CHAPTER 3

Biology: The Mechanisms of Life

Life Is Generated in Scientist’s Tube

By WILLIAM L. LAURENCE

“Bottle babies,” predicted by Aldous Huxley for the distant future in a “brave new world” where children will be born in test tubes, have been brought at least part way toward actuality by Dr. Gregory Pincus at the Harvard Biological Institute.

A report of his work, made here [in Washington] today at the annual meeting of the Federation of American Societies for Experimental Biology, told of several spectacular developments on the frontiers of the science of life.

Dr. Pincus took the female and the male elements of rabbits, and fertilized them outside the body in a test tube. This in itself was formerly impossible to do, but Dr. Pincus went an important step further.

Allowing the artificially fertilized ovum to reach a stage of early development in the test tube, Dr. Pincus removed it from the bottle and transplanted it into a living female rabbit.

The transplanted embryo developed and matured in the host-mother just as in nature. In due course of time normal rabbits were born, the world’s first “semi-ectogenetic rabbits.”

Extension of the Theory

As rabbits and men belong to the mammalian group, the work is viewed as pointing toward the possibility of human children being brought into the world by a “host-mother” not related by blood to the child.

It is reasoned that eventually women capable of having children whose health does not permit them to do so may “hire” other women to bear their children for them, children actually their own flesh and blood.

To one who desires to speculate at this point the Harvard experiment offers another possibility. Theoretically, at least, it may become possible for a woman so inclined, particularly in a country influenced by eugenic considerations, to bring into the world twelve children a year by “hiring” twelve “host-mothers” to bear their test-tube-conceived children for them.

Advocates of “race betterment” might urge such procedures for men and women of special aptitudes, physical, mental or spiritual.

“Eliminating” the Male

But the Harvard biologist reported on another advance in the experiments, “eliminating” the male in reproduction. He put a rabbit ovum in a test tube and fertilized it with a strong salt solution.

Finding that even this salt solution was not necessary, Dr. Pincus accomplished the same results by exposing the ovum for a few minutes to a high temperature of 45 degrees centigrade, or 113 degrees Fahrenheit.

The ovum, fertilized by a strong salt solution or exposure to high temperature, was then transplanted into a living host-mother rabbit.

The rabbit-embryo developed to the early embryonic stage as in the normal way. At the end of a week the experiment was stopped to allow the scientists to check on the results.

Further experiments will be carried on in this field with the object of bringing into the world the first mammalian creature having as its “father” a salt solution or a high temperature.

“Fatherless” Offspring Females

Dr. Pincus pointed out in an interview, however, that all rabbits produced from an ovum fertilized artificially by salts or heat would be all female because the process would lack the sex-determining “Y-chromosome” which is supplied by the male.

Even the early stages of activation of the rabbit ovum, Dr. Pincus reported, could now be brought about experimentally without the male, either by the administration of hormones from the anterior pituitary gland, or by electrical stimulation of the cervical sympathetic nerves.

Activation by electrical stimulus was achieved at the Harvard Laboratories by Dr. H. B. Friedgood and Professor Walter B. Cannon of the Harvard Medical School.

Functioning of Brain Areas

New light was thrown on the functions of different areas of the brain by experiments reported by Dr. C. R. Jacobsen, Dr. F. V. Taylor and Dr. G. M. Haslerud of Yale University’s primate biology laboratory, before the central nervous system section of the American Physiological Society.

They removed completely the frontal and motor areas of the cerebral cortex of monkeys.

When the motor area was removed from an adult monkey the result was almost complete and permanent paralysis. The animal was unable to make any further voluntary movements. The same operation in infant monkeys, however, produced only a temporary paralysis. The animals soon were able to run, climb and manipulate objects.

Extirpation of the frontal association areas from adult animals caused total impairment of “recall” memory, although recognition memory was little disturbed. The results were essentially the same in the infants.

“It seems probable that this difference in recovery after motor and frontal area lesions arises from partial destruction of a dynamic system in the former instance, and complete removal in the latter,” the report stated.

“Reversing Locomotion”

An experiment which produced “reversed locomotion” in salamanders was reported to the Physiological Society by Dr. Paul Weiss of the University of Chicago.

On the theory that a nerve becomes specified by its muscle and responds selectively to specific impulses from the brain intended for that muscle, he transposed right and left front legs of the salamanders so that the right leg was connected with the brain by the nerve fibers which had served the left leg, and vice versa.

Stating that “the movements exhibited by the transplanted limb in the various phases of locomotion should be expected to be exact mirror images of the ones that the normal limb would perform at the same instant,” he said:

“This was actually found to be the case with eleven salamanders in which the developed forelimbs had been interchanged. These limbs moved always in the reverse direction.

“In the progressing animal they strode backward instead of forward and, although this seriously interfered with the locomotion of the body, the central pattern has never been changed and adjusted to the new conditions.”

New Heart-Reviving Method

A new surgical technique to revive hearts which have nearly stopped beating because of coronary occlusion, or blocking of the coronary arteries, was described to a section of the Physiological Society by Dr. C. J. Wiggers of Western Reserve University.

He reported that the method had been successful in reviving dogs from five to seven minutes after their hearts had entered the stage known as fibrillation, after which heart action stops. He said that it should be of value when applied to human hearts which start fibrillating in the course of surgical operations.

Two or three years ago it was found that fibrillation could be stopped and strong action revived by the brief passage through the heart of an alternating current applied through padded electrodes. This was only true, however, provided the coronary occlusion was removed and fibrillation had not lasted more than two or three minutes.

Dr. Wiggers found, however, that by massaging the heart immediately before applying the electric shock—that is by compressing the ventricles with the hand about forty times a minute and each time forcing blood into the aorta—the expectancy period for revival could be tripled or quadrupled.

Dr. R. H. Cheney of Long Island University, reporting on an experiment with a group of college girls, said that caffeine increased both speed and accuracy, but taken in the form of coffee was only about half as effective as when minute amounts of the pure alkaloid were administered.

Extraction of a hitherto unknown chemical substance from the bacillus of leprosy was reported to the American Society of Biological Chemists by Dr. R. J. Anderson, Dr. J. A. Crowder, M. S. Newman and Dr. F. M. Stodola of Yale University.

The material, which has been named leprosin, is a snow-white amorphous powder. It can be resolved into a new acid of high molecular weight which has been named leprosinic acid.

A machine for milking rats and guinea pigs was described by Warren H. Cox Jr. and Arthur J. Mueller of Evansville, Ind. Comparison of rat’s milk with cow’s milk shows the former to be richer in fat and protein, while containing half as much sugar.

—March 27, 1936

Clue to Chemistry of Heredity Found

A scientific partnership between an American and a British biochemist at the Cavendish Laboratory in Cambridge has led to the unraveling of the structural pattern of a substance as important to biologists as uranium is to nuclear physicists. The substance is nucleic acid, the vital constituent of cells, the carrier of inherited characters and the fluid that links organic life with inorganic matter.

The form of nucleic acid under investigation is called DNA (desoxyribonucleic acid) and has been known since 1869.

But what nobody understood before the Cavendish Laboratory men considered the problem was how the molecules were grooved into each other like the strands of a wire hawser so they were able to pull inherited characters over from one generation to another.

Further Tests Slated

The two biochemists, James Dewey Watson, a former graduate student of the University of Chicago, and his British partner, Frances H. C. Crick, believe that in DNA they have at last found the clue to the chemistry of heredity. If further X-ray tests prove what has largely been demonstrated on paper, Drs. Watson and Crick will have made biochemical history.

Dr. Watson has now returned to the United States, where he intends to join Dr. Linus Pauling, of California, who has done most of the pioneer work on the problem.

[In Pasadena, Calif., Dr. Pauling said that the new Crick-Watson solution appeared to be somewhat better than the proposal for the structure of the nucleic acids worked out by Dr. Pauling and associates at the California Institute of Technology. The California solution was published in the February 1953 issue of the Proceedings of the National Academy of Sciences.]

Dr. Crick may leave Britain, too, when he has done some more work on the problem. Right now, he said, it “simply smells right” and confirms research in many institutions, particularly the Rockefeller Foundation in the United States and at King’s College in London.

The acid DNA, Dr. Crick explained, is a “high polymer”—that is, its chemical components can be disentangled and rearranged in different ways.

DNA is the essential constituent of the miscroscopic life-threads called chromosomes that carry the genes of heredity like beads on a string.

In all life cells, including those of man, DNA is the substance that transmits inherited characters such as eye color, nose shape and certain types of blood and diseases. The transmission occurs at the vital moment of mitosis or cell division when a tangle of DNA containing chromosomes becomes thicker and the cell separates into two daughter cells.

Forming of Molecular Chain

Although DNA has never been synthesized, Drs. Watson and Crick knew it was composed of horizontal hook-ups of bases (sugars and phosphates) piled one above the other in chain-like formations. The problem was to find out how these giant molecules could be fitted together so they could duplicate themselves exactly.

By a method of scientific doodling with hand-drawn models of the molecules, Drs. Watson and Crick worked out which molecules could be joined together with regard to the fact that some molecules were more rigid than others and had critical angles of attachment. Some months ago they decided that the only possible interrelation of the molecules was in the form of two chains arranged in a double helix—like a spiral staircase, with the upper chain resembling the staircase handrail and the lower resembling the outside edge of the stairs.

New evidence for double DNA chains in helical form now has been obtained from the King’s College Biophysics Department in London, where a group of workers extracted crystalline DNA from the thymus gland of a calf and bombarded it with X-rays.

The resulting X-ray diffraction photographs showed a whirlpool of light and shade that could be analyzed as the components of a double helix.

Dr. Crick emphasized that years of work still must be applied to the helical carriers of life’s characteristics. But a working model to aid in the genetical studies of the future now has been laid out in blueprint form by Drs. Watson and Crick—or so most biochemists here believe.

Looks Good, Pauling Says

Reached by telephone in Pasadena, Dr. Pauling said last night that the Crick-Watson proposal for the structure of the nucleic acids “looks very good.” Dr. Pauling has just returned from London, where he talked with Dr. Crick and with Dr. Watson, who was formerly a student at California Institute of Technology.

Dr. Pauling said that he did not believe the problem of understanding “molecular genetics” had been finally solved, and that the shape of the molecules was a complicated matter. Both the California and the Crick-Watson explanations of the structure of the substances that control heredity are highly speculative, he remarked.

—June 13, 1953

50 Years Later, Rosalind Franklin’s X-Ray Fuels Debate

By DENISE GRADY

Fifty years ago, a casual gesture at a laboratory in London became a defining moment in the history of science. James D. Watson was visiting King’s College late one afternoon near the end of January 1953 when a researcher named Maurice Wilkins showed him an X-ray photograph of a molecule of DNA.

Describing the encounter years later in The Double Helix, Dr. Watson wrote, “The instant I saw the picture my mouth fell open and my pulse began to race.”

The image was one of many by various researchers that hinted at a helix, but its singular clarity helped lead Dr. Watson and his colleague Francis Crick to the structure of DNA.

The scientist who took the picture was Dr. Rosalind Franklin, and though they cited other work she had done, Dr. Watson and Dr. Crick did not acknowledge the photograph itself, or additional work by her they had used, in their paper.

Some historians say that is of little importance because the two would have deduced the structure even without the image. Besides, they say, Dr. Franklin herself did not seem to recognize the picture’s importance; she had put it aside.

But for others, over the years, Dr. Franklin has come to symbolize the plight of women in science, as men close ranks against them.

Dr. Franklin’s X-ray image, labeled “Photograph 51,” showed a distinctive X-shaped pattern. On the train back to Cambridge that night, Dr. Watson sketched on his newspaper the details he remembered from the picture, clues to the angles and spacing within the helix. By the time he got home, he had decided that its most likely structure was a double helix, and that he and Francis Crick should build a model to see if the pieces would fit.

The pressure was on: in America, Dr. Linus Pauling was at work, too, and he could not be far from cracking it.

A month later, the Watson-Crick team won the race: the pieces fit, they soon published a paper, and they went on to win the Nobel Prize, along with Dr. Wilkins.

But a question remains: had they used Dr. Franklin’s data without her permission or knowledge, and without giving her adequate credit?

It was Dr. Franklin, not her colleague Dr. Wilkins, who created Photograph 51, an image of what was known as the B form of DNA. Dr. Wilkins, who did not get along with Dr. Franklin, showed Dr. Watson the picture without telling her. Dr. Watson and Dr. Crick also used a report Dr. Franklin had written, passed to them by Max Perutz, a colleague and member of a research oversight committee.

“Rosy, of course, did not directly give us her data,” Dr. Watson wrote. “For that matter, no one at King’s realized they were in our hands.”

But Dr. Crick does not share this perception. Dr. Franklin “must have known we knew most of it,” he said in an interview.

For one thing, Dr. Franklin had made her data public at a seminar both men had been invited to attend. Unfortunately, Dr. Watson misinterpreted her presentation and Dr. Crick was not there.

As a result, the photograph Dr. Wilkins showed Dr. Watson was “the thing that triggered this off,” Dr. Crick said in an interview. But he added: “We could have got that information from earlier work. It would have made a big difference if I’d gone to that seminar.”

“We never had a discussion afterward,” he said of Dr. Franklin. “She never raised the issue.”

Dr. Watson and Dr. Crick did acknowledge other work by Dr. Wilkins and Dr. Franklin in their paper, but left it to Dr. Wilkins to decide whether he and Dr. Franklin should share authorship, an offer he declined. Dr. Franklin and Dr. Wilkins themselves published much of their data on DNA, including the famous photograph, in the same issue of Nature as the Watson and Crick paper.

As for the 1962 Nobel Prize, Dr. Franklin could not have been included; she died in 1958 of ovarian cancer and the Nobel is never awarded posthumously. Whether she would have been included is not clear; the prize is not split more than three ways.

In any case, neither Dr. Watson nor Dr. Crick mentioned Dr. Franklin during his Nobel speech, though Dr. Wilkins did.

Dr. Watson’s Double Helix has, if anything, contributed to the view that Dr. Franklin was unfairly deprived of credit she deserved. The book is peppered with snide comments about her looks and describes her as so snappish and fierce that Dr. Watson and Dr. Wilkins, who towered over her, supposedly feared she would hit them.

“Clearly Rosy had to go or be put in her place,” Dr. Watson wrote in Chapter 2 and added, later, “The thought could not be avoided that the best home for a feminist was in another person’s lab.”

In a biography published in October, Rosalind Franklin: The Dark Lady of DNA, Brenda Maddox theorizes that Dr. Watson portrayed Dr. Franklin as hostile and unreasonable to justify using her data without telling her. Ms. Maddox writes that Dr. Watson added a “pious epilogue” praising Dr. Franklin only after numerous colleagues who read a draft expressed outrage at his depiction of her.

According to Ms. Maddox’s biography, Dr. Watson and Dr. Crick eventually became friendly with Dr. Franklin. After her death, both men praised her generously in public forums.

“At no time did Rosalind, as far as is known, express any resentment at our having solved the structure,” Dr. Crick said.

In a recent interview in which he discussed Dr. Franklin, Dr. Watson said: “She never felt she was robbed. People say, ‘Well, she never knew we saw the B photo.’ That was a question between Maurice and her.”

—February 25, 2003

Scientist Reports First Cloning Ever of Adult Mammal

By GINA KOLATA

In a feat that may be the one bit of genetic engineering that has been anticipated and dreaded more than any other, researchers in Britain are reporting that they have cloned an adult mammal for the first time.

The group, led by Dr. Ian Wilmut, a 52-year-old embryologist at the Roslin Institute in Edinburgh, created a lamb using DNA from an adult sheep. The achievement shocked leading researchers who had said it could not be done. The researchers had assumed that the DNA of adult cells would not act like the DNA formed when a sperm’s genes first mingle with those of an egg.

In theory, researchers said, such techniques could be used to take a cell from an adult human and use the DNA to create a genetically identical human—a time-delayed twin. That prospect raises the thorniest of ethical and philosophical questions.

Dr. Wilmut’s experiment was simple, in retrospect. He took a mammary cell from an adult sheep and prepared its DNA so it would be accepted by an egg from another sheep. He then removed the egg’s own DNA, replacing it with the DNA from the adult sheep by fusing the egg with the adult cell. The fused cells, carrying the adult DNA, began to grow and divide, just like a perfectly normal fertilized egg, to form an embryo.

Dr. Wilmut implanted the embryo into another ewe; in July, the ewe gave birth to a lamb, named Dolly. Though Dolly seems perfectly normal, DNA tests show that she is the clone of the adult ewe that supplied her DNA.

“What this will mostly be used for is to produce more health care products,” Dr. Wilmut told the Press Association of Britain early today, the Reuters news agency reported.

“It will enable us to study genetic diseases for which there is presently no cure and track down the mechanisms that are involved. The next step is to use the cells in culture in the lab and target genetic changes into that culture.”

Simple though it may be, the experiment, to be reported this coming Thursday in the British journal Nature, has startled biologists and ethicists. Dr. Wilmut said in a telephone interview last week that he planned to breed Dolly next fall to determine whether she was fertile. Dr. Wilmut said he was interested in the technique primarily as a tool in animal husbandry, but other scientists said it had opened doors to the unsettling prospect that humans could be cloned as well.

Dr. Lee Silver, a biology professor at Princeton University, said last week that the announcement had come just in time for him to revise his forthcoming book so the first chapter will no longer state that such cloning is impossible.

“It’s unbelievable,” Dr. Silver said. “It basically means that there are no limits. It means all of science fiction is true. They said it could never be done and now here it is, done before the year 2000.”

Dr. Neal First, a professor of reproductive biology and animal biotechnology at the University of Wisconsin, who has been trying to clone cattle, said the ability to clone dairy cattle could have a bigger impact on the industry than the introduction of artificial insemination in the 1950s, a procedure that revolutionized dairy farming. Cloning could be used to make multiple copies of animals that are especially good at producing meat or milk or wool.

Although researchers have created genetically identical animals by dividing embryos very early in their development, Dr. Silver said, no one had cloned an animal from an adult until now. Earlier experiments, with frogs, have become a stock story in high school biology, but the experiments never produced cloned adult frogs. The frogs developed only to the tadpole stage before dying.

It was even worse with mammals. Researchers could swap DNA from one fertilized egg to another, but they could go no further. “They couldn’t even put nuclei from late-stage mouse embryos into early mouse embryos,” Dr. Silver said. The embryos failed to develop and died.

As a result, the researchers concluded that as cells developed, the proteins coating the DNA somehow masked all the important genes for embryo development. A skin cell may have all the genetic information that was present in the fertilized egg that produced the organism, for example, but almost all that information is pasted over. Now all the skin cell can do is be a skin cell.

Researchers could not even hope to strip off the proteins from an adult cell’s DNA and replace them with proteins from an embryo’s DNA. The DNA would shatter if anyone tried to strip it bare, Dr. Silver said.

Last year, Dr. Wilmut showed that he could clone DNA from sheep embryo cells, but even that was not taken as proof that the animal itself could be cloned. It could just be that the embryo cells had DNA that was unusually conducive to cloning, many thought.

Dr. Wilmut, however, hit on a clever strategy. He did not bother with the proteins that coat DNA, and instead focused on getting the DNA from an adult cell into a stage in its normal cycle of replication where it could take up residence in an egg.

DNA in growing cells goes through what is known as the cell cycle: it prepares itself to divide, then replicates itself and splits in two as the cell itself divides. The problem with earlier cloning attempts, Dr. Wilmut said, was that the DNA from the donor had been out of synchrony with that of the recipient cell. The solution, he discovered, was, in effect, to put the DNA from the adult cell to sleep, making it quiescent by depriving the adult cell of nutrients. When he then fused it with an egg cell from another sheep—after removing the egg cell’s DNA—the donor DNA took over as though it belonged there.

Dr. Wilmut said in the telephone interview last week that the method could work for any animal and that he hoped to use it next to clone cattle. He said that he could use many types of cells from adults for cloning but that the easiest to use would be so-called stem cells, which give rise to a variety of other cells and are present throughout the body.

In his sheep experiment, he used mammary cells because a company that sponsored his work, PPL Therapeutics, is developing sheep that can be used to produce proteins that can be used as drugs in their milk, so it had sheep mammary cells readily available.

For Dr. Wilmut, the main interest of the experiment is to advance animal research. PPL, for example, wants to clone animals that can produce pharmacologically useful proteins, like the clotting factor needed by hemophiliacs. Scientists would grow cells in the laboratory, insert the genes for production of the desired protein, select those cells that most actively churned out the protein and use those cells to make cloned females. The cloned animals would produce immense amounts of the proteins in their milk, making the animals into living drug factories.

But that is only the beginning, Dr. Wilmut said. Researchers could use the same method to make animals with human diseases, like cystic fibrosis, and then test therapies on the cloned animals. Or they could use cloning to alter the proteins on the surfaces of pig organs, like the liver or heart, making the organs more like human organs. Then they could transplant those organs into humans.

Dr. First said the “exciting and astounding” cloning result could shake the dairy industry. It could allow the cloning of cows that are superproducers of milk, making 30,000 or even 40,000 pounds of milk a year. The average cow makes about 13,000 pounds of milk a year, he said.

“I think that if—and it’s a very big if—cloning were highly efficient,” Dr. First said last week, “then it could be a more significant revolution to the livestock industry than even artificial insemination.”

Although Dr. Wilmut said he saw no intrinsic biological reason humans, too, could not be cloned, he dismissed the idea as being ethically unacceptable. Moreover, he said, it is illegal in Britain to clone people. “I would find it offensive” to clone a human being, Dr. Wilmut said, adding that he fervently hoped that no one would try it.

But others said that it was hard to imagine enforcing a ban on cloning people when cloning got more efficient. “I could see it going on surreptitiously,” said Lori Andrews, a professor at Chicago-Kent College of Law who specializes in reproductive issues. For example, Professor Andrews said last week, in the early days of in vitro fertilization, Australia banned that practice. “So scientists moved to Singapore” and offered the procedure, she said. “I can imagine new crimes,” she added.

People might be cloned without their knowledge or consent. After all, all that would be needed would be some cells. If there is a market for a sperm bank selling semen from Nobel laureates, how much better would it be to bear a child that would actually be a clone of a great thinker or, perhaps, a great beauty or great athlete?

“The genie is out of the bottle,” said Dr. Ronald Munson, a medical ethicist at the University of Missouri in St. Louis. “This technology is not, in principle, policeable.”

Dr. Munson called the possibilities incredible. For example, could researchers devise ways to add just the DNA of an adult cell, without fusing two living cells? If so, might it be possible to clone the dead?

“I had an idea for a story once,” Dr. Munson said, in which a scientist obtains a spot of blood from the cross on which Jesus was crucified. He then uses it to clone a man who is Jesus Christ—or perhaps cannot be.

On a more practical note, Dr. Munson mused over the strange twist that science has taken.

“There’s something ironic” about study, he said. “Here we have this incredible technical accomplishment, and what motivated it? The desire for more sheep milk of a certain type.” It is, he said, “the theater of the absurd acted out by scientists.”

In his interview with the Press Association, Britain’s domestic news agency, Dr. Wilmut added early today: “We are aware that there is potential for misuse, and we have provided information to ethicists and the Human Embryology Authority. We believe that it is important that society decides how we want to use this technology and makes sure it prohibits what it wants to prohibit. It would be desperately sad if people started using this sort of technology with people.”

—February 23, 1997

Pas de Deux of Sexuality Is Written in the Genes

By NICHOLAS WADE

When it comes to the matter of desire, evolution leaves little to chance. Human sexual behavior is not a free-form performance, biologists are finding, but is guided at every turn by genetic programs.

Desire between the sexes is not a matter of choice. Straight men, it seems, have neural circuits that prompt them to seek out women; gay men have those prompting them to seek other men. Women’s brains may be organized to select men who seem likely to provide for them and their children. The deal is sealed with other neural programs that induce a burst of romantic love, followed by long-term attachment.

So much fuss, so intricate a dance, all to achieve success on the simple scale that is all evolution cares about, that of raising the greatest number of children to adulthood. Desire may seem the core of human sexual behavior, but it is just the central act in a long drama whose script is written quite substantially in the genes.

In the womb, the body of a developing fetus is female by default and becomes male if the male-determining gene known as SRY is present. This dominant gene, the Y chromosome’s proudest and almost only possession, sidetracks the reproductive tissue from its ovarian fate and switches it into becoming testes. Hormones from the testes, chiefly testosterone, mold the body into male form.

In puberty, the reproductive systems are primed for action by the brain. Amazing electrical machine that it may be, the brain can also behave like a humble gland. In the hypothalamus, at the central base of the brain, lie a cluster of about 2,000 neurons that ignite puberty when they start to secrete pulses of gonadotropin-releasing hormone, which sets off a cascade of other hormones.

The trigger that stirs these neurons is still unknown, but probably the brain monitors internal signals as to whether the body is ready to reproduce and external cues as to whether circumstances are propitious for yielding to desire.

Several advances in the last decade have underlined the bizarre fact that the brain is a full-fledged sexual organ, in that the two sexes have profoundly different versions of it. This is the handiwork of testosterone, which masculinizes the brain as thoroughly as it does the rest of the body.

It is a misconception that the differences between men’s and women’s brains are small or erratic or found only in a few extreme cases, Dr. Larry Cahill of the University of California, Irvine, wrote last year in Nature Reviews Neuroscience. Widespread regions of the cortex, the brain’s outer layer that performs much of its higher-level processing, are thicker in women. The hippocampus, where initial memories are formed, occupies a larger fraction of the female brain.

Techniques for imaging the brain have begun to show that men and women use their brains in different ways even when doing the same thing. In the case of the amygdala, a pair of organs that helps prioritize memories according to their emotional strength, women use the left amygdala for this purpose but men tend to use the right.

It is no surprise that the male and female versions of the human brain operate in distinct patterns, despite the heavy influence of culture. The male brain is sexually oriented toward women as an object of desire. The most direct evidence comes from a handful of cases, some of them circumcision accidents, in which boy babies have lost their penises and been reared as female. Despite every social inducement to the opposite, they grow up desiring women as partners, not men.

“If you can’t make a male attracted to other males by cutting off his penis, how strong could any psychosocial effect be?” said J. Michael Bailey, an expert on sexual orientation at Northwestern University.

Presumably the masculinization of the brain shapes some neural circuit that makes women desirable. If so, this circuitry is wired differently in gay men. In experiments in which subjects are shown photographs of desirable men or women, straight men are aroused by women, gay men by men.

Such experiments do not show the same clear divide with women. Whether women describe themselves as straight or lesbian, “Their sexual arousal seems to be relatively indiscriminate—they get aroused by both male and female images,” Dr. Bailey said. “I’m not even sure females have a sexual orientation. But they have sexual preferences. Women are very picky, and most choose to have sex with men.”

Dr. Bailey believes that the systems for sexual orientation and arousal make men go out and find people to have sex with, whereas women are more focused on accepting or rejecting those who seek sex with them.

Similar differences between the sexes are seen by Marc Breedlove, a neuroscientist at Michigan State University. “Most males are quite stubborn in their ideas about which sex they want to pursue, while women seem more flexible,” he said.

Sexual orientation, at least for men, seems to be settled before birth. “I think most of the scientists working on these questions are convinced that the antecedents of sexual orientation in males are happening early in life, probably before birth,” Dr. Breedlove said, “whereas for females, some are probably born to become gay, but clearly some get there quite late in life.”

Sexual behavior includes a lot more than sex. Helen Fisher, an anthropologist at Rutgers University, argues that three primary brain systems have evolved to direct reproductive behavior. One is the sex drive that motivates people to seek partners. A second is a program for romantic attraction that makes people fixate on specific partners. Third is a mechanism for long-term attachment that induces people to stay together long enough to complete their parental duties.

Romantic love, which in its intense early stage “can last 12–18 months,” is a universal human phenomenon, Dr. Fisher wrote last year in The Proceedings of the Royal Society, and is likely to be a built-in feature of the brain. Brain imaging studies show that a particular area of the brain, one associated with the reward system, is activated when subjects contemplate a photo of their lover.

The best evidence for a long-term attachment process in mammals comes from studies of voles, a small mouselike rodent. A hormone called vasopressin, which is active in the brain, leads some voles to stay pair-bonded for life. People possess the same hormone, suggesting a similar mechanism could be at work in humans, though this has yet to be proved.

Researchers have devoted considerable effort to understanding homosexuality in men and women, both for its intrinsic interest and for the light it could shed on the more usual channels of desire. Studies of twins show that homosexuality, especially among men, is quite heritable, meaning there is a genetic component to it. But since gay men have about one-fifth as many children as straight men, any gene favoring homosexuality should quickly disappear from the population.

Such genes could be retained if gay men were unusually effective protectors of their nephews and nieces, helping genes just like theirs get into future generations. But gay men make no better uncles than straight men, according to a study by Dr. Bailey. So that leaves the possibility that being gay is a byproduct of a gene that persists because it enhances fertility in other family members. Some studies have found that gay men have more relatives than straight men, particularly on their mother’s side.

But Dr. Bailey believes the effect, if real, would be more clear-cut. “Male homosexuality is evolutionarily maladaptive,” he said, noting that the phrase means only that genes favoring homosexuality cannot be favored by evolution if fewer such genes reach the next generation.

A somewhat more straightforward clue to the origin of homosexuality is the fraternal birth order effect. Two Canadian researchers, Ray Blanchard and Anthony F. Bogaert, have shown that having older brothers substantially increases the chances that a man will be gay. Older sisters don’t count, nor does it matter whether the brothers are in the house when the boy is reared.

The finding suggests that male homosexuality in these cases is caused by some event in the womb, such as “a maternal immune response to succeeding male pregnancies,” Dr. Bogaert wrote last year in the Proceedings of the National Academy of Sciences. Antimale antibodies could perhaps interfere with the usual masculinization of the brain that occurs before birth, though no such antibodies have yet been detected.

The fraternal birth order effect is quite substantial. Some 15 percent of gay men can attribute their homosexuality to it, based on the assumption that 1 percent to 4 percent of men are gay, and each additional older brother increases the odds of same-sex attraction by 33 percent.

The effect supports the idea that the levels of circulating testosterone before birth are critical in determining sexual orientation. But testosterone in the fetus cannot be measured, and as adults, gay and straight men have the same levels of the hormone, giving no clue to prenatal exposure. So the hypothesis, though plausible, has not been proved.

A significant recent advance in understanding the basis of sexuality and desire has been the discovery that genes may have a direct effect on the sexual differentiation of the brain. Researchers had long assumed that steroid hormones like testosterone and estrogen did all the heavy lifting of shaping the male and female brains. But Arthur Arnold of the University of California, Los Angeles, has found that male and female neurons behave somewhat differently when kept in laboratory glassware. And last year Eric Vilain, also of UCLA, made the surprising finding that the SRY gene is active in certain cells of the brain, at least in mice. Its brain role is quite different from its testosterone-related activities, and women’s neurons presumably perform that role by other means.

It so happens that an unusually large number of brain-related genes are situated on the X chromosome. The sudden emergence of the X and Y chromosomes in brain function has caught the attention of evolutionary biologists. Since men have only one X chromosome, natural selection can speedily promote any advantageous mutation that arises in one of the X’s genes. So if those picky women should be looking for smartness in prospective male partners, that might explain why so many brain-related genes ended up on the X.

“It’s popular among male academics to say that females preferred smarter guys,” Dr. Arnold said. “Such genes will be quickly selected in males because new beneficial mutations will be quickly apparent.”

Several profound consequences follow from the fact that men have only one copy of the many X-related brain genes and women two. One is that many neurological diseases are more common in men because women are unlikely to suffer mutations in both copies of a gene.

Another is that men, as a group, “will have more variable brain phenotypes,” Dr. Arnold writes, because women’s second copy of every gene dampens the effects of mutations that arise in the other.

Greater male variance means that although average IQ is identical in men and women, there are fewer average men and more at both extremes. Women’s care in selecting mates, combined with the fast selection made possible by men’s lack of backup copies of X-related genes, may have driven the divergence between male and female brains. The same factors could explain, some researchers believe, why the human brain has tripled in volume over just the last 2.5 million years.

Who can doubt it? It is indeed desire that makes the world go round.

—April 10, 2007

My Genome, Myself: Seeking Clues in DNA

By AMY HARMON

The exploration of the human genome has long been relegated to elite scientists in research laboratories. But that is about to change. An infant industry is capitalizing on the plunging cost of genetic testing technology to offer any individual unprecedented—and unmediated—entrée to their own DNA.

For as little as $1,000 and a saliva sample, customers will be able to learn what is known so far about how the billions of bits in their biological code shape who they are. Three companies have already announced plans to market such services, one yesterday.

Offered the chance to be among the early testers, I agreed, but not without reservations. What if I learned I was likely to die young? Or that I might have passed on a rogue gene to my daughter? And more pragmatically, what if an insurance company or an employer used such information against me in the future?

But three weeks later, I was already somewhat addicted to the daily communion with my genes. (Recurring note to self: was this addiction genetic?)

For example, my hands hurt the other day. So naturally, I checked my DNA.

Was this the first sign that I had inherited the arthritis that gnarled my paternal grandmother’s hard-working fingers? Logging onto my account at 23andMe, the start-up company that is now my genetic custodian, I typed my search into the “Genome Explorer” and hit return. I was, in essence, Googling my own DNA.

I had spent hours every day doing just that as new studies linking bits of DNA to diseases and aspects of appearance, temperament and behavior came out on an almost daily basis. At times, surfing my genome induced the same shock of recognition that comes when accidentally catching a glimpse of oneself in the mirror.

I had refused to drink milk growing up. Now, it turns out my DNA is devoid of the mutation that eases the digestion of milk after infancy, which became common in Europeans after the domestication of cows.

But it could also make me question my presumptions about myself. Apparently I lack the predisposition for good verbal memory, although I had always prided myself on my ability to recall quotations. Should I be recording more of my interviews? No, I decided; I remember what people say. DNA is not definitive.

I don’t like brussels sprouts. Who knew it was genetic? But I have the snippet of DNA that gives me the ability to taste a compound that makes many vegetables taste bitter. I differ from people who are blind to bitter taste—who actually like brussels sprouts—by a single spelling change in our four-letter genetic alphabet: somewhere on human chromosome 7, I have a G where they have a C.

It is one of roughly 10 million tiny differences, known as single nucleotide polymorphisms, or SNPs (pronounced “snips”) scattered across the 23 pairs of human chromosomes from which 23andMe takes its name. The company generated a list of my “genotypes”—ACs, CCs, CTs and so forth, based on which versions of every SNP I have on my collection of chromosome pairs.

For instance, I tragically lack the predisposition to eat fatty foods and not gain weight. But people who, like me, are GG at the SNP known to geneticists as rs3751812 are 6.3 pounds lighter, on average, than the AAs. Thanks, rs3751812!

And if an early finding is to be believed, my GG at rs6602024 means that I am an additional 10 pounds lighter than those whose genetic Boggle served up a different spelling. Good news, except that now I have only my slothful ways to blame for my inability to fit into my old jeans.

And although there is great controversy about the role that genes play in shaping intelligence, it was hard to resist looking up the SNPs that have been linked—however tenuously—to I.Q. Three went in my favor, three against. But I found hope in a study that appeared last week describing a SNP strongly linked with an increase in the I.Q. of breast-fed babies.

Babies with the CC or CG form of the SNP apparently benefit from a fatty acid found only in breast milk, while those with the GG form do not. My CC genotype meant that I had been eligible for the 6-point I.Q. boost when my mother breast-fed me. And because, by the laws of genetics, my daughter had to have inherited one of my Cs, she, too, would see the benefit of my having nursed her. Now where did I put those preschool applications?

I was not always so comfortable in my own genome. Before I spit into the vial, I called several major insurance companies to see if I was hurting my chances of getting coverage. They said no, but that is now, when almost no one has such information about their genetic make-up. In five years, if companies like 23andMe are at all successful, many more people presumably would. And isn’t an individual’s relative risk of disease precisely what insurance companies want to know?

Last month, alone in a room at 23andMe’s headquarters in Mountain View, Calif., with my password for the first time, I wavered (genetic?) and walked down the hall to get lunch.

Once I looked at my results, I could never turn back. I had prepared for the worst of what I could learn this day. But what if something even worse came along tomorrow?

Some health care providers argue that the public is unprepared for such information and that it is irresponsible to provide it without an expert to help put it in context. And at times, as I worked up the courage to check on my risks of breast cancer and Alzheimer’s, I could see their point.

One of the companies that plans to market personal DNA information, Navigenics, intends to provide a phone consultation with a genetic counselor along with the results. Its service would cost $2,500 and would initially provide data on 20 health conditions.

DeCODE Genetics and 23andMe will offer referrals. Although what they can tell you is limited right now, all three companies are hoping that people will be drawn by the prospect of instant updates on what is expected to be a flood of new findings.

I knew I would never be able to pass up the chance to fill in more pieces of my genetic puzzle.

But I had decided not to submit my daughter’s DNA for testing—at least not yet—because I didn’t want to regard anything about her as predestined. If she wants to play the piano, who cares if she lacks perfect pitch? If she wants to run the 100-meter dash, who cares if she lacks the sprinting gene? And did I really want to know—did she really want to know someday—what genes she got from which parent and which grandparent?

I, however, am not age three. Whatever was lurking in my genes had been there my entire life. Not looking would be like rejecting some fundamental part of myself.

Compelled to know (genetic?), I breezed through the warning screens on the site. There would be no definitive information, I read, and new discoveries might reverse whatever I was told. Even if I learned that my risk for developing a disease was high, there might well be nothing to do about it, and, besides, I should not regard this as a medical diagnosis. “If, after considering these points, you still wish to view your results,” the screen read, “click here.”

I clicked.

Like other testers of 23andMe’s service, my first impulse was to look up the bits of genetic code associated with the diseases that scare me the most.

But in the bar charts that showed good genes in green and bad ones in red, I found a perverse sense of accomplishment. My risk of breast cancer was no higher than average, as was my chance of developing Alzheimer’s. I was 23 percent less likely to get Type 2 diabetes than most people. And my chance of being paralyzed by multiple sclerosis, almost nil. I was three times more likely than the average person to get Crohn’s disease, but my odds were still less than one in a hundred.

I was in remarkably good genetic health, and I hadn’t even been to the gym in months!

Still, just studying my DNA had made me more acutely aware of the basic health risks we all face. I renounced my midafternoon M&M’s.

And then I opened my “Gene Journal” for heart disease to find that I was 23 percent more likely than average to have a heart attack. “Healthy lifestyle choices play a major role in preventing the blockages that lead to heart attacks,” it informed me.

Thanks, Gene Journal. Yet somehow even this banal advice resonated when the warning came from my own DNA.

Back in New York, I headed to the gym despite a looming story deadline and my daughter’s still-unfinished preschool applications. At least I had more time. I had discovered a SNP that likely increased my life span.

But in what I have come to accept as the genomic law of averages, I soon found that I might well be sight impaired during those extra years. According to the five SNPs for macular degeneration I fed into the “Genome Explorer,” I was nearly 100 times more likely to develop the disease than someone with the most favorable A-C-G-T combination.

And unlike the standard eat-right-and-exercise advice for heart health, there was not much I could do about it. Still, I found the knowledge of my potential future strangely comforting, even when it was not one I would wish for. At least my prospects for nimble fingers in old age were looking brighter. I didn’t have the bad form of that arthritis SNP.

Maybe I was just typing too much.

—November 17, 2007

His Fertility Advance Draws Ire

By SABRINA TAVERNISE

To most people, the word “mitochondria” is only dimly familiar, the answer to a test question in some bygone high school biology class. But to Shoukhrat Mitalipov, the mysterious power producers inside every human cell are a lifelong obsession.

“My colleagues, they say I’m a ‘mitochondriac,’ that I only see this one thing,” he said recently in his modest, clutter-free office at Oregon Health and Science University. He smiled. “Maybe they are right.”

With a name that most Americans can’t pronounce (it is Shoe-KHRAHT Mee-tuhl-EE-pov) and an accent that sounds like the villain’s in a James Bond film, Dr. Mitalipov, 52, has shaken the field of genetics by perfecting a version of the world’s tiniest surgery: removing the nucleus from a human egg and placing it into another. In doing so, this Soviet-born scientist has drawn the ire of bioethicists and the scrutiny of federal regulators.

The procedure is intended to help women conceive children without passing on genetic defects in their cellular mitochondria. Such mutations are rare, but they can cause severe problems, including neurological damage, heart failure and blindness. About one in 4,000 babies in the United States is born with an inherited mitochondrial disease; there is no treatment, and few live into adulthood.

Mitochondria have their own sets of genes, inherited solely from mothers, and women who carry mitochondrial mutations are understandably eager to not pass them to their children. Dr. Mitalipov’s procedure would allow these women to bear children by placing the nucleus from the mother’s egg into a donor egg whose nucleus has been removed. The defective mitochondria, which float outside the nucleus in the egg’s cytoplasm, are left behind.

“It was a major breakthrough,” said Douglas C. Wallace, a professor of pathology and laboratory medicine at the University of Pennsylvania. “He’s an exceptionally talented person.”

But the resulting baby would carry genetic material from three parents—the mother, the host egg’s donor and the father—an outcome that ethicists have deplored.

That specter drew critics from all over the country to a hotel in suburban Maryland late last month, where Dr. Mitalipov tried to persuade a panel of experts convened by the Food and Drug Administration that the procedure, which he has pioneered in monkeys, was ready to test in people.

Some told the officials that the technique could introduce new genetic mutations into the human gene pool. Others warned that it could be used later for something ethically murkier—perhaps, said Marcy Darnovsky, executive director of the Center for Genetics and Society, “to engineer children with specific character traits.”

Back in his office, Dr. Mitalipov waved off those warnings. Mitochondrial DNA comprises just 37 genes, which direct the production of enzymes and molecules that the cell needs for energy, he noted. They have nothing to do with traits like eye and hair color, which are encoded in the nucleus.

“There are always people trying to stir things up,” said Dr. Mitalipov, an American citizen who grew up in what is now Kazakhstan. “Many of them made their careers by criticizing me.”

The United States is not the only country weighing mitochondrial replacement. In Britain, the government has issued draft regulations that would govern clinical trials in people. If accepted into law by Parliament, such trials, which are now banned, would be allowed to go forward, although regulators would have to license any clinical application.

Dr. Mitalipov’s fixation on mitochondria began in graduate school in Russia in the 1990s. After graduating from an agricultural institute—and a brief, unhappy stint as a manager on a collective farm—he began work on his doctoral thesis at the Research Center of Medical Genetics, a prestigious state-funded institution in Moscow. He focused on embryonic stem cells, which can be grown in the laboratory and turned into any type of cell in the body.

He noticed a strange thing. When stem cells were extracted from a mouse embryo and put in a petri dish, they stopped aging but remained healthy and growing, as if frozen in time. Somewhere in the cell, it seemed, was a clock that determined its life span.

The search for the clock took him to Utah State University for postdoctoral research in the mid-1990s. He developed an interest in cloning, a process in which the cellular clock is not only stopped but reset. Why, he wondered, do cloned animals have normal life spans?

The answer to the riddle of cellular aging was not to be found in the cell’s nucleus, Dr. Mitalipov concluded, but in the surrounding cytoplasm. In the mitochondria.

“Everything was falling into place in my head,” he said.

As researchers began to suspect defective mitochondria as a cause in more diseases, Dr. Mitalipov wondered whether replacing them might be possible.

Scientists already had experimented with combining genetic material from three people to make a baby. About 15 years ago, researchers in New Jersey injected a bit of cell fluid from donor eggs into the eggs of women who were having fertility problems. Those experiments, which came shortly after the cloning of Dolly the sheep, set off such an uproar that the F.D.A. eventually told researchers that they could not perform them without special permission.

Dr. Mitalipov persevered. At Oregon Health and Science University’s National Primate Research Center, one of eight in the country, he spent years perfecting a way to create monkey eggs with donated mitochondria. He persuaded software developers to adapt a program that would allow real-time viewing of the necessary microsurgery. A special microscope was developed so that human hands, too blunt an instrument on their own, could conduct the operation with joysticks that look like upside-down flashlights.

“He’s just a really practical guy,” said Daniel M. Dorsa, senior vice president for research at the university. “He just nose-to-the-grindstone plowed through and figured out what it took.”

Success came in 2008 in a darkened, hot laboratory room. On April 24, 2009, twin male rhesus monkeys, Mito and Tracker, were born with replaced mitochondria. Later, with some adjustments Dr. Mitalipov replicated the procedure in human eggs. Because of federal rules against genetic manipulation, the eggs were not allowed to mature.

His research has brought persistent criticism. “If these procedures are carried out, it crosses a very bright line,” said Ms. Darnovsky of the genetics center.

She said that the current goal, mitochondrial replacement, may be narrow, but that Dr. Mitalipov’s genetic techniques could lead to broader applications and eventually to a situation in which scientists or governments “compete to enhance future generations,” such as producing soldiers who never need sleep.

Sheldon Krimsky, a bioethicist who attended the F.D.A. meeting on behalf of the Council for Responsible Genetics, argues that mitochondrial replacement is simply unnecessary. There are other options for women with mitochondrial defects to have healthy children, such as getting an egg from a donor, or having prenatal genetic diagnosis to find eggs with fewer mutations, he said.

“There’s that genetic chauvinism that says unless my DNA is in the child, it will not be truly my child,” he said.

Would-be parents, on the other hand, have been following Dr. Mitalipov’s work with the intensity of the hungry waiting for food. When he came back from the meeting in Maryland, his inbox contained an avalanche of emails from women with mitochondrial mutations and other fertility problems.

Dr. Dorsa said the university still has not decided whether to formally ask the F.D.A. for permission to move forward with clinical trials.

Dr. Mitalipov, for his part, is determined.

“We are ready now to move on to the next stage,” he said. “Not in 10 years, but in the next few years.”

—March 18, 2014