Research

The itch that rashes

by reestheskin on 15/01/2020

Comments are disabled

My earliest conscious memory of disease and doctors was in the management of my atopic dermatitis. Here is Sam Shuster writing poetically about atopic dermatitis in ‘World Medicine’ in 1983.

A dozen years of agony; years of sleeplessness for child and parents, years of weeping, itching, scaling skin, the look and feel of which is detested.

The poverty of our treatments is made all the worse by the unfair raising of expectations: I don’t mean by obvious folk remedies; I mean medical folk remedies like the recent pseudoscientific dietary treatments which eliminate irrelevant allergens. There neither is nor ever was good evidence for a dietary mechanism. And as for cows’ milk, I would willingly drown its proponents in it. We have nothing fundamental for the misery of atopic eczema and that’s why I would like to see a real treatment—not one of those media breakthroughs, and not another of those hope raising nonsenses like breast-feeding: I mean a real and monstrously effective treatment. Not one of your P<.05 drugs the effect of which can only be seen if you keep your eyes firmly double-blind, I mean a straightforward here today and gone tomorrow job, an Aladdin’s salve—put it on and you have a new skin for old.

Nothing would please me more in the practice of clinical dermatology than never again to see a child tearing its skin to shreds and not knowing how long it will be before it all stops, if indeed it does.

Things are indeed better now, but not as much we need: we still don’t understand the itch nor can we easily block the neural pathways involved. Nor has anything replaced the untimely murder of ‘World Medicine’. A glass of milk has never looked the same since, either.

You don’t have to be mad to read this

by reestheskin on 13/01/2020

Comments are disabled

There is an interesting review in the Economist of the ‘Great Pretender: The Undercover Mission that Changed out Understanding of Madness,’ written by Susan Cahalan. The book is the story of the American psychologist David Rosenhan who “recruited seven volunteers to join him in feigning mental illness, to expose what he called the ‘undoubtedly counter-therapeutic’ culture of his country’s psychiatry”.

Rosenthal’s studies are well known and were influential, and some might argue that may have had have a beneficial effect on subsequent patient care. The question is whether they were true. The review states:

in the end Rosenham emerges as an unpalatable symptom of a wider academic malaise”.

As for the ‘malaise’, the reviewer goes on:

Many of psychology’s most famous experiments have recently been discredited or devalued, the author notes. Immense significance has been attached to Stanley Milgram’s shock tests and Philip Zimbardo’s Stanford prison experiment, yet later re-runs have failed to reproduce their findings. As Ms Cahalan laments, the feverish reports on the undermining of such theories are a gift to people who would like to discredit science itself.

I have a few disjointed thoughts on this. There are plenty of other considered critiques of the excesses of modern medical psychiatry. Anthony Clare’s ‘Psychiatry in Dissent’ was for me the best introduction to psychiatry. And Stuart Sutherland’s “Breakdown’ was a blistering and highly readable attack on medical (in)competence as much as the subject itself (Sutherland was a leading experimental psychologist, and his account is autobiographical). And might the cross-country diagnostic criteria studies not have happened without Rosenham’s work?

As for undermining science (see the quote above), I think unreliable medical science is widespread, and possibly there is more of it than in many past periods. Simple repetition of experiments is important but not sufficient, and betrays a lack of of understanding of why some science is so powerful.

Science owes its success to its social organisation: conjectures and refutations, to use Popper’s terms, within a community. Just repeating an experiment under identical conditions is not sufficient. Rather you need to use the results of one experiment to inform the next, and with the accumulation of new results, you need to build a larger and larger edifice which whilst having greater explanatory power is more and more intolerant of errors at any level. Building large structures out of Lego only works because of the precision engineering of each of the component bricks. But any errors only become apparent when you add brick-on-brick. When a single investigator or group of investigators have skin in the game during this process — and where experimentation is possible — science is at its strongest (the critiques can of course come from anywhere).

An alternative process is when the results of a series of experiments are so precise and robust that everyday life confirms them: the lights go on when I click the switch. This harks back to the reporting of science as ‘demonstrations’.

By these two standards much medical science may be unreliable. First, because the fragmentation of enquiry discourages the creation of broad explanatory theories or tests of the underlying hypotheses. The ‘testing’ is more whether a publishable unit can be achieved rather than nature understood. Second, in many RCTs or technology assessments there is little theoretical framework on which to challenge nature. Nor can everyday practice act as the necessary feedback loop in the way the tight temporal relationship between flipping the switch and seeing the light turn on can.

Knowing more than we can see

by reestheskin on 05/12/2019

Comments are disabled

I spent near on ten years thinking about automated skin cancer detection. There are various approaches you might use — cyborg human/machine hybrids were my personal favourite — but we settled on more standard machine learning approaches. Conceptually what you need is straightforward: data to learn from, and ways to lever the historical data to the future examples. The following quote is apposite.

One is that, for all the advances in machine learning, machines are still not very good at learning. Most humans need a few dozen hours to master driving. Waymo’s cars have had over 10m miles of practice, and still fall short. And once humans have learned to drive, even on the easy streets of Phoenix, they can, with a little effort, apply that knowledge anywhere, rapidly learning to adapt their skills to rush-hour Bangkok or a gravel-track in rural Greece.

Driverless cars are stuck in a jam – Autonomous vehicles

You see exactly the same thing with skin cancer. With a relatively small number of examples, you can train (human) novices to be much better than most doctors. By contrast, with the machines you need literally hundreds and thousands of examples. Even when you start with large databases, as you parse the diagnostic groups, you quickly find out that for many ‘types’ you have only a few examples to learn from. The rate limiting factor becomes acquiring mega-databases cheaply. The best way to do this is to change data acquisition from a ‘research task’ to a matter of grabbing data that was collected routinely for other purposes (there is a lot of money in digital waste — ask Google).

Noam Chomsky had a few statements germane to this and much else that gets in the way of such goals (1).

Plato’s problem: How can we know so much when the evidence is do slight.

Orwell’s problem: How do we remain so ignorant when the evidence is so overwhelming.

(1): Noam Chomsky: Ideas and Ideals, Cambridge University Press, (1999). Neil Smith.

Downward mobility for all!

by reestheskin on 02/12/2019

Comments are disabled

Obituaries are a source of much joy and enlightenment. None more so than those in the Economist. Last week’s was devoted to the ’60’s photographer Terry O’Neill (you can see some of his iconic images here.

Stars had been his subject since 1962, when he was sent to photograph a new band at the Abbey Road Studios. The older blokes at the Sketch scorned that kind of work, but the young were clearly on the rise, and he was by far the youngest photographer in Fleet Street at the time. At the studios, to get a better light, he took the group outside to snap them holding their guitars a bit defensively: John, Paul, George and Ringo. Next day’s Sketch was sold out, and he suddenly found himself with the run of London and all the coming bands, free to be as creative as he liked. A working-class kid from Romford whose prospects had been either the priesthood or a job in the Dagenham car plant, like his dad, had the world at his feet. He wouldn’t have had a prayer, he thought, in any other era.

And obviously it couldn’t last. In a couple of years he would find a proper job, as both the Beatles and the Stones told him they were going to. For it was hardly serious work to point your Leica at someone and go snap, snap.

Obituary: Terry O’Neill died on November 16th – Catching the moment

The reason I found this particularly interesting is the way social mobility appeared to work and the way it was tied to genuine innovation and social change. I have always loved the trope that when jobs are plentiful, and your committments minimal, you can literally tell the boss to FO on a Friday and start another job on the Monday. Best of all you can experiment and experiment lifts all. This to me is one of the best 1960’s rock n’ roll stories.

If you lift your head above the parapet in universities you come across various conventional wisdoms. One relates to ‘mental wellbeing’ or ‘mental issues’, and another is the value of education in increasing social mobility. My problem is that in both cases there seem (to me at least) many important questions that remain unanswered. For the former, are we talking about mental illness (as in disease) or something else? How robust is the data — aside from self-reporting? The widely reported comments from the former President of the Royal College of Pyschiatrists receive no answer (at last not in my institution). An example: I have sat in a meeting in which one justification for ‘lecture capture’ (recording of live lectures) was to assist students with ‘mental health issues’. But do they help in this context? Do we trust self-reflection in this area? Under what conditions do we think they help or harm?

Enhancing life chances and social mobility is yet another area that I find difficult. I picked up on a comment from Martin Wolf in the FT

We also believe that changing individual characteristics, principally via education, will increase social mobility. But this is largely untrue. We need to be far more honest.

He was referring to the work of John Goldthorpe in Oxford. Digging just a little beneath the surface made me realise that much of what I had believed may not true. Goldthorpe writes:

However, a significant change has occurred in that while earlier, in what has become known as the golden age of mobility, social ascent predominated over social descent, the experience of upward mobility is now becoming less common and that of downward mobility more common. In this sense, young people today face less favourable mobility prospects than did their parents or their grandparents.

This research indicates that the only recent change of note is that the rising rates of upward, absolute mobility of the middle decades of the last century have levelled out. Relative rates have remained more or less constant back to the interwar years. According to this alternative view, what can be achieved through education, whether in regard to absolute or relative mobility, appears limited.

[Jnl Soc. Pol. (2013), 42, 3, 431–450 Cambridge University Press 2013 doi:10.1017/S004727941300024X]

There is a witty exchange in Propect between the journalist (JD) and Goldthorpe (JG).

JD: Would you say that this is something that politicians, in particular, tend not to grasp?

JG: Yes. Tony Blair, for instance, was totally confused about this distinction [between absolute and relative rates of mobility]. He couldnʼt see that the only way you can have more upward mobility in a relative perspective is if you have more downward mobility at the same time. I remember being in a discussion in the Cabinet Office when Geoff Mulgan was one of Blairʼs leading advisors. It took a long time to get across to Mulgan the distinction between absolute and relative rates, but in the end he got it. His response was: “The Prime Minister canʼt go to the country on the promise of downward mobility!”

On both these topics I am conflicted. And on both these topics there are the tools that characterize scholarly inquiry to help guide action: this is what universities should be about. I am however left with a strong suspicion that few are interested in digging deep, rather we choose sound bites over understanding. Working in a university often feels like the university must be somewhere else. That is the optimistic version.

Not only God plays dice

There is an article this week in Nature about how some funders are explicitly funding grant proposals randomly (lotteries). The cynic might say they have been doing this for a longtime.

Dark matters.

by reestheskin on 21/11/2019

Comments are disabled

Frank Davidoff had a telling phrase about clinical expertise. He likened it to “Dark Matter”. Dark Matter makes up most of the universe, but we know very little about it. In the clinical arena I have spent a lot of time reading and thinking about ‘expertise’,  without developing any grand unifying themes of my own worth sharing. But we live in a world where ‘expertise’ in many domains is under assault, and I have no wise thoughts to pull together what is happening. I do however like (as ever) some nice phrases from Paul Graham. I can’t see any roadmap here just perspectives and shadows.

When experts are wrong, it’s often because they’re experts on an earlier version of the world.

any

Instead of trying to point yourself in the right direction, admit you have no idea what the right direction is, and try instead to be super sensitive to the winds of change.

How to Be an Expert in a Changing World

Medicine is just one technology

by reestheskin on 08/11/2019

Comments are disabled

From Wikipedia.

Putt’s Law: “Technology is dominated by two types of people, those who understand what they do not manage and those who manage what they do not understand.”

 

Putt’s Corollary: “Every technical hierarchy, in time, develops a competence inversion.” with incompetence being “flushed out of the lower levels” of a technocratic hierarchy, ensuring that technically competent people remain directly in charge of the actual technology while those without technical competence move into management.

Putt’s Law and the Successful Technocrat – Wikipedia

Strangers to ourselves (and student learning).

by reestheskin on 04/11/2019

Comments are disabled

The quote below is from a paper in PNAS on how students misjudge their learning and what strategies maximise learning. The findings are not surprising (IMHO) but will, I guess, continue to be overlooked (NSS anybody?). As I mention below, it is the general point that concerns me.

Measuring actual learning versus feeling of learning in response to being actively engaged in the classroom.

In this report, we identify an inherent student bias against active learning that can limit its effectiveness and may hinder the wide adoption of these methods. Compared with students in traditional lectures, students in active classes perceived that they learned less, while in reality they learned more. Students rated the quality of instruction in passive lectures more highly, and they expressed a preference to have “all of their physics classes taught this way,” even though their scores on independent tests of learning were lower than those in actively taught classrooms. These findings are consistent with the observations that novices in a subject are poor judges of their own competence (27⇓–29), and the cognitive fluency of lectures can be misleading (30, 31). Our findings also suggest that novice students may not accurately assess the changes in their own learning that follow from their experience in a class.

Measuring actual learning versus feeling of learning in response to being actively engaged in the classroom | PNAS

The authors go on:

These results also suggest that student evaluations of teaching should be used with caution as they rely on students’ perceptions of learning and could inadvertently favor inferior passive teaching methods over research-based active pedagogical approaches….

As I say above, it is the general rather than the particular that concerns me. Experience and feeling are often poor guides to action. We are, after all, creatures that represent biology’s attempt to see whether contemplation can triumph over reflex. There remains a fundamental asymmetry between expert and novice, and if there isn’t, there is little worth learning (or indeed worth paying for).

  • The title is from Timothy Wilson’s book, Strangers to Ourselves, a good place to start on this topic. However, this whole topic is of much more importance than just how we teach students. Lessons for medicine too.

The art of the insoluble

by reestheskin on 30/10/2019

Comments are disabled

The following is from an advert for a clinical academic in a surgical specialty, one with significant on call responsibilities. (It is not from Edinburgh).

‘you will be able to define, develop, and establish a high quality patient-centred research programme’

‘in addition to the above, you will be expected to raise substantial research income and deliver excellent research outputs’

Leaving aside the debasement of language, I simply cannot believe such jobs are viable long term. Many years ago, I was looked after by a surgical academic. A few years later he/she moved to another centre, and I was puzzled as to why he/she had made this career move. I queried a NHS surgeon in the same hospital about this career path. “Bad outcomes”, was the response. She/He needed a clean start somewhere else…

Traditional non-clinical academic careers include research, teaching and administration. Increasingly it is recognised that it is rarely possible to all three well. For clinical academics the situation is worse, as 50% of your time is supposed to be devoted to providing patient care. Over time the NHS workload has become more onerous in that consultants enjoy less support from junior doctors and NHS hospitals have become much less efficient.

All sorts of legitimate questions can be asked about the relation between expertise and how much of your time is devoted to that particular role. For craft specialities — and I would include dermatology, pathology, radiology in this category — there may be ways to stay competent. Subspecialisation is one approach (my choice) but even this may be inadequate. In many areas of medicine I simply do not believe it is possible to maintain acceptable clinical skills and be active in meaningful research.

Sam Shuster always drilled in to me that there were only two reasons academics should see patients: to teach on them, and to foster their research. Academics are not there to provide ‘service’. Some juniors recognise this issue but are reticent about speaking openly about it. But chase the footfall, or lack of it, into clinical academic careers.

A time for everything

by reestheskin on 22/10/2019

Comments are disabled

Terrific interview with Sydney Brenner about the second greatest scientific revolution of the 20th century.

I think it’s really hard to communicate that because I lived through the entire period from its very beginning, and it took on different forms as matters progressed. So it was, of course, wonderful. That’s what I tell students. The way to succeed is to get born at the right time and in the right place. If you can do that then you are bound to succeed. You have to be receptive and have some talent as well…

To have seen the development of a subject, which was looked upon with disdain by the establishment from the very start, actually become the basis of our whole approach to biology today. That is something that was worth living for.

This goes for more than science and stretches out into far more mundane aspects of life. Is there any alternative?

Kings Review

Of Reliability and validity

by reestheskin on 16/10/2019

Comments are disabled

One of the mantras of psychometrics 101 is that you cannot have validity without reliability. People expel this phrase, like others equilibrate after eating curry and nan-breads with too much gassy beer. In truth, the Platonic obsession with reliability diminishes validity. The world of science and much professional practice, remains messy, and vague until it is ‘done’. The search space for those diamonds of sense and order remains infinite.

Many years in the making, DSM-5 appeared in 2013, to a chorus of criticism; Harrington summarises this crisply (Gary Greenberg’s 2013 Book of Woe gives a painful blow-by-blow account). Harrington suggests that the proliferating symptom categories ceased to carry conviction; in the USA, the leadership of the US National Institutes of Health pivoted away from the DSM approach—“100% reliability 0% validity”, as Harrington writes—stating they would only fund projects with clearly defined biological hypotheses. The big players in the pharmaceutical industry folded their tents and withdrew from the field, turning to more tractable targets, notably cancer. For some mental health problems, psychological therapies, such as cognitive behaviour therapy (CBT), are becoming more popular, sometimes in combination with pharmacotherapy; as Harrington points out, even as far back as the 1970s, trials had shown that CBT outperformed imipramine as a treatment for depression.

Biological psychiatry’s decline and fall | Anne Harrington, Mind Fixers: Psychiatry’s Troubled Search for the Biology of Mental Illness, W W Norton (2019), p. 384, US$ 27·95, ISBN: 9780393071221 – ScienceDirect

Innovation theatre: because you are worth it.

by reestheskin on 03/10/2019

Comments are disabled

I used to use the phrase — with apologies to Freud — ‘eppendorf envy’ to describe the bias in much medical innovation whereby useful advance pretended it owed its magic to ‘basic’ science. Doctors wore white coats in order to sprinkle the laboratory magic on as a veneer. But I like this cognate term also: innovation theatre.

To be fair to the banks, they weren’t the first institutions to recognise the PR value of what Rich Turrin has dubbed innovation theatre. Many institutions before them had cottoned on to the fact that it was a way to score easy points with the public and investors. Think of high impact campaigns featuring “the science bit” for L’Oréal’s Elvive shampoo or Tefal appliance ads: “We have the technology because we have the brains”.

The financial sector has seen enough innovation theatre | Financial Times. The orignal reference is here.

Software is eating..

Comparison of the accuracy of human readers versus machine-learning algorithms for pigmented skin lesion classification: an open, web-based, international, diagnostic study.

You can dice the results in various ways, but software is indeed eating the world — and the clinic. The (slow) transition to this new world will be interesting and eventful. A good spectator sport for some of us. (Interesting to note that this study in Lancet Oncology received no specific funding. Hmmm).

Direct URL for this post.

What is science for: dangerous thoughts.

The quote below was from a piece in the Lancet by Richard Horton.

Reading [Bertrand]Russell today is a resonant experience. Existential fears surround us. Yet today seems a long way from the dream of Enlightenment. Modern science is a brutally competitive affair. It is driven by incentives to acquire money (research funding), priority (journal publication), and glory (prizes and honours). Science’s metrics of success embed these motivations deep in transnational scientific cultures. At The Lancet, while we resist the idea that Impact Factors measure our achievements, we are not naive enough to believe that authors do not judge us by those same numbers. It is hard not to capitulate to a narrow range of indicators that has come to define success and failure. Science, once a powerful force to overturn orthodoxy, has created its own orthodoxies that diminish the possibility of creative thought and experiment. At this moment of planetary jeopardy, perhaps it is time to rethink and restate the purpose of science.

Offline: What is science for? – The Lancet

I am just musing on this. We like to think that ‘freedom’ was necessary for a modern wealthy state. We are not so certain, now. We used to think that certain freedoms of expression underpinned the scientific revolution. We are having doubts about this, too. Maybe it is possible to have atom bombs and live in a cesspool of immorality. Oops…

Direct URL for this post.

Precision medicine and a den of robbers

I have removed the name of the institution only because so many queue to sell their vapourware in this manner

Precision Medicine is a revolution in healthcare. Our world-leading biomedical researchers are at the forefront of this revolution, developing new early diagnostics and treatments for chronic diseases including cancer, cardiovascular disease, diabetes, arthritis and stroke. Partnering with XXXXX, the University of XXXX has driven … vision in Precision Medicine, including the development of a shitload of infrastructure to support imaging, molecular pathology and precision medicine clinical trials……  XXXXXX is now one of the foremost locations in a three mile radius to pursue advances in Precision Medicine.

And He declared to them, “It is written: ‘My house will be called a house of prayer. But you are making it ‘a den of robbers.'” Matthew 21:13

Direct URL for this post.

The pleasures of tenure

Mr Sammallahti is not a recluse, nor lacking in ambition. He travels the world taking photographs; a book, “Here Far Away”, was published in 2012; another, of bird pictures, comes out later this year. But he shuns the art scene, believing that commercial pressures undermine quality. He does not lecture and rarely gives interviews. In 1991 he received an unprecedented 20-year grant from the Finnish government. Its sole condition was that he should concentrate on photography, so he gave up teaching. “I want to work in peace,” he explains, “to be free to fail.”

Economist

Direct URL for this post.

TEF or REF?

Smith was supported by earnings from his professorship at Glasgow, where a university teacher’s earnings depended on fees collected directly from students in the class. This contrasted with Oxford, where Smith had spent six unhappy years, and where, he observed, the dons had mostly given up even the pretence of teaching.

But Smith relinquished his professorship in 1763, and the writing of ‘Wealth…’ and the remainder of his career was financed by the Duke of Buccleuch, who as a young man employed Smith as a tutor.

Is there more to Adam Smith than free markets? | Financial Times

Direct URL for this post.

Blasts from the past

Digging deep into some of my old notes, I came across this obituary of John Ziman written by Jerry Ravetz. I know both through their written work and was lucky enough to meet and chat briefly with John Ziman not long before he died. Ziman’s book “Real Science” is for me the classic account of what has happened to science as it moved from a ‘way of life’ to a job.

Jerry Ravetz writes:

I first became aware of him through his 1960 radio talk Scientists – Gentlemen Or Players?, where he observed how a career in science was starting to change, from being a vocation to being a job.

There was a paradox running through his later career, to which he must have been sensitive. He was a “Renaissance man” in a way highly desirable for a scientist, but he did not exert the influence that he might have hoped to. This was due less to the passion he deployed in argument than the times in which he found himself. The age of such eminent scientist-savants as JBS Haldane, JD Bernal and Joseph Needham was passing, while a new generation of socially responsible scientists had yet to establish itself. Those who reminded scientists of their social responsibilities were viewed with suspicion; and those who had stopped doing research were treated as defectors.

Obituary: John Ziman | Education | The Guardian

Direct URL for this post.

“It appears to me, the doing what little one can to encrease [sic] the general stock of knowledge is as respectable an object of life as one can in any likelihood pursue.”

Darwin. Letter to his sisters from the Beagle. Quoted in the London Review of Books 23-May-2019, Rosemary Hill.

Direct URL for this post.

Where’s the next frontier?

In a 1963 letter to molecular biologist Max Perutz, he wrote, “It is now widely realized that nearly all the ‘classical’ problems of molecular biology have either been solved or will be solved in the next decade…The future of molecular biology lies in the extension of research to other fields of biology, notably development and the nervous system.”

Sydney observed, and predicted, the flow of science: “Progress depends on the interplay of techniques, discoveries, and ideas, probably in that order of decreasing importance,” he said.

Man, the toolmaker. In this particularly case, a very special one.

Sydney Brenner (1927–2019) | Science [Obit of Sydney Brenner]

Direct URL for this post.

WD (Bill) Hamilton

Scope for recognizing and accommodating exceptional individuals has been diminishing in British universities ever since. Hamilton published relatively few papers, in generally low status journals, and gained only a handful of grants much later in life. Bureaucratic measures of performance are increasingly important and judge the impact of an article only by the journal it is published in. This seriously undervalues radical originality, which although extremely rare is utterly vital to science. It is disturbing that a young Bill Hamilton today would probably find an academic career even more difficult to pursue.

Alan Grafen, in his obituary of Bill Hamilton (Biogr. Mems Fell. R. Soc. Lond. 50, 109–132 (2004)).

I post this excerpt following a discussion with somebody who had never heard of him. Hamilton’s enormous contributions to biology are not well known. You also have to wonder if the lack of a Nobel for biology diminishes medicine in the long run. Some things do indeed get worse.

Direct URL for this post.

Arrogance before men; humility before your subject.

by reestheskin on 29/04/2019

Comments are disabled

Sydney Brenner has died. Not quite the last of the handful of scientists who made one of the two scientific revolutions of the 20th century. The first half belonged to physics, the second to the biology that he co-created.

A precocious boy—a student at the University of the Witwatersrand by the time he was 15—and bullied for it, reading was his connection to the wider world. Courses, he said, never taught him anything. The way to learn was to get a book that told you how to do things, and then to start doing them, whether it was making dyes or, later in life, programming computers. If he thought more deeply than the other great biologists of his age, which he did, it was surely because he read further, too.

Reading Brenner was a staccato of insights. I hadn’t come across the ‘courses’ quote before, but no surprises there.

Obituary: Sydney Brenner died on April 5th – Irrepressible

What universities are about

by reestheskin on 08/04/2019

Comments are disabled

James Williams worked at Google in a senior role for ten years, but has moved into philosophy at Oxford (for the money obviously….). He has written a wonderful short book, with the title “Stand out of our Light”. The name comes from a humorous account of a meeting between Diogenes and Alexander the Great (no spoilers, here).

His book is a critique of much digital technology that — to use his analogy — does not act as an honest GPS, but instead entices you along paths that make your journay longer. All in the name of capturing your attention, such that you are deflected from your intentions.

He starts chapter 3, with something comical and at the same time profound.

When I told my mother I was moving to the other side of the planet to study technology ethics at a school that’s almost three times as old as my country, she asked, “Why would you go somewhere so old to study something so new? In a way the question contained its own answer.

For me that is the power of the academic ideal.

Science and nonscience

by reestheskin on 03/04/2019

Comments are disabled

I like statistics and spent most of my intercalated degree ‘using’ medical stats (essentially, writing programs on an IBM 360 mainframe to handle a large dataset, that I could then interrogate using the GLIM package from the NAG). Yes, the days of batch processing and punchcards. I found — and still find — statistics remarkably hard.

I am always very wary of people who say they understand statistics. Let me rephrase that. I am very suspicious of non-professional statisticians who claim that they find statistics intuitive. I remember that it was said that even the great Paul Erdos got the Monty Hall problem wrong.

The following is from a recent article in Nature:

What will retiring statistical significance look like? We hope that methods sections and data tabulation will be more detailed and nuanced. Authors will emphasize their estimates and the uncertainty in them — for example, by explicitly discussing the lower and upper limits of their intervals. They will not rely on significance tests. When P values are reported, they will be given with sensible precision (for example, P = 0.021 or P = 0.13) — without adornments such as stars or letters to denote statistical significance and not as binary inequalities (P  < 0.05 or P > 0.05). Decisions to interpret or to publish results will not be based on statistical thresholds. People will spend less time with statistical software, and more time thinking.

Scientists rise up against statistical significance

There is lots of blame to go around here. Bad teaching and bad supervision, are easy targets (too easy). I think there are (at least) three more fundamental problems.

  1. Mistaking a ‘statistical hypothesis’ for a scientific hypothesis, and falling into the trap of believing that statistical testing can operate as some sort of truth machine. This is the intellectual equivalent of imagining we can create a perpetual motion machine, or thinking of statistics as a branch of magic . The big offenders in medicine are those who like adding up other people’s ‘P’ values — the EBM merchants, keen to sell their NNT futures.
  2. The sociology of modern science and modern scientific careers. The Mertonian norms have been smashed. It is one of the counterintuitive aspects of science that whatever its precise domain of interest — from astronomy to botany — its success lies less with a set of formal rules than a set of institutional and social norms. Our hubris is to have imagined that whilst we cling to the fact that our faith in science relies on the ‘external test in reality’, we ignored how easy it is for the scientific enterprise to be subverted.
  3. This is really a component of the previous point (2). Although communication of results to others — with the goal of allowing them to build on your work — is key, the insolence of modern science policy has turned the ‘endgame’ of science into this communication measured as some ‘unit’ based on impact factor or ‘glossy’ journal brand. But there is more to it than this. The complexity of modern science often means that the those who produce the results of an experiment or observation are not in a position to build upon them. The publication is the end-unit of activity. So, some bench assay or result on animals might lead others to try and extend the work into the clinic. Or one trial might be repeated by others with little hard thought about what exactly any difference means.Contrast this with the foundational work performed by Brenner, Crick and others. Experiments were designed to test competing hypotheses, and were often short in duration — one or maybe two iterations might be performed in a day. Inaccuracy or mistakes were felt by the same investigator, with the goal being the creation of a large infrastructure of robust knowledge. Avoiding mistakes and being certain of your conclusions would allow you not to (subsequently) waste your own time. If you and your family are going to live in a house, you are careful where you lay the foundations. If you plan to build something, and then sell to make a fast buck, the incentives lie in a different place. Economists may be wrong about a lot of things — and should be silent on much more — but they are right about two important things: institutions and incentives matter. Period.

Science has been thought of as a form of ‘reliable knowledge’. This form of words always sounded almost too modest to me, especially when you think how powerful science has been shown to be. But in medicine we are increasingly aware that much modern science is not a basis for honest action at all. Blake’s words were to the effect that ‘every honest man is a prophet’. I once miswrote this in an article I wrote as ‘every honest man is for profit’. Many an error….

’Once you have a shiny building, decline follows’

by reestheskin on 03/01/2019

Comments are disabled

The quotes below are from an article in the FT (awhile back). They echo one of my rules, a rule that is more of the exception that proves the rule. Just as “no good lab has space” (because the bench space will always be taken up because many will want to work there), so when the grand new building arrives, the quality of work will already be past its peak (because how else would you have justified your future except by looking back). It is all about edge people, and just as social change usually starts at the edge, so do good ideas.

The principle of benign neglect may well operate on a larger scale. Consider Building 20, one of the most celebrated structures at Massachusetts Institute of Technology. The product of wartime urgency, it was designed one afternoon in the spring of 1943, then hurriedly assembled out of plywood, breeze-blocks and asbestos. Fire regulations were waived in exchange for a promise that it would be pulled down within six months of the war’s end; in fact the building endured, dusty and uncomfortable, until 1998.

During that time, it played host not only to the radar researchers of Rad Lab (nine of whom won Nobel Prizes) but one of the first atomic clocks, one of the first particle accelerators, and one of the first anechoic chambers — possibly the one in which composer John Cage conceived 4’33. Noam Chomsky revolutionised linguistics there. Harold Edgerton took his high-speed photographs of bullets hitting apples. The Bose Corporation emerged from Building 20; so did computing powerhouse DEC; so did the hacker movement, via the Tech Model Railroad Club.

Building 20 was a success because it was cheap, ugly and confusing. Researchers and departments with status would be placed in sparkling new buildings or grand old ones — places where people would protest if you nailed something to a door. In Building 20, all the grimy start-ups were thrown in to jostle each other, and they didn’t think twice about nailing something to a door — or, for that matter, for taking out a couple of floors, as Jerrold Zacharias did when installing the atomic clock.

Somewhat reminiscent of Stewart Brand’s ‘How Buildings Learn

[FT Link]

In climate science, you can check out of the lab anytime you like, but you can never leave.

How I stave off despair as a climate scientist.

Dave Reay, University of Edinburgh, quoted in Nature this week.

Statistical pitfalls of personalized medicine

by reestheskin on 14/12/2018

Comments are disabled

This is from an article by Stephen Senn in Nature. He keeps making this point — for the very good reason that people want to pretend there is no problem. But there is.

Personalized medicine aims to match individuals with the therapy that is best suited to them and their condition. Advocates proclaim the potential of this approach to improve treatment outcomes by pointing to statistics about how most drugs — for conditions ranging from arthritis to heartburn — do not work for most people. That might or might not be true, but the statistics are being misinterpreted. There is no reason to think that a drug that shows itself to be marginally effective in a general population is simply in want of an appropriate subpopulation in which it will perform spectacularly.

When you treat patients with chronic diseases such as psoriasis, it quickly becomes clear that there is considerable within person variation is response to treatments. We do not understand what this variation is due to. What we do know however, is that assuming variation in response between people at single time points may be misleading in that we have no measure of within person variance. This is only one of the problems. But hey, precision, personalised.. whatever: it shifts units (as Frank Zappa once said of Michael Jackson).

Red..well any hair colour, again.

by reestheskin on 11/12/2018

Comments are disabled

Genome-wide study of hair colour in UK Biobank explains most of the SNP heritability.

Michael D. Morgan, Erola Pairo-Castineira, Konrad Rawlik, Oriol Canela-Xandri, Jonathan Rees, David Sims, Albert Tenesa & Ian J. Jackson

[Link to Nature Comm paper]  https://doi.org/10.1038/s41467-018-07691-z

My guess is this is likely my last ‘research paper’ (although I now choose to redefine what counts as research). But not my last ‘thinking paper’. I cannot help but contrast the sheer volume of activity with that from our original papers on red hair. Things seemed so much simpler when we were young. But it is a nice coda to a career fugue.

Peanuts….I wish I had said that

by reestheskin on 28/11/2018

Comments are disabled

This is from an editorial in the NEJM, discussing the results of a trial of a synthetic peanut antigen to facilitate tolerance. Prevously the ‘raw’ stuff had been shown to be useful. The synethic version will of course cost a lot, and might be considered IPR created through regulatory arbitrage.

AR101 and other, similar products such as CA002, which is being developed by the Cambridge group, would therefore appear to have a role in initial dose escalation. The potential market for these products is believed to be billions of dollars. It is perhaps salutary to consider that in the study conducted by the Cambridge group, children underwent desensitization with a bag of peanut flour costing peanuts.

Costing penauts: I wish I had said that

Oral Desensitization to Peanuts | NEJM

The frenzy of metrics rolls on

by reestheskin on 27/11/2018

Comments are disabled

What are metrics good for? Reflections on REF and TEF from Dorothy Bishop