You Can’t Catch Alzheimer’s Disease, Can You?

You Can’t Catch Alzheimer’s Disease, Can You?

By Guest Blogger,
Tyler Kokjohn, PhD.

Transmissible ADAlzheimer’s disease (AD) does not spread from person to person like a cold virus, but some recent findings suggest the unsettling possibility it might be transmitted through medical procedures (1).

Deadly diseases have been transmitted through medical procedures such as blood transfusions, organ transplants and surgery.  In fact, this new concern about AD was sparked by the grim legacy of a past medical practice in which hormone preparations obtained from human cadavers were injected into children who were not growing normally.  What the physicians did not know at the time was that pathologic prions, abnormally shaped proteins producing the rapidly lethal neurodegenerative illness known as Creutzfeldt-Jakob disease (CJD), contaminated some of these hormone preparations.  Over two hundred cases of fatal CJD appeared ultimately in patients who had received cadaveric growth hormone supplements (2).

An unforeseeable sequence of events is thought to have led to the cadaveric growth hormone therapy tragedy.  CJD is a rare disease most often appearing in persons over age 60 (3).  Although clinically obvious CJD is rare, protein mis-folding occurs spontaneously during normal aging and many outwardly healthy persons die with some pathologic prions in their brains.  Perhaps these individuals would have succumbed to CJD if they had lived a little longer.  Hormone therapy necessitated pooling pituitary tissue from large numbers of deceased donors some of whom probably harbored toxic CJD prions without exhibiting any signs or symptoms of disease.  Unfortunately, over 200 hormone recipients received enough pathologic prions during their treatments to develop CJD in short order.

Examination of brain tissue samples from a small group of the growth hormone recipients who died of CJD revealed half of them had amyloid deposits reminiscent of those found in AD patients.  However, these patients were much younger than the typical AD patient and finding such amyloid deposits in them was unexpected.  After ruling out the possibility the results could be explained by genetic mutations linked producing early onset AD, the investigators recognized there was an alarming possibility some CJD prion-contaminated growth hormone injections also transmitted this key pathologic change linked to AD dementia as well.

Another medical procedure, transplantation of cadaveric dura mater, the tough outer covering of the brain, has also been recognized to have transmitted CJD.  A second study of several deceased CJD patients who had received transplants of cadaveric dura mater (the tough outer covering of the brain) revealed the presence of AD amyloid pathology in some of them.  The observations may be explained in several ways, but the results are consistent with the idea that that dura mater transplants also promoted amyloid pathology development.

These new observations have potentially staggering implications.  Scientists do not know how prions produce the massive neurodegeneration characteristic of CJD, but they have convincing evidence the process begins when a normal protein changes its shape.  These abnormal prions seed and spread this neurotoxic change throughout the brain by initiating a relentless chain reaction which forces their remaining normal relatives to adopt the pathologic shape.  The toxic seeds may appear spontaneously, but CJD has been confirmed to have been transferred through several types of medical interventions including contaminated growth hormone injections, surgical procedures and transplants.  Pathological changes associated with several neurodegenerative disorders may spread through the brain using similar prion-like mechanisms (4), prompting concern that medical procedures could also spread AD and other conditions as well.  Discovering some recipients of cadaveric growth hormones and dura mater grafts who died of CJD (5) also had amyloid deposits suggests these treatments introduced the seeds necessary to initiate both CJD and AD-like pathologic changes.

CJD is a rare disease and to see an explosion of cases due to hormone replacement therapy and transplants was shocking.  Cadaveric pituitary hormone replacement therapy was eliminated over 30 years ago when brain extracts were supplanted by synthetic preparations and dura mater grafts are no longer performed.  While the epidemic of induced CJD seems to have subsided, the question now is whether another problem has been exposed.  AD is a far more common affliction than CJD, suggesting that hormone replacement injections and transplants were much more likely to have introduced amyloid seeds than CJD prions.  The true proportion of persons injected with cadaveric hormones or receiving dura mater transplants who consequently developed amyloid deposits in their brains is unknown.  This group is still comparatively young and only a small number of them have come to autopsy and been studied to date.  Conceivably a high proportion of them are incubating prions today and could go on to ultimately develop dementia or suffer the toxic effects of amyloid deposits.

Unfortunately, because AD is widespread, if the ideas as to how this pathology extends itself are correct the number of persons being seeded with toxic amyloid through medical procedures might be enormous.  Pathologic prions are notoriously difficult to inactivate (6) and with neurosurgery where there is a high risk they might be present, stringent methods are employed to prevent their spread.  Because pathologic prions are so tough to eliminate there is a possibility that medical protocols performed with less stringent precautions such as general surgery conducted at other body sites, transplants and blood transfusions have all been inadvertently spreading the seeds of toxic amyloid.  It is important to note that what has been seen in the deceased pituitary hormone and dura mater graft recipients is not precisely AD, but an apparent transmission of amyloid pathology similar to that typical of demented patients.  In addition, to date only brain-associated materials have been identified as a possible source of putatively neurotoxic amyloid seeds.  However, even if ‘only’ an amyloid pathology was seeded and spread within these patients, such deposits are potentially toxic and therefore cause for great concern.

AD is not contagious, but is it transmissible by medical procedures?  At this point we still have only a vague understanding of the natural history of prion diseases.  Newly arising information suggests a pathological change linked to AD, amyloid deposits, could be seeded or accelerated by some invasive medical interventions, but the frequency of such events and the degree of threat posed by them is uncertain.  Work is in progress to confirm these observations and establish their potential implications for human health

_________________

(1)   A. Abbott.  2016. The red-hot debate about transmissible Alzheimer’s.  Nature 16 March 2016. http://www.nature.com/news/the-red-hot-debate-about-transmissible-alzheimer-s-1.19554

(2)   B. S. Appleby et al.  2013.  Iatrogenic Creutzfeldt-Jakob disease from commercial cadaveric human growth hormone.  Emerging Infectious Disease. 19(4): 682–684. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647424/)

(3)   Creutzfeldt-Jakob Disease Fact Sheet.  http://www.ninds.nih.gov/disorders/cjd/detail_cjd.htm

(4)   G. Miller. 2009.  Could they all be prion diseases? Science 326:1337-1339.  http://science.sciencemag.org/content/326/5958/1337.full

(5)   A. Abbott.  2016.  More evidence emerges for ‘transmissible Alzheimer’s’ theory.  Nature 26 January 2016. http://www.nature.com/news/more-evidence-emerges-for-transmissible-alzheimer-s-theory-1.19229

(6)   D. Dormont.  2002.  Prion diseases: Pathogenesis and public health concerns. FEBS Letters 529:17-21.  http://onlinelibrary.wiley.com/doi/10.1016/S0014-5793(02)032684/abstract;jsessionid=A70616D5CBA695BB66402DBAB86FBBEC.f04t02

###

War of the Worlds – Devising the Zoning Plan for Invading Mars

War of the Worlds – Devising the Zoning Plan for Invading Mars

by Guest Blogger,
Tyler Kokjohn, PhD. 

MarsSpaceX plans to land an unmanned capsule on Mars a few years from now (1).  The ultimate goal is planetary colonization and missions with humans might follow as early as the middle of the next decade.  If all goes as planned the company could be hard at work on the red planet 10 years or more ahead of NASA.

A few technical details need to be clarified.  To begin, NASA officials may wish to establish precisely where on the Mars the SpaceX engineers intend to land.  This is important because The Outer Space Treaty of 1967 requires nations exploring the solar system to adopt reliable measures to avoid contaminating them.  NASA has a formal program to develop and implement protection measures to conform to this agreement (2).  How the proposed SpaceX mission(s) will fit into the established planetary protection framework and coordinate with NASA exploration goals is unclear.

Mars is so interesting scientifically because of the likelihood life emerged there independently and the chance viable organisms are still present today.  Because of the risk of forward contamination by terrestrial microbes, spacecraft landing on Mars are cleaned exhaustively.  However, even the most scrupulously operated clean rooms harbor some microbes (3) and probes already sent to the red planet have almost certainly brought along a few fugitive terrestrial bacteria (4).   Scientists essentially know nothing about the Martian biosphere, but there is a strong possibility hitchhiking terrestrial microbes might find conditions on the red planet are quite hospitable.  This threat of contamination by stowaway microbes has led NASA to delineate Martian Special Regions where conditions might be warm or wet enough to theoretically support life as we know it today (5) and restrict the scope of explorations in them for the time being.  Finding relict evidence of Martian life or living indigenous species would be a momentous discovery, but NASA has been proceeding with extraordinary deliberateness in order accomplish the critical scientific objective of testing pristine samples.

SpaceX will probably be most interested in exploring Martian locations where water, a critical resource for future colonists, could be present.  While the initial surveillance missions could probably be done in a way that would satisfy planetary protection obligations, human colonization in Martian Special Regions would be impossible to reconcile with the goal of avoiding contamination with terrestrial microbes.  Humans are literally enveloped in a cloud of microbes (6) meaning everything we touch, excrete or come near becomes contaminated which will make the future Mars pioneers the high-tech interplanetary reincarnation of Johnny Appleseed.

Private enterprise is challenging the traditional ways of exploring outer space and NASA scientists are now seeing their plans and timetables pushed hard by a corporate collaborator turned agile competitor.  However, human colonization of Mars seems incompatible with on-going Special Region preservation efforts.  Will NASA be able to dictate or negotiate when and where SpaceX craft may land?  Or will SpaceX assert it needs no license to explore and ultimately subdivide the red planet into cities as it deems fit and profitable?  Will NASA investigators be forced to hasten their sampling efforts before scientifically valuable untouched areas are occupied by humans or their devices?  Realistically, can NASA hope to keep pace with private companies with deep pockets and driving ambitions?  What will be the fate of NASA if SpaceX explorers discover the first definitive proof of life on Mars?

SpaceX is poised to invade Mars.  However, raw ambition enabled by technological prowess has far outrun scientific knowledge.  Eager to achieve a dream, the effort might unleash entities visible and invisible that could change the Martian biosphere or erase it altogether.  Who is in charge of devising a zoning plan for Mars?  That question must be answered soon because the invasive terrestrial species known as Homo sapiens never travels alone and nothing is the same after it arrives.

______________

(1)   K. Chang. SpaceX says it plans to send a probe to Mars. New York Times, 27 April 2016.http://www.nytimes.com/2016/04/28/science/mars-spacex-dragon-landing-2018.html?_r=0

 

(2)   NASA Office of Planetary Protection http://planetaryprotection.nasa.gov/about.

 

(3)   W. E. Leary.  In NASA’s sterile areas, plenty of robust bacteria. New York Times, 9 October 2007.http://www.nytimes.com/2007/10/09/science/09clea.html

 

(4)   K. Chang.  Mars is pretty clean. Her job at NASA is to keep it that way.  New York Times, 5 October 2015.  http://www.nytimes.com/2015/10/06/science/mars-catharine-conley-nasa-planetary-protection-officer.html

 

(5)   P. Rettberg et al. 2016. Planetary protection and Mars special regions – a suggestion for updating the definition. Astrobiology 16(2):119-125. http://online.liebertpub.com/doi/10.1089/ast.2016.1472

 

(6)   Z. Schlanger. Your microbiome extends in a microbial cloud around you, like an aura. Newsweek, 22 September 2015.  http://www.newsweek.com/microbial-cloud-aka-auras-are-basically-real-375010

 

Also of interest on JayVay – Dissecting the NASA Announcement of Water on Marshttps://jayvay.wordpress.com/2015/09/28/dissecting-the-nasa-announcement-of-water-on-mars/

 

###

Trust Them?

Trust Them?
Drawing Ethical Lines in an Approaching CRISPR Technology Whirlwind

by Guest Blogger,
Tyler Kokjohn, PhD.

 
Tornado

Should we trust scientists and governments to set ethical boundaries for research and therapeutic use of CRISPR gene editing technology?  This provocative question was posed in a recent Chicago Tribune editorial (1). The potential of CRISPR is clearly immense, but the total scope of its implications cannot be delineated because much lies beyond what even the scientists themselves can presently imagine.

When Kary Mullis invented the polymerase chain reaction (PCR) method for copying DNA (2), it was obvious the technique was extremely valuable.  Yet how many of his colleagues sensed this breakthrough would precipitate a crisis of confidence in our criminal justice system?  Others soon seized on the new technology and applied it novel ways.  The Innocence Project (3) utilized the capabilities of the new PCR-based DNA analysis technology to examine forensic evidence with unprecedented reliability and precision.  To date, their efforts have resulted in complete exonerations for several hundred persons convicted of serious crimes.  Years earlier when Thomas Brock described a strange microbe living in a Yellowstone National Park hot spring it seems doubtful anyone devoted much thought to its future utility or could have envisioned its role in the cascading developments to come (4).  Yet this tiny curiosity harbored a thermostable enzyme that made automated DNA analysis by PCR practical, helped launch a new biotech industry and sparked a revolution that turned forensics and medical science upside down.

Past experience suggests even scientists can fall short when it comes to predicting the full implications of their work.  The fast pace of CRISPR research developments already has regulators struggling to catch up.  However, new discoveries will supercharge synergistic processes of invention in which unforeseen implications and applications will emerge continuously.  Recognizing and coping with the burgeoning ramifications will be an enormous challenge.

Notwithstanding a long history of trustworthy self-policing, the scientific community and vested commercial interests cannot be allowed to remain the sole judges of the proper uses of gene editing technology.  Our leaders must ensure a broad cross-section of the public is included in future decision-making processes regarding CRISPR technology.  In turn, citizens cannot relinquish their responsibility to stay informed about the issues and help foster reasoned resolutions regarding the appropriate applications and limits of new genetic editing capabilities. We are about to experience a scientific whirlwind in which discerning and drawing ethical lines will become incalculably difficult.

___________

(1)   “Editing human genes the CRISPR way,” Chicago Tribune editorial, 27 April 2016http://www.chicagotribune.com/news/opinion/editorials/ct-crispr-gene-editing-northwestern-mcnally-edit-0428-jm-20160427-story.html

(2)   The History of PCR. Smithsonian Institution Archives. http://siarchives.si.edu/research/videohistory_catalog9577.html

(3)    http://www.innocenceproject.org/

(4)   T. D. Brock.  1997.  The value of basic research: Discovery of Thermus aquaticus and other extreme thermophiles. Genetics 146:1207-1210. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1208068/pdf/ge14641207.pdf

 

###