Manifold Show, episode 2: Bobby Kasthuri and Brain Mapping

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Our plan is to release new episodes on Thursdays, at a rate of one every week or two.

We've tried to keep the shows at roughly one hour length -- is this necessary, or should we just let them go long?

Corey and Steve are joined by Bobby Kasthuri, a Neuroscientist at Argonne National Laboratory and the University of Chicago. Bobby specializes in nanoscale mapping of brains using automated fine slicing followed by electron microscopy. Among the topics covered: Brain mapping, the nature of scientific progress (philosophy of science), Biology vs Physics, Is the brain too complex to be understood by our brains? AlphaGo, the Turing Test, and wiring diagrams, Are scientists underpaid? The future of Neuroscience.

Bobby Kasthuri Bio
https://microbiome.uchicago.edu/directory/bobby-kasthuri 

The Physicist and the Neuroscientist: A Tale of Two Connectomes
http://infoproc.blogspot.com/2017/10/the-physicist-and-neuroscientist-tale.html

COMPUTING MACHINERY AND INTELLIGENCE, A. M. Turing https://www.csee.umbc.edu/courses/471/papers/turing.pdf


man·i·fold /ˈmanəˌfōld/ many and various.

In mathematics, a manifold is a topological space that locally
resembles Euclidean space near each point.

Steve Hsu and Corey Washington have been friends for almost 30 years, and between them hold PhDs in Neuroscience, Philosophy, and Theoretical Physics. Join them for wide ranging and unfiltered conversations with leading writers, scientists, technologists, academics, entrepreneurs, investors, and more.

Steve Hsu is VP for Research and Professor of Theoretical Physics at Michigan State University. He is also a researcher in computational genomics and founder of several Silicon Valley startups, ranging from information security to biotech. Educated at Caltech and Berkeley, he was a Harvard Junior Fellow and held faculty positions at Yale and the University of Oregon before joining MSU.

Corey Washington is Director of Analytics in the Office of Research and Innovation at Michigan State University. He was educated at Amherst College and MIT before receiving a PhD in Philosophy from Stanford and a PhD in a Neuroscience from Columbia. He held faculty positions at the University Washington and the University of Maryland. Prior to MSU, Corey worked as a biotech consultant and is founder of a medical diagnostics startup.

The Future of Genomic Precision Medicine

As I mentioned in this earlier post, I'll be in the UK next week for a Ditchley Foundation conference on the intersection of machine learning and genetic engineering.

I'll present these slides at the meeting.

The slides review the rapidly evolving situation in genomic prediction, focusing on disease risk predicted using inexpensive genotyping. There are now 10-20 disease conditions for which we can identify, e.g., the top 1% outliers with 5-10x normal risk for the disease. The papers reporting these results have almost all appeared within the last year or so!

On the last slide I give a simple cost-benefit analysis of population wide genotyping and conclude that the net benefit is already positive given the tools we have. The numbers used are per capita. The UK NHS is already headed in this direction.

I use breast cancer as the example on the slide, but since the same genotype can be used for 10+ disease risks (including diabetes, atrial fibrillation, hypothyroidism, etc.) the net benefit is potentially much larger than what is obtained from breast cancer alone. The point is that G is really small compared to the potential benefit.

Details of breast cancer calculation below. I am sure one can do much better, but it provides a quick back of the envelope estimate of the numbers.

Spend $100 per person to genotype all women in the population. Identify those with top 1% risk score. About 33% of these individuals will get breast cancer. Treat the risk outliers by giving them, e.g., regular mammograms starting a decade earlier than usual (~$100 annual mammogram x 10y = $1k). In the slide I assume the average cost of the intervention / treatment is $1k and the average benefit is $30k. All of the high risk women (1%) get the intervention, but only the 33% percent that get breast cancer (or some subset of that group) benefit from early detection. This paper estimates that early detection of breast cancer saves typically tens of thousands of dollars per individual, so my numbers are not crazy.

On with the Show

Our YouTube / podcast show is live!

Show Page

YouTube Channel

Podcast version available on iTunes and Spotify.

Our plan is to record a new one every 1-2 weeks. We're in the process of scheduling now, so if you have contacted me to be on the show, or have suggested a guest, please bear with us as we get going.

Manifold man·i·fold /ˈmanəˌfōld/ many and various

In mathematics, a manifold is a topological space that locally resembles Euclidean space near each point.

Steve and Corey have been friends for almost 30 years, and between them hold PhDs in Neuroscience, Philosophy, and Theoretical Physics. Join them for wide ranging and unfiltered conversations with leading writers, scientists, technologists, academics, entrepreneurs, investors, and more.

Steve Hsu is VP for Research and Professor of Theoretical Physics at Michigan State University. He is also a researcher in computational genomics and founder of several Silicon Valley startups, ranging from information security to biotech. Educated at Caltech and Berkeley, he was a Harvard Junior Fellow and held faculty positions at Yale and the University of Oregon before joining MSU.

Corey Washington is Director of Analytics in the Office of Research and Innovation at Michigan State University. He was educated at Amherst College and MIT before receiving a PhD in Philosophy from Stanford and a PhD in a Neuroscience from Columbia. He held faculty positions at the University Washington and the University of Maryland. Prior to MSU, Corey worked as a biotech consultant and is founder of a medical diagnostics startup.

Ditchley Foundation Conference: The intersection of machine learning and genetic engineering

I'll be back in the UK soon for the meeting described below. Above, Ditchley House.

The intersection of machine learning and genetic engineering: what should be our check list for society and state as we blast off?

07 - 09 FEB 2019

Advances in machine learning and genetic engineering are combining to produce rapid advances in medicine, development of materials and genetic engineering. Parallel advances in robotics and automation have made the practical process of gene editing scalable. The possibility exists that advances in quantum computing could further accelerate progress on machine learning, bringing a second boost to this technological rocket.

This Ditchley conference will bring together an unusual mix of deep expertise and scientific renown in the disciplines; thinkers on religion, ethics and law; investors fueling innovation; and political leaders looking to shape the approach of society and state to fast emerging possibilities. We will attempt to establish sufficient common understanding of what the science promises and what it doesn’t and then explore the opportunities and risks that are likely to unfold at speed. This will be a first pass at preparation for potential blast off – what should be our moral, legal, economic and national security checklist as we wait on the launch pad of a new age?

The progress on machine learning is quite narrow in scope – deep learning using neural networks and other techniques on large data sets that now exist that didn’t previously and that are store-able and computable in a way that was not possible previously. But whereas progress towards general AI is often overstated, full general AI is not required to radically accelerate gene sequencing, editing and programming, with costs falling all the time and scale and speed increasing.

We will examine and try to come to preliminary conclusions on questions such as the following:

How should the most aggressive genetic engineering technologies be regulated?

How can societies best assess the ethical issues raised by these technologies to find an optimal balance between fostering genetic technologies for the common good while preventing abuse?

What are the implications for the global economy and economic cooperation and competition between states? Are we entering a period of bio-nationalism as well as AI nationalism? Should this be compared to the space race of the Cold War? How can we avoid competition between states driving abandonment of norms and moral standards? What will be the impact on the labour force of the new combined technologies of AI and bio-engineering? Within countries, will potential applications of the new technologies further intensify the concentration of wealth and power in a few hands?

What are the implications of rapid combined advances in AI and bioengineering for defence and national security? Will countries be tempted to pursue military applications either through bio-weapons or through the genetic improvement of military forces? What new materials will emerge and how will they affect the balance of power in warfare?

What are the implications for medicine and public health? If we are able to find targeted genetic cures for diseases like cancer then what will the impact be on the population? What are the implications for ageing or declining populations?

How should we handle the implications of deeper knowledge about the influence of our genes on our characteristics and on the characteristics of groups? How do we chart a course between remaining scientifically objective and providing material that could be misused to support racist conclusions by those tending to that view?

What opportunities and threats are there in the potential of these combined technologies for democracies and the equal value put on the view point of each citizen in the electoral system and the rule of law? More philosophically, how can we make sure the development of these technologies contributes to a positive sense of human progress and meaning, rather than to a sense of alienation and loss of purpose? How can we manage the tension between science and religion as human capability to shape the genetic world increases?

I'm only briefly in London on my way there, but might be able to squeeze in a few meetings :-)

See also:

The Future of IVF and Gene-Editing (Psychology Today interview)

The Future is Here: Genomic Prediction in MIT Technology Review

Genomic Prediction of Complex Disease Risk (bioRxiv)

Babylon Health (BBC documentary)

On my last trip to London I learned that the startup Bablyon Health is causing a huge stir. Babylon received some initial funding from the founders of DeepMind (leading AI company acquired by Google; I was visiting them to give a talk).

Babylon created an AI phone app (a chatbot) to gather information from patients. The AI does triage and directs the patient (depending on severity of situation) to a GP (General Practitioner). The GP interaction takes place over video chat. The AI also suggests diagnoses to the GP who sees the recommendations on their computer screen. In tests the AI performed similarly to an average human GP and better than the worst GPs.

Already ~500k Londoners (including the UK Health Minister!) have chosen Bablyon as their NHS GP.

The BBC documentary above is really good.

2019 Digital Business Projections

Love this guy.

A Grand Experiment

I've been making secret preparations for a YouTube / Podcast show :-)

We've taped a first episode and are working on a few more. The whole thing is an experiment -- no telling whether it will work out, and no promises I'll have time to really do it right.

Please give me suggestions for people you'd like to see interviewed on the show. Or volunteer yourself if you have something to share. I think we'll probably allow pseudonymous guests, so your identity can be kept private.

I'm especially interested in knowledgeable people who could give us insight on

Silicon Valley (Big Tech and startups and VC)
Financial Markets
Academia (Good, Bad, and Ugly)
The View from Europe
The View from Asia (Life in PRC? Fear and Loathing of PRC?)
Frontiers of Science (AI, Genomics, Physics, ...)
Frontiers of Rationality
The Billionaire Life
MMA / UFC
What Millennials think us old folks don't understand
True things that you are not allowed to say
Bubbles that are ready to pop?
Under-appreciated Genius?
Overrated Crap and Frauds?


Here are two old videos I'm in that are already on YouTube:

Slate Star Codex Meetup -- Berkeley

I will be at this meetup later today:

BAY MEETUP 1/6 UPDATE

POSTED ON JANUARY 4, 2019 BY SCOTT ALEXANDER
Due to rain, we’re switching to holding the meetup indoors at 3045 Shattuck Ave, Berkeley, 94705. There will be several floors of space available for overflow, so hopefully it won’t be too crowded. Thanks to Claire, REACH, and Event Horizon for setting this up.

Time is still 3:30 PM on Sunday, 1/6. There’s also a Facebook event here.

For the unfamiliar, Slate Star Codex is one of the best blogs on the planet, with a large devoted following of rationalists. Scott is an incredibly talented writer and thinker, and I envy him his readership and commentariat :-)

Serotonin: Houellebecq and Gilets Jaunes

In Houellebecq on Tocqueville, Democracy, and Nietzsche (2015) I pointed out that most intellectuals and elites have been so strongly conditioned by the existing cultural hegemony that they cannot understand obvious realities about the world. In that case I referred specifically to Houellebecq's previous novel Soumission.

Events since 2015 -- Trump's election and populist movements in Europe -- have stimulated a vague (but distorted) understanding in the minds of brainwashed elites as to populist discontent, its causes and origins. The reaction of our "thought leaders" is to decry the (previously sacred) democratic process by which the masses exercise their limited influence on society.

Individuals who told me confidently before the election that Trump had no chance of winning now forget how wrong they were then. They continue to express great confidence in their understanding of world events and political/economic processes.

So few are capable of updating prior beliefs in the face of new information. So many are overconfident in their powers of rationality.

Houellebecq has shown again that he understands reality much better than his critics.

Guardian: Serotonin, the story of a lovesick agricultural engineer who writes trade reports for the French agriculture ministry and loathes the EU, has been hailed by the French media as scathing and visionary. The novel rails against politicians who “do not fight for the interests of their people but are ready to die to defend free trade”.

Written before the current gilets jaunes anti-government movement began blockading roundabouts and tollbooths across France, it features desperate farmers in Normandy who stage an armed blockade of roads amid police clashes.

... In a recent article for Harpers, Houellebecq lauded Donald Trump for his protectionist policies, calling him “one of the best American presidents I’ve ever seen”, and praised Brexit: “The British get on my nerves, but their courage cannot be denied.” Serotonin, which will be published in English in September, viciously criticises free trade.

In Houellebecq on Tocqueville, Democracy, and Nietzsche, Houellebecq discusses Tocqueville's insight concerning the manner in which democracy is likely to be subverted: by a soft tyranny that

Tocqueville (Democracy in America, chapter 6) ... covers the surface of society with a network of small complicated rules, minute and uniform, through which the most original minds and the most energetic characters cannot penetrate, to rise above the crowd. The will of man is not shattered, but softened, bent, and guided; men are seldom forced by it to act, but they are constantly restrained from acting. Such a power does not destroy, but it prevents existence; it does not tyrannize, but it compresses, enervates, extinguishes, and stupefies a people, till each nation is reduced to nothing better than a flock of timid and industrious animals, of which the government is the shepherd.

Soma, Serotonin, soft censorship of dangerous ideas -- call it what you will.

See also Paris 2018: Global Capital and Its Discontents.

Mama Said Choke You Out

If you do Judo, MMA, or BJJ you've probably seen someone choked all the way out. In this video CrossFit athlete Brooke Ence learns how to do hadaka jime (naked choke) and goes out herself. Very interesting if you've never seen it before :-)

Judo/BJJ chokes block blood flow to the brain, not air flow to the lungs. Deprived of blood (hence, oxygen), the brain transitions to unconsciousness quickly and rather abruptly, with interesting effects on memory and awareness.

I trained for years with a former Navy SEAL who would fight a submission to the end, so I choked him out on a number of occasions. Sometimes he would wake up afterward and ask me what happened. He also made the same little gurgling noise that Ence makes in the video.

See also Mama said knock you out and here for the LL Cool J reference ;-)

The Golden State

Apologies for the lack of posts. I've been enjoying some time with the family in CA :-) Kids have the MI middle school state swimming championships coming up and we got some good training done in a beautiful outdoor pool. I'm using USRPT methods, which seem to work well for my kids. I wish we had it when I was competing.

We had really good luck with the weather, sunny and 60s every day on the central coast.

Now I'm in the bay area for this meeting:

37th Annual J.P. Morgan HEALTHCARE CONFERENCE
January 7 - 10, 2019
Westin St. Francis Hotel | San Francisco, California