Sunday Sermonette: Hit the snooze button

 No post yesterday, I've been thinking deep thoughts. I may post on a relatively small issue later today.

Chapter 17 is consistent with the story in Samuel -- God says David won't build the Temple but his son will -- but Chronicles is exceedingly long-winded about the matter. Again, this probably comes from much older source material which has been lost. It goes on tediously and says very little, so I will say no more.

17 After David was settled in his palace, he said to Nathan the prophet, “Here I am, living in a house of cedar, while the ark of the covenant of the Lord is under a tent.”

² Nathan replied to David, “Whatever you have in mind, do it, for God is with you.”

³ But that night the word of God came to Nathan, saying:

⁴ “Go and tell my servant David, ‘This is what the Lord says: You are not the one to build me a house to dwell in. ⁵ I have not dwelt in a house from the day I brought Israel up out of Egypt to this day. I have moved from one tent site to another, from one dwelling place to another. ⁶ Wherever I have moved with all the Israelites, did I ever say to any of their leaders^[a] whom I commanded to shepherd my people, “Why have you not built me a house of cedar?”’

⁷ “Now then, tell my servant David, ‘This is what the Lord Almighty says: I took you from the pasture, from tending the flock, and appointed you ruler over my people Israel. ⁸ I have been with you wherever you have gone, and I have cut off all your enemies from before you. Now I will make your name like the names of the greatest men on earth. ⁹ And I will provide a place for my people Israel and will plant them so that they can have a home of their own and no longer be disturbed. Wicked people will not oppress them anymore, as they did at the beginning ¹⁰ and have done ever since the time I appointed leaders over my people Israel. I will also subdue all your enemies.

“‘I declare to you that the Lord will build a house for you: ¹¹ When your days are over and you go to be with your ancestors, I will raise up your offspring to succeed you, one of your own sons, and I will establish his kingdom. ¹² He is the one who will build a house for me, and I will establish his throne forever. ¹³ I will be his father, and he will be my son. I will never take my love away from him, as I took it away from your predecessor. ¹⁴ I will set him over my house and my kingdom forever; his throne will be established forever.’”

¹⁵ Nathan reported to David all the words of this entire revelation.

David’s Prayer

¹⁶ Then King David went in and sat before the Lord, and he said:

“Who am I, Lord God, and what is my family, that you have brought me this far? ¹⁷ And as if this were not enough in your sight, my God, you have spoken about the future of the house of your servant. You, Lord God, have looked on me as though I were the most exalted of men.

¹⁸ “What more can David say to you for honoring your servant? For you know your servant, ¹⁹ Lord. For the sake of your servant and according to your will, you have done this great thing and made known all these great promises.

²⁰ “There is no one like you, Lord, and there is no God but you, as we have heard with our own ears. ²¹ And who is like your people Israel—the one nation on earth whose God went out to redeem a people for himself, and to make a name for yourself, and to perform great and awesome wonders by driving out nations from before your people, whom you redeemed from Egypt? ²² You made your people Israel your very own forever, and you, Lord, have become their God.

²³ “And now, Lord, let the promise you have made concerning your servant and his house be established forever. Do as you promised, ²⁴ so that it will be established and that your name will be great forever. Then people will say, ‘The Lord Almighty, the God over Israel, is Israel’s God!’ And the house of your servant David will be established before you.

²⁵ “You, my God, have revealed to your servant that you will build a house for him. So your servant has found courage to pray to you. ²⁶ You, Lord, are God! You have promised these good things to your servant. ²⁷ Now you have been pleased to bless the house of your servant, that it may continue forever in your sight; for you, Lord, have blessed it, and it will be blessed forever.”

Footnotes

1. 1 Chronicles 17:6 Traditionally judges; also in verse 10

I am stupid

 Major premise: People are stupid.

Minor premise: Isaac Asimov is (was) a person

Conclusion: Isaac Asimov is stupid

(Sorry, no post yesterday because I was doing some heavy cerebral processing.)

He'd have been the first to admit it. All of us are susceptible to cognitive errors and biases. I'd like to think that Asimov was less susceptible than most, but he must have had his own foibles. It's a constant struggle to be mindful and think straight. 

For my own part, I once had a romanticized view of the Chinese revolution, I was an anthropogenic climate change skeptic, and I entertained the likelihood that medical intervention, on balance, did more harm than good. (Viz Illich, Medical Nemesis.) 

One of my pervasive misconceptions was believing that mental states are far more influential for physical health than they really are. I thought that placebos had a direct effect on biological functioning, and that physical maladies such as gastric ulcers, inflammatory bowel disease, acne and various forms of chronic inflammation, among others, were caused by or at least associated with emotional states. Actually ulcers turn out to be an infectious disease caused by a bacterium, placebos affect self-reports of symptoms but not measurable biological parameters, and most of the other sorts of syndromes I mentioned are autoimmune or allergic disorders.

Chronic stress is associated with high blood pressure, and people with serious mental diagnoses tend to have a lot of comorbidity and shortened life expectancies, although the exact mechanisms are uncertain. So it's not that there's nothing to it, just that many people have an exaggerated and even fundamentally incorrect view of the relationship between the brain and the rest of the body. A positive attitude won't cure or prevent cancer. The etiology of asthma is not well understood but it is definitely not caused by psychodynamic processes. Maternal smoking in utero is a risk factor,  in many cases it seems to be basically an allergic disease, and it may be related to infections or toxic exposures.

Nevertheless, the brain is a physical organ and it is connected to the rest of the body. Chronic fatigue syndrome, fibromyalgia, chronic pain syndromes of all kinds, are probably basically neurological in origin. The circuits that send pain signals to the brain have gotten stuck open, to put it crudely. This doesn't mean the person is crazy or that the fundamental cause is repressed anger or childhood memories or anything like that. Physical or psychological trauma likely may be involved in causing these syndromes but it isn't happening because of any ongoing psychodynamic cause, it's a misfunction of the nervous system. But the point is, I now have an open mind about these questions and I acknowledge what we, and therefore I, don't know.

It's probably a good exercise to think about prior beliefs of your own that have changed. What might you be convinced of today that could turn out to be wrong? What beliefs could you reexamine? And what are the obstacles that might be stopping you?

 

 

Wednesday Bible Study: Hit song

As far as I can tell, Chapter 16 has no real basis in Samuel.  I doubt that it's actually original, but the source material has been lost. This shows the Chronicler's usual obsession with lists of meaningless names, but the main act is a song. Now seems as good a time as any to mention that the Book of Psalms is traditionally attributed  to David, but that's nonsensical. It was compiled centuries after his death, if he ever existed. Presumably this song reflects theology at the time Chronicles was written, probably in the 4th Century BCE, in the Second Temple period. 

I'll just make a couple of points that I think are noteworthy. In the KJV, what appears here as a cake of raisins in Verse 3 is translated as a flagon of wine. I can't account for the discrepancy, but I will say that the Bible is generally in favor of drinking alcohol, which conflicts with much of modern Protestantism, so it's possible these translators of the New International Version favored the non-alcoholic version. The song seems ambivalent about polytheism. The Lord (I assume the text has Adonai rather than Yahweh) is " is to be feared above all gods, which seems to acknowledge that other gods exist, but "all the gods of the nations are idols,   but the Lord made the heavens." And then "²⁸ Ascribe to the Lord, all you families of nations, ascribe to the Lord glory and strength." The Israelites are God's chosen people, but this seems to call upon others to acknowledge him as a universal God. 

Unfortunately, this song makes a prediction which failed. "¹⁵ He remembers^[c] his covenant forever, the promise he made, for a thousand generations, ¹⁶ the covenant he made with Abraham,the oath he swore to Isaac. ¹⁷ He confirmed it to Jacob as a decree,  to Israel as an everlasting covenant: ¹⁸ “To you I will give the land of Canaan  as the portion you will inherit.” 

About 400 years after this was written --- well before 1,000 generations -- the Romans destroyed the Temple and expelled the Jews from the land.

16 They brought the ark of God and set it inside the tent that David had pitched for it, and they presented burnt offerings and fellowship offerings before God. ² After David had finished sacrificing the burnt offerings and fellowship offerings, he blessed the people in the name of the Lord. ³ Then he gave a loaf of bread, a cake of dates and a cake of raisins to each Israelite man and woman.

⁴ He appointed some of the Levites to minister before the ark of the Lord, to extol,^[a] thank, and praise the Lord, the God of Israel: ⁵ Asaph was the chief, and next to him in rank were Zechariah, then Jaaziel,^[b] Shemiramoth, Jehiel, Mattithiah, Eliab, Benaiah, Obed-Edom and Jeiel. They were to play the lyres and harps, Asaph was to sound the cymbals, ⁶ and Benaiah and Jahaziel the priests were to blow the trumpets regularly before the ark of the covenant of God.

⁷ That day David first appointed Asaph and his associates to give praise to the Lord in this manner:

⁸ Give praise to the Lord, proclaim his name;
    make known among the nations what he has done.
⁹ Sing to him, sing praise to him;
    tell of all his wonderful acts.
¹⁰ Glory in his holy name;
    let the hearts of those who seek the Lord rejoice.
¹¹ Look to the Lord and his strength;
    seek his face always.

¹² Remember the wonders he has done,
    his miracles, and the judgments he pronounced,
¹³ you his servants, the descendants of Israel,
    his chosen ones, the children of Jacob.
¹⁴ He is the Lord our God;
    his judgments are in all the earth.

¹⁵ He remembers^[c] his covenant forever,
    the promise he made, for a thousand generations,
¹⁶ the covenant he made with Abraham,
    the oath he swore to Isaac.
¹⁷ He confirmed it to Jacob as a decree,
    to Israel as an everlasting covenant:
¹⁸ “To you I will give the land of Canaan
    as the portion you will inherit.”

¹⁹ When they were but few in number,
    few indeed, and strangers in it,
²⁰ they^[d] wandered from nation to nation,
    from one kingdom to another.
²¹ He allowed no one to oppress them;
    for their sake he rebuked kings:
²² “Do not touch my anointed ones;
    do my prophets no harm.”

²³ Sing to the Lord, all the earth;
    proclaim his salvation day after day.
²⁴ Declare his glory among the nations,
    his marvelous deeds among all peoples.

²⁵ For great is the Lord and most worthy of praise;
    he is to be feared above all gods.
²⁶ For all the gods of the nations are idols,
    but the Lord made the heavens.
²⁷ Splendor and majesty are before him;
    strength and joy are in his dwelling place.

²⁸ Ascribe to the Lord, all you families of nations,
    ascribe to the Lord glory and strength.
²⁹ Ascribe to the Lord the glory due his name;
    bring an offering and come before him.
Worship the Lord in the splendor of his^[e] holiness.
³⁰     Tremble before him, all the earth!
    The world is firmly established; it cannot be moved.

³¹ Let the heavens rejoice, let the earth be glad;
    let them say among the nations, “The Lord reigns!”
³² Let the sea resound, and all that is in it;
    let the fields be jubilant, and everything in them!
³³ Let the trees of the forest sing,
    let them sing for joy before the Lord,
    for he comes to judge the earth.

³⁴ Give thanks to the Lord, for he is good;
    his love endures forever.
³⁵ Cry out, “Save us, God our Savior;
    gather us and deliver us from the nations,
that we may give thanks to your holy name,
    and glory in your praise.”
³⁶ Praise be to the Lord, the God of Israel,
    from everlasting to everlasting.

Then all the people said “Amen” and “Praise the Lord.”

³⁷ David left Asaph and his associates before the ark of the covenant of the Lord to minister there regularly, according to each day’s requirements. ³⁸ He also left Obed-Edom and his sixty-eight associates to minister with them. Obed-Edom son of Jeduthun, and also Hosah, were gatekeepers.

³⁹ David left Zadok the priest and his fellow priests before the tabernacle of the Lord at the high place in Gibeon ⁴⁰ to present burnt offerings to the Lord on the altar of burnt offering regularly, morning and evening, in accordance with everything written in the Law of the Lord, which he had given Israel. ⁴¹ With them were Heman and Jeduthun and the rest of those chosen and designated by name to give thanks to the Lord, “for his love endures forever.” ⁴² Heman and Jeduthun were responsible for the sounding of the trumpets and cymbals and for the playing of the other instruments for sacred song. The sons of Jeduthun were stationed at the gate.

⁴³ Then all the people left, each for their own home, and David returned home to bless his family.

Footnotes

1. 1 Chronicles 16:4 Or petition; or invoke
2. 1 Chronicles 16:5 See 15:18,20; Hebrew Jeiel, possibly another name for Jaaziel.
3. 1 Chronicles 16:15 Some Septuagint manuscripts (see also Psalm 105:8); Hebrew Remember
4. 1 Chronicles 16:20 One Hebrew manuscript, Septuagint and Vulgate (see also Psalm 105:12); most Hebrew manuscripts inherit, / ¹⁹ though you are but few in number, / few indeed, and strangers in it.” / ²⁰ They
5. 1 Chronicles 16:29 Or Lord with the splendor of

More on critical thinking: what's wrong with our brains

Well, there's not necessarily anything wrong with your gray matter, that's an evaluative judgment. But it evolved to be functional for apes on the African savanna and that's not the world we live in now. Our brains do not simply or reliable convert sensory input into an accurate rendition of reality, and the stories we tell ourselves to make sense out of events -- whether we experience them directly or learn about them from reports of others or mass media -- aren't reliable either. Neither are our memories.

People have written whole books about the myriad ways in which we fool ourselves. In my recent series on clinical trials I have referred, directly or obliquely, to a few of them. But to try to back up to a very broad statement that will fit on a blog post, we can't take in new information without hanging it on a pre-existing framework..Over our  lifetimes, we accumulate a story, a narrative about how the world works -- or possibly more than one that don't necessarily fit together, that we apply to different kinds of problems or under different circumstances. Information that doesn't fit into that story or stories may simply be ignored or rejected; or modified to fit. We notice information that appears to confirm our narrative or is at least compatible with it; and contrary information, one way or another, gets shitcanned.

This is the basis of confirmation bias, and its opposite, which I would call rejection bias. But it also simply creates patches of ignorance that are extremely difficult to fill in. For example, a few years ago I worked with a group of people living with HIV who were advising me on some research, providing the patient's point of view. Some of them had quite a lot of education -- four year college or master's degrees. But they hadn't studied a lot of biology, which is true of the vast majority of people, and that made it almost impossible for me to explain to them what was the most important fact about their health, that is viral drug resistance.

People did understand a basic idea their doctors had told them: that the medications they were taking work to stop the progress of HIV disease, but they can stop working if the people don't take them consistently. All of them, every single one -- and just about every one of a much larger number of people who I surveyed -- interpreted this to mean that their bodies would become resistant to the medication, that drug resistance is a change in the person's body.

For those people who had a history of opioid dependence or other addictive drug use, this was a readily available analogy. For others, it was just a readily understandable idea. It's wrong, but I discovered that explaining why it's wrong and what really happens was a massive project and not attainable in many cases. I talked with people who do health education for people living with HIV and they all basically told me that they don't even bother to try. But the wrong idea can lead to some wrong conclusions and harmful behavior.

You may already know the real story but even if you do, think about how far down to biology 101 you need to go to explain it. You have to explain the nature of a virus, that it's a package of genetic material that has somehow gotten loose in the world. But what does that mean? You have to explain about DNA and RNA and how they work together to manufacture proteins, and what proteins are, which means oh yeah, what cells are. You have to explain how the virus -- or rather, its genetic material -- gets into a cell and what happens when it gets there. You have to explain at least in broad terms how the antiviral medications work, and then you have to explain Darwinian evolution and how this works for a virus in the context of exposure to an antiviral compound. Only then can you explain that drug resistance is a change in the virus, not in your body, and how it comes about. 

This difference is vitally important both for your the sake of your own health -- your "adherence" to your prescriptions, keeping appointments and getting tested -- and to others who you could potentially infect. That's because another part of the story is that if your medications are working fully and you're taking them regularly, you won't be infectious to others. But if you do develop viral drug resistance and don't know it, not only could you infect other people, but you'll infect them with a strain of the virus against which the drugs don't work. 

This story isn't important only to people living with HIV: some slightly different version of it is important for every human being who has a treatable infection of any kind, and for the future of humanity. But apes don't have to understand anything like that. This is just one parable and I could tell you many more. I should also tell you that people's beliefs about taking medications are not only affected by how well they are able to understand the biological story, but also by what is convenient or practical in the context of the rest of their lives. In other words, there's a lot of motivated reasoning going on as well as cognitive burden. But the same basic problems apply to people's political views, and public policy judgements, and how they vote. As Isaac Asimov succinctly put it, "People are stupid." That means all of us. It's hard work not to be.

More on pseudoscience and other nonsense

Homeopathy was not invented by hippies of New Age mystics. It was first propounded in 1796 by a German named Samuel Hahnemann. It became popular in the U.S. in the 19th Century, understandably so. As homeopathy does absolutely nothing, it was superior to most medical treatments of the time. There were even homeopathic medical schools. But, in the 20th Century, as scientific understanding of health and disease emerged, homeopathy was discredited by the medical profession and became a fringe practice. Nevertheless it persists. 

 

Among the prominent proponents of homeopathy was His Royal Highness Charles, Prince of Wales, who is now His Majesty King Charles III. If you don't believe me enter Prince Charles and homeopathy into your favorite Internet search engine. He is not a hippie nor a New Ager. Homeopathic remedies are manufactured and sold by capitalists, who only want your money, in the CVS and Walmart, for the same reason. 

Such pseudoscience has not historically been the particular province of Left or Right, nor of countercultures. The modern anti-vax movement largely traces to a medical fraudster named Andrew Wakefield, whose politics otherwise he does not discuss, but its champions included the purportedly liberal Robert Kennedy Jr. and various Hollywood celebrities who at least came out of a relatively liberal milieu. However, it has now migrated very decisively to the Right. It just so happens at this historical moment that pseudoscience is largely the preserve of self-styled "conservatives," for no evident reason other than it's promotion by their object of cultish adoration, but that has not always been the case.

So, I'm reading The Skeptics Guide to the Universe by Steve Novella (M.D.), which has me thinking again - as I have always done - about the underlying reasons for human folly. Having described what good scientific evidence for a treatment would look like, I will now turn my attention to the way our brains get the world wrong. Stay tuned..

Sunday Sermonette: Now for something completely different

While the previous chapter was basically lifted from Samuel, this one is not. 2 Samuel 6 tells of David bringing the Ark to Jerusalem, but the accompanying details in Chronicles are not in Samuel at all. We see the Chronicler's obsessive interest in lists of names here, but also an interest in orthodoxy. The idea that only the Levites can carry the Ark is not in Samuel, but it's a major emphasis here. Samuel also lacks all of the details about the musicians and the music.

 

On the other hand this version very much downplays Micah's displeasure at seeing David dance. It's briefly mentioned at the end but not explained, nor is the denouement presented. In  Samuel, David danced nearly naked, wearing only an ephod, and Micah -- who, also unmentioned in Chronicles, was David's first wife -- was offended, telling him sarcastically, "How glorious was the king of Israel to day, who uncovered himself to day in the eyes of the handmaids of his servants, as one of the vain fellows shamelessly uncovereth himself!" To which David replied "God chose me as king over your father and your family. I will play before him if I want to. So I will be even more vile than that. I will be disgusting in my own sight, but honored by all the slave girls in the kingdom." God punishes Micah for criticizing David by making her childless. Anyway, the point is, the Chronicler cleans up David's image throughout, and this is just one more example.

15 After David had constructed buildings for himself in the City of David, he prepared a place for the ark of God and pitched a tent for it. ² Then David said, “No one but the Levites may carry the ark of God, because the Lord chose them to carry the ark of the Lord and to minister before him forever.”

³ David assembled all Israel in Jerusalem to bring up the ark of the Lord to the place he had prepared for it. ⁴ He called together the descendants of Aaron and the Levites:

⁵ From the descendants of Kohath,

Uriel the leader and 120 relatives;

⁶ from the descendants of Merari,

Asaiah the leader and 220 relatives;

⁷ from the descendants of Gershon,^[a]

Joel the leader and 130 relatives;

⁸ from the descendants of Elizaphan,

Shemaiah the leader and 200 relatives;

⁹ from the descendants of Hebron,

Eliel the leader and 80 relatives;

¹⁰ from the descendants of Uzziel,

Amminadab the leader and 112 relatives.

¹¹ Then David summoned Zadok and Abiathar the priests, and Uriel, Asaiah, Joel, Shemaiah, Eliel and Amminadab the Levites. ¹² He said to them, “You are the heads of the Levitical families; you and your fellow Levites are to consecrate yourselves and bring up the ark of the Lord, the God of Israel, to the place I have prepared for it. ¹³ It was because you, the Levites, did not bring it up the first time that the Lord our God broke out in anger against us. We did not inquire of him about how to do it in the prescribed way.” ¹⁴ So the priests and Levites consecrated themselves in order to bring up the ark of the Lord, the God of Israel. ¹⁵ And the Levites carried the ark of God with the poles on their shoulders, as Moses had commanded in accordance with the word of the Lord.

¹⁶ David told the leaders of the Levites to appoint their fellow Levites as musicians to make a joyful sound with musical instruments: lyres, harps and cymbals.

¹⁷ So the Levites appointed Heman son of Joel; from his relatives, Asaph son of Berekiah; and from their relatives the Merarites, Ethan son of Kushaiah; ¹⁸ and with them their relatives next in rank: Zechariah,^[b] Jaaziel, Shemiramoth, Jehiel, Unni, Eliab, Benaiah, Maaseiah, Mattithiah, Eliphelehu, Mikneiah, Obed-Edom and Jeiel,^[c] the gatekeepers.

¹⁹ The musicians Heman, Asaph and Ethan were to sound the bronze cymbals; ²⁰ Zechariah, Jaaziel,^[d] Shemiramoth, Jehiel, Unni, Eliab, Maaseiah and Benaiah were to play the lyres according to alamoth,^{[e] 21} and Mattithiah, Eliphelehu, Mikneiah, Obed-Edom, Jeiel and Azaziah were to play the harps, directing according to sheminith.^{[f] 22} Kenaniah the head Levite was in charge of the singing; that was his responsibility because he was skillful at it.

²³ Berekiah and Elkanah were to be doorkeepers for the ark. ²⁴ Shebaniah, Joshaphat, Nethanel, Amasai, Zechariah, Benaiah and Eliezer the priests were to blow trumpets before the ark of God. Obed-Edom and Jehiah were also to be doorkeepers for the ark.

²⁵ So David and the elders of Israel and the commanders of units of a thousand went to bring up the ark of the covenant of the Lord from the house of Obed-Edom, with rejoicing. ²⁶ Because God had helped the Levites who were carrying the ark of the covenant of the Lord, seven bulls and seven rams were sacrificed. ²⁷ Now David was clothed in a robe of fine linen, as were all the Levites who were carrying the ark, and as were the musicians, and Kenaniah, who was in charge of the singing of the choirs. David also wore a linen ephod. ²⁸ So all Israel brought up the ark of the covenant of the Lord with shouts, with the sounding of rams’ horns and trumpets, and of cymbals, and the playing of lyres and harps.

²⁹ As the ark of the covenant of the Lord was entering the City of David, Michal daughter of Saul watched from a window. And when she saw King David dancing and celebrating, she despised him in her heart.

Footnotes

1. 1 Chronicles 15:7 Hebrew Gershom, a variant of Gershon
2. 1 Chronicles 15:18 Three Hebrew manuscripts and most Septuagint manuscripts (see also verse 20 and 16:5); most Hebrew manuscripts Zechariah son and or Zechariah, Ben and
3. 1 Chronicles 15:18 Hebrew; Septuagint (see also verse 21) Jeiel and Azaziah
4. 1 Chronicles 15:20 See verse 18; Hebrew Aziel, a variant of Jaaziel.
5. 1 Chronicles 15:20 Probably a musical term
6. 1 Chronicles 15:21 Probably a musical term

Clinical Trials 101: Lecture 5

Okay, you've made it through the preliminary rounds and now you've gotten funding for your Phase III trial. In the old days, you could just go ahead and do it and if your sponsoring drug company didn't like the results, they would just bury them and not publish. Or, you could do what are called post hoc analyses, trolling through your data to find some endpoint that seemed to come out positive for some sub-group within your sample, and then pretend that's what you were looking for all along. Without getting too deep into the philosophical weeds, if you do that, your p values are bogus and the effect probably isn't real -- but it was very common to do it anyway.

Nowadays, if you have federal funding, or if you want the FDA to consider your trial in the drug approval process, you need to register your trial in advance. That means you need to state very specifically:

1. What are the eligibility criteria for the study? That means both inclusion criteria -- you need to have a diagnosis of creeping crud, confirmed by some specified means, probably within a particular (likely early) stage of the disease; and exclusion criteria -- for example, you can't be pregnant, you can't have certain other comorbidities, you have to be over 18 and under 65, you have to speak English.

2. How will people be assigned to the intervention group or groups -- i.e. people might get different doses or courses of treatment -- and the control group or groups -- i.e. some people might get only placebo, others an alternative treatment. There are complicated reasons for such different study designs, but you need to explain the rationale and it needs to satisfy ethical requirements. In general, assignment is random, although you could "stratify" the random assignment, for example by assuring that there are equal numbers of men and women in each group.

3. What are your hypothesized outcomes? This is very important. Again, if you don't state specifically that you are looking for, say a statistically significant and clinically meaningful difference in reported symptoms between the intervention and control group; or a significant reduction in the frequency of certain complications or other bad outcomes such as for example death; then your statistical methods for hypothesis testing will not be valid. Also, if you want to look at results for some sub-group, say just older people or just women, you have to specify that in advance as well. Otherwise you're "p hacking," and that's a no no.

4. You have to specify how initial disease severity and outcomes will be measured. If at all possible, this should be done by people who are "blinded" to who is in the intervention and who is in the control group. 

5. You need to specify how long your follow-up period will be (probably not long enough, in the real world) and how you are going to look for adverse effects, whether people are really taking the pills or not, at what intervals you are going to take your measurements.

6. What is the sample size for intervention and control groups? What is it's "power" to detect the differences you have hypothesized, in other words is it big enough to make chance differences unlikely to be important? (How unlikely is a matter of convention, there's no standard written in the structure of the universe.). . 

There may be more but I think I've hit the most important points. Obviously, in the first place, this is going to be quite expensive. As I say, you won't get to this point without a lot of preliminary evidence. There will be heterogeneity of treatment effect, that is some people will seem to benefit but in most cases others will not. Figuring why that is and what people are the best candidates for the treatment, and who should avoid it, will usually require even further study, although to some extent this can be done by "post marketing surveillance" rather than more randomized controlled trials. In practice, however, even when the FDA mandates post marketing surveillance, it often doesn't happen. There are more problems and limitations of this, which I will talk about, but under most circumstances, it's the only way to get convincing evidence that a treatment really works.

Unfortunately, for asinine political reasons, we were forced to spend a whole lot of money to prove that ivermectin and hydroxychloroquine are ineffective for Covid-19, which we already knew. That has been proved. That story is over.

Clinical Trials 101: A digression

 I'm going to take a break from explaining the right way to do clinical trials to say a bit about a really, terribly, awful bad way to do it. That would be homeopathy. The link is to a piece about a consumer organization that is suing CVS for putting homeopathic "remedies" on the shelf next to actual over the counter medications that might do something useful. (A lot of them don't really either but that's another story.)

First there's the question of biological plausibility. Homeopathy is radically and irremediably inconsistent with everything we know about physics, chemistry and biology. If we believe everything we have learned since the 19th Century, it's absurd and impossible. That means nobody is going to invest in high quality clinical trials of any homeopathic remedy because we already know that they cannot possibly work. 

Second, there's the issue of the placebo effect. Trials of homeopathy are small and poorly controlled (see above). We know that if we give people with some form of physical or emotional complaint an inert substance, many of them will report that they feel better. That's not necessarily bad in itself but it's definitely bad if it stops them from seeking effective treatment when they don't have a self-limiting disease, and especially bad if they have a progressive disease that is going to cause them more pain and disability and maybe kill them.

The problem is, I know this, everybody who goes to medical school or studies biology, chemistry and/or physics ought to know this, I hope you know it -- but many people passionately believe in the truth of homeopathy. I don't know about the people who manufacture these products -- maybe most of them are just con artists who are happy to take people's money. And maybe some people who buy them are just as the lawsuit alleges: deceived by their placement on the shelf in the CVS, and don't really think about it. But there are a lot of true believers.

Which brings us back to the earlier question of ivermectin and hydroxychloroquine as treatments for Covid. People believe in these for reasons other than the kind of evidence that I find convincing or even suggestive. They have reasons to believe that lie outside of the realm of empirical evidence. This is a big problem facing humanity right now because there are a lot of very important true facts that we all need to believe if we are to save our sorry asses, and a whole lot of people are choosing not to believe them. That's an emergency.

 

 

Wednesday Bible Study: A twice-told tale

 Ch. 14 is largely lifted from 2 Samuel 5, although it skips a lot. Basically it skips ahead to verse 13 of 2 Samuel 5, leaving out the fact that David already had a whole lot of wives and concubines. The reason for the Chronicler's selective lifting from Samuel isn't clear, but in general he seems to be trying to clean up David's image. In case you've forgotten, the David of Samuel is one horrible son of a bitch. On the other hand, why the Chronicler felt the need to reprint this in the first place is equally unclear. To make it easy on you, I'm going to provide the matching passages from Samuel after this.

1 Chronicles 14

14 Now Hiram king of Tyre sent messengers to David, along with cedar logs, stonemasons and carpenters to build a palace for him. ² And David knew that the Lord had established him as king over Israel and that his kingdom had been highly exalted for the sake of his people Israel.

³ In Jerusalem David took more wives and became the father of more sons and daughters. ⁴ These are the names of the children born to him there: Shammua, Shobab, Nathan, Solomon, ⁵ Ibhar, Elishua, Elpelet, ⁶ Nogah, Nepheg, Japhia, ⁷ Elishama, Beeliada^[a] and Eliphelet.

David Defeats the Philistines

⁸ When the Philistines heard that David had been anointed king over all Israel, they went up in full force to search for him, but David heard about it and went out to meet them. ⁹ Now the Philistines had come and raided the Valley of Rephaim; ¹⁰ so David inquired of God: “Shall I go and attack the Philistines? Will you deliver them into my hands?”

The Lord answered him, “Go, I will deliver them into your hands.”

¹¹ So David and his men went up to Baal Perazim, and there he defeated them. He said, “As waters break out, God has broken out against my enemies by my hand.” So that place was called Baal Perazim.^{[b] 12} The Philistines had abandoned their gods there, and David gave orders to burn them in the fire.

¹³ Once more the Philistines raided the valley; ¹⁴ so David inquired of God again, and God answered him, “Do not go directly after them, but circle around them and attack them in front of the poplar trees. ¹⁵ As soon as you hear the sound of marching in the tops of the poplar trees, move out to battle, because that will mean God has gone out in front of you to strike the Philistine army.” ¹⁶ So David did as God commanded him, and they struck down the Philistine army, all the way from Gibeon to Gezer.

¹⁷ So David’s fame spread throughout every land, and the Lord made all the nations fear him.

Footnotes

1. 1 Chronicles 14:7 A variant of Eliada
2. 1 Chronicles 14:11 Baal Perazim means the lord who breaks out.

 

2 Samuel 5 (beginning with verse 11)

 

¹¹ Now Hiram king of Tyre sent envoys to David, along with cedar logs and carpenters and stonemasons, and they built a palace for David. ¹² Then David knew that the Lord had established him as king over Israel and had exalted his kingdom for the sake of his people Israel.

¹³ After he left Hebron, David took more concubines and wives in Jerusalem, and more sons and daughters were born to him. ¹⁴ These are the names of the children born to him there: Shammua, Shobab, Nathan, Solomon, ¹⁵ Ibhar, Elishua, Nepheg, Japhia, ¹⁶ Elishama, Eliada and Eliphelet.

David Defeats the Philistines

¹⁷ When the Philistines heard that David had been anointed king over Israel, they went up in full force to search for him, but David heard about it and went down to the stronghold. ¹⁸ Now the Philistines had come and spread out in the Valley of Rephaim; ¹⁹ so David inquired of the Lord, “Shall I go and attack the Philistines? Will you deliver them into my hands?”

The Lord answered him, “Go, for I will surely deliver the Philistines into your hands.”

²⁰ So David went to Baal Perazim, and there he defeated them. He said, “As waters break out, the Lord has broken out against my enemies before me.” So that place was called Baal Perazim.^{[c] 21} The Philistines abandoned their idols there, and David and his men carried them off.

²² Once more the Philistines came up and spread out in the Valley of Rephaim; ²³ so David inquired of the Lord, and he answered, “Do not go straight up, but circle around behind them and attack them in front of the poplar trees. ²⁴ As soon as you hear the sound of marching in the tops of the poplar trees, move quickly, because that will mean the Lord has gone out in front of you to strike the Philistine army.” ²⁵ So David did as the Lord commanded him, and he struck down the Philistines all the way from Gibeon^[d] to Gezer.

Footnotes

1. 2 Samuel 5:8 Or are hated by David
2. 2 Samuel 5:9 Or the Millo
3. 2 Samuel 5:20 Baal Perazim means the lord who breaks out.
4. 2 Samuel 5:25 Septuagint (see also 1 Chron. 14:16); Hebrew Geba

 

 

Clinical Trials 101: Lecture 4

Okay, you've convinced a funder that it's worth investing in a trial of Eontof as a treatment for CC. The first thing you have to do is make sure that Eontof is reasonably safe, get an idea of what dosage is tolerable and its "pharmacokinetics," which basically means how blood concentrations vary over time after you take it, and what its metabolites are. If it's already being used for a different application, you might already know this, but otherwise you need to do what's called a Phase I trial. 

 

Before you even do this, you need some confidence that it's safe, based on trying it on animals and whatever you know about its biological activity. Then you find a small number of people who you think would qualify for the larger scale trial you have in mind and give a couple of them a very small dose. If parts don't start falling off you gradually up the dose with a few more people and measure how they're blood plasma levels change over time, and if they seem to have any adverse effects. You'll take a glance at whether it seems to be having an effect on their CC but that's pretty much just for yucks at this point, you haven't set up the experiment to demonstrate that. 

If everything looks good, nobody died or required a brain transplant, you can go to Phase II. This is a larger but still relatively small scale trial to inform the design of your full-scale, Phase III trial, or if there's bad news, pull the plug. Here's where we introduce the concept of statistical power. If you toss a coin once, the probability of heads is .5 (or 50%, same thing). If you toss a coin 10 times the most likely outcome is 5 heads and 5 tails, but the probability of getting 6 heads is more than 20%, so that wouldn't be enough to prove that the coin is biased. Even if you toss the coin 20 times and get 12 heads that probability is still about .12, which still isn't all that convincing. That probability - of getting what appears to be a difference between two outcomes purely by chance, when there isn't really any difference -- is called the p value. For completely arbitrary reasons, it has to be .05 (5%) or less before you're aloud to announce a "significant" finding, but even that is pretty much bogus because there are all sorts of risks of bias that can get you to p<.05 when there's really nothing there.

To cut to the chase, in order to get funding for your Phase III trial you need to specify a big enough sample size that, based on a credible estimate of the effect size, a positive outcome will have p<.05. For our Phase II trial, the sample size probably isn't big enough, but you need to do it to get an estimate of the effect size that you can plug into the sample size calculation for your Phase III trial. Also, obviously, the trend has to be in the right direction and it still needs to appear safe. In other words, it's looking good enough to keep going, and you have some idea what to expect. There's a whole lot more to think about, however, which we'll get to next time.

 

 

 

Aministrative note: an apology

 I discovered that a couple of months back, and prior to that for quite a long time, I thought that Blogger was sending me an e-mail every time somebody offered a comment. It turns out that was not the case and there were a whole lot of comments I would have published if I had known about them, but I didn't. This applies particularly to Chuck and some others. So if you stopped commenting because you thought I didn't want to publish your comments, this may not have been the case. (It is the case for some people, you know who you are.) So please try again if you wish, I know now that I have to check for comments every time I log in.

Clinical Research 101: Lecture 3

Now that we've cleared away a bit of the underbrush, let's say you think that Eye of Newt Toe of Frog (Eontof) is potentially therapeutically useful against Creeping Crud (CC), and you want to test it. You face a whole lot of considerations. One is that you're going to need funding, which means you need to persuade somebody -- either the National Institutes of Health or a pharmaceutical company, most likely -- to invest in your idea. They're going to want to know that there's a reasonable chance of success with Eontof, and in the case of the pharmaceutical company that they can make money off of it, which brings in other problems we'll put aside for now. 

You basically have three possible kinds of argument for why Eontof is worth testing. The first is biological plausibility: you understand, or have a hypothesis about, the etiology of CC and there is a biologically plausible argument for why Eontof will interrupt the disease process. If there is a so-called animal model for CC, that is rats or rabbits or guinea pigs or whatever can have a similar disease, you can test Eontof in animals and see if it works. Don't get too excited though, what works in rats often doesn't work in humans. Finally, doctors might already be giving Eontof to people for some other reason and they notice purely by serendipity that it seems to be effective against CC. 

How you and your potential funder interpret all this, and what your next steps are, depend on the nature of CC, which I might have discussed first but I have to take all this in some order so this is the one I chose. Infectious diseases are usually self-limiting, in other words the immune system kicks in and kicks the pathogen out, but the ones that worry us the most and are likely to attract funding for clinical trials will sometimes go on to produce serious disease that threatens long term harm or death. Examples are mostly famous -- plague, smallpox, influenza, Covid-19 . .  . 

 

Before you undertake a clinical trial you need to specify your endpoints, in other words you need to state exactly what your hypotheses are about the effect Eontof will have. Presumably these might be a smaller percentage of people who experience severe disease -- which you have to define -- a lower mortality rate, obviously, and maybe faster recovery on average -- which you also have to define. It's a lot more complicated, however, because the risks of CC vary according to people's pre-existing characteristics -- maybe age, sex, socioeconomic status, overall state of health, but also maybe things you don't know about or can't readily measure such as genetics, prior exposure, diet, whatever. Another problem if you're relying on people telling you how they feel to define and measure recovery is the so-called placebo effect. If you give people a completely inert pill, that they think might do some good, they'll be more likely to report that they feel better even if there is no measurable biological reason for them to say so.

The problem of endpoints is different if CC is, let's say a chronic or progressive disease that is rarely self-limiting. (Even cancer and maybe some auto-immune diseases will occasionally spontaneously remit so I don't want to say never.) Then your endpoints might be slower progression or symptom relief rather than cure. The issue may purely be risk - the probability of a heart attack, let's say. But it's still the case that you need to be concerned about other "confounding" factors such as age, sex, other health conditions etc., and the placebo effect. 

We'll design our clinical trial next time. But for now, just keep in mind that the people who touted hydroxychloroquine and ivermectin for Covid-19 didn't

Sunday Sermonette: Jumping Ahead

As we have seen, the Chronicler has no interest in chronological order. He's wandering through time and space. Now he jumps ahead from David's years as a guerilla leader to the early years of his kingship, skipping entirely over the theft of the Ark by the Philistines, its recovery (a tale involving golden hemorrhoids, as you may recall), and David's ascension to the throne, to David's decision to move the Ark to Jerusalem from Kiriath Jearim, where it happened to land after the Philistines sent it back. This chapter is largely derived from 2 Samuel 6, either with some light rewriting, or based on an alternative version of the original. David is as nonplussed as you will likely be that God decides to kill Uzzah for reaching out to prevent the Ark from falling over, which seems to have been an appropriate reaction.

Minor contradictions with the canonical version of 2 Samuel 6 include the name of the threshing floor where Yahweh wacked Uzzah (Chidon vs. Nachon), and the size of David's entourage when he went to recover the Ark (30,000 chosen men in Samuel vs. all of Israel in Chronicles). Some of the language, however, is identical. 

 

13 David conferred with each of his officers, the commanders of thousands and commanders of hundreds. ² He then said to the whole assembly of Israel, “If it seems good to you and if it is the will of the Lord our God, let us send word far and wide to the rest of our people throughout the territories of Israel, and also to the priests and Levites who are with them in their towns and pasturelands, to come and join us. ³ Let us bring the ark of our God back to us, for we did not inquire of^[a] it^[b] during the reign of Saul.” ⁴ The whole assembly agreed to do this, because it seemed right to all the people.

⁵ So David assembled all Israel, from the Shihor River in Egypt to Lebo Hamath, to bring the ark of God from Kiriath Jearim. ⁶ David and all Israel went to Baalah of Judah (Kiriath Jearim) to bring up from there the ark of God the Lord, who is enthroned between the cherubim—the ark that is called by the Name.

⁷ They moved the ark of God from Abinadab’s house on a new cart, with Uzzah and Ahio guiding it. ⁸ David and all the Israelites were celebrating with all their might before God, with songs and with harps, lyres, timbrels, cymbals and trumpets.

⁹ When they came to the threshing floor of Kidon, Uzzah reached out his hand to steady the ark, because the oxen stumbled. ¹⁰ The Lord’s anger burned against Uzzah, and he struck him down because he had put his hand on the ark. So he died there before God.

¹¹ Then David was angry because the Lord’s wrath had broken out against Uzzah, and to this day that place is called Perez Uzzah.^[c]

¹² David was afraid of God that day and asked, “How can I ever bring the ark of God to me?” ¹³ He did not take the ark to be with him in the City of David. Instead, he took it to the house of Obed-Edom the Gittite. ¹⁴ The ark of God remained with the family of Obed-Edom in his house for three months, and the Lord blessed his household and everything he had.

Footnotes

1. 1 Chronicles 13:3 Or we neglected
2. 1 Chronicles 13:3 Or him
3. 1 Chronicles 13:11 Perez Uzzah means outbreak against Uzzah.

  

Clinical Research 101: Lecture 2

 Editor's note: Only about 15 million people so far have gotten the new bivalent Covid booster that's specifically formulated against the Omega variants that are currently circulating. I got it a few days ago, Walgreen's was offering appointments the same day! I got the flu shot at the same time, both absolutely free. Do it!

So, picking up where we left off, to determine whether an intervention is beneficial, harmful or basically useless you ordinarily need a comparison group. There are actually exceptions. You don't need a randomized controlled trial for parachutes when jumping out of airplanes because you already know what happens just about every time you jump out of an airplane without one. But few medical conditions are like that. Even ordinarily progressive conditions, such as cancer or multiple sclerosis, can spontaneously remit, at least temporarily, and anyway we might like to slow them down even if we can't cure them. But infectious diseases in particular are a battle between the pathogen and the immune system, and the immune system usually wins eventually. So you have to measure the difference between people who get eye of  newt and toe of frog, and those who don't.

Unfortunately, it's not that simple. I can round up a bunch of people who have had Creeping Crud and compare the outcomes of those who have taken Eontof and those who haven't, but that's unlikely to prove anything. For starters, the two groups may have been different in all sorts of ways to begin with. Maybe the people who got Eontof were more likely to be insured or otherwise relatively privileged, therefore probably healthier to start with. On the other hand maybe they got it because they were sicker, and therefore their doctor was more likely write a prescription. The latter is called confounding by indication, and it can make an intervention look bad when it's actually helpful. 

There are many more problems with this. If I'm asking about the past, it really isn't possible to measure accurately or reliably how sick they were, or how long it took them to recover. As a matter of fact, if I want the intervention to work -- and I probably do -- then consciously or unconsciously I could skew my assessment of original severity and subsequent recovery, even if I'm following both groups from the beginning. This is called ascertainment bias and believe me, it is a very powerful effect. And if the sample is too small, any differences between the two groups could be due purely to chance. 

For these and other reasons, it is very commonly the case that positive results in small, preliminary trials aren't confirmed by more rigorous studies. This is what happened with ivermectin and hydroxychloroquine.  Some doctors gave them to some patients and had the impression that those patients did better than expected. But  people with even minimal expertise in this field knew immediately that the evidence was weak or useless. It is also important to note that there was no biological plausibility for these claims. These are antiparasitic agents that are toxic to metazoans. There is absolutely no plausible argument as to why they would be effective against a virus.

Unfortunately, because claims about these agents became politically controversial, NIH felt it had to fund rigorous clinical trials even though in normal circumstances there would not have been any justification for spending all that money. The results were as expected. Both of them are completely useless against Covid-19 in all stages of the disease and all populations, and they can have serious adverse effects. So, waste of money, harm to population, and yet we still have politicians, their followers, and quack doctors promoting these harmful practices.

Next time, I'll explain the requirements for a properly designed clinical trial, the limitations thereof, and how we can augment well crafted randomized controlled trials with other kinds of evidence to get the most compelling information.

Clinical Research

This subject is quite complicated and it will be difficult for me to address it coherently in the space of a blog post. Lay people, unfortunately, are prone to many misunderstandings of clinical research and lately political opportunists have taken to exploiting these misunderstandings. Joseph Ladapo, the Florida Surgeon General, is one of these. He either doesn't know what he's doing when it comes to epidemiological research, or he's just a liar. Probably a little bit of both. The entire community of relevant experts rejects his conclusion that young men should not get the Covid vaccine, not because they don't like the conclusion, but because his evidence is not valid.

For some reason, insisting on medical falsehoods has become a passionate cause for the political right in the U.S. Opposing vaccination, promoting ineffective and harmful treatments, opposing sensible measures to protect health and lives -- these have all become emblems of "freedom" for people who are not exercising freedom at all, but championing ignorance and error. Viz:.

 

 

So, let me try to explain a few things quickly.  If you want to know whether an intervention is safe and effective, you face several problems. ("Intervention" is the standard term in clinical and public health research for doing something, basically -- whether it be administering a drug or a vaccine, surgery, changing people's behavior or the physical or social environment, whatever.) The first is being able to make an appropriate comparison. As an obvious example, if you just give a bunch of people who have, let's say, a cold, some sort of a pill, and a week or ten days later they're mostly feeling better, does that mean the pill works? On the other hand, if people have cancer, and you give them a treatment, and six months later most of them are worse off does that mean the treatment harmed them? Obviously you don't actually know either way.

At least it should be obvious, but for 2,000 years, since Hippocrates, it evidently wasn't obvious to physicians. They kept bleeding people and giving them emetics and purgatives. Why? Well, most of them got better anyway and if they didn't, it was because the doctors weren't "heroic" enough, so they bled the people all the more and purged them all the more and if they died, it wasn't the doctor's fault, they'd done the best they could.

I think that's enough for now and I'll continue in the next post. Meanwhile, you can think about this a bit.

A couple of things . . . .

Just to be clear, and I say this in no uncertain terms with the backing of the CDC, FDA, Dr. Peter Hotez, and innumerable other experts, the Surgeon General of Florida is a quack. This is not debatable, it is a fact. However, I didn't need all these other experts to confirm it because I am qualified to figure it out for myself. I am an actual expert on clinical research, and I can tell when a paper is bullshit. I am an academic editor for a medical journal and I peer review publications all the time. So don't try to tell me what to think about this, if you are actually completely ignorant of these matters.

 

With that out of the way, I want to briefly revisit the matter of autocracy. In 1812, Napoleon invaded Russia at the head of an army of 500,000, which is said to have been the largest military assemblage ever as of that date. His plan was to conquer Russia, then march south and seize India from Britain. If that sounds insane, it's because it is. 

According to authoritative accounts, only 10,000 of those 500,000  men made it back alive. (Some put it a bit higher, but certainly less than 40,000.) They died of typhus, dysentery, starvation and cold. The Tsar's soldiers helped a bit, but mostly they just stood back and let the French army perish. Napoleon, of course, fled back to Paris in disguise, in a sleigh, leaving his men to their horrific fate.

This was, quite arguably, the worst military debacle in world history. But did it loosen Napoleon's grip on power even a tiny bit? No. In fact as far as the historical record can tell us, it didn't even occur to anyone that Napoleon should abdicate or be replaced. On the contrary, he raised another army and went to war with the rest of Europe, ultimately leading to his famous defeat at Waterloo and exile to the island of Elba, imposed not by his subjects but by the enemies who defeated him. But then guess what? He escaped from Elba in a small boat, landed in France, and was welcomed back as emperor by the French people. That didn't last long -- the European allies beat the crap out of him again and this time, they sent him to a remote island in the Atlantic. 

So don't expect Vladimir Putin to go away any time soon.

 

Wednesday Bible Study: Unstuck in Time

One norm of story telling that doesn't interest the Chronicler is chronological order. First he told us about the return from Babylon, then he abruptly jumped back centuries to the death of Saul, without any warning. Now he jumps back in time again to the period when David was a pretender to the throne and hiding out with a guerilla band. Modern story tellers may certainly use flashbacks but they also have some way of helping us keep track. If you didn't already know the story, you would be hopelessly confused by now.

While Chapter 12 is not inconsistent with Samuel, unlike previous material it evidently has a different source. It uses different language and provides a lot of different detail, specifically the names of all of David's captains and lieutenants. It mentions his stint as a mercenary for the Philistines only in passing, whereas Samuel devotes some attention to it. It is conceivable that the source is the lost Chronicles of the Kings of Israel, which the Deuteronomist history refers to several times as containing additional detail, but who knows? 

You might want to argue that the existence of more than one source supports the likelihood that this contains historical truth, but I'm not convinced of that. Folk tales generally metastasize, and this certainly spent a while as oral tradition before it was written down. As for why the Chronicler thinks we need this in addition to Samuel, I can only say that he has a weird obsession with lists of names.

12 These were the men who came to David at Ziklag, while he was banished from the presence of Saul son of Kish (they were among the warriors who helped him in battle; ² they were armed with bows and were able to shoot arrows or to sling stones right-handed or left-handed; they were relatives of Saul from the tribe of Benjamin):

³ Ahiezer their chief and Joash the sons of Shemaah the Gibeathite; Jeziel and Pelet the sons of Azmaveth; Berakah, Jehu the Anathothite, ⁴ and Ishmaiah the Gibeonite, a mighty warrior among the Thirty, who was a leader of the Thirty; Jeremiah, Jahaziel, Johanan, Jozabad the Gederathite,^{[a] 5} Eluzai, Jerimoth, Bealiah, Shemariah and Shephatiah the Haruphite; ⁶ Elkanah, Ishiah, Azarel, Joezer and Jashobeam the Korahites; ⁷ and Joelah and Zebadiah the sons of Jeroham from Gedor.

⁸ Some Gadites defected to David at his stronghold in the wilderness. They were brave warriors, ready for battle and able to handle the shield and spear. Their faces were the faces of lions, and they were as swift as gazelles in the mountains.

⁹ Ezer was the chief,

Obadiah the second in command, Eliab the third,

¹⁰ Mishmannah the fourth, Jeremiah the fifth,

¹¹ Attai the sixth, Eliel the seventh,

¹² Johanan the eighth, Elzabad the ninth,

¹³ Jeremiah the tenth and Makbannai the eleventh.

¹⁴ These Gadites were army commanders; the least was a match for a hundred, and the greatest for a thousand. ¹⁵ It was they who crossed the Jordan in the first month when it was overflowing all its banks, and they put to flight everyone living in the valleys, to the east and to the west.

¹⁶ Other Benjamites and some men from Judah also came to David in his stronghold. ¹⁷ David went out to meet them and said to them, “If you have come to me in peace to help me, I am ready for you to join me. But if you have come to betray me to my enemies when my hands are free from violence, may the God of our ancestors see it and judge you.”

¹⁸ Then the Spirit came on Amasai, chief of the Thirty, and he said:

“We are yours, David!
    We are with you, son of Jesse!
Success, success to you,
    and success to those who help you,
        for your God will help you.”

So David received them and made them leaders of his raiding bands.

¹⁹ Some of the tribe of Manasseh defected to David when he went with the Philistines to fight against Saul. (He and his men did not help the Philistines because, after consultation, their rulers sent him away. They said, “It will cost us our heads if he deserts to his master Saul.”) ²⁰ When David went to Ziklag, these were the men of Manasseh who defected to him: Adnah, Jozabad, Jediael, Michael, Jozabad, Elihu and Zillethai, leaders of units of a thousand in Manasseh. ²¹ They helped David against raiding bands, for all of them were brave warriors, and they were commanders in his army. ²² Day after day men came to help David, until he had a great army, like the army of God.^[b]

Others Join David at Hebron

²³ These are the numbers of the men armed for battle who came to David at Hebron to turn Saul’s kingdom over to him, as the Lord had said:

²⁴ from Judah, carrying shield and spear—6,800 armed for battle;

²⁵ from Simeon, warriors ready for battle—7,100;

²⁶ from Levi—4,600, ²⁷ including Jehoiada, leader of the family of Aaron, with 3,700 men, ²⁸ and Zadok, a brave young warrior, with 22 officers from his family;

²⁹ from Benjamin, Saul’s tribe—3,000, most of whom had remained loyal to Saul’s house until then;

³⁰ from Ephraim, brave warriors, famous in their own clans—20,800;

³¹ from half the tribe of Manasseh, designated by name to come and make David king—18,000;

³² from Issachar, men who understood the times and knew what Israel should do—200 chiefs, with all their relatives under their command;

³³ from Zebulun, experienced soldiers prepared for battle with every type of weapon, to help David with undivided loyalty—50,000;

³⁴ from Naphtali—1,000 officers, together with 37,000 men carrying shields and spears;

³⁵ from Dan, ready for battle—28,600;

³⁶ from Asher, experienced soldiers prepared for battle—40,000;

³⁷ and from east of the Jordan, from Reuben, Gad and the half-tribe of Manasseh, armed with every type of weapon—120,000.

³⁸ All these were fighting men who volunteered to serve in the ranks. They came to Hebron fully determined to make David king over all Israel. All the rest of the Israelites were also of one mind to make David king. ³⁹ The men spent three days there with David, eating and drinking, for their families had supplied provisions for them. ⁴⁰ Also, their neighbors from as far away as Issachar, Zebulun and Naphtali came bringing food on donkeys, camels, mules and oxen. There were plentiful supplies of flour, fig cakes, raisin cakes, wine, olive oil, cattle and sheep, for there was joy in Israel.

Footnotes

1. 1 Chronicles 12:4 In Hebrew texts the second half of this verse (Jeremiah … Gederathite) is numbered 12:5, and 12:5-40 is numbered 12:6-41.
2. 1 Chronicles 12:22 Or a great and mighty army