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Our future, our universe, and other weighty topics


Sunday, October 1, 2017

The Bioscience "Hypedemic" Continues

There is an ever-worsening hype problem and exaggeration problem involving scientific research.  One problem is what is called medical ghost-writing, in which pharmaceutical companies will hire people to write up a study, and then recruit doctors to sign their names to the study, even if the doctors had little or no involvement in the study.  A wikipedia.org article on the topic says, "A 2009 New York Times article estimated that 11% of New England Journal of Medicine articles, 8% of JAMA, Lancet and PLoS Medicine articles, 5% of Annals of Internal Medicine articles and 2% of Nature Medicine were ghost written."  It was revealed that medical ghost-writers had written some of the scientific papers promoting Vioxx, a drug that caused many thousands to have unnecessary heart attacks before they died. 

Another problem is that press releases issued by universities, colleges, and various other institutions are frequently announcing scientific research in ways that include exaggerations, unwarranted claims or outright falsehoods.

A study published in the British Medical Journal highlighted the problem. The study examined 462 press releases issued by 20 leading institutions. Here is one site's summary of this study:

Overall, 40% of those releases contained health advice that was more explicit than anything found in the actual article. One-third emphasized possible cause and effects when the paper merely reported correlations. And 36% of releases about studies of cells or animals over-inflated the relevance to humans.

Such exaggeration and poor reporting is common not merely in press releases about biomedical research, but also all kinds of other research. A recent example of an erring university press release was a press release issued by Brandeis University. The press release announced what would be a monumental achievement if it were true: “After a 30-year quest, a Brandeis professor has discovered the molecule that stores long-term memories — it's called calcium/calmodulin dependent protein kinase, or CaMKII for short.” Scientists have been trying to understand how memory works for many decades. So if it were true that a scientist had actually discovered that memory is stored in some specific molecule, that would be an epic discovery on the same scale as the discovery of DNA. The press release claims, "The discovery of the memory molecule resolves one of the oldest mysteries in neuroscience — how do our brains create and retain long-term memories?"

But, funny thing, there has been almost no press coverage of this supposed epic breakthrough. Which is good, because the supposed breakthrough is not at all a breakthrough. Nothing has been observed or discovered that warrants any claim that human memory is stored in some particular molecule.

There are two general reasons why it is nonsensical to claim that very long-term memory could be stored in a protein molecule such as CaMKII. The first is that protein molecules are not suitable for storing information (other than which amino acids ingredients make up the protein itself). A nucleic acid such as DNA or RNA has millions of nucleotide base pairs which make an area that can be used for information storage. One DNA molecule can store different information from another DNA molecule, because its sequence of nucleotide base pairs might be different from some other DNA molecule's sequence of base pairs. But a protein molecule has no string of nucleotide base pairs that might store information. Unlike 20 DNA molecules that might each be different, 20 protein molecules of a particular type will be the same. So there's no way a protein molecule can store some unique set of information in the same way that a blank page can or a DNA molecule can.

Another reason why it is invalid to claim that very long-term memory could be stored in a molecule such as CaMKII is that such a molecule is way too short-lived. Protein molecules in the brain have short lifetimes averaging a few weeks or less. But humans can remember things for 60 years. The CaMKII protein has an average lifetime of only about 30 hours.  

Some memory theorists have tried to salvage the notion that memories could be stored in molecules such as CaMKII, by resorting to extremely far-fetched speculations. They speculate that there could be some kind of network of such molecules that could somehow store information in a stable way, even though the individual parts of the network were constantly being replaced. There is no evidence for such speculations, and they seem to be a case of resorting to speculative extremes to avoid believing what we have discovered about the lifetimes of protein molecules. It's kind of like “pull out all the stops to avoid facing reality.”

We can compare such theories to a theory of permanent information storage in maple tree leaves. We know that maple tree leaves fall to the ground and decay every year. So nature has firmly told us: maple tree leaves are not suitable for storing information for decades. But suppose someone had his heart set on believing that maple tree leaves can store information for decades. Using all of his powers of imagination and speculation, a person might come up with a weird theory that might speculate that there is some type of animal or tree spirit that writes down all the information someone might write on a tree leaf, and then rewrites such information back on the leaf when the leaf regrows in the spring, after falling and rotting in the previous fall. So, according to such a theory, you can write a love letter to your sweetheart on maple tree leaves, and such a love letter will persist decades into the future, because the information is preserved, even though the particular items that stored the information are constantly being replaced.

Of course, such a theory would be extremely ridiculous. The theories that try to suggest ways in which short-lived protein molecules can be the building blocks of stable, permanent information storage structures are no less ridiculous. The protein molecules are like the leaves with short lifetimes, except that protein molecules have much shorter lifetimes than leaves. 

The memory theories I refer to manage to be both extremely detailed (imagining all kinds of undiscovered complex molecular arrangements) and also very half-baked, because they say nothing at all about how memory encoding might work. Imagine that there was some complex arrangement of molecules that might act as a kind of toggle or bit-switch (to use the “bistability” idea of some of these theories). That wouldn't explain memory, since our experience isn't binary and isn't digital. We know of no way by which a brain could convert something like word inputs and sight inputs into a digital or binary form that might allow such a storage system to work. Computers can store things in binary because they have a whole series of encoding schemes (such as the English alphabet, the ASCII code, and the ASCII-to-binary code) that have been carefully designed. But brains that naturally arose should have no such encoding schemes, which would be a hundred times harder-to-explain (if they existed) than the hard-to-explain genetic code. 

science speculation
 
The book here makes a statement that contradicts the claims of the Brandeis press release:

In the mid-1980's there was much excitement about the idea that autophosphorlyated CaMKII might serve as a self-perpetuating signal that could subserve permanent memory storage. However, a variety of experimental results generated since then suggests that perpetual activation of CaMKII does not occur with LTP-inducing stimulation or memory storage.

This scientific paper also contradicts the claims of the Brandeis press release:

Previous models have suggested that CaMKII functions as a bistable switch that could be the molecular correlate of long-term memory, but experiments have failed to validate these predictions....The CaMKII model system is never bistable at resting calcium concentrations, which suggests that CaMKII activity does not function as the biochemical switch underlying long-term memory.

What does the Brandeis press release cite to try to back up its claim of a memory breakthrough? It cites evidence so meager it is laughable: what sounds like an experiment with a single rat. I use the phrase “single rat” because the press release talks just exactly as if only a single rat was tested. Here is what it says:

He and his team placed a rat on a rotating platform. Every time the animal passed a designated location it got a small shock. Eventually the animal learned to avoid the shock zone by running in the opposite direction. Lisman and his team then turned off the CaMKII molecules inside the rodent's brain. The rat ceased getting off the platform to avoid the shock. The animal's memory of the location of the shock zone had been erased.

The last line in this paragraph (“the animal's memory of the location of the shock zone had been erased”) is just a case of jumping to a conclusion without adequate evidence. You are not entitled to draw any conclusion at all from a memory experiment with a single animal. Even if a result like this had been reported with each of 100 rats tested, that would still not justify drawing any conclusion about memory erasing. We have no idea whether this process of “turning off the CaMKII molecules inside the rodent's brain” might have had some effect that might have produced a result that could be incorrectly interpreted as forgetting – an effect such as distraction or confusion or dulled perception or dulled concentration or dulled spatial orientation. Nor do we have any idea whether this "ceased getting off the platform to avoid the shock" is something that would show up repeatedly and consistently in repeated experiments with lots of rats. 

I looked at the abstract of the scientific paper mentioned in the Brandeis release. The abstract does not mention experiments with multiple rats. The paper is hidden behind a paywall.

The wikipedia.org article on this CAMKII molecule tells us the following, which is incompatible with the claims of the Brandeis press release:

Irvine and colleagues in 2006 showed that preventing autophosphorylation of CaMKII cause mice to have impaired initial learning of fear conditioning. However, after repeated trials, the impaired mice exhibited similar fear memory formation as the control mice.

This is a result that would not have been reported were it true that this CaMKII is storing long-term memories.

In short, there is no sound basis for the claim of the Brandeis press release that “a Brandeis professor has discovered the molecule that stores long-term memories.” We do not understand how memories are formed, and do not even understand whether they are actually stored in brains.  We have been constantly taught the unproven dogma that all memories are stored in brains. But when we actually subject such an idea to detailed scrutiny, pondering such things as 50-year-old memories, the short lifetimes of protein molecules,  instantaneous memory recall, and the issue of encoding protocols, we encounter a host of grave difficulties discussed in this series of posts,  difficulties so great as to cast great doubt on such a dogma.

Because the CaMKII molecule in question is a very short-lived molecule with a half-life of less than a month, it is an extraordinarily implausible candidate as a molecule that might store memories that last for 50 years. No one has ever presented a remotely plausible theory describing in detail how long-term human memories could be stored in molecules (something that would require a wealth of encoding schemes and translation schemes that would be a “miracle of design” if it existed). No one has done even so much as storing a tiny bit of information (such as the word "cat") in one or more protein molecules such as CaMKII.  CaMKII is an enzyme, a molecule that serves to speed up reactions. Trying to portray a short-lived enzyme as a long-term storage site is like trying to claim that your skateboard is a bank. 

Who is it who wrote this inaccurate press release making this  claim that “a Brandeis professor has discovered the molecule that stores long-term memories”? The press release was written by Lawrence Goodman. You can use this link to see his profile. The profile describes his previous writing work, which is all for non-scientific publications. Goodman's profile does not suggest that he did any science writing or science study or science work before getting his current “Science Content Editor” job at Brandeis. So we should not attach any great weight or authority to his interpretation of this matter.

When reading university press releases on science topics, we should remember that the press release might well have been written by someone with only a fragmentary understanding of the complex subject he is writing about. 

Postscript:  The memory theories I have criticized here try to suggest that some hypothetical binary 2-state switch might be storing our memories.  Such an idea involves an assumption that memories are stored as binary data -- that, for example, your memory of your first kiss is stored somehow as something like:

00101010001110101010110110101010101010010101100

The assumption in question is nonsensical. Human memories could never be stored in binary form. If humans could store memories in binary form, then brain cells would necessarily have encoding schemes and translation schemes so precise and sophisticated -- so much like designed computers -- that it would be a "miracle of design" absolutely beyond any possible naturalistic explanation.