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Elof Axel Carlson

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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.

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'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.

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Egypt has long been considered a land of mystery and magic. Above, the Magical Circle of Anubis is discussed in ‘The Golden Bough.’

By Elof Axel Carlson

In 1890 Sir James George Frazer (1854-1941) wrote “The Golden Bough.” Frazer was Scottish, educated in Glasgow and then in Cambridge studying classical literature (Greek and Roman). He studied mythology, comparative religion and anthropology. His book argues that magic gave rise to religion and religion to science.

Magic assumes there are supernatural powers that some people can invoke or possess as innate gifts. With magic, what seems impossible can be made possible, at least to the observers of magical acts. Most professional magicians deny that they possess such gifts, and Houdini spent considerable time duplicating the tricks and illusions other magicians (and charlatans) used to deceive the public.

Frazer surmises the earliest humans believed in magical acts and associated them into rituals and myths with a belief in gods, often family ancestors, mythic heroes who were founders of a tribe, clan or larger population and sky gods. He believed the idea of resurrection came from the seasonal observation that plants die, scatter seeds and in the spring a resurrection occurs. He calls this “the dying corn god.”

Religion largely replaced magic as the basis for interpreting how the world arose, how society should function and how we relate to our gods. Religion in turn led to science with mathematics replacing numerology, astronomy coming out from astrology and chemistry from alchemy. The pursuit of knowledge from pseudoscience led to a weeding out of the failed experiments and predictions and a respect for more empirical and reason-based studies of the material, living and psychological universe in which we live.

Contemporary historians and philosophers differ with Frazer and among themselves on the origins of science. Some use a Marxist interpretation that farmers and workers laid the groundwork for science by their practical approaches to cultivate nature. Some argue that science is actually a cultural consensus or construction that shifts to new consensus and constructions in response to political and cultural changes.

Most scientists reject these social views of science and favor a material universe that can be explored, interpreted and manipulated with tools, experimentation, reason and data replacing myth, ideology or the supernatural. At issue in these debates are the ways scientists see the universe and their efforts to understand it. Science sometimes overthrows prevailing beliefs seen as truths. More often, it modifies its findings and its implications, incorporating the old as a portion of the new.

Newton’s laws of motion and gravity were not negated by Einstein’s theories of relativity or space-time. They became a more limited application useful for studying Earth and its solar system. Science is limited in what it can predict. We do not know if there are few, many or an unending number of scientific laws that may emerge in the centuries and millennia to come.

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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Most snakes ... have no sign of limb development when X-rayed or when their skeletons are studied by anatomists.

By Elof Axel Carlson

Elof Carlson
Elof Carlson

The re-discovery of Mendelism in 1900 greatly enhanced breeding for new varieties of animals and plants. Similarly, the discovery of sex chromosomes and the chromosome theory of heredity enhanced Mendelism five years later. The discovery in the 1970s of genes controlling embryonic organs and body plans enhanced both embryology and genetics.

Also in the late 20th century a molecular approach was worked out that allows detection of genes and their functions using DNA sequencing and tools for isolating and inserting genes from one species into another. A good example of this is the analysis of limb development in vertebrates.

We are vertebrates because we have a spinal column and so do fish, frogs and tetrapods (four-limbed organisms like mice, humans, deer and lizards).

But some vertebrates lack limbs. Snakes are the best example of this. Boas and pythons do have internal vestigial hind limbs but totally lack any rudiments of limbs for their forelimbs. Most snakes, like vipers, have no sign of limb development when X-rayed or when their skeletons are studied by anatomists.

How did the snakes lose their limbs? The earliest ancestors of snakes did have hind limbs. Those ancestral types are only known from the fossil record. In the 1970s Hox genes, which determine development from the head to the tail, were found in vertebrates. The Hox gene for limb development is Hox C-6. It is regulated by another gene called sonic hedgehog or Shh. In vipers the Shh gene regulating Hox C-6 is mutated for both fore and hind limb production. In pythons it is nonfunctional for forelimbs but mutated with an aborted development preventing full growth of the hind limb buds.

Just this year, molecular biologists used the new techniques of gene removal and transfer (using a tool called CRSPR) and removed the Shh gene from a mouse fertilized egg. It resulted in a limbless baby mouse. When they put a python’s Shh gene in a mouse embryo whose Shh gene was removed, the resulting baby mouse had vestigial nubbins. When a mouse fertilized egg had its own Shh gene removed and replaced by that of a fish or human Shh gene, the baby mouse had perfectly normal limb development.

This work by Axel Visel and colleagues at Lawrence Biology Laboratories in Berkeley was published in the journal Cell. What makes science so attractive to scholars is its convincing logic, tested by experiments, to explore, confirm or rule out different interpretations of a puzzle. The puzzle of nature in this case is why snakes lost their limbs.

Those who see it in human terms (because we often use the ancient Greek dictum “Man is the measure of all things”) may invoke that the snake was punished for its role in corrupting humans. The scientist, however, likes to see things in more detail. There is comparative anatomy, the fossil record, experimental embryology, gene identification for function, sequencing for recognizing the gene, molecular tools for isolating the gene and experimental means of altering fertilized eggs to follow their fate.

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

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Dolly the sheep. File photo

By Elof Axel Carlson

Dolly was a Dorset Finn breed of sheep born in 1996 in Scotland. She was conceived from a nucleus taken from a breast cell of an adult healthy sheep that was transferred into the cytoplasm of an egg of a different breed whose nucleus had been removed.

Dolly was the first successful live-born lamb out of about 250 tries. She was named for Dolly Parton. Ian Wilmut and Keith Campbell were the scientists who constructed her. Dolly began developing arthritis at age 5 and died a year later showing signs of old age. Normal life expectancy for a Dorset sheep is 12 years. It was thought that the cloning nucleus from the donor Dorset sheep passed on its age to Dolly at birth and that this led to her premature aging. That turned out to be false.

Kevin Sinclair, a developmental biologist in England, obtained four live clones from the breast tissue that was used to make Dolly. The successful live-born sheep were named Debbie, Diana, Daisy and Denise. They are now (2016) 9 years old and in perfect health.

Cloning is still inefficient and more failures (mostly during early embryonic stages) occur than successes. Success with dogs in Japan has led some pet owners to pay for a cloned twin of a favored aging pet. In Dolly’s case an electric shock was used after the transfer of the nucleus to stimulate the cell to divide. For some embryologists a series of transfers to fresh enucleated eggs is required to achieve success.

Why most fail is not known, but the field of epigenetics may supply some of the answers. Genes are coated chemically by the organism in body tissues. Normally, in males and females these coatings, which regulate whether genes are on or off, are removed in the testes or ovaries where reproductive cells are made. I do not doubt that in a decade or so scientists will learn to do that in a test tube or Petri dish. Will that technology be used commercially? Very likely. Prize race horses and beef or milk cattle could be cloned if the success rate was about 70 percent. It will probably not be better than that because natural fertilization fails in about one third of fertilized eggs, a substantial part of that being extra or missing chromosomes when sperm or egg nuclei are produced.

Living things are very complex and the chance of getting almost 100 percent “perfect” cells is virtually impossible to achieve. That is why many couples attempting to have children often take months or years before they become pregnant or seek help from an in vitro fertilization clinic.

The success of Dolly’s cloned sibling sheep worries some medical ethicists that, if applied to humans, this could be abused by narcissistic personalities who want to clone themselves. So far that hasn’t happened and many countries (and states in the U.S.) have banned cloning using human tissues. For those who enjoy watching (and betting on) horses, it raises an interesting idea. If races were eventually done with cloned champions, it would favor the training over the breeding as the basis for who wins. Imagine a field of a dozen cloned Seabiscuits and trying to figure out whose training was the best.

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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