Hi everyone. I'm Bryan Bishop, a biohacker and programmer working on fintech, banking, crypto and biotech. I am best known as a contributor to the open-source Bitcoin project, but have also worked on projects in molecular biology and genetic engineering, such as the commercialization of human embryo genetic engineering. Before this, I co-founded Custodia Bank (previously Avanti Bank & Trust) where from 2020-2022 I worked as CTO. From 2014-2018, I was a Senior Software Engineer at LedgerX, the first federally-regulated bitcoin options exchange, where I currently sit on the Board of Directors.

Ask me anything! I will be here Wednesday, April 12. Use the comments below to add questions, and upvote any questions you'd like to see me answer.

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Why do you think we don't have more people starting ambitious genetic engineering projects?

There is definitely a bizarre social taboo surrounding the pursuit of some of these projects. Another constraint is that even if someone is doing the work, they can't exactly be public especially in germline because the privacy of the child is of utmost importance.

Researchers in academia are mostly focused on grants for curing various diseases because that's what appeals to the appetite of federal funding agencies and the philanthropic organizations. The academic biologists tend to be extremely sensitive to public opinion because the public controls much of the federal funding. As a result, they have felt the burn from the anti-GMO people and the attempts at stopping embryonic stem cell research. They absolutely do not want further prohibitions on research and they worry about people outside of academia doing things that cause a backlash on federal funding of researchers.

Thankfully, you don't need to do this work inside of academia.

Focusing on diseases will never lead to extremely cheap interventions; there's simply not enough sick people with the same problem. Nobody really focuses on enhancements. As a result, costs are going to remain high because the market for a specific disease can be incredibly small. Meanwhile the market for general broad spectrum mass market enhancement has a potential population of almost 8 billion people.

I also think that biologists don't paint that interesting of a future. They usually talk about curing diseases but don't have any vision beyond that point. What are we going to do after we cure all diseases? The silicon people have visions of computronium painting the universe. The biologists don't really promote visions of a flourishing biosphere across the entire cosmos or some other moral vision for progress.

There's some good news though. Since not everyone is working on the ambitious projects, there's lots of low-hanging fruit available. I think there's enough people working on curing all diseases or ending aging/anti-aging/longevity. Other ambitious projects include intelligence/memory enhancement, protein engineering, molecular nanotechnology, the complete control over cellular morphological form, brain preservation, brain uploading, cryonic preservation and resuscitation, etc. (I will also note here that longevity is getting lots of attention, but not as much for young people or germline; older people in my opinion might already be aged and that might be irreversible with technology in the next 30-50 years for all I know). I think we should be very excited about the future and work on really hard, important technologies. I think sometimes people might get complacent because it's hard to realize that just several hundred generations ago we were all completely destitute and barely picking ourselves up out of the mud. We aren't that far from where we came from. We absolutely must accelerate.

I would also say that there isn't really VC for ambitious biotech. The way that VC works in biotech is that it's mostly about funding the professor and his 12 postdocs that invented something (call it X) and then they spin out of a university and you fund the company doing X. That's basically the main model. It doesn't leave a lot of room for biology projects that aren't spin outs. "Techbio" has been a recent improvement but it seems to be a lot of software startups? I'm not sure.

On longevity, I should add that I think more people working on ending aging would be good. In the past 5-10 years a lot more companies and funds have formed around longevity so that's very exciting to see. But admittedly we don't have an over-abundance of people working on extreme aging interventions; maybe a few million more people would be good to work on that problem?

How much is innovation in genetic engineering held back by regulation?

Human and agricultural work is held back somewhat. Golden rice was actually rather simple but the biologists took 14 years of safety testing before it was deployed. Several million people went blind in the meantime. This was completely avoidable. GMO rice is not going to take over the world and should not require 14 years of "safety testing". The precautionary principle gives people brain worms. Not the fun genetically modified kind of brainworms either.

Regulation in general holds back a lot of progress in biology. During the pandemic, the FDA suspended the rules and suddenly we had extremely rapid innovation. When they suspended the rules, I thought that was ridiculous. If we know the rules are wrong and broken, then we should get rid of the rules, not have a temporary suspension.

With the excess regulation, you also end up increasing the cost of getting drugs or other things to market and as a result you cut off the lower end of the market. This increases the costs and then investors need to get even higher returns in order to recoup investment.

There is a competitive market for investment yield and regulation sort of shapes the kind of yields that you can get in biotech. As a result, money flowing into biotech innovation is pretty constrained, even if the money is available and people are theoretically interested in funding these kinds of things.

https://www.capitalismmagazine.com/2019/07/the-federal-death-agency-fda/

What are the best near-term/foreseeable applications of genetic engineering? What is the low-hanging fruit here that we can see and define and should go after first?

I have a few other genetic interventions and modifications in the comments, but see also https://diyhpl.us/wiki/genetic-modifications/ for a list.

Hi. Maybe ten years ago, thanks to your role in maintaining #hplusroadmap, you seemed to me a leader of a new generation in transhumanism. Since then, while technology has kept advancing, and various futurist dreams have remained alive, I feel that "transhumanism" as a movement or subculture or identity, lost some of its momentum and its avantgarde character. One way to put it, is that in the 1990s there was a transhumanist futurism centered on Eric Drexler and nanotechnology, but in the 2010s it was eclipsed by the rationalist futurism centered on Eliezer Yudkowsky and artificial intelligence. Of course there have been many many other movements, personalities, and technologies of interest; but I think one could tell a plausible story about the radical techno-futurism of recent decades, in which a cultural transition from transhumanism to rationalism, is at the heart of the narrative. 

Meanwhile, your own bio says that you got heavily into crypto, something I never got into, but which went from a "cypherpunk" fantasy, to a headline phenomenon, and ultimately to a financial ecosystem with a nominal worth of something like a trillion US dollars, and which, pardon my bluntness, seems to be riddled with at least as much hype, scamming, and corruption, as anything in mainstream finance. I would be interested to know how the recent history of transhumanism and futurism looks, from the perspective of someone who took your path, into the world of startups and legal commerce. 

Well, look, if someone wants to join a community that is interested in building cool things then consider hplusroadmap: https://diyhpl.us/wiki/hplusroadmap we recently added a discord bridge. We've been going for 15 years at this point. We have funding available for cool wacky projects, or for not-so-wacky projects, and people are always interested in collaborating or at least providing some input on ideas or what's up. I think the problem is that the extropians, as much as I like them, didn't keep going, and they didn't continue to build or learn or educate and they ended up stagnating. At some level, maybe they were just a group writing cool emails about cool concepts they found interesting? At another level, maybe they really were the origination point of the financial singularity (bitcoin) and maybe their work with the cypherpunks on PGP and SSL and other technologies really should be attributed to the transhumanists...  But for a lot of other tech (like germline engineering, human cloning, etc), we could have done this decades ago and it simply hasn't been done yet. Why? We should encourage more people to build and work on these things. I don't have the culture stuff solved & I'm open to ideas.

My interest in bitcoin could by some be considered a distraction from the more important projects you mention, but with regards to the scams and frauds, I'd point out that my interest has been in bitcoin- which is built by a very conservative group of programmers- and the edge between open-source permissionless innovation and figuring out how to interface with the regulated financial system. This started first with my work at LedgerX, the first CFTC-regulated bitcoin options exchange and clearinghouse, and then with the state-chartered bank in Wyoming that I co-founded. If bitcoin is going to grow and be physically accessible to the general public, then there are going to need to be regulated interfaces into the rest of the world of finance.

I know that might sound a little odd, because the wild west of bitcoin is all about decentralization and often the anarchists promote a very "screw the government" message or what not. But the reality is that only a few people can live like that, in the current environment. If you really want to impact people, there needs to be a transitory pathway available. There are trillions of dollars of financial assets operating on completely archaic systems and rails, and this directly limits our overall liquidity and financial wealth as a society. Likewise, with do-it-yourself biology and biohacking there needs to be a way to do things the right way and take things outside the system and unite them back into the global mainstream systems when the time is right.

More people should just do important things that move progress forward. Laws, policies, regulations and approvals can be figured out. I have faith in this because it's fundamentally moral to work on making things better, even if "better" (or working on "better") has been temporarily defined as unethical by precautionauts/precautioneers. I think that future history will show that working on technological progress is good and important.

Separately my interest in startups, writing software for income, and cryptocurrency has been that this is one way of funding all of the other cool and interesting projects for the transhumanist future. It's kind of interesting to think that the extropians almost missed the financial singularity. Oops?

As for lesswrong.. I think Eliezer Yudkowsky and lesswrong have been something of a "false flag" of technological acceleration. If you were a nerdy kid interested in artificial intelligence, then the watering hole on the internet that you would most likely find would eventually be lesswrong. On the surface, it looks like it has all the things you would want: people interested in talking about AI, people talking about star lifting, or black hole engineering, or total cosmological flourishing of a quadrillion quadrillion humans for the next trillion years. But the more they hang out on lesswrong, the deeper into the philosophy you dwelve, you find that it's mostly a watering hole designed to suck people into a precautionary ideology. As I said, it's something of an ongoing "false flag". I think that many people could have been working on leveling up their skills and projects in biology, chemistry, mechanical engineering, rocketry, or many other subjects, and instead they get sucked into writing long posts about why we shouldn't do anything and how dangerous it all is and how if you do the math just right there's no reason to do anything ever or whatever. I know many of you will say this is an unfair characterization, but I really do believe that lesswrong has done more harm than good to this population that would otherwise have been working on building things.

((While I am ranting about this, I would also like to register a complaint against the form of argumentation that goes like "well if you don't agree with us that AI x-risk is the most important totalizing thing in the world and that all of your actions should be aligned with preventing that outcome then you simply don't understand the arguments" and I assure you I certainly do understand. I have been here for a while lol. But it's a very effective way of dismissing people on the edge of that community who disagree. It's a cool immune system really, you have to admire it for what it is.))
 

What are the most cogent fears about genetic engineering, given the state of the art and what's technically feasible?

Conversely, what are some prominent fears that are unlikely to ever be realised?

One thing that I see is that people are concerned about a loss of genetic diversity or we all become a mono-culture. I don't see that as a reasonable fear. Have you tried to stomp out human diversity before? People are very resilient. They are creative and diverse. They will figure out all kinds of new weird forms and ways to live, even if you don't like it. Only way I see a mono-culture is if we somehow have a world government enforcing it or something, and why would we want that anyway?

If regulation, money, and public opinion were no constraint, how many IQ points could a "CRISPR-baby" gain with modern technology?

How much of an issue is the "causal tagging problem" (i.e. knowing that the genes you're editing actually increase intelligence)?

How much of an issue are off target mutations?

How many IQ points could be gained with just embryo selection?

How much of an issue are off target mutations?


It really depends on your technique. If you are doing CRISPR microinjection (which is very simple, and you should probably not do, because there are other better techniques) then there will likely be off-target mutations. However, in other techniques, you can do quality control, screening, and sequencing before the cells divide or before the embryo implants etc. There are lots of quality control things that can be done which haven't been done yet for human embryo modification.

How many IQ points could be gained with just embryo selection?

It depends on how many embryos you have available. For a normal round of IVF, you're only looking at like 8 embryo choices. It depends on the parents as well. If they don't have the mutations in the first place, then there's nothing to select. I actually think memory is something that should be easier to test for and figure out. If we really wanted to figure out biological intelligence, then we should run a long-term large-scale animal breeding experiment where we try to breed an animal for higher intelligence. We have never done that before, ever. ((Dogs don't count here. Working dogs have specific jobs and while that's smarter, it's not the same thing as selecting for overall general intelligence. I'd imagine that kind of dog would be disruptive in the farm work environment anyway... especially an intermediate along the way to higher intelligence.))

how many IQ points could a "CRISPR-baby" gain with modern technology?

If by "CRISPR baby" you mean "every available means" and not specifically "CRISPR microinjection", then I think there's some IQ points, like the copy number variation one that showed an increase of 2-3 IQ points per copy, but I think we can get some good results even without focusing on IQ. For example, with short sleep you can dramatically increase the number of useful waking hours throughout an entire lifespan. There's also a single mutation that seems likely to improve working memory capacity by 19-21% which is quite useful.

 

How much of an issue is the "causal tagging problem" (i.e. knowing that the genes you're editing actually increase intelligence)?

I am not that big on "polygenic traits modified through hundreds/thousands of point mutations". I think there are other interesting things to do. For example, what if we worked on allowing the neurons to double one more time before becoming post-mitotic? There are other things for us to look at, I think, other than GWAS studies.

what are some examples of beating regulations when it hinders innovation? 

It's interesting how many of these questions are about regulators. I wouldn't have expected that. I think that what's most important is progress, innovation, followed by safety and quality assurance testing, and then getting things out into the markets, followed by fitting it into the forms that regulators expect & working with regulators to create a sane environment for innovation.

Having worked in regulated fintech, I strongly believe that the only way to do good work is by doing good high quality work. Yeah, sure, sometimes you luck out and you get a regulator that understands what's going on and how to do things well. But often you just get precautionary principle stuff from the regulators instead of good help doing QA/testing. Sometimes you can impress them with systems that aren't archaic/legacy and they appreciate the effort you put into doing things well with modern tooling, even if it doesn't conform to the archaic expectations enforced by other regulators. etc. There's some hope here, but not a lot.

What brings me some hope is to think about permissionless innovation. Ultimately you don't have to ask for permission to start a family or birth a new child. Biology is the north star of decentralization. Every single person is a biological lifeform with their own cellular material and DNA. Technological progress means turning our intelligence and thoughts inward and modifying our DNA and our self-defining programs over time. This is not even a matter of free speech, it is a matter of personal agency and freedom to try to fix ourselves or be better or achieve whatever other goals we each have for ourselves and our futures.

At the end of the day, you really don't want a totalitarian government regulating people such that they can't move forward and self-actualize. Thankfully biology is already pretty decentralized and widely available. DNA is one of the most successful technologies of all time.

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