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Are clones less likely to be fertile?

Are clones less likely to be fertile?


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I know that hybrid animals like mules are infertile. What about clones? Do cloned animals show the same fertility as their original?


Cloned animals, at least in the first generation, are often subfertile and have lower viability than their progenitors. The reasons for this are complicated but often are related to epigenetic changes that lead to altered gene regulation.

Further reading:

Although the technology of SCNT has been applied successfully by many research teams, some SCNT animals have abnormal or lethal phenotypes, including facial abnormalities, pulmonary hypertension [3], contracted tendons [9], low birth weight [10, 11], as well as distinct depigmentation of the skin and hair… Based on previous studies, insufficient epigenetic reprogramming of somatic donor cells may result in phenotypic abnormalities in the offspring…

--Dysregulation of genome-wide gene expression and DNA methylation in abnormal cloned piglets

The epigenetic state of the ES cell genome was found to be extremely unstable. Similarly, variation in imprinted gene expression was observed in most cloned mice, even in those derived from ES cells of the same subclone. Many of the animals survived to adulthood despite widespread gene dysregulation, indicating that mammalian development may be rather tolerant to epigenetic aberrations of the genome.

--Epigenetic instability in ES cells and cloned mice.

Because few clones survive to birth, the question remains whether survivors are normal or merely the least severely affected animals, making it to adulthood despite harboring subtle abnormalities originating from inadequate nuclear reprogramming… Our results suggest that many expression abnormalities are common to the NT procedure whereas some reflect the particular donor nucleus. These results further emphasize the severity of placental dysfunction and illustrate abnormalities in clones surviving to birth.

--Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei

Although clone D had a poorer libido and entered puberty later than those of the other cloned male cats, he produced gonadal hormones within the average range. Four of the cloned male cats had normal fertility.

--Reproductive fertility of cloned male cats derived from adult somatic cell nuclear transfer.

(Note that this paper concluded that the cloned male cats had "normal fertility", but one of four (25%) had reproductive abnormalities (reduced libido and delayed puberty); the numbers are too small for anything definite but I would say this is evidence for abnormal fertility, not the reverse)

Some early papers do claim normal fertility of cloned mice, but those are simply based on the fact that the cloned mice could have offspring (i.e. were not completely infertile) and didn't actually compare fertility of cloned vs. "normal" laboratory mice.

  • Wakayama, T., Perry, A.C.F., Zuccotti, M., Johnson, K.R. & Yanagimachi, R. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 394, 369-374 (1998).
  • Wakayama, T. & Yanagimachi, R. Cloning of male mice from adult tail-tip cells. Nature Genet. 22, 127-128 (1999).

Fertility expert: 'I can clone a human being'

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Fertility expert: 'I can clone a human being'

1 /5 Fertility expert: 'I can clone a human being'

Fertility expert: 'I can clone a human being'

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Fertility expert: 'I can clone a human being'

166370.bin

Fertility expert: 'I can clone a human being'

166369.bin

Fertility expert: 'I can clone a human being'

166368.bin

Fertility expert: 'I can clone a human being'

166367.bin

A controversial fertility doctor claimed yesterday to have cloned 14 human embryos and transferred 11 of them into the wombs of four women who had been prepared to give birth to cloned babies.

The cloning was recorded by an independent documentary film-maker who has testified to The Independent that the cloning had taken place and that the women were genuinely hoping to become pregnant with the first cloned embryos specifically created for the purposes of human reproduction.

Panayiotis Zavos has broken the ultimate taboo of transferring cloned embryos into the human womb, a procedure that is a criminal offence in Britain and illegal in many other countries. He carried out the work at a secret lab-oratory, probably located in the Middle East where there is no cloning ban. Dr Zavos, a naturalised American, also has fertility clinics in Kentucky and Cyprus, where he was born. His patients – three married couples and a single woman – came from Britain, the United States and an unspecified country in the Middle East.

None of the embryo transfers led to a viable pregnancy but Dr Zavos said yesterday that this was just the "first chapter" in his ongoing and serious attempts at producing a baby cloned from the skin cells of its "parent".

"There is absolutely no doubt about it, and I may not be the one that does it, but the cloned child is coming. There is absolutely no way that it will not happen," Dr Zavos said in an interview yesterday with The Independent.

"If we intensify our efforts we can have a cloned baby within a year or two, but I don't know whether we can intensify our efforts to that extent. We're not really under pressure to deliver a cloned baby to this world. What we are under pressure to do is to deliver a cloned baby that is a healthy one," he said.

His claims are certain to be denounced by mainstream fertility scientists who in 2004 tried to gag Dr Zavos by imploring the British media not to give him the oxygen of publicity without him providing evidence to back up his statements. Despite a lower profile over the past five years, scores of couples have now approached Dr Zavos hoping that he will help them to overcome their infertility by using the same cloning technique that was used to create Dolly the sheep in 1996.

"I get enquiries every day. To date we have had over 100 enquiries and every enquiry is serious. The criteria is that they have to consider human reproductive cloning as the only option available to them after they have exhausted everything else," Dr Zavos said.

"We are not interested in cloning the Michael Jordans and the Michael Jacksons of this world. The rich and the famous don't participate in this."

It took 277 attempts to create Dolly but since then the cloning procedure in animals has been refined and it has now become more efficient, although most experts in the field believe that it is still too dangerous to be allowed as a form of human fertility treatment. Dr Zavos dismissed these fears saying that many of the problems related to animal cloning – such as congenital defects and oversized offspring – have been minimised.

"In the future, when we get serious about executing things correctly, this thing will be very easy to do," he said. "If we find out that this technique does not work, I don't intend to step on dead bodies to achieve something because I don't have that kind of ambition. My ambition is to help people."

Dr Zavos also revealed that he has produced cloned embryos of three dead people, including a 10-year-old child called Cady, who died in a car crash. He did so after being asked by grieving relatives if he could create biological clones of their loved ones.

Dr Zavos fused cells taken from these corpses not with human eggs but with eggs taken from cows that had their own genetic material removed. He did this to create a human-animal hybrid "model" that would allow him to study the cloning procedure.

Dr Zavos emphasised that it was never his intention to transfer any of these hybrid embryos into the wombs of women, despite Cady's mother saying she would sanction this if there was any hope of her child's clone being born.

"I would not transfer those embryos. We never did this in order to transfer those embryos," Dr Zavos said. "The hybrid model is the thing that saved us. It's a model for us to learn. First you develop a model and then you go on to the target. We did not want to experiment on human embryos, which is why we developed the hybrid model."

Dr Zavos is collaborating with Karl Illmensee, who has a long track record in cloning experiments dating back to pioneering studies in the early 1980s. They are about to recruit 10 younger couples in need of fertility treatment for the next chapter in his attempts at producing cloned babies.

"I think we know why we did not have a pregnancy," said Dr Zavos. "I think that the circumstances were not as ideal as we'd like them to be. We've done the four couples so far under the kind of limitations that we were working under.

"We think we know why those four transfers didn't take. I think with better subjects – and there are hundreds of people out there who want to do this – if we choose 10 couples, I think we will get some to carry a pregnancy."

All the cloning attempts, which date back to 2003, were filmed by Peter Williams, a distinguished documentary maker, for the Discovery Channel, which will show the programme tonight at 9pm.

Williams said that he was present at the secret laboratory when the cloning was carried out by Dr Illmensee. "There's never been any question of concealment, because we'd have known about it," Williams said.

The little girl who could 'live' again

Little Cady died aged 10 in a car crash in the US. Her blood cells were frozen and sent to Dr Zavos, who fused them with cow eggs to create cloned human-animal hybrid embryos.

These hybrid embryos were developed in the test tube and used to study the cloning process, but were not transferred into a human womb, despite Cady's mother saying she would sanction this if there was a chance the clone of her little girl could be born. Dr Zavos said he would never transfer hybrid animal clones into the human womb.

However, cells from Cady's "embryo" could in the future be extracted from the frozen hybrid embryo and fused with an empty human egg with its nucleus removed. This double cloning process could produce a human embryo that Dr Zavos said could be transferred into the womb to produce Cady's clone.

Frontiers of fertility: The key questions

Q. What does he claim to have done?

A. Panayiotis Zavos says he has created 14 human embryos and transferred 11 of them into the wombs of four women. Some of these embryos only developed to the four-cell stage before being transferred, but some developed to the 32-cell stage, called a morula. He also claims to have created human-bovine hybrid clones by transferring the cells of dead people into the empty eggs of cows. However, these hybrid embryos were used for research purposes and were not transferred to the womb.

Q. How does this compare to scientists' previous achievements?

A. Other scientists have created human-cloned embryos but not for the purposes of transferring them to wombs in order for women to give birth to babies. Those researchers created cloned human embryos in the test tube to extract stem cells for research. Dr Zavos has gone further (and broken a taboo) by creating embryos specifically for human reproduction, and he has attempted to create a viable pregnancy by transferring the cloned embryos into women.

Q. Hasn't he made similar claims before?

A. In 2004, Dr Zavos claimed to have transferred a cloned human embryo into a woman's womb but did not produce hard evidence. He has now produced more cloned human embryos, some at an advanced stage, and transferred them into the wombs of three more women. An independent documentary maker vouches for him.

Q. Why is this such a controversial thing to do?

A. Studies on animal cloning have shown time and time again that it is unsafe. The cloned animals suffer a higher-than-normal risk of severe developmental problems and the pregnancies often end in miscarriage. Mainstream scientists believe cloning is too dangerous to be used on humans.

Q. How likely is it that he will succeed?

A. He is determined to succeed and has a long line of people eager to sign up to his cloning programme, at a cost of between $45,000 and $75,000. Cloning attempts in other species, including primates, suggest there is no insuperable barrier to cloning humans.


Lessons from mouse genome

When they compared the results to the Mouse Genomic Informatics Knockout database they found 123 genes that corresponded with functional annotation of abnormal extraembryonic tissue morphology, 121 associated with embryonic lethality, and 14 with abnormal embryo implantation.

By day 34 of development, however, the pattern of gene expression was much more similar to control cows derived from artificial insemination, suggesting that these surviving clones were able to implant in the uterus and begin to form a placenta. These results indicate that the large losses of cloned cows before implantation probably result from problems with critical developmental genes in the extraembryonic tissue.

The study also revealed other points of potential failure for the clones, including problems with hormonal signaling between the developing cloned embryo and the pregnant cow. For example, the study found down-regulation of genes involved in interferon tau, the major signal of pregnancy recognition. The clones also appeared to have an effect on the gene expression of the pregnant cows themselves on day 34, some uterus tissue showed grossly different gene expression, which could affect the placenta.

“Our data confirm that the interactions between the uterus and the extraembryonic tissues is critical during implantation, making this step a major hurdle for the progression of pregnancy,” said Sandra.

“We now understand why clones fail, which can lead to improvements in the process of cloning of animals,” said Lewin. But, he cautioned, “Our discoveries also reinforce the need for a strict ban on human cloning for any purposes.”

“It’s amazing that the process works at all, demonstrating the great plasticity that developing animals have to adapt to extreme conditions,” Lewin said.


Monkeys cloned in world first, scientists reveal

Two monkeys are the first ever primates to be cloned using the technique that created Dolly the sheep.

The technique brings the prospect of cloned human beings even more closer. But scientists caution that there may be no good reason to create such clones, and that ethical and legal questions need to be answered about such research.

More immediately, the technique will allow researchers to create whole labs full of genetically identical monkeys. That could prove tremendously useful in scientific and medical research – allowing doctors to watch how specific treatments affect the genetic makeup of animals that are otherwise exactly the same, for instance.

1 /7 First monkey clones

First monkey clones

Chinese Academy of Sciences

First monkey clones

Qiang Sun and Mu-ming Poo, Chinese Academy of Sciences

First monkey clones

Qiang Sun and Mu-ming Poo, Chinese Academy of Sciences

First monkey clones

Chinese Academy of Sciences

First monkey clones

Qiang Sun and Mu-ming Poo, Chinese Academy of Sciences

First monkey clones

Qiang Sun and Mu-ming Poo, Chinese Academy of Sciences

First monkey clones

Qiang Sun and Mu-ming Poo, Chinese Academy of Sciences

The two identical long-tailed macaques – named Zhong Zhong and Hua Hua – were born eight and six weeks ago at a laboratory in China. They represent the furthest reaches of cloning technology, genetically resembling each other entirely.

They aren’t, strictly, the first primates to have been cloned. But they are the first to be produced using the single cell nuclear transfer (SCNT) technique, which involves transferring cell nucleus DNA to a donated egg cell that is then prompted to develop into an embryo, and is the same process used for Dolly the sheep. Previous work has relied on splitting embryos, which is the same phenomenon that happens when twins are born and can only produce four offspring.

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The two monkeys were part of a total of 79 different transfer attempts, which used different techniques. Scientists had some luck cloning monkeys using adult cells, but those were only able to survive for a few days.

That genetic symmetry of the monkeys means that scientists could create a whole experiment’s worth of identical monkeys, save for the specific genetic changes that they want to study.

“You can produce cloned monkeys with the same genetic background except the gene you manipulated,” said Dr Qiang Sun, the Chinese scientist who led the team that produced the research published in the journal Cell.

“This will generate real models not just for genetically based brain diseases, but also cancer, immune or metabolic disorders, and allow us to test the efficacy of the drugs for these conditions before clinical use.”

But the research has already led to fears about where it could lead. The scientists stress they did the work under strict international codes, and co-author Muming Poo said the team was aware “that future research using non-human primates anywhere in the world depends on scientists following very strict ethical standards”.

The breakthrough means that it would theoretically be easier to clone a human, since primates share so much of their makeup with us. But actually doing so is much less likely, given the ethical and regulatory objections there would be to any such plan.

“While they succeeded in obtaining cloned macaques, the numbers are too low to make many conclusions, except that it remains a very inefficient and hazardous procedure,” said Robin Lovell-Badge from the stem cell biology and developmental genetics laboratory at the Francis Crick Institute.

“Because they are non-human primates, macaques are obviously evolutionary much closer to humans than other animals typically used in research, and the aim of the work was to use the cloning methods to allow production of genetically identical macaques to use in biomedical research, where confounding factors of genetic variability could otherwise complicate experiments.

“However, with only two produced it would have been far simpler to just split a normal early embryo into two, to obtain identical twins. The work in this paper is not a stepping stone to establishing methods for obtaining live born human clones. This clearly remains a very foolish thing to attempt, it would be far too inefficient, far too unsafe, and it is also pointless. Clones may be genetically identical, but we are far from only being a product of our genes.”

Any cloned human would require a great deal of work and probably produce someone very different from the person being cloned – the effects of people’s upbringing and environment is just too strong to mean that it would be a matter of creating another version of a person.

“We do need to think about not only is it not acceptable, but it is a bit pointless anyway,” said Darren Griffin, professor of genetics at the University of Kent. ”What are people trying to achieve if they attempted to do that?

“Because realistically a clone would only be somewhat similar to the individual they came from. They would be less similar than an identical twin: they would have a different upbringing, born from a different womb, and brought up in a different era.”

Scientists will keep watch on Zhong Zhong and Hua Hua, who for now appear to be growing and developing like normal monkeys. They expect more clones to be born in the coming months.


Niche Technology

Ultimately, cloning may remain most useful in the area for which it was developed: to improve livestock breeding. Eggan says scientists didn’t know enough about animal genetics 25 years ago to boost traits they wanted and minimize ones they didn’t, so cloning ideal specimens seemed like the way to go. Cloning is still used for that purpose, especially for high-value animals, such as bulls.

In some animals, like pigs, cloning remains the most effective way to add desirable traits, says Angelika Schnieke, chair of livestock biotechnology at the Technical University of Munich. A pig embryo is colored, making it nearly impossible even with a microscope to see inside the embryo to add genes, she says. Up to now, there have been no iPSC or embryonic stem cell lines for rabbits, pigs or sheep, so cloning was the only option to make precise changes to cells from those species, Schnieke says. Cloning can be used to pass on genetic changes made in the lab, bypassing normal reproduction. Some researchers are also combining cloning and genome editing to make, for instance, pigs that are resistant to diseases, she says.

Ultimately, cloning will never be more than a niche technology, says Sir Ian Wilmut, the scientist who led the cloning of Dolly. But he’s more than satisfied that his work inspired a new understanding of cellular versatility, and all the benefits that have come from it. “iPS cells are by far the biggest inheritance from the cloning experiment,” Wilmut says. And what about all those frightful fantasies of being overrun by copies of ourselves? Or finding out that we’re only alive to serve the needs of someone with our genetic makeup? Eggan says we can now scratch those off our list of fears forever. iPSCs can do nearly everything that cloned cells could do, without the need for replicas. “That dystopian vision is in the rearview mirror now,” he says.

This story is part of "The Future of Fertility" a new series on Discover exploring the frontiers of reproduction. Read more:


OCR Biology: Module 4

e.g There will be no significant difference in/of . compared with .

n = no. of pairs of data, find correct n row in table, go along to p=0.05 value, and compare rs value to p = 0.05 value

if rs is higher than p=0.005 value then only 5% chance the correlation was by chance i.e 95% confident that correlation was not due to chance

e.g if rs = 0.6500 when n=10, less than 5% that correlation was due to chance, however not less than 2% that correlation was down to chance

behavioural
- the way an organism acts

camouflage
- harder for predators to spot it

teeth
- for diet e.g sharp teeth for meat, continuously growing teeth for tough plants

courtship
e.g dance
- increases chance of reproduction

migration
- get better food, climate

water-holding (e.g cacti, camel)

similar because they have adapted to similar climates and food supplies

different reproduction methods reflect that they are still different

2) organisms whose characteristics are best adapted to selection pressures have an increased chance of survival and successful reproduction
(less well-adapted species die)

3) successful organisms pass the allele with the advantageous characteristic onto their offspring
(organisms w/o aa less likely to successfully pass it on)

4) repeated for every generation and over time the proportion of individuals with the advantageous adaption increases. Frequency of the allele that codes for particular characteristic increases in populations gene pool.


The Genotype and the Individual

The genetic makeup of an individual is its genotype. The phenotype refers to what the individual is, which includes not only the individual’s external appearance or anatomy, but also its physiology, as well as behavioral predispositions and attributes, encompassing intellectual abilities, moral values, aesthetic preferences, religious values, and, in general, all other behavioral characteristics or features, acquired by experience, imitation, learning, or in any other way throughout the individual’s life, from conception to death. The phenotype results from complex networks of interactions between the genes and the environment.

A person’s environmental influences begin, importantly, in the mother’s womb and continue after birth, through childhood, adolescence, and the whole life. Impacting behavioral experiences are associated with family, friends, schooling, social and political life, readings, aesthetic and religious experiences, and every event in the person’s life, whether conscious or not. The genotype of a person has an unlimited number, virtually infinite, of possibilities to be realized, which has been called the genotype’s “norm of reaction,” only one of which will be the case in a particular individual (37). If an adult person is cloned, the disparate life circumstances experienced many years later would surely result in a very different individual, even if anatomically the individual would resemble the genome’s donor at a similar age.

An illustration of environmental effects on the phenotype, and of interactions between the genotype and the environment, is shown in Fig. 2 (38). Three plants of the cinquefoil, Potentilla glandulosa, were collected in California—one on the coast at about 100 ft above sea level (Stanford), the second at about 4,600 ft (Mather), and the third in the Alpine zone of the Sierra Nevada at about 10,000 ft above sea level (Timberline). From each plant, three cuttings were obtained in each of several replicated experiments, which were planted in three experimental gardens at different altitudes, the same gardens from which the plants were collected. The division of one plant ensured that all three cuttings planted at different altitudes had the same genotype that is, they were genetic clones from one another. (P. glandulosa, like many other plants, can be reproduced by cuttings, which are genetically identical.)

Interacting effects of the genotype and the environment on the phenotype of the cinquefoil Pontentilla glandulosa. Cuttings of plants collected at different altitudes were planted in three different experimental gardens. Plants in the same row are genetically identical because they have been grown from cuttings of a single plant plants in the same column are genetically different but have been grown in the same experimental garden. Reprinted with permission from ref. 13.

Comparison of the plants in any row shows how a given genotype gives rise to different phenotypes in different environments. Genetically identical plants (for example, those in the bottom row) may prosper or not, even die, depending on the environmental conditions. Plants from different altitudes are known to be genetically different. Hence, comparison of the plants in any column shows that in a given environment, different genotypes result in different phenotypes. An important inference derived from this experiment is that there is no single genotype that is best in all environments.

The interaction between the genotype and the environment is similarly significant, or even more so, in the case of animals. In one experiment, two strains of rats were selected over many generations one strain for brightness at finding their way through a maze and the other for dullness (Fig. 3 ref. 39). Selection was done in the bright strain by using the brightest rats of each generation to breed the following generation, and in the dull strain by breeding the dullest rats of every generation. After many generations of selection, the descendant bright rats made only about 120 errors running through the maze, whereas dull rats averaged 165 errors. That is a 40% difference. However, the differences between the strains disappeared when rats of both strains were raised in an unfavorable environment of severe deprivation, where both strains averaged 170 errors. The differences also nearly disappeared when the rats were raised with abundant food and other favorable conditions. In this optimal environment, the dull rats reduced their average number of errors from 165 to 120. As with the cinquefoil plants, we see (i) that a given genotype gives rise to different phenotypes in different environments and (ii) that the differences in phenotype between two genotypes change from one environment to another—the genotype that is best in one environment may not be best in another.

Results of an experiment with two strains of rats: one selected for brightness and the other for dullness. After many generations of selection, when raised in the same environment in which the selection was practiced (normal), bright rats made about 45 fewer errors than dull rats in the maze used for the tests. However, when the rats were raised in an impoverished (restricted) environment, bright and dull rats made the same number of errors. When raised in an abundant (stimulating) environment, the two strains performed nearly equally well. Reprinted with permission from ref. 13.


Biology to blame for women sexual preference?

A photo from The History Channel series "How Sex Changed the World." The age-old question, 'What do women want' could be rooted in biology, according to two new studies that show women prefer sexy, masculine men during ovulation, but dependable "husband material" the rest of the month. (Photo: CORBIS-BETTMAN, THE HISTORY CHANNEL)

Story Highlights

  • Studies find women are more likely to prefer, and flirt with, "manly men" when ovulating
  • During the height of fertility, they are looking for the best genes for their children, researchers say
  • Knowing our biological motivations doesn't mean we must follow them, biologists say

The age-old question, "What do women want" may be rooted in biology, according to two new studies.

While most women have no idea when they are ovulating, the studies show that women in the most fertile part of their cycle prefer the stereotypical sexy man, and one suggests they are more likely to flirt with him.

The studies are being presented at a meeting of The Society for Personality and Social Psychology in Austin, Texas, this weekend.

One, a UCLA analysis to be published Feb. 24 in the Psychological Bulletin, looked at dozens of studies on more than 5,000 women to see if there was evidence across the studies that women's preference in a mate shifts during ovulation. It found that when women are ovulating, they are more interested in men with masculine bodies, symmetrical facial features, dominant behavior, and certain body odors. This attraction to men with more masculine characteristics doesn't last all month, just during the height of fertility.

Findings suggest that when women are highly fertile they look for the most desirable genes to pass on to their children, says Martie Haselton, a professor at UCLA and the paper's senior author.

"On fertile days of the cycle women prefer the George Clooney type of guys, the sexy ones," she says. "Whereas on the less fertile days of the cycle women prefer the partner that will be there for them potentially and help them care for their offspring, someone more stable."

A second study, from the University of Minnesota, looked beyond attraction, to whether women's behavior actually changes during ovulation — whether they become more flirtatious, for example. That study will be published in Psychological Science in the spring.

"We wanted to know what women do behaviorally if they find a man attractive when they are ovulating," says Jeff Simpson, a psychology professor at the University of Minnesota and a researcher on the study. "We looked at verbal and nonverbal behavior and found women are more likely to signal interest or flirt with the more dominant, charismatic man they are attracted to during ovulation."

Simpson says the researchers studied the way 31 women acted during different parts of their cycle with a masculine man who may have a shorter-term mating pattern, vs. a "good dad" or more stable long-term partner. The women rated their preference for the men and researchers compared their verbal and non-verbal flirting behaviors when they were ovulating and not.

As in Haselton's review, the Minnesota study found that women were more interested in masculine men during ovulation. It also found that they were more likely to display a behavior change and flirt with them. Simpson says ovulating women also showed a decrease in interest in short-term relationships with men deemed "good dads," and instead preferred more masculine men.

Simpson said studies on women's sexual attraction may help explain why women can fall for a man they know won't be a good long-term partner.

"A woman may want a steady long-term relationship, but meets someone when she is ovulating and is drawn in by the charismatic dominant tendencies that may not be a good long-term person," Simpson says. "It's important to know women might be biased to find certain men attractive at certain points."

Steve Gangastad, a professor of evolutionary development at the University of New Mexico, who was not involved in either of the studies, says the studies open the door to other questions about women's sexual attraction during other parts of their cycle.

"The emphasis has been on what about men women distinctively prefer closer to ovulation," Gangastad says. "There's been relatively little attention to what characteristics women might prefer when they are not fertile."

Haselton says there is power in knowing where certain urges come from. "While men are driven by biological motivations, the same is true for women," she says. "We are driven by motives that have a biological foundation but people can choose not to follow them."


RESEARCHERS FIND BIG RISK OF DEFECT IN CLONING ANIMALS

Four years after researchers in Scotland startled the world by announcing that they had cloned a sheep named Dolly, scientists say evidence is mounting that creating healthy animals through cloning is more difficult than they had expected.

The clones that have been produced, they say, often have problems severe enough -- developmental delays, heart defects, lung problems and malfunctioning immune systems -- to give pause to anyone thinking of cloning a human being. In one example that seems like science fiction come true, some cloned mice that appeared normal suddenly, as young adults, grew grotesquely fat.

It is not that one particular thing goes wrong or one specific aspect of development goes awry, researchers say. Rather, leading cloning experts and developmental biologists said in recent interviews, the cloning process seems to create random errors in the expression of individual genes. Those errors can produce any number of unpredictable problems, at any time in life.

Before Dolly's debut in 1997, scientists thought mammals could not be cloned. But now they have cloned not only sheep but also mice, cows, pigs and goats. With mice, they have even made clones of clones on down for six generations. Dolly is apparently normal. Two infertility specialists recently announced that they wanted to clone humans.

Initial fears -- that clones would age rapidly or develop cancer -- turned out to be unfounded, scientists said. But as scientists gained more experience, and tried to discern why efforts so often ended in failure, new questions about the safety of cloning arose. Fewer than 3 percent of all cloning efforts succeed.

In cloning, scientists slip a cell from an adult into an egg with its genetic material removed. The egg then reprograms the adult cell's genes so that they are ready to direct the development of an embryo, then a fetus, then a newborn that is genetically identical to the adult whose cell was used to start the process. No one knows how the egg reprograms an adult cell's genes, but that, scientists think, is the source of the cloning calamities that can occur. The problem, they say, seems to be that an egg must do a task in minutes or hours that normally takes months or years. In the months it takes sperm to mature, their genes are being reprogrammed. The same thing happens in eggs, where over years they slowly mature in the ovaries. And this reprogramming must be perfect, scientists say, or individual genes can go amiss at any time in development or later life.

''With cloning, you are asking an egg to reprogram in minutes or, at most, in hours,'' said Dr. Rudolph Jaenisch, a professor of biology at the Whitehead Institute at the Massachusetts Institute of Technology. ''That's where the major problem is.''

All the evidence so far, scientists say, indicates that the breathtakingly rapid reprogramming in cloning can introduce random errors into the clone's DNA, subtly altering individual genes with consequences that can halt embryo or fetal development, killing the clone. Or the gene alterations may be fatal soon after birth or lead to major medical problems later in life.

Some scientists say they shudder to think what might happen if human beings are cloned with today's techniques. While arguments over the ethics of human cloning have dominated the debate, these scientists say the real issue is the likelihood that clones would have genetic abnormalities that could be fatal or subtle but devastating. Until that problem is solved, they say, human cloning should be out of the question.

''It would be morally indefensible,'' said Dr. Brigid Hogan, a professor of cell biology at Vanderbilt University Medical Center in Nashville and an investigator with the Howard Hughes Medical Institute.

Dr. Jaenisch said, ''It would be reckless and irresponsible,'' adding, ''What do you do with humans who are born with half a kidney or no immune system?'' And, he said, what about the possibility of creating children who appear to be normal but whose genes for neurological development work improperly?

Scientists say they see what appear to be genetic problems almost every time they try to clone.

For example, some mouse clones grow fat, sometimes enormously obese, even though they are given exactly the same amount of food as otherwise identical mice that are not the products of cloning. The fat mice seem fine until an age that would be the equivalent of 30 for a person, when their weight starts to soar, said Dr. Ryuzo Yanagimachi, a University of Hawaii researcher who first cloned these animals and has studied cloning's consequences in them.

Cloned mice also tend to have developmental abnormalities, taking longer to reach milestones like eye opening and ear twitching, Dr. Yanagimachi has found.

Cow clones are often born with enlarged hearts or lungs that do not develop properly, said Dr. Mark E. Westhusin, a cloning expert at Texas A & M University in College Station, Tex. Dolly herself, while apparently healthy, grew fat and had to be separated from the other sheep and put on a diet. But her experience is difficult to interpret since it is hard to draw conclusions about a propensity to obesity from one animal.

The genetic effects most often seem to be fatal at the very start of life, researchers say. With cattle, for example, 100 attempts to create a clone typically result in a single live calf, Dr. Westhusin said.

Cloning mice is more efficient, Dr. Yanagimachi said. But even then, only 2 percent to 3 percent of his attempts succeed.

'ɼloned embryos have serious developmental and genetic problems,'' Dr. Yanagimachi said, which usually kill them before birth. Just after birth, he said, more die, usually of lung problems. He added that inbred strains are much harder to clone than hybrid strains of mice, which makes sense, he said. Inbred animals have much less genetic diversity and so less opportunity to bypass genetic errors than hybrid animals.

Dr. Westhusin says that when he thinks about what happens in cloning, ''it's a wonder it works at all.''

Scientists knew that every cell in the body has the same genes so, in theory, all the instructions for making a new copy of an adult are present in every cell. But most of the genes in an adult cell, like a skin cell or a brain cell or a liver cell, are silenced. That is why those cells, which have reached their final stage of development, never change. A skin cell does not turn into a heart cell. A brain cell does not turn into a liver cell. And no one expected an egg cell to be able to reprogram such an adult cell, somehow stripping its genes bare of their chemical masks.

Dr. Jaenisch and Dr. Westhusin say that from preliminary molecular biology experiments they are starting to see confirmation of their belief that reprogramming can go awry. They are looking at molecular patterns of gene expression in embryos created by cloning and comparing them to the patterns in embryos created by normal fertilization. Their results so far are consistent with their hypothesis that reprogramming can result in random errors in almost any gene.

But scientists say that every species is different, and it remains possible that it will be easier and safer to clone humans than it is to clone other species.

Mouse eggs are fragile, Dr. Jaenisch said, which may complicate efforts to clone. The solutions used to bathe cattle embryos while they are grown in the laboratory seem to create a large-calf syndrome, resulting in large placentas and huge calves that often die around the time of birth. But clinics for in-vitro fertilization have vast experience in growing human embryos in the laboratory and have perfected the method.

Some -- like Dr. Richard Rawlins, who directs the in-vitro fertilization laboratory for the Rush Health System in Chicago -- say it is only a matter of time before someone announces that a human has been cloned. ''In my opinion,'' he said, 'ɺll it takes right now is time, money and talent.'' The only question is who will do it first, he added. It may be the two fertility experts who recently announced that they wanted to clone a human, Dr. Panayiotis Zavos of the Andrology Institute in Lexington, Ky., and Dr. Severino Antinori, a fertility doctor in Rome. Or it may be a relative unknown.

Academic scientists say they would not dare to think of cloning a human at this time. The very experiment would be so controversial that they would become scientific pariahs, said Dr. Alan H. DeCherney, chairman of the department of obstetrics and gynecology at the University of California in Los Angeles. ''Youɽ ruin your career,'' he said.

In the meantime, the House Energy and Commerce Subcommittee on Oversight Investigations will hold hearings on human cloning on Wednesday, with a witness list including ethicists and scientists.


Watch the video: reality shifting: WHAT ARE CLONES? (December 2022).