Life lines 6

WRITING THE HISTORY OF BIOTECHNOLOGY

I attended a three-day conference on the history of biotechnology held at the Cold Spring Harbor Laboratory. I serve as a member of the advisory board for the CSHL Library archives and looked forward to the presentations. As preparation for the meetings, I reviewed a book that just came out by a fellow geneticist and historian of science, Krishna Dronamraju [Emerging Consequences of Biotechnology]. Dronamraju’s account was a history of controversy over genetically modified foods, diminishing biodiversity as much of the natural world’s forests are chopped down around the world and not replaced, diminished numbers of cultivars (varieties) of domesticated food crops, biopiracy (the theft of natural products and their medicinal uses in underdeveloped countries and their exploitation for profit by large corporations in the US and Europe), and battles over patenting and intellectual property rights. Very little of that was raised at the CSHL Conference. There were lots of papers on the founding of biotechnology companies and why most failed and some succeeded. I learned that it takes 17 years for a scientific idea to become a marketed product. I learned that during the start up years many of the scientists were unpaid, and depended on their university salaries to feed their families. Their rewards during those lean years of development being the gourmet lunches and dinners they had as the companies wooed venture capitalists and brought along their top scientists to discuss how the product works. I learned that many of the scientists and the wealthy individuals who provided the millions of dollars to build the factory, buy the equipment, and pay the salaries of the employees were idealists who believed they were “saving the world” by providing new products, most of them made by engineered or inserted genes, to act as vaccines, to help sick people lacking the hormones their bodies need, to treat cancers, to prolong life, to modify plants so they won’t be eaten by insects or reduced to spores by harmful molds. It is a high-risk industry. Only one idea in a hundred reaches the market. Most don’t work when tested on humans or tested in greenhouses or tested in fields or brought to other countries and don’t work in those exotic environments.

Both of these presentations are largely true. One doesn’t nullify the other. But trying to get the Greenpeace activists, environmentalists, and poor farmers in developing nations to applaud the sacrifices of those founders of biotechnology companies is as difficult as getting venture capitalists, CEOs, and board member scientists to appreciate the outrage a Brazilian collector of herbal medicines feels when his product is brought to an American corporation, its product extracted and patented, its local name used and copyrighted and the local collector finds himself sued for not paying royalties for selling his local product under its original name. The poor and undereducated are unaware of the ways of the well educated and well paid industrialized owners and workers. The well to do scientists in industrialized nations are largely ignorant of the ways poor people make a living, who see in their soil a culture and heritage that goes back for millennia. Each feels the other side is greedy or misguided or ideologically rigid. As globalization increases, as Peace Corps type volunteerism increases around the world, as our news media reflect both sides of these controversies without reducing them to political conflicts, and as these new technologies are done by local scientists in developing nations, perhaps using biotechnology will be as common and local as using electricity.

Life lines 5

THE HOUSE WE LIVE IN TELLS STORIES

When I was a teenager I read a small novel by Rumer Godden called Take Three Tenses. It was a story told by a house of the families that had lived in it for about four generations. It told the stories of loving, fighting, laughter, illness, death, and weddings, of children scampering up and down stairs and each room had a secret to tell. I thought of that as our house on 19 Mud Road went up for sale, and if we sell, we shall be moving to Bloomington, Indiana, to a smaller one level home, easier to manage for two old folks who are creaky with arthritis. Frank Erk, who helped me look for houses after I joined the faculty at Stony Brook in 1968, first took me to this house. This was about the tenth house I had seen and as soon as I saw the large L-shaped living-dining room with its huge cathedral ceiling, I fell in love with it. After we moved in and guests began to arrive it was called the Ross house. Dean Stanley Ross had lived there with his family before moving on to the University of Texas. About a year after we arrived friends from California visited. They collected bitters bottles and I told them that when we moved from Sunnyside Avenue in Mar Vista California to Mud Road, we learned that the street was named for the path to the town dump, the site of Gelinas Junior High School. Their eyes lit up and soon with our shovel in hand we marched to the border of the field and the woods east of the junior high building and they dug for not more than fifteen minutes before hitting a trove of purple, brown, and amber bottles of various sizes that held what in the old days was patent medicine or what is today called snake oil. It took five years before our house was no longer called the Ross House. New faculties have no historical knowledge of their predecessors.

We added on as the years went by and our family grew. We added a library downstairs. We added a deck in the back. We enlarged the kitchen. When our daughter Erica lost her job and brought her large family and my mother in law came to live with us, we added on behind our house. One innovation was a sewing room for making quilts, as both Nedra and her mother and our daughter liked to sew. Shortly after the construction on the large addition began our daughter got a job as a toy designer in Florida and our home was now too big for only three occupants. But we were still working so we each made an office out of a bedroom. Nedra added up the statistics as her village of 3000 IVF babies grew in numbers and I designated my upstairs office as my computer room and happily composed my lectures, articles, and book drafts. As I got older I thought of Rumer Godden and her novel. Setauket goes back to the 1650s and the first settlers here were evicted by a forged document bearing King Charles’ seal by a swindler who fomented the war against New Amsterdam. He sold the land to British investors using other forged documents. Setauket housed an enclave of supporters of George Washington in a Tory territory. Often when I used to walk from my home to the Emma Clark Library, I would commune with those patriot feet that trod this path two centuries ago.

The day may come when we leave our beloved home on Mud Road and begin the final leg of our journey through life. I will imagine in my Bloomington moments of meditation that a new occupant with a young family resides on Mud Road and guests of that family who are getting to know them will prepare to visit the Carlson house, a name that will bemuse the new occupants for some five years, before the past is embraced in the silent walls of the house we live in.

Life lines 4

SOME INSIGHTS INTO THE ORIGIN OF MULTICELLULAR ANIMALS

Most animals that you have encountered are worms, insects, snails, clams, fish, lizards, snakes, amphibians, birds, or your fellow mammals. Some of you may have gone scuba diving and increased your repertoire of animals including corals, jellyfish, tunicates, and sponges. The least complicated in body plan of all these animals belongs to the sponges. They have only a few cell types. One of these, known as collar cells, have a filament (called a flagellum) that whips around inside a fringe-like collar attached to the cell. The flagellum sweeps up bacteria and smaller protozoa and digests them inside the cell. Very similar to these specialized cells of the sponges are protozoan single cells called choanoflagellates (a very fancy name for collared cells). When I was a graduate student at Indiana University taking a course in invertebrate zoology, I imagined that these choanoflagellates might have been ancestors of sponges in a distant evolutionary past.

In 2008 a team of California scientists coordinated by Nicole King and Daniel Rokhsar published a DNA analysis of a species of choanoflagellates, Monosiga brevicollis. It has about 9200 genes, which is about one half what most multicellular animals have (we have 23,000 genes in a sperm or egg). Monosiga has split genes, like humans, but its genes have slightly fewer “junk DNA” insertions (an average of 6.6 per gene compared to 7.7 in our genes). What were more interesting were the functions of some of Monosiga’s genes. They had several associated with cell adhesion (what makes cells stick to one another as they do in our muscles or skin), cell recognition, and immunological defense. Before King and Rokhsar’s work, these genes were thought to be unique to multicellular animals and missing in single celled protozoa.

The authors compared Monosiga’s genes with genomes of other plants, animals, and fungi. They found that of 24 genes associated with multicelled animals, only 3 were shared in fungi and plants, but Monosiga shared 16 of them. This is a striking association that suggests many of the components for animal evolution were present in protozoa like Monosiga. Very likely around 600 million years ago, an era called the Precambrian, the first gathering of cells by adhesion took place and by the Cambrian era the proliferation of animal types appeared in the fossil record. Future studies of the 125 known species of choanoflagellates and related protozoa and simple animal forms may reveal the way these different body plans came into being.

The difference between my vague suspicions some fifty years ago and the molecular and biochemical analysis possible today is stunning. Evolution studies are now providing models of how cellular processes, embryonic processes, and genetic processes participate in bringing about an evolution that predates the fossilized skeletal remains of more advanced forms of animals first appearing about 500 million years ago.

Life lines 3

HOW TERATOGENS CAUSE BIRTH DEFECTS

The life cycle of literature runs from birth through infancy, childhood, adulthood, middle age, and old age culminating in death. It is the subject of art, literature, and philosophic reflection. But the late and early twentieth century added some additional components to our life cycle. There is the peri-fertilization period when sperm or eggs form, unite, and a pre-implantation embryo forms. It leaves the oviduct and implants in the uterus. Those events from fertilization to implantation take about five days. The next fifty days are associated with something called organogenesis. The body symmetry is laid out; head vs. tail, dorsal (back) vs. ventral (belly), left vs. right side, and the various systems are established producing organs. After the 55^th day we become a fetus and enlarge and perfect those organ systems.

Here’s the problem. A woman does not look pregnant during those first 55 days. She may not even be aware she is pregnant for three or four weeks after fertilization. It is the most vulnerable stage of her pregnancy because there are agents that can interfere with organ formation. Such agents are called teratogens. The most well known teratogen was thalidomide, an over the counter tranquillizer made in Germany and sold to millions of people in Europe in the late 1950s and early 1960s. It led to the formation of 8,000 babies with missing or deformed arms or legs and other birth defects and an unknown number of aborted embryos that were incompatible with further life. The US was lucky, Dr. Frances Kelsey at our Food and Drug Administration felt it had not been tested sufficiently. She did not like reports of long-lasting constipation and peripheral neuritis (numbness or tingling sensations of the arms and legs) reported in Germany. Despite howls of protest about overregulation and government red tape harming industry from the American company hoping to market it, she stuck to her role as a protector of public health.

There are other agents that damage organ formation. Alcohol leads to a fetal alcoholism syndrome. Exposure of the pregnant woman in early pregnancy with German measles can lead to damaged hearts and brains. Parasites in feces of household pets (toxoplasma) can cause such damage. X-rays (especially exposure to occupational or repeated doses) can be damaging to an embryo. What does this tell us? It tells us that women need to protect themselves in early pregnancy when they are most at risk. They should have their husbands clean up the cat or dog excretions. They should avoid over the counter self-medication or prescription drugs unless they have asked an important question to their physicians: “Has this product been tested for teratogenicity?” Memorize it. Write it on a card and keep it in your purse. Most physicians, health providers, and pharmacists are conscientious and they will look up that possibility for you.

As in most concerns about our human biology, it is not easy to test everything new entering the market. Testing on pregnant mice and rabbits is one way to see if new products damage organ formation. We need that regulation to prevent future disasters.

Lifelines 2

AUSCHWITZ DEFIES OUR CAPACITY FOR REASON

I attended a meeting at the Collegium Medicum at the Jagellonian University in Krakow, Poland. It is a beautiful city with medieval and renaissance churches and buildings that were spared the damage of two world wars. It is also the city where the astronomer, Copernicus, lived and taught before moving to Frauenberg. The house of his student, Rheticus, still stands across the street from a very fine Museum of the History of Medicine which I visited.

I also visited Auschwitz, an hour’s bus ride to the west of Krakow that passes the Vistula River and beautiful monasteries, churches, and farms until it encounters the coal mines of Silesia a few miles from Oswecim, or Auschwitz, as the Germans called it during their occupation. There were actually three Auschwitz camps. The first consists of about thirty brick buildings that served as an army barracks during World War I. The second, called Birkenau, about a mile away, was built by slave labor. It is much larger and consisted of 300 barracks, most of them wooden, and most of them destroyed by fire as the Nazis left, or they were later stripped of their lumber by local residents to rebuild the surrounding country side after the war. The third Auschwitz is no longer in existence. It was the industrial factory system of German chemical manufacturers (I. G. Farben, especially) and it made synthetic rubber during the war. It was called Morowitz. It continues today as a Polish industrial complex.

The first camp, or Auschwitz I, opened in 1939 and until 1941 it housed mostly Polish intellectuals and others considered threats to the Nazis. They were executed by firing squads and that wall still stands. From 1942 on it began filling with deported Jews and Birkenau or Auschwitz II was built to meet the immense influx of them. Auschwitz I added the first gas chambers and crematoria to dispose of the dead when the stack of bodies exceeded the ground’s capacity for their burial. Birkenau was designed as a death camp with more efficient gas chambers and crematoria.

As I walked from barrack to barrack and saw the displays of shoes, toothbrushes, hair, artificial limbs, and eye glasses looted from the dead, I felt numbed by the capacity of educated middle class cultured people to kill their fellow human beings, stripping them of their humanity as easily as shaving off the hair from their naked bodies. Most painful to contemplate, were the small mountains of children’s clothes and toys. Only 700 children (out of more than a million) survived. Most of the survivors were twins, subjects of medical experiments of Dr. Josef Mengele.

I picked up a few fallen leaves from the trees at Auschwitz I. The trees were planted by the inmates on orders from the Nazi who wished to disguise what was going on in Auschwitz I. There were no trees in Birkenau. It was intended to be quickly dismantled after the war and converted back to farm. I thought it fitting to think of the dead as anonymous as the fallen leaves and as reminders of the capacity of life to find renewal.

Lifelines 1

ASTRONOMERS PROJECT THE PRESENT INTO A FUTURE MANY BILLIONS OF YEARS TO COME

While enjoying a variety of magazines in the Emma Clark Library in Setauket, I came across the June 2008 issue of Astronomy. What caught my eye was an article by Abraham Loeb and T. J. Cox. It concerns the future of our galaxy. We live near an outer arm of a pinwheel shaped galaxy called the Milky Way. On a clear night we see the cloudy concentration of stars in these arms overhead. Our galaxy has about 200 billion stars. There is a similar pinwheel galaxy we can see in the night sky as a fuzzy dot. It is called Andromeda. It is somewhat larger than the Milky Way. It would take two and half million years traveling at the speed of light to reach its outer arms. Unlike most of the billions of galaxies in the universe, Andromeda is moving toward us, not away from us. It is “blue-shifted” instead of “red-shifted” when its spectrograph is taken. It is hurtling toward us at a sped of 220,000 miles per hour. The Milky Way and Andromeda are the largest galaxies in a cluster of mostly much smaller galaxies collectively called the local group.

About 5 billion years from now the gravitational attraction of our two large galaxies will result in a collision. Nothing will explode, however, because the stars in each galaxy are one or more light years apart (a few trillions of miles apart at their closest). Instead, the two galaxies (and probably the smaller members of the local group) will merge into a single galaxy shaped like a blunted football. The gas and energy associated with that merger will lead to the birth of millions of new stars. The authors call this future galaxy “Milkomeda”.

Our own sun will then be about 10 billion years old, making it an old star, with most of its hydrogen having been used up making helium and heavier elements. Such old stars begin to expand and turn red. They are called red giants. Our earth, if it is engulfed or heated up will have its life sizzled away. But I expect that long before that merger takes place our descendants, whatever species they may be, if still intelligent to have scientists will have long colonized other planets in near-by stars and may have done so for millions of generations. But among those planets in newer stars there may be intelligent life emerging with 20th century capacities of understanding and knowledge of the universe. They would not know of the origin of Milkomeda from two pinwheel galaxies and they might consider this their original galaxy.

If that life out there continued for another ten or 20 billion years the expansion of the universe would cause all other galaxies to have receded so far away from us that none of these galaxies could have their light reach our Milkomeda galaxy. Astronomers in that futuristic world, who lack this history of the past, would then assume that Milkomeda is the entire universe.

Introducing Lifelines articles

I have moved from Setauket, New York to Bloomington Indiana or from one college town to another. I am an emeritus professor from Stony Brook University and I met my wife Nedra here in Bloomington in 1958. It is nice to be back. At 79 years of age, I continue to write and enjoy learning. Since we moved here a year ago in November 2009, I have written three books, one under contract, one being considered, and one (a novel) that I am still revising. I was fortunate that my newspaper column, Lifelines, that appears every second Thursday in The Village Times in Setauket NY is still appearing in the Times-Beacon-Record newspapers of publisher Leah Dunaieff [northshoreoflongisland.com]. When I began this column for her papers, we agreed that I would have use of the articles for my own publication. I thus will be placing all my past articles so that a wider audience can read them. I begin today with ten of them. I have written about 300. I will post about ten a week and then I may slow down after the first 100 are posted because I no longer have computer copies of them, just printouts. I may have to retype them and that will mean a less frequent posting. I hope you enjoy them. I certainly get a lot of pleasure writing them.