In one of Paul Graham’s essays, he writes about the relation between a thriving society and how parents behave (he does not use these terms). He argues that whilst it is natural for parents to seek advantage for their (own) children, in the interests of efficiency, society should try to to limit this tendency. I agree but the details matter.

In the LRB there is a review written by Adam Swift of a few books that deal with this topic. And for those who like to sell higher educationhigher education, the review makes uncomfortable reading.

Education, which promised to be the solvent that would lessen the class structure, has become an effective means of preserving it.

That used not to be obvious to me. Swift however pulls out a lovely quote that illuminates much of the smug complacency shown by some of the ‘educated classes’ and how they see the world. Many of our current political troubles have cognate origins.

Robin Cook’s memoir repeats a story told by a journalist to Roy Hattersley. Tony Blair, asked why he had sent his son Euan to the Oratory, despite the inevitable political flak, said: ‘Look at Harold Wilson’s children.’ The journalist demurred: one of Wilson’s sons had become a headmaster, the other a university professor. Blair replied that he certainly hoped his children would do better than that.

Adam Swift · What’s fair about that? Social Mobilities · LRB 13 January 2020

Alfred North Whitehead: “Some of the major disasters of mankind have been produced by the narrowness of men with a good methodology” (The Function of Reason).

Comments that seem germane to some of our current day covid-19 debates.

’Scuse Me While I Kiss the Sky | by A.J. Lees | The New York Review of Books

People are always demanding that medical students must learn this or that (obesity, psychiatry, dermatology, ID, eating disorders). The result is curriculum overload, a default in favour of rote learning by many students, and the inhibition of curiosity. It was not meant to be like this, but amongst others, the GMC, the NHS, and others have pushed a vision of university medical education that shortchanges both the students and medical practice over the long term. Short-termism rules. Instead of producing graduates who are ready to learn clinical medicine is an area of their choice, we expect them to somehow come out oven-ready at graduation. I do not believe it is possible to do this to a level of safety that many other professions demand, nor is this the primary job of a university. Sadly, universities have given up on arguing, intimidated by the government and their regulatory commissars, and nervous of losing their monopoly on producing doctors.

But I will make a plea that one area really does deserve more attention within a university : the history of how medical advance occurs. No, I do not mean MCQs asking for the date of birth of Robert Koch or Lord Lister, but a feel for the historical interplay of convention and novelty. Without this our students and our graduates are almost confined to living in the present, unaware of the past, and unable to doubt how different the future will be. Below is one example.

”In 1938 Albert Hofmann, a chemist at the Sandoz Laboratories in Basel, created a series of new compounds from lysergic acid. One of them, later marketed as Hydergine, showed great potential for the treatment of cerebral arteriosclerosis. Another salt, the diethylamide (LSD), he put to one side, but he had “a peculiar presentiment,” as he put it in his memoir LSD: My Problem Child (1980), “that this substance could possess properties other than those established in the first investigations.

In 1943 he prepared a fresh batch of LSD. In the final process of its crystallization, he started to experience strange sensations. He described his first inadvertent “trip” in a letter to his supervisor:

At home I lay down and sank into a not unpleasant, intoxicated-like condition, characterized by extremely stimulated imagination. In a dream-like state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors.

After eliminating chloroform fumes as a possible cause, he concluded that a tiny quantity of LSD absorbed through the skin of his fingertips must have been responsible. Three days later he began a program of unsanctioned research and deliberately ingested 250 micrograms of LSD at 4:20 PM. Forty minutes later, he wrote in his lab journal, “Beginning dizziness, feeling of anxiety, visual distortions, symptoms of paralysis, desire to laugh.” He set off home on his bicycle, accompanied by his laboratory assistant. This formal trial of what Hofmann considered a minute dose of LSD had more distressing effects than his first chance exposure:

Every exertion of my will, every attempt to put an end to the disintegration of the outer world and the dissolution of my ego, seemed to be wasted effort. A demon had invaded me, had taken possession of my body, mind, and soul. I jumped up and screamed, trying to free myself from him, but then sank down again and lay helpless on the sofa…. I was taken to another world, another place, another time.

A doctor was summoned but found nothing amiss apart from a marked dilation of his pupils. A fear of impending death gradually faded as the drug’s effect lessened, and after some hours Hofmann was seeing surreal colors and enjoying the play of shapes before his eyes.

Lees writes:

Many editors of learned medical journals now automatically turn down publications describing the sort of scientific investigation that Albert Hofmann carried out on himself. Institutional review boards are often scathing in their criticism of self-experimentation, despite its hallowed tradition in medicine, because they consider it subjective and biased. But the human desire to alter consciousness and enrich self-awareness shows no sign of receding, and someone must always go first. As long as care and diligence accompany the sort of personal research conducted by Pollan and Lin, it has the potential to be as revealing and informative as any work on psychedelic drugs conducted within the rigid confines of universities.

Richard Horton in the Lancet writes:

Imagine if the entire edifice of knowledge in medicine was built upon a falsehood. Systematic reviews are said to be the highest standard of evidence-based health care. Regularly updated to ensure that treatment decisions are built on the most up-to-date and reliable science, systematic reviews and meta-analyses are widely used to inform clinical guidelines and decision making. Powerful organisations have emerged to construct a knowledge base in medicine underpinned by the results of systematic reviews. One such organisation is Cochrane, with 11 000 members in over 130 countries. This extraordinary movement of people is justifiably passionate about the idea that it is contributing to better health outcomes for everyone, everywhere. The industry that drives the production of systematic reviews today is financed by some of the most influential agencies in medical research. Cochrane, for example, points to three funders providing over £1 million each—the UK’s National Institute for Health Research (NIHR), the US National Institutes of Health (NIH), and Australia’s National Health and Medical Research Council (NHMRC).

Well, it really is a bit late for all this soul searching. See my earlier post here ‘Mega-silliness’ (commenting on what others had already pointed out); or my Evidence Based Medicine: the Epistemology That Isn’t, written over 20 years ago;  and my contribution to the wake (even if I didn’t put my hand in my pocket), Why we should let “evidence-based medicine” rest in peace. The genesis of EBM was as a cult whose foundational myth was that P values could act as a true machine. Those followers who had originally hoped for a place in the promised afterlife, soon settled for paying the bills, and EBM morphed into a career opportunity for those who found accountancy too daring. So, pace John Mayall on Jazz Blues Fusion, don’t come here to listen to an old record. I promise.

Offline: The gravy train of systematic reviews – The Lancet

Things we share with China. reestheskin Blog https://t.co/dLzllM437p pic.twitter.com/df6gQD1x2c

— jonathan rees (@reestheskin) March 20, 2020

Dr Chris Day writes:

Two weeks ago, I swabbed my first positive Covid-19 patient during an A&E Locum shift. I must say back then, I hadn’t fully taken in what we as a country will have to face over the coming months. The reports from colleagues in Italy and China are beyond belief.

The UK has been left to fight Covid-19 with half the Intensive Care beds per capita of Italy. Back in 2014, the trigger for my whistleblowing case was my attempt to try and secure more ICU resources for South East London (see Private Eye).

Instead of spending 5 years and £700k fighting /smearing me and damaging whistleblowing law, the NHS could have just fixed the problem. There has never been a more important time for the public and the politicians to understand Intensive Care resourcing and what is decided on their behalf by NHS leaders.

Some links here and here

Michael Chabon writing in the NYRB:

The Film Worlds of Wes Anderson | by Michael Chabon | The New York Review of Books

The world is so big, so complicated, so replete with marvels and surprises that it takes years for most people to begin to notice that it is, also, irretrievably broken. We call this period of research “childhood.”

There follows a program of renewed inquiry, often involuntary, into the nature and effects of mortality, entropy, heartbreak, violence, failure, cowardice, duplicity, cruelty, and grief; the researcher learns their histories, and their bitter lessons, by heart. Along the way, he or she discovers that the world has been broken for as long as anyone can remember, and struggles to reconcile this fact with the ache of cosmic nostalgia that arises, from time to time, in the researcher’s heart: an intimation of vanished glory, of lost wholeness, a memory of the world unbroken. We call the moment at which this ache first arises “adolescence.” The feeling haunts people all their lives.

Everyone, sooner or later, gets a thorough schooling in brokenness. The question becomes: What to do with the pieces? Some people hunker down atop the local pile of ruins and make do, Bedouin tending their goats in the shade of shattered giants. Others set about breaking what remains of the world into bits ever smaller and more jagged, kicking through the rubble like kids running through piles of leaves. And some people, passing among the scattered pieces of that great overturned jigsaw puzzle, start to pick up a piece here, a piece there, with a vague yet irresistible notion that perhaps something might be done about putting the thing back together again.

Statistical significance and clinical evidence

Two letters in Lancet Oncology. This bloody story never ends. We have not invented truth machines: judgement has never been exiled from discovery.

Zombies.

I wish I had said that

In discussing some aspects of Higher Education, Dennis Tourish writes:

On all sides, it seems that long-term loyalty is an idea without a long-term future.

Stanley Cohen has died. A special place for those of us hooked on the ectoderm. Some nice comments about him in the Lancet from Geoff Watts.

A May, 1962, issue of the Journal of Biological Chemistry included a deceptively arcane study on the isolation of a protein that could accelerate incisor eruption and eyelid opening in newborn mice. The author, Stanley Cohen, later to become Professor Emeritus of Biochemistry at Vanderbilt University School of Medicine (VUSM) in Nashville, TN, USA, had named his protein “tooth-lid factor”. Cohen’s subsequent studies would not only lead him to rename the protein epidermal growth factor (EGF), but also mark him out as one of the founders of a new area of biology and eventually win him a Nobel Prize.

[says Lawrence Marnett], “When he came here he began studying some growth factors in animal cell extracts. One was of mouse submaxillary gland…It had peptides in it, and when he injected them into newborn mice their teeth broke though earlier than normal, and their eyelids opened sooner.” Cohen’s subsequent studies revealed that his extract worked by stimulating the growth of epidermal cells. Having consequently renamed the material EGF, he devoted the rest of his career to studying it. “He went on to identify the EGF receptor and define target cells that would respond to EGF”, recalls Graham Carpenter, Emeritus Professor of Biochemistry at VUSM, who joined Cohen’s lab in 1973 and worked with him on EGF as a postdoctoral fellow. The EGF receptor proved to be a useful target for drugs, and Cohen’s discoveries opened the door to research on diseases ranging from dementia to cancer. “He understood EGF’s biological importance”, says Carpenter. “But we did not have any idea that this would extend to cancer biology in a major way.”

And as for that most successful of all biology labs, the style of exploration  is familiar.

[Graham Carpenter] “In contrast to today, his research group was very small, seldom more than four people—himself, two technicians, and a postdoc…He was central to whatever was going on in the lab.” [Lawrence] Marnett also recalls that determination: “He was one of those guys that was just driven by his desire to understand how things work…It was a classic example of making an observation and then drilling down to try to understand it, not knowing what you’re going to find.” And at that time there was plenty to be found. Cohen, as Marnett puts it, was basically “mining gold”.