Could Alzheimer’s Disease be Genetically Programmed?

We often say when describing the actions of a patient suffering from Alzheimer’s Disease (AD) that they are behaving like a child.  They throw the same kind of tantrums, they often don’t understand situations, they deny responsibility for things that they have done, and so on. Up to now no-one has come up with a convincing theory of what the causative mechanism of AD really is.  Yes, there have been findings of plaques or tangles of various proteins in the brains of AD sufferers, but no-one knows if they are causative or secondary by-products of AD.

One fact that is known is that the brains of most AD patients shrink quite dramatically. Now it occurred to me that the brains of humans grow from childhood through teen years and develop significantly into adulthood.  This is clearly a genetically controlled process, during which brain cells develop and very many synapses are made. These then constitute the connections that make the adult human brain so powerful, both in cognitive ability and memory.  These are precisely the two main functions that are lost with the onset and development of AD.

It occurred to me that the process of AD could be a reversal, not necessarily exact, of the genetically controlled process of brain development and growth.  Suppose there is a trigger that initiates a process that causes brain development to reverse.  This might explain the puzzling findings that the brains of some sufferers from AD do not shrink significantly, while other people without AD do have shrunken brains.  It may depend not on the actual size of the brain, but what brain cells die and what synapses are lost. If there is such a process, it must be genetically controlled, a kind of reversal of brain evolution.

This might be considered parallel to the process of cell death known as apoptosis.  It was discovered in the 1950’s that certain cells spontaneously die by a genetically controlled process termed programmed cell death or apoptosis that starts with specific changes to the cell’s biochemistry (with the formation of specific proteases called caspases and then production of specific endo-nucleases that degrade the cell’s DNA in a characteristic manner into units of a certain uniform size).   What is somewhat mysterious about this process is that in a given organ or cellular structure, as cell’s divide other cells enter apoptosis, but it is impossible to predict which ones in a large cell cluster will be the ones to die in this manner.  It is similar to a nuclear reaction in which a certain number of atoms will spontaneously split according to a precise mathematical equation, but it is impossible to predict which ones will do so.

There is a known rare early onset form of AD that is familial and therefore inherited and results from mutations in specific chromosomes. But, perhaps generally AD is a result of a genetically controlled process of brain regression that nominally reverses the process of brain development.  This is only a conjecture, but perhaps one that is worth pursuing.

Vulnerable yet resilient

It occurred to me how vulnerable we humans are when a few nights ago my wife and I were cowering under our blankets because we heard the droning of a mosquito.  I turned on the light, but we could not see it.  I opted to spray myself with mosquito repellent, but my wife simply cowered, only her nose extruding from the sheets.  Two huge animals, a trillion times bigger, cowering from a tiny insect.

Also a few nights ago while watching TV I noticed that I had something in my eye.  I assumed that it was an eye-lash, and I went and washed out my eye, but it did not go away.  So I tried again and again, also using a saline spray that usually works, but it did not do so.  It bothered me so much that I could not sleep and got up at 5,30 am to have a shower in the hope of washing it out.  When it did not, I went to the clinic, but the nurse wouldn’t touch my eye and said go to a doctor or an eye doctor.  Since my GP’s office was close by I went there and he saw me after a short wait (unusual) and told me he could not see any lash in my eye, but I did have a small infection that might develop into a sty. He gave me antibiotic drops.  So a tiny infection in my eye basically brought me to a standstill. 

Yet, on the other hand, human beings can be amazingly adaptable and can survive under incredibly adverse conditions.  My friend who survived the Shoah as a child lived under such appalling conditions of deprivation, starvation, cold and illness, being unable to make noise or play while in hiding in Poland for three long years.  But, he did survive and now has many grandchildren in Israel.  We humans are very vulnerable, but can also be very resilient.

Transcendence

Transcendence” is the title of a movie about Artificial Intelligence (AI).  I was interested in this movie because I recently wrote a long short story that I entitled “The Brain Collector” based on the concept that the human brain is significantly more capable computationally and in terms of energy efficiency than any super-computer that has been devised by man.  So why not use the human brain as a computer?  I submitted my story to a sci-fi magazine and I’m waiting for their decision.

The movie is based on the concept that at a certain point in time in the future computer AI and the human brain will coalesce, a point that has been labelled “the singularity” by the futurist Ray Kurzweil.  The time after that occurs according to this movie will be “the transcendence.”  The plot of the movie is that a very clever computer scientist, who has managed to make breakthroughs in monitoring the activity of monkey brains using computer technology is shot by anti-technology extremists, and while he is dying he has himself attached to the computer and “uploads” his own brain activity into the computer. Together with the internet this makes him omnipotent and he starts to replan the future of mankind according to his own decisions about its needs.  

This film could be labelled science fiction, except that it veers very strongly into science fantasy.   There were several aspects about this movie that disturbed me.  1. The plot takes a decidedly anti-technology turn, namely that the anti-technology extremists are shown to be right, namely once this man’s brain is absorbed into the computer he becomes dictatorial and begins to control everyone and everything; 2. When his brain activity combines with the internet he is seen to be unstoppable and the only way to stop the all-powerful computer-brain is to turn off the internet; 3. By setting up his own energy source and carrying out experiments with plants and humans he is able to make ultra-strong followers who cannot be killed; 4. He develops through the use of nano-technology mini-bots that can reproduce themselves and “take-over” the world; 5. The idea that the US Govt. would not know about this huge development in the desert (how could they build it without being detected) and that in response the US Govt. would send two trucks and one artillery gun is ludicrous. 

This is all very silly.  First, the internet is merely a source of information that anyone can access (for good or ill).  It’s like saying get rid of libraries because there is evil in some books. Second, nano-technology is merely a means of making very small things, it cannot solve all the world’s problems.  Thus, the idea that some nanotechnology mini-bots would somehow come out of the ground and rebuild photovoltaic cells and plants and humans is pure fantasy, and has nothing to do with the central question of whether or not a human brain can be combined with AI.  

But, by definition AI is not natural intelligence.  In fact the test devised to tell when AI has been achieved is the Turing Test, when a man could not tell whether or not he is communicating with a machine or another man.  Therefore, a human brain has natural intelligence not AI and so does not need AI to function effectively.  The idea that AI will somehow augment and improve the natural functions of the brain is pure fantasy.  AI merely attempts to achieve the level of intelligence exhibited by the human brain. Nevertheless, the movie “Transcendence” is a good start in exploring some of these issues, if only they had stuck with science fiction and did not extend into stupid science fantasy.

Alternative universes

I saw a very interesting program in a series about science entitled “Genius” that was presented by Stephen Hawking, the British astrophysicist.  In episode three, in order to give three contestants  experiences whereby they would have to draw certain conclusions about “Why we are here?” Hawking and others devised three experiments, briefly described here.

Experiment one had their dinner plates suspended above the table and spinning. This looked like magic!  But it didn’t take long for them to realize this was due to spinning magnets under the table and magnets on the bottom of the plates.  So as someone has said “science is the nearest thing we have to magic.”  The conclusion was that the laws of physics operate everywhere at all times and there is no such thing as magic.

The second experiment was a graphic demonstration of how their brain waves showed that there were actually changes occurring in their brains at least one second before they made a conscious decision to push a button that exploded fireworks.  This was interpreted to mean that their brains had decided unconsciously before they had done so consciously when to push the button.  This was taken to mean that free will is a myth.

The third experiment had dozens of people wearing photos of the same faces as the three contestants, also wearing the same color coded clothes, lining up behind each of them on a grid.  Each time a buzzer sounded each of them moved one step to left or right.  It didn’t take long before the whole field was covered and it was obvious that there were many possible solutions, in other words, many possible parallel universes in which different choices could have been made.

I feel that the last two experiments could be subject to different interpretations.  In the case of the brain waves, isn’t is obvious that the brain must take a finite time to react when a decision is about to be made.  The electromagnetic wave does not prove that the decision had already been made by the brain unconsciously before the conscious decision, it only means that there was brain activity before the conscious decision and that could have been the brain preparing itself for the decision.  For example, a pianist strikes hundreds of keys in playing a concerto without referring to music.  He or she has in their brain a plan of which notes to strike before they are actually touched, this must require a prior decision in the brain, with an accompanying electromagnetic wave, before the actual key is struck.

Because the fundamental particles of nature obey quantum mechanics, which includes a degree of uncertainty, it is assumed that it is impossible to predict the future state of the universe.  The interaction of a large number of potential reactions to a given state of the universe therefore encompasses a huge potential number of outcomes.  But, as I see it, these outcomes are purely that, potential, only one outcome really exists in reality and that is the one that is actually selected or chosen as the finite outcome of the choices that were made by those who are faced by choices.  All the other choices are theoretical, they did not actually come to pass, only the reality of the choices made at every second is what is real.  Therefore there is only one actual universe at any given instant in time.  This allows the determinism of classical mechanics to be subsumed into the world of uncertain outcomes where there is free will, thus satisfying both.

 

Life on Planet Alz

Here is the Preface of my new book “Life on Planet Alz,” soon available on Amazon.com (search for “Jack Cohen” and/or “Life on Planet Alz” or at http://www.createspace.com/6867909 ).

This is a true story about coping with my beloved wife’s devastating diagnosis of Alzheimer’s disease (AD), the terrible scourge of our age.  In general, people are living longer and diseases of the aged are becoming more prevalent.  The major neurological disease of the aged is in fact AD.

There have been many excellent books and descriptions of AD and its ravages upon the minds and lives of people, so why write another account?  Whenever a person is diagnosed with AD, their spouse automatically becomes their primary carer and unwittingly also becomes a prisoner of the disease.

Each case of AD is unique and two novel aspects of this account are: (i) the focus on the way that AD imprisons both the patient and their spouse in a constant process of deterioration, and (ii) the inclusion of an almost daily journal describing raw incidents that can be enlightening for the reader, and especially for the spouse of an AD sufferer.  This illustrates the vicissitudes and the almost total preoccupation that this disease encompasses.

The author hopes that his particular take on his predicament as a spouse of an AD patient can help those who are dealing with this situation or who may have to do so in the future.  It illustrates how the initial shock of the situation gives way to the realization that one has to learn to deal with it, and finally the acceptance that must come with time and experience.

How to describe memory?  It’s like a landscape where snow has fallen.  At first the surface is white and pristine.  But as time goes by people trudge across the field and leave footprints.  Then a cart goes by leaving parallel tracks, and then a car drives along the lane, leaving tire marks.  Then the scene gets busier, children on bikes on the way to school or to play leave their tire tracks and women going shopping and so on, until the surface is criss-crossed with memories of what had happened.  The analogy for Alzheimer’s disease is that all the tracks get intertwined and mixed up and confusing, and then it all starts to melt!

The Environmental Danger

I am a scientist who until now has not been persuaded by the predictions of gloom that have regularly been issued by environmentalists saying that the world is doomed due to man-made pollution.  But, as the evidence keeps accumulating, I must say that I am gradually coming around to accept that global warming is a real phenomenon.  Here is the evidence that I find compelling:

  1. Global carbon dioxide levels.  CO2 is the main product of burning fossil fuels and its global level has been rising above normal atmospheric background levels for the past 200 years of the industrial revolution.  But, in the past 60 years this had become a steep and increasing rise to what is now at least 5 times the level before the industrial revolution.
  2. Global warming: The over-abundance of CO2 in the atmosphere contributes to global warming because the sun’s rays are trapped in the atmosphere by this “greenhouse gas.”  This has given rise to the catastrophic melting of glaciers and the concomitant rise of sea levels. This has been amply documented around the northern hemisphere where glaciers from Switzerland to Alaska are retreating and the ice cover around Greenland is rapidly melting.
  3. Plankton blooms: Much of sea life depends on the presence of plankton, tiny creatures that every year bloom and form the staple food for small fish and whales alike.  Scientists have recently shown that the plankton bloom in the Pacific Ocean has been reduced over 20 years by 40%.  This is a huge and increasing danger to the health of the oceans and the fish in them, upon which much land-life depends.  Part of this decrease can be attributed to the increase in CO2 that dissolves in the ocean and forms acidic carbonic acid.  This is also thought to be mainly responsible for the increasing dying of many reefs, including parts of the Australian Barrier Reef.
  4. Cows and other livestock: Over time the number of cows and sheep being reared in the world for human consumption and production of milk has increased significantly, so that there are now more cows than humans.  Each cow produces several liters of methane gas (CH4) per day.  This gas is 23 times more effective as a greenhouse gas than CO2.  Many experts now believe that the production of methane from cattle-breeding is a greater source of global warming than CO2 production from industry and cars burning fossil fuels, although the effect of both is additive.
  5. Animal extinctions: Within human history thousands of animal and plant species have gone extinct, mainly due to the reduction in habitat, environmental conditions, over-hunting and over-fishing .  Whales, lions, tigers, elephants, rhinoceros, cod, tuna, turtles, pigeons, dolphins, and many smaller and rarer animals are on the point of extinction or have already disappeared.  Bees and amphibians (frogs) are also being wiped out by unknown factors.

There are several lessons to be drawn from these facts:

  1. We must reduce our dependence on milk and meat.  I am a believer in this, since I am both allergic to lactose, being lactase deficient, and also sensitive to fat, of which there is too much in meat.  The net conclusion is that we should eat more plant produce, vegetables and fruits.  Most adult humans are not adapted to drink large quantities of milk, and it is only the existence of refrigeration in modern times (that also burns much fuel) and the advertizing of the milk industry that causes us to drink too much milk.  The same applies to the abundance of meat.  We should instead be eating more fish.
  2. We must reduce the use of fossil fuels: By switching from coal to oil and then natural gas (methane from the degradation of oil) the burning process becomes more efficient.  Also, the production of hybrid and electric cars and higher efficiency air flight (including the use of solar power)  will greatly contribute to the reduction in CO2 and other air pollution.
  3. We must develop alternative energy sources: Of course, the development of solar, wind, wave and other forms of energy production can eventually make fossil fuels obsolete. But, the world over-production in oil, and the availability of shale oil and the use of fracking all have caused the current drop in the price of oil.  Only when the price of oil rises again will the alternative sources of energy become more economical. Nevertheless, the improvement in solar panels and the use of deep-sea wave energy can eventually replace our dependence on fossil fuels and lead to a healthier climate.

Medical advances

The human body is a very complex organism, consisting of many interconnecting and interdependent systems.  These include the nervous system and the brain, the blood circulatory system and the heart, the urinary and genital systems, the lymphatic system, the musculo-skeletal system, the sensory systems of sight, smell, hearing and touch, and so on.  The functioning of the organism results from the whole being greater than the sum of its parts.

It is not surprising therefore that there are many diseases resulting from aberrant or malfunctioning of any one of these systems. These diseases can result from indigenous faults such as genetic errors, from exogenous infections or from physical factors, such as accident, repetitive use, or from aging.  More and more, as people are living longer and infections evolve, new diseases become prevalent, such as AIDS and Alzheimer’s Disease.

Recent research at Tel Aviv University (TAU) Sackler Medical Center on melanoma, the most dangerous skin cancer, has shed light on its mechanism of development that has potential for curative prevention.  It was discovered by a team working with Dr. Carmit Levy that prior to the spread of the cancer it sends out tiny vesicles containing molecules of mictro-RNA.  The researchers also found chemical substances that can stop this process of metastasis, leading to possible drug condidates.

It is now necessary to approach genetic diseases such as cancer with genetic analysis.  For example, what is called lung cancer is but a name for the organ where the cancer develops, but genetic analysis has shown that there are 4 distinct forms of lung cancer each with a different genetic profile, i.e. a different combination of genes that are activated.  The current drug treatment for lung cancer only affects three of them, but the other is resistant to this treatment.  Hence knowing the genetic profile of lung cancer or any other form of cancer can be crucial in making treatment decisions.