Life Lines

By Elof Axel Carlson

Elof Axel Carlson

It is impossible to know ourselves in all the aspects of our lives that we can examine. But we can know a lot about ourselves through science. 

I will start at the level most of us operate in — the macroscopic world in which we see ourselves as a person. I see myself as an old person, almost 85 years old. I see myself as a male, a husband, a father (three out of six of our children still living). I also see myself functionally — I am a scientist, a geneticist and historian of science.  

I have 12 grandchildren and three great-grandchildren. I am an American, born and mostly raised in Brooklyn. I did my undergraduate work at NYU. I got my doctorate at Indiana University with Nobel laureate H. J. Muller. I presently live in Bloomington, Indiana. I have sailed around the world twice teaching on board Semester at Sea. I have had 12 books published. I loved teaching and doing research at Queen’s University in Canada, at UCLA and at Stony Brook University. 

Biologically I have some knowledge of much of my gross anatomy and as a biologist I have some familiarity with my organ systems and how they work. I have observed some of my cells under a microscope when I took a course on histology at NYU as an undergraduate and I prepared slides of my blood. I have seen my 46 chromosomes when I had my karyotype taken some 50 years ago at UCLA. I have not yet had any of my 20,000 genes sequenced. 

But even if I had my entire genome sequenced, I know that no one reading those sequences would be able to infer my life described in the first three paragraphs of this essay because our social traits are largely acquired by where we grow up, the circumstances of our lives in the generation in which we are born and a good measure of luck.

 It was luck that gave me an opportunity to read classical literature aloud for five years to a blind teacher in my high school.  It was luck that made me meet the person to whom I am now married, and Nedra and I have had 58 wonderful years together.  

I am part cyborg with eye glasses (for reading), cataract-free plastic lenses in my eyeballs, six implants in my jaws and two hearing aids. I have the benefit of an altered immune system created by vaccinations that have spared me from diphtheria, typhoid fever, smallpox, pneumonia and many varieties of influenza. I’ve lived through measles, mumps and chicken pox without bad outcomes. When traveling around the world, I prevented malaria by taking daily Atabrine pills. I would probably have died 10 years ago had there not been statins to regulate my cholesterol metabolism.  

I know how I am connected in many ways. My biological ancestors are Swedish on my father’s side and Ashkenazic Ukraine on my mother’s side. My intellectual pedigree through Muller I have traced to Darwin, Newton and Galileo. It made me aware of how few compose the world of scholars in the immense diversity of humanity. 

I owe to many books aspects of my personality, values and goals in life. From Goethe, I have a Faustian personality and try not to repeat my activities each year. From Montaigne I learned to write personal essays. From Samuel Pepys I learned to keep a diary (over 100 volumes and still going). From Freud I learned to sublimate my discontents into works that enrich civilization. From Darwin I learned how all of life is connected and can be related to the past through his theory of evolution by natural selection. 

From Socrates I learned the importance of trying his credo, “Know thyself.” From Job I learned the inscrutability of fate and how limited is our control over our lives. From Kant I learned that ethics and moral behavior can be constructed from reason. From Epicurus and Epictetus I learned that one of the great benefits of life is choosing well and using, as best we can, what talents we have within the limits imposed by society’s circumstances. 

I think of myself as composed of layers of units. I am a unique organism. I have numerous organs that compose my physical being. I am composed of several trillion cells. 

The gene activity in my body and mind are in constant associations with past, present and anticipated activities of cells, some switched on, others off, and at different times and in different places in my body. It is a biological symphony of which I am mostly unaware.  

My cells have organelles that are also working on and off to make molecules, digest molecules and recycle molecules.  My organelles are composed of macromolecules whose organization and function have been worked out mostly since I was born. I know nothing of my life at the level of individual atoms save for those that are passing through membranes and ion channels or transported by proteins in my cells. 

I also know an important lesson of life. There is an enormous amount we do not know and humility alone should restrain us from acting as if we have certainty on our side, especially if our beliefs lead to intentional or unintentional bad consequences.  Know thyself may and does celebrate life but it can also be taken as a warning.  

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.

in Greek mythology, he Caucasian Eagle was tasked by Zeus to torture Prometheus every day.

By Elof Axel Carlson

Elof Axel Carlson

Science is a way of knowing. In today’s world it is based on reason, experimentation, technology and a belief that the natural world can be explained without invoking the supernatural as an explanation. Components of this definition of science have been around ever since humans formed communities and left traces of their daily lives in caves, burial sites and waste disposal sites.  

But in oral lore and written accounts more than 2,000 years ago, three supernatural explanations were used to explain how science arose. In Genesis, we are told the story of Adam and Eve and how Eve was tempted to eat of one of two forbidden trees in the Garden of Eden. Eve and Adam ate of the fruit from the tree of knowledge. For this disobedience Adam and Eve were cursed with a life cycle ending in death as well as pain and a struggle to survive.  

We owe to Greek mythology two different ways knowledge came to humans. Prometheus felt sorry that humans were helpless victims of difficult environments and he gave them a tool, fire, to warm themselves and make their own tools and form a civilization. For this, Prometheus was punished and chained to a rock by Zeus and had an eagle devour his liver every day only to have it regenerate at night.    

The other Greek myth involves Pandora who was given guardianship of a closed box containing the environments of the future. Her curiosity got the best of her and she opened it, shutting in hope and releasing all the ills of the world — disease, hunger, war, failure and madness.   

Note that the biblical version uses material reward (appetite or self-indulgence) as the motivation for disobedience. Adam and Eve and all of humanity to come are punished for their act. Note that Prometheus, not mankind, is punished for giving a tool to humanity. Note that Pandora’s curiosity is blamed for the ills of society.  

These three mythic views of how knowledge came to humanity reveal a tension between the world seen by those invoking the supernatural and the views of those who innovate, who explore their curiosity about the world and who show how to apply knowledge to advance human happiness and desire for improvement of their circumstances.  

The tension between religion and science is not a winner takes all choice with either one side or the other being correct, historically or in practice. Scientists can betray the ideal of science through fraud, conflict of interest or indifference to real or possible bad outcomes of their work. Religious or not, humans frequently rationalize their behavior.  

It is the Prometheus version of the gift of fire to make tools and apply science to human welfare that most scientists would favor. Science is seen as a way of describing the world and changing harmful environments into safe ones. It is a tool that leads to new knowledge and experiments and endless applications.   

In Pandora’s universe curiosity is not seen as beneficial. It is seen as a dangerous behavior leading to the release of the evils of this world. What kept us safe before Pandora was some supernatural box in which those evils were contained. Pandora, like Eve, could not resist satisfying her curiosity. But unlike Adam and Eve, she was not looking for a material benefit symbolized by forbidden fruit.  

Note the role of compassion in the motivation of Prometheus. Note the lustful anticipation in Eve’s gullible acceptance of the snake’s guile and to the sexual nature of knowledge reflected by Adam and Eve making clothes as their first act after eating the fruit. Note the lack of forethought to unintended consequences in Pandora’s opening the box.  

While all generations of humanity have faced similar hardships of finding food, building shelters, raising a family and finding meaning in their lives, different generations have interpreted knowledge and its applications in many ways. But all three ancient views of the acquisition of knowledge share a belief, regardless of its origins or its occasional shortcomings, in the importance of knowledge and technology in order to live a better life.    

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University

The flowering plant Amborella trichopoda is the oldest ancestral form of the angiosperms .

By Elof Axel Carlson

Elof Axel Carlson

Flowering plants are familiar to us as bouquets and garden plantings that delight us as they emerge in spring and summer. They are collectively part of the angiosperms, which also include familiar trees with generous-sized leaves that are shed in the fall.

They first appear in the fossil record about 130 million years ago. For those not familiar with how old life on Earth is estimated to be by biologists, that is about 60 million years before the dinosaurs went extinct.

Ferns, mosses and conifer trees (like gingkoes) existed long before the angiosperms. If the angiosperms are arranged in a sequence from oldest to most recent types, the oldest ancestral form of the angiosperms alive today is found in the Pacific Ocean on New Caledonia, an island northeast of Australia and northwest of New Zealand. That flowering plant is known as Amborella trichopoda.

A lot has been learned about the biology and history of Amborella. Its pollen, or ovule, has 13 chromosomes (and thus its leaf, stem and root cells have 26 chromosomes each). The Amborella ancestor gave rise to 250,000 species of flowering plants. About 75 percent of them have seeds with two fleshy modified leaves called cotyledons.

If you eat a fresh green pea from a pod and look at it before you pop it into your mouth, it has two halves, which is why you call it split pea soup when you cook a bag of dried peas.

The flower of the Amborella trichopoda

The DNA of Amborella has been worked out. It has 870 million base pairs. These are organized as 25,347 genes. Shortly before Amborella arose, it had experienced a doubling of its chromosome number. No major changes have occurred in its chromosomes since that event. Its nuclear genes have few inserted repetitive sequences. But, curiously, its mitochondrial DNA has many horizontally transferred genes from algae, mosses and lichens.

The ancestral genome of the angiosperms can be inferred because the major branches of the angiosperms share that core set of genes. This will allow botanists and chemists studying plant evolution to work out the functions of these shared genes as well as the distinctive genes that gave rise to the six major branches of flowering plants.

Quite different is the loblolly pine. It is a gymnosperm rather than angiosperm. They have a much longer history on Earth than the angiosperms. The conifers are the most familiar of the gymnosperms whose seeds are “naked” and enclosed in cones. Imagine the pine cones used in foods and compare them to the peas and beans in your soups.

The loblolly pine can live up to 300 years.

The loblolly pine, or Pinus taeda, is a common pine tree found from Florida to Texas and as far north as New Jersey. The trees can live 300 years and they are a major source of industrial lumber and paper pulp. The name loblolly is from an English idiom for food boiled in pots producing soups, broths or porridges. It has the largest known genome of any living organism, 23.2 billion base pairs (about seven times more than human cells and about 22 times that of Amborella. Unlike Amborella, 82 percent of its DNA is repetitive (formerly called junk DNA) caused by infectious insertions of tiny sequences of DNA. It has 50,172 genes in its pollen, or ovule, genome and they are located in 12 chromosomes per gamete.

One of my six students who got their doctorates with me at UCLA, Ronald Sederoff, pioneered the molecular biology of woody plants using the loblolly pine. He devised a technique to insert genes into woody plants, enabling his laboratory to study how wood is formed and how genes could be studied without waiting many years to study their genetics.

I was very pleased to learn that he was the recipient of the Wallenberg Prize, which is given by the king of Sweden for a contribution to plant biology, a field that is usually overlooked in the Nobel physiology and medicine prize. He attended the ceremony in Stockholm last October.

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.

The Dionne sisters, born in 1934, are the first quintuplets known to have survived beyond infancy.

By Elof Axel Carlson

Elof Axel Carlson

Cloning is a fancy word for making identical twins. Another fancy word is calling twins monozygotic, meaning that the two (or more) identical twins arose from a single fertilization of an egg that produced a mass of cells that split into two or more batches of cells, each batch forming an individual.

The Dionne sisters in Canada (five of them) were the most famous set of identical twins. Artificial cloning, or making twins in animals, began with the work of Hans Driesch in the 1890s.  He used sea urchins to separate cells after fertilization, and the individual cells became identical twins. 

A more surprising technique was developed by Robert Briggs and Thomas King in the 1950s; they used cell nuclei from early embryos to insert into enucleated eggs and make clones of frogs.

Ian Wilmut made Dolly in 1996, the first cloned sheep from a cell nucleus taken from the breast of an adult female sheep. Since then lots of animals have been cloned, including pet dogs and cats.

The leaders in this effort to commercialize animal cloning have been South Korea and China.  China has now taken the lead of combining gene editing (replacing one gene with another by microsurgical techniques called CRISPR-9). They believe this will change how research in human diseases will be done. They cloned a beagle after editing one of its donor cells to produce a medical condition of a form of blood vessel damage that leads to heart attacks and strokes.

The arguments for this are based on human welfare. By having a healthy dog as a control and its altered clone with  the culprit gene to be followed in the course of disease, they have dogs differing in only one known gene. They can try methods to regulate that gene, isolate its gene product or functions as it creates a disease later in that dog or they can try using agents that might block the gene from acting or block the product of the inserted gene so it does not lead to heart disease or strokes.

Some people feel medical experimentation should never be done on animals, only on consenting humans. Some feel it is cruel to be created not as a loved pet but as a “thing” to be used in research. Much of human conflict has been based not on conflicts of good versus evil but on the perceived goods of one faction against the perceived goods of a different faction.

I suspect that American (and some other countries) pharmaceutical companies wanting to avoid legislation banning animal cloning  will just have that research done in China or other countries that do not recognize the rights of animals.

Living with contradictions is part of being human.  We claim “thou shall not kill” is mandated to us, but we allow killing by intent in war, self-defense,  execution of condemned prisoners and by neglect (low wages and a government that assumes health is a private matter and not the responsibility of government beneficence).

We could do the same with “thou shall not covet” and apply it to making money. Are not billionaires coveting money when they use lobbyists to change inheritance tax laws and place their money where it cannot be taxed and is shielded by legal loopholes?    

The combination of gene editing and artificial cloning by nuclear transplantation will have major benefits in medicine for those diseases that have identified genes. For single gene defects this is about 2000 known birth defects and other conditions most parents would not wish to have afflicted on their children.

If humans do not prevent diseases by medical research, nature will take its toll in reaping the sick and disabled as it did for centuries until the era of modern medicine began with the germ theory, public health movements and the shift of medicine from an art to a science.

I much prefer having had my cataracts removed so I can now drive without eyeglasses than to find myself unable to read books and articles or be a menace on the road.   

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.

Gray mouse lemur

By Elof Axel Carlson

Elof Axel Carlson

In 2016 a 54.5-million-year-old set of some 25 bones were unearthed in Gujarat, India. They belonged to the closest ancestor of all primates that lived about 56 million years ago. One branch of that ancestor produced the lemurs, lorises and an extinct group of adapoids. A longer branch produced the tarsiers and an extinct group of omomyids. Even more recently from that tarsier branch came the New World monkeys, followed by the Old World monkeys and most recently the apes and humans. The Gujarat primate has bones that are like a mixture of the lemurlike and monkeylike lineages.

The primates arose from an earlier line of dermopterans, and they in turn came from a line of tree shrews. The dermopterans are represented by a nearly extinct line of flying mammals that superficially look like bats but that differ in their mode of flight. They have a flap of skin that serves as a gliding organ, and they can glide about 200 feet from tree to tree in a forest. They are not good climbers, lack opposable thumbs and are nocturnal. Their diet consists of fruits, leaves and sap. 

One species lives in the Philippines. They are called by their popular name, colugos. Colugos are unusual in the trade-offs they have made in adapting to the rain forests in which they live. They gave up the marsupial pouch as they shifted to the placental pregnancies of mammals, but like marsupials, the colugo babies are born immature and are shielded by their mothers for about six months in the skin flaps that serve as both gliders and a pseudopouch.

We humans (Homo sapiens) can decide which of our ancestors to call human. The Neanderthals and Denisovans are our closest ancestors, and we acknowledge that they shaped tools, lived in communities and even bred with us, leaving behind as much as 3 percent of their genes in our genomes in many parts of the world.

The 54.5 million-year-old animal would have most closely resembled the gray mouse lemur.

Less human in appearance are Homo erectus and Homo habilis. All of these walked upright, unlike apes. Their skeletons are more humanlike than apelike. The very fact that they could reach reproductive age and survive tells us they knew how to shape the environments in which they lived or extract from them the protection, food and materials needed for their survival. 

Humans are remarkable in their plasticity of opportunities. They can migrate to frigid arctic or antarctic climates or live in deserts, in high altitude or sea level, in four seasons or one.   

As a geneticist I am aware that the contribution of any one of my Homo sapiens ancestor’s genes some 200,000 years ago had a low probability of remaining in contact with its neighboring genes, and in all likelihood those genes in me are from virtually all of the individuals alive then. 

When we do genealogy, assuming four generations per century, it only takes 2,000 years for any one of those ancestors in our family history to have less than 1 percent of our genes. If we are lucky (like royalty) to have records of our ancestors going back to the Middle Ages, we would likely find ourselves related to everyone in an ancestral region (a person like me whose father was from Sweden would be related to virtually every Swede in the age of the Vikings a little over 1,000 years ago).

In many ways our past genetic heritage is like the history of my Montblanc fountain pen, which was given to me by my students at UCLA in 1968. In the 40 years I wrote with it, I sent it to be repaired dozens of times either because I dropped it or a part wore out. Each time my pen came back looking new. I still think of it as the 1968 gift, but I doubt if there is any part that is still of the original pen given to me then.

This makes it unlikely that there is a genetic basis for behavior traits in a family that can go through more than 10 generations. The processes of shuffling genes every time we make eggs or sperm breaks up whatever cluster of genes we wish to assign to a human behavior. This is good because the genes of conquerors were spread widely while they held power, but having one of Ivan the Terrible’s genes or Genghis Khan’s genes would not make us a predatory monster in our relations with others. We inherit genes, not essences. If there is a mark of Cain, it is not engraved in our genes.

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.