The number of new drugs is declining

Why Are So Few Blockbuster Drugs Invented Today?

since 1950, the number of new drugs approved has fallen by half roughly every nine years, meaning a total decline by a factor of 80. They called this Eroom’s Law, because it resembled an inversion of Moore’s Law

Graph from In the Pipeline (more here)

Why has the worm not been emulated?

"The way the prophets of the twentieth century went to work was this. They took something or other that was certainly going on in their time and then said that it would go on more and more until something extraordinary happend." G. K. Chesterton

What if you could emulate the brain the way we emulate computer worms?

C elegans is a 1mm long worm with 302 neurons, 3 Nobel prizes and has survived a space shuttle crash. It is one of the simplest animals and has been studied in massive detail. Like the fruitfly or ecoli anything these lab animals do that you cant explain you wont be able to explain in people either.

Whole brain emulation is a prediction that we will be able to simulate the brain in enough detail to create artificial intelligence very like us.

Robin Hanson on econtalk talked about the possible results of whole brain emulation.
"This scenario, which we've called whole brain emulation--taking a whole brain and emulating it on a computer--requires three technologies. One is scanning--you have to be able to scan something in sufficient detail; have to see exactly which parts are where and what they are made of. Two, you have to have models of these cells, a model of the cell input signature and then what comes out of it as a mapping--doesn't have to be exactly right, just has to be close enough. Three, you need a really big computer. A lot of cells, a lot of interactions."
Hanson blogs about brain emulation here. There are interesting fights about whether whole brain emulation is a reasonable prediction or just "the rapture for nerds".

Many biologists seem to think computer people are completely misunderstanding how complicated biological systems are and computer sciencey whole brain Emulation types say that biologists do not understand abstractions because they deal with this complexity all the time.
'[Robin] Hanson’s fundamental mistake is to treat the brain like a human-designed system we could conceivably reverse-engineer rather than a natural system we can only simulate. We may have relatively good models for the operation of nerves, but these models are simplifications, and therefore they will differ in subtle ways from the operation of actual nerves. And these subtle micro-level inaccuracies will snowball into large-scale errors when we try to simulate an entire brain, in precisely the same way that small micro-level imperfections in weather models accumulate to make accurate long-range forecasting inaccurate.' is an example of the biologists argument against brain emulation.

'We should expect brain emulation to be feasible because brains function to process signals, and the decoupling of signal dimensions from other system dimensions is central to achieving the function of a signal processor.

"We can do trend extrapolation and say: Where are we now; if trends continue how long would it take? The computing technology has a nice solid trend; we can project that pretty confidently into the future. The problem is we don't really know how detailed we're going to need to go into these cells. The scanning technology, we have decent trends. This is a vastly smaller industry; small demand. That technology actually looks likely to be ready first. We've actually done a scanning of a whole mouse brain at a decent resolution. A thousandth smaller than a human brain. What does that mean--scanning of a brain? They slice a layer, do a two-dimensional scan of that layer at a fine resolution, go across each cell, and then they slice another layer and do the same thing again. Let me ask again, sort of naive question: If you could take a person's brain out of their head while they were still alive, are you going to be able to get access to my memories in this process? my creativity? All these things we think of as more than a physical process, but of course as you say, it's just chemicals interacting. Is it imaginable that we would be able to reconstruct my memories? To the extent we are confident that your memories and personality are encoded in these cells and where they are and how they talk to each other, so we get that right, we get it all right. That's all you are. Let me say it differently. Looking at it isn't enough. Scanning means noticing the chemical densities. There's thousands of kinds of cells in your brain, and each cell sort of behaves a bit differently. What we need is to know when a cell gets a signal from the outside, electrical or chemical signal, how does that change a cell and what kind of signal does it send out. So, we need to have a model of each of those cell types. We have, actually, models of a wide range of cell types. Doesn't seem that hard to model these cells. We just have a lot of cells to go through and not that much motivation to do it all in a rush. We have actually pretty good models of some particular cells. We have a cell on a dish, we send a signal in, model on the computer, do the same things."

Both sides here. The brain is really complicated squishy stuff and the simcity looks like a real city if you squint sides here could be right. I want a comparison of the predictions of these two theories now and not in 2040 though.

If we had Hanson's 1,2,3 met for an organism and we were not emulating it that would seem to be a problem for the theory.

One is scanning--you have to be able to scan something in sufficient detail;

The c elegans connectome was mapped in 1986
Two, you have to have models of these cells, a model of the cell input signature and then what comes out of it as a mapping--doesn't have to be exactly right, just has to be close enough. There are not many types of neurons in c elegans so we should have a fairly good model of when they will fire.


Three, you need a really big computer. A lot of cells, a lot of interactions."
How big a computer would you need to model all these cells and interactions?

In When will computer hardware match the human brain?
Hans Moravec (1997) gives some nice graphs of how much processing you get for $1000



Kurzweil gives similar figures here

This puts the amount of processing available to a C. elegans at about 1990 levels for $1000. So in 1986 that processing power would have easily been available to university researchers. Maybe that graph is optimistic but if it is out by 25 years for something as simple as c elegans that means predictions of whole brain emulation by 2050 also on the graph will be out as well.

For the last 25 years we have had the power to emulate the whole brain of C. Elegans. Why haven't we?

1. We have not actually because our neuron firing models has not been accurate enough
2. No one cares about emulation fo a worm. A lot of people care about this worm the numbers of neuroscience papers on it confirm this.
3. They are just a bit delayed. There is a thread here on less wrong about this
an open source project openworm*
4. It is hard to get output from a worm 'Our first goal is to combine the neuronal model with this physical model in order to go beyond the biophysical realism that has already been done in previous studies. The physical model will then serve as the "read out" to make sure that the neurons are doing appropriate things.' Pixar, special effects companies and computer game programmers must have fairly good worm emulation programs. If there is a big problem making an animal bodies simulation surely one of them could easily enough make a good model of a tiny bag of gunk?

'Whole Brain Emulation A Roadmap' acknowledges the gap that exists in our emulation of the animal and suggests alternatives ' While the C. elegans nervous system has been completely mapped (White, Southgate et al., 1986), we still lack detailed
electrophysiology, likely because of the difficulty of investigating the small neurons. Animals
with larger neurons may prove less restrictive for functional and scanning investigation but
may lack sizable research communities'

Why 25 years after having a good map and enough computation to run the calculation have we not emulated C Elegans? If it is the modelling of the cells
'I have talked several times to one of the chief scientists who collected the original connectome data and has been continuing to collect more electron micrographs (David Hall, in charge of www.wormatlas.org). He has said that the physiological data on neuron and synapse function in C. elegans is really limited and suggests that no one spend time simulating the worm using the existing datasets because of this. I.e. we may know the connectivity but we don't know even the sign of many synapses.'

The openworm project is really cool. and it might be a good way to get some evidence into the whole brain emulation debate now.

'The problem is we don't really know how detailed we're going to need to go into these cells. '

If Ken Hayworth is right and it is just that 'He has said that the physiological data on neuron and synapse function in C. elegans is really limited' is this because the biologists are right and step 2 the cell models will not be as easy to build as supporters of whole brain emulation claim?
These is a project here to emulate C Elegans. And a good paper here on the problem involved Dynamics of the model of the C Elegans neural network. Just in time to make me look more stupid is A Worm's Mind In A Lego Body. It is not full emulation yet but it is at lest on the path there. * An article from Popular Science on Whole Brain Emulation here that made me resurrect this post I drafted two years ago. Since then the openworm project has moved on massively.

Drones and Ecology

Drones have become wildly popular recently. They seem to be on the path of military, geeks, specific industries ->everything that successful tech seems to go through. It seems likely that large numbers of small deliveries will take place by drone in ten years time. One thing that damaged bird sized tech in the past was hawks. Jon Bentley described in 'More Programming Pearls'

The computers at the two facilities were linked by microwave, but printing the drawings at the test base would have required a printer that was very expensive at the time. The team therefore drew the pictures at the main plant, photographed them, and sent 35mm film to the test station by carrier pigeon, where it was enlarged and printed photographically. The pigeon's 45-minute flight took half the time of the car, and cost only a few dollars per day. During the 16 months of the project the pigeons transmitted several hundred rolls of film, and only two were lost (hawks inhabit the area; no classified data was carried). Because of the low price of modern printers, a current solution to the problem would probably use the microwave link.

Hawks have a habit of attacking small things we send through the skies. There is this great piece on the effect of Amazon drones on ecology. The Dark Extropian Report: The Evolution of Amazon’s “Prime Air” Drone Delivery Service

Hawks and other birds of prey taking issue with these noisy (for now) airborne intruders into their territory. Everyone was worried about people below shooting them down, but it turns out there may be another threat that can’t be so easily policed; outlaw avians....A delivery drone that takes its shape and forms that outline in the sky will not be attacked by a lesser predator, even if it’s not already wired into their genetic memory

The article suggests creating drones that look like very big hawks to discourage natural hawks from attacking them.

This effect doe not just apply to birds of prey though. Prey species hide when they see the outline of a bird of prey. And doing this increases their anxiety enough to reduce feeding and decrease numbers drastically over time. The drones that look like birds of prey will not have to prey. Just being in the sky with the right silhouette will drastically reduce the number of vermin.

According to this article

Changes to ecology have unpredictable effect on the environment. Less pigeons would seem an improvement to the urban environment but they do eat bread and other foodstuffs. If numbers are reduced enough to prevent this bad things could happen.

tldr: 1. there will be lots of drones 2. They will look like birds of prey 3. They will have a big effect on rats, pigeons and other prey species.

Water Protest Maps

Liam Hogan and Joan Byrne made a great google map here of the water protests in Ireland on November 1st. They kindly let me use their data to create some graphs.

The code and data is here. I will update is as data improves. And maybe to improve the labels on the graphs.

First the number of protestors per county

Number of protestors as a percentage of population of each county

An interesting way of looking at this would be in terms of blocks of 27,640 people. this is the average number of people per TD in Ireland

Dublin has the most variation on the number of protestors. The number in the main O'Connell Street protest was the largest and the one with the most variation in estimated numbers. Other than this most people seem to agree with the numbers Liam and Joan have on their map.

Apple were never about home computers

According to Wikipedia Steve Jobs' first TV interview was in 1980 in Ireland with Pat Kenny. He talks about the apple being sent up on the space shuttle.

Pat:'Do you actually believe that every home, in the short term at least, will have a personal computer?'

Steve:'We base our theory on the fact that we make personal computers that can be used irrespective of location. The home just happens to be one of the locations apples can be used in'

This shows a fair amount of ambition given it was 4 years before the Macintosh was released.

Making Ebooks More Physical

For this invention will produce forgetfulness in the minds of those who learn to use it, because they will not practice their memory. Their trust in writing, produced by external characters which are no part of themselves

Socrates to Plato in Phaedrus

"A new study which found that readers using a Kindle were "significantly" worse than paperback readers at recalling when events occurred in a mystery story is part of major new Europe-wide research looking at the impact of digitisation on the reading experience." ... "The Kindle readers performed significantly worse on the plot reconstruction measure, ie, when they were asked to place 14 events in the correct order."

The researchers suggest that "the haptic and tactile feedback of a Kindle does not provide the same support for mental reconstruction of a story as a print pocket book does".

"When you read on paper you can sense with your fingers a pile of pages on the left growing, and shrinking on the right," said Mangen. "You have the tactile sense of progress, in addition to the visual ... [The differences for Kindle readers] might have something to do with the fact that the fixity of a text on paper, and this very gradual unfolding of paper as you progress through a story, is some kind of sensory offload, supporting the visual sense of progress when you're reading. Perhaps this somehow aids the reader, providing more fixity and solidity to the reader's sense of unfolding and progress of the text, and hence the story."

From the Guardian If haptic and tactile feedback to give a sense of progress in a book is so important how could this be added to ebook readers? One possibility is a weight that moves from one side of the ebook reader to another as you progress. This would mirror the feeling of a book starting heavier on the right and ending heavier on the left. Assuming you are reading English and not Manga or other back to front based moving system. This could be accomplished with by moving a marble as the book progresses.

Another option is to change the weight based on how far through the book you are. By adding Pez dispenser to the back of the ebook reader that dispensed sweets at points during the book a physical change in the book would result.

Once you are doling out sweets anyway you could flavour them based on the book in question. That would mean you could supply a flavour for the text at certain points which would provide the sort of physical feedback books currently do not. What flavours would go with which books and where? I have never been able to get access to the kindle SDK. But this seems like the sort of hardware project you could try at a hack weekend if you had access to the kindle api.

The Great Stagnation, Football Ball Edition

'Since 2002, panel numbers have roughly halved every four years: 32 in 2002, 14 in 2006 and eight in 2010. Thus, by the 2022 World Cup, players should be kicking a single-panel ball around the pitch.' claimed Ken Bray here. I will call this Brays law 'The number of panels on the World Cup football ball will half every tournament'. This is not quite as epoch defining as Moore's law but still cool I think.

This year according to projections the soccer ball in the world cup should have at most 4 panels. Instead the ball has 6. 50% more panels then you would expect if progress continued at the rate Bray predicted. The Great Stagnation is the belief that things are not improving as quickly as they used to and is used to explain why we still have homeless people but not flying cars.

The number of panels each world cup ball has is found on each balls individual Wikipedia page.

2014 the Adidas Brazuca: 'The ball has been made of six polyurethane panels'

2010 the Adidas Jabulani: 'The ball was constructed consisting of eight (down from 14 in the 2006 World Cup) thermally bonded, three-dimensional panels'

2006 the Adidas Teamgeist:'The Teamgeist ball differs from previous balls in having just 14 curved panels rather than the 32 that have been standard since 1970. Like the 32 panel Roteiro which preceded it'

Fewer panels mean the ball is smoother and should fly more true. The ball flying true involves the interaction of several variables other than the panel number though. The 2010 ball was notorious for wobbly flight for example. For this reason just reducing the number of panels at the expense of the quality of the ball is a bad idea and may explain why Bray's law has failed. Still not being able to make a ball work with fewer panels indicates a technological innovation slow down to me. The aerodynamics of soccer balls and why there is a race to fewer panels is described in Brays article 'A fly walks round a football'.

Lets All Move to No Insurance Land

Ryanair have finally set up their own country. In order not to buy insurance you have to select that option from the country of residence option. Because the UX of select insurance clearly is to choose from a country this option makes complete sense.

If you are going to have a new country of 'don't insure me' it is clearly not in some sort of non country section of the drop down but resides just after Denmark.

I've talked before about where Ryanair if people did what they asked they would disappear. But I still like them, I just like pointing out when some company acts oddly.

There is a level of hiding extra charges from people. Setting up your own country to get an extra few quid out of people really shows commitment.

Goodreads Recruitment Hack

I entered in some of the node.js books I have been reading into my goodreads list. And they mentioned that they were recruiting.

The programmer who told recruiters about github meet the same fate as the police officer at the end of the wicker man. But at the risk of the same thing happening to me this is a really clever idea. If you are looking for people who know about an area checking if they read the books is one way. Only goodreads can advertise on their site but anyone can look up book reviews. The other surprising thing is with 800k followers goodreads twitter mentions must be like looking at the digital rain from the Matrix. But they noticed that I mentioned their recruitment idea and replied.