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HeatDeath comments on [Link] The real end of science - Less Wrong
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It's easy to point fingers at a very sick subset of scientific endeavors - biomedical research. The reasons it is messed up and not very productive are myriad. Fake and non-reproducible results that waste everyone's time are one facet of the problem. The big one I observed was that trying to make a useful tool to solve a real problem with the human body is NOT something that the traditional model can handle very well. The human body is so immensely complex. This means that "easy" solutions are not going to work. You can't repair a jet engine by putting sawdust in the engine oil or some other cheap trick, can you? Why would you think a very small molecule that can interact with any one of tens of thousands of proteins in an unpredictable manner could fix anything either? (or a beam of radiation, or chopping out an entire sub-system and replacing it with a shoddy substitute made by cannibalizing something else, or delivering crude electric shocks to a huge region. I've just named nearly every trick in the arsenal)
Most biomedical research is slanted towards this "cheap trick" solution, however. The reason is because the model encourages it. University research teams usually consist of a principle investigator and a small cadre of graduate students, and a relatively small budget. They are under a deadline to come up with something-anything useful within a few years, and the failures don't receive tenure and are fired. Pharmaceutical research teams also want a quick and cheap solution, generally, for a similar reason. Most of the low hanging fruit - small molecule drugs that are safe and effective - has already been plucked, and in any case there is a limit to the problems in biological systems that can actually be fixed with small molecules. If a complex machine is broken, you usually need to shut it off and replace major components. You are not going to be able to spray some magic oil and fix the fault.
For example, how might you plausible cure cancer? Well, what do cancer cells share in common? Markers on the outside of the cells? Nope, if there were, the immune system would usually detect them. Are the cells always making some foreign protein? Nope, same problem. All tumors share mutated genes, and thus have mRNAs present in the cells that you can detect.
So how might you exploit this? Somehow you have to build a tool that can get into cells near the tumor and detect the ones with these faulty mRNAs(and kills them). Also, this tool needs to not affect healthy cells.
If you break down the components of the tool, you realize it would have to be quite complex, with many sub-elements that have to be developed. You cannot solve this problem with 10 people and a few million dollars. You probably need many interrelated teams, all of whom are tasked with developing separate components of the tool. (with prizes if they succeed, and multiple teams working on each component using a different method to minimize risks)
No one is going to magically publish a working paper in Nature tomorrow where they have succeeded in such an effort overnight. Yet, this is basically what the current system expects. Somehow someone is going to cure cancer tomorrow without there being an actual integrated plan, with the billions of dollars in resources needed, and a sound game plan that minimizes risk and rewards individual successes.
Professors I have pointed this out to say that no central agency can possibly "know" what a successful cancer cure might look like. The current system just funds anyone who wants to try anything, assuming they pass review and have the right credentials. Thus a large variety of things are tried. I don't see it. I don't think there is a valid solution to cancer that can be found with a small team just trying things with a million or 2 of equipment, supplies, and personnel.
Growing replacement organs is a similar endeavor. Small teams have managed to show that it is viable - but they cannot actually solve the serious problems because they lack the resources to go about it in a systematic and likely to succeed way. While Wake Forest has demonstrated years ago that they can make a small heart that beats, there isn't a huge team of thousands systematically attacking each element of the problem that has to be solved to make full scale replacement hearts.
One final note : this ultimately points to gross misapplication of resources. Our society spends billions to kill a few Muslims who MIGHT kill some people violently. It spends billions to incarcerate millions of people for life who individually MIGHT commit some murders. It spends billions on nursing homes and end of life care to statistically extend the lives of millions by a matter of months.
Yet real solutions to problems that kill nearly everyone, for certain, are not worth the money to solve them in a systematic way.
The reason for this is lack of rationality. Human beings fear emotionally extremely rare causes of death much more than extremely likely, "natural" causes. They fear the idea of a few disgruntled Muslims or a criminal who was let out of prison murdering them far more than they fear their heart suddenly failing or their tissues developing a tumor when they are old.
The institution of medicine, defined as "understanding the human body well enough to, from basic principles, directly and intentionally repair diagnosed faults", only barely exists, and it is called surgery.
The historic division between medicine (as descended from folk remedies and alchemy) and surgery (as descended from the unsubtle craft of closing wounds and amputating limbs) is illustrative here. Medicine, by definition, is holistic. It descends from folk remedies, alchemy, and enchanted unguents. It has only recently and intermittently shown the slightest interest in drug mechanisms, and even that only to the extent that the analysis of drug mechanisms facilitates the development of new and profitable drugs. Medicine has never been about anything /but/ "adding small molecules to the oil", though it has been far more prestigious then surgery for about a century, since the late 19th century discoveries of narcotics, antibiotics, and vaccines. [Prior to this surgeons were considered far more reliable within their area of expertise, although neither had the degree of professionalization and societal status that they enjoy today.] You make the argument, and I'm inclined to agree, that medicine may very well be playing itself out - that the model that grabbed all the low hanging fruit there is more or less obsolete.
The future of medicine isn't medicine at all. It's nano-surgery. Though I suspect there will be a big turf war between medical professionals and surgical professionals as the medical professionals seek to redefine themselves as the ones implementing the procedures that actually work.
Meh, another buzzword. I actually don't think we'll see nanosurgery for a very long time, and we should be able to solve the problem of "death" many generations of tech before we can do nano-surgery.
Think about what you actually need to do this. You need a small robot, composed of non-biological parts at the nanoscale. Presumably, this would be diamondoid components such as motors, gears, bearings, etc as well as internal power storage, propulsion, sensors, and so on. The reason for non-biological parts is that biological parts are too floppy and unpredictable and are too difficult to rationally engineer into a working machine.
Anyways, this machine is very precisely made, probably manufactured in a perfect vacuum at low temperatures. Putting it into a dirty liquid environment will require many generations of engineering past the first generation of nanomachinery that can only function in a perfect vacuum at low temperatures. And it has to deal with power and communication issues.
Now, how does this machine actually repair anything? Perhaps it can clean up plaques in the arteries, but how does it fix the faulty DNA in damaged skin cells that cause the skin to sag with age? How does it enter a living cell without damaging it? How does it operate inside a living cell without getting shoved around away from where it needs to be? How do it's sensors work in such a chaotic environment?
I'm not saying it can't be done. In fact, I am pretty sure it can be done. I'm saying that this is a VERY VERY hard engineering problem, one that would require inconceivable amounts of effort. Using modern techniques this problem may in fact be so complex to solve that even if we had the information about biology and the nanoscale needed to even start on this project, it might be infeasible with modern resources.
If you have these machines, you have a machine that can create other nanomachines, with atomically precise components. Your machine probably needs a vacuum and low temperatures, as before. Well, that machine can probably make variants of itself that are far simpler to design than a biologically compatible repair robot. Say a variant that instead of performing additive manufacturing at the nanoscale, it can tear down an existing object at the nanoscale and inform the control machinery about the pattern it finds.
Anyways, long story short : with a lot less effort, the same technology needed for nanosurgery to be possible could deconstruct preserved human brains and build computers powerful enough to simulate these brains accurately and at high speed. This solves the problem of "death" quite neatly : rather than trying to patch up your decaying mass of biological tissue with nanosurgery, you get yourself preserved and converted into a computer simulation that does not decay at all.
I think you may have misunderstood me. By "nanosurgery" I meant not solely Drexlerian medical nanobots (though I wasn't ruling them out). Any drug whose design deliberately and intentionally causes specific, deliberate, and intentional changes to cell-level and molecular-level components of the human body, deliberately and consciously designed with a deep knowledge of the protein structures and cellular metabolic pathways involved, qualifies as nanosurgery, by my definition.
I contrast nanosurgery: deliberate, intentional action controlling the activity or structure of cellular-components - with medicine: the application of small molecules to the human metabolism to create a global, holistic effect with incomplete or nonexistent knowledge of the specific functional mechanisms. Surgery's salient characteristic is that it is intentional and deliberate manipulation to repair functionality. Medicine's salient characteristic is that it is a mapping of cause [primarily drug administration] to effect [changes in reported symptoms], with significantly reduced emphasis on the functional chain of causation between the two. As you said above, medicine is defined as "cheap tricks". That's what it does. That's what it's always been. When you're doing something intentional to a specific piece of a human to modify or repair it's functionality, that's surgery, whether it's done at the cellular or molecular level (nanosurgery) or at the macroscopic level (conventional surgery).
Prior to about 20 years ago, the vast majority of drugs were developed as medicine. Nowadays, more and more attempts at drug design are at least partially attempts to engineer tools for nanosurgery, per this definition. This is a good thing, and I see the trend continuing. If Drexlerian medical nanobots are possible at all, they would represent the logical endpoint of this trend, but I agree they represent an incredible engineering challenge and they may or may not end up being an economical technology for fixing broken human bodies.
Again, this is one of those approaches that sounds good at a conference, but when you actually sit there and think about it rationally, it shows it's flaws.
Even if you know exactly what pathway to hit, a small molecule by definition will get everywhere and gum up the works for many, many other systems in the body. It's almost impossible not to. Sure, there's a tiny solution space of small molecules that are safe enough to use despite this, but even then you're going to have side effects and you still have not fixed anything. The reason the cells are giving up and failing as a person ages is that their genetic code has reached a stage that calls for this. We're still teasing out the exact regulatory mechanisms, but the evidence for this is overwhelming.
No small molecule can fix this problem. Say one of the side effects of this end of life regulatory status is that some cells have intracellular calcium levels that are too high, and another set has them too low. Tell me a small molecule exists out of the billions of possibilities that can fix this.
DNA patching and code update is something that would basically require Drexelerian nanorobotics, subject to the issues above.
Methods to "rollback" cells to their previous developmental states, then re-differentiate them to functional components for a laboratory grown replacement organ actually fix this problem.
For some reason, most of the resources (funding and people) is not pouring into rushing Drexelerian nanorobotics or replacement organs to the prototype stage.
Great analysis. A lot of people think that science follows an inevitable and predetermined progression of truths - a "tech tree" determined by the cosmos - but that's clearly not the case, especially in the field of medicine.
Sometimes I rant about how computer vision's fatal flaw is that it is intellectually descended from Computer Science, and so the field looks for results conceptually similar to the great achievements of CS - fast algorithms, proofs of convergence, complexity bounds, fully general frameworks, etc. But what people should really be doing is studying images - heading out into the world and documenting the visual structures and patterns they observe.