MIRI's 2015 Winter Fundraiser!
MIRI's Winter Fundraising Drive has begun! Our current progress, updated live:
Like our last fundraiser, this will be a non-matching fundraiser with multiple funding targets our donors can choose between to help shape MIRI’s trajectory. The drive will run until December 31st, and will help support MIRI's research efforts aimed at ensuring that smarter-than-human AI systems have a positive impact.
Less Wrong Study Hall: Now With 100% Less Tinychat
Eight months ago, I announced that the Less Wrong Study Hall, a virtual coworking space where people do pomodoros together, has moved to Complice. Complice is a software system I made to help people achieve their goals. About 20% of rationalists who've tried it have started using it full-time, which by my math gives signing up positive expected value. Anyway...
What follows is a brief history of the LWSH's development thus far. If you just wanna try it, click here: complice.co/room/lesswrong
By embedding the original tinychat window within a larger page, I let users see what the pomodoro timer was up to as soon as they joined, and the page also doesn't let breaks run overtime because the timer just keeps ticking. Also, users could now show a persistent status of what they're working on.
Attention! Financial scam targeting Less Wrong users
Recently, multiple suspicious user accounts were created on Less Wrong. These accounts don't post any content in the forum. Instead, they are used only to send private messages to the existing users.
Many users have received a copy of the same message, but different variants exist, too. Here are the examples I know about. If you have received a different variant, please post it in a comment below this article:
Hi good day. My boss is interested on donating to MIRI's project and he is wondering if he could send money through you and you donate to miri through your company and thus accelertaing the value created. He wants to use "match donations" as a way of donating thats why he is looking for people in companies like you. I want to discuss more about this so if you could see this message please give me a reply. Thank you!
I don't know yet about anyone who replied and got scammed, so this is all based on indirect evidence. If you got scammed, please tell me. If you are ashamed, I can publish your story anonymously. Your story could help other potential victims.
Most likely, the scheme is the following:
- The scammer will send you money.
- Then they will ask some of the money back because they changed their mind, or they mistakenly sent you more than they wanted, or their financial situation suddenly changed, or whatever.
- After receiving the money from you, they will flag the original transaction as a fraud, so they get back the money they originally sent you, plus the money you sent them back. Then they disappear, or it will turn out they used a stolen identity, etc.
(Thanks to
If you replied to the original message and now you are already in the middle of the process, please inform your bank as soon as possible! Even if the step 2 didn't happen yet, so you can still get out without losing money, warning your bank about the scammer could help other potential victims.
Warning: If you have already received a check or a payment confirmation, and someone is asking you to send the overpayment back quickly, do not send anything. The check or the payment confirmation is fake, and the goal is to make you send money before you find out. (Thanks to
A Medical Mystery: Thyroid Hormones, Chronic Fatigue and Fibromyalgia
Summary:
- Chronic Fatigue and Fibromyalgia look very like Hypothyroidism.
- Thyroid Patients aren't happy with either the diagnosis or treatment of Hypothyroidism.
- It is possible that lots of FMS/CFS cases are 'something wrong with the thyroid system that doesn't show up on laboratory hormone level tests'.
- It's possible that it's not too difficult to fix these CFS/FMS cases with thyroid hormones.
- I believe that there may have been a stupendous cock-up that's hurt millions.
- Less Wrong should be interested, because it could be a real example of how bad inference can cause the sciences to come to false conclusions, as well as a good practice problem for the things we really care about.
Edit:
I found a possible answer here:
http://lesswrong.com/lw/nbm/thyroid_hormones_chronic_fatigue_and_fibromyalgia/
I do not believe it, because I do not understand it, but contemplation of it seems to be enlightening. In particular, the problem is much broader than I originally thought.
A summary of the argument in the first two posts, together with links to lots of evidence in the literature:
http://lesswrong.com/r/discussion/lw/nef/the_thyroid_madness_core_argument_evidence/
And this is pretty much proof, I think:
http://lesswrong.com/lw/nhs/the_thyroid_madness_two_apparently_contradictory/
At this point, I think I'm as confident as I can be without some sort of formal trial (so 25% maybe?)
But certainly, if you're suffering from Chronic Fatigue Syndrome/Fibromyalgia/Major Depression/Irritable Bowel Syndrome, or any of the many similar disorders which just seem to be different names for 'hypothyroidism with normal TSH', I reckon this is worth trying!
I have done, and it worked for me. For about four months now...
Original Post:
I believe that I've come across a genuine puzzle, and I wonder if you can help me solve it. This problem is complicated, and subtle, and has confounded and defeated good people for forty years. And yet there are huge and obvious clues. No-one seems to have conducted the simple experiments which the clues suggest, even though many clever people have thought hard about it, and the answer to the problem would be very valuable. And so I wonder what it is that I am missing.
I am going to tell a story which rather extravagantly privileges a hypothesis that I have concocted from many different sources, but a large part of it is from the work of the late Doctor John C Lowe, an American chiropractor who claimed that he could cure Fibromyalgia.
I myself am drowning in confirmation bias to the point where I doubt my own sanity. Every time I look for evidence to disconfirm my hypothesis, I find only new reasons to believe. But I am utterly unqualified to judge. Three months ago I didn't know what an amino acid was. And so I appeal to wiser heads for help.
Crocker's Rules on this. I suspect that I am being the most spectacular fool, but I can't see why, and I'd like to know.
Setting the Scene
Chronic Fatigue Syndrome, Myalgic Encephalitis, and Fibromyalgia are 'new diseases'. There is considerable dispute as to whether they even exist, and if so how to diagnose them. They all seem to have a large number of possible symptoms, and in any given case, these symptoms may or may not occur with varying severity.
As far as I can tell, if someone claims that they're 'Tired All The Time', then a competent doctor will first of all check that they're getting enough sleep and are not unduly stressed, then rule out all of the known diseases that cause fatigue (there are a very lot!), and finally diagnose one of the three 'by exclusion', which means that there doesn't appear to be anything wrong, except that you're ill.
If widespread pain is one of the symptoms, it's Fibromyalgia Syndrome (FMS). If there's no pain, then it's CFS or ME. These may or may not be the same thing, but Myalgic Encephalitis is preferred by patients because it's greek and so sounds like a disease. Unfortunately Myalgic Encephalitis means 'hurty muscles brain inflammation', and if one had hurty muscles, it would be Fibromyalgia, and if one had brain inflammation, it would be something else entirely.
Despite the widespread belief that these are 'somatoform' diseases (all in the mind), the severity of them ranges from relatively mild (tired all the time, can't think straight), to devastating (wheelchair bound, can't leave the house, can't open one eye because the pain is too great).
All three seem to have come spontaneously into existence in the 1970s, and yet searches for the responsible infective agent have proved fruitless. Neither have palliative measures been discovered, apart from the tried and true method of telling the sufferers that it's all in their heads.
The only treatments that have proved effective are Cognitive Behavioural Therapy / Graded Exercise. A Cochrane Review reckoned that they do around 15% over placebo in producing a measurable alleviation of symptoms. I'm not very impressed. CBT/GE sound a lot like 'sports coaching', and I'm pretty sure that if we thought of 'Not Being Very Good at Rowing' as a somatoform disorder, then I could produce an improvement over placebo in a measurable outcome in ten percent of my victims without too much trouble.
But any book on CFS will tell you that the disease was well known to the Victorians, under the name of neurasthenia. The hypothesis that God lifted the curse of neurasthenia from the people of the Earth as a reward for their courage during the wars of the early twentieth century, while well supported by the clinical evidence, has a low prior probability.
We face therefore something of a mystery, and in the traditional manner of my people, a mystery requires a Just-So Story:
How It Was In The Beginning
In the dark days of Victoria, the brilliant physician William Miller Ord noticed large numbers of mainly female patients suffering from late-onset cretinism.
These patients, exhausted, tired, stupid, sad, cold, fat and emotional, declined steeply, and invariably died.
As any man of decent curiosity would, Dr Ord cut their corpses apart, and in the midst of the carnage noticed that the thyroid, a small butterfly-shaped gland in the throat, was wasted and shrunken.
One imagines that he may have thought to himself: "What has killed them may cure them."
After a few false starts and a brilliant shot in the dark by the brave George Redmayne Murray, Dr Ord secured a supply of animal thyroid glands (cheaply available at any butcher, sautée with nutmeg and basil) and fed them to his remaining patients, who were presumably by this time too weak to resist.
They recovered miraculously, and completely.
I'm not sure why Dr Ord isn't better known, since this appears to have been the first time in recorded history that something a doctor did had a positive effect.
Dr Ord's syndrome was named Ord's Thyroiditis, and it is now known to be an autoimmune disease where the patient's own antibodies attack and destroy the thyroid gland. In Ord's thyroiditis, there is no goiter.
A similar disease, where the thyroid swells to form a disfiguring deformity of the neck (goiter), was described by Hakaru Hashimoto in 1912 (who rather charmingly published in German), and as part of the war reparations of 1946 it was decided to confuse the two diseases under the single name of Hashimoto's Thyroiditis. Apart from the goiter, both conditions share a characteristic set of symptoms, and were easily treated with animal thyroid gland, with no complications.
Many years before, in 1835, a fourth physician, Robert James Graves, had described a different syndrome, now known as Graves' Disease, which has as its characteristic symptoms irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhoea, and weight loss. Unfortunately Dr Graves could not think how to cure his eponymous horror, and so the disease is still named after him.
The Horror Spreads
Victorian medicine being what it was, we can assume that animal glands were sprayed over and into any wealthy person unwise enough to be remotely ill in the vicinity of a doctor. I seem to remember a number of jokes about "monkey glands" in PG Wodehouse, and indeed a man might be tempted to assume that chimpanzee parts would be a good substitute for humans. Supply issues seem to have limited monkey glands to a few millionaires worried about impotence, and it may be that the corresponding procedure inflicted on their wives has come down to us as Hormone Replacement Therapy.
Certainly anyone looking a bit cold, tired, fat, stupid, sad or emotional is going to have been eating thyroids. We can assume that in a certain number of cases, this was just the thing, and I think it may also be safe to assume that a fair number of people who had nothing wrong with them at all died as a result of treatment, although the fact that animal thyroid is still part of the human food chain suggests it can't be that dangerous.
I mean seriously, these people use high pressure hoses to recover the last scraps of meat from the floors of slaughterhouses, they're not going to carefully remove all the nasty gristly throat-bits before they make ready meals, are they?
The Armour Sausage company, owner of extensive meat-packing facilities in Chicago, Illinois, and thus in possession of a large number of pig thyroids which, if not quite surplus to requirements, at the very least faced a market sluggish to non-existent as foodstuffs, brilliantly decided to sell them in freeze-dried form as a cure for whatever ails you.
Some Sort of Sanity Emerges, in a Decade not Noted for its Sanity
Around the time of the second world war, doctors became interested in whether their treatments actually helped, and an effort was made to determine what was going on with thyroids and the constellation of sadness that I will henceforth call 'hypometabolism', which is the set of symptoms associated with Ord's thyroiditis. Jumping the gun a little, I shall also define 'hypermetabolism' as the set of symptoms associated with Graves' disease.
The thyroid gland appeared to be some sort of metabolic regulator, in some ways analogous to a thermostat. In hypometabolism, every system of the body is running slow, and so it produces a vast range of bad effects, affecting almost every organ. Different sufferers can have very different symptoms, and so diagnosis is very difficult.
Dr Broda Barnes decided that the key symptom of hypometabolism was a low core body temperature. By careful experiment he established that in patients with no symptoms of hypometabolism the average temperature of the armpit on waking was 98 degrees Fahrenheit (or 36.6 Celsius). He believed that temperature variation of +/- 0.2 degrees Fahrenheit was unusual enough to merit diagnosis. He also seems to have believed, in the manner of the proverbial man with a hammer, that all human ailments without exception were caused by hypometabolism, and to have given freeze-dried thyroid to almost everyone he came into contact with, to see if it helped. A true scientist. Doctor Barnes became convinced that fully 40% of the population of America suffered from hypometabolism, and recommended Armour's Freeze Dried Pig Thyroid to cure America's ills.
In a brilliant stroke, Freeze Dried Pig's Thyroid was renamed 'Natural Desiccated Thyroid', which almost sounds like the sort of thing you might take in sound mind. I love marketing. It's so clever.
America being infested with religious lunatics, and Chicago being infested with nasty useless gristly bits of cow's throat, led almost inevitably to a second form of 'Natural Desiccated Thyroid' on the market.
Dr Barnes' hypometabolism test never seems to have caught on. There are several ways your temperature can go outside his 'normal' range, including fever (too hot), starvation (too cold), alcohol (too hot), sleeping under too many duvets (too hot), sleeping under too few duvets (too cold). Also mercury thermometers are a complete pain in the neck, and take ten minutes to get a sensible reading, which is a long time to lie around in bed carefully doing nothing so that you don't inadvertently raise your body temperature. To make the situation even worse, while men's temperature is reasonably constant, the body temperature of healthy young women goes up and down like the Assyrian Empire.
Several other tests were proposed. One of the most interesting is the speed of the Achilles Tendon Reflex, which is apparently super-fast in hypermetabolism, and either weirdly slow or has a freaky pause in it if you're running a bit cold. Drawbacks of this test include 'It's completely subjective, give me something with numbers in it', and 'I don't seem to have one, where am I supposed to tap the hammer-thing again?'.
By this time, neurasthenia was no longer a thing. In the same way that spiritualism was no longer a thing, and the British Empire was no longer a thing.
As far as we know, Chronic Fatigue Syndrome was not a thing either, and neither was Fibromyalgia (which is just Chronic Fatigue Syndrome but it hurts), nor Myalgic Encephalitis. There was something called 'Myalgic Neurasthenia' in 1934, but it seems to have been a painful infectious disease and they thought it was polio.
Finally, Science
It turned out that the purpose of the thyroid gland is to make hormones which control the metabolism. It takes in the amino acid tyrosine, and it takes in iodine. It releases Thyroglobulin, mono-iodo-tyrosine (MIT), di-iodo-tyrosine (DIT), thyroxine (T4) and triiodothyronine (T3) into the blood. The chemistry is interesting but too complicated to explain in a just-so story.
I believe that we currently think that thyroglobulin, MIT and DIT are simply by-products of the process that makes T3 and T4.
T3 is the hormone. It seems to control the rate of metabolism in all cells. T4 has something of the same effect, but is much less active, and called a 'prohormone'. Its main purpose seems to be to be deiodinated to make more T3. This happens outside the thyroid gland, in the other parts of the body ('peripheral conversion'). I believe mainly in the liver, but to some extent in all cells.
Our forefathers knew about thyroxine (T4, or thyronine-with-four-iodines-attached), and triiodothyronine (T3, or thyronine-with-three-iodines-attached)
It seems to me that just from the names, thyroxine was the first one to be discovered. But I'm not sure about that. You try finding a history-of-endocrinology website. At any rate they seem to have known about T4 and T3 fairly early on.
The mystery of Graves', Ord's and Hashimoto's thyroid diseases was explained.
Ord's and Hashimoto's are diseases where the thryoid gland under-produces (hypothyroidism). The metabolism of all cells slows down. As might be expected, this causes a huge number of effects, which seem to manifest differently in different sufferers.
Graves' disease is caused by the thyroid gland over-producing (hyperthyroidism). The metabolism of all cells speeds up. Again, there are a lot of possible symptoms.
All three are thought to be autoimmune diseases. Some people think that they may be different manifestations of the same disease. They are all fairly common.
Desiccated thryoid cures hypothyroidism because the ground-up thyroids contain T4 and T3, as well as lots of thyroglobulin, MIT and DIT, and they are absorbed by the stomach. They get into the blood and speed up the metabolism of all cells. By titrating the dose carefully you can restore roughly the correct levels of the thyroid hormones in all tissues, and the patient gets better. (Titration is where you change something carefully until you get it right)
The theory has considerable explanatory power. It explains cretinism, which is caused either by a genetic disease, or by iodine deficiency in childhood. If you grow up in an iodine deficient area, then your growth is stunted, your brain doesn't develop properly, and your thyroid gland may become hugely enlarged. Presumably because the brain is desperately trying to get it to produce more thyroid hormones, and it responds by swelling.
Once upon a time, this swelling (goitre) was called 'Derbyshire Neck'. I grew up near Derbyshire, and I remember an old rhyme: "Derbyshire born, Derbyshire bred, strong in the arm, and weak in the head". I always thought it was just an insult. Maybe not. Cretinism was also popular in the Alps, and there is a story of an English traveller in Switzerland of whom it was remarked that he would have been quite handsome if only he had had a goitre. So it must have been very common there.
But at this point I am *extremely suspicious*. The thyroid/metabolic regulation system is ancient (universal in vertebrates, I believe), crucial to life, and it really shouldn't just go wrong. We should suspect either an infectious cause, or a recent environmental influence which we haven't had time to adjust to, an evolved defence against an infectious disease, or just possibly, a recently evolved but as yet imperfect defence against a less recent environmental change.
(Cretinism in particular is very strange. Presumably animals in iodine-deficient areas aren't cretinous, and yet they should be. Perhaps a change to a farming from a hunter-gatherer lifestyle has increased our dependency on iodine from crops, which crops have sucked what little iodine occurs naturally out of the soil?)
It's also not entirely clear to me what the thyroid system is *for*. If there's just a particular rate that cells are supposed to run at, then why do they need a control signal to tell them that? I could believe that it was a literal thermostat, designed to keep the body temperature constant at the best speed for the various biological reactions, but it's universal in *vertebrates*. There are plenty of vertebrates which don't keep a constant temperature.
The Fall of Desiccated Thyroid
There turned out to be some problems with Natural Desiccated Thyroid (NDT).
Firstly, there were many competing brands and types, and even if you stuck to one brand the quality control wasn't great, so the dose you'd be taking would have been a bit variable.
Secondly, it's fucking pig's thyroid from an abattoir. It could have all sorts of nasty things in it. Also, ick.
Thirdly, it turned out that pigs made quite a lot more T3 in their thyroids than humans do. It also seems that T3 is better absorbed by the gut than T4 is, so someone taking NDT to compensate for their own underproduction will have too much of the active hormone compared to the prohormone. That may not be good news.
With the discovery of 'peripheral conversion', and the possibility of cheap clean synthesis, it was decided that modern scientific thyroid treatment would henceforth be by synthetic T4 (thyroxine) alone. The body would make its own T3 from the T4 supply.
Alarm bells should be ringing at this point. Apart from the above points, I'm not aware of any great reason for the switch from NDT to thyroxine in the treatment of hypothyroidism, but it seems to have been pretty much universal, and it seems to have worked.
Aware of the lack of T3, doctors compensated by giving people more T4 than was in their pig-thyroid doses. And there don't seem to have been any complaints.
Over the years, NDT seems to have become a crazy fringe treatment despite there not being any evidence against it. It's still a legal prescription drug, but in America it's only prescribed by eccentrics. In England a doctor prescribing it would be, at the very least, summoned to explain himself before the GMC.
However, since it was (a) sold over the counter for so many years, and (b) part of the food chain, it is still perfectly legal to sell as a food supplement in both countries, as long as you don't make any medical claims for it. And the internet being what it is, the prescription-only synthetic hormones T3 and T4 are easily obtained without a prescription. These are extremely powerful hormones which have an effect on metabolism. If 'body-builders' and sports cheats aren't consuming all three in vast quantities, I am a Dutchman.
The Clinical Diagnosis of Hypothyroidism
We pass now to the beginning of the 1970s.
Hypothyroidism is ferociously difficult to diagnose. People complain of 'Tired All The Time' well, ... all the time, and it has literally hundreds of causes.
And it must be diagnosed correctly! If you miss a case of hypothyroidism, your patient is likely to collapse and possibly die at some point in the medium-term future. If you diagnose hypothyroidism where it isn't, you'll start giving the poor bugger powerful hormones which he doesn't need and *cause* hypermetabolism.
The last word in 'diagnosis by symptoms' was the absolutely excellent paper:
Statistical Methods Applied To The Diagnosis Of Hypothyroidism
by W. Z. Billewicz, R. S. Chapman, J. Crooks, M. E. Day, J. Gossage, Sir Edward Wayne, and J. A. Young
Connoisseurs will note the clever and careful application of 'machine learning' techniques, before there were machines to learn!
One important thing to note is that this is a way of separating hypothyroid cases from other cases of tiredness at the point where people have been referred by their GP to a specialist at a hospital on suspicion of hypothyroidism. That changes the statistics remarkably. This is *not* a way of diagnosing hypothyroidism in the general population. But if someone's been to their GP (general practitioner, the doctor that a British person likely makes first contact with) and their GP has suspected their thryoid function might be inadequate, this test should probably still work.
For instance, they consider Physical Tiredness, Mental Lethargy, Slow Cerebration, Dry Hair, and Muscle Pain, the classic symptoms of hypothyroidism, present in most cases, to be indications *against* the disease.
That's because if you didn't have these things, you likely wouldn't have got that far. So in the population they're seeing (of people whose doctor suspects they might be hypothyroid), they're not of great value either way, but their presence is likely the reason why the person's GP has referred them even though they've really got iron-deficiency anaemia or one of the other causes of fatigue.
In their population, the strongest indicators are 'Ankle Jerk' and 'Slow Movements', subtle hypothyroid symptoms which aren't likely to be present in people who are fatigued for other reasons.
But this absolutely isn't a test you should use for population screening! In the general population, the classic symptoms are strong indicators of hypothyroidism.
Probability Theory is weird, huh?
Luckily, there were lab tests for hypothyroidism too, but they were expensive, complicated, annoying and difficult to interpret. Billewicz et al used them to calibrate their test, and recommend them for the difficult cases where their test doesn't give a clear answer.
And of course, the final test is to give them thyroid treatment and see whether they get better. If you're not sure, go slow, watch very carefully and look for hyper symptoms.
Overconfidence is definitely the way to go. If you don't diagnose it and it is, that's catastrophe. If it isn't, but you diagnose it anyway, then as long as you're paying attention the hyper symptoms are easy enough to spot, and you can pull back with little harm done.
A Better Way
It should be obvious from the above that the diagnosis of hypothyroidism by symptoms is absolutely fraught with complexity, and very easy to get wrong, and if you get it wrong the bad way, it's a disaster. Doctors were absolutely screaming for a decisive way to test for hypothyroidism.
Unfortunately, testing directly for the levels of thyroid hormones is very difficult, and the tests of the 1960s weren't accurate enough to be used for diagnosis.
The answer came from an understanding of how the thyroid regulatory system works, and the development of an accurate blood test for a crucial signalling hormone.
Three structures control the level of thyroid hormones in the blood.
The thyroid gland produces the hormones and secretes them into the blood.
Its activity is controlled by the hormone thyrotropin, or Thyroid Signalling Hormone (TSH). Lots of TSH works the thyroid hard. In the absence of TSH the thyroid relaxes but doesn't switch off entirely. However the basal level of thyroid activity in the absence of TSH is far too low.
TSH is controlled by the pituitary gland, a tiny structure attached to the brain.
The pituitary itself is controlled, via Thyroid Releasing Hormone (TRH), by the hypothalamus, which is part of the brain.
This was thought to be a classic example of a feedback control system.
hypothalamus->pituitary->thyroid
It turns out that the level of thyrotropin TSH in the blood is exquisitely sensitive to the levels of thyroid hormones in the blood.
Administer thyroid hormone to a patient and their TSH level will rapidly adjust downwards by an easily detectable amount.
So:
In hypothyroidism, where the thyroid has failed, the body will be desperately trying to produce more thyroid hormones, and the TSH level will be extremely high.
In Graves' Disease, this theory says, where the thyroid has grown too large, and the metabolism is running damagingly fast, the body will be, like a central bank trying to stimulate growth in a deflationary economy by reducing interest rates, 'pushing on a piece of string'. TSH will be undetectable.
The original TSH test was developed in 1965, by the startlingly clever method of radio-immuno-assay.
[For reasons that aren't clear to me, rather than being expressed in grams/litre, or mols/litre, the TSH test is expressed in 'international units/liter'. But I don't think that that's important]
A small number of people in whom there was no suspicion of thyroid disease were assessed, and the 'normal range' of TSH was calculated.
Again, 'endocrinology history' resources are not easy to find, but the first test was not terribly sensitive, and I think originally hyperthyroidism was thought to result in a complete absence of TSH, and that the highest value considered normal was about 4 (milli-international-units/liter).
This apparently pretty much solved the problem of diagnosing thyroid disorders.
Forgetfulness
It's no longer necessary to diagnose hypo- and hyper-thyroidism by symptoms. It was error prone anyway, and the question is easily decided by a cheap and simple test.
Natural Desiccated Thyroid is one with Nineveh and Tyre.
No doctor trained since the 1980s knows much about hypothyroid symptoms.
Medical textbooks mention them only in passing, as an unweighted list of classic symptoms. You couldn't use that for diagnosis of this famously difficult disease.
If you suspect hypothyroidism, you order a TSH test. If the value of TSH is very low, that's hyperthyroidism. If the value is very high then that's hypothyroidism. Otherwise you're 'euthyroid' (greek again, good-thyroid), and your symptoms are caused by some other problem.
The treatment for hyperthyroidism is to damage the thyroid gland. There are various ways. This often results in hypothyroidism. *For reasons that are not terribly well understood*.
The treatment for hypothyroidism is to give the patient sufficient thyroxine (T4) to cause TSH levels to come back into their normal range.
The conditions hyperthyroidism and hypothyroidism are now *defined* by TSH levels.
Hypothyroidism, in particular, a fairly common disease, is considered to be such a solved problem that it's usually treated by the GP, without involving any kind of specialist.
Present Day
It was found that the traditional amount of thyroxine (T4) administered to cure hypothyroid patients, was in fact too high. The amount of T4 that had always been used to replace the hormones that had once been produced by a thyroid gland now dead, destroyed, or surgically removed appeared now to be too much. That amount causes suppression of TSH to below its normal range. The brain, theory says, is asking for the level to be reduced.
The amount of T4 administered in such cases (there are many) has been reduced by a factor of around two, to the level where it produces 'normal' TSH levels in the blood. Treatment is now titrated to produce the normal levels of TSH.
TSH tests have improved enormously since their introduction, and are on their third or fourth generation. The accuracy of measurement is very good indeed.
It's now possible to detect the tiny remaining levels of TSH in overtly hyperthyroid patients, so hyperthyroidism is also now defined by the TSH test.
In England, the normal range is 0.35 to 5.5. This is considered to be the definition of 'euthyroidism'. If your levels are normal, you're fine.
If you have hypothyroid symptoms but a normal TSH level, then your symptoms are caused by something else. Look for Anaemia, look for Lyme Disease. There are hundreds of other possible causes. Once you rule out all the other causes, then it's the mysterious CFS/FMS/ME, for which there is no cause and no treatment.
If your doctor is very good, very careful and very paranoid, he might order tests of the levels of T4 and T3 directly. But actually the direct T4 and T3 tests, although much more accurate than they were in the 1960s, are quite badly standardised, and there's considerable controversy about what they actually measure. Different assay techniques can produce quite different readings. They're expensive. It's fairly common, and on the face of it perfectly reasonable, for a lab to refuse to conduct the T3 and T4 tests if the TSH level is normal.
It's been discovered that quite small increases in TSH actually predict hypothyroidism. Minute changes in thyroid hormone levels, which don't produce symptoms, cause detectable changes in the TSH levels. Normal, but slightly high values of TSH, especially in combination with the presence of thyroid related antibodies (there are several types), indicate a slight risk of one day developing hypothyroidism.
There's quite a lot of controversy about what the normal range for TSH actually is. Many doctors consider that the optimal range is 1-2, and target that range when administering thyroxine. Many think that just getting the value in the normal range is good enough. None of this is properly understood, to understate the case rather dramatically.
There are new categories, 'sub-clinical hypothyroidism' and 'sub-clinical hyperthyroidism', which are defined by abnormal TSH tests in the absence of symptoms. There is considerable controversy over whether it is a good idea to treat these, in order to prevent subtle hormonal imbalances which may cause difficult-to-detect long term problems.
Everyone is a little concerned about accidentally over-treating people, (remember that hyperthyroidism is now defined by TSH<0.35).
Hyperthyroidism has long been associated with Atrial Fibrillation (a heart problem), and Osteoporosis, both very nasty things. A large population study in Denmark recently revealed that there is a greater incidence of Atrial Fibrillation in sub-clinical hyperthyroidism, and that hypothyroidism actually has a 'protective effect' against Atrial Fibrillation.
It's known that TSH has a circadian rhythm, higher in the early morning, lower at night. This makes the test rather noisy, as your TSH level can be doubled or halved depending on what time of day you have the blood drawn.
But the big problems of the 1960s and 1970s are completely solved. We are just tidying up the details.
Doubt
Many hypothyroid patients complain that they suffer from 'Tired All The Time', and have some of the classic hypothyroid symptoms, even though their TSH levels have been carefully adjusted to be in the normal range.
I've no idea how many, but opinions range from 'the great majority of patients are perfectly happy' to 'around half of hypothyroid sufferers have hypothyroid symptoms even though they're being treated'.
The internet is black with people complaining about it, and there are many books and alternative medicine practitioners trying to cure them, or possibly trying to extract as much money as possible from people in desperate need of relief from an unpleasant, debilitating and inexplicable malaise.
THE PLURAL OF ANECDOTE IS DATA.
Not good data, to be sure. But if ten people mention to you in passing that the sun is shining, you are a damned fool if you think you know nothing about the weather.
It's known that TSH ranges aren't 'normally distributed' (in the sense of Gauss/the bell curve distribution) in the healthy population.
If you log-transform them, they do look a bit more normal.
The American Academy of Clinical Biochemists, in 2003, decided to settle the question once and for all. They carefully screened out anyone with even the slightest sign that there might be anything wrong with their thyroid at all, and measured their TSH very accurately.
In their report, they said (this is a direct quote):
In the future, it is likely that the upper limit of the serum TSH euthyroid reference range will be reduced to 2.5 mIU/L because >95% of rigorously screened normal euthyroid volunteers have serum TSH values between 0.4 and 2.5 mIU/L.
Many other studies disagree, and propose wider ranges for normal TSH.
But if the AACB report were taken seriously, it would lead to diagnosis of hypothyroidism in vast numbers of people who are perfectly healthy! In fact the levels of noise in the test would put people whose thyroid systems are perfectly normal in danger of being diagnosed and inappropriately treated.
For fairly obvious reasons, biochemists have been extremely, and quite properly, reluctant to take the report of their own professional body seriously. And yet it is hard to see where the AACB have gone wrong in their report.
Neurasthenia is back.
A little after the time of the introduction of the TSH test, new forms of 'Tired All The Time' were discovered.
As I said, CFS and ME are just two names for the same thing. Fibromyalgia Syndrome (FMS) is much worse, since it is CFS with constant pain, for which there is no known cause and from which there is no relief. Most drugs make it worse.
But if you combine the three things (CFS/ME/FMS), then you get a single disease, which has a large number of very non-specific symptoms.
These symptoms are the classic symptoms of 'hypometabolism'. Any doctor who has a patient who has CFS/ME/FMS and hasn't tested their thyroid function is *de facto* incompetent. I think the vast majority of medical people would agree with this statement.
And yet, when you test the TSH levels in CFS/ME/FMS sufferers, they are perfectly normal.
All three/two/one are appalling, crippling, terrible syndromes which ruin people's lives. They are fairly common. You almost certainly know one or two sufferers. The suffering is made worse by the fact that most people believe that they're psychosomatic, which is a polite word for 'imaginary'.
And the people suffering are mainly middle-aged women. Middle-aged women are easy to ignore. Especially stupid middle-aged women who are worried about being overweight and obviously faking their symptoms in order to get drugs which are popularly believed to induce weight loss. It's clearly their hormones. Or they're trying to scrounge up welfare benefits. Or they're trying to claim insurance. Even though there's nothing wrong with them and you've checked so carefully for everything that it could possibly be.
But it's not all middle aged women. These diseases affect men, and the young. Sometimes they affect little children. Exhaustion, stupidity, constant pain. Endless other problems as your body rots away. Lifelong. No remission and no cure.
And I have Doubts of my Own
And I can't believe that careful, numerate Billewicz and his co-authors would have made this mistake, but I can't find where the doctors of the 1970s checked for the sensitivity of the TSH test.
Specificity, yes. They tested a lot of people who hadn't got any sign of hypothyroidism for TSH levels. If you're well, then your TSH level will be in a narrow range, which may be 0-6, or it may be 1-2. Opinions are weirdly divided on this point in a hard to explain way.
But Sensitivity? Where's the bit where they checked for the other arm of the conditional?
The bit where they show that no-one who's suffering from hypometabolism, and who gets well when you give them Desiccated Thyroid, had, on first contact, TSH levels outside the normal range.
If you're trying to prove A <=> B, you can't just prove A => B and call it a day. You couldn't get that past an A-level maths student. And certainly anyone with a science degree wouldn't make that error. Surely? I mean you shouldn't be able to get that past anyone who can reason their way out of a paper bag.
I'm going to say this a third time, because I think it's important and maybe it's not obvious to everyone.
If you're trying to prove that two things are the same thing, then proving that the first one is always the second one is not good enough.
IF YOU KNOW THAT THE KING OF FRANCE IS ALWAYS FRENCH, YOU DO *NOT* KNOW THAT ANYONE WHO IS FRENCH IS KING OF FRANCE.
It's possible, of course, that I've missed this bit. As I say, 'History of Endocrinology' is not one of those popular, fashionable subjects that you can easily find out about.
I wonder if they just assumed that the thyroid system was a thermostat. The analogy is still common today.
But it doesn't look like a thermostat to me. The thyroid system with its vast numbers of hormones and transforming enzymes is insanely, incomprehensibly complicated. And very poorly understood. And evolutionarily ancient. It looks as though originally it was the system that coordinated metamorphosis. Or maybe it signalled when resources were high enough to undergo metamorphosis. But whatever it did originally in our most ancient ancestors, it looks as though the blind watchmaker has layered hack after hack after hack on top of it on the way to us.
Only the thyroid originally, controlling major changes in body plan in tiny creatures that metamorphose.
Of course, humans metamorphose too, but it's all in the womb, and who measures thyroid levels in the unborn when they still look like tiny fish?
And of course, humans undergo very rapid growth and change after we are born. Especially in the brain. Baby horses can walk seconds after they're born. Baby humans take months to learn to crawl. I wonder if that's got anything to do with cretinism.
And I'm told that baby humans have very high hormone levels. I wonder why they need to be so hot? If it's a thermostat, I mean.
But then on top of the thyroid, the pituitary. I wonder what that adds to the system? If the thyroid's just a thermostat, or just a device for keeping T4 levels constant, why can't it just do the sensing itself?
What evolutionary process created the pituitary control over the thyroid? Is that the thermostat bit?
And then the hypothalamus, controlling the pituitary. Why? Why would the brain need to set the temperature when the ideal temperature of metabolic reactions is always 37C in every animal? That's the temperature everything's designed for. Why would you dial it up or down, to a place where the chemical reactions that you are don't work properly?
I can think of reasons why. Perhaps you're hibernating. Many of our ancestors must have hibernated. Maybe it's a good idea to slow the metabolism sometimes. Perhaps to conserve your fat supplies. Your stored food.
Perhaps it's a good idea to slow the metabolism in times of famine?
Perhaps the whole calories in/calories out thing is wrong, and people whose energy expenditure goes over their calorie intake have slow metabolisms, slowly sacrificing every bodily function including immune defence in order to avoid starvation.
I wonder at the willpower that could keep an animal sane in that state. While its body does everything it can to keep its precious fat reserves high so that it can get through the famine.
And then I remember about Anorexia Nervosa, where young women who want to lose weight starve themselves to the point where they no longer feel hungry at all. Another mysterious psychological disease that's just put down to crazy females. We really need some female doctors.
And I remember about Seth Robert's Shangri-La Diet, that I tried, to see if it worked, some years ago, just because it was so weird, where by eating strange things, like tasteless oil and raw sugar, you can make your appetite disappear, and lose weight. It seemed to work pretty well, to my surprise. Seth came up with it while thinking about rats. And apparently it works on rats too. I wonder why it hasn't caught on.
It seems, my female friends tell me, that a lot of diets work well for a bit, but then after a few weeks the effect just stops. If we think of a particular diet as a meme, this would seem to be its infectious period, where the host enthusiastically spreads the idea.
And I wonder about the role of the thyronine de-iodinating enzymes, and the whole fantastically complicated process of stripping the iodines and the amino acid bits from thyroxine in various patterns that no-one understands, and what could be going on there if the thyroid system were just a simple thermostat.
And I wonder about reports I am reading where elite athletes are finding themselves suffering from hypothyroidism in numbers far too large to be credible, if it wasn't, say, a physical response to calorie intake less than calorie output.
I've been looking ever so hard to find out why the TSH test, or any of the various available thyroid blood tests are a good way to assess the function of this fantastically complicated and very poorly understood system.
But every time I look, I just come up with more reasons to believe that they don't tell you very much at all.
The Mystery
Can anyone convince me that the converse arm has been carefully checked?
That everyone who's suffering from hypometabolism, and who gets well when you give them Desiccated Thyroid, has, before you fix them, TSH levels outside the normal range.
In other words, that we haven't just thrown, though carelessness, a long standing, perfectly safe, well tested treatment, for a horrible disabling disease that often causes excruciating pain, that the Victorians knew how to cure, and that the people of the 1950s and 60s routinely cured, away.
Celebrating All Who Are in Effective Altruism
Elitism and Effective Altruism
Many criticize Effective Altruists as elitist. While this criticism is vastly overblown, unfortunately, it does have some basis, not only from the outside looking in but also within the movement itself, including some explicitly arguing for elitism.
Within many EA circles, there are status games and competition around doing “as much as we can,” and in many cases, even judging and shaming, usually implicit and unintended but no less real, of those whom we might term softcore EAs. These are people who identify as EAs and donate money and time to effective charities, but otherwise lead regular lives, as opposed to devoting the brunt of their resources to advance human flourishing as do hardcore EAs. To be clear, there is no definitive and hard distinction between softcore and hardcore EAs, but this is a useful heuristic to employ, as long as we keep in mind that softcore and hardcore are more like poles on a spectrum rather than binary categories.
We should help softcore EAs feel proud of what they do, and beware implying that being softcore EA is somehow deficient or simply the start of an inevitable path to being a hardcore EA. This sort of mentality has caused people I know to feel guilty and ashamed, and led to some leaving the EA movement. Remember that we all suffer from survivorship bias based on seeing those who remained, and not those who left - I specifically talked to people who left, and tried to get their takes on why they did so.
I suggest we aim to respect people wherever they are on the softcore/hardcore EA spectrum. I propose that, from a consequentialist perspective, negative attitudes toward softcore EAs are counterproductive for doing the most good for the world.
Why We Need Softcore EAs
Even if the individual contributions of softcore EAs are much less than the contributions of individual hardcore EAs, it’s irrational and anti-consequentialist to fail to acknowledge and celebrate the contributions of softcore EAs, and yet that is the status quo for the EA movement. As in any movement, the majority of EAs are not deeply committed activists, but are normal people for whom EA is a valuable but not primary identity category.
All of us were softcore EAs once - if you are a hardcore EA now, envision yourself back in those shoes. How would you have liked to have been treated? Acknowledged and celebrated or pushed to do more and more and more? How many softcore EAs around us are suffering right now due to the pressure of expectations to ratchet up their contributions?
I get it. I myself am driven by powerful emotional urges to reduce human suffering and increase human flourishing. Besides my full-time job as a professor, which takes about ~40 hours per week, I’ve been working ~50-70 hours per week for the last year and a half as the leader of an EA and rationality-themed meta-charity. As all people do, when I don’t pay attention, I fall unthinkingly into the mind projection fallacy, assuming other people think like I do and have my values, as well as my capacity for productivity and impact. I have a knee-jerk pattern as part of my emotional self to identify with and give social status to fellow hardcore EAs, and consider us an in-group, above softcore EAs.
These are natural human tendencies, but destructive ones. From a consequentialist perspective, it weakens our movement and undermines our capacity to build a better world and decrease suffering for current and future humans and other species.
More softcore EAs are vital for the movement itself to succeed. Softcore EAs can help fill talent gaps and donating to effective direct-action charities, having a strong positive impact on the outside world. Within the movement, they support the hardcore EAs emotionally through giving them a sense of belonging, safety, security, and encouragement, which are key for motivation and mental and physical health. Softcore EAs also donate to and volunteer for EA-themed meta-charities, as well as providing advice and feedback, and serving as evangelists of the movement.
Moreover, softcore EAs remind hardcore EAs of the importance of self-care and taking time off for themselves. This is something we hardcore EAs must not ignore! I’m speaking from personal experience here.
Fermi Estimates of Hardcore and Softcore Contributions
If we add up the amount of resources contributed to the movement by softcore EAs, they will likely add up to substantially more than the resources contributed by hardcore EAs. For instance, the large majority of those who took the Giving What We Can and The Life You Can Save pledges are softcore EAs, and so are all the new entrants to the EA movement, by definition.
To attach some numbers to this claim, let’s do a Fermi Estimate that uses some educated guesses to get at the actual resources each group contributes. Say that for every 100 EAs, there are 5 hardcore EAs and 95 softcore EAs. We can describe softcore EAs as contributing anywhere from 1 to 10 percent of their resources to EA causes (this is the range from The Life You Can Save pledge to the Giving What We Can pledge), so let’s guesstimate around 5 percent. Hardcore EAs we can say give an average of 50% of their resources to the movement. Using the handy Guesstimate app, here is a link to a model that shows softcore EAs contribute 480 resources, and hardcore EAs contribute 250 resources per 100 EAs. Now, these are educated guesses, and you can use the model I put together to put in your own numbers for the number of hardcore and softcore EAs per 100 EAs, and also the percent of their resources contributed. In any case, you will find that softcore EAs contribute a substantial amount of resources.
We should also compare the giving of softcore EAs to the giving of members of the general public to get a better grasp on the benefits provided to improving the world by softcore EAs. Let’s say a typical member of the general public contributes 3.5% of her resources to charitable causes, by comparison to 5% for softcore EAs. Being generous, we can estimate that the giving of non-EAs is 100 times less effective than that of EAs. Thus, using the same handy app, here is a link to a model that demonstrates the impact of giving by a typical member of the general public, 3.5, vs. the impact of giving by a softcore EA, 500. Now, the impact of giving by a hardcore EA is going to be higher, of course, 5000 as opposed to 500, but again, we have to remember that there are many more softcore EAs who give resources. You’re welcome to plug in your own numbers to get estimates if you think my suggested figures don’t match your intuitions. Regardless, you can see the high-impact nature of how a typical softcore EA compares to a typical member of the general public.
Effective Altruism, Mental Health, and Burnout: A Personal Account
About two years ago, in February 2014, my wife and I co-founded our meta-charity. In the summer of that year, she suffered a nervous breakdown due to burnout over running the organization. I had to - or to be accurate, chose to - take over both of our roles in managing the nonprofit, assuming the full burden of leadership.
In the Fall of 2014, I myself started to develop a mental disorder from the strain of doing both my professor job and running the organization, while also taking care of my wife. It started with heightened anxiety, which I did not recognize as something abnormal at the time - after all, with the love of my life recovering very slowly from a nervous breakdown and me running the organization, anxiety seemed natural. I was flinching away from my problem, not willing to recognize it and pretending it was fine, until some volunteers at the meta-charity I run – most of them softcore EAs – pointed it out to me.
I started to pay more attention to this, especially as I began to experience fatigue spells and panic attacks. With the encouragement of these volunteers, who essentially pushed me to get professional help, I began to see a therapist and take medication, which I continue to do to this day. I scaled back on the time I put into the nonprofit, from 70 hours per week on average to 50 hours per week. Well, to be honest, I occasionally put in more than 50, as I’m very emotionally motivated to help the world, but I try to restrain myself. The softcore volunteers at the meta-charity I run know about my workaholism and the danger of burnout for me, and remind me to take care of myself. I also need to remind myself constantly that doing good for the world is a marathon and not a sprint, and that in the long run, I will do much more good by taking it easy on myself.
Celebrating Everyone
As a consequentialist, my analysis, along with my personal experience, convince me that the accomplishments of softcore EAs should be celebrated as well as those of hardcore EAs.
So what can we do? We should publicly showcase the importance of softcore EAs. For example, we can encourage publications of articles that give softcore EAs the recognition they deserve, as well as those who give a large portion of their earnings and time to charity. We can invite a softcore EA to speak about her/his experiences at the 2016 EA Global. We can publish interviews with softcore EAs. Now, I’m not suggesting we should make most speakers softcore EAs, or write most articles, or conduct most interviews with softcore EAs. Overall, my take is that it’s appropriate to celebrate individual EAs proportional to their labors, and as the numbers above show, hardcore EAs individually contribute quite a bit more than softcore EAs. Yet we as a movement need to go against the current norm of not celebrating softcore EAs, and these are just some specific steps that would help us achieve this goal.
Let’s celebrate all who engage in Effective Altruism. Everyone contributes in their own way. Everyone makes the world a better place.
Acknowledgments: For their feedback on draft versions of this post, I want to thank Linch (Linchuan) Zhang, Hunter Glenn, Denis Drescher, Kathy Forth, Scott Weathers, Jay Quigley, Chris Waterguy (Watkins), Ozzie Gooen, Will Kiely, and Jo Duyvestyn. I bear sole responsibility for any oversights and errors remaining in the post, of course.
A different version of this, without the Fermi estimates, was cross-posted on the EA Forum.
EDIT: added link to post explicitly arguing for EA elitism
Recent updates to gwern.net (2014-2015)
“Receive my instruction, and not silver; and knowledge rather than choice gold. / For wisdom is better than rubies; and all the things that may be desired are not to be compared to it.”
Sorted by topic:
Darknet market related:
- Darknet Market archives, 2011-2015: 1.5tb of mirrors of scores of Tor-Bitcoin black-markets & forums 2013-2015, and other material; this is the single largest public archive of all DNM materials, and creating it was a major focus of mine since December 2013. The release also marks the end of my career as DNM expert - I’ve lost interest in the topic due to the apparent stability of the DNMs & being trapped in a local equilibrium
- DNM arrests compilation: a census of all known arrests Jan 2011-June 2015
- “Silk Goxed: How DPR used MtGox for hedging & lost big”
- there was an ICE subpoena on my Reddit account
Statistics & decision theory:
- When Does The Mail Come? A subjective Bayesian decision-theoretic analysis of local mail delivery times
resortertool for statistically re-ranking a set of ratings- analysis of Effective Altruists’ donations as reported in the LW survey
- anthology on how “everything is correlated”
- electric vs stove kettle boiling-time analysis: collected some simple data on my kettles & demonstrated some statistics tools on the dataset like a Bayesian measurement-error model
- dysgenics power analysis: how much genetic data would it take to falsify those claims?
- noisy polls: modeling potentially falsified poll data
- Value of Information for suicide (example cost-benefit analysis of weakly predicting suicide)
- Air conditioner upgrade cost-benefit analysis
- probability/gerontology problem: can one visit 566 centenarians before any die? No.
- do causal networks explain why correlation≠causation is so often true?
- a little example of estimating scores from censored data
QS related:
- 2015 modafinil community survey (not quite finished)
- Bitter Melon experimental & cost-benefit analysis
- Redshift self-experiment: screen-reddening software shifts bedtime forward by 20 minutes
- magnesium citrate experiment finished: initial benefits but apparent cumulative overdose led to net negative effect and mixed effects on sleep
- playing with inferring Bayesian networks for my Zeo & body weight data (powerful generalization of SEMs, but requires a lot of data before networks stabilize)
- Nootropics: initial results on LLLT correlated with large increases; but the followup randomized experiment showed zero effect
- LLLT re-analysis: no change in sleep as hypothesized by another LLLT user
- analysis of sceaduwe’s spirulina/allergies self-experiment (no reduction in allergies)
- Noopept experiment (no benefits)
- Treadmill spaced repetition experiment: expanded analysis to cover treadmill’s impact on successive reviews with SEM (no additional damage to recall beyond that implied by the original damage)
- lithium orotate experiment finished: no effects positive or negative
-
sleep correlations:
- alcohol: no harm
- optimal bedtime: a little earlier than usual
- optimal wakeup time: a little earlier than usual
Tech:
- “Effective Use of arbtt”: My window tracker/time-logger of choice is arbtt which records X window info for later classification and analysis; but one of the challenges is you don’t know how to set up arbtt or improve your environment or write classifications rules. So I wrote a tutorial.
- Time-lock crypto: wrote a Bash implementation of serial hashing time-lock crypto, link to all known implementations of hash time-lock crypto; discuss recent major theoretical breakthroughs involving Bitcoin
Debunking:
- Bicycle face
- “Rail travel at high speed is not possible because passengers, unable to breathe, would die of asphyxia.”
- did Fifty Shades of Gray have only 4k readers as the original Twilight fanfiction?
gwern.net-related:
- switched to Patreon for donations
- continued sending out my newsletter; up to 24 issues now
- rewrote
gwern.netCSS to be mobile-friendly; should now be readable in an iPhone 6 browser - optimized website loading (removed Custom Search Engine, A/B testing, non-validating XML, outbound link-tracking; simplified Disqus; minified JS, and fully async/deferred JS loading)
-
A/B testing:
- proposal towards recurrent neural network for reinforcement learning of CSS
- metadata test: indicates moving it from the sidebar to the top of page works as well
- indentation test: no real result, defaulted to 2em
- floating footnotes test: verified no apparent harm (as hoped)
- paragraph indentation test (responding to anonymous complaint; they were wrong)
Bay Area Solstice 2015

The winter solstice marks the darkest day of the year, a time to reflect on the past, present, and future. For several years and in many cities, Rationalists, Humanists, and Transhumanists have celebrated the solstice as a community, forming bonds to aid our work in the world.
Last year, more than one hundred people in the Bay Area came together to celebrate the Solstice. This year, we will carry on the tradition. Join us for an evening of song and story in the candlelight as we follow the triumphs and hardships of humanity.
The event itself is a community performance. There will be approximately two hours of songs and speeches, and a chance to eat and talk before and after. Death will be discussed. The themes are typically Humanist and Transhumanist, with a general audience that tends to be those who have found this site interesting, or care a lot about making our future better. There will be mild social pressure to sing along to songs.
When: December 12 at 7:00 PM - 9:00 PM
Where: Humanist Hall, 390 27th St, Oakland, CA 94612
Get tickets here. Bitcoin donation address: 1ARz9HYD45Midz9uRCA99YxDVnsuYAVPDk
Feel free to message me if you'd like to talk about the direction the Solstice is taking, things you like, or things you didn't like. Also, please let me know if you'd like to volunteer.
MIRI's 2016 Fundraiser
Our 2016 fundraiser is underway! Unlike in past years, we'll only be running one fundraiser in 2016, from Sep. 16 to Oct. 31. Our progress so far (updated live):
Employer matching and pledges to give later this year also count towards the total. Click here to learn more.
MIRI is a nonprofit research group based in Berkeley, California. We do foundational research in mathematics and computer science that’s aimed at ensuring that smarter-than-human AI systems have a positive impact on the world. 2016 has been a big year for MIRI, and for the wider field of AI alignment research. Our 2016 strategic update in early August reviewed a number of recent developments:
- A group of researchers headed by Chris Olah of Google Brain and Dario Amodei of OpenAI published “Concrete problems in AI safety,” a new set of research directions that are likely to bear both on near-term and long-term safety issues.
- Dylan Hadfield-Menell, Anca Dragan, Pieter Abbeel, and Stuart Russell published a new value learning framework, “Cooperative inverse reinforcement learning,” with implications for corrigibility.
- Laurent Orseau of Google DeepMind and Stuart Armstrong of the Future of Humanity Institute received positive attention from news outlets and from Alphabet executive chairman Eric Schmidt for their new paper “Safely interruptible agents,” partly supported by MIRI.
- MIRI ran a three-week AI safety and robustness colloquium and workshop series, with speakers including Stuart Russell, Tom Dietterich, Francesca Rossi, and Bart Selman.
- We received a generous $300,000 donation and expanded our research and ops teams.
- We started work on a new research agenda, “Alignment for advanced machine learning systems.” This agenda will be occupying about half of our time going forward, with the other half focusing on our agent foundations agenda.
We also published new results in decision theory and logical uncertainty, including “Parametric bounded Löb’s theorem and robust cooperation of bounded agents” and “A formal solution to the grain of truth problem.” For a survey of our research progress and other updates from last year, see our 2015 review. In the last three weeks, there have been three more major developments:
- We released a new paper, “Logical induction,” describing a method for learning to assign reasonable probabilities to mathematical conjectures and computational facts in a way that outpaces deduction.
- The Open Philanthropy Project awarded MIRI a one-year $500,000 grant to scale up our research program, with a strong chance of renewal next year.
- The Open Philanthropy Project is supporting the launch of the new UC Berkeley Center for Human-Compatible AI, headed by Stuart Russell.
Things have been moving fast over the last nine months. If we can replicate last year’s fundraising successes, we’ll be in an excellent position to move forward on our plans to grow our team and scale our research activities.
The strategic landscape
Humans are far better than other species at altering our environment to suit our preferences. This is primarily due not to our strength or speed, but to our intelligence, broadly construed -- our ability to reason, plan, accumulate scientific knowledge, and invent new technologies. AI is a technology that appears likely to have a uniquely large impact on the world because it has the potential to automate these abilities, and to eventually decisively surpass humans on the relevant cognitive metrics. Separate from the task of building intelligent computer systems is the task of ensuring that these systems are aligned with our values. Aligning an AI system requires surmounting a number of serious technical challenges, most of which have received relatively little scholarly attention to date. MIRI's role as a nonprofit in this space, from our perspective, is to help solve parts of the problem that are a poor fit for mainstream industry and academic groups. Our long-term plans are contingent on future developments in the field of AI. Because these developments are highly uncertain, we currently focus mostly on work that we expect to be useful in a wide variety of possible scenarios. The more optimistic scenarios we consider often look something like this:
- In the short term, a research community coalesces, develops a good in-principle understanding of what the relevant problems are, and produces formal tools for tackling these problems. AI researchers move toward a minimal consensus about best practices, normalizing discussions of AI’s long-term social impact, a risk-conscious security mindset, and work on error tolerance and value specification.
- In the medium term, researchers build on these foundations and develop a more mature understanding. As we move toward a clearer sense of what smarter-than-human AI systems are likely to look like — something closer to a credible roadmap — we imagine the research community moving toward increased coordination and cooperation in order to discourage race dynamics.
- In the long term, we would like to see AI-empowered projects (as described by Dewey [2015]) used to avert major AI mishaps. For this purpose, we’d want to solve a weak version of the alignment problem for limited AI systems — systems just capable enough to serve as useful levers for preventing AI accidents and misuse.
- In the very long term, we can hope to solve the “full” alignment problem for highly capable, highly autonomous AI systems. Ideally, we want to reach a position where we can afford to wait until we reach scientific and institutional maturity -- take our time to dot every i and cross every t before we risk "locking in" design choices.
The above is a vague sketch, and we prioritize research we think would be useful in less optimistic scenarios as well. Additionally, “short term” and “long term” here are relative, and different timeline forecasts can have very different policy implications. Still, the sketch may help clarify the directions we’d like to see the research community move in. For more on our research focus and methodology, see our research page and MIRI’s Approach.
Our organizational plans
We currently employ seven technical research staff (six research fellows and one assistant research fellow), plus two researchers signed on to join in the coming months and an additional six research associates and research interns.1 Our budget this year is about $1.75M, up from $1.65M in 2015 and $950k in 2014.2 Our eventual goal (subject to revision) is to grow until we have between 13 and 17 technical research staff, at which point our budget would likely be in the $3–4M range. If we reach that point successfully while maintaining a two-year runway, we’re likely to shift out of growth mode. Our budget estimate for 2017 is roughly $2–2.2M, which means that we’re entering this fundraiser with about 14 months’ runway. We’re uncertain about how many donations we'll receive between November and next September,3 but projecting from current trends, we expect about 4/5ths of our total donations to come from the fundraiser and 1/5th to come in off-fundraiser.4 Based on this, we have the following fundraiser goals:
Basic target - $750,000. We feel good about our ability to execute our growth plans at this funding level. We’ll be able to move forward comfortably, albeit with somewhat more caution than at the higher targets.
Growth target - $1,000,000. This would amount to about half a year’s runway. At this level, we can afford to make more uncertain but high-expected-value bets in our growth plans. There’s a risk that we’ll dip below a year’s runway in 2017 if we make more hires than expected, but the growing support of our donor base would make us feel comfortable about taking such risks.
Stretch target - $1,250,000. At this level, even if we exceed my growth expectations, we’d be able to grow without real risk of dipping below a year’s runway. Past $1.25M we would not expect additional donations to affect our 2017 plans much, assuming moderate off-fundraiser support.5
If we hit our growth and stretch targets, we’ll be able to execute several additional programs we’re considering with more confidence. These include contracting a larger pool of researchers to do early work with us on logical induction and on our machine learning agenda, and generally spending more time on academic outreach, field-growing, and training or trialing potential collaborators and hires. As always, you're invited to get in touch if you have questions about our upcoming plans and recent activities. I’m very much looking forward to seeing what new milestones the growing alignment research community will hit in the coming year, and I’m very grateful for the thoughtful engagement and support that’s helped us get to this point.
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1 This excludes Katja Grace, who heads the AI Impacts project using a separate pool of funds earmarked for strategy/forecasting research. It also excludes me: I contribute to our technical research, but my primary role is administrative. (back)
2 We expect to be slightly under the $1.825M budget we previously projected for 2016, due to taking on fewer new researchers than expected this year. (back)
3 We're imagining continuing to run one fundraiser per year in future years, possibly in September. (back)
4 Separately, the Open Philanthropy Project is likely to renew our $500,000 grant next year, and we expect to receive the final ($80,000) installment from the Future of Life Institute's three-year grants. For comparison, our revenue was about $1.6 million in 2015: $167k in grants, $960k in fundraiser contributions, and $467k in off-fundraiser (non-grant) contributions. Our situation in 2015 was somewhat different, however: we ran two 2015 fundraisers, whereas we’re skipping our winter fundraiser this year and advising December donors to pledge early or give off-fundraiser. (back)
5 At significantly higher funding levels, we’d consider running other useful programs, such as a prize fund. Shoot me an e-mail if you’d like to talk about the details. (back)

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