Friday, November 26, 2010

Life Lines 60

The 2007 Nobel Prize in Medicine was awarded to Mario Capecchi (University of Utah), Martin Evans (University of Cardiff), and Oliver Smithies (University of North Carolina) for their work in using molecular techniques to create genetically engineered mice. Specifically, some 25 years ago they found a way to isolate a specific gene, alter it so it would not function, attach it to a another gene as an identification tag, insert the altered tagged gene into an embryonic stem cell of a mouse, and replace the normal gene in that cell. The resulting mice grown from that embryonic cell were eventually inbred to produce the tagged knocked out gene in every cell of those new tagged mice. The technique is known among geneticists as targeted knock out genes. Through this technique the three scientists and their colleagues around the world have created over five thousand strains of genetically engineered mice.
Why is this significant? For basic science it enables scientists to study the function of each of the 15,000 genes in a mouse sperm or egg. For medical science it allows scientists to identify diseases or other changes in the knock out strains that are comparable to human diseases. So far about 500 human diseases that have some genetic connection are found in mice. This is no surprise because humans and mice, both being mammals, share about 90 percent of their genes in common. The mice genes include those associated with cancer, heart diseases, neurological disorders, diabetes, and hypertension among the more familiar disorders of humans as well as rare types of single gene defects like cystic fibrosis. It is easier to do research on mice to find the way disease causing mutations work and how to treat such diseased mice than it is to do so directly on humans. For one thing, you can mate mice to yield important genetic information but you can’t manipulate human reproduction to get the same information unless your values are that of a Nazi medical scientist in a concentration camp. We don’t sacrifice prisoners, psychotics, or enemies in such experiments because we have some higher good in mind. We treat adult subjects as human beings, not guineas pigs. Trying out new cancer destroying agents is now much easier because of the existence of targeted knock out mice. Testing for new prescription drugs is also easier because of their work. One interesting but not surprising finding is that about 15 percent of mouse genes cannot be isolated as genetically engineered strains because they are lethal to embryonic development and abort. Lethal genes in animals have long been known (since 1912; they were first found in fruit flies). Those will likely turn out to be genes that form organs vital to life or genes that are essential for individual cells to survive or divide. The award of the Nobel Prize will give added weight to those scientists and physicians hoping to apply the findings of mouse stem cell research to human stem cell research.

Life Lines 59


Aphids are sometimes called plant lice. They are sometimes seen in large numbers sucking sap out of stems of leafy plants. The aphids don’t reveal to anyone but a scientist that they are also being parasitized by a bacterium. The bacterium, called Buchnera, has one of the smallest genomes of any cellular organism, a mere 460 genes. It lives in the cells of the aphid. The aphid, curiously, has one of the largest genomes of any cellular organism, over 35, 000 genes, almost twice that of a human. Only a few of its genes have been given to it by Buchnera. Most of its genes are due to numerous duplication of genes. Among the genes given by Buchnera to the aphid are genes for making amino acids. Eleven of these genes came from Buchnera to help make six amino acids. But for two of these amino acids the last step in making the amino acid is done by a gene of the aphid. This makes those two amino acids examples of a mutually beneficial system. Each helps the other for amino acids they both need and neither can survive without the presence of the other.

We often think of animals at war with each other and for predator and prey relations that is true. But many organisms form mutually beneficial relations. Most ecologists would argue that the world of life is interdependent, with all animals dependent ultimately on the foods made by plants through photosynthesis. There are more intimate relations than the groceries we select for our meals. Most trees have roots penetrated with bacteria or fungi that make nitrogen or other essential nutrients for the plant. In return the fungi or bacteria living in the roots have protection and nourishment.

I have often wondered why the public image [“nature red in tooth and claw”] of evolution is based on the predator-prey relation and not the mutualistic or beneficial interplay of organisms with one another. We need a Tennyson to interpret that more positive image of evolution for us. My own feeble effort of “nature rich in share and change” wouldn’t resonate to our emotions nor would it convey the powerful imagery of that bloody evolution as we imagine dinosaurs tearing hunks of flesh from their victims. There is far more mutual benefit going on in nature than an unceasing warfare between species. When we cut up land with roads and fences we quickly eliminate the migration of many species that will perish because they do not have territory to breed or forage. Our image is the hunter with the rifle but the reality for most deer, pheasants, and small mammals is the difficulty of finding food when human barriers isolate them. Organisms die from diseases and malnutrition more often than they do from carnivorous predators devouring them. Evolution is an outcome of both beneficial and horrifying ways to live. A grandmother making clothing is as beneficial as a young hunter bringing home game for all to eat. What is remarkable in the Buchnera-aphid story is the cooperation in amino acid synthesis that developed at a molecular level. It is a relatively recent event, not as ancient as our own cellular ancestry. All of our cells have mitochondria that were derived from bacteria in the early emergence of eukaryotic cells (cells with nuclei). Most of those bacterial genes entered the nuclei of our cells or were permanently lost as our mitochondria became transformed into oxygen breathing and energy producing organelles of our cells.

Life Lines 58


A century ago journalists and critics who exposed filthy slaughter houses [Upton Sinclair], corruption in municipal governments [Lincoln Steffens], and monopolies in restraint of trade [Teddy Roosevelt] were called muckrakers. The privileged and the powerful despised them and smeared them as unpatriotic. Because of them some terrible abuses were regulated by our Federal government. Nedra and I saw Michael Moore’s Sicko and it was both funny, as good satire can be when skillfully done, and sad because of the personal stories of patients dumped from one hospital to another by being shoved out of taxis to transport them, middle class people brought to bankruptcy because their medical insurance did not cover their needs, or insurance workers who quit because they couldn’t take denying insurance to clients who were sick. There were doctors frustrated by insurance companies that did not pay them and insurance companies that would not allow them to recommend tests or treatment they felt were essential for their patients.

In 2001 after the 9-11 attack we were on board ship in the Pacific Ocean where I was teaching on Semester at Sea. The State Department took over our voyage, fearful that some 600 college students from 100 colleges (most of them from wealthy or upper middle class families) might be at risk. All our Islamic ports were cancelled and we did not know until a day ahead where our next port would be. One of the safe ports we were allowed by the State Department (Bush administration, no less) to visit was Havana. Castro threw a banquet for the entire shipboard community and gave a four hour lecture on terrorism (hotel fires and bombings by anti-Castro terrorists from Florida, he claimed, which are rarely reported in the US press). I was interested in health care in Cuba and got to see their neighborhood health units (one on every block), their secondary health (one within walking distance for every neighborhood), and their tertiary care (where major surgery, referred rare conditions, and trauma were handled). While it was clear to me that Cuba was a controlled state I would not choose to live in, the health care delivery was available to everyone. One reason Cuba has the lowest infant mortality and one of highest longevity rates in our hemisphere is that everyone has to visit a physician once a year. If not, the local doctor knocks on your door and does a house call.

In Moore’s Sicko we learn what local citizens and ex-patriate Americans think of free health care in Canada, France, and the United Kingdom. They love it and so do their physicians because they can treat people without worrying about HMO approvals, the red-tape of insurance companies, and the horror of seeing their patients forced from their care by hospital policy set by profit-making corporations. Moore argues for a government that values “We, the People,” rather than “Me, the lucky.” We don’t argue that police should be paid out of private funds and those who can’t afford it should not be protected. We tolerate a shameful health system that has been bloated in costs to the benefit of a few and the detriment of an unacceptable portion of our fellow citizens. Note with sadness that virtually every candidate, Republican and Democratic, running for President, has been given generous donations by lobbyists from the few who represent the privileged who wish it to remain that way.

Life Lines 57


Seymour Benzer died in December 2007. He was 86 and did most of his work in genetics at Caltech. Benzer approached genetics with the outlook of a physicist. He greatly admired Max Delbrück, a physicist turned biologist who founded the field of bacteriophage genetics. Benzer’s first great contribution to that field, beginning in 1955, was his discovery of genetic fine structure. He used viral mutants that caused the plaques or holes in the bacterial lawn of food to change size or texture. By using mixtures of these mutants (some arising spontaneously and others induced chemically) he mapped the position of each mutant lesion to produce a map of the gene he was using.

At the same time his work was appearing, I was just starting a similar approach on fruit flies in Muller’s laboratory at Indiana University (Benzer at that time was at Purdue University). His work had an electrifying effect on me and other geneticists because it brought together classical genetics and molecular biology. It was like being there when the west coast and east coast railroad lines were joined at Promontory, Utah in 1869 to form the first transcontinental railroad. Benzer used operational philosophy, developed by physicist Percy Bridgman, to define his gene as a unit of mutation (muton), recombination (recon), and function (cistron). The fine structure of his muton map corresponded to the number of nucleotides in the inferred gene’s DNA. Each of his cistrons had one hundred or more sites that could be mapped. His mutons were mostly single nucleotide pairs in a DNA molecule. Today those terms have largely disappeared as the focus of interest shifted from the structure of genes to the functions of them. Benzer had gone as far it was possible to go without using DNA itself to analyze gene structure and function.

Benzer shifted his work to the nervous system using fruit flies. He induced mutations for behavioral traits, starting with the ability of flies to move to light (think of moths swarming towards light on a summer night). He analyzed these and sorted out those with defects associated with flying, with recognition of light, and with defects in the eyelets of their compound eyes. The fly’s brain, essentially a ganglionic mass of cells, was sophisticated and Benzer could distinguish many behaviors, including courtship rituals (which are innate in flies) and gender recognition (he even isolated genes for same sex preference in fruit flies). Benzer mapped these genes and studied their anatomical and physiological activities.

I do not know why Benzer did not win a Nobel Prize for his work. His ideas and findings had enormous influence on other biologists throughout the last half of the twentieth century. He was witty, passionately committed to experimental science, and a brilliant lecturer. His only rivals for creativity and generating new ways to think about life were Linus Pauling and Francis Crick.

Life Lines 56


Most of my male readers are 46,XY in their chromosome description. Similarly, most of my female readers are 46,XX in their chromosome description. That means we “define” humans as having 46 chromosomes; two of them are sex chromosomes called X and Y. By “most” I mean 99% of humanity. About 1% of humanity can be 45,X (Turner syndrome females), 47,XXY (Klinefelter syndrome males), sex reversed XY females, sex reversed XX males, mosaic or chimeric individuals with both XX cells and XY cells, or what should have been normal 46, XX females whose embryos were masculinized (think penis and scrotum) because their genetically mutated adrenal glands flooded their developing bodies with male hormones. Are you with me? These babies did nothing wrong. Their parents did nothing wrong. Their problem arose because nature is not perfect.

Having reversed or ambiguous sexual status is rarely life threatening. Sexuality may be essential for our species but it is not a vital function like having kidneys, lungs, or a heart. So here’s the problem: Society doesn’t know how to deal with nature’s mistakes. We shift in values. A good example is those babies who have 47, +21 (trisomy 21 or Down syndrome). Before the 1970s they were called Mongoloid idiots, a name both racist and insulting or insensitive. They were usually institutionalized from the 1920s to 1970s but now they are usually raised at home. While we accept birth defects more in today’s generation than 50 or more years ago, we are still unsure what to do with babies having mixed sexual status (a penis and a vagina; ovaries and testes; a female athlete who tests positive for a Y chromosome but whose genetic disorder makes her unresponsive to male hormone). The list is large. Some parents select surgery to “normalize” the child. It is not possible in some cases and it may be worse, psychologically, for that individual than leaving the child to grow up and choose a sex he or she feels more comfortable adopting.

Should intersex babies be allowed to marry? Does a 46,XY woman have a legal right to marry a 46,XY male? Does the same 46,XY female individual risk being regarded as participating in same sex marriage if she chooses a 46,XX female as her partner because males should legally be defined as 46,XY? We like a simple answer in our cultural standards and laws but nature gives us its variations from accidents of gene mutation and cell division and the occasional union of mutant genes that have been passed unnoticed for several generations. Biologists know this but society still insists that every baby must be a 46, XX female or a 46, XY male. Why do we accept the humanity of a 47,+21 Down syndrome baby, recognizing its special needs, but force intersex babies into an “either male or female” classification that nature has denied to them? In Greek mythology, Procrustes lopped off the feet of those who couldn’t fit into the beds of his inn. Is this what we should do with genitalia for those who don’t fit the culturally desired uniformity that everyone should be an unambiguous male or an unambiguous female?

Life Lines 55


Almost all mammals can see yellow and blue which is associated with a gene that is not on a sex chromosome. In humans a mutation of the yellow-blue gene results in vision that sees only black and white, like movies or TV sets in an earlier generation. Mammals also see green. The genes involved produce proteins called opsins, which are sensitive to color. In African primates a duplication of the green opsin gene occurred and eventually mutated to become sensitive to longer wavelengths we associate with red. We humans thus have three opsin genes – for the yellow-blue, the green, and the red. Persons who are color deficient are usually defective for the green or red opsin gene an event that happens relatively frequently because the red and green genes are tandem duplications and frequently mispair leading to a product that may be defective for the red or green opsin gene. An eye doctor can readily tell, by using color charts, whether a colorblind person has a mild or severe loss of the green or red gene.

Mice, like most mammals, have the green and the yellow-blue genes. They do not see red. Scientists at Johns Hopkins University and at Santa Barbara inserted a gene for the red opsin gene into a fertilized egg of a mouse and bred the resulting mouse and its offspring to produce a strain of mice with the red opsin gene present. They then tested the mice using red or green plastic levers to release food when pressed, a standard animal psychology approach. The modified mice could recognize the red lever and distinguish it from green, but control mice could not, with both the red and the green levers appearing identical. This demonstrated that the mammalian brain is capable of learning new experiences never encountered before. They could interpret new wavelengths (which we see as red) and respond in a similar way to people who are not colorblind. The capacity to see red (or presumably any color) is a matter of the wavelength sensitivity of the opsin genes present.

Theoretically humans could do the same thing to themselves, and it might be possible to add the red or green opsin gene to a human zygote after fertilization and instead of a color-blind boy (the trait is X-linked in humans) the child might have normal color vision. It is also possible that opsin-like genes present in butterflies and bees, which recognize ultraviolet as a color, might be added and we could extend our color range. Similarly, the red-opsin gene could be altered and added to allow some people to see infrared and greatly increase their night vision. Genetic manipulation is not yet a precise science and lots of risks may abound from inserting genes in inappropriate places. For those who fantasize those problems will be solved and who want the benefits of such genetic manipulation, consider the possible disruption in sleeping patterns and the inability to get rid of distractions like the warm bodies glowing in a dark room (a theatre or movie house) or the persistent images of warm objects (like radiators or hot water pipes in the walls) while you try to sleep. Extending our color range by adding opsin genes may lead to a Midas touch of surfeit color.

Life Lines 54


During war or the threat of war, there is an alliance between science and government. We think of the Manhattan Project giving us atomic weapons, the RadLab giving us radar, and the space program giving us spy satellites and the rockets to strike targets anywhere in the world. Without scientific cooperation there would be no weapons of mass destruction. Whether these are acts of patriotism, an unholy alliance, or a morally corrupted use of science is largely a reflection of our political priorities, ethics, and religious values. But during times of peace science is not a welcome guest when it raises questions about global warming, funding stem cell research, industrial polluters, safety standards for foods and other commodities, or the health consequences of a vast uninsured or underinsured underclass not favored by birth or luck to be raised in middle or upper class circumstances. Instead of wooing scientists (as they do if they need help in making weapons), governments tell scientists to “stick to their last” like shoemakers and not poke their noses into government where it doesn’t belong.

Let us assume science acts like an obedient dog and slinks off to another room, what are the consequences of mutual exclusion in peacetime? If the issue of climate change is real but not pushed into government concern, how prepared would we be for the long term damage of rising sea levels, more frequent storms, habitat destruction, droughts, and other disasters down the road? If jet travel around the world carries new germs from Asia, Africa, or the Americas and moves them in days or weeks around the world, how prepared would we be to respond when pandemics arise? If increased population and consumerism lead to greater and riskier demands on air transportation, production of pot-holed roads, and collapsing bridges, how do we repair or prevent these hazards and how much talent and budget do we set aside for it? If we do not provide health care to meet serious health needs, how much do we pay for lost wages, absenteeism for health reasons, and the higher costs of neglected diseases (like hypertension and diabetes) that could have been prevented? Clearly the voices of science should be heard. At present our system is defective. We have the National Academies of Science, which are funded by Congress and respond to its inquiries. We have an optional presidential science advisor who is appointed by the White House. We can do better. We need a more representative organization of sciences and there is one – it is privately funded by scientists themselves and it is called the American Association for the Advancement of Science. Virtually every scientist in the US is a member of the AAAS. Less than 1 percent of scientists are in the National Academies. The science advisor to the President should not be a political appointment. Science should be neither Republican nor Democratic. Its role should be advisory, for the President to reject or accept, but the advice should not be censored, as it presently is, to fit White House ideology. Finally we need a vast increase in science literacy throughout local, state, and federal government. I am not asking for scientists to run for President (e.g., Herbert Hoover was an engineer and not one of our most revered presidents). But we need more briefings by science of legislators, legislative staff, and long-range planning commissions so prevention and preparedness rather than hasty reaction and incompetence are our responses.

Life Lines 53


Richard Leaky is an autodidact and high school dropout who is one of the world’s leading anthropologists. He is also a Visiting Professor at Stony Brook University and has been here these past seven years thanks to the efforts of President Kenny and Dean Lawrence Martin, a fellow anthropologist. Leaky was raised in Kenya and learned early from his father how to survive in the bush. He chose to drop out of school and set his own course in human paleontology, sometimes working with his father and sometimes on his own. He is one of the most renowned citizens of Kenya and established a national museum in Mombassa.

Leaky’s vision, when he joined the SBU faculty, was establishing an international center for the study of human origins. He raised several million dollars for this project so that graduate students and postdoctoral students (especially from Africa) could participate in field trips, and in the careful analysis of specimens. He also used the Institute for an annual meeting to bring anthropologists studying human origins from around the world to the Stony Brook campus. A unique feature of this conference is that after the public presentation of their papers, the 100 or so scholars get together for four days on the Stony Brook campus and discuss their work informally and “open old sores and generate new ideas.”

I enjoyed talking with Professor Leaky. He lost his legs in an airplane accident and manages to get around with his artificial ones. He considers himself a Kenyan and spends part of his time at Stony Brook, part in Kenya, and part traveling around the world. As he gets older, travel becomes more difficult but he keeps up his optimism and uses the enthusiasm of his gaining new knowledge as a way to keep going. He is planning a web site (very likely with National Geographic) for human origins that will enable millions of people around the world to see the specimens, follow the analysis, enjoy the debates among anthropologists, and find pleasure in reconstructing their ancestry over the past several millions of years since human-like form and behavior began to emerge. He also hopes his fellow anthropologists will play a leading role in countering the “disrespect for science” shown by those who would offer bad science, dilute the findings of evolution, or pretend to scientific knowledge with a hidden religious agenda substituting supernatural interpretations for scientific ones.

Leaky said this is one of the most exciting times to be an anthropologist. The work on finding new fossil humans and their ancestors is increasing around the world. He cited the findings in Indonesia of the small Homo erectus-like specimens called H. floresiensis. He also found the confirmation of fossil sequences and age through DNA analysis (especially comparative genomics) exhilarating. He felt the United States had more resources and opportunities to learn than any country on earth and he hopes his institute will help foster a greater interest among the public in our ancient ancestry.

Life Lines 52


I studied radiation genetics with H. J. Muller, the geneticist who founded the field of radiation genetics. I learned how to induce gene mutations and chromosome breakage by exposing fruit flies to x-rays and used this technique to induce a number of mutations in a given gene to study its structure. In the 1950s when I was Muller’s student, the world was steeped in debates about the effects of radiation from nuclear bomb testing and the world was fearful of an atomic war between the two sides of the on-going Cold War. Muller discovered the induction of gene mutations by x-rays in 1927. As he analyzed and tried to map these mutations he noted that a significant portion of these must be associated with something that prevented their being mapped. By 1929 he and his colleagues showed that these events were caused by chromosome breakage that rotated parts of chromosomes, deleted portions of others, or switched pieces among the chromosomes. This left behind a puzzle. At the high doses he used, about 90 percent of the eggs laid did not hatch. He called these dominant lethals. It was not until 1940 that he designed experiments with his student G. Pontecorvo, and showed that these were caused by breakage leading to what Barbara MacClintock called “the breakage-fusion bridge cycle.” In Muller and Pontecorvo’s analysis, they proved that the death of these embryos was caused by the abnormal joining of chromosome fragments that tied up cell division and killed the cell.

The recognition of the breakage-fusion-bridge cycle allowed Muller to interpret radiation sickness in Hiroshima and Nagasaki, where the cells of dividing tissues (such as our skin, guts, blood vessel linings, and blood-forming tissues) die and produce the symptoms of that disease. It also made Muller an advocate of radiation protection, because he and his colleagues had demonstrated that the induction of gene mutations or chromosome breaks was proportional to the dose received. He even showed that diagnostic doses of x-rays induce gene mutations and cautioned medical personnel to shield their patients and themselves from these minor doses, which are cumulative. It took a long time to educate the public about radiation protection. In the 1920s x-rays were used to measure foot size in shoe-stores, to straighten out bowlegs in children, to induce ovulation in infertile women, and to check the position of a fetus in the last trimester of pregnancy. None of these practices are done today.

What we need to know is how to balance medical need and our own risks. We need to know that at diagnostic doses (chest x-rays, dental x-rays) that risk is very low (but not non-existent). We also need to know that shielding protects our reproductive cells and thus diagnostic radiation cannot induce mutations to be passed on to future generations. We also need to know that in a choice between living now or dying much later from a possible tumor cell induced for treatment of another immediate disease, it makes sense to be treated with chemotherapy or radiation treatment. Because I am science literate I requested shielding for my family and myself at a time when it wasn’t standard practice to do so by physicians and dentists. Weighing risk and benefit should be our choice as much as possible.

Life Lines 51


Here are some questions rarely asked in presidential debates. Unlike questions about being a Mormon, a pot smoker, a cold woman, a Creationist, a philanderer, and other mud-slinging questions both the press and the candidates themselves resort to, my questions are about issues that touch our lives in fundamental ways. They are also unlikely to be answered in 30-second responses or smaller sound bites on the evening news. OK candidates; let’s hear your reasoned replies:

1. What is your timetable for the consequences of climate change? Are you thinking five, ten, twenty, or one hundred years down the road? What is your evidence for your timetable of concern? If you doubt there is such a problem, what are your scientific sources of your doubts?
2. How would you go about fixing or preventing the deterioration of the infrastructure of our roads, ports, airports, bridges, and dams? How would you assess our needs? What would you regulate? What would you allocate? Who would supervise the assessment and response and assure compliance?
3. What would you do to encourage, subsidize, or promote non-carbon, renewable energy sources over the next generation—especially geothermal, tidal, solar, and wind energy sources? What incentives would you give carbon-based energy companies to shift to these other forms of energy production?
4. How would you bring about health coverage for all Americans? Are you willing to abandon the uncovered children and the poor, the underinsured middle class whose employers have ended or cut back their insurance for employees? If not, how will you fund a program that assures a minimum adequate coverage?
5. How aggressively will you press industrial polluters to clean up their own messes and regulate industries that dump wastes in rivers, lakes, or oceans or ship them to poor countries willing to trade health for money? If you believe waste is not an individual’s nor an industry’s financial responsibility, are you willing to have the government pay for its proper disposal?
6. How should the public health be protected from hazardous contamination of foods, toys, and other commodities brought in from other countries? Should US inspectors sent abroad do this or should products be quarantined until shown to be safe? Or should the US work with International Agencies to set up standards and see that they are enforced? Who should pay for this?
7. What steps should we take to assure our population that new diseases arising anyplace in the world do not overwhelm our own population? Is our present reliance on the Center for Disease Control adequate? Should we subsidize non-profitable drugs for rare diseases or for worldwide major diseases (like malaria) that are not common in the United States?
8. How willing are you to prevent religious views of some religions about science from being national, state, or local policy for all other religions or for scientists themselves? Would you speak out against breaches of the “wall of separation” between politics and religion that Thomas Jefferson urged as national policy?

Sunday, November 21, 2010

Life Lines 50


I enjoyed reading Ronald Lindsay’s Future Bioethics: Overcoming Taboos, Myths, and Dogmas (Prometheus 2008). It was a provocative analysis of several controversial issues dealing with science and society. One of these is the enhancement of skills. We have multiple standards on what is ethical. If the very rich shower their children with private schools, tutors, test-enhancing study programs, trips to exotic museums and places around the world, we do not demand equality for the impoverished who are denied such enhancements and who will rarely score as well on examinations for admissions to prestigious schools. But we do get upset when athletes cheat by using muscle and stamina enhancing hormones or other drugs to boost their performance. Lindsay properly points out that in sports there are always rules and rulebooks. The fun of watching athletes is our premise that natural talents are the only skills that can be exercised and that secretly used artificial agents to give an advantage is a form of cheating. One can resolve this by banning such enhancement drugs (and punishing those who use them) or by making them available to all athletes (although the ethics of delayed health effects from using them might be quite important). But what if genetic enhancement of skills became possible in the decades ahead? Would it be appropriate for parents to enhance their children’s talents and academic skills by such means?

Lindsay argues we have always used enhancements to improve our lives. He is right. Since Prometheus (who gave fire to humans and angered his fellow gods) and Adam and Eve (who chose eating the fruit of the tree of knowledge giving them a sense of good and evil), humans have chosen to enhance their skills. We do this for our senses (telescopes, microscopes, x-rays to see inside our bodies, night vision goggles used in war). We enhance our immune systems by using antibiotics or vaccinations to cheat and kill invading bacteria. All of medicine is an enhancement to cheat nature of its evolutionary toll of our less efficient genotypes. If our biblical allotment of life is threescore years and ten, we would not complain of shifting it to 90 for our children because of the enhancements of modern technology that keep them from that lesser expectation. We may argue that using DNA in some distant future to enhance our personal lives or our children’s lives is unnatural, but we wallow in unnatural technologies to keep us alive or functional, including devices like eyeglasses, hearing aids, pacemakers, insulin for diabetics, and many other chemical and mechanical means. Most of our choices are based on risk-benefit analysis in which we weigh the value of the unnatural (false teeth) against the natural (a mushy diet) and make a choice. This is true for restorative devices (hearing aids) or enhancing devices (telephones, the internet) to communicate with those far away. We enhance our children by straightening their teeth, using cosmetic surgery to reshape a nose, minor surgery to remove warts and serious blemishes. The cosmetic industry is based on the principle of enhancement and few of us can claim a life unadorned by some cosmetic use in our lifetime.

Life Lines 49


When I was an undergraduate taking a course on mediaeval and renaissance history, I got to read St Francis’s Fioretti (The Little Flowers). In it he describes a meeting of Brother Giles and King Louis of France who visited his monastery dressed as a mendicant. They embraced when they recognized each other and they looked into each other’s eyes where they read each other’s hearts, without exchanging a word. It reminded me of an incident in another book I had read, the Biography of Sri Ramakrishna by Vivekananda. Ramakrishna described a legend to some of his followers of baby Krishna who is being held in his mother’s arms and as Yashoda looked into his open mouth she saw the universe. I thought over the years how privileged a few humans are to have the opportunity to be at one with the universe and how rare this must be. But as I became more saturated in science, I realized that this was not necessarily so.

Our universe consists of hundreds of billions of galaxies like our own Milky Way. All of these galaxies had a common origin, if we accept the prevailing Bing Bang theory of the universe, from some “singularity,” as astronomers like to call it, that in a minute fraction of a second underwent a massive explosion some 13 to 14 billion years ago. All of the galaxies must then have the same type of atoms found in our Milky Way, including our own sun. So when we look out on a clear starry night we see stars trillions of miles away composed of atoms that once danced in gaseous swirls with atoms that are present in our bodies. Astronomer Carl Sagan made that image even more vivid for me when he pointed out in his Cosmic Connection that our earth was composed in part from the debris of a dying star that helped make our own sun and its planets so that we can consider ourselves “star children.”

Evolution, of course, makes us kin with all of life going back to the first virus-like genes or DNA that began to form from nucleotides synthesized by natural processes in a carbon and nitrogen rich earth. Even more remarkable is that every human who has ever lived has exhaled air and voided water that has recycled through all of humanity in the thousands of generations that have belonged to our human species. This means that some of my favorite people, like Socrates, Euripides, Epictetus, Marcus Aurelius, Dante, Montaigne, Galileo, Mendel, Marie Curie, Goethe, Van Gogh, Mozart, Lincoln, Franklin Roosevelt, and Martin Luther King, Jr have contributed atoms to my own body Not only can I commune with their words and thoughts, but I can resonate with a sense that they have been incorporated physically into my cells as well.

Unlike the mystic visions described by St. Francis and Ramakrishna, this state of being at one with the universe (or any object outside ourselves) does not require a spiritual trance, chanting a mantra, or inducing an occasional state of satori for a private experience that cannot be shared. Rather, science gives us an understanding of ourselves at levels of cells, metabolism, molecules, and atoms that all of humanity can learn and experience, sometimes with a mystic’s awe.

Life Lines 48


One of Goya’s famous paintings is called “dreams of reason” and emanating from those dreams of a drowsy scholar are the evils of the world, like a Pandora’s opened box. It is a cautionary metaphor often used to humble the arrogance of those social reformers who seek planned societies controlled from the top down. It is also applied to scientists when they hope their rational approaches to the world’s problems will provide solutions to everything wrong. The eugenics movement is one such “dream of reason” that has gone bad more often than it has fulfilled a social good. But we seldom reflect on the opposite of Goya’s message, the “nightmares of reason.” When is it time to act when scientists see damage to the environment, to the human gene pool, or to the diversity of life? When should we worry about global warming, resource depletion, overcrowding, and the unlimited destruction we can design into our weapons? We follow the Golden Rule in our health practices and almost every parent wishes to treat a child with a condition that might be deforming or life threatening. If those conditions have an underlying genetic basis, we then allow the cure or treatment to give those genes a chance to be passed on. In the absence of public health and modern medicine most of those infants would have died before maturity or never had an opportunity to reproduce. The field of in vitro fertilization, for instance, has given infertile couples opportunities to reproduce with their own gametes. Normally about ten percent of humanity is sterile (organisms have an imperfect machinery). With today’s technology the vast majority of those sterile couples will become parents. The male fertility mutations and the female fertility mutations will thus be passed on to a future generation. If this is done for dozens of generations then a doubling or more of the incidence of infertile couples will be the lot of those attempting to have children a millennium from now.

The nightmares of reason tell us that we cannot just do what we want. We pay a price for everything. There is a price for doing nothing. There is a price for intervening with prenatal diagnosis or with gene therapy in somatic tissue or with gene therapy that alters reproductive cells. Doing nothing just passes the buck to the future and most of humanity prefers that. Who cares two or three generations from now when we are safely dead and cannot be blamed for our inaction or bad action? What we desire is good action. But what is that will-o-the-wisp we desire? Do our values extend to a future that is three or more generations ahead? When do we feel the future should take care of itself –one, ten, or 100 generations from now? And if we owe only the living our values, isn’t that a selfishness offensive to our values, especially if our industrial and political values are permeated with self-interest that creates most of those nightmares? What is remarkable is that we have the scientific knowledge to predict those changes in our genetic constitution into distant generations but population geneticists who do so might find they are regarded as bringing back eugenics. Similarly those who study patterns of climate change or resource depletion or desertification, or loss of arable land, or diminishing water tables are dismissed as Jeremiahs. Sometimes they are. The great difficulty each generation faces is that it knows less than it pretends to know and most of us are afraid to act without certainty. That will never happen and imperfect knowledge is what all governments and individuals must face in making decisions.

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Congenital heart disease is one of the more common forms of birth defects. With estimates running from 19 to 75 cases per 1000 births depending on what heart conditions are included. Cardiologists usually classify such babies as having one of three types of disorders. The first involve “cyanotic” or blue baby conditions associated with the blood vessels in the heart. The second involve defects of the left ventricle and its supporting valves. The left ventricle pumps blood through the aorta to the rest of the body. The third involves “septation defects” which we usually think of as holes in the inner walls of the heart separating the chambers from each other.

My brother Roland (1929-1975) was born with a congenital heart defect that limited his activities growing up. In those days in elementary school the sick kids were put in a “sunshine class.” This exempted them from gym and going up steps to other classrooms. My brother never married. He worked initially as a “printer’s devil” for a Swedish -American newspaper (Nordsjörnan) in New York, then as an elevator operator, then as an illustrator at UCLA, and finally as a graphic artist for the Nielsen ratings company. He was a much-loved uncle always enjoying a game of chess with his nephews and nieces and never failing to visit without bringing some candy to distribute. As a child, I used to listen to the thumping of his heart. It enlarged over the years and he had the bluish lips and clubbing of fingers associated with advanced heart disease. He appreciated the years he had lived because at birth our mother was told he would probably die within six months. There was no surgery available in the years of his youth.

The molecular biology of the heart is being worked out. Genes for two embryonic tissues that form on days 15-32 of pregnancy produce a crescent shaped sandwich of two layers that differentiate into the future left ventricle and aorta from the first heart field and the right ventricle and two atrial chambers that form from the second heart field. That process takes place during the first trimester of pregnancy (roughly to about 90 days after fertilization). These genes can be studied in mice to see how they produce these cardiac defects. While there are specific genes involved in heart defects, the genetics is still complex, with different types of abnormalities among the relatives instead of a consistent fidelity to one of the three original forms of malformation. No one knows why this variation in expression exists.

One of the surprising findings for cardiologists is the outcome of childhood surgery for these defects. It certainly extends life expectancy and gives some degree of normalcy in blood flow and oxygen-carrying capacity to these infants and children, but in their mature life there is a much higher risk for a different heart disease (an enlargement and failure of cardiac muscle) but cardiologists still don’t know why that occurs and thus the importance for them to study this in mouse models of human cardiac defects. Almost all of these genetic and molecular aspects of congenital heart defects have been worked out in the past ten years so this is a rapidly evolving field of human biology and medicine.

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I got a call from a neighbor who was a teacher of two of our children and who was a student in one of my classes. She told me of her efforts to track down a rumor that the strawberry color in one of her favorite foods was made from bugs. I immediately thought of the dye called carmine. It was familiar to me because years ago when reading about the history of dyes used for microscopy, I read about the first dye to be used in 1857 by a German anatomist named Joseph von Gerlach. He discovered that he could dye cells with acetocarmine. Within the next twenty years German scientists were using both natural dyes and artificial dyes to work out microscopic anatomy. I recall the course I had at NYU as an undergraduate preparing my own slides with synthetic, mostly aniline, dyes like eosin and hemotoxylin. Later I prepared fruit fly salivary gland squashes using acetocarmine.

Carmine dye is obtained from an insect that feeds on cactus. It is a hemipteran bug Dactylopius coccus and the Aztecs were using it when the Spanish arrived. They sent back the dye (called carmine) to Europe where it was widely used in the clothing industry. The British Red Coats in our Revolutionary War were dyed with carmine. The insects are scraped off the cactus and then dried and pulverized and the red dye extracted.
Today virtually all clothing is dyed red with aniline dyes. We like to have a bright red color for our meats and for the various fruit fillings, puddings, yoghurts, and other foods with strawberries or raspberries in them. Unfortunately natural red coloring of these meats and fruits tend to fade and in countries like Georgia in the Caucasian Mountains, where I once visited, the meat looks grey or a faded red. To Americans used to supermarket cheerful solid colors for their food, it looks repulsive. Hence much of our foods are dyed to look as we want them to look. But many people also prefer the organic and the natural to the artificial, so manufacturers try to oblige with natural dyes. But we consider eating insects repulsive so our manufacturers using natural products list the item as “carmine” instead of “bugs” in their contents. It’s a no win situation because some of the artificial aniline dyes are potent carcinogens and they have been banned for many years. Imagine how difficult it is for the food perfectionist to track down what is in food. Would a kosher Jew eat a dairy product that contained carmine as a dye? Probably not, because hemipteran bugs do not fall in the category of approved bugs (hind legs taller than the other legs, like grasshoppers) in the Bible. Would a strict vegetarian eat a fruit dessert that contained carmine? Probably not, if that person knew carmine was prepared by pulverizing thousands of cochineal bugs to extract the dye. One might get around this by making carmine synthetically but I have no idea how purists would respond to that—it may still be unnatural and not kosher to experts assessing these products.

Food is almost never free of products we should avoid or that for ideological or religious reasons we are taught to avoid. Some mushroom species have very high levels of mutagens. Some cereal grains and nuts get infected with fungi that produce carcinogens. Organic foods are more likely than treated foods to experience that. But the treatment to prevent spoilage may itself contain carcinogenic additives. After all, how does the sprayed agent kill the fungi you want to avoid? If it damages the DNA of the fungi isn’t it plausible it could damage your DNA?

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Not all science is logical, matches our common sense or experiences, or makes us comfortable. Evolution by natural selection creates an order out of chance mutations that are sifted by largely unpredictable environments organisms encounter throughout their lives. The size of atomic particles is minuscule compared to the size of an atom and this means that solid matter is mostly empty space. We find it strange that light can both be shown to produce wavelengths and at the same time to consist of photons, having enough mass to bend when passing the sun during an eclipse. We find the idea of quantum mechanics virtually opaque to our experience and cannot comprehend why an electron can be only in one level or another and not in between levels or why we can study the motion but not the location of an atomic particle. Science is not easy to master and it is difficult to learn enough science to feel comfortable talking about it because it requires a lot of time to build one concept on top of another. The terms used by science have fairly defined meanings and scientists will gladly spell those out. But the names often given have a misleading implication in popular thinking. The uncertainty principle about velocity and location of an atomic particle makes some people think life is uncertain and nothing is knowable. Relativity of motion becomes relativity of values in people’s minds. Quantum movements where particles can be suddenly shifted without apparent motion or cause is interpreted as humans passing through brick walls if they live long enough to experience such a quantum event (probably measured as once in many quadrillions of years or more). If the Copernican revolution is a paradigm shift (in which the relations and names of things is reassigned) some people jump to the conclusion that everything new in science is a paradigm shift.

Why does this confusion take place? I believe most of us have fantasies of controlling our lives more than nature allows us to do so. If we learn that telomere shortening leads to cell death we imagine that all we have to do to be immortal is prevent telomere shortening. If we learn the speed of light is a constant, we imagine traveling faster than the speed of light. If a person dies we imagine there are people somewhere who will communicate with the dead (no spiritualist has won the Amazing Randi’s million dollar award for demonstrating this to professional magicians). We want to believe that our birthdays have significance in a cosmic sense and we vaguely assign characteristics of our personality to our birth dates or to the location of planets in the night sky. If we win very large sums of money in a lottery or win on many occasions when gambling we assume we possess a quality called luck. If a new mathematical approach to complex problems uses “fuzzy logic” we think all problems we can’t handle can be solved by using fuzzy logic (with more fuzz than logic). Belief in the supernatural, whether religious or involving superstitions (broken mirrors, black cats, walking under ladders), requires some sort of faith. Science cannot provide support for them. But by our own bad logic we like to equate such faith in the supernatural with a scientist’s faith that there are laws of the universe that can be studied and which are constant or the scientist’s faith that science is worth doing. The scientist has to demonstrate the validity of new findings and most scientists can show abundant evidence that science is worth doing. Most of those who indulge in sloppy interpretations of science will reveal their insecurity: they seek medical science, not faith healing, when they are seriously ill.

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In 1974 I taught a large course -- Biology 101-102 with about 600 students per semester and a small course, a freshman seminar with 12 students. I held the seminar course in my house on Mud Road in Setauket. We car-pooled to get there. Nedra baked the cookies and cakes and tried not to repeat her offerings and tied them to the books and articles we read. One of the students was Steven Galson. I had long forgotten about Steve’s undergraduate days at Stony Brook until I received an email from President Kenny’s office inviting me to a luncheon with Rear Admiral Galson, the Acting Surgeon General of the United States. I called my daughter Claudia in New York because she was a classmate of Steve’s and she spoke highly of his enthusiasm for whatever he did and his idealism and good humor. She asked me to present Steven with a volume of her poems that were recently published.

I was delighted to recognize Dr. Galson and he was quite delighted to see me. He told me that he didn’t become a premed until his senior year and that he appreciated the mentoring that helped him to finally realize his goal. He went to Mount Sinai Medical School and felt a similar good fortune in being mentored there by faculty in an area of particular interest to him – public health. As an undergraduate at Stony Brook, Dr. Galson brought the NY Public Interest Research Group [NYPIRG] to campus. He went to Harvard after medical school and got a master’s degree in public health. He then worked his way up the federal system of public health, the Center for Disease Control, and the Food and Drug Administration. In October of 2007 he was asked to bring stability to the office of the Surgeon General, which had been buffeted by political controversy. Dr. Galson has done so because he is well known to the staff of these agencies and understands the need for independence of these agencies so they can do the jobs required of them by federal law. He also knows how progress comes incrementally and he chose issues that he felt produced a lot of misery and could be prevented or greatly reduced if the Surgeon General used that office as a “bully pulpit” for change. One of his interests is childhood obesity. Americans spend a lot of their money on food and they overeat. They also have switched from being active in sports to just watching sports or TV or playing video games as children and teenagers in their K-12 experience. We eat too much sugar in our foods and we eat too many calories. Galson’s mission is to change this by education. He pointed out that childhood obesity leads to adult obesity and that leads to an explosion of type 2 Diabetes and to hypertension. Both are major killers and they do so through chronic illness that is costly and involves prolonged pain and disability. Galson would like all our foods labeled with the calories per serving and menus in restaurants having that information on the meals served. People can’t make decisions if they are ignorant of the number of calories in their foods. He also is looking around the country for good models. He suggested a good one for Long Island, a farm to school program that would introduce Long Island vegetables and fruits directly from farmers to the schools, benefiting both in a “win-win” approach. Such a program he first discovered was introduced successfully at the local level in Portland, Oregon. Instead of soft drinks with excessive sugars, students would have fruit juices, fruits, and items like carrots, celery, string beans and other edible fresh vegetables in their cafeterias and snack machines.

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About a year ago I wrote a Life Lines column about some fossil monotremes found in Australia. The monotremes are the oldest branch of mammals. They lay eggs rather than gestating an embryo in a uterus. They also nurse their newborn with milk but lack breasts with nipples. The marsupials (which have pouches into which their embryos crawl and attach to a nipple) and the placentals (like us) are the other two branches of mammals. The fossil monotremes had more bird-like and reptilian skeletal features than the platypus, the best-known living monotreme. For those unfamiliar with the platypus, it has a beak like a duck, hair instead of feathers covering its body, a tail like a beaver’s, and in platypus males, spurs on its lower legs that can inject venom.

An international group of scientists worked out the sequence of the platypus DNA. The platypus (Ornithorhynchus anatinus) has 1.84 billion base pairs in its DNA (we have about 3 billion). The platypus genome encodes 18,527 protein-coding genes (we encode about 23,000 protein forming genes). Some 82% of platypus genes are shared with other mammals. Its genes for producing milk are similar to those of humans and other placental mammals. It has some genes involved in making its eggs that are similar to those found in birds and reptiles. Those genes are absent in humans and other placental animals. Many genes found in birds, reptiles, and fish are found in the platypus but they are missing in more familiar mammals like cats, dogs, mice, cattle, or humans. They have special genes for smelling chemicals under water but they lack the genes for smelling in air when they emerge to breathe or make rare appearances on land. Most of the time the platypus lives in rivers, especially in or along its muddy banks.

The monotreme line split off from a mammal-like reptilian line to form an early branch of mammals some 166 million years ago. The remaining branch split again 148 million years ago to form the marsupials and the placental mammals. Note that all three branches of the mammals existed some 80 million years before the dinosaurs went extinct. The dinosaurs died out about 65 million years ago. Monotremes are found in Australia and neighboring South Pacific islands. Marsupials are largely confined to Australia, New Zealand, and Tasmania with the exception of the opossum in North America that we occasionally see flattened out as road kill. Placental mammals are now world wide and proved very versatile in hitching rides on debris and spreading from continent to continent.

Isolating the platypus genome and comparing it to fish, amphibians, reptiles, and other mammals will reveal what portion of the 18% unshared genes (those not found in mammals) are unique to the monotremes and what portion belong to earlier ancestors, especially among the reptilian denizens of our ancient past. These coming decades will be rich in phylogenetic trees constructed from comparative genomics. They will show far more step-by-step changes in the evolution of life than the scant surviving bones, teeth, shells, and scattered remains left behind tens of millions of years ago.

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Most scientists are not public figures. They do their work in their laboratories and find sufficient pleasure in adding to new knowledge. Some people would like it to be that way and feel that scientists, like shoemakers, should stick to their last. My mentor, Hermann Muller was not that way and Matthew Meselson’s mentor, Linus Pauling, was not that way. When I interviewed Meselson recently at Harvard, I learned that Pauling told him, as a graduate student, not to get involved in protests because his authority as a graduate student would be minimal and his real value to science (and society) was through his contributions and comments on those contributions in his later career. Muller said much the same to his students. He said we would find ourselves increasingly called upon in our careers to speak out on issues (like radiation protection) and we would find ourselves in the public eye not always in a happy way.

Meselson followed Pauling’s advice and for his dissertation he introduced a new technique, density gradient centrifugation, that turned out to be just the tool he (and a fellow graduate student, Frank Stahl) needed to test the then recently introduced double helix model of DNA that Watson and Crick had published. They proved the key predictions of how DNA replicated and their paper became an icon of science (it was the subject of a book by a historian of science who called it the most elegant experiment in the 20th century).

Meselson was recruited to Harvard and asked, a few years later to participate in seminars on nuclear arms disarmament (Kissinger was one of the participants). He shifted from nuclear arms to something he knew more effectively as a chemist and molecular biologist. He sought to ban chemical and biological warfare. He was asked by the American Association for the Advancement of Science to go to Vietnam in 1969 with a scientific team to evaluate the health hazards and ecological damage from spraying herbicides on crops and foliage (mostly with Agent Orange). He played a role in getting the program cut back and in getting President Nixon (via his friend and colleague, Henry Kissinger) to submit the 1925 Geneva Protocol outlawing chemical warfare agents (including herbicides and incapacitating agents) during war -- a policy abided by Roosevelt, Truman, and Eisenhower, but rejected by Kennedy, Johnson, and Nixon (until Nixon changed his mind).

A decade later Meselson investigated an alleged use of poisonous toxins by the USSR in S. E. Asia called Yellow Rain. He went to Laos and other places where the attacks were alleged to have taken place and he showed that the Yellow Rain was not poison but was actually bee feces, mostly mixed local pollen that he was able to identify through his microscopic analysis. Meselson also went with his wife, Jeanne Guillemin (a sociologist at Boston College) to Sverdlovsk and they studied a Cold War episode of an anthrax epidemic that killed about 60 people that the USSR claimed was due to contaminated meat and not from a nearby germ warfare laboratory. Meselson used old weather reports and showed they fitted the distribution of the released cloud in the Sverdlovsk area proving that the outbreak was from the germ warfare facility and not contaminated meat.

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I was saddened by the mess Jim Watson found himself in when he went to London. Contrary to what most people think occurred, Watson was not interviewed in England on a book tour when his racist and sexist remarks occurred but interviewed earlier in the United States by a former student whom he had recruited from an English girl’s school. A former student of mine in Edinburgh sent me the 12-page article on Watson. In it the author of the article described Watson’s beneficial influence on her life and his views on genetics and society. He had recruited the student ten years ago to help bring more women into science. She described his positive accomplishments at Cold Spring Harbor bringing many of the most creative scientists there to make substantial contributions to our knowledge of human genetics and health. She gave a balanced account and remarked that his thinking and conversation was often erratic and blunt, sometime hurting his own reputation and she cited several of these from his past. She also recounted his remarks about IQ and race and it was this that led to his resignation from the Chancellorship of the CSH Laboratory and the Watson school. This does not exonerate Watson if he made those remarks. He apologized immediately for them and felt he was quoted out of context.

I read his latest book, Avoid Boring People. It is part autobiography and part a homily on how to be an effective scientist. Any young science student reading it will get a lot of practical advice and good insights in how to have a successful career. He mentions growing up in Chicago in the Depression. His parents were both liberal Democrats who believed in Roosevelt’s programs. He mentions sneaking a peak at his own IQ scores in high school and finding to his dismay that at best his IQ was 120. Those are not boasting scores; they are five points above the upper end of normalcy. He would need another 20 to 25 points to be in the genius category (145 and up). To Watson’s credit he succeeded in his career and he did not let his modest IQ prevent him from achieving eminence as a scientist. It is also to Watson’s credit that he insisted on a portion of the funding of the money for the human genome project to go to studies of the ethical, legal, and social aspects of the use of that new knowledge. When I heard Watson give a talk on the history of CSHL Press in 1999 he spoke of the importance of subsidizing books on the history of genetics and eugenics. I asked him if he would read a manuscript I was working on that covered the history of allegedly “unfit people” from Biblical times to the present. He not only read it, he recommended it for publication to CSHL Press. On many occasions when I was working with groups at CSHL on various eugenic history studies, he stated the importance of making all of the “skeletons in the closet” at CSHL to be made available on line for the world to see so the errors of the past will not be repeated. I would rather associate myself with a person who does good things and occasionally says regretful things than a person who says good things and acts to undermine those things by deeds that damage what we were misled to believe. I felt sorry for Reverend Jesse Jackson for his incautious comments some years ago but he is a person who far more consistently acts for the public good. We live in an age where off the cuff remarks become epitaphs to destroy reputations built over decades.

Sunday, November 14, 2010



Americans have had a long love/hate relation to measuring intelligence, giving it a name (the IQ or Intelligence Quotient), and using its categories (idiot, moron, normal, gifted, genius) as insults or pats on the back. It began in France in 1905 when Alfred Binet made the first attempt to identify students suited for more education or attention. It became the IQ in Germany a few years later and then became a national mania in the US to prepare standardized tests and administer these by the millions in schools. I took the test three times in public school and once as an entrance exam for freshman at NYU. My scores kept going up. I learned to sneak a peak at my scores in high school and my NYU advisor had the evaluation scores of my tests on her desk and I read them upside down. My scores went up by 49 points: 116, 136, 149, 165. I attribute this not to gene expression being turned on as I shifted to my teens, but to a passion to read widely, encouraged by my teachers and parents. I was a teacher’s pet and loved their praise and the demands they placed on me, from grading papers to preparing posters for school projects and events.

IQ scores were abused. If your ancestors came from Italy, Greece, the Balkans, Russia, or Poland you were considered less intelligent than Western Europeans and Harry Laughlin from the Eugenics Record Office would produce tables of IQ scores of immigrants and their children to prove why they should be barred from coming to the US where they would debase the national IQ score. That was the 1920s and it led to a discriminatory immigration law based on national origins. In the 1960s and 1970s criticisms of IQ scores erupted when they shifted to racial classification. Blacks, Hispanics, and Native Americans did not fare as well on tests designed by middle and upper class whites whose tests reflected their experiences and values. Too many school were using IQ tests to shift students into bright, average, and slow learners. The slow learners were frequently isolated to prevent the brighter students from being slowed down. The bright students effectively entered honors classes with enriched programs (we read Hamlet; the average students got Idylls of the King).

The IQ controversy is a complex one. IQ scores are rising around the world because more people are literate, go to school more, and they are exposed to more varied environments. This is called the Flynn effect, for a New Zealand psychologist who first reported the trend. Most psychologists refer to multiple intelligences. This makes sense. We vary in aptitude for art, music, “street smarts”, common sense, social relations, determination, persistence, dexterity, and creativity. These are not measured by a mass tested single number representing who you are or what you can become. Jim Watson’s IQ may be 120, but I am not 45 points smarter than he is and I would gladly trade my extra 45 points for his contributions to my field of genetics.



All societies for all of human awareness have experienced inequalities, prejudice, and failures that are felt most by those who are least powerful and influential. Some gross inequalities have virtually disappeared from democracies and industrial nations like slavery or child labor. Prejudices against class, race, religion, ethnicity, sex, or mental and physical disability still abound even in democracies like ours. Part of this thinking is associated with a belief in the innate inferiority of certain groups. Bolsheviks saw capitalists and the Czarist families they deposed as unworthy of living and reproducing and they shot them. Blacks in America were shunned or marginalized after their release from slavery. Women for generations were deprived of the right to vote. Labor organizers were frequently beaten, imprisoned, or killed by hired thugs to prevent unions from organizing. During the first half of the twentieth century these less fortunate members of America were described as “the unfit” and several thousands were sterilized in the 30 states that had such compulsory sterilization laws. Today much of that overt prejudice has disappeared. Injustices still exist. Those who are comfortable with their lives often marginalize those who lack power, especially the unemployed, the poor, the handicapped, the sick, and the old. Sometimes the comfortable look upon the unfortunate as victims of their own failings either through bad genes (and hence should not reproduce their kind) or lacking the moral stamina to prevent their misfortunes.

Each group of victims has its own cause and its own needs. We shuffle our priorities depending on the attention they receive. This in turn is dependent on the leadership of these causes. Opposed to the needy are those who do not wish to be taxed to support them. Also opposed to the needy are those who feel it is not the government’s job to bail them out. Hence corporations use lobbying efforts to avoid paying for pensions, health insurance, and charges of gender discrimination or of race discrimination. If the laws pass to prevent such abuses, corporations move to third world countries to avoid all the payments for social inequalities because most third world countries are not thriving democracies representing the people and many are corrupt. The corporations blame their woes on “greedy” unions and not on their own responsibilities or the need for government action. Public philanthropy certainly makes an effort to provide soup kitchens, to help build houses for the poor, and many other services. But most people do not give that much to the private charities to meet these immense needs. Most churches consider themselves lucky to provide a living for their minister and staff.

The real inequality in America, to me, is not of the poor versus the rich, or minorities versus privileged whites. The real inequality is the influence of lobby groups by the powerful to deny help to working people, to minorities, or to others who require the basic needs the privileged take for granted—clean and safe neighborhoods in which to live, health expenses that do not bankrupt them, educational opportunities (especially a college education) for their children, and care for their aging relatives. While new causes will pop up almost as often as old ones are solved, they will be sure to encounter the resistance of lobbying groups protecting the privileges of the powerful.



Back in the 1950s I saw a movie called The Fly. Vincent Price played a scientist experimenting with teleportation (pre Star Wars no less) but as he moves himself a fly accompanies him and he emerges in two scrambled chimeras, his body with a fly head and forearm and the bulk of the fly’s body with his human head. It was a great science fiction classic and scared the wits out of those seeing it. Vincent Price was a master at horror pictures. Recently I read an item from a Belgian team at Antwerp and Louvain Universities. They isolated the normal and three different mutant forms of a gene associated with a neurological and muscular wasting disease. It is called the Charcot-Marie-Tooth syndrome [CMT]. There are mutant forms located on chromosomes 1, 16, and 17 as well as on the human X. Most are dominant mutations. Children with CMT begin to show muscle wasting in their lower limbs when they are approaching age 13. It is progressive and can cause lots of problems, including loss of sensation and progressive paralysis. In most the fatty sheath along nerve cells degenerates so nerve impulses cannot be transmitted. Some die early but others live into their 80s with the disease. There is no cure or treatment.

The Belgian group identified one of the genes involved for CMT as a near universal gene found in all cells from bacteria to humans. It is a gene associated with protein synthesis called YARS. The normal human YARS has no effect when inserted into fruit fly sperm or eggs. But any of the three mutant forms inserted had dramatic effects in the flies inheriting that defective YARS gene. They could not fly, they had difficulty moving about, and their nerves showed signs of the same deterioration of the fatty sheaths around the nerves. One could argue that the fruit flies were expressing CMT disease.

This is valuable because animal models are usually done with mammals, which are expensive to maintain and slow breeding. Fruit flies, by contrast, can be grown by the thousands in a matter of a couple of weeks. This will allow the Belgian scientists to study ways in which the YARS gene interferes with nerve sheath formation and maintenance. It may someday lead to drugs that might prevent that deterioration.

What strikes me as interesting is our perception of flies and science seen in 1958 and seen slightly more than a half century later. In 1958 it was pure speculation about what we share in common with flies. Very little was known about the biochemical functions or developmental functions of the genes in fruit flies. Today virtually every gene in fruit flies has been assigned a biochemical function and the sequence of every gene in fruit flies is known. A half-century of progress in molecular biology is making it possible to study human diseases in fruit flies. I do not doubt that counterpart genes in fruit flies will be found for Huntington disease and Alzheimer syndrome and that will add to our knowledge of how genes associated with the nervous system function when they are introduced into fruit flies and used to study the disease process at a molecular level. It may not be as exciting as a B rated horror picture, but to the families involved it will be a cause for hope.



The debate over stem cell research will soon disappear or shift to a more esoteric philosophic or theological level. Three scientific teams have learned how to shift normal differentiated adult skin cells of mice into embryonic stem cells that were capable of producing an embryonic mouse. In a few years this will likely happen in humans and persons with neurologically degenerative disease, pancreatic diabetes, spinal cord injury, damaged heart muscle, or other infirmities will have their own cells to generate the stem cells they need to insert into the defective organ. At present the trick is done using four genes introduced by viruses. But introducing viruses can lead to cancers so look forward to synthetic carriers of these genes that do not induce cancers. If we are lucky this will happen in five years or less because you can bet that dozens of laboratories will be racing to find ways to improve this new technique.

Very frequently in science, especially the life sciences, there is a huge outcry against new techniques as immoral (when anesthesia was first used for childbirths, male critics of this technique in the 1840s argued that women were supposed to endure pain as punishment for giving Adam the apple and disobeying God). Life sciences are vulnerable to such religious attacks because humans are living things and religion pays more attention to humans than the physical world. One could argue that this is legitimate practice because without those outcries wicked techniques would be used indefinitely. This is not likely because science and technology always change. Without religious protests cars, TVs and refrigerators have changed. We do not drive Model Ts, watch TV in black and white, or get a cold drink out of the ice box.

Here’s the rub. By converting a human skin cell into an embryonic cell, you have avoided using gametes for potential life. But you have created quite a few potential embryonic cells each of which (or clusters of which) could become a clonal twin of a person whose skin cell was donated. If the critics of stem cell research are motivated by the potential and not the source of stem cells, they should oppose all stem cells no matter how derived, because cells set back to a blastomere state (such as cells found a few divisions after fertilization) are still functionally like blastomeres. I suspect that this shift in attitude won’t happen because the donor will be the sick person, the recipient will be the same sick person, and the cures will convince most of humanity that they would rather be healthy than chronically ill or prematurely dead. Tens of thousands of infertile women around the world have conceived by in vitro fertilization and have voted by raising healthy children rather than remaining childless. Are these women to be told they were wicked because they used artificial means to bring about a reproduction using their own gametes (fertilization in a dish)? Should their physicians be condemned as immoral for providing children to the infertile?

If stem cells do successfully treat human diseases the incentives to invest more staff and funding for improved techniques will mushroom. This is good news for medical science and patients in need. I hope it will not disappoint, too much, those who favor mortification of the flesh and admire those who reject new allegedly immoral treatments in favor of being “chastened and hastened” through pain and dying for the greater glory of their unburdened souls.



A few years ago I wrote a Life Lines column about Napoleon’s death. For several decades historians believed Napoleon was poisoned by the addition of arsenic to his food while he was in exile at St. Helena. As evidence they cited studies of a sample of his hair, bombarded with neutrons, which demonstrated a high incidence of arsenic in the hairs. I felt at that time, that was not a sufficient proof and I cited a news article I had remembered reading a generation earlier when Clare Booth Luce was an Ambassador to Italy and lived in Rome. She got quite sick from what turned out to be arsenic poisoning caused by her inhaling arsenic dust that flaked off from the paint in her room.

In a recent issue of Science, I noted that an Italian study of hair from Napoleon as a child as well as hair from members of his family and other contemporaries who never went to St. Helena, showed a similar high amount of arsenic in their hairs. Arsenic was widely used in paints, cosmetics, and as food additives in those days. The Italian Institute of Nuclear Physics concluded that homicide could be ruled out in the face of this widespread arsenic contamination of French middle class and wealthy people. To prove homicide something other than the presence of arsenic in the hair would be required.

The presence of arsenic in the hair is at best a necessary but not sufficient evidence of the deliberate poisoning of Napoleon. Most physicians who examined Napoleon’s body after he died concluded he died of stomach cancer although in those days there was no cell theory to back that up. While we may never know what caused Napoleon’s death, we at least can cast doubt that he was murdered. We crave certitude but science tells us we are limited to what we know and can’t let speculation substitute for knowledge. This is why the problem of Agent Orange exposure (or its dioxin contaminant) is so difficult. The presence of dioxins in veterans at parts per trillion (which is a very small amount compared to Napoleon’s arsenic) is a necessary but not sufficient piece of evidence that a veteran’s cancer, or enlarged prostrate, or diabetes is associated with that exposure. Because there is no proof that Agent Orange exposure causes human health problems other than chloracne (a skin disease) the National Academy of Sciences in the US uses a statistical association. If there are more veterans than predicted with a particular type of cancer, then those veterans are given the benefit of the doubt and their medical costs are covered. But if a veteran exposed to Agent Orange gets, let us say bladder cancer, and there is no excess association between those veterans and bladder cancer, that veteran does not get government provided medical care. The problem is really more social than scientific. If all people (or veterans) were covered by a national health insurance, then all people would have government-provided reimbursement for health care. We have done that with Social Security for retirement since the 1930s and someday we will extend that outlook to our health. Proof requires standards of science that are sometimes difficult to achieve, like the effects of low doses of radiation on cancer or mutation production, the effect of microwaves on cancer or mutation induction, and the possible health hazards of hundreds of chemicals in our environments and diets. In general harm from heavy, chronic or acute doses of exposure are easier to prove or disprove.



Teachers learn that any one thing is connected to everything. Students initially believe that no one thing is connected to anything. A semester of literature, mathematics, history, and science are disconnected in all but a scholar’s mind. Let me give you an example. What do Setauket, diaries, treason, New Amsterdam, the Vatican, ship-design, forgery, murder, map-making and habeas corpus have in common? I learned that they were all part of the life of John Scott. Because I keep a diary, inspired by Samuel Pepys’ entries in the 1660s, I checked out a book at the Emma Clark Library in Setauket by James and Ben Long, The Plot Against Pepys. Pepys was Secretary of the Admiralty and a founder of the Royal Society of Science during the reign of Charles II in the 1660s and 1670s.

John Scott was born in England and raised by his widowed mother in Southampton, Long Island. As a young adult he began to pursue wealth and power. He went back to England on money he had stolen and sold land he didn’t own to wealthy British investors. He returned to Long Island and forced those living in Setauket to move, using forged documents from the royal family. He played off Connecticut and Long Island in a land dispute and instigated the British to attack New Amsterdam and drive the Dutch from New York. He was imprisoned in Connecticut but escaped and when he was turned down for a government position on Long Island, he left for Europe, serving as a spy for Britain, France, and the Netherlands. He forged military maps of Britain to sell to the Dutch and French; and he forged maps of France and the Netherlands to sell to the British. In 1679 he returned to England and developed a scheme to frame Pepys and other supporters of James Stuart (King Charles’s Catholic brother) as part of a “Papist plot” to kill King Charles and return Great Britain to the Catholic Church.

Pepys, who was not Catholic, was arrested and sent to the Tower of London. After several months, he managed to get released on habeas corpus (ironically freed of its loopholes by the plotting members of Parliament who wanted to prevent James from ascending to the throne). Pepys assembled a powerful defense by having his friends obtain documents of the fraud, forgery, perjury, thefts, escapes, and assaults that Scott had accumulated in his pathological career. The charges were dropped after Scott killed a coach driver in a drunken brawl. Pepys was restored to his post in the Admiralty and his good name was restored. Scott escaped to the Netherlands and stayed there until Charles II died. When James II ascended to the throne, Scott joined the forces of William of Orange in the Netherlands and returned to England with a Dutch armada. James fled to exile and the House of Orange became the new royal line for Great Britain. As a reward for his service, Scott was given a pardon for his murder and sent to Montserrat in the Caribbean as a government official, where he led a comfortable life and died of old age. Pepys was forced to retire after James fled and spent his last years preparing his library and papers for donation to Oxford University.

I would certainly not have believed in 1948, when I first read excerpts of Pepys’ diaries and started my own, that I would connect these 60 years later, through Scott’s life to Setauket where I now live.



While at Harvard doing research for a book on Agent Orange, I came across a book given to Matt Meselson by Dr. John Constable. It was written by Le Cao Dai, a Vietnamese surgeon and published in English (Memoirs of War—The Central Highlands: a North Vietnamese Journal of Life on the Ho Chi Minh Trail 1965-1973 Hanoi, The Gioi, 2004). Dr. Constable was a friend of Dr. Dai and helped the Vietnamese establish plastic surgery units before, during, and after, the Vietnamese war. Dr Dai’s book is based on a journal he kept to be given to his wife in case he was killed. Dr Dai and his fellow soldiers were instructed to be like Robinson Crusoe once they left North Vietnam. They would have to improvise from the resources of the tropical rain forest after they established their portable field hospital.

This they did. They quickly learned to keep dry by sleeping in hammocks. If two trees were not close enough, they tied one end of the hammock to the spokes of a parked bicycle. For their trucks they always made sure to carry a pole cut from a young tree so that if the truck tipped over in the muddy terrain, they could right it, using the pole as a lever. They made their own sandals from unrepairable automobile or truck tires. They brewed their own alcohol from a plant with high sugar content and thus could carry out antiseptic surgery. They kept hospital records on the backs of can labels when they ran out of paper. They never assembled more than ten people in any one location and the last person in a marching column would erase the footprints of the group on the trail. They preserved rice and beans from rotting by storing them in tied condoms. They covered their flashlights and punched a hole in the cover allowing a spaghetti thin beam to see their way in the dark. They set up decoy smoking hearths in areas that would then be sprayed, sparing their own covert position. If they did happened to get sprayed, they could dismantle their field hospital and move it to a new location in a matter of hours, long before the herbicides caused the leaves to fall.

One of the important lessons frequently ignored in war, is not to underestimate the enemy. When we thought of the Vietnamese as “gooks” and reduced their personalities to their (or our) worst propaganda, we erred by failing to see them as resourceful human beings like us. Just as we enjoyed reading Robinson Crusoe as children, so did our Vietnamese adversaries, either in Vietnamese or French (as French Indochina before their civil war began, they were bilingual). The other important lesson is that everything is connected. Daniel Defoe read the story of Alexander Selkirk, a Scottish adventurer who was abandoned on an island in the Atlantic Ocean and who was rescued several years later. Had Defoe not embellished Selkirk’s story, turning him into the memorable character Robinson Crusoe, we would probably never have heard of Selkirk’s adventure. But as a literary classic written more than 200 years ago, it lives on around the world and captured the imaginations of the Viet Cong living in the Ho Chi Minh Trail as vividly as it did to each of us when as a youngster we thrilled to Robinson Crusoe’s resourcefulness, courage, and passion to live. .



For most of the time we have existed as a species we have been self-aware and know that each person has a unique personality and sense of self. We call that self our mind. In some religious traditions that self is also identified with the soul, but other theologians have distinguished the mind and the soul. We know that a baby’s mind develops and we are not the same person at 25 as we were when we were 2. For that matter, if we live into our 80s or 90s we may find our minds are not what they were in our 30s, and we tend to forget and our skills diminish. We prefer a soul (if we believe there is a survival of the self after death) that is at its peak of efficiency, not at its state in premature death (an infant, for example) or in senescence with a severely impaired mental awareness.

Things changed after the cell theory showed a variety of tissues existed. Our brain is composed of neurons, about 100 billion of them. Studies of injuries or strokes revealed that the brain has regions specific to vision, hearing, judgment, emotions, control over our limbs, memory, learning, association, and other functions. These set aside neurons in specific regions of the brain are stimulated by nerve impulses brought by our peripheral nerves or sense organs and they cause neurons in the brain receiving the signals to form synapses or fusions of nerve fibers between the incoming nerves and the regional neurons receiving the signals. The more the region is stimulated by signals, the more the fibers connect and form permanent or long–lasting associations. This was first discovered by a Canadian psychologist, Donald Hebb. And the easy way students learn it is “neurons that fire together, wire together” Neurobiologists have learned how a stimulus travels along a nerve, what chemicals are released to stimulate the wiring of synapses, and what happens if a limb is amputated or we lose one of our senses (like sight or hearing). From these twentieth century findings, neurobiologists have learned how opiates and other painkillers work and how some chemicals produce feelings of elation or peace in a troubled individual. It has led to a shift in psychiatry from “talk therapy” for psychotics to chemical control of those centers of the brain that are functioning abnormally in the psychotic. It also has taught psychiatrists how some illegal (i.e., controlled) substances lead to addiction and behavioral changes. For many neurobiologists the mind or self is a creation of our neurons and unique to just our life and will die with us, surviving only in a metaphorical or historical sense through our writings or other creations and the lives we have touched.

Some people are troubled by that scientific assessment. I am not. I cherish my uniqueness and protect it from harm. When I studied the genetic effects of LSD at UCLA, I used Sandoz LSD supplied by the National Institute of Mental Health, and found it was not mutagenic and did not break chromosomes and did not lead to chromosome loss. Despite my access to the LSD I never tried it on myself. It was not a lack of curiosity, it was my belief that my mind is a product of my neurons and if I chemically alter or damage them, I am taking a risk, especially since my mother was a paranoid schizophrenic. Since I shared half her genes, I did not want to test the expression of them under conditions where I had no control and no certain knowledge of those risks. I much prefer being guided by science than by luck.



Before the 1940s there was little that could be done for families with children born with hereditary disorders. Nature usually solved the problem because the children with the defect, if severe, had difficulty reaching reproductive age and if they did, they might have found it difficult to find a partner with whom to have children. Parents who wanted to try again usually had no one around to give them advise on the inheritance of the trait. Things began to change after 1946 as knowledge of human heredity improved and a new field of genetic counseling began to appear in a few university hospitals. But even if the odds were made known, this did not help parents who wanted a normal child and not another child with a debilitating illness. When little of the science is known about a misfortune, people attribute their bad luck to being punished for some transgression in their past. Or they become fatalists and accept whatever happened as divine will or fate. Or they fall back on superstition and believe they were harmed by some unhappy event that occurred while pregnant or just before becoming pregnant. In the nineteenth century women giving birth to a child with port-wine birth mark on the face frequently blamed this on escaping from a fire at home or seeing a friend’s or relative’s home burn down.

But science trades these non-scientific explanations with a technical one that often makes them do a lot of soul-searching on how to apply that knowledge. This happened with the invention of prenatal diagnosis in the 1960s. Once scientists learned that we have 46 chromosomes (in 1955) and that Down syndrome had 47 (in 1959) it took less than a decade for physicians to insert a needle into the amniotic cavity of pregnant women at risk and for the cells in that fluid to be cultured, photographed and interpreted. If the cells showed trisomy-21 (the extra chromosome present in Down syndrome) women could elect to end the pregnancy and try again. About 95% of women who have faced those bad news outcomes of amniocentesis as the process is called, have chosen to abort the embryo. This is a potent moral wallop for all involved and despite all the controversy over it, most women are choosing a healthy child over one that involves a lot of medical problems. Not everyone feels ennobled by hard times whether it is poverty or raising a child with severe limitations. This is particularly true for conditions that involve a deteriorating early death of a sick child (like Tay Sachs syndrome). There are ways to shift the decision-making from a two or three month old fetus to a pre-implantation embryo in a dish, but this is much more costly to do and usually applies to those who already know they have a high probability of a repeat birth defect for their child. Genetic services provide information and options. Persons at risk have to exercise their autonomy and wrestle with their values to make a decision that best fits their situation. At least that is the prevailing model of autonomy for patients dealing with medical problems. Fifty years ago there was still a lingering desire for the state or the physician to tell the patient what to do or not do for what most of us consider a private decision. Science makes important discoveries that add to our knowledge of how different aspects of the universe, including life, works. The vast majority of humanity is not scientifically literate and until risk or tragedy strikes we think of these problems in theoretical terms (especially theological ones). When science is applied we are forced to confront our values.



When Darwin worked out the evidence for a past evolution of life and presented a theory of natural selection to account for that evolution, he did not have the advantage of a theory of heredity. That would not enter evolutionary studies for another 35 to 50 years. What Darwin described were things he saw which we call phenotypes. My hazel eyes and full head of hair at age 77 are phenotypes. It would take a genetic analysis to reveal the genes involved in those two phenotypes and today that is largely done at a molecular level, the actual genes being isolated, sequenced, and their functions worked out in the cells where they are expressed. For most of the traits Darwin studied, he assumed that change was very gradual to bring about increases in size, change in intensities of color, developing visual acuity, or other biological functions necessary for survival. In the late 1890s most biologists thought such factors involved in character formation were numerous each with a slight effect and things like height would be a consequence of these numerous factors sorting themselves out into bell-shaped curves. It was the prevailing idea from the 1920s to the 1970s for measuring human intelligence with IQ tests.

What was surprising to me at the 74th Cold Spring Harbor laboratory Symposium on evolution that ended in early June 2009 was how different we interpret such changes in appearance today. Instead of thousands of barely observable changes that distinguish a dachshund from a wolf only about a dozen major genes are involved. Similarly the difference between an eyeless albino cave fish and one that has full sight and pigmentation is also due to a dozen or so genes. In both cases one can deconstruct the recent and bring it back to the past by genetic breeding in only a fraction of a human life time. I was discussing this with my former student, Ron Sederoff at the meeting when Jim Watson joined us and said, “What this conference has shown is that gradualism is dead”. Sederoff and I continued our discussion and we agreed that small numerous changes leading to domestic breeds of animals and plants were not true. But there are traits like coat color in cereal grains and human skin color where about five pairs of genes can distribute color in bell-shaped curve. Such quantitative traits, like the beak size and shape of finches in the Galapagos may depend on a similar small number of factors that form such bell-shaped curves. What is exciting about the analysis of domesticated forms or the evolutionary changes in cave fish where no human intervention was involved, is the small number of genetic changes that led to the “degeneration” of the eyes and coat color of the fish and the small number of changes that led to the development of more acute sensing of pressure in the dark cavern waters they live in.

What this illustrated to me is the fallacy we often fall into of assuming that what we see (the phenotype) corresponds to our imagined mechanism of how it came to be (the genotype). Genotypes are resolved by breeding analysis or by molecular analysis of the genes involved. The wonderful thing about science is that analysis and experimentation are far superior to doctrine and logic as guides to the past, whether that doctrine is “creationism” in any of its forms or “Darwinian gradualism” in any of its premolecular forms.