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Elof Axel Carlson

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.

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Above, a Greenland shark with the parasite copepod Ommatokoita elongata on its eye. The parasite destroys the corneal tissue, rendering the shark partially blind. Stock photo

By Elof Axel Carlson

I was reading an article on the Greenland shark, Somniosus microcephalus, and I thought of my only other encounter with a shark (other than a slab on my dinner plate). That was when I was getting my bachelor’s at NYU and taking comparative anatomy.

One organism we dissected was the dogfish shark, Squalus acanthias. The sharks have no bones. They have a skeleton made of cartilage. The difficult challenge for my classmates and me was dissecting the inner ear within the cartilaginous capsule encasing it. I learned to respect surgeons, especially those working on the ears (like correcting otosclerosis of its calcareous deposits without breaking the coated set of bones that normally help us hear).

I learned that most sharks give birth to live young (puppies) rather than depositing eggs. Sex for sharks is a bit of a contortion act since the male (usually smaller than the female) uses one of its modified tail fins in lieu of a penis to inseminate a female. I also learned that they are quite ancient in the evolutionary scale, dominating the seas in the mid-Devonian era (about 390 million years ago) before the bony fishes out did them in adaptability.

That brings us back to S. microcephalus, which translates from its Latin name to an insulting “sluggish shark with a tiny head.” As its common name implies, these fish are located mostly in the Arctic circle and are spared an endangered species status as they are toxic to humans (and other predators) because they accumulate trimethylamine oxide in their tissues.

Inuits and others who live in that frosty region have learned to treat and ferment the fish so it is not as toxic; but even as a delicacy for the adventurous, it is not a popular item for those who catch fish for a living.

The sharks grow very slowly (less than half an inch a year) and swim at a leisurely pace of about one foot per hour. In addition to accumulating the toxic trimethylamine oxide, they also accumulate large amounts of urea in their tissues, which also contributes to their unsavory reputation among gourmets.

To make matters worse, the Greenland sharks are pretty ugly because they have luminescent parasites (copepod Ommatokoita elongata) that attach to their eyelids and use this to attract prey to their mouths. Although an opportunistic predator with much of their diet being decayed meat from drowned tetrapods and dead fish — they can swallow the floating carcass of a caribou — the sharks have been known to ambush and eat sleeping seals.

So why would such a revolting creature be attractive to research biologists? The answer is surprising. Greenland sharks are the longest lived vertebrates, living to be about 392 (272-512) years from radioactive carbon dating of crystals that are deposited in lenses of their eyes, which are layered like onions. They become sexually mature at about age 150 and attain a full mature adult size of 18 to 21 feet in length.

There is an irony to some of life’s winners of desired traits. Want to live as long as a Greenland shark? OK, make yourself toxic and marinate in urea. Try visiting your relatives at a speedy swimming rate of one foot per hour. Want to be cancer free no matter how old you get? OK, be like a naked mole rat (if you like subterranean life and ant hill type living).

We admire diversity among the millions of species of living things; but in addition to the instructive lessons of life (“Go to the ant thou sluggard”), we can find irony and humor in the knowledge we gain.

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

What do the Empire State Building, the Metropolitan Museum of Art, the Flat Iron Building and the Yankee Stadium all have in common? They are all made of Indiana limestone whose quarries are chiefly in Monroe County where Bloomington, Indiana, and Indiana University are located.

The limestone industry got its start when the Welsh founder of New Harmony, Indiana, a British millionaire by the name of Robert Owen, tried establishing a utopian community (it lasted less than five years). He returned to Great Britain but his two sons liked American culture. One became the president of Purdue University and the other became a geologist at Indiana University and promoted the virtues of the limestone he studied in the Bloomington area.

By the 1830s with the advent of railroads, limestone crushed into pebbles was widely used for railroad track construction. In the 1880s the era of skyscrapers in large cities began and Indiana limestone was favored because it was easily shaped and cut.

Limestone is calcium carbonate that was formed 330 million years ago when most of the Midwest was an inland sea. Most of life on Earth was in the sea. Ameba-like protozoa sometimes formed calcium carbonate shells. So did crinoids or sea lilies, which are related to echinoderms like starfishes. The limestone for buildings came from a region of the inland sea that had mostly protozoa raining down their external skeletons when they died, forming a fine silt dozens of feet thick.

When I was a graduate student getting my doctorate in genetics, I would sometimes go on field trips to visit the caves and limestone quarry holes. One of the delights was scooping water from a quarry hole and bringing it back to Indiana University to look at a very rare organism — Craspedacusta — a freshwater jellyfish. Most jellyfish are found in saltwater oceans. Craspedacusta are small, about a half inch in diameter, and they pulsate as they swim in water. During the summer when we have visits from family and friends, we like to take our guests to Lake Monroe and collect fossils, mostly crinoids, in the fractured limestone gravel along the lake’s beachfront.

The limestone industry has supplied courthouses throughout the United States, government buildings like the Pentagon, thousands of limestone war memorials, cemetery headstones and hundreds of skyscrapers around the world.

The quarry holes are not used as landfills for trash. They dot the south central hilly terrain of southern Indiana. Sometimes the homeless or runaways live in the caves that have been dug into the sides of the quarry hole. The land around them slowly turns green with new grasses and trees. Those who work in the stone trade are like a medieval guild, with stone cutters whose families have done this for three or more generations.

In the 1979 movie, “Breaking Away,” which portrayed the Little 500 IU Bicycle Race, the children of the stone workers called their team “the cutters” and many townspeople still wear T-shirts with the word “Cutters” as a mark of pride. We are often connected without knowing it. In my childhood and youth, I was unaware as a Yankee fan that the house that Ruth built was made of limestone that would make my future retirement home (whose façade is made of limestone). I did not know the magnificent paintings I looked at and studied at the Metropolitan Museum of Art were housed in limestone. I did not know that the Flat Iron Building and the Empire State Building that I saw hundreds of times in my youth were made from the same limestone quarries that would house the laboratory in Indiana University where I studied genetics.

Sometimes life imitates art where a skilled writer hopes that in a novel the reader will end up seeing everything connected to everything.

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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One of the marvels of being a conscious organism is our capacity to interpret the things we do.

By Elof Axel Carlson

Elof Axel Carlson

Nedra had her right knee replaced on Sept. 13, 2017, and our daughter Christina and I waited in Indiana University’s General Hospital in Bloomington. She was groggy after some of the anesthesia wore off, and I was surprised that during the same day she was shown how to get out of bed and use a walker to get to the bathroom.

The next day she learned from an occupational therapist how to dress and undress. Also that second day she learned about 10 different exercises in bed to move her right leg. This included sliding her foot along the bed back and forth with her knee elevated and doing a half snow angel movement with her right leg.

I vaguely knew that the mechanics of body motion were first worked out by Giovanni Borelli (1608-1679). Borelli was taught by one of Galileo’s students and was skilled in mathematics, physics and medicine. He also used a microscope for his studies and discovered the stomata of plant leaves and the corpuscles in blood. He did experiments and claimed all body motion is caused by muscle contractions and he worked out the mathematics of animal motion, identifying where the limbs were in relation to the body’s center of gravity.

One of the marvels of being a conscious organism is our capacity to interpret the things we do. Many of those things — like walking, running, holding things or grooming our bodies — we do without a knowledge of the science that is involved in making them possible. We also assign other functions to body motions besides their pragmatic uses. Nedra and I both take Tai Chi for Arthritis at our local YMCA and the slow graceful motions provide exercise of all our joints. The “chi,” or vital energy, I equate in my mind with the same sensation as phantom limbs for amputees, which is neurologically based and not a psychiatric lament for the slow withdrawal of that feeling.

Body motion is paramount for those who dance, relating motion to music and the bonding and unbonding of partners as they go through a dance routine. Judo and tae kwan do are martial arts and can be used for aggressive or defensive activities among combatants. Yoga provides a spiritual aspect to body motion accompanied by meditation for those who practice it. Virtually all of us enjoy spectator sports whether watching baseball, football, basketball, tennis or the myriad of activities in winter or summer Olympic Games.

Anatomists today are well acquainted with the way muscles and bones and their tendons interact for any motion of our limbs, neck, head, hands, feet or other parts of our body. The one activity I did not include in this list is one that I find particularly appealing. The name given to it was by Thoreau who tells us in his Walden diaries that he enjoyed sauntering. It is walking with no direction or goal in mind, just wandering about in the woods or along a stream to take in the delights of nature and to stimulate thoughts for his writing.

When I was in high school and as an undergraduate, I loved solitary walks through Central Park in Manhattan, and my favorite discovery was a spot where I could sit and there were no buildings from Central Park West or Fifth Avenue visible to my eye. I thought of myself as an urban nature boy.

Nedra spent three days in the hospital and she then moved to a rehabilitation facility in a retirement community called Bell Trace. It is nice to see Nedra doing her exercises, converting pain into progress, and we look forward to her returning to our home which will be safety checked before she arrives to prevent slips and falls. For those coming days and weeks our daughter Erica, followed by two of our granddaughters and their husbands, will be out to enjoy Nedra’s progress to experience the confident walking by those with successful knee surgery enjoy.

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.