Bold Conjectures with Paras Chopra

Can you crowdsource your way to discovering a new drug?

Alpha Lee's startup PostEra launched a crowdsourced effort (called Covid Moonshot) to discover drugs that are effective in treating covid-19. This was the first of its kind effort that combined research efforts from several groups across the world to design a drug that treats covid-19, is free from patents and can be made cheaply and easily anywhere in the world.

== What we talk about ==
0:04 - Introduction
1:28 - What does your company, PostEra, do?
4:58 - Why is the traditional method of discovering drugs inefficient and hard?
9:52 - How do you find whether a computationally discovered drug will work?
11:25 - How do you optimize the drugs for toxicity, solubility, and other properties?
12:03 - How are you able to come up with a chemical synthesis pathway in a finite time?
16:44 - What are the areas where deep learning models have become better than humans in drug development?
19:18 - What’s the origin story of Covid Moonshot? How did it grow into what it is now? 25:24 - How was the experience managing people from around the world working on this project, especially when there is no central authority?
27:47 - The process of finding the target molecule
34:17 - Since Covid moonshot is all pro-bono and you are not filing for a patent, how do you see the process of regulatory trials, which is very costly, being done?
37:19 - By the time your drug comes, do you think the Covid-19 will be a much lesser threat? 39-49 - Do you plan to use the same approach for different diseases? And do you also envision driving the whole process of drug discovery in the future, and not just enablement?
41:41 - How do you align your science research interests with commercial interests?
43:46 - Haș an insight, while working on a problem, inspired a scientific question?
45:23 - The marriage of use of basic science and real-world problems
46:38 - How can someone help in the Covid Moonshot mission?

== About the guest ==
Dr Alpha Lee is the co-founder of PostEra, a start-up that offers medicinal chemistry as a service powered by machine learning. He did his Ph.D. at the University of Oxford. Currently, he’s at the University of Cambridge where his research group explores the integration of physics, statistics, and machine learning. 

Schizophrenia affects 20 million people worldwide and there's no treatment for it.

There is growing evidence that psychedelic drugs like psilocybin (as found in "magic mushrooms") could help treat it. I explore this fascinating topic with Gaige Clark who writes a popular blog https://mad.science.blog detailing the science of mental illnesses and their potential treatments.

== What we talk about ==
0:04 - Introduction
1:13 - How did you get interested in the science of psychedelics and the mind?
6:21 - What is schizophrenia?
9:10 - How common is schizophrenia? How does it impact people’s lives?
11:16 - The role of genetics and stress in being prone to these disorders including schizophrenia?
15:44 - Making sense of hallucinations as an aftereffect of schizophrenia
20:05 - How do you define psychedelics? And how do they work?
41:35 - It seems counterintuitive that the drugs which make you hallucinate can cure you of the hallucinations happening because of schizophrenia - how is this happening?
59:50 - How much have we progressed in using psychedelics as a therapy?
1:02:43 - Is psychedelics being researched upon to be used as a cure for anything else apart from schizophrenia and addiction? 

== About the guest == 
Gaige Clark is currently studying psychology at UC Merced, focusing on neuroscience, pharmacology, and neuropsychology, especially in relation to psychedelic therapy. He reads bucket loads of papers on the science of mental disorders and documents them on this blog. Through personal experiments and emerging support in science, he now believes in the hypothesis that psychedelics may treat schizophrenia.

The best way to understand how life arose on Earth is to try to create it in a lab. But can we do it?

Lee Cronin at the Glasgow University is trying to do make the simplest life possible using nothing but inorganic chemicals.

== What we talk about ==
0:04 - Introduction
1:16 - How did you become interested in the origin of life?
5:37 - How close are we to finding out the origin of life?
10:22 - The definition of life
17:47 - Low & high information objects
21:05 - Is the process of life a continuum?
24:53 - How will we know we've found life if it's too alien (say made of inorganic molecules)? 30:19 - What is the assembly theory?
44:06 - How inorganic chemicals become self-replicating systems?
48:32 - How far are we from starting a new branch of life on Earth?
50:19 - Why is all life on Earth DNA based? Why not a variety?
55:05 - Do you have any hopes that we will find life on Mars?
57:29 - What are the minimum viable conditions which have to be there for life to exist?
1:04:04 - What is a chemical computer?
1:08:42 - What is a chemical computer good for?
1:11:16 - Can you use your assembly theory to reverse engineer any chemical and then make it?
1:15:11 - What’s the reaction of the chemistry community on the work you are doing?

== About the guest == 

Professor Lee Cronin is the Regius Chair of Chemistry in the School of Chemistry at the University of Glasgow, UK. 

He is interested in the intersection of computation, life and chemistry. His research group is trying to recreate life from scratch by mimicking the atmospheric and terrestrial conditions of early Earth. In his pursuit of figuring out how life arises, Prof Lee Cronin has ended up pushing chemistry to its limits, the most recent manifestation of which is the chemputer - a computer that can be programmed to synthesize almost any chemical you can imagine. 

Unlike many other scientists who study the origin of life, he is unique in his approach in trying to study life from its inorganic precursors - that is, how can complex organic molecules that life needs can form from inorganic molecules that get formed in the core of stars.

How do our bodies know what to become?

There are no instructions in our genes that code for the exact 3D structure of our bodies. There's no tiny human contained in our DNA. So, what powers the transformation of the first cell in the embryo to a full-blown organism?

Dr Michael Levin is attacking this problem and, in the process of answering it, his lab is uncovering an entirely new way of looking at biology.

== What we talk about ==
0:04 - Introduction
1:20 - You were a software engineer. How did you get interested in biology?
6:50 - Can bacteria exhibit intelligent behavior?
7:46 - How do organisms take their final shape?
22:51 - How do cells in our body know when to stop multiplying?
27:49 - Analogs of software and hardware in developmental biology
34:20 - Where are the body plans stored in complex organisms like ours?
43:33 - What post-DNA paradigms are important in biology?
48:20 - What is regenerative medicine?
50:20 - How far have we progressed in regenerative medicine?
52:52 - Xenobots: world's first synthetic organisms
1:00:12 - How to program Xenobots
1:05:13 - How do you handle the ethical dilemma while you are working with conscious organisms?
1:10:22 - How do you enable the scientific creativity in your lab and amongst your students? And is it a teachable skill?

== About the guest ==
Michael Levin is a Distinguished Professor in the Biology department at Tufts and serves as director of the Allen Discovery Center. He holds a PhD in biology from the Harvard University. At Tufts, his research group is interested in figuring out how our bodies know what to become. 

He believes that what guides our body plans is bio-electric communication between different units. Our bodies take shape the way they have because each of our subunits - cells, tissues, organs - collectively decides it to be that way.

Hinting at the perceived sluggish rate of innovation in recent decades, Peter Theil famously said that “we were promised flying cars and all we got is 140 characters”.

Today, I’m going to pick Jose’s brain on whether technological and scientific progress is indeed slowing down, and what that suggests for our society’s future.

== What we talk about ==
0:04​ - Introduction
0:50​ - What does being an independent researcher mean for you?
2:50​ - How did you become an independent researcher?
9:40​ - You don't publish in peer-review journals, why?
12:35​ - How do you pick your research subjects?
15:48​ - Being an independent researcher, how do you get feedback on your research?
21:14​ - What is the great stagnation and why do people believe that it exists?
28:24​ - What is the narrative behind it and why does it matter?
33:59​ - Is there great stagnation in technology?
43:07​ - How should we interpret the possibility of productivity slowing down?
49:21​ - Why should the world care about productivity and efficiency?
52:01​ - Is the marginal cost of new knowledge increasing?
59:36​ - Even when we have more cumulative knowledge, the rate at which the economy grows still has been constant. Your views on this?
1:02:30​ - How do you make sense of laws like Moore's law?
1:09:42​ - With your diverse research background, what have you changed your mind on?

== About the guest ==
José is an independent researcher who likes to get into details of things. On his blog https://nintil.com​, among a wide range of topics, he writes about how science is done, advances in human longevity research, economics and innovation.

How does our consciousness arise?

In this episode, I and Dr Philip Goff explore the increasingly popular view that everything in our universe is conscious (panpsychism).

== What we talk about ==
0:04​ - Introduction
1:02​ - How did you get interested in the problem of consciousness?
5:10​ - The role of philosophy in understanding consciousness
10:30​ - How can philosophy and science come together to help understand consciousness
13:40​ - What is your definition of consciousness?
22:35​ - The philosophical vs scientific frameworks in consciousness. And why does consciousness matter?
29:57​ - How do you situate the discussion on consciousness historically?
45:44​ - What is the current contemporary view of panpsychism?
53:43​ - Dualism vs panpsychism
56:33​ - What are the open questions in panpsychism?

== About the guest ==
Dr Philip Goff is a professor in the Department of Philosophy at the University of Durham in the UK. He’s the author of a book called Galileo's Error in which he defends panpsychism, the view that consciousness is a fundamental and ubiquitous feature of the physical world. 

He acknowledges it sounds a bit crazy, but in his book and research papers he tries to show that it avoids the difficulties faced by its rivals which are materialism (consciousness can be explained in terms of physical processes in the brain) and dualism (consciousness is separate from the body and brain).

Balaji is a deep thinker on crypto and its implications. Formerly the CTO of Coinbase and General Partner at Andreessen Horowitz, he’s seen how technologies evolve over time, which ones change the world and which ones fizzle out as a fad.

He believes crypto technologies such as bitcoin represent the former. To him, crypto will emerge as something that’s as important as the Internet and influence our society for decades to come.

What we talk about

0:04​ – Introduction
1:28​ – How did you get interested in crypto?
7:40​ – Your sense-making algorithm when you come across something strange and new like crypto?
20:44​ – Role of dissatisfied entrepreneurs in changing the status quo
26:40​ – Decentralized vs centralized networks
29:20​ – The demonstrated benefits of crypto
41:27​ – Is crypto a general-purpose technology like the internet?
55:24​ – Is the money being made or being transferred in the crypto ecosystem?
1:12:00​ – Valuations in crypto – actual value vs speculation?
1:17:47​ – Hindsight bias when analyzing crypto
1:25:24​ – What are crypto states? And why do you think nation-states will evolve towards them?

The way science is funded today is broken. 

Writing grant proposals for raising funds takes a significant amount of time and, unlike papers, they aren’t published in journals or valued for their scientific contribution. With grant rates now in single digits in many fields, scientists are spending more time raising funds than doing actual science. Is there a better way? 

Kevin Gross, professor at North Carolina State University, urges us to explore alternative ways of funding science. One such suggestion is using partial lotteries to award grants which, according to the models he’s built, generate more scientific output for the society than current methods.

What we talk about

1:55​ – How did you get interested in meta-science?
6:45​ – What progress have we made in the science of science?
8:45​ – Existing science funding mechanisms
16:15​ – Psychological pressure on scientists from the perspective of funding
22:54​ – Why hasn’t the funding been kept up with the number of scientists applying for funding?
26:22​ – How do the review panels rank the proposals for funding?
33:21​ – What are the most prominent issues with the current funding system?
36:48​ – Alternative ideas to improve the current funding system
54:04​ – Is there any empirical evidence for the alternative ideas you have for funding systems?
57:42​ – Why should society care about how science is funded?

Can we eliminate suffering? 

David Pearce thinks so. He is a British philosopher who has played a key role in defining and promoting transhumanism – a movement that challenges humans to explore what it means to go beyond our biological evolved limitations and constraints. 

He is most known for Hedonist Imperative, a manifesto he wrote in 1995 which outlines how modern technology can and should be used to eliminate all suffering in all sentient life, replacing it with bliss. David calls this the abolitionist project.

What we talk about

4:13​ – How do you define suffering?
7:03​ – What is hedonic zero?
8:21​ – What is negative utilitarianism and why do you promote it?
11:45​ – Is painless death a type of suffering?
13:16​ – Is suffering essential to create meaning for humans?
20:20​ – What are the steps you see for eliminating suffering? And can it start today?
29:07​ – After we reduce suffering, will our hedonic default reset and we’ll suffer anyway?
34:22​ – Why sensitivity between different hedonic states is important
36:31​ – Why did evolution design let suffering evolve?
39:40​ – Do depressed people have a better understanding of the world?
41:54​ – Delegating human suffering to machines
44:09​ – How do you characterise addiction? Is it good or bad?
49:21​ – Are short-term pleasures (like smoking) that turn into addiction worth it?
51:44​ – Are plants consciousness and if so, what is your take on veganism and vegetarianism?
55:36​ – Why would a human brain produce consciousness and a plant would not?
1:00:15​ – Have you noticed any progress since the time you published ‘The Hedonistic Imperative’?

What are the origins of language? What role did evolution play in it?

In this episode, Micheal Corballis backs up the idea that languages evolved gradually and some version of it existed much before Homo Sapiens arrived on the scene.

About the guest

Michael Corballis is an emeritus professor at the Department of Psychology at the University of Auckland. His research interests intersect cognitive neuroscience with language and evolution. He is deeply interested in big questions such as how did language evolve, why our brain is asymmetrical and what it means to be human. He has authored several books on language and mind.

What we talk about

1:23 – What led you to be curious about the evolution of language?
2:49 – Why are our brains asymmetrical?
6:36 – Noam Chomsky’s work on the evolution of language
8:26 – Did language emerge suddenly?
13:25 – How did language evolve?
15:17 – Did the evolution of language start from gestural communication?
17:34 – Transition from gestural communication to vocal
20:34 – How do we prove the evolution of language when there is no archeological evidence?
23:47 – Why did we not stop at gestural communication?
28:35 – Theory of mind is a critical part of language
31:29 – Mental time-travel and theory of mind in language for humans
36:53 – Is there a connection between our open-ended imagination and language being generative?
39:50 – What aspects of language differentiate humans from other animals
41:03 – Do we think in languages?
42:29 – Which language do differently-abled people think?
44:45 – Language is not essential for thoughts, it is just a way for communicating
45:34 – Why do we have so many languages?
49:47 – Is there any language inherently better than any other language?
52:53 – How do children pick up any language without formal teaching?
54:37 – Why is there better adoption of vocal language than written language?
58:20 – What is the future of language?

Dive into Michael Corballis’ research

TEDx talk on language origins
Publications
Books written