This year, the genetic revolution that James D. Watson and Francis Crick ushered in with their discovery of the structure of DNA celebrates its 50th birthday.
The molecule that for so long exemplified youthful bravado, vast promise and vaster self-regard has become another aging, pot-bellied baby boomer.
In the view of some biologists, nothing would better suit the DNA industry than a genuine midlife crisis, a realization that this most mythologized of bio-abbreviations may not, after all, be the fulcrum around which the Milky Way wheels. As these biologists see it, DNA may be elegant, but it often has been accorded far greater powers than it possesses.
With all the breathless talk of human DNA as a grand epic written in three billion runes, the scientists complain that an essential point is forgotten: DNA, on its own, does nothing. It can't make eyes blue, livers bilious or brains bulging.
It holds bare-bones information — suggestions, really — for the construction of the proteins of which all life forms are built, but that's it. DNA can't read those instructions, it can't divide, it can't keep itself clean or sit up properly — proteins that surround it do all those tasks. Stripped of context within the body's cells, those haggling florid ecosystems of tens of thousands of proteinaceous fauna, DNA is helpless, speechless — DOA. By the same token, cells need their looping lanyards of genes and would grow as dull as hairballs without them.
Nowhere is an appreciation for the perpetual cross talk between gene and scene more important, these scientists say, than in understanding human nature.
Loose talk about genes "for" neurotic or novelty-seeking behavior, sexual orientation or schizophrenia is misguided not only because such language neglects the surely multigenic nature of nearly all characteristics worth studying, but because the phrase puts genes at the command post and ignores the ineluctably packaged, interactive deal that is DNA and its setting at every stage of life.
The researchers are desperate to demolish what they see as a false yet obdurate dichotomy, variously rendered as nature versus nurture, genes versus the environment, culture versus biology or evolution versus social construction.
However it is phrased, said Dr. Peter J. Richerson, an expert in cultural evolution at the University of California at Davis, "The whole dichotomy makes no sense, and it should be pitched out." You might as well speak of a rectangle's having a length versus a width, he said.
Yet while virtually all scientists and academicians profess a commitment to interactionism, and acknowledge that, yes, of course, everyone knows that nature and nurture need each other, only some are willing to explore what that means in real time.
"Everyone calls themselves an interactionist," said Dr. David Sloan Wilson, an evolutionary biologist at Binghamton University in New York. "Yet often, when you scratch below the surface, you find a sociobiologist who marginalizes the importance of culture, or a social constructivist who hates the very idea of sociobiology, and they end up painting caricatures of each other. True integrative thinking is in the very early stages."
In his recent book, "The Dependent Gene," Dr. David S. Moore, a professor of psychology at Pitzer College and Claremont Graduate University in California, offers a multitude of examples that challenge a reader's assumptions about what is innate and what isn't, and what it means to call something a "genetically" determined trait.
He cites the disease phenylketonuria, or PKU. As a result of a defect in a single gene, children with the condition are unable to produce a protein that breaks down the amino acid phenylalanine, a common component of foods like milk, eggs, meat and bread. That unmetabolized phenylalanine can build up in the body, leading to tremors, seizures and brain damage.
The condition was once a major cause of mental retardation, but in the 1950's doctors devised a simple treatment for it: dietary intervention. If young children with PKU are kept away from foods with phenylalanine, the amino acid doesn't clog their bodies and brains, and they do fine.
So is this disease "really" genetic, or "really" environmental? Both, Dr. Moore argues.
No matter how seemingly hard-wired a trait, Dr. Moore says, the outside finds its way in, and the inside responds.
For example, the attraction of baby mallards to their mother's call was long thought to be "instinctive," caused by genetic factors operating independent of the environment. After all, even ducklings that develop in an incubator, with no prenatal exposure to mother's quacks, immediately prefer upon hatching the sound of a mallard call over that of any other bird.
However, Dr. Gilbert Gottlieb, a developmental psychobiologist, went beyond the usual knee-jerk assumptions to ask: could the ducklings' own prehatching peeps be the priming factor here, teaching their developing brains key aspects of the proper mallard melody?
Sure enough, Dr. Gottlieb discovered that embryonic ducklings deprived of the ability to vocalize in the egg would, on hatching, respond as readily to a chicken cluck as to a mallard call. The budding duck brain learns by listening to the song of itself.
As developmental biologists are learning, genes and tissues engage in astonishing calls and responses during fetal growth. Dr. Jill A. Helms, an orthopedic surgeon and researcher at the University of California at San Francisco, and her colleagues reported in the Jan. 24 issue of the journal Nature the results of some rather bizarre transplant experiments.
Working with early embryonic ducks and quails, the scientists exchanged nubs of cells destined to be the birds' beaks, placing the bill-to-be clump in the quail, and the beak-to-be cell ball in the duck. As a result, the quail sprouted a duck's bill, while the duck grew a quail's much shorter, pointier beak. This happened not simply because the implanted cells carried genetic information from the donor embryo and grew into what they were "programmed" to be, but because the installed cells released molecular signals and persuaded the neighboring host tissue to override their resident genes, and switch species allegiance.
Behind the capacity of the birds to be nasally modified like so many feathered Nicole Kidmans is their shared genetic heritage. What the transplanted tissue did was to speed up or slow down the timing of embryonic events to assume a more duck-like or quail-like schedule. The genetic and temporal aspects of development, it seems, are intertwined like the snakes of the doctor's caduceus — health, the integrity of structure and pattern, life itself, depend on their union.
The importance of timing is by no means limited to fetal development.
Dr. Martha McClintock, a professor of biopsychology at the University of Chicago, and her colleagues recently showed that the timing of a rat's mating determines one of the most fundamental "genetic" facts of all: whether she bears sons or daughters.
A female rat that ventures out before sundown to solicit partners will give birth to mostly sons, while a female who prefers her matings after dark ends up bearing a litter rich with daughters. The very hormones that bind to the female's brain and prod her to mate early or late, said Dr. McClintock, in turn affect her uterus and its relative hospitality to the implantation of male or female embryos.
"There's a constant back and forth between genes and the environment," Dr. McClintock said. "It's important to remember that genes came to be what they are solely because of their capacity to interact with the environment, and make the right products in response to the environment."
As Dr. Wilson sees it, genes exist, not to call the shots or delimit the possibilities, but to create "miniature evolutionary processes" that continue throughout life, he said.
Consider the immune system, he said, which relies on a very limited number of genes for constructing the building blocks of immune cells and immune proteins. But it is a blast from the outside, the invasion of a new pathogenic threat, that determines what shapes, sizes and numbers of immune components will be slapped together on any given day.
Dr. Richerson proposes that many human behaviors may have a kind of immune-system dynamic to them, with a minimum number of genetically influenced algorithms, or set of multipurpose rules, giving rise to a huge diversity of behaviors.
He points out that one big difference between chimpanzees and humans is that humans are far more docile, more susceptible to social reinforcement than chimpanzees are. People have tried to raise chimpanzees as they would children, he said, and the chimpanzees are clever and do a lot of humanlike things, but they are not nearly as responsive as children are to praise and scolding. "They're rougher back," said Dr. Richerson. "They're the terrible twos gone berserk."
So what does our docility and social responsiveness get us? It makes humans quite good at living in a group, learning from the group, and adapting to ever-shifting group dynamics.
"In ambiguous or novel situations, you can apply the conformist rule and imitate other people," Dr. Richerson said. "The community is a source of good information about what the best local adaptations may be, and it's been shown with mathematical models that it's often advantageous to do what the majority is doing."
The tendency to ape the group as no ape can do may even shift the contours of our brains as we move from tribe to tribe. Dr. Richard E. Nisbett, a professor of psychology at the University of Michigan, has found that Asians and Westerners think differently from each other in significant and measurable ways, as he describes in his new book, "The Geography of Thought."
"Westerners focus on some kind of central object," he said in an interview. "They attend to its attributes and try to find out what rules apply to its behavior, with the goal of categorizing it."
By contrast, he said, Asians tend to see an object in a much broader field. "They're not as interested in categorizing objects," Dr. Nisbett said, "and they don't have as many linear deterministic rules of behavior."
These differences are revealed even in tests of perceptual and visual skills: Westerners score higher on the ability to remember the absolute size of an object; Easterners do better with recalling its dimensions relative to something else.
Significantly, the cognitive styles are not fixed, but shift after a person has spent only a few months living on the other side of the globe. Whether it must tilt holistic or dualistic, defend nature, nurture or neither, the human brain will find a way to fit in with the crowd.
File Date: 02.26.03