Fall Color

My wife and I just returned from a 3-day trip to visit friends and take in the fall color.  The trip took us north to US Hwy 2 from Duluth, MN to Wakefield, MI and then south to Winchester, WI.  My home town is on that route and I have driven HWY 2 both ways to Minnesota and Michigan hundreds of times.  When you are an old man like me with a personality like mine – that means a lot of associations along the way.

The overriding themes seemed to be feeling grateful, being lucky and particle spirituality.  I have posted about my blue-collar origins in the past.  Much of that comes down to railroads, mines, relatives I never met, and the thousands of people I have interacted with.  The railroaders include a grandfather and a great-grandfather and three more recent railroad employees - my father, brother, and uncle.  My earliest introduction to Hwy 2 was driving with my family to Ironwood, MI 30 miles away to pick up my father. He would drive a freight train down to the Fox River Valley, sleep on a locker room bench overnight, and then return to Ironwood rather than our home town.  I never found out why he was never delivered to his starting point.  I was always focused on the image of that hard wooden bench he was sleeping on - especially as he got older and started to look more fatigued.

Railroad jobs were highly valued.  The pay was good if you could work, but there was a seniority system that strung a lot of people along.  It seemed like a prolonged residency program – all of the work and inconvenience and none of the rewards.  There was plenty of work in the local switch yards that my father could rarely get because of that system.  Instead, he worked 40 hours in 4 days and slept on a bench 2 nights per week.  Six decades later that still raises a lot of questions for me and there is nobody around for the answers. 

Apart from the work-related trips, we would drive over to the Upper Peninsula of Michigan (UP) to buy margarine.  Until 1967, Wisconsin had a law that banned adding yellow food coloring to margarine.  Without it - the sticks of margarine were an aesthetically unappealing white in color.  We drove over to Michigan to get the yellow stuff.  Wisconsin became the last state to repeal that law in 1967.           

Hwy 2 starts as an exit off US35N in Duluth. The freeway drops quickly down a long hill to that exit.  From that hill you can see the Richard I Bong Memorial Bridge.  It is an impressive piece of engineering and it seems to be aging well.  We lived there my first three years out of residency training as part of a National Health Service Scholarship arrangement.  I really liked that city even though the lake kept it cold.  When I lived in Duluth, I was a member of the Duluth Speedskating team.  Before we had ice we would do dry land training out to the middle of the Bong Bridge.  Rhythmic side to side motions from an extreme flexed position at the waist.  It was done at night in darkness, in the gales of November, uphill to the middle of the bridge – the highest point -  and back down again.  There were about a dozen of us following a coach who was my age at the time.  By the end of the month, we were on a 400m oval of ice that we flooded ourselves.  

In the summer, I would cycle to my office across the Bong.  That involved 5 miles on the Skyline Drive in Duluth until I could drop down a steep avenue to the bridge.  There were days when I imagined myself in a movie – cycling over Lake Superior to and from work.  It was that unreal.

I am reminded of my cycling escapades along this route. On my first attempt I thought it was going to be an easy romp down an old railroad right of way right 60 miles into my home town.  The trail was about 100 yards north of Hwy 2.  Railroads are built on a bed of gravel called ballast that is tightly packed to support the immense weight of trains.  The ballast is about 18-24” deep.  There are about 3,240 wooden ties per mile and each tie is about 9” x 9” x 96” or 4 cubic feet.  The rails rest on those ties.  That means when the rails and ties are removed about 6 inches of loose gravel covers the surface.  When I took an undersized mountain bike down that trail it was quite a mess.  It is impossible to move forward when your wheels are buried in gravel.  You can go about 6 feet and eventually collapse to one side or spin out and fall over.  I made it about 27 miles and got picked up in Maple by my wife.  My second attempt was on a road bike that involved cycling over the Bong on my usual route but taking Hwy 53 south from Superior to Pattison Park and then county roads east and north to Poplar, WI.  From there is was all Hwy 2 and battling heavy traffic for the next 47 miles into my home town. Looking back both of those cycling adventures were foolish.  That is affirmed by the loss of two of my friends.  Both were experienced cyclists.  Both killed while cycling. I will never put myself in high traffic areas again.

The most rewarding part of that trip was pulling into my grandmother's driveway and walking in to see her with my three young cousins.  My grandmother was always worried that I cycled too much.  I did not want to add to that by describing any of the close calls.  I made a joke instead and my youngest cousin laughed the loudest and the longest.  It was an infectious laugh that made the rest of us laugh. I think about that every time I see her - 30 years later.  

There was always plenty of sports related travel both ways on Hwy 2.  Football, baseball, basketball, track, canoeing, and kayaking.  We drove over two rivers that I had canoed and kayaked multiple times, including one where I was almost killed twice in one day.  The Montreal River was not very visible from the road.  I was guessing it is fairly tame this time of the year.  In the spring it moves 1800+ cubic feet per second down a steep gradient through a narrow canyon with steep rock walls.  In some stretches the gradient looks like you are going down a staircase.  If you go down in that water, there is no way out. The day I tried it with the friend I was driving to see and 4 novices in 3 aluminum canoes I was trapped against the bottom by a canoe full of water and then an aluminum canoe wrapped around a boulder holding me down. I was lucky to get loose – twice.  

I think about the games played not so much about the scores or seasons. I was quarter miler in high school and think about a qualifying heat I ran in Ironwood. I was trying to run a sub 50 second quarter mile and failed. I really knew nothing about running or training.  When I finally started learning about the biomechanics of running and realized I could train indefinitely – I beat that time at age 45 on the high school track in my hometown. 

I thought about football practice and weight lifting back in those days. How much more or less am I lifting now as an old man? In high school we used homemade weights fashioned out of concrete set in coffee cans at the ends of an iron bar.  I think they were estimated to weigh 60-80 pounds.  Our weight-lifting area was behind the spectator bleachers on the football field.  I still get a mental image of all of my teammates and the expressions on their faces going through practice.  I remember who went on to college and where they ended up.  I remembered who is no longer with us and the last time I talked to them.   I remember how hot it could get and how bad all of the equipment smelled.  At times I think about what I would have changed over 50 years ago on those fields.

And then it is on to other friends.  I drive past a courthouse and think of my friend who took care of it for decades. He never owned a car and would either walk or cycle to this building to makes sure it was running right – even on the bleakest winter night.  As we were driving up Birch Hill - headed east outside of Odanah I had thoughts about coming down that hill in the opposite direction in a 1963 Plymouth Valiant.  My friend Bob – had his father’s car and decided to see how far it could coast from the top.   It was a standard transmission.  He reasoned it would coast a long way.  It’s the kind of thing that teenage boys did before there was an Internet and Smartphones.  I tell my wife the story about a guy from my hometown who was coming down this hill one night on his new Norton Interceptor when he decided to put the kickstand down and crashed.  But the hill is most famous as a line of demarcation between the mild to moderate snowfalls of Wisconsin and the epic ones of the UP.

All the while music is playing in the background.  Rock music by the decade from a streaming service.  No more cassettes or CDs. Just tell the phone what you want.  In the past - we had to carry separate briefcases just for the media. I used to be able to sing along to the falsetto parts but no more.  I can strain to hit "Goin' Up the Country" on a good day but no more Steve Perry or old time Robert Plant. I start talking about vocal ranges of rock singers.  I know Grace Slick is a contralto.  I think Jim Morrison was an alto – but might be wrong.  Lately I have been playing his tracks over and over again. I have seen many videos of his band mates praising his lyrical ability. His song Soul Kitchen started playing spontaneously at home as we were leaving.  The music cuts out several times as we go off the grid reminding me that we are streaming and not listening to downloads.

I think about my relatives along the way – the ones with the greatest impact on my life. My life story is one of many tragedies and I start to think about life being tragic.  I have the recurrent thought – “You did not really plan anything – you were just lucky.”  As usual I can’t disprove it.  At no point in my early life along this highway did I say to myself: “You need a plan to (go to college, get a job, join the Peace Corps, avoid the draft. etc).”  My early life was a series of desperate last-minute decisions.  I had to do something.  In some cases, the decisions were failure based. In some cases like a high lottery number when I was 1A during the Vietnam War draft - luck was clearly a factor.  In some cases, I was just moving along to the next failure.  I think about those failures and what I was like at the time. I think about how everything seemed to fall in place after those desperate decisions.  My life seemed out of control until I was in my thirties. 

And whenever I think about that random walk through life, I always end up thinking about my undergraduate professors.  They were people who believed in me and they were not shy about saying it.   They were people who had clear life plans and philosophies and knew how to live life.  They were people very comfortable about living life outside of a blue-collar world. They were people who the friends we were visiting and I later agreed were the best people you could ever meet.  It is still a mystery to me how I thrived at a small, now defunct college by identifying with those professors and realizing I had a genuine knack for academics.  We did summer projects along Hwy 2.  The focus was water chemistry leading us to remote rivers and creeks – in some cases driving down logging roads.  As we drove down those roads we talked about the Watergate scandal.  We took hundreds of water samples and then ran all of the analyses ourselves back in the chem lab - in triplicate.  In biology classes we sampled the insects and plankton living in streams and rivers and did all of the taxonomy.  It opened up a whole new level of thinking in the place where I grew up.

At some point in the trip my mind wanders to composite particles and elementary particles.  A few years ago, I discovered that protons and neutrons lasted a trillion trillion years (10⁵⁰ to 10⁵² years).  Almost all of the protons were formed when the universe formed.  The protons in my body are 13.8 billion years old and they have plenty of life left in them.  If I am cremated 96% to 98% of my body is oxidized or vaporized as carbon dioxide, water, and nitrogen gas.  My protons are back out into the universe to live again - for billions of years.  If I am buried it takes slightly longer but the same process prevails in the end. That seems like a spiritual process to me, but I am trying to get opinions from experts.  From my own reading it seems consistent with what Spinoza called a single unified and infinite substance identical with God.  He saw individual humans as temporary perturbations in the infinite substance.  I am part way through 2 books on particle physics and the origins of the atoms in the human body from the cosmos.  During a recent phone call with one of my undergrad classmates, he thought my reading and connections to protons over 50 years after our last chemistry class together was quite humorous. 

As we drive through Ironwood, Hurley, and Bessemer – the last time I was here Hwy 2 was just 2 lanes wide.  Now it is 4 lanes wide with a lot of traffic.  Just to the north is Copper Peak – a ski flying hill.  It has been out of business for 20 years but it is being rebuilt with a large grant.  My wife and I watched a ski flying competition there back in the 1980s.  There were three guys from my hometown standing behind us that day. One of them was the funniest guy I ever knew. He was killed in a car accident a few years later.  One of the other guys was the nicest guy I ever knew.  He died in an industrial accident about 10 years later.  The third guy is still alive. He was responsible for my first dental crown when he elbowed me in the mouth playing basketball and broke tooth number 24 in half.  I get an image of all of us standing there, talking, and joking.

When we get to Wakefield, I think of the first time I was there as a kid to visit my aunt and uncle.  My uncle worked in a copper mine setting explosive charges.  As we drove around Sunday Lake to find their house, I remembered a spillway on the opposite side of the lake but did not look for it this time.  We still had 22 miles to go down S. County Hwy 519.   The fall color along that route was spectacular and I don’t know why.  The weather there is probably subject to what is happening on both Lake Superior and Lake Michigan.  At some point big lakes bring the baseline temperatures down, especially in low lying inland areas.       

When we finally arrive at our destination – we are greeted by a couple I have known since 1970.  We stayed in touch through the lean times, the industrious times of medical careers, and now in retirement.  We caught up on families, common interests, activities, and the medical infirmities of aging or as my friend put it “an organ recital”.  Among the four of us we have 4 knee replacements, 1 shoulder replacement, 1 hip replacement, 3 ablations for arrhythmias, a pacemaker placement, and various other necessary surgeries.   Nobody is upset about it.  The general attitude is do what is necessary to keep going.  There is some reminiscing but not a lot.  I want them to do as well as they want us to do.  The two days we spend there flies by and we are back on Hwy 2 headed home – hoping to see them a lot sooner next time.  On the road again I think of how important this relationship has been.

In the past few years, I have touched on semantics on this blog and the increasingly well-worn phrase: “The map is not the territory.”  My territory as I have outlined it involves extended connections to people at almost every fork in a 274-mile stretch of road.  There are so many of these connections they can be overwhelming, especially considering the emotional aspects.  With a few exceptions it is impossible to estimate the impact of all of these people on my life.  I am always happy to see them and I miss them when I don’t.  Some people reading this might be surprised.  I am considered to be a loner and asocial on the surface but I don’t think many people really are.  Especially if they have an active memory and can recall the details of what happened to them on Hwy 2 or anywhere else. 

They are just quieter…

 

George Dawson, MD, DFAPA

 

Supplementary 1:

I tried to capture some of my personal experience - the way I think most of the time as I went along this trip.  It has a lot of room for improvement - but at the same time it covers a lot of ground.  I debated constructing a diagram of all the people I would think about along this route and probably will at some point laying it over the route on the map.  I also wanted to provide details of how semantic memory automatically created meaning from these relationships but will defer that to another time. I could not include everything and that may seem paradoxical for a guy with few apparent relationships.  

Supplementary 2:

Some people might argue that my associations and experiences in locations has nothing to do with a map.  The experience of the geography is also different.  The best example I can think of is the Blueberry Store.  With my hundreds of trips on Hwy 2,  I could always count on seeing the Blueberry Store on the west side of Maple, WI on the south side of the road.  Over the decades of my life it went from being a weathered appearing general store to a run down appearing store to an abandoned store.  It was eventually demolished in 2019.  Even though I never went inside - it was a familiar landmark and every time I drive by - I remember what it looked like.  Every time I drive past that empty lot - I see mental images of the Blueberry Store.  Not ghosts - real mental images.  So the territory for me is people, relationships, and memories - none of which are on the map.

Supplementary 3: 

If you think you have had an important interaction with me in the past - you are probably right.  I intentionally used few names in this essay.  But whether you played football with me every night for years, asked me for help when I was a lab assistant, or was the last person to see me before I left for the Peace Corps I remember you.  And if you were in the Peace Corps with me - my head is still full of those images and conversations from 50 years ago and I wish I was talking with you right now. 

References:

1:  Wenliang Li ,The proton’s next secret. Science 393,663-664(2026). DOI:10.1126/science.aek0574

2:  Spinoza, Benedictus de. "Ethica, ordine geometrico demonstrata." In Opera Posthuma. [Amsterdam: Jan Rieuwertsz], 1677.  (Grapevine Kindle edition and translation – Benedictus de Spinoza.  Ethics. 2023.

Depression Is Not A Proton and Other Nosological Musings....

 

I have been thinking about protons a lot lately. Probably not too unusual for an old science guy.  After all we used them in chemistry and physics.  I have been doing some reading about stellar evolution lately and how the elements were formed. In that reading I came across the fact that a proton has a life of 10^32 years. Some estimates say 10^34 years.  And proton decay doesn’t happen slowly over time. At some point it is just instantaneous.  A proton is a composite particle rather than an elementary particle – composed of three valence quarks resulting in a net positive charge. But in chemistry and biochemistry they are generally written as a simple H⁺.  When protons decay – it happens instantaneously to a positron and a pion.  The positron is antimatter so it collides with an electron and is annihilated and gives off gamma photons.  The pion explodes doing the same.  The proton is converted to energy. This process is so rare it has never been directly observed although there is a massive experiment in progress to see if it can be done.

Practically all the protons in the universe today, were made during the Big Bang about 13.8 billion years ago.  Some protons are made in the universe today but it is a very small process compared with the original source. That means that all of the protons in my body (and yours) are recycled and will be for the next 10^23 years.  That’s nearly a trillion trillion (10^24) years.  The various estimates for the death of the universe range from tens of billions of years to 10^100 years.  And of course, life on Earth and Earth as a habitable planet is much shorter.

All of these thoughts about protons brings to mind Carl Sagan’s various quotes about how we are all made of stardust.  His thoughts go far beyond protons to every element in our bodies and how they were synthesized in stars and temporarily borrowed by us. Each one of us is an aggregate of this star dust maintained by energy input and localization. Part of Sagan’s intent was to point out how this can be reassuring and spiritual.  I do find it that way.

There is something else about protons. The verbal description of protons may vary slightly between disciplines (physics, particle physics, chemistry, biochemistry) but everyone is in agreement that protons exist and can see the logic of all of the notations and definitions.  Everyone agrees that there is one type of proton and it will be around forever.

A lot of people will say species are qualitatively different from disease and protons are qualitatively different from organisms and diseases.  Without using any philosophical words – species, protons, and diseases have different rules of existence, boundaries, and causal mechanisms.  To cite one example – no biological organism or disease originated in the Big Bang and is expected to last forever. The rules of existence are much different for a proton. It also does not adapt, process information, or experience or feel anything.  An organism has emergent rather than summed properties, is subject to evolutionary pressure, complex organization, and a finite lifespan. At the basic level the proton is a thing and an organism is a process over time – a qualitative difference.

The comparison of species to disease shows that species are generally individuals and diseases are abstract classes.  The individuals are organized in an evolutionary or phylogenic classification and diseases are organized as a disruption of normal physiological or mental function in an individual.  The species move through time and the disease happens to an individual at one point in time. As the appreciation of disease complexity has increased over time there is now an understanding that the lines that blur the distinction between species can also occur with diseases. 

That obviously is the case in biology and medicine. From taxonomy, we can find rare cases of organisms that are the only match to their phenotype – there is one description of a single genus and species.  We can also find identical phenotypes that can be separated into genus and species only by genetic subtyping. We can find monogenic diseases that produce several phenotypes and polygenic diseases that produce many more. In other words – the match between description and consensus-based reality is far from perfect.

I attempted to capture this phenomenon in the diagram at the top of this post.  I eschew the idea of a spectrum or continuum, the categories are presented here just to give estimates of possible numbers of subtypes in each category and the associated uncertainty. Some may take issue with including speciation with diseases.  In that case I will defer to Linnaeus who classified both and invented the predominant classification nomenclature still used in taxonomy.  

To be clear – this graphic is literally an apple to oranges comparison.  The first issue is the physical wave-particle compared to biological entities.  The second is the different levels within biology.  Species occur at the population level over time defined by properties such as reproductive isolation, morphological distinguishability, and monophyly.  The boundaries between species reflect evolutionary divergence rather than trait variation.  

To cite few examples moving from left to right. The proton is off the chart because there is no discrepancy between description and there is only one agreed upon type.  The first three organisms (Gingko biloba, Balaeniceps rex, and Thermus aquaticus) all have just one species through evolutionary mechanisms.  I did not equate them to a proton because being trained in biology (and without looking it up) – I am sure there are various descriptions but common recognition they are the same species.

Things get interesting with the Bornean Fanged Frog.  In this case all of the frogs look exactly alike and can only be separated into 18 different species by molecular genetics (1).  The authors specific quote “single species has been split into 18 genetically divergent yet morphologically indistinguishable species.”  This is the definition of a cryptic species but they also point out controversy about that definition and say that cryptic species are common in the Tree of Life and understanding them is critical to understanding biodiversity. 

Moving on to monogenic diseases, most of which can be identified by molecular tests there are also limited number of phenotypes that do not add much to classification but can be important in terms of treatment. Infection and toxic agents are generally thought of as being defined by the agent involved but there are a number of possible phenotypes based on host susceptibility, organ system involved, disease state, lethality of the infection agent or toxin, and in the case of the latter – toxidromes. 

That brings me to major depression – one of the most maligned diagnostic criteria in the DSM.  When I read the critiques, it seems like some people believe there will be a magical verbal description of depression and all of our worries will be over.  The sun will shine and we will never have to worry about actually treating the vagaries of depression on a clinical basis. The new pure description will be perfect enough to lead to an improvement in biological research and therapeutics.  The other more insidious part of that criticism is “I know more about depression than anybody and this is how it should be classified and diagnosed.” 

I don’t buy that criticism.  And here is why – I have seen tens of thousands of people with severe depression and bipolar disorder successfully treated during the eras of the DSM-III, DSM-IV, and DSM-5 and have worked with the thoughtful experts involved.  I don’t think for a second that it matters what was in those manuals or what turns up in the DSM-6.  Assessing and treating depression and differentiating it from other conditions doesn’t depend on what is in the DSM or the ICD.  It depends on what is in the mind of the psychiatrist, how that mind was trained, and what that mind experienced. 

As far as the classification goes – I can show the table of contents of Kraepelin’s text Clinical Psychiatry (2) to any practicing psychiatrist today and they will recognize what he is talking about over a hundred years ago.  It seems that we have to deny the validity of previous observations or label them as “pragmatic” but otherwise meaningless. The newer hierarchical or network-based schemes don’t mention the circularity of being based on descriptions pulled directly out of the DSM and all previous observations.

The diagram shows that based on the DSM criteria there are 227 possible phenotypes of varying frequency and a recent study showed that only 170 were observed in a large clinical sample.  Genomic studies often use a compromised phenotype by using the PHQ-9 or PHQ-2.  Nobody ever suggests that is a “practical” research compromise when you are analyzing the genomes of many more people than several psychiatrists would see in their lifetime.  But that is one reason some people think we need better criteria. How will better criteria be useful in rapidly characterizing 100,000 people for a genomics study?  Let me go out on a limb here and say there will be no better verbal or written criteria.  There is a limit of what you can classify with just words – especially in biology.

The proof is evident in the next three categories.  Everyone can recognize a domestic dog. There is tremendous phenotypic diversity in dogs based on morphology and behavior.  And they are all the same genus and species. Atopic dermatitis or eczema is one of the most common dermatological conditions and based on IgE status, age at onset, course, endotype, molecular endotype, chronicity, fillagrin mutation status, and severity there are 6,144 combinations although there is clinical overlap and there has been no clinical investigation into how many of those variants exist. From a morphological standpoint - many different rashes from eczema can exist on the same person at the same time and specialists in dermatology are the best people to diagnose that.  The same analysis can be done for systemic lupus erythematosus (SLE) using formal criteria and that produces 27,648 combinations of signs, symptoms, and lab findings.        

There is a range to the limits of verbal classification in biology and medicine.  In the case of cryptic species, we have a phenotype that presents very little perceptual or verbal information for classification and that classification depends on molecular biology.  In some cases, there is a one-to-one mapping of classification onto species.  That rarely if ever works in medicine and examples abound. I would not expect it to happen at high rates in biological organisms with stochastic processes, genetic mechanisms like incomplete penetrance, variable expressivity, polygenic modification of monogenic risk, epistasis, pleiotropy, allelic heterogeneity, epigenetic variability, and compound inheritance all increasing the gap between genotypes and expected phenotypes.  Approximate classifications are not a deterrent to science or clinical practice even though that is a common critical opinion. 

Stay tuned for an even deeper dive into biological classification of diseases based on some of these concepts. 

 

George Dawson, MD, DFAPA

 

References:

1:  Kin Onn Chan, Dario N Neokleous, Shahrul Anuar, Rafe M Brown, Carl R Hutter, Indraneil Das, Stefan T Hertwig, A Genomic Perspective on Cryptic Species Reveals Complex Evolutionary Dynamics in the Gray Zone of the Speciation Continuum, Systematic Biology, 2026;, syag001, https://doi.org/10.1093/sysbio/syag001 (open access).

2:  Kraepelin E.  Clinical Psychiatry.  The MacMillan Company/Norwood Press, Norwood,MA 1902, 1907. 628 p.

3:  Kendler KS. The Phenomenology of Major Depression and the Representativeness and Nature of DSM Criteria. Am J Psychiatry. 2016 Aug 1;173(8):771-80. doi: 10.1176/appi.ajp.2016.15121509. Epub 2016 May 3. PMID: 27138588.

4:  Zachar P, Kendler KS. The Philosophy of Nosology. Annu Rev Clin Psychol. 2017 May 8;13:49-71. doi: 10.1146/annurev-clinpsy-032816-045020. PMID: 28482691.

Graphics Credit:

An original from me - generated with MS Visio.