18 ms·

Biology Is Eating the World

181 points by yarapavan 7y ago

Nokinside 7y ago
#1 Supercomputer today is Summit - IBM Power System AC922, IBM POWER9 22C 3.07GHz, NVIDIA Volta GV100, Dual-rail Mellanox EDR Infiniband #1 Brain today (unknown but someone like Terence Tao, Edward Witten, Magnus Carlsen, or Donald Trump) https://aiimpacts.org/brain-performance-in-flops/ https://aiimpacts.org/brain-performance-in-flops/ #1 Supercomputer performance: 148,600 TFlop/s power: 10,096 kW 1# Brain performance: 9,000 - 337,000 TFlop/s power: 20 W. Biology (=organic chemistry) has has huge computational power/watt advantage.
- AllegedAlec 7y ago
  > 1# Brain > performance: 9,000 - 337,000 TFlop/s > power: 20 W. Yeah, not really. These measurements mostly rely on the entire brain firing all at once, while a real brain does not do that.
  - Razengan 7y ago
    GP did specify a generous range.
    - ben_w 7y ago
      Not as broad as the range given in the summary at the top of the link, which says 10^12 to 10^28 FLOPS. The lower end (5e10 operations per Joule) is worse than existing hardware: Google’s first generation TPUs were reported as 40 W for 92 TOPS (8-bit) = 2.3e12 o/J, and Apple’s “Neutral Engine” cores are similar (I can’t find specific values for power use, but that was 5 TOPS (8-bit) and therefore plausibly between 1 and 10 watts).
  - TeMPOraL 7y ago
    I wouldn't even call them "measurements"; last time I checked, the brain didn't run on IEEE 754.
    - adrianN 7y ago
      I did my own measurements, I got about 0.01 floating point multiplications per second out of my brain.
      - thatcat 7y ago
        It's almost like your brain doesn't even have an FPU
        6gvONxR4sf7o 7y ago
        It does! But it's only good for counting up to 3 or 4.
- buboard 7y ago
  That just means we have to use brain-based computers
- asynch8 7y ago
  LMAO did you just reference Donald Trump as the #1 brain today? was this a joke?
  - ben_w 7y ago
    Jokes about Trump being indistinguishable from a Markov chain trained on his tweets notwithstanding, the difference in natural language comprehension between the smartest and dumbest deciles of humans appears to be quite small compared to be small compared to the difference between AI and the average human. Or it was until recently, it’s hard to keep up.
  - jacobush 7y ago
    Textbook neural network local optimum...
hardmaru 7y ago
Literally.
trevyn 7y ago
>The bio companies of the future will take learnings from predecessors in other spaces: consumer, enterprise, fintech, and beyond. The horrors have just begun.
zxcb1 7y ago
Engineering is the opposite of evolution. No?
- tiborsaas 7y ago
  Not sure. I'd say they are parallel things. I think both processes are pointing to the same direction to optimize things towards a certain goal.
  - faceplanted 7y ago
    Evolution doesn't have a goal though, evolution is more like maintenance and jerry rigging than it is engineering.
    - tiborsaas 7y ago
      If obeying thermodynamics count, then it counts as a goal. There's a theory that life (and thus evolution too) exists to better dissipate energy. "England’s calculations suggested that groups of atoms that are driven by external energy sources can behave differently: They tend to start tapping into those energy sources, aligning and rearranging so as to better absorb the energy and dissipate it as heat... England sees life, and its extraordinary confluence of form and function, as the ultimate outcome of dissipation-driven adaptation and self-replication." https://www.quantamagazine.org/first-support-for-a-physics-theory-of-life-20170726/ https://www.quantamagazine.org/first-support-for-a-physics-t...
      - selimthegrim 7y ago
        England’s proof says nothing about how you get to that sink in the first place
    - hoseja 7y ago
      Iterative, empirically driven engineering is evolution-like.
    - Agebor 7y ago
te_chris 7y ago
Welcome to MaddAddam
tiborsaas 7y ago
The world is eating itself
Merrill 7y ago
Interesting summary of biomedical progress, but the extrapolation at the end is a leap too far.
DrAwdeOccarim 7y ago
I've been wondering how long it would be until a16z said something along these lines. I agree completely and am blown away by the progress we have made on informational medicines in the past decade. I would highly recommend to you, if you're a tech-focused person, to get into the field now. I feel like the internet era has matured significantly to the point where the frontier aspect of it has been tamed. Now it's time to move into biology. Look for foundational companies that power the biological information revolution.
- criddell 7y ago
  So what would you tell a kid about to graduate high school that thinks this stuff sounds interesting? What fundamentals should they focus on?
  - DissidentSci 7y ago
    Read about genetics and genomics. Get good at programming and study maths. Aim to do a PhD at the Broad or the Sanger.
    - DrAwdeOccarim 7y ago
      Eh. You can literally do a PhD anywhere (in western countries) and as long as you're good and your skill set is complementary, you will find a good job in industry science. Going to a top-tier university for a PhD may get you a better network, but ultimately when I hire I really don't pay attention to where the degree comes from. Nor do I care about papers beyond did you get your name on (any author position) at least one during your graduate work. The key is complementary and practical skill sets and being able to speak passionately about your work--even if it's arcane or boring.
  - DrAwdeOccarim 7y ago
    Get into a lab doing primary research as soon as possible. Full stop. It can be a college/university lab, government, foundation, anything. In my opinion, information medicines is the fantastic convergence of bio and tech, so I would look for biochemistry labs that focus on DNA and RNA. Once you have a list of local research institutes, I can help you pick a lab to focus on. Then you just hammer them constantly by email and in person asking questions about the work until they hire you to wash the dishes :)
Razengan 7y ago
If the last time was an indication I fear we might be in for an spate of "X is eating the world" posts again.
warlog 7y ago
Or: Biology is really hard, and returns to investors in the space have been pretty tame, and taken longer than promised (expected). See commentary by Peter Thiel in Zero to One for more on this topic. In response to this reality, one tactic is to create a narrative that sells the vision of biotech as a tech or engineering discipline to an investor audience that is naive about biology and uber bullish on tech eg, this article). "Biology? It's just engineering, we can engineer things, we'll just engineer biology (please invest in us as if we're tech]". Never mind that engineering is a tradition built on minimizing variation, while biology is a science founded on understanding a built-in mechanism for generating variation. "Life finds a way". Indeed. I've been on numerous synbio projects and one thing is certain, evolution is always driving against the engineered design. And by driving against, I mean undoing. Entropy might slowly undue engineering, but mutation and selection? It's an entropic accelerant for engineered outcomes. Also, engineering is about "parts" and synbio is constantly dreaming of building things by putting parts (promotors, genes, etc) together from a catalogue. In reality, biology is interactions, where the expression of almost everything is dependent on the context of all the other parts. So outcomes aren't simply "the sum of the parts". When they are it's for a minority of cases. Finally, as you scale a process (say from a test tube to a 1,000,000L industrial sized fermentation tank, biology almost never cooperates. Biotech's dirty secret is that biology is Not engineering (it is still a discovery science)...but the music is still playing folks, dance on! (Sorry, it's early, I'm still pre caffeinated, and this topic always rankles me).
- ohduran 7y ago
  "Life finds a way", Jurassic Park jokes aside, was the moral of the whole saga: Thou shall not mess with systems you do not understand. Taleb talks about caution all the time for a reason, complex systems are, indeed, complex.
  - TeMPOraL 7y ago
    And here I thought the moral was "thou shall not be stupid or arrogant". The only way we can understand a complex system is by messing with it.
fabian2k 7y ago
This seems horribly naive and dramatically understates just how difficult drug development is. We simply don't understand enough of the complex interactions that happen in a biological organism, and in the end we have to do very expensive trial and error to determine whether any drug or intervention actually works.
- randcraw 7y ago
  Yes to this. At the Very Big Pharma where I work about 20 years ago we took some baby steps toward adopting an engineering approach toward bio-based systems engineering. Systems biology and in silico modeling of disease had long promised to short circuit the protracted process of drug development. And maybe one day that may yet prove true. But after 15 years of building models of disease or therapy based on data gleaned from lab assays and preclinical/ clinical studies, we found that there were still far too many 'degrees of freedom' in the parameter space of interest to convince the biologists that our models could add sufficient real value to their work for our work to continue. Fortunately, medicinal chemists have fared better in silico, often employing computational techniques to reduce their search space for a compound desired behavior. But I think no one would describe their models of molecular docking / binding as manifestations of engineering or systems biology.
floki999 7y ago
A VC hyping-up its own book & strategy. Biology is certainly not an engineering discipline. This claim that it is reflects how little the authors know about biological systems and our limited understanding of biological diversity. Reads like lame sell-side broker research. I recall the promises of biotech of the mid 80’s, the promises of bioinformatics etc etc. Same story, different decade.
- georgeek 7y ago
  Is this the hype train? Yes to a large extent. However some people at a16z do know what they are talking about. Ex: Vijay Pande is a partner there and an (adjunct) professor of Bioengineering at Stanford. He and the team around him do have an educated guess how biotech today is different from 20 years ago.
  - floki999 7y ago
    I’m quite sure that a16z folks are smart, and perhaps the hyping-up does achieve an intended purpose. What bugs me is the non-stop need to feed narratives which dum-down and embellish reality.
    - boringg 7y ago
      Well said.
- boringg 7y ago
  Feel the same way about reading this. Felt like gross marketing speak - which to me felt like lazy writing. To the other persons comment (sorry for not replying to your thread) - of course there are smart people at A16z though it is important to read that smart != correct.
euroPoor 7y ago
It’s called ‘millenium’ non-plural.
Udo 7y ago
> Bio today is where information technology was 50 years ago: on the precipice of touching all of our lives. Bio has been touching all of our lives for a long time now, from vaccines to food to basic research yielding large advancements in medical understanding. What we are on the precipice of may be personalized or customized biochemistry, which is something we desperately need if we ever want to attack diseases like cancer, enable radical regenerative intervention, or tackle the effects of aging. On a side note, I feel that we should put a moratorium on the phrase "X is eating the world". Right now we're using it whenever something needs to be hyped and it's becoming quite cringy.
hanuman 7y ago
Biology has been eating the world for 4 billion years. MA: "Bio today is where information technology was 50 years ago." Bio today is still in the pre-transistor era of IT. There is no tool that doubles our capabilities to manipulate molecular processes every 18 months. No, genome sequencing does not count, it is "read only." No, as amazing and as promising as it is, CRISPR does not count. For the present we continue to merely tinker, which is invaluable and necessary to more forward. Maybe once we figure out how to efficiently, reproducibly engineer enzymes, which truly accelerate molecular processes, we can claim that human-directed bio is eating the world. Until then, nature-driven bio is still on top.
tompccs 7y ago
I am very bear-ish on biotech. These are not systems we humans have built from the ground up. Computers are built by humans from the ground up: literally every aspect of a computer is deterministic and documented. And yet even computers can throw up surprises to programmers on a pretty regular basis. The idea that our understanding of molecular biology is as mature and stable as our understanding of the field effect transistor was in the 1950s is frankly laughable. I predict many many investors getting burnt by biotech, as well as some pretty nasty externalities if regulators buy the hype. edit: improve sentence structure
skywhopper 7y ago
Ugh. We've heard all of this before for decades. Yes, progress is being rapidly made on understanding biological processes, but with as many steps back as forward, as we realize there are entirely new categories of things that we didn't even know we don't know. The hubris on display here is typical of tech VCs, who eventually believe their own hype. If it's hard for humans to comprehend, just rub some machine learning on it... ignore that we're finally realizing that machine learning's limitations are significant, but that we can only discover how wrong they can be on results that humans can double-check. And the naive application of software engineering buzzwords like "modular" and "iterative" to drug development and biological processes is seriously dangerous. You don't want to move fast and break things when we're talking about human health and genetics. This article is full of misleading claims and overstatements of reality. It's easy to make things sound great when you entirely ignore the reality of existing and potential technology, but of course I don't expect anything different from these folks.
nscalf 7y ago
Let's say you're a tech expert, how do you get involved with the biotech revolution. Is there any resources to learn what is currently available, how you can contribute, etc? I think this field will likely yield some of the most impactful tools and innovations we've ever seen.
- madhadron 7y ago
  This is something I have dealt with a few times. There really isn't a good resource to point someone from a math, informatics, physics, etc. to so they can get an understanding of how the field works. People end up recommending books like Alberts or other things that provide lots of pictures and names in a particular, small area of biology but don't give any idea of what the field covers or what thought processes work in it. The closest thing I have is twenty-ish pages of notes I braindumped for a colleague who had just entered bioinformatics from computer science, but those already assumed lots of conversations and information already in place. It's made even weirder because biology is three fields inextricably intertwined (genetics, physiology, natural history). For each one you can start at the beginning, but how do you provide some kind of linear path through all three at once?
  - haihaibye 7y ago
    With age and humility has your view of the field tempered with time from "Fuck you, bioinformatics. Eat shit and die."[1]? I totally get your point, and it maddens me daily but I take the interesting + meaningful work/money tradeoff and enjoy being one of the best coders in a building (much harder in pure tech) [1] http://madhadron.com/posts/2012-03-26-a-farewell-to-bioinformatics.html http://madhadron.com/posts/2012-03-26-a-farewell-to-bioinfor...
    - madhadron 7y ago
      Oh boy, that rant. Doubtless the most far reaching and influential thing I have ever written. It gets assigned in bioinformatics classes around the world, which puzzles me in the extreme, and I get emails every couple of months from new readers of it asking my position. My usual response these days is that if it's raising red flags for them, they should explore what troubles them until they have satisfied themselves rather than taking the word of some random guy on the Internet. From here inside my head, I think my criticisms are still accurate, nor have I seen any actual refutation of them. Lots of ad hominems. Many people not understanding that terms like "computationally difficult" are precise terms of art, and have nothing to do with intellectual or conceptual difficulty. With age and humility and, more importantly, absence, my attitude is probably better described as "meh."
cdcox 7y ago
I think the biology revolution will look less like the computing (1940s-2010s) or transportation (1890s-1970s) revolutions and more like the chemistry revolution (1800s-1950s). It will be less iterating on one process and more years of seemingly stagnant progress while people tinker with the last big thing until the next big thing roars out of the gates. Iteration will be brief and seemingly unimpressive. The only real progress will be, that which was expensive and hard will become cheap, but unlike compute that won't necessarily be the driver of progress. For instance early genetic testing revealed a huge number of disorders that could be linked to single genes that changed the game for how a certain sub-population has kids and treatment for a handful of disorders. Then it turned out a lot of stuff was multigenic or only very partially genetic and progress has stalled. As genetic testing has gotten cheaper we have learned more, but actual usable insights are rare. Or take lab grown insulin from 1980s, it was a huge deal, everyone worked on similar technologies and knock ins and for a handful of disorders it was a complete game changer that petered out medically speaking. It saw a weird second life in farming and GMOs for a time that helped improve processes but didn't really move the needle in a big way. Then as it got cheaper, and new more efficient tools emergedm it reexploded as the field of biologicals, which have been great drugs since the mid-2000s. And as the technology gets really cheap we are seeing products like lab meats, Impossible leading the charge there, emerge. Now we are on CRISPR, RNA-sequencing, CAR-T, and tissue engineering all of which, when they hit will have massive impact, but then slow down for a bit until the next big thing revs up. This parallels chemistry where the theories of thermodynamics and gas laws emerged, sped everything forward, then petered out. Then organic chemistry emerged using a lot of the ideas developed by the previous field, sped everything forward for a while then slowed down. Then inorganic and solid state chemistry etc. But there was never a 18 month doubling it was more like a 10 year lull followed by 1000x in 5 years, if you were counting for example, the number of compounds developed. You could smooth the curve and pretend it was like compute but it's not. We'll just look back in 20ish years, or even look back today at the 1950s, and say 'wow there is a lot of stuff in our life that was based on biological research where did that come from'. Just like someone in the 1940s would look back and be like 'wow where did all this plastic/metal fab come from'.
- DrScientist 7y ago
  Good points - but the thing that struck me the most with the comparison to chemistry was how many of those new wonder materials turned out to be more dangerous than we originally thought. The risks with poorly conceived GMO's are so much higher... but fortunately the technology to do it has been out of the reach of all but a few large companies or institutes who have by and large been very careful. But now the technology is becoming accessible even to individual enthusiasts..... It's like nuclear technology becoming in reach of the ordinary citizen.
tito 7y ago
A16Z has only published "Eating the World" articles two other times, to great success: Mobile is eating the world (2016) Software is eating the world (2011)
qsymmachus 7y ago
"People who excel at software design become convinced that they have a unique ability to understand any kind of system at all, from first principles, without prior training, thanks to their superior powers of analysis. Success in the artificially constructed world of software design promotes a dangerous confidence." http://idlewords.com/talks/sase_panel.htm http://idlewords.com/talks/sase_panel.htm
DrScientist 7y ago
Imagine a solar-powered, self-replicating, self-repairing machine that can do carbon capture, clean the air, and improve biodiversity in one go and it's ridiculously cheap and easy to operate and maintain. Yep a tree. It always amazes me that people get excited about a new car, new phone or a new software release from a technical angle ( not what you can do with it - that's fine ) - but also don't see the amazing machines called life all around us as interesting at all! You are always the most complex type of machine in the room - by many orders of magnitude. Yep, the risks are higher in biotech, yep the rewards are perhaps not as good as a Google etc, and it's way harder. On the other hand it's more interesting and in the end these companies are creating new treatments for cancer or heart failure etc. Disclosure: I was part of a biotech 'unicorn'. In terms of whether we are at the cusp of a biotech revolution - I'd say it really kicked off 20-30 years ago and is already here - the new wave of immuno-oncology drugs transforming cancer treatment are a good example. I think the role of computers in the future is a little overhyped - it's necessary, but not the fundamental driver - the drivers are the new experimental technologies generating the data at unprecedented scale.
- eikenberry 7y ago
  IMO this is easy to explain by people's infatuation with novelty. Say you took that tree, engineered it to grow to 2 feet tall with bio-luminescent leaves and people would be fascinated by it... until that became old-hat, then it'd be ignored again.
- themacguffinman 7y ago
  I think the tree example is silly, trees aren't good tech because they're not very controllable and often very difficult to modify. And like many biological things, they're not really optimized for our convenience. Imagine a disease/bug-prone, space inefficient, waste dropping, telemetry-less, allergy-inducing machine that requires continuous water deliveries and a multi-year build process. Yep a tree. I won't try to tell you that you can't find trees and other biological constructs more interesting, and they certainly pose harder problems, but I'd think (and hope) that the future isn't overly complicated biotech adapted from even more complicated and wasteful natural systems. Right now we have to deal with heart failure and cancer because our crappy bodies are the best we've got, but I would think that the long-term future belongs to engineered systems that we can control, optimize, and understand.
maerF0x0 7y ago
One thing about this that scares me is looking at the negative parallels, black mirror style, between computing and biology. When I hear "iterative" design I think of shitty car infotainment or router software that only works half the time and never is updated/supported... Except its under my skin and I cannot get it out. When I hear designer molecules + DNA I think of DRM and a lack of "right to repair" . But now its inside your body and the business owns it.. err you...
carapace 7y ago
Biology is the world. The single most important aspect of all of this is the metaphysics. https://en.wikipedia.org/wiki/I_and_Thou https://en.wikipedia.org/wiki/I_and_Thou > Buber's main proposition is that we may address existence in two ways: > 1. The attitude of the "I" towards an "It", towards an object that is separate in itself, which we either use or experience. > 2. The attitude of the "I" towards "Thou", in a relationship in which the other is not separated by discrete bounds. Biology is Thou. - - - - When Prof. Michael Levin talks about "What Bodies Think About: Bioelectric Computation Outside the Nervous System" (youtube.com) https://news.ycombinator.com/item?id=18736698 https://news.ycombinator.com/item?id=18736698 he keeps saying, "What if our technology could do this?" The answer is, our technology already does "this". We are 4By-old nanotechnology. You've heard of Grey Goo? It turns out that the oceans are already "Blue" Goo. https://en.wikipedia.org/wiki/Grey_goo https://en.wikipedia.org/wiki/Grey_goo > Gray goo (also spelled grey goo) is a hypothetical global catastrophic scenario involving molecular nanotechnology in which out-of-control self-replicating machines consume all biomass on Earth while building more of themselves,[1][2] a scenario that has been called ecophagy ("eating the environment", more literally "eating the habitation").[3] The original idea assumed machines were designed to have this capability, while popularizations have assumed that machines might somehow gain this capability by accident. https://en.wikipedia.org/wiki/Marine_bacteriophage https://en.wikipedia.org/wiki/Marine_bacteriophage > Marine viruses, although microscopic and essentially unnoticed by scientists until recently, are the most abundant and diverse biological entities in the ocean. Viruses have an estimated abundance of 10^30 in the ocean, or between [10^6 and 10^11] per millilitre. > Although marine viruses have only recently been studied extensively, they are already known to hold critical roles in many ecosystem functions and cycles. We keep making discoveries (like the bacteriophages) that show us that we have no real idea what's going on in the biosphere, which includes our bodies. I think it behooves us to wait a few centuries before we go hog wild on the only known ecosystem in the entire Universe, eh?
angel_j 7y ago
For context, simply click all 37 links in this article.
babesh 7y ago
Shouldn't we (at least in the US) be more concerned with getting health care costs under control and universal? This manifesto is mostly about making money rather than about general human welfare. The issues are not due to technological limitations.
- pcwalton 7y ago
  I mean, yes, we should do that, but we also need medical advances. Right now, if you get Alzheimer's disease, it doesn't matter how much money you have: you will suffer a long cognitive decline until you are no longer recognizable, at which point you will die. The entire process places an enormous social and financial burden on society. We need to fix that.
- djeric3 7y ago
  Personally, I see no greater advance for humanity than curing diseases. Some of these illnesses have been with us since before humans became modern humans, and now for the first time ever, we have a chance at curing or preventing them. I'd take new disease cures over colonizing Mars. But more to your point, I understand health care costs are crazy (especially in the US), but I am concerned that capping health care expenditures will dis-incentivize companies from taking risks on new vaccines and therapies.
6gvONxR4sf7o 7y ago
>We are at the beginning of a new era, where biology has shifted from empirical science to an engineering discipline. What the hell do they think doctors and other healthcare providers have done for all of history? What do they think surgery is? This is such fluffy hype, I feel insulted.
breck 7y ago
If anyone is interested in a revolutionary new type of medical records system where you can copy/paste your entire medical records in a safe way, we are working on a system here called Pau (https://github.com/treenotation/pau https://github.com/treenotation/pau). Imagine if you could just copy/paste your medical records in an email to change doctors. Or participate in a new medical study via a simple copy/paste. Or if you were in an acute care setting and your healthcare providers could instantly call up all your relevant medical history. We are going to enable those sort of things.
ljw1001 7y ago
Hype and cliches are eating the world. You heard it here first.
m3kw9 7y ago
Immune related diseases won’t really be solved unless we really understand how the immune system works. Because of the complexity there seem to be little incentive to fix root causes rather than just inhibit the immunes response I.e. patching

181 points by yarapavan 7y ago

#1 Supercomputer today is Summit - IBM Power System AC922, IBM POWER9 22C 3.07GHz, NVIDIA Volta GV100, Dual-rail Mellanox EDR Infiniband #1 Brain today (unknown but someone like Terence Tao, Edward Witten, Magnus Carlsen, or Donald Trump) https://aiimpacts.org/brain-performance-in-flops/ https://aiimpacts.org/brain-performance-in-flops/ #1 Supercomputer performance: 148,600 TFlop/s power: 10,096 kW 1# Brain performance: 9,000 - 337,000 TFlop/s power: 20 W. Biology (=organic chemistry) has has huge computational power/watt advantage.

AllegedAlec 7y ago
> 1# Brain > performance: 9,000 - 337,000 TFlop/s > power: 20 W. Yeah, not really. These measurements mostly rely on the entire brain firing all at once, while a real brain does not do that.
- Razengan 7y ago
  GP did specify a generous range.
  - ben_w 7y ago
    Not as broad as the range given in the summary at the top of the link, which says 10^12 to 10^28 FLOPS. The lower end (5e10 operations per Joule) is worse than existing hardware: Google’s first generation TPUs were reported as 40 W for 92 TOPS (8-bit) = 2.3e12 o/J, and Apple’s “Neutral Engine” cores are similar (I can’t find specific values for power use, but that was 5 TOPS (8-bit) and therefore plausibly between 1 and 10 watts).
- TeMPOraL 7y ago
  I wouldn't even call them "measurements"; last time I checked, the brain didn't run on IEEE 754.
  - adrianN 7y ago
    I did my own measurements, I got about 0.01 floating point multiplications per second out of my brain.
    - thatcat 7y ago
      It's almost like your brain doesn't even have an FPU
      - 6gvONxR4sf7o 7y ago
        It does! But it's only good for counting up to 3 or 4.
buboard 7y ago
That just means we have to use brain-based computers
asynch8 7y ago
LMAO did you just reference Donald Trump as the #1 brain today? was this a joke?
- ben_w 7y ago
  Jokes about Trump being indistinguishable from a Markov chain trained on his tweets notwithstanding, the difference in natural language comprehension between the smartest and dumbest deciles of humans appears to be quite small compared to be small compared to the difference between AI and the average human. Or it was until recently, it’s hard to keep up.
- jacobush 7y ago
  Textbook neural network local optimum...

hardmaru 7y ago

Literally.

trevyn 7y ago

>The bio companies of the future will take learnings from predecessors in other spaces: consumer, enterprise, fintech, and beyond. The horrors have just begun.

zxcb1 7y ago

Engineering is the opposite of evolution. No?

tiborsaas 7y ago
Not sure. I'd say they are parallel things. I think both processes are pointing to the same direction to optimize things towards a certain goal.
- faceplanted 7y ago
  Evolution doesn't have a goal though, evolution is more like maintenance and jerry rigging than it is engineering.
  - tiborsaas 7y ago
    If obeying thermodynamics count, then it counts as a goal. There's a theory that life (and thus evolution too) exists to better dissipate energy. "England’s calculations suggested that groups of atoms that are driven by external energy sources can behave differently: They tend to start tapping into those energy sources, aligning and rearranging so as to better absorb the energy and dissipate it as heat... England sees life, and its extraordinary confluence of form and function, as the ultimate outcome of dissipation-driven adaptation and self-replication." https://www.quantamagazine.org/first-support-for-a-physics-theory-of-life-20170726/ https://www.quantamagazine.org/first-support-for-a-physics-t...
    - selimthegrim 7y ago
      England’s proof says nothing about how you get to that sink in the first place
  - hoseja 7y ago
    Iterative, empirically driven engineering is evolution-like.
  - Agebor 7y ago

te_chris 7y ago

Welcome to MaddAddam

tiborsaas 7y ago

The world is eating itself

Merrill 7y ago

Interesting summary of biomedical progress, but the extrapolation at the end is a leap too far.

DrAwdeOccarim 7y ago

I've been wondering how long it would be until a16z said something along these lines. I agree completely and am blown away by the progress we have made on informational medicines in the past decade. I would highly recommend to you, if you're a tech-focused person, to get into the field now. I feel like the internet era has matured significantly to the point where the frontier aspect of it has been tamed. Now it's time to move into biology. Look for foundational companies that power the biological information revolution.

criddell 7y ago
So what would you tell a kid about to graduate high school that thinks this stuff sounds interesting? What fundamentals should they focus on?
- DissidentSci 7y ago
  Read about genetics and genomics. Get good at programming and study maths. Aim to do a PhD at the Broad or the Sanger.
  - DrAwdeOccarim 7y ago
    Eh. You can literally do a PhD anywhere (in western countries) and as long as you're good and your skill set is complementary, you will find a good job in industry science. Going to a top-tier university for a PhD may get you a better network, but ultimately when I hire I really don't pay attention to where the degree comes from. Nor do I care about papers beyond did you get your name on (any author position) at least one during your graduate work. The key is complementary and practical skill sets and being able to speak passionately about your work--even if it's arcane or boring.
- DrAwdeOccarim 7y ago
  Get into a lab doing primary research as soon as possible. Full stop. It can be a college/university lab, government, foundation, anything. In my opinion, information medicines is the fantastic convergence of bio and tech, so I would look for biochemistry labs that focus on DNA and RNA. Once you have a list of local research institutes, I can help you pick a lab to focus on. Then you just hammer them constantly by email and in person asking questions about the work until they hire you to wash the dishes :)

Razengan 7y ago

If the last time was an indication I fear we might be in for an spate of "X is eating the world" posts again.

warlog 7y ago

Or: Biology is really hard, and returns to investors in the space have been pretty tame, and taken longer than promised (expected). See commentary by Peter Thiel in Zero to One for more on this topic. In response to this reality, one tactic is to create a narrative that sells the vision of biotech as a tech or engineering discipline to an investor audience that is naive about biology and uber bullish on tech eg, this article). "Biology? It's just engineering, we can engineer things, we'll just engineer biology (please invest in us as if we're tech]". Never mind that engineering is a tradition built on minimizing variation, while biology is a science founded on understanding a built-in mechanism for generating variation. "Life finds a way". Indeed. I've been on numerous synbio projects and one thing is certain, evolution is always driving against the engineered design. And by driving against, I mean undoing. Entropy might slowly undue engineering, but mutation and selection? It's an entropic accelerant for engineered outcomes. Also, engineering is about "parts" and synbio is constantly dreaming of building things by putting parts (promotors, genes, etc) together from a catalogue. In reality, biology is interactions, where the expression of almost everything is dependent on the context of all the other parts. So outcomes aren't simply "the sum of the parts". When they are it's for a minority of cases. Finally, as you scale a process (say from a test tube to a 1,000,000L industrial sized fermentation tank, biology almost never cooperates. Biotech's dirty secret is that biology is Not engineering (it is still a discovery science)...but the music is still playing folks, dance on! (Sorry, it's early, I'm still pre caffeinated, and this topic always rankles me).

ohduran 7y ago
"Life finds a way", Jurassic Park jokes aside, was the moral of the whole saga: Thou shall not mess with systems you do not understand. Taleb talks about caution all the time for a reason, complex systems are, indeed, complex.
- TeMPOraL 7y ago
  And here I thought the moral was "thou shall not be stupid or arrogant". The only way we can understand a complex system is by messing with it.

fabian2k 7y ago

This seems horribly naive and dramatically understates just how difficult drug development is. We simply don't understand enough of the complex interactions that happen in a biological organism, and in the end we have to do very expensive trial and error to determine whether any drug or intervention actually works.

randcraw 7y ago
Yes to this. At the Very Big Pharma where I work about 20 years ago we took some baby steps toward adopting an engineering approach toward bio-based systems engineering. Systems biology and in silico modeling of disease had long promised to short circuit the protracted process of drug development. And maybe one day that may yet prove true. But after 15 years of building models of disease or therapy based on data gleaned from lab assays and preclinical/ clinical studies, we found that there were still far too many 'degrees of freedom' in the parameter space of interest to convince the biologists that our models could add sufficient real value to their work for our work to continue. Fortunately, medicinal chemists have fared better in silico, often employing computational techniques to reduce their search space for a compound desired behavior. But I think no one would describe their models of molecular docking / binding as manifestations of engineering or systems biology.

floki999 7y ago

A VC hyping-up its own book & strategy. Biology is certainly not an engineering discipline. This claim that it is reflects how little the authors know about biological systems and our limited understanding of biological diversity. Reads like lame sell-side broker research. I recall the promises of biotech of the mid 80’s, the promises of bioinformatics etc etc. Same story, different decade.

georgeek 7y ago
Is this the hype train? Yes to a large extent. However some people at a16z do know what they are talking about. Ex: Vijay Pande is a partner there and an (adjunct) professor of Bioengineering at Stanford. He and the team around him do have an educated guess how biotech today is different from 20 years ago.
- floki999 7y ago
  I’m quite sure that a16z folks are smart, and perhaps the hyping-up does achieve an intended purpose. What bugs me is the non-stop need to feed narratives which dum-down and embellish reality.
  - boringg 7y ago
    Well said.
boringg 7y ago
Feel the same way about reading this. Felt like gross marketing speak - which to me felt like lazy writing. To the other persons comment (sorry for not replying to your thread) - of course there are smart people at A16z though it is important to read that smart != correct.

euroPoor 7y ago

It’s called ‘millenium’ non-plural.

Udo 7y ago

> Bio today is where information technology was 50 years ago: on the precipice of touching all of our lives. Bio has been touching all of our lives for a long time now, from vaccines to food to basic research yielding large advancements in medical understanding. What we are on the precipice of may be personalized or customized biochemistry, which is something we desperately need if we ever want to attack diseases like cancer, enable radical regenerative intervention, or tackle the effects of aging. On a side note, I feel that we should put a moratorium on the phrase "X is eating the world". Right now we're using it whenever something needs to be hyped and it's becoming quite cringy.

hanuman 7y ago

Biology has been eating the world for 4 billion years. MA: "Bio today is where information technology was 50 years ago." Bio today is still in the pre-transistor era of IT. There is no tool that doubles our capabilities to manipulate molecular processes every 18 months. No, genome sequencing does not count, it is "read only." No, as amazing and as promising as it is, CRISPR does not count. For the present we continue to merely tinker, which is invaluable and necessary to more forward. Maybe once we figure out how to efficiently, reproducibly engineer enzymes, which truly accelerate molecular processes, we can claim that human-directed bio is eating the world. Until then, nature-driven bio is still on top.

tompccs 7y ago

I am very bear-ish on biotech. These are not systems we humans have built from the ground up. Computers are built by humans from the ground up: literally every aspect of a computer is deterministic and documented. And yet even computers can throw up surprises to programmers on a pretty regular basis. The idea that our understanding of molecular biology is as mature and stable as our understanding of the field effect transistor was in the 1950s is frankly laughable. I predict many many investors getting burnt by biotech, as well as some pretty nasty externalities if regulators buy the hype. edit: improve sentence structure

skywhopper 7y ago

Ugh. We've heard all of this before for decades. Yes, progress is being rapidly made on understanding biological processes, but with as many steps back as forward, as we realize there are entirely new categories of things that we didn't even know we don't know. The hubris on display here is typical of tech VCs, who eventually believe their own hype. If it's hard for humans to comprehend, just rub some machine learning on it... ignore that we're finally realizing that machine learning's limitations are significant, but that we can only discover how wrong they can be on results that humans can double-check. And the naive application of software engineering buzzwords like "modular" and "iterative" to drug development and biological processes is seriously dangerous. You don't want to move fast and break things when we're talking about human health and genetics. This article is full of misleading claims and overstatements of reality. It's easy to make things sound great when you entirely ignore the reality of existing and potential technology, but of course I don't expect anything different from these folks.

nscalf 7y ago

Let's say you're a tech expert, how do you get involved with the biotech revolution. Is there any resources to learn what is currently available, how you can contribute, etc? I think this field will likely yield some of the most impactful tools and innovations we've ever seen.

madhadron 7y ago
This is something I have dealt with a few times. There really isn't a good resource to point someone from a math, informatics, physics, etc. to so they can get an understanding of how the field works. People end up recommending books like Alberts or other things that provide lots of pictures and names in a particular, small area of biology but don't give any idea of what the field covers or what thought processes work in it. The closest thing I have is twenty-ish pages of notes I braindumped for a colleague who had just entered bioinformatics from computer science, but those already assumed lots of conversations and information already in place. It's made even weirder because biology is three fields inextricably intertwined (genetics, physiology, natural history). For each one you can start at the beginning, but how do you provide some kind of linear path through all three at once?
- haihaibye 7y ago
  With age and humility has your view of the field tempered with time from "Fuck you, bioinformatics. Eat shit and die."[1]? I totally get your point, and it maddens me daily but I take the interesting + meaningful work/money tradeoff and enjoy being one of the best coders in a building (much harder in pure tech) [1] http://madhadron.com/posts/2012-03-26-a-farewell-to-bioinformatics.html http://madhadron.com/posts/2012-03-26-a-farewell-to-bioinfor...
  - madhadron 7y ago
    Oh boy, that rant. Doubtless the most far reaching and influential thing I have ever written. It gets assigned in bioinformatics classes around the world, which puzzles me in the extreme, and I get emails every couple of months from new readers of it asking my position. My usual response these days is that if it's raising red flags for them, they should explore what troubles them until they have satisfied themselves rather than taking the word of some random guy on the Internet. From here inside my head, I think my criticisms are still accurate, nor have I seen any actual refutation of them. Lots of ad hominems. Many people not understanding that terms like "computationally difficult" are precise terms of art, and have nothing to do with intellectual or conceptual difficulty. With age and humility and, more importantly, absence, my attitude is probably better described as "meh."

cdcox 7y ago

I think the biology revolution will look less like the computing (1940s-2010s) or transportation (1890s-1970s) revolutions and more like the chemistry revolution (1800s-1950s). It will be less iterating on one process and more years of seemingly stagnant progress while people tinker with the last big thing until the next big thing roars out of the gates. Iteration will be brief and seemingly unimpressive. The only real progress will be, that which was expensive and hard will become cheap, but unlike compute that won't necessarily be the driver of progress. For instance early genetic testing revealed a huge number of disorders that could be linked to single genes that changed the game for how a certain sub-population has kids and treatment for a handful of disorders. Then it turned out a lot of stuff was multigenic or only very partially genetic and progress has stalled. As genetic testing has gotten cheaper we have learned more, but actual usable insights are rare. Or take lab grown insulin from 1980s, it was a huge deal, everyone worked on similar technologies and knock ins and for a handful of disorders it was a complete game changer that petered out medically speaking. It saw a weird second life in farming and GMOs for a time that helped improve processes but didn't really move the needle in a big way. Then as it got cheaper, and new more efficient tools emergedm it reexploded as the field of biologicals, which have been great drugs since the mid-2000s. And as the technology gets really cheap we are seeing products like lab meats, Impossible leading the charge there, emerge. Now we are on CRISPR, RNA-sequencing, CAR-T, and tissue engineering all of which, when they hit will have massive impact, but then slow down for a bit until the next big thing revs up. This parallels chemistry where the theories of thermodynamics and gas laws emerged, sped everything forward, then petered out. Then organic chemistry emerged using a lot of the ideas developed by the previous field, sped everything forward for a while then slowed down. Then inorganic and solid state chemistry etc. But there was never a 18 month doubling it was more like a 10 year lull followed by 1000x in 5 years, if you were counting for example, the number of compounds developed. You could smooth the curve and pretend it was like compute but it's not. We'll just look back in 20ish years, or even look back today at the 1950s, and say 'wow there is a lot of stuff in our life that was based on biological research where did that come from'. Just like someone in the 1940s would look back and be like 'wow where did all this plastic/metal fab come from'.

DrScientist 7y ago
Good points - but the thing that struck me the most with the comparison to chemistry was how many of those new wonder materials turned out to be more dangerous than we originally thought. The risks with poorly conceived GMO's are so much higher... but fortunately the technology to do it has been out of the reach of all but a few large companies or institutes who have by and large been very careful. But now the technology is becoming accessible even to individual enthusiasts..... It's like nuclear technology becoming in reach of the ordinary citizen.

tito 7y ago

A16Z has only published "Eating the World" articles two other times, to great success: Mobile is eating the world (2016) Software is eating the world (2011)

qsymmachus 7y ago

"People who excel at software design become convinced that they have a unique ability to understand any kind of system at all, from first principles, without prior training, thanks to their superior powers of analysis. Success in the artificially constructed world of software design promotes a dangerous confidence." http://idlewords.com/talks/sase_panel.htm http://idlewords.com/talks/sase_panel.htm

DrScientist 7y ago

Imagine a solar-powered, self-replicating, self-repairing machine that can do carbon capture, clean the air, and improve biodiversity in one go and it's ridiculously cheap and easy to operate and maintain. Yep a tree. It always amazes me that people get excited about a new car, new phone or a new software release from a technical angle ( not what you can do with it - that's fine ) - but also don't see the amazing machines called life all around us as interesting at all! You are always the most complex type of machine in the room - by many orders of magnitude. Yep, the risks are higher in biotech, yep the rewards are perhaps not as good as a Google etc, and it's way harder. On the other hand it's more interesting and in the end these companies are creating new treatments for cancer or heart failure etc. Disclosure: I was part of a biotech 'unicorn'. In terms of whether we are at the cusp of a biotech revolution - I'd say it really kicked off 20-30 years ago and is already here - the new wave of immuno-oncology drugs transforming cancer treatment are a good example. I think the role of computers in the future is a little overhyped - it's necessary, but not the fundamental driver - the drivers are the new experimental technologies generating the data at unprecedented scale.

eikenberry 7y ago
IMO this is easy to explain by people's infatuation with novelty. Say you took that tree, engineered it to grow to 2 feet tall with bio-luminescent leaves and people would be fascinated by it... until that became old-hat, then it'd be ignored again.
themacguffinman 7y ago
I think the tree example is silly, trees aren't good tech because they're not very controllable and often very difficult to modify. And like many biological things, they're not really optimized for our convenience. Imagine a disease/bug-prone, space inefficient, waste dropping, telemetry-less, allergy-inducing machine that requires continuous water deliveries and a multi-year build process. Yep a tree. I won't try to tell you that you can't find trees and other biological constructs more interesting, and they certainly pose harder problems, but I'd think (and hope) that the future isn't overly complicated biotech adapted from even more complicated and wasteful natural systems. Right now we have to deal with heart failure and cancer because our crappy bodies are the best we've got, but I would think that the long-term future belongs to engineered systems that we can control, optimize, and understand.

maerF0x0 7y ago

One thing about this that scares me is looking at the negative parallels, black mirror style, between computing and biology. When I hear "iterative" design I think of shitty car infotainment or router software that only works half the time and never is updated/supported... Except its under my skin and I cannot get it out. When I hear designer molecules + DNA I think of DRM and a lack of "right to repair" . But now its inside your body and the business owns it.. err you...

carapace 7y ago

Biology is the world. The single most important aspect of all of this is the metaphysics. https://en.wikipedia.org/wiki/I_and_Thou https://en.wikipedia.org/wiki/I_and_Thou > Buber's main proposition is that we may address existence in two ways: > 1. The attitude of the "I" towards an "It", towards an object that is separate in itself, which we either use or experience. > 2. The attitude of the "I" towards "Thou", in a relationship in which the other is not separated by discrete bounds. Biology is Thou. - - - - When Prof. Michael Levin talks about "What Bodies Think About: Bioelectric Computation Outside the Nervous System" (youtube.com) https://news.ycombinator.com/item?id=18736698 https://news.ycombinator.com/item?id=18736698 he keeps saying, "What if our technology could do this?" The answer is, our technology already does "this". We are 4By-old nanotechnology. You've heard of Grey Goo? It turns out that the oceans are already "Blue" Goo. https://en.wikipedia.org/wiki/Grey_goo https://en.wikipedia.org/wiki/Grey_goo > Gray goo (also spelled grey goo) is a hypothetical global catastrophic scenario involving molecular nanotechnology in which out-of-control self-replicating machines consume all biomass on Earth while building more of themselves,[1][2] a scenario that has been called ecophagy ("eating the environment", more literally "eating the habitation").[3] The original idea assumed machines were designed to have this capability, while popularizations have assumed that machines might somehow gain this capability by accident. https://en.wikipedia.org/wiki/Marine_bacteriophage https://en.wikipedia.org/wiki/Marine_bacteriophage > Marine viruses, although microscopic and essentially unnoticed by scientists until recently, are the most abundant and diverse biological entities in the ocean. Viruses have an estimated abundance of 10^30 in the ocean, or between [10^6 and 10^11] per millilitre. > Although marine viruses have only recently been studied extensively, they are already known to hold critical roles in many ecosystem functions and cycles. We keep making discoveries (like the bacteriophages) that show us that we have no real idea what's going on in the biosphere, which includes our bodies. I think it behooves us to wait a few centuries before we go hog wild on the only known ecosystem in the entire Universe, eh?

angel_j 7y ago

For context, simply click all 37 links in this article.

babesh 7y ago

Shouldn't we (at least in the US) be more concerned with getting health care costs under control and universal? This manifesto is mostly about making money rather than about general human welfare. The issues are not due to technological limitations.

pcwalton 7y ago
I mean, yes, we should do that, but we also need medical advances. Right now, if you get Alzheimer's disease, it doesn't matter how much money you have: you will suffer a long cognitive decline until you are no longer recognizable, at which point you will die. The entire process places an enormous social and financial burden on society. We need to fix that.
djeric3 7y ago
Personally, I see no greater advance for humanity than curing diseases. Some of these illnesses have been with us since before humans became modern humans, and now for the first time ever, we have a chance at curing or preventing them. I'd take new disease cures over colonizing Mars. But more to your point, I understand health care costs are crazy (especially in the US), but I am concerned that capping health care expenditures will dis-incentivize companies from taking risks on new vaccines and therapies.

6gvONxR4sf7o 7y ago

>We are at the beginning of a new era, where biology has shifted from empirical science to an engineering discipline. What the hell do they think doctors and other healthcare providers have done for all of history? What do they think surgery is? This is such fluffy hype, I feel insulted.

breck 7y ago

If anyone is interested in a revolutionary new type of medical records system where you can copy/paste your entire medical records in a safe way, we are working on a system here called Pau (https://github.com/treenotation/pau https://github.com/treenotation/pau). Imagine if you could just copy/paste your medical records in an email to change doctors. Or participate in a new medical study via a simple copy/paste. Or if you were in an acute care setting and your healthcare providers could instantly call up all your relevant medical history. We are going to enable those sort of things.

ljw1001 7y ago

Hype and cliches are eating the world. You heard it here first.

m3kw9 7y ago

Immune related diseases won’t really be solved unless we really understand how the immune system works. Because of the complexity there seem to be little incentive to fix root causes rather than just inhibit the immunes response I.e. patching