N.B. on ‘Blue Mars’ by Kim Stanley Robinson

Case N1

I consider the epic SF Mars trilogy by K.S. Robinson (K.S.R) as one of the 20th-century genre literature achievements on par with “The Lord of the Rings”.  Not only the characters and societies are plausible and  3D detailed, I cannot fault the description of biology with the usual “heightened reality” caveat. On the strength of this, I trust all science I don’t know such as geology as in any popular science book.

But recently, while re-reading the trilogy. I found a small chink in the armor that made me doubt the rest of the book science. The last book in the trilogy, Blue Mars,  published in 1996 deals with the aftermath of Mars and Earth revolutions.

One of the main characters, Nirgal, notices that his Mars farm plants start suffering from a disease. The disease is a viroid –  a plant virus that consists of a short looped RNA.

pstviroid

Structure of PST viroid. A chain of RNA nucleotides pairs with itself creating a double-stranded structure with bubbles of unpaired nucleotides. (Image by Jakub Friedl  via Wikimedia Commons, GNU)

From the novel:

Viroids like this one caused several plant diseases, including pale cucumber disease, chrysanthemum stunt, chlorotic mottle, cadang-cadang, citrus exocortis.

This is all true. But the quote below is not:

Viroids had also been confirmed as the agent in some animal brain diseases, like scrapie, and kuru, and Creutzfeldt-Jakob disease in humans.

All the diseases above are caused by self-replication and accumulation of a misfolded form of protein PrP, prion. The ‘protein only’ heredity of kuru,  an endemic disease of cannibals, was postulated by Pruisner in the 1960s. Nobody believed him but as the evidence accumulated, he was awarded the Nobel prize in 1997, not long after the first edition of the Blue Mars.

Considering that the list of books by K.S.R. on the cover inside of my copy has Galileo’s Dream (2009), long after epidemics of mad cow disease forced prions out of science arcana into public consciousness not editing this is sloppy.

More on this topic.

Another quote from Blue Mars:

A  stained slice of a brain of a Creutzfeldt-Jakob disease sufferer. Note large white spots where the cells (stained pink) were killed by accumulation prion. Also, note long “strings”, this is accumulated prion made of PrP protein. (Image by Dr. Al Jenny via Wikimedia Commons).

The viroids used host enzymes to reproduce and then were taken to be regulatory molecules in the nuclei of infected cells, disturbing growth-hormone production in particular.

Right in a vague sort of way.

Case N2

There is a brilliant mathematician in the book. And one of the main male characters wonders how a woman can be a genius in math and why there wasn’t one. Ever.

Hello?

Hypatia – one of the first known scientists;

Ada Lovelace – mother of computer programming;

Emmy Noether –  lauded by Albert Einstein.

Robinson tries not to be sexist by imagining that in the future a female math genius will be possible just as terraforming Mars will be possible, but fails to research the topic or  -even worse – dismisses all women as not good enough.

 

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Why do we bury our dead: transmissible Alzheimer’s revisited

A protein molecule is like an origami: it folds and folds in mysterious ways until you have a 3D structure. But beware of incorrect folding, it gives your aggregation and diseases. Image by OpenStax College [CC BY 3.0 ], via Wikimedia Commons

In my earlier post, I wrote about a finding that transfusion of a contaminated protein, growth hormone, led to the patients developing not only “mad cow disease” (CJD) but  also – more unexpectedly – Alzheimer’s disease.

The good news is that the finding, as it often happens with much-publicized results, is not a fluke. It’s been confirmed by an independent study. The bad news  – there’s a new way of Alzheimer’s disease transmission in town.

The Swiss scientists studied people who were transplanted tissue that covers the brain and spinal cord, called dura. Seven of dura recipients died from CJD. Their brains were studied postmortem – the only way to diagnose CJD – and five of them had signs of Alzheimer’s. The patients were too young to acquire this disease of old age.

This finding can be confirmed by a third independent group in Japan, although it’s as yet unpublished.

There’s need to panic. Just as HIV is not transmitted by touch and cuddle and kiss, short of injecting or transplanting the diseased matter, there is no way you will be infected by interaction with an Alzheimer’s patient. The doctors do not use hormones or dura purified from cadavers anymore. They were replaced by synthetic replacements, which don’t have diseases seeds.

On the other hand, surgical procedures are not designed with CJD and Alzheimer’s ‘seeds’ in mind. The seeds are very resistant to the usual sterilisation treatments, which kill bacteria and viruses. They are just incorrectly folded protein and don’t need DNA for reproduction. With the number of old patients who have more chance of having Alzheimer’s rising the chances of seeds, transmission raises as well, unless the doctors do something about it.

Transmission of Alzheimer’s disease in humans

Life is the mode of existence of protein bodies… It is precisely the most essential vehicle of cell-formation, protein, that decomposes first of all, and so far it has never been built up again.

                                  Dialectics of Nature. Frederick Engels (1883)

To perform their functions,  proteins have to keep up a correct structure. An incorrect structure due to a mutation or environmental damage leads to protein misfolding and aggregation. Imagine that you are making a butter for pancakes. A good butter is smooth, but if you mix it incorrectly it is full of annoying hard little lumps, composed of undissolved flour. Now, “butter” is you normal protein state, while “nubbins” – incorrectly folded protein, which form aggregates.

Currently, we are experiencing an epidemic of “misfolded protein diseases”. Misfolded proteins accumulate as “inclusions” or “plaques”, causing pathologies of nervous systems such as Creutzfeldt–Jakob disease (CJD) or Alzheimer’s disease.

A  stained slice of a brain of a CJD sufferer. Note large white spots where the cells (stained pink) were killed by accumulation prion. Also, note long “strings”, this is accumulated prion made of PrP protein. (Image by Dr. Al Jenny via Wikimedia Commons).

The misfolding of a protein called PrP causes Creutzfeldt–Jakob disease. Ten years ago, there was a consensus that  CJD and other prion diseases were the only ones caused by a “protein-only infectious particles”  (prions). Prion diseases transmit between species and people via for example eating raw meat or, in case of humans, transfusion of contaminated protein medical products.  The misfolded PrP converts the normal copy of the protein molecule into the pathological form.

Alzheimer’s disease develops mostly after the age of 65 as a result of an accumulation of a misfolded protein called Aβ. Alzheimer’s disease, previously thought as localised, “dead end” pathology was eventually transmitted in primates and rodents after inoculation with diseased brain tissue. However, there is a gap between infecting animals in artificial conditions and proving that  Alzheimer’s transmits between humans.

The prions were unknown before 1990th and as a result, 200 patients treated with human growth hormone contaminated with prion developed CJD and died. The article by Zane Jaunmuktane et al.  found that tissue samples from eight patients out of  200 also accumulated Aβ plaques – the hallmark of Alzheimer’s disease.  The plaque accumulation is unusual for these relatively young people (the patients were 36-51 years old) or their genetics (they didn’t have gene variants, which predispose to the Alzheimer’s development).

116 patients with other prion diseases did not show Alzheimer’s pathology. In their tissues slices, the Aβ plaques did not overlap PrP deposits. Formation of independent aggregates a parallel transfer of  Aβ with the particular hormone prep, rather than cross-seeding of misfolded Aβ and PrP. So the case sounds like co-infection with hepatitis virus   and HIV, which also were transferred via contaminated blood products before the tests for HIV. 

A slice of stained brain tissue of Alzheimer’s patient. Triangular elongated cells are neurons. Round circles are Aβ plaques. Image by KGH from Wikimedia Commons.

The article confirms an emerging consensus that despite their differences, “misfolded protein diseases”, including CJD and Alzheimer’s, have the same mechanisms of development and propagation. The epidemic of prion diseases predicted after the UK outbreak of the 1980s and 1990s failed to materialise and the governments withdrew money for prion research. But the precautionary measures against these diseases may have been limiting the spread of other, more common misfolded protein diseases.

Elementary, S1E17, “Possibility Two”

English: Very low mag. Image: Cerebral amyloid...

Cross-section of dye-stained CAA tissue. Blue blobs – cells, brown – insoluble protein deposits (Photo credit: Wikipedia)

Wikipedia’s plot summary:

 Holmes investigates when a wealthy philanthropist believes he was intentionally infected with an incurable illness — cerebral amyloid angiopathy (CAA); Holmes sends Joan to a suspicious dry cleaners to teach her deductive skills.

CAA  is the result of an insoluble protein accumulating in the  brain cells. In the episode  this is caused by a drug-like molecule, which “specifically targets the gene”, which is impossible. If they’d only changed “gene” to the protein itself, it would have been much  more believable.

Secondly, the detective receives the drug formula as a picture to his mobile and spends a night “solving the formula, determining where carbon, oxygen and nitrogen atoms go “. The formula on the screen briefly, and looks complete – anybody with a bit of chemistry training,  for example his sidekick Joan Watson, would have told him the formula.

What I did like was the idea that blood test can be faked by mixing a “DNA-less” blood-like substance (for example, artificial plasma and anybody’s red blood cells – they don’t contain nucleus = DNA) with DNA synthesised to match a suspect 11 genetic markers (bits of his DNA). As nobody determines sequence of the whole length DNA, relying on the markers match, I cannot find a fault with the idea.