Field of Science

Will quantum physics help us cure Alzheimer's disease?

There's an interesting bit of writing out in the journal ChemMedChem by Jean-Louis Kraus, a medicinal chemist in France who has worked on drug discovery for Alzheimer's disease. The article is essentially a summary of Kraus's pessimistic outlook towards current therapies and approaches addressing Alzheimer's disease. Kraus has worked for a long time in medicinal chemistry and his words reflect experience and not just opinion. The article starts off with some well-founded skepticism but ends up sounding...let's say a little questionable.

For the most part I agree with Kraus that Alzheimer's research in the last decade has seen one disappointment after another and that we are still largely groping in the dark. He refers to the fact that all the concerted research into the disease and the billions of dollars in funding have resulted in only a handful of drugs and a handful of protein targets. None of the drugs even partially repair the damage and none of the proteins have been shown to be decisive as targets for treatment. Beta-secretase, gamma-secretase, the NMDA receptor, acetylcholine esterase; all of these have seen their day in the sun, followed by a disappointing set of results usurping them from front stage. That doesn't mean that none of them are important, it's just that targeting them with therapies seems to have no direct causal connection with treating the disease.

But what is even more disappointing is that the basic hypothesis driving the field - the amyloid hypothesis - has now been seriously questioned. A series of high-profile clinical trial failures have sent researchers scurrying back to their benches and while amyloid almost certainly has an important connection with the disease, it's now not clear at all whether actually targeting the infamous protein aggregates will bring any benefits. What seemed like a promising and rather direct direction of research has devolved into a scientific mess that will need at least a few years to be sorted out. As far as Alzheimer's disease goes, we are still fighting with sticks and stones.

As Kraus says, much of this failure eventually is a failure to understand the basic biology of the disease, which in turn entails a failure to understand the brain on a more general level, including mechanisms of memory generation and storage. Even now, much of drug discovery fails because of ignorance of the detailed biology of the disease and its perturbation by small molecules. What is regarded as a sound mechanistic hypothesis is often thwarted by the complex realities of signal transduction. With Alzheimer's disease we seem to have been biting off more than we could chew, and we need to keep untangling the complex interplay of amyloid, the protein tau, the secretases and a multitude of other biochemical components before we can truly start developing therapies. Thus it's inevitable and essential that in addition to chemists and biologists, we will need crucial input from neuroscientists to target the disease.

But will we also need quantum physicists? Kraus's thoughts on the relevance of subatomic science to AD left me slightly nonplussed. He says that:

The theories behind black holes generally suggest that subatomic particles (electrons, protons, neutrons) are themselves black holes, in which time expands in the opposite direction of our proper (perceived) time. Huge amounts of information could be stored by the spin number of photons present in these particle black holes. Could it be possible that the organization of brain matter, in terms of the properties of subatomic particles (quantum mechanics), confers on brain matter the capacities of memory and cognition, and that these phenomena are not encountered in other types of matter structure in the human body?

Come again? I was not familiar with electrons, protons and neutrons being black holes. But even if they are, I fail to see their direct relevance to understanding memory and cognition. Sure, it's a trivial fact that it's a very specific organization of subatomic particles that leads to a brain rather than to a liver or a chair. But the real action all takes place at the level of aggregates of these particles which we call molecules. I get the feeing that Kraus is indulging in a classic reductionist fallacy here. While subatomic particles do constitute the brain, understanding the brain can only come at a higher level, that of rather old-fashioned physics and chemistry involving ionic currents and neurotransmitters.

But Kraus finds a valuable place for quantum physicists in the war on neurodegenerative disorders:

To me it has become mandatory to create an AD scientific community that includes not only medicinal chemists, pharmacologists, biologists, and medical doctors, but also quantum physicists, in order to understand how aging alters the intimate structure of brain matter, where memory and cognition are located, with the hope of finding new AD treatment research orientations.

To me this sounds suspiciously like Roger Penrose's argument in his rather startling book "Shadows of the Mind" in which he postulated a relationship between wavefunction superposition in quantum mechanics and the growth and shrinkage of microtubules as significantly contributing to consciousness. Even a cursory look at that argument raised serious doubts about the relevance of quantum behavior in microtubules and more formal analysis seemed to confirm these doubts. I am not saying that physicists won't be a valuable asset on a drug discovery team, it's just that they are probably not going to use the tools of quantum gravity to map out cognitive pathways anytime soon.

Somewhat ironically, Kraus ends his piece by extolling the role of a systems biology approach in addressing a problem as complex as Alzheimer's disease. With this I wholeheartedly agree, but systems biology is the opposite of reductionism, where new emergent phenomena provide causal explanations that cannot be reduced to the laws underlying their substrates. We do need a suite of analytical tools operating at various hierarchical levels to address the issue, but given enough time and smart people, we should be able to do the job using standard chemistry and biology, albeit at a more sophisticated level. No fancy biophoton entanglement may be necessary.

Kraus, J. (2011). Why as a Medicinal Chemist I Am Not Optimistic about the Possibility of Finding, in a Reasonable Timeframe, Small-Molecule Drugs Capable of Curing the Evolution of Alzheimer’s Disease ChemMedChem DOI: 10.1002/cmdc.201100431


  1. As I understand it, the whole sub-atomic particles as black holes thing comes about because if you look at the equations the right way, you can treat a black hole as a multi-kilogram, non-unit-charged subatomic particle. You can then run the extrapolation backwards to see that there's no difference in behavior between an electron, and a black hole with the mass and charge of a single electron. It's a little hand-wavy and is not a universally accepted viewpoint, but from what I can tell it has at least the same validity as any of the other non-"an electron is an electron: now shut up and calculate"-viewpoints.

    Regarding the persistent viewpoint that the brain must rely on esoteric quantum processes, I think it in large part stems from the thought "we have a hard time understanding even a fraction of what the human brain is capable of - there's no way all of that is built from the simple parts we currently know about. There must be some new, very complicated/esoteric stuff going on to produce that." The reality, of course, is that we have a devil of a time understanding even very simple systems. Even a moderately complex system can produce emergent behavior that baffles us. We don't necessarily need to invoke special quantum weirdness in order to get complex, inexplicable systems.

    1. Thanks, I looked up the Wikipedia page. Seems like there's almost no chance that they will probe down to those kinds of radii (and energies). And of course, what I saw makes the connection to memory and cognition even more tenuous.

      You are right that you don't need to resort to quantum weirdness to explain ordinary weirdness. Classical deterministic chaos and biochemical feedback circuits are just two examples.

  2. If this is an accuracy summary of what Kraus believes about black holes and subatomic particles, it is absolute shit. Does he understand the difference between Einstein's general relativity field equations, and say, the anonical Veltman-T-Hooft gauge theory renormalization. No he does not. Or perhaps he's read about Hawking radiation, the link between black holes and the generation of subatomic particles at the edge of the event horizon. However, on further reading, he will find that black-holes must obey the Second Law of Thermodynamics, and conclude that the event horizon must shrink as the temperature of the radiation must shrink. Where the hell are the stable configurations of spin states going to sit?

    Still, there is the even worse misunderstanding that Krauss shares with Penrose when they think that quantum mechanics will somehow explain biology in the future, because quantum mechanics is already there. If you have *discrete energy* levels in a molecular system, you have quantum superposition. After all, the original motivation of the development of quantum mechanics was the surprising observation that light spectra from the elements came in discrete frequencies. A failure to understand shows a fundmental misunderstanding of what quantum mechanics is.

    1. Quite true. I usually want to criticize ultra-reductionist physicists who want to shoehorn quantum mechanics into all kinds of chemistry and biology. But here we have a slightly different case, a medicinal chemist who is invoking quantum weirdness to explain his own discipline. The fun never ceases.

  3. ....that they are probably not going to use the tools of quantum gravity to map out cognitive pathways anytime soon.

    Well, I suppose I can scrap that grant application, then.....

    As I've mentioned before, there are plenty of challenging problems that people still love to argue about in far more classical realms of physical science. Also, if you've looked at microtubule structures - I at least don't see any reasonable similarities to the photosynthetic complexes, which is usually what the "quantum biology" crowd loves to cite. There's a GTP binding site in tubulin, if my recollection is correct - there's a ridiculous amount of integral photochemical cofactors in photosynthetic complexes. Not quite the same.....

    Also, one of my countless pet peeves - are there still "quantum physicists" running around nowadays? Most of the major fields of physics research could be considered "quantum physics," after all. Outside of things like classical fluid dynamics, theoretical mechanics, and such.

  4. Yes, bonafide "quantum physicists" seem straight out of either 'Watchmen' or one of Deepak Chopra's books. As for photosynthesis, I am curious to know if the quantum biology crowd has actually demonstrated the direct relevance of things like entanglement and superposition for understanding the (experimentally verified) details of the process?

    1. I'm always reminded that it's not enough to say "what goes up must come down" - we'd also like to know when and where it comes down. The appeal to quantum mechanics seems to be what some resort to when pressed for details about some phenomenon, and figure they can just wave it all away.

      There was a report in 2010 of long-lived quantum coherences (up to ~ 200 fs) in a photosynthetic system at ambient temperature (294 K) - see here by 2D photon echo spectroscopy. A different group had shown such data for a different photosynthetic system earlier, albeit at 77 K, also by 2D PE spectroscopy here. There have been a few other publications on this topic, but these are the most frequently cited ones that I can recall. I personally can remember papers viewing energy transfer in photosynthetic systems as excitons well over a decade ago, though, so I'm not sure just how much of a giant surprise this may have been, in the end.


Markup Key:
- <b>bold</b> = bold
- <i>italic</i> = italic
- <a href="">FoS</a> = FoS