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Life Lines

Oxford University, Gilman Hall

By Elof Axel Carlson

Elof Axel Carlson

If I had to praise a virtually unknown person as having had the greatest impact on our lives, I would choose Daniel Coit Gilman (1831–1908). Gilman attended Yale University and majored in geography. He became an administrator and founded the Sheffield School of Science at Yale, became the president of the University of California and in 1876 became the first president of Johns Hopkins University. He also helped set up the Carnegie Institution for Science in Washington, D.C.

In 1875 when he was asked to be president of Johns Hopkins University, he embarked on a tour of Europe. He liked the German university emphasis on scholarly research, the ideas of Thomas Huxley on liberal education, and came back with several European scholars who agreed to teach at Johns Hopkins, which opened its program in 1876.

Gilman started his university with a graduate school, then added an undergraduate program and eventually a medical school. He felt the German model was flawed by giving too much power to a single professor in a department who chose subordinates to teach or assist in research. Instead Gilman created departments with several professors committed to scholarship so they could stimulate their research and mentor graduate students who benefited from the multiple outlooks of the department.

By 1910 the success of the Johns Hopkins graduate program shifted the flow of scholars going from the United States to Germany, and after World War I the flow of scholars moved westward to American graduate schools. Gilman’s ideas led to the overwhelming success in Americans winning Nobel Prizes especially in physics, chemistry and the life sciences. It also flooded industries, hospitals and agencies with talented people applying their skills and creativity to their work.

I wish every science teacher would read T. H. Huxley’s “A Liberal Education and Where to Find It” and “On a Piece of Chalk.” They were published about 1868. The first essay shows how Huxley approached education as a way to connect the sciences, art and humanities, shifting knowledge away from an exclusive focus on Greek and Roman civilization as it was then in British schools and toward our connection to the universe in which we live.

Daniel Coit Gilman

The second is an example of good teaching. When I first read his essay when I was about 19 or 20, I could see him in my mind lecturing to the public and holding a piece of chalk in his hand and describing some shavings of it under the microscope revealing the miniature snail-like skeletons of plankton that dribbled down to build the chalk cliffs of Dover. I wanted to be like Huxley, creating lectures that would send shivers of surprise and delight at new knowledge that touched students’ lives.

I singled out Gilman as an educator who changed how knowledge can be learned and transmitted. Our Nobel Prizes and the esteem of rewards are showered on those who make wonderful contributions to knowledge. They are rarely given to founders of institutions that make new ways of learning possible. Both are necessary in our lives.

If I had to single out the one scientist who made the greatest contribution to humanity, I would give that honor to Louis Pasteur for introducing the germ theory of contagious diseases. His use of the microscope to investigate the spoilage of wines turning to vinegar showed that small round yeast cells were replaced by smaller rod-shaped bacteria. His experiments demonstrated numerous infectious diseases as stemming from specific bacteria. It led to vaccinations, public health programs, pasteurization of the milk children drink and the reduction of infant mortality, allowing mean life expectancy to rise from about 45 years at birth to about 80 years today.

New knowledge and inquisitive minds are what make civilization possible.

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

By Elof Axel Carlson

Elof Axel Carlson

Why is the term race rarely used by geneticists? The term race is not a scientific one. It is largely cultural when applied to humans. It is too ambiguous a term for describing a population of any one species.

For example, suppose I were a breeder of dachshunds and I specialized in two varieties — one that had a black coat of fur and the other that had a tan coat of fur. I would not call them black or tan races. I would call them varieties of a specific breed called dachshunds of dogs who are described by biologists as the species Canis vulgaris.

The term race is vague. Is it the varietal difference? Is it the collection of traits that we use for dogs, cats, horses, cattle and other domesticated animals? If it is applied to the color of dachshunds, does that mean humans are divided into thousands of races if I were to use McKusick’s online reference work on Mendelian inheritance in humans?

That work describes thousands of genetic traits caused by single gene malfunctions. Geneticists use the term breed for genetically manipulated traits or collections of traits by human selection or breeding. They use the term varieties or naturally occurring variations in a population or for new varieties arising by mutation in a sperm or egg.

Racism is used to describe a social application of race to designate rights and to assign attributes to other races by members of a specific race. There is far more genetic variation within a single race than there is between any two races. The criteria for classifying human races are often arbitrary and are based on skin color, facial appearance, hair texture and other visually distinctive traits. Many of these traits involve quantitative factors (like skin color), and thus racial mixture quickly obliterates the sharp racial traits initially used to describe a person of a specific race.

Quite a few people who have considered themselves and their immediate family as white are surprised when they send off DNA to be analyzed and discover they have percentages of African, Asian, Hispanic, Native American or Jewish ancestry along with their majority Caucasian Western European ancestry.

Racism is particularly destructive in assigning behavioral traits (personality, intelligence and social failure or inadequacy) to race. Most of those traits are determined by how we are raised and not by a roll of genes in forming our parents’ sperm or eggs. If they were to follow their own criteria, racists would find that white Catholics and Protestants are inferior to Jews and Orientals in intelligence measured by intelligence tests or IQs.

The revival of racist ideology among groups like the KKK, neo-Nazis and white supremacy groups is not based on biology or genetics. It is based on prejudice passed down by people who feel victimized if people different from them are treated with justice, fairness and equal opportunity.

The Civil War was fought over slavery. Thousands of abolitionists participated to hide escaped slaves, write books and pamphlets denouncing slavery and demanded the freedom of all slaves. The Confederacy seceded from the U.S. and fought to keep its slaves, many slave owners justifying slavery on biblical grounds — that it was a divine punishment for the descendants of a son who laughed at his drunken naked father.

Most ministers and priests in the North denounced that interpretation. We are not born with a knowledge of our past history. It has to be learned and it has to be taught. It is easier to avoid talking about our past errors than to ignore them.

Germany made a special effort after World War II to teach the racism of its Nazi past to all its school children so that error would never again be repeated. Let us hope that we teach our youth that we are one living species, Homo sapiens, and in the Judeo-Christian tradition we all have one ancestor in common.

In the scientific tradition we also have one human species in recorded history and enormous genetic variation that is constantly changing as humans migrate around the world, settle down or move on to new areas of the Earth. Most of that variation is in Africa where our species first arose.

It is ironic that whites who enslaved or colonized Africa diminished, in their minds, this genetic variation and reduced it to racist formulas of a handful of physical or behavioral traits. I hope this revived racism will recede and our focus will shift to problems that can and should be solved by our elected representatives. Those problems are overwhelmingly caused by our social and economic conditions and not by our genes.

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

By Elof Axel Carlson

Elof Axel Carlson

We tend to generalize in making judgments about ourselves and others. Some claim they are self-made and promote their work ethic as the reason for their success. Some claim they are victims of circumstances over which they had limited control. Examples exist of people who have moved from rags to riches, and no one would blame victims of racial prejudice or the Holocaust for the misery they or their family members experienced.

In my own life I can think of many such events that have either made my life possible or significantly influenced it. My father told my brother and me that when his father was on a business trip from Stockholm, Sweden, to Hamburg, Germany, he was walking down a street when a German officer was walking directly toward him.

It was the custom there to step in the gutter to let a military officer have the right of way. My grandfather felt no such sense of obligation and felt his side of the road was appropriate for continuing his walk. The officer pulled out his sword and slapped my father’s face with it. The insult made him a pacifist, and that outlook was passed on to my father and to me. It also made him shorten his trip, and he went to Normandy to visit friends and relatives who had a summer house near the Baltic Sea.

There he met the young woman he eventually married, my grandmother, Amanda, who lived near Göteborg. I can say that I owe my existence to a slap in the face. My parents, too, met in a strange circumstance.

My mother was selling key rings on Broadway in Manhattan on a cold winter day. She entered a hotel entrance on 75th street to warm up, and the doorman told her to go downstairs to warm up in the employee’s room. There she met a Swedish elevator operator who was changing out of his uniform to go home. He took her to dinner and that began the courtship of my parents. I could say I owe my existence to a sympathetic doorman who felt compassion on a woman down on her luck.

When I was a graduate student at Indiana University, I met my wife Nedra, also by a curious circumstance. I had written letters to my parents and friends and lacked 3-cent stamps to mail them. I asked around and was told there was a girl who may have stamps who was usually working in a laboratory the floor above me. I knocked on the door and met a nervous undergraduate who did have stamps and I invited her to tea. When she did not come, I brought the tea to her. That was our first day of courtship. I could say that I owe my marriage to Nedra to a 3-cent stamp.

I do not doubt that such chance events play major roles in our lives. But most of our lives are under our control and shaped by habits and circumstances. We do not choose our partners randomly. Assortative mating is influenced by religion, race, ethnicity, social class, education, looks, personality and many other features that steer us toward or away from possible partners. Before the 20th century most marriages were arranged or required parental approval.

But it is not just social factors that determine how we come into this world. Each act of intercourse involves tens of millions of sperm. The odds of the one that made you on a particular day were not predictable when that sperm was in a testis or when it made its initial way to the cervix of the uterus and eventually to the oviduct where it would meet the egg that formed you.

That is quite a contrast to the injection of single sperm into an egg during a form of in vitro fertilization (IVF) used by infertile couples where the sperm has problems wiggling its tail or having the right surface proteins to recognize it is encountering an egg. In that case we get the paradoxical conclusion that the child born by the IVF procedure owes its existence to the father being sterile!

Life is filled with rare events, the overwhelming number of them not even being recognized as significant in our lives. At the same time society is so organized that much of what we do is planned and anticipated and goes essentially as we hoped it would.

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

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By Elof Axel Carlson

Elof Axel Carlson

Yeasts are single-celled organisms belonging to the eukaryotes. They have a nucleus with chromosomes and a surrounding cytoplasm with embedded organelles. There are 1,500 species of yeasts (in contrast to the small number of species of the genus Homo). Most of these yeast species reproduce by mitosis without a sexual phase.

Some species use a process of budding, with the dividing nucleus producing one nucleus entering a small bleb of cytoplasm at the surface and the other staying with the large mass of cytoplasm of the original cell.

The yeast that gives civilization a boost is Saccharomyces cerevisiae. It converts sugars into carbon dioxide and ethyl alcohol. Different strains of this species are used to make beer, wine, mead and other alcoholic beverages that prolonged life expectancy because the alcohol killed harmful bacteria in the water that humans needed. Other strains of this species lead to the rising of bread during baking and helped bring about the agricultural revolution that tamed humanity into cultural communities.

Beer making goes back to at least 6,000 years ago. In Africa a different species, S. pombe, was used to make a beer from millet.

There are also species of yeast that are harmful to humans. Some cause urinary tract and vaginal infections, especially Candida albicans. Yeast strains are also involved in babies’ mouths (thrush) or in toenail and fingernail infections.

The yeast cell has 16 distinct chromosomes and its DNA has 13 million base pairs. Its genes produce 5,800 different proteins. Its mitochondrial DNA has almost 86,000 base pairs and 35 genes.

Molecular biologists have used yeast as engineering systems for producing pharmaceutical products. Yeast chromosomes can be identified, and genes from other organisms can be inserted into them. The yeast genome can also be used for basic science, and each of its 5,800 protein products can be studied for function in the cell.

Yeasts are also being used to study synthetic genetics where genes and chromosomes are designed by scientists and inserted into one or more yeast chromosomes. Artificial yeast chromosomes are reliable for inserting one or more genes designed for commercial use.

Within 10 years scientists hope to have the first artificial nucleus with all the essential yeast genes needed to allow yeast cells to divide and grow and make alcohol. That nucleus will have 16 synthetic chromosomes made by putting together the nucleotide sequences of the genes in each chromosome without using a living system to do so. They will tag each chromosome with inserted genes that can serve as switches to make them machines capable of turning specific genes or groups of genes on or off. The switches will respond to temperature, pH or chemical signals to activate the switches.

No one knew what yeast was some 6,000 years ago. The cell theory did not come into our awareness until 1838. Brick yeast was not sold until 1867. Granulated yeasts (like the packets available in supermarkets) did not exist before 1872. Instead, bakers would save some of the raised dough and mix it into a fresh batch of flour and water.

Similarly, wine makers or beer makers would take samples from their fermenting kegs and use that to start a new batch of cereal mash or crushed fruits to start the fermentation process. Even if those were not available, there was usually a lot of naturally occurring yeast cells on the surface of grains or fruits to generate fermentation. Yeasts have been domesticated to make alcoholic beverages. Bacteria and other fungi have also been domesticated to make sour cream, yogurt and cheeses. Since the 1940s, fungi and bacteria have been used to make antibiotics that have saved millions of lives from pneumonia, gangrene, sepsis and other infections.

Diphtheria, anthrax, bubonic plague, typhoid fever and typhus are no longer threats to the lives of those in industrialized nations that have access to antibiotics, public health measures and sanitation. We owe to Pasteur and Koch in the last decades of the nineteenth century the knowledge of the microbial germ theory of infectious diseases. Their work explained what produces some foods we love through fermentation by microbes, the microbial basis of rotting or spoilage of food and the microbial basis of contagious diseases.

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

By Elof Axel Carlson

Elof Axel Carlson

Science is a way of interpreting the universe in the era in which we live. One of the realities of our lives is that we do not know how much of the world we think we know is really incomplete.

Think of it this way — If you grew up when the American Revolutionary War was being fought, you would not know a lot. You would not know your body is composed of cells. You would not know that heredity is transmitted by genes located on chromosomes present in nuclei of cells because no one knew there were nuclei, chromosomes or genes.

You would also not know there are biochemical pathways that carry out your metabolism in cell organelles because no one then knew there was such a thing as metabolism, biochemical pathways or cell organelles. And you would not know that infectious diseases are associated with bacterial and viral infections nor would you know that your body is regulated by hormones. If you created a time line of scientific findings in the life sciences, the cell theory was introduced in 1838. Cells were named in 1665, but Robert Hooke thought they accounted for the buoyancy of cork bark. He drew them as empty boxes.

When Schleiden and Schwann described cells, they were filled with fluid; and Schwann thought nuclei were crystallizing baby cells being formed in a cell. The cell doctrine (all cells arise from pre-existing cells) did not come until Remak and Virchow presented evidence for it. Mitosis, or cell division, was not worked out until the late 1870s; and meiosis of reproductive cells (sperm and eggs) was not worked out until the 1990s.

Fertilization involving one sperm and one egg was first seen in 1876, while most cell organelles were worked out for their functions and structure after the invention of the electron microscope in the 1930s. There was no organic chemistry before Wöhler synthesized molecules like urea in 1823, and biochemical pathways were not worked out until the 1940s.

DNA was not known to be the chemical composition of genes until 1944, the structure of DNA was worked out in 1953, molecular biology was not named until 1938 and the germ theory was worked out in the 1870s and 1880s by Pasteur and by Koch, who both demonstrated bacteria specific for infectious diseases. Embryology was worked out in 1759 by Wolff, while hormones were first named and found in 1903 by Bayliss and Starling.

What the history of the life sciences reveals is how dependent science is on new tools to investigate life. Microscopes up to 30 power came from Hooke’s efforts in 1665. A better microscope by Leeuwenhoek distinguished living organisms (“animalcules”) at up to 500 power.

It was not until the 1830s that microscopes were able to overcome optical aberrations and not until the 1860s that a stain technology developed to see the contents of cells. This boosted observation to 2000 power. For the mid-20th century, cell fractionation made use of centrifuges and chromatography to separate organelles from their cells and work out their functions.

Experimental biology began in England with Harvey’s study in 1628 of the pumping action of the heart. Harvey was educated in Padua, Italy, where experimental science had been stressed by Galileo and his students who began applying it to the motion of the body relating bones and muscles to their functions. No one alive in 1750 (or earlier) could have predicted DNA, oxidative phosphorylation, the production of oxygen by plants, Mendel’s laws of heredity or the role of insulin in diabetes.

But what about the present? How complete is our knowledge of life processes? Are there major findings in the centuries to come that will make our present understanding look as quaint as reading the scientific literature in the 1700s?

We can describe what we would like to know based on our knowledge of the present and likely to be achievable. We cannot predict what may turn out to be new functions or structures in cells. At best (using what we do know) we can hope to create a synthetic cell that will be indistinguishable from the living cell from which it was chemically constructed. But that assumes the 300 or so genes in a synthetic cell will account for all the activities of the vague cytoplasm in which metabolism takes place.

For the level of viruses there are no such barriers and the polio virus has been synthesized artificially in cell-free test tubes in 2002 (an accomplishment of Eckard Wimmer at Stony Brook University).

Within a few years ongoing studies of bacteria and of yeast cells with artificial chromosomes, may resolve that question for the genome of a eukaryotic cell. I hope that an artificial cytoplasm will be worked out in that effort. That might be more of a challenge than presently assumed.

By Elof Axel Carlson

There are projects underway to test the feasibility of sequencing every species on Earth (including extinct species where their DNA is still available). The largest of these programs is in China, which is hoping to sequence the 1.5 million known named species of animals, plants and microbes.

Elof Axel Carlson

Phase one will sequence one species from each of 9,000 families (the taxonomic unit above the genus level). The second phase will sample one each of the 200,000 forms of life described as belonging to a genus. Phase three will look at all the species remaining.

It is a daunting amount of work. Think of it this way. There are 6.8 billion telephones on Earth. If you entered every telephone book into one computer site, you would have access to more than 90 percent of all living people.

Looking up a phone number would also give you information on the person’s name, country that person lives in and the home or business address. For perhaps one billion of them who are listed in Yellow Books, it would tell you what they do for a living.

But DNA sequences will do more than identify a species. The sequence of genes and their functions will classify the organism and tell us if it is a plant, animal or microbe, and what it does as a particular species. We would know its anatomy, physiology, metabolism, life cycle, mean life expectancy, where to find it on Earth, what it eats and how it lives.

For humans it would show how we are related to the 7 billion other humans on Earth. It would provide abundant information on how all of us are related in an evolutionary pathway of immense size. The Chinese company, BGI, located in Shenzhen, estimates it will take 10 years and cost about $5 billion to complete the project.

There are six other projects underway around the world. One is seeking to sequence all vertebrates, a second wants to do that for arthropods (mostly insects, spiders and crustaceans), a third is looking at marine invertebrates, a fourth is interested in the world’s ants, a fifth prefers to sequence the world’s birds, and the sixth is seeking to identify all African food crops.

As far as I know, no one is trying to do a genome sequencing of all human beings. The closest to doing that is the country of Iceland, which has asked its citizens to volunteer and give a sample of saliva for DNA sequencing. Half of Iceland’s people have done so. They are mostly descendants of Viking settlers and their DNA studies are immensely helpful for looking at genes involved in human disease risks (such as birth defects, Alzheimer syndrome, cancer, hypertension, risk of late-onset diabetes, heart disease and strokes).

The implications of this effort to gain knowledge of the world’s genomes are numerous. For evolutionary studies they are a remarkable resource. For medical diagnosis they are equally valuable. They will be a gold mine of rich ores for the pharmaceutical industry. Think of all the antibiotics that will be mined from the microbial genome data. Just as there are tens of thousands of projects engineers do for buildings, electronics, infrastructure and transportation so, in the coming decades, will thousands of projects emerge and new fields of science from applications of this immense resource of the all Earth genome project.

Will this also involve bad outcomes of new knowledge? Certainly. We did not abolish engineering because engineers have designed most of the weapons used in war. We did not abolish chemical industries because some of them gave us environmentally toxic or harmful agents like DDT, Agent Orange, gas in World War I or thalidomide. We do not condemn X-ray diagnosis because radiation can induce gene mutations. What we do is regulate our technological innovations.

Think of regulation in industry as something like criminal law in society. We punish those who break laws (embezzlement, theft, assault, rape, slander, robbery, kidnapping, extortion, bribery). Regulation addresses many issues only one of which is misconduct. Similarly, law addresses wrongs, not all of which are criminal (we call that noncriminal law civil law). Some politicians want to do away with regulation of industries.

Is not dumping wastes into rivers a criminal act? Is not choking a city with industrial gases a criminal act? Laws can be changed or even abolished, but loss of human life, damaged health, destruction of ecosystems and putting the brunt of waste disposal on those most vulnerable (the poor) should be regulated.

I am an optimist, not a Pollyanna, about the future of the all Earth genome projects. We need both new knowledge and new regulation.

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

By Elof Axel Carlson

On March 20, 1997, I was happy to see my first Life Lines column in the Arts and Lifestyles section of publisher Leah Dunaief’s North Shore newspapers. Since then more than 400 Life Line columns have appeared for which I am grateful.

It has been my good fortune, since I was a teenager, to be a storyteller. I learned that the best way to understand something is to tell it out loud like a story. It worked in high school and it has been an asset in my teaching whether at the graduate level or for courses on science for nonmajors.

This column has been my connection to a largely unknown audience. When I was teaching at Stony Brook University, I regularly ran into strangers at the supermarket who would give me feedback. I learned from Editor Heidi Sutton that the online version of the TBR newspaper site has a substantial number of readers of this column.

To celebrate this anniversary, I will share with you the story of the newest field of the life sciences, synthetic genomics. A team of scientists led by Jef Boeke at NYU published an article in Science describing their success in making synthetic chromosomes for yeast cells. Yeast has 16 chromosomes and 6,275 genes. Those 16 chromosomes also contain 12,156,677 base pairs that make up its DNA.

The DNA sequence was worked out in 1996 so that knowledge goes back to the time I was writing the first batch of articles for this column. The NYU study has synthesized five of the 16 chromosomes and tested them in yeast cells to show that they function. They removed nonfunctional genes and inserted components that do not play a role in gene function or metabolism.

They also have created a 17th chromosome that contains a set of genetic tools. These include genes that repair mutations, genes that shuffle genes more effectively to speed up new mutation production when a desired type is sought, and genes that make new products or boost their production. Different strains of yeast cells make bread, beer and wine.

Boeke’s team hopes to complete the remaining chromosomes this year. For their long-range plans they hope the synthetic yeasts they make will produce antibiotics, vitamins, painkillers, hormones and other biological products for the pharmaceutical industry. They hope their synthetic yeasts will have a wide range of uses in making breads fortified with vitamins and proteins.

Think of having synthetic yeast-made varieties of food on a space journey to Mars where opportunities to grow plants are limited for a journey that might take months or years. They are following federal regulations to make sure their yeast is safe and they do not plan on making new species or new forms of life. But all new inventions of science lead to new outlets; so I will not be surprised years from now to see artificial life-forms made to do useful things like digesting industrial wastes and degrading them to harmless components.

Imagine if you could engineer a yeast cell to concentrate the gold from ocean water. Imagine a synthetic yeast that could pull the carbon dioxide from the air and turn it into gasoline or coal so that carbon dioxide levels are actually lowered while carbon-based fuels are made without mining for them.

I have never been a practical person and such applications, while easy for me to imagine, are not as satisfying as the knowledge that synthetic genomics can provide. Synthesizing the 16 chromosomes from off-the-shelf chemicals and forcing yeast cell cytoplasm to accept an artificial nucleus is not the same to me as finding out what that cytoplasmic material does and how it works.

Is it, as one geneticist remarked, a “playground for the genes?” Or will it turn out to house something so new to our field of biology that we can’t even imagine its components and functions? Will this too be synthesized once it is successfully tackled by a future generation of scientists?

I am not worried about applications to germ warfare. Most military planners know that germ warfare is a risky way to wage it because it is not easy to immunize your own nation’s citizens before you manufacture and launch new germ warfare agents against an enemy. There is also the war crimes risk for those involved if they are on the losing side of the war.

I am also not worried about runaway contagions as unexpected consequences of scientific studies. I strongly believe government regulations are essential to protect the public’s health and the NYU team is rigidly following those guidelines.

I celebrate this accomplishment because it is opening up a new field of science and some of the persons learning about this might be among the first to apply that new scientific knowledge to medicine, industry and our ever-changing conception of life and our stewardship for fostering it.

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

'A trip to the American Museum of Natural History was my idea of being in heaven.' - Elof Carlson

By Elof Axel Carlson

The life sciences are vast in the number of specialties that exist for those pursuing a career as a biologist. A majority of college biology majors are premedical or seek some sort of health-related field. As much as possible they hope the biology they learn will find its way into the health field they seek to enter. Persons who want to be scholars in biology are often motivated by a desire to know as much about life as they can. I was one of those from early childhood when a trip to the American Museum of Natural History was my idea of being in heaven.

Elof Axel Carlson

I loved learning about evolution and the diversity of life. I knew I wanted to be a geneticist when I was in ninth grade and learned about Paul Müller’s Nobel Prize work on inducing mutations. Like a duckling, I felt imprinted and wanted to work with Müller someday.

Graduate work was different. As a teaching assistant I got to see about 90 different specimens each week for the various organ systems displayed by students. Unlike the textbook perfect illustrations, veins and arteries could be slightly off in the specimens I looked at. Their colors differed. Their texture differed.

I also learned how much we didn’t know about life. For my specialty of genetics (with Müller, as I had hoped) I felt steeped in experimental design, techniques and ways of thinking. Doing a Ph.D. allowed me to examine a gene using the tools of X-raying to produce mutations of a particular gene and subtle genetic design to combine pieces of a gene — taking it apart and combining pieces that were slightly different. It gave me an insight into that gene (dumpy, in fruit flies) that for a short time (until I published my work) I was the only person in the world that knew its structure.

In my career I have taught biology for majors, biology for nonscience majors, genetics, human genetics and the history of genetics. I have taught lower division and upper division courses, graduate courses and first-year medical classes. I learned that sharing new knowledge with students excited their imaginations. I learned that the human disorders I discussed led to office visits; and if I didn’t know the information they sought, I went with them to the medical library and we looked up articles in the Index Medicus and discussed their significance.

Often that student was married and had a child with a birth defect (born without a thyroid, having a family trait that might appear like cystic fibrosis). I would prepare a genetic pedigree and give it to the student to stick in a family bible for future generations to read. I also delighted in going to meetings to discuss genetics with colleagues whose work I had read.

I was pleased that I shared a body plan with other mammals. I liked comparative anatomy, which taught me how other body plans work (mollusks, arthropods, worms, coelenterates, echinoderms). As a graduate student taking a vertebrate biology course, I went into a cave and plucked hibernating bats from a ceiling.

The world under a microscope is very different. To see amoebas, ciliated protozoans, rotifers and other organisms invisible to the naked eye or as mere dust-like specks is a thrill. I can go back in time and imagine myself as a toddler, a newborn, an embryo in my mother’s uterus or an implanting blastocyst rolling out of her fallopian tube. I can imagine myself as a zygote, beginning my journey as a one-celled potential organism typing this article into a computer. I can go back in time to my prehistoric ancestors and trace my evolution back to the first cellular organism (bacteria-like) more than 3 billion years ago.

I learned, too, that I contain multitudes of ancestors who gave me one or more of their genes for the 20,000 I got from my father’s sperm and the matching 20,000 genes in my mother’s egg nucleus. I contain some 37 trillion (that is, 37,000,000,000,000) cells or 2 to the 45th power, which means some 45 mitotic cell divisions since I was a zygote. I know that the warmth of my body is largely a product of the mitochondrial organelles in my cells that using the oxygen from the air I breathe and converting small molecules of digested food to provide energy that runs the metabolism of my body and disposes carbon dioxide that eventually is expelled from my lungs. This knowledge makes me aware of my vulnerability at the cellular level, the chromosome level and the genetic level of my DNA to the agents around me that can lead to birth defects cancers, and a premature aging.

Knowing my biology allows me to know my risks as well as new ways to celebrate my life.

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

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Charles Darwin

By Elof Axel Carlson

Elof Axel Carlson

An intellectual pedigree traces the power of mentoring across many generations. I got my Ph.D. in genetics with Nobel laureate Hermann J. Muller at Indiana University. Muller got his Ph.D. in genetics with Thomas H. Morgan also a Nobel laureate at Columbia University. Morgan got his Ph.D. in embryology with William K. Brooks at Johns Hopkins University.

Brooks got his Ph.D. in comparative anatomy with Louis Agassiz at Harvard. Agassiz came from Europe. He got his Ph.D. in ichthyology (fossil and live fishes) with Georges Cuvier in Paris. Cuvier got his doctorate in comparative anatomy from Ignaz Döllinger in Germany. Döllinger got his Ph.D. at Padua in Italy studying embryonic development. He was mentored by Antonio Scarpa at Modena in Italy.

Scarpa was mentored by Giovanni Morgagni at Padua. Morgagni was mentored by Antonio Valsalva who named the Eustachian tube, and he was mentored by Marcello Malpighi an early microscopic anatomist. Malpighi was mentored by Giovanni Borelli who first used physics to describe animal motion relating bones and muscles to function. Borelli was mentored, in turn, by Benedetto Castelli a mathematician and astronomer who studied sun spots. Castelli was mentored by Galileo Galilei.

I followed the history two more generations. Galileo was mentored by Ostillio Ricci. Ricci was mentored by Niccolò Fontana Tartaglia, another mathematician whose text on applied mathematics was a best seller in Renaissance Italy. From my Ph.D. in 1958 to Tartaglia’s years of birth and death (1499-1557) is a span of about 450 years.

If I number Tartaglia as 1, I am generation 16. Not all had a Ph.D. as their highest degree. Some had the M.D. The modern university as a research and teaching institution dates to the late 1700s in Germany. The Medieval and Renaissance university was based on the seven liberal arts leading to the B.A degree. Students could then choose law, medicine, theology,. or philosophy as a specialty leading to a M.A., M.D. or Ph.D. Nicolaus Copernicus got degrees in canon law (laws applied to and by the church), medicine and philosophy.

The M.D. degree until the late 1890s used to require a book-length dissertation as did the Ph.D. Note that German science was influenced by the Italian universities that took an interest in observational and experimental science in the Renaissance. It was Döllinger who brought this tradition back from Padua.

There was no scientific tradition at the university or college level in the United States until the 1870s when Cornell, Yale and Johns Hopkins stressed the Ph.D. as a scholar’s degree. Prior to that most American colleges stressed training for the ministry. Agassiz brought that scholarly tradition to Harvard to bolster American science.

I have done intellectual pedigrees for William Castle, Ralph Cleland, Seymour Benzer, Theodosius Dobzhansky, J.B.S. Haldane, Barbara McClintock and a few other geneticists. They usually differ. That means not all roads lead to Galileo. A few plug in to Agassiz or Döllinger. I was pleased to trace McClintock back to Carl Linnaeus. They are fun to do and you can use Wikipedia for the biography of a scholar you wish to follow. It will give (most of the time) the person who supervised a thesis or the names of that person’s best known students.

I also learned that sometimes there is more than one major mentor in a scholar’s life. Morgan was mentored by Brooks, but he was also mentored by H. Newell Martin who was a student of Michael Foster who was a student of Thomas H. Huxley, who was mentored by Charles Darwin. That means, I too, have a branch that leads to Darwin.

I learned from these pedigrees that we are shaped by what we experience. We are shaped by our parents and their community. We are shaped by mentors in high school or college. Sometimes it is through a course we take. Sometimes it is in our volunteer or extracurricular activities. Also, we have influence on more students than those who come for a Ph.D. research experience. In my career, this can be through the courses I taught, the office visits I had or the chance encounters with students while eating lunch, serving on committees that brought me in contact with them or serving as an academic advisor for my department.

Life gives us opportunities to be thankful. I thank the 15 generations that preceded me in my life as a scientist and teacher. What each generation gave was an opportunity to discover and to learn, to relate and to communicate, to lecture and to write.

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

By Elof Axel Carlson

Elof Axel Carlson

There are millions of species of living things. Until the 1860s biologists divided them into two kingdoms, animals and plants.

Louis Pasteur revealed a third group of microscopic bacteria that caused disease, fermented foods (like cheeses), rotted food and decomposed dead organisms. In the mid-20th century this third group, known as prokaryotes, was shown to consist of eubacteria and archaea, differing mostly in how they used energy to carry out their living activities.

Bacteria mostly use oxygen, sunlight and carbon dioxide as fuels and an energy source. Some bacteria are like green plants and use chlorophyll to convert carbon molecules to food and release oxygen. Most of Earth’s atmosphere arose from that early growth of photosynthetic bacteria. Archaea mostly use sulfur, superheated water and more extreme environmental conditions (like deep sea vents) for their energy.

Biologists today identify cellular life as having three domains — archaea, bacteria and eukaryotes. We belong to the eukaryotes whose cells have nuclei with chromosomes. The eukaryotes include multicellular animals, multicellular plants, unicellular protozoa (protists), unicellular algae and fungi.

The two prokaryotic domains and the five eukaryotic groups are designated as kingdoms. A rough time table of early life on Earth would put prokaryotic life about 3.5 to 3.8 billion years ago, the first free oxygen in our atmosphere about 3.5 billion years ago, the first eukaryotic cells about 2.5 billion years ago and the first multicellular organisms about 1.5 billion years ago.

The branches of the tree of life biologists construct have an earliest ancestor called LUCA (for the last universal common ancestor of a particular branch). There may have been a biochemical evolution preceding the formation of the first cellular LUCA with RNA and protein associations, RNA and DNA associations and virus-like sequences of nucleic acids.

The three domains have produced six million different genes. Molecular biologists have identified 355 genes that all cellular organisms share in common. This is possibly the genome of the LUCA of all living cellular organisms. Whether such a synthetic DNA chromosome could be inserted into a bacterial or archaeal cell or even a eukaryotic cell whose own DNA has been removed has not yet been attempted. It may not work because we know little about the non-DNA components of bacterial or archaeal cells.

Biologists have known for some time that a nucleus of a distant species (e.g., a frog) placed in a mouse egg whose nucleus has been removed will not divide or produce a living organism. But two closely related species (like algae of the genus Acetabularia) can develop after swapping nuclei. In such cases the growing organism with the donated nucleus resembles the features of the nuclear donor.

There is a LUCA for the first primate branch with the genus Homo. We are described as Homo sapiens. Anthropologists and paleontologists studying fossil human remains have worked out the twigs of the branch we identify as the genus Homo. Neanderthals and Denisovans (about 500,000 years ago) are the two most recent branches that preceded the origins of H. sapiens (about 160,000 years ago). Most humans have a small percentage of Neanderthal or Denisovan genes. Fossils of Homo erectus (about 1.8 million years ago) or Homo habilis (about 2.8 million years ago) are much older than the recent three species of Homo. Those fossils do not have DNA that can be extracted from teeth.

A second objective of studying LUCA’s 355 genes will be the identification of each gene’s function. That will tell biologists what it is that makes these genes essential in all cellular organisms.

I can think of a third important consequence of studying LUCA. There are millions of different viruses on Earth, especially in the oceans. If cellularity arose from clusters of viruses, the genes of the mother of all LUCAs may be scattered among some of those viruses and give biologists insights into the step-by-step formation of that first LUCA cell.

In Gilbert and Sullivan’s operetta, “The Mikado,” one character boasts of tracing his ancestors to a primordial bit of protoplasm. The genome of LUCA might become an unexpected example where science imitates art.

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