal more to it than that. For example:


Throwing, as a form of social tool use, is also unique because it likely develops in captive chimpanzees (and possibly wild apes) by way of very different processes and reinforcement contingencies compared with other forms of tool use, notably those described for the purposes of food extraction. . . . In contrast, the rewards associated with throwing are quite different because they are not nutritive in form. Throwing in wild chimpanzees is seldom, if ever, observed for the purposes of obtaining food, but rather is almost always directed towards other chimpanzees or humans. In captivity, it is difficult to imagine that human caretakers would overtly reward a chimpanzee with food immediately after they had just been soiled with faeces by the very same ape. In short, what appears to be the main reward for throwing is the simple ability to control or manipulate the behaviour of the targeted individual (ape or human).



Some have suggested that the increased selection for neural synchrony of rapid muscular sequencing routines associated with actions such as throwing are similar to the motor programming demands of language and speech, and therefore engage similar neural systems, notably Broca's area [24]. Moreover, because the left hemisphere is dominant for language, some have argued that the foundations for left hemisphere lateralization in language may have evolved from an initial preadaptation for right-handedness in throwing


There is a good deal more and it's quite fascinating. This is in a themed issue, "'From action to language: comparative perspectives on primate tool use, gesture and the evolution of human language." That the neural correlates of overhand throwing and language are closely related may seem counterintuitive, but it is a meaningful piece in the puzzle of neuroscience. As a practical matter, it may contribute to rehabilitation from brain injury and to our understanding of human development. Children enjoy all sorts of games involving throwing, including simply throwing rocks at targets or playing catch, and those are part of our early socialization, while their language skills are also developing. 


The point I want to make here is that the essential spirit of science is exploration and discovery for its own sake. We never know what practical benefits may shake out in the end, but it would be a huge mistake to limit scientists to endeavors with an obvious practical end. If we had done that historically, we would be as ignorant as we were 1,000 years ago. 

Sunday, February 21, 2021

Sunday Sermonette: Well okay then

I think Deuteronomy 28 is the longest chapter in the Torah, though I haven't tried to confirm that. Anyway, it's actually an expanded version of Leviticus 26, which recites the blessings the people will receive if they obey Yahweh and the evil that will befall them if they don't. It even uses some of the same language; the blessing section is quite similar, but it adds a lot to the curse part. I actually do recommend that you read this, for the black comedy value. 

Update: After I posted this, by coincidence I learned that Flavius Josephus, in his account of the rebellion against Roman rule that culminated in the sack of Jerusalem and destruction of the temple in 70 CE, tells the story of a starving woman who eats her own infant. Josephus was Jewish (he was born Yosef ben Matityahu), and I suspect he got the idea from this chapter. His account of the war is generally considered to include invented material. 

28 “And if you obey the voice of the Lord your God, being careful to do all his commandments which I command you this day, the Lord your God will set you high above all the nations of the earth. And all these blessings shall come upon you and overtake you, if you obey the voice of the Lord your God. Blessed shall you be in the city, and blessed shall you be in the field. Blessed shall be the fruit of your body, and the fruit of your ground, and the fruit of your beasts, the increase of your cattle, and the young of your flock. Blessed shall be your basket and your kneading-trough. Blessed shall you be when you come in, and blessed shall you be when you go out.

“The Lord will cause your enemies who rise against you to be defeated before you; they shall come out against you one way, and flee before you seven ways. The Lord will command the blessing upon you in your barns, and in all that you undertake; and he will bless you in the land which the Lord your God gives you. The Lord will establish you as a people holy to himself, as he has sworn to you, if you keep the commandments of the Lord your God, and walk in his ways. 10 And all the peoples of the earth shall see that you are called by the name of the Lord; and they shall be afraid of you. 11 And the Lord will make you abound in prosperity, in the fruit of your body, and in the fruit of your cattle, and in the fruit of your ground, within the land which the Lord swore to your fathers to give you. 12 The Lord will open to you his good treasury the heavens, to give the rain of your land in its season and to bless all the work of your hands; and you shall lend to many nations, but you shall not borrow. 13 And the Lord will make you the head, and not the tail; and you shall tend upward only, and not downward; if you obey the commandments of the Lord your God, which I command you this day, being careful to do them, 14 and if you do not turn aside from any of the words which I command you this day, to the right hand or to the left, to go after other gods to serve them.

Warnings against Disobedience

15 “But if you will not obey the voice of the Lord your God or be careful to do all his commandments and his statutes which I command you this day, then all these curses shall come upon you and overtake you. 16 Cursed shall you be in the city, and cursed shall you be in the field. 17 Cursed shall be your basket and your kneading-trough. 18 Cursed shall be the fruit of your body, and the fruit of your ground, the increase of your cattle, and the young of your flock. 19 Cursed shall you be when you come in, and cursed shall you be when you go out.

20 “The Lord will send upon you curses, confusion, and frustration, in all that you undertake to do, until you are destroyed and perish quickly, on account of the evil of your doings, because you have forsaken me. 21 The Lord will make the pestilence cleave to you until he has consumed you off the land which you are entering to take possession of it. 22 The Lord will smite you with consumption, and with fever, inflammation, and fiery heat, and with drought,[a] and with blasting, and with mildew;


they shall pursue you until you perish. 23 And the heavens over your head shall be brass, and the earth under you shall be iron. 24 The Lord will make the rain of your land powder and dust; from heaven it shall come down upon you until you are destroyed.

25 “The Lord will cause you to be defeated before your enemies; you shall go out one way against them, and flee seven ways before them; and you shall be a horror to all the kingdoms of the earth. 26 And your dead body shall be food for all birds of the air, and for the beasts of the earth; and there shall be no one to frighten them away. 27 The Lord will smite you with the boils of Egypt, and with the ulcers and the scurvy and the itch, of which you cannot be healed. 28 

KJV has hemorrhoids rather than ulcers, and I expect that's more accurate. 

The Lord will smite you with madness and blindness and confusion of mind; 29 and you shall grope at noonday, as the blind grope in darkness, and you shall not prosper in your ways; and you shall be only oppressed and robbed continually, and there shall be no one to help you. 30 You shall betroth a wife, and another man shall lie with her; you shall build a house, and you shall not dwell in it; you shall plant a vineyard, and you shall not use the fruit of it. 31 Your ox shall be slain before your eyes, and you shall not eat of it; your ass shall be violently taken away before your face, and shall not be restored to you; your sheep shall be given to your enemies, and there shall be no one to help you. 32 Your sons and your daughters shall be given to another people, while your eyes look on and fail with longing for them all the day; and it shall not be in the power of your hand to prevent it. 33 A nation which you have not known shall eat up the fruit of your ground and of all your labors; and you shall be only oppressed and crushed continually; 34 so that you shall be driven mad by the sight which your eyes shall see. 35 The Lord will smite you on the knees and on the legs with grievous boils of which you cannot be healed, from the sole of your foot to the crown of your head.

36 “The Lord will bring you, and your king whom you set over you, to a nation that neither you nor your fathers have known; and there you shall serve other gods, of wood and stone. 37 And you shall become a horror, a proverb, and a byword, among all the peoples where the Lord will lead you away. 38 You shall carry much seed into the field, and shall gather little in; for the locust shall consume it. 39 You shall plant vineyards and dress them, but you shall neither drink of the wine nor gather the grapes; for the worm shall eat them. 40 You shall have olive trees throughout all your territory, but you shall not anoint yourself with the oil; for your olives shall drop off. 41 You shall beget sons and daughters, but they shall not be yours; for they shall go into captivity. 42 All your trees and the fruit of your ground the locust shall possess. 43 The sojourner who is among you shall mount above you higher and higher; and you shall come down lower and lower. 44 He shall lend to you, and you shall not lend to him; he shall be the head, and you shall be the tail. 45 All these curses shall come upon you and pursue you and overtake you, till you are destroyed, because you did not obey the voice of the Lord your God, to keep his commandments and his statutes which he commanded you. 46 They shall be upon you as a sign and a wonder, and upon your descendants for ever.

47 “Because you did not serve the Lord your God with joyfulness and gladness of heart, by reason of the abundance of all things, 48 therefore you shall serve your enemies whom the Lord will send against you, in hunger and thirst, in nakedness, and in want of all things; and he will put a yoke of iron upon your neck, until he has destroyed you. 49 The Lord will bring a nation against you from afar, from the end of the earth, as swift as the eagle flies, a nation whose language you do not understand, 50 a nation of stern countenance, who shall not regard the person of the old or show favor to the young, 51 and shall eat the offspring of your cattle and the fruit of your ground, until you are destroyed; who also shall not leave you grain, wine, or oil, the increase of your cattle or the young of your flock, until they have caused you to perish. 52 They shall besiege you in all your towns, until your high and fortified walls, in which you trusted, come down throughout all your land; and they shall besiege you in all your towns throughout all your land, which the Lord your God has given you. 53 And you shall eat the offspring of your own body, the flesh of your sons and daughters, whom the Lord your God has given you, in the siege and in the distress with which your enemies shall distress you. 54 The man who is the most tender and delicately bred among you will grudge food to his brother, to the wife of his bosom, and to the last of the children who remain to him; 55 so that he will not give to any of them any of the flesh of his children whom he is eating, because he has nothing left him, in the siege and in the distress with which your enemy shall distress you in all your towns. 56 The most tender and delicately bred woman among you, who would not venture to set the sole of her foot upon the ground because she is so delicate and tender, will grudge to the husband of her bosom, to her son and to her daughter, 57 her afterbirth that comes out from between her feet and her children whom she bears, because she will eat them secretly, for want of all things, in the siege and in the distress with which your enemy shall distress you in your towns.

Yep, you'll eat your own children. 

58 “If you are not careful to do all the words of this law which are written in this book, that you may fear this glorious and awful name, the Lord your God, 59 then the Lord will bring on you and your offspring extraordinary afflictions, afflictions severe and lasting, and sicknesses grievous and lasting. 60 And he will bring upon you again all the diseases of Egypt, which you were afraid of; and they shall cleave to you. 61 Every sickness also, and every affliction which is not recorded in the book of this law, the Lord will bring upon you, until you are destroyed. 62 Whereas you were as the stars of heaven for multitude, you shall be left few in number; because you did not obey the voice of the Lord your God. 63 And as the Lord took delight in doing you good and multiplying you, so the Lord will take delight in bringing ruin upon you and destroying you; and you shall be plucked off the land which you are entering to take possession of it. 64 And the Lord will scatter you among all peoples, from one end of the earth to the other; and there you shall serve other gods, of wood and stone, which neither you nor your fathers have known. 65 And among these nations you shall find no ease, and there shall be no rest for the sole of your foot; but the Lord will give you there a trembling heart, and failing eyes, and a languishing soul; 66 your life shall hang in doubt before you; night and day you shall be in dread, and have no assurance of your life. 67 In the morning you shall say, ‘Would it were evening!’ and at evening you shall say, ‘Would it were morning!’ because of the dread which your heart shall fear, and the sights which your eyes shall see. 68 And the Lord will bring you back in ships to Egypt, a journey which I promised that you should never make again; and there you shall offer yourselves for sale to your enemies as male and female slaves, but no man will buy you.”


  1. Deuteronomy 28:22 Another reading is sword

Saturday, February 20, 2021


Back in the time of Archimedes, and right through Galileo, Benjamin Franklin,  Isaac Newton, and Darwin, it was possible for a lone investigator to make important scientific discoveries with easily affordable apparatus, or just by thinking. Scientists were mostly people of means, who had the leisure to pursue science essentially as a hobby, and perhaps spend small sums on experimental gadgetry. We still think of Albert Einstein as the archetypal scientists, a lone genius who developed profound insights while working at a fairly menial job.


The only reward for these intellectual pioneers was fame, and in Einstein's case a professorship. Galileo's reward was prison. While many of their discoveries had economic value almost immediately, and all did in the long run, none of it went into  their pockets because nobody owns basic knowledge. Patentable technology is fundamentally different. It seldom consists of or incorporates new scientific discoveries. Rather, it takes advantage of known phenomena in new ways. For example, when Newcomen and Watt developed the first commercially useful steam engines, everybody knew that heated water turned into steam that expanded and could be used to push a cylinder. They just hadn't assembled all the parts successfully.

Scientific discovery makes new technologies possible, but there is seldom incentive to invest in basic scientific research because even if you did end up making some sort of patentable discovery -- which the theory of relativity or the heliocentric solar system or the germ theory of disease are not -- there is no way to predict that will happen or what it might be worth. And with very rare exceptions, important scientific discoveries can no longer be made by solitary tinkerers and dreamers. They require very expensive apparatus and teams of investigators and support staff. The scientific enterprise, as opposed to technological research and development, is therefore largely funded by governments, with a much smaller contribution from foundations.

The National Institutes of Health spends about $42 billion a year on biomedical and public health research. Most of that money -- about 80% -- goes as grants to outside investigators, mostly in universities. The National Science Foundation, with a budget of about $8.5 billion, funds research in other areas such as mathematics and computer science. NASA, the Department of Defense, and other federal agencies also fund some scientific research. It is because of scientific discoveries made through this public investment that the technological wonders of today are possible.

In 2000 the Joint Economic Committee of Congress issued a report estimating that the annual return on investment from NIH was 25-40%. Of course, NIH doesn't capture that money, it goes to private corporations who make use of the discoveries and to all of us who ultimately benefit.  Federally funded studies contributed to the development of every single one of 210 new drugs approved between 2010 and 2016

So if you want to call me a socialist or a commie for suggesting that NIH directly fund clinical trials of antibiotics, you have to explain why you think that is bad. I can call you a poopyhead and a dipshit, and I do, but that isn't an argument. Scientific knowledge is the purest example of what even Milton Friedman would call a public good: non-excludable and non-rivalrous.What that means is that nobody can make you pay for using it, and your use of it doesn't stop anybody else from using it too. And even Milton Friedman knew that such goods are underproduced by the market, if they are produced at all. That makes him a commie.

True fact: 100% of NIH grants are fully public information. You can look up the names of the investigators, their institutions, the amount of the awards, and a summary of the research on-line. There are no secret grants at all. Not a single one. There is no corruption in the grantmaking process. Grants are awarded based on peer review by panels of experts, and no contact is allowed between applicants and reviewers. Reviewers who work with the applicants or have other relationships that might create an appearance of bias are required to recuse themselves.

Friday, February 19, 2021

New drug development: the case of antibiotics

I was going to wait to discuss recommendations for encouraging new drug development that better matches public health needs until I had provided more background. It's complicated, and it depends on the specific issue. But let me take the example of antibiotics. 


This is an urgent global problem. As most people know, microbes continually evolve and they will evolve to become resistant to commonly used antibiotics. This article in Clinical Infectious Diseases explains the problem and also why drug companies are not doing enough to develop new classes of antibotics.

Antimicrobial resistance is a profound global health threat of the 21st century. The United Kingdom’s AMR Review estimates that by 2050 as many as 10 million persons a year will die of drug-resistant infections if solutions are not found [1]. The World Bank projects that, without containment of antimicrobial resistance, annual global gross domestic product will decrease by 1%, that is, >$1 trillion annually from 2030, and the hardest hit will be persons in low-income countries [2].

Although resistance levels are increasing globally, the world currently lacks the drug candidates to ensure a diverse and robust pipeline of antibacterial drugs to withstand technical attrition and increasing drug resistance [3, 4]. As of December 2016, there were only 38 candidates in the antibacterial clinical development pipeline [5]. Most of these products will not reach the market, and only a handful of candidates are expected to have activity against urgent threat pathogens. The World Health Organization has identified a list of 12 pathogens that represent the global public health need for new antibiotics [6]. Without new antibiotics targeting these pathogens, mortality rates for untreatable infections are expected to increase. This would represent a step backward in modern medicine, not only for the treatment of infections but also for the ability to perform standard surgeries and cancer chemotherapy, areas that require effective antibiotics as prophylaxis [7].

The lack of antibacterial drug candidates is a function of both the scientific challenges of antibacterial drug development and the lack of profitability that currently exists in the antibiotic market, particularly when compared with other therapeutic areas. Antibacterial drug development is hampered by the conventional pharmaceutical business model, in which revenues are based on volume sales. Antibiotics are unique in that the more that they are used, the faster resistance develops [8]. Therefore, society should actually value and reward access to new antibiotics against specified unmet public health needs, not sales volumes.

As further background, the main incentive for new drug development is basically the same as the incentive for all technological innovation, the patent system. In the case of pharmaceuticals it's a bit more complicated because companies apply for a 20-year patent when they discover a drug candidate, but it typically requires 7 years or more of clinical trials before they can get FDA approval to actually sell it. So they can get additional exclusive rights from the FDA. Typically, market exclusivity lasts for 12 to 14 years.  But, this doesn't suffice to incentivize new antibiotics. If you read the CID article, you will read that the Generating Antibiotic Incentives Now (GAIN) Act provides 5 additional years of exclusivity for new antibiotics. While five antibiotics have received this benefit, none has a novel mode of action, in other words they don't do anything to address the problem of drug resistance. As the article says:

Without an attractive market for antibiotics, private sector investment will continue to decrease. The number of large pharmaceutical companies that invest in antibacterial R&D has decreased significantly in the last 3 decades, to only about 5 companies today [17].

The point is that ordinary market incentives don't work to serve the public interest. The article discusses various ways that incentives can be adjusted. I don't want to get into the weeds of that, I just want to make the point that governments need to manage incentives. The most straightforward way to do that is to invest directly in antibiotic development. This could be done through agreements with pharmaceutical companies that will allow them to sell the resulting product, but at a pre-specified price that allows them only a reasonable profit for manufacturing it, and doesn't enable them to profit from co-opting the public investment; and also allows them to gradually repay the government for its investment. 


Yeah I know. Soshulism.  

Basic literacy: The entire point of this post, and the carefully sourced and well-reasoned scholarly article on which I base it, is that marketing exclusivity does not result in the necessary development of new antibiotics. That is literally the exact conclusion this essay arrives at. Also, almost all basic biomedical research in the United States is funded by the federal government, mostly through the National Institutes of Health, which is largely responsible for the extraordinary revolution in medical science and therapeutics in the past 100 years. Yabbut that's socialism.

Thursday, February 18, 2021

More on clinical trials

Previously, I discussed the basic concept of randomized controlled trials, but didn't go into all the complexities. Actually, I can't go into all the complexities without writing a very big book, and that's not the book I want to write. However, there are some important points I'd like to cover here.

First, there's the question of what drugs (or possibly other kinds of interventions) even get into clinical trials in the first place. In order to conduct trials, the sponsor needs to get approval of what's called an Investigational New Drug Application from the FDA. This requires a reasonable expectation of safety and evidence of pharmacological activity, usually from trials in animals. Note, however, that this is not required for a trial of an already approved drug for an off-label use, since the safety profile of the chemical is already known and it's legal to prescribe it. This is unusual, however, because the only value to the manufacturer would be approval to market the drug for a new purpose and that doesn't often promise sufficient profitability to make the trial worthwhile economically. 

Because trials are enormously expensive, companies will not undertake them if they don't a) have a reasonable expectation that the stuff will be safe and effective and b) have an expectation that it will be profitable enough to justify the expense of the trial. These calculations depend in part on the laws about how long they will have exclusive rights to sell the drug, which are a bit complicated and I'll get to them later. They also obviously depend on the size of the potential market for the drug, and how much they can get away with charging for it. 

What all this means is that the decisions about what drugs to develop and try to get approved don't necessarily align well with what might offer the most benefit to public health. Drug companies are in business to enrich their executives and shareholders, not to benefit humanity. One of the lowest risk investments the companies can make is so-called "evergreening." If they have a profitable drug for which they are about to lose exclusive rights, they can test a slightly different formulation, get brand new rights to it, and then try to convince doctors that the new formulation is sufficiently better that they will prescribe it rather than prescribing a generic version of the old drug. That threat may discourage companies from making a generic version of the old drug so it actually ceases to be available.

There is also a lot of money to be made developing treatments for terminal diseases that only prolong life for a short time, because people are desperate and they're willing to pay a lot for those drugs -- or more precisely it's politically imperative for Medicare and private insurance to pay for them. So cancer treatments that only prolong life by a few months and cost $100,000 or more will be paid for because of the "death panels" argument. Note, by the way, that is not true in the UK where there is a cost-benefit requirement for drug approval. That's another complicated issue I'll have to expand on later.


The last thing I'll say today is that there are many problems with translating clinical trial results into actual benefit for patients. Clinical trials happen in a very different universe from the real world in which a drug will actually be used. Participants are selected specifically not to have certain comorbid conditions that are common in the general population. They may be restricted by age. They are also generally monitored to make sure they are taking the drug as prescribed, which many people don't do in reality. And there is heterogeneity of treatment effect. Just because a drug has a net benefit on average in a sample doesn't mean it's benefiting everybody, and it might even be harming some people. But that is very difficult to sort out and establishing it requires a whole new expensive trial, which the companies have no obvious incentive to do. (You can't just go back and look at how sub-groups did in your original trial because that violates the rules of inference. That's an important philosophical question which I may discuss at the risk of boring people.)

To be continued.

Wednesday, February 17, 2021

Andrew Cuomo

I have no idea why people think I'm an Andrew Cuomo fan. He is in fact universally despised among progressives. Fortunately, CNN is willing to hold him to account

Going back more than a hundred years, New York has held the dubious distinction of being a corruption leader among US states and has struggled to ensure integrity in state government. In recent years, high-profile bribery cases have ensnared the leaders of both legislative bodies and Governor Andrew Cuomo's former right-hand man. Now, a different kind of potential abuse of the public trust has come to light, and this time Governor Cuomo himself is in the hot seat.

Late last month, New York State Attorney General Letitia James issued a scathing report about how nursing homes in the state handled Covid-19, including a finding that the state's Department of Health undercounted Covid deaths at nursing homes by approximately 50%. While the discrepancy didn't change the overall number of New York Covid-19 deaths, it attributed deaths where a nursing home resident had been transferred to a hospital for treatment to the hospital instead of the nursing home.

This is perhaps something of a tempest in a teapot: it was likely originally just a bureaucratic mistake. However, the response was first to try to cover it up, then to excuse it away. Cuomo is just generally not a model of transparency or commitment to principle, and he cooperated with the so-called Independent Democratic Conference to allow Republicans to control the Senate even though Democrats held the most seats. (Long story.) The IDC is in the past, however, as Democrats now have a supermajority, which is a good thing because they can override Cuomo's vetoes. Anyway shut up about Andrew Cuomo already. I don't like him either. 

However, I don't live in New York and there are plenty of governors to complain about, so there's no particular reason to expect me to write about him.


BTW, CNN has been covering this story extensively for weeks.

Wednesday Bible Study: A strange assortment

Deuteronomy 27 is something of a head scratcher. It strongly emphasizes a set of rules, two of which overlap with the Big Ten, the rest of which are a weird potpourri. Deuteronomy often has this feeling of having been thrown together more or less at random.

27 Now Moses and the elders of Israel commanded the people, saying, “Keep all the commandment which I command you this day. And on the day you pass over the Jordan to the land which the Lord your God gives you, you shall set up large stones, and plaster them with plaster; and you shall write upon them all the words of this law, when you pass over to enter the land which the Lord your God gives you, a land flowing with milk and honey, as the Lord, the God of your fathers, has promised you. And when you have passed over the Jordan, you shall set up these stones, concerning which I command you this day, on Mount Ebal, and you shall plaster them with plaster. And there you shall build an altar to the Lord your God, an altar of stones; you shall lift up no iron tool upon them. You shall build an altar to the Lord your God of unhewn[a] stones; and you shall offer burnt offerings on it to the Lord your God; and you shall sacrifice peace offerings, and shall eat there; and you shall rejoice before the Lord your God. And you shall write upon the stones all the words of this law very plainly.”

I isn't clear whether they're supposed to write all the laws from this entire book -- which would be a really big fresco, or just the stuff which follows in this chapter, which would be a weird monument indeed. Why God doesn't want the stones of the altar to be hewn I cannot say.

And Moses and the Levitical priests said to all Israel, “Keep silence and hear, O Israel: this day you have become the people of the Lord your God. 10 You shall therefore obey the voice of the Lord your God, keeping his commandments and his statutes, which I command you this day.”

Twelve Curses

11 And Moses charged the people the same day, saying, 12 “When you have passed over the Jordan, these shall stand upon Mount Ger′izim to bless the people: Simeon, Levi, Judah, Is′sachar, Joseph, and Benjamin. 13 And these shall stand upon Mount Ebal for the curse: Reuben, Gad, Asher, Zeb′ulun, Dan, and Naph′tali. 14 And the Levites shall declare to all the men of Israel with a loud voice:

15 “‘Cursed be the man who makes a graven or molten image, an abomination to the Lord, a thing made by the hands of a craftsman, and sets it up in secret.’ And all the people shall answer and say, ‘Amen.’

16 “‘Cursed be he who dishonors his father or his mother.’ And all the people shall say, ‘Amen.’

17 “‘Cursed be he who removes his neighbor’s landmark.’ And all the people shall say, ‘Amen.’

18 “‘Cursed be he who misleads a blind man on the road.’ And all the people shall say, ‘Amen.’

19 “‘Cursed be he who perverts the justice due to the sojourner, the fatherless, and the widow.’ And all the people shall say, ‘Amen.’

I can get behind the last three or four.

20 “‘Cursed be he who lies with his father’s wife, because he has uncovered her who is his father’s.’[b] And all the people shall say, ‘Amen.’

I get that extra rules are required for polygamy. Note that under the norms of the time, your father's second wife could easily be as young or younger than you, and might indeed be more interested in you than your elderly father. I can imagine this being a real problem. However, that it gets such a prominent place here seems a bit surprising. It has been mentioned before, BTW.

21 “‘Cursed be he who lies with any kind of beast.’ And all the people shall say, ‘Amen.’

22 “‘Cursed be he who lies with his sister, whether the daughter of his father or the daughter of his mother.’ And all the people shall say, ‘Amen.’

23 “‘Cursed be he who lies with his mother-in-law.’ And all the people shall say, ‘Amen.’

24 “‘Cursed be he who slays his neighbor in secret.’ And all the people shall say, ‘Amen.’

Well yeah.

25 “‘Cursed be he who takes a bribe to slay an innocent person.’ And all the people shall say, ‘Amen.’

26 “‘Cursed be he who does not confirm the words of this law by doing them.’ And all the people shall say, ‘Amen.’


  1. Deuteronomy 27:6 Heb whole
  2. Deuteronomy 27:20 Heb uncovered his father’s skirt

Tuesday, February 16, 2021

Lies and the lying liars . . .

I draw your attention to this essay by Eric Boehlert, (you may have to click through a subscription solicitation but you can read it) which makes the cogent but obvious point that the corporate media, for the duration of the recent Residency, refused to use the word "lie" or "liar" with respect to Mr. Trump. He focuses particularly on an interview given by WaPo editor Marty Baron, who seems to regret this failure but weasels out of taking real responsibility. One of his weasel points is that deference must be paid to the president but of course this began before the 2016 election, during the campaign. 

Another weasel point is that they couldn't know his state of mind, maybe he was misinformed, but of course this is also ridiculous because he often repeated the same lie more than 100 times even after it had been repeatedly debunked. Baron also weasels that it wouldn't have mattered anyway. I agree that most MAGAts don't read the WaPo or the New York Times but this also applies to the major TV news operations that more people are exposed to and in any case, if your excuse is that your publication isn't very influential you should probably be looking for another job. 

Granted many of them did start calling the claim of a stolen election a lie, but I actually think that helped. Yes, a lot of Republicans believe the lie but IIRC (not bothering to look for polls right now) it's something like 60%, which also means a lot of them don't and many people are leaving the party. Faux News doesn't 100% determine the beliefs of some of them, and it's the responsibility of ethical journalists to tell the truth, and that includes calling a lie a lie. I hope they're starting to learn.

Sunday, February 14, 2021

Commenting policy

It is not the case -- it is never the case -- that I reject comments merely because I disagree with them. I do not publish comments that are irrelevant, uninterpretable, offensive, or false.

For example, it is irrelevant to my recent post about hydroxychloroquine that there are other treatments that people have tried or are trying that have not been demonstrated in randomized controlled trials. Just asserting that well-known fact -- i.e., I do agree with it, that is true -- does not make any point that pertains to the post. It is not somehow an objection to what I wrote.

As I have said very often, one goal I have here is to promote critical thinking. Comments must generally be on topic, logically coherent, and factually correct. If your comment doesn't get published, that's why.

Sunday Sermonette: Some platitudes

 Nothing really to say about this, it doesn't say much.

26 “When you come into the land which the Lord your God gives you for an inheritance, and have taken possession of it, and live in it, you shall take some of the first of all the fruit of the ground, which you harvest from your land that the Lord your God gives you, and you shall put it in a basket, and you shall go to the place which the Lord your God will choose, to make his name to dwell there. And you shall go to the priest who is in office at that time, and say to him, ‘I declare this day to the Lord your God that I have come into the land which the Lord swore to our fathers to give us.’ Then the priest shall take the basket from your hand, and set it down before the altar of the Lord your God.

“And you shall make response before the Lord your God, ‘A wandering Aramean was my father; and he went down into Egypt and sojourned there, few in number; and there he became a nation, great, mighty, and populous. And the Egyptians treated us harshly, and afflicted us, and laid upon us hard bondage.

This is a reference to Joseph, of course, but he wasn't wandering, his brothers sold him into slavery.

Then we cried to the Lord the God of our fathers, and the Lord heard our voice, and saw our affliction, our toil, and our oppression; and the Lord brought us out of Egypt with a mighty hand and an outstretched arm, with great terror, with signs and wonders; and he brought us into this place and gave us this land, a land flowing with milk and honey. 10 And behold, now I bring the first of the fruit of the ground, which thou, O Lord, hast given me.’ And you shall set it down before the Lord your God, and worship before the Lord your God; 11 and you shall rejoice in all the good which the Lord your God has given to you and to your house, you, and the Levite, and the sojourner who is among you.

12 “When you have finished paying all the tithe of your produce in the third year, which is the year of tithing, giving it to the Levite, the sojourner, the fatherless, and the widow, that they may eat within your towns and be filled, 13 then you shall say before the Lord your God, ‘I have removed the sacred portion out of my house, and moreover I have given it to the Levite, the sojourner, the fatherless, and the widow, according to all thy commandment which thou hast commanded me; I have not transgressed any of thy commandments, neither have I forgotten them; 14 I have not eaten of the tithe while I was mourning, or removed any of it while I was unclean, or offered any of it to the dead; I have obeyed the voice of the Lord my God, I have done according to all that thou hast commanded me. 15 Look down from thy holy habitation, from heaven, and bless thy people Israel and the ground which thou hast given us, as thou didst swear to our fathers, a land flowing with milk and honey.’

Concluding Exhortation

16 “This day the Lord your God commands you to do these statutes and ordinances; you shall therefore be careful to do them with all your heart and with all your soul. 17 You have declared this day concerning the Lord that he is your God, and that you will walk in his ways, and keep his statutes and his commandments and his ordinances, and will obey his voice; 18 and the Lord has declared this day concerning you that you are a people for his own possession, as he has promised you, and that you are to keep all his commandments, 19 that he will set you high above all nations that he has made, in praise and in fame and in honor, and that you shall be a people holy to the Lord your God, as he has spoken.”

Saturday, February 13, 2021

A primer on the evaluation of therapeutics

I'm actually going to talk here mostly about how we decide that medications are effective, but the basic principles apply to other kinds of interventions such as surgery, physical therapy, or devices. However, those do present some additional difficulties, which I won't go into right now. 

Conventionally, we speak of a hierarchy of evidence, from least to most persuasive. The weakest form of evidence is anecdote. Dr. Fell says he gave eye of newt to several of his patients with crotch rot and they got better. (This is essentially what started the hydroxychloroquine madness.) 


There are many reasons why doctors all over the world don't rush out and start giving eye of newt to all their patients. Dr. Fell may simply be a nut. But even if he's sincere, with most diseases, presumably including crotch rot, and including Covid-19, most people normally get better. So Dr. Fell's observation doesn't show that eye of newt actually helped. He may be unconsciously motivated to see more or faster improvement than expected, because he wants his treatment to be useful. And there may be adverse effects that he overlooked or haven't emerged yet. He may also have, perhaps unconsciously, given the nostrum to patients who would be most expected to improve. There are more reasons to doubt this but I'll stop there.

The next level of evidence is still considered too weak to draw any conclusions about the safety and effectiveness of a medication. This is called a retrospective cohort study. It usually isn't feasible because it would require that some substantial number of physicians are prescribing a drug for an unapproved indication, but this is what happened fairly early in the Covid-19 pandemic during the HCQ craze. In this form of study, researchers find a group of people who have had the disease and they look back to see which of them were prescribed the drug, then look for differences in their outcomes.

You probably don't need a Ph.D. to see why this sort of evidence is usually not very persuasive. The people who were prescribed the drug might be different from those who weren't for many reasons. In the case of Covid-19 specifically, doctors who prescribed HCQ might have been in practices with more affluent and lower risk patients. Given that it is known to present a risk for cardiac complications, they likely would have chosen not to prescribe it to people with risk factors such as heart disease or obesity, which also happen to be risk factors for worse outcomes of Covid-19. You can try to adjust for some of these potential "confounders" in your statistical analysis, but you can't adjust for ones you hadn't thought of or that you can't measure.  In the case of a specific study which has been brought to my attention, only a small number of patients were actually prescribed HCQ, which means the sample size was small, and as it happens the effect was only marginally significant. It is possible to massage your regression until you get a confidence interval that doesn't cross zero, and unfortunately that sort of post hoc analysis is all too easy to do in this situation.

Furthermore, there is the problem of publication bias. One of these studies might get a significant result just by chance, while others do not. But the negative studies won't be published. The particular study in question was published in an open access journal that evidently has low standards, and it has been superseded by later, higher quality studies that find no effect, or even a possible risk of harm.

These studies are called randomized controlled trials, and they are the only way to get FDA approval. The problem of publication bias has also been ameliorated for these studies because they have to be registered in advance. That means the data will be available regardless of whether they are published. In these studies, a group of patients with the disease -- probably matched in some way such as disease severity and stage -- are randomly assigned to receive the drug, or a "placebo" that is physically indistinguishable. Neither the patient, the treating physician, or the assessor who judges outcomes knows who did and did not get the real drug. Then the patients are followed for a time to see how they do with respect to the disease, and also to look for adverse effects. If a large sample is randomly assigned, chances are the intervention and control arms will have similar characteristics, but statistical techniques can be used to adjust for any major differences that happen by chance. You don't have to worry about prescriber bias because the intervention was assigned at random.

In the case of HCQ, after the anecdotes and retrospective studies that in some cases indicated the treatment might be promising, investigators undertook large, high quality randomized controlled trials at every stage -- for prophylaxis, for treatment of moderate disease, and for treatment of hospitalized patients. They were all, uniformly negative. It doesn't work for Covid-19 under any circumstances, and it may be harmful. The editors of the New England Journal of Medicine, The Lancet, and other leading medical journals have all come to his conclusion, as has the FDA. You don't know more than they do, and you don't know more than I do about this subject either.

Let me conclude by saying that unfortunately, this is an all too common pattern. People hype therapies based on weak evidence, the corporate media pick up on the hype, and later, more rigorous studies find the snake oil doesn't work. We see it again and again. What we don't see is an ignoramus occupying the office of president of the United States joining in the hype. That's because usually, they aren't ignorant idiots and they know better.

Addendum: Everything I have written here is absolutely, irrefutably true and you will learn this if you take a basic course in medical school or a school of public health. It is not to be confused with what doctors actually do, because if a drug is approved for any use, they are legally allowed to prescribe it however they want, and sometimes doctors prescribe drugs "off label." That doesn't mean the drugs actually work, it just means some doctors think they do, or might. The FDA can also issue what's called an Emergency Use Authorization, in cases of a public health crisis, which they in fact did in the case of HCQ. Then they withdrew it when good evidence came in. Doctors are trying other therapies for Covid-19 now, but just because they are trying some doesn't mean we know they work. Most of them will turn out not to, if the usual pattern follows.