Sperm From Female Stem Cells

British scientists have created early-stage, human sperm from female stem cells, according to a news report in New Scientist magazine. It is claimed that the research will pave the way for same sex couples to have children that are genetically their own. However, other scientists are sceptical that this procedure would ever be possible.
Professor Karim Nayernia at the University of Newcastle initially fertilised mice with sperm derived from embryonic stem cells (ESCs) in 2006, which gave rise to seven pups, six of which survived. In more recent work, he took human male stem cells from bone marrow and formed 'spermatogonia', primitive sperm cells that can form mature sperm cells by going through a process called meiosis. Nayernia has now apparently done the same using human female stem cells, work that has yet to be published.
The next stage in the process would be to make these primitive sperm cells undergo meiosis, which Nayernia claims he has started to do. The result could be that female eggs are fertilised by 'female' sperm, thereby eradicating the need for male gametes. However, Dr Robin Lovell-Badge, a stem cell expert at the National Institute of Medical Research in London, does not think the approach will work. He told the Telegraph newspaper that the 'presence of two X chromosomes is incompatible with this. Moreover they need genes from the Y chromosome [from the male sperm] to go through meiosis. So they are at least double damned'. Safety issues have also been raised, since the mice pups in Nayernia's initial study had health problems.
A Brazilian team of scientists lead by Dr Irina Kerkis at the Butantan Institute in Sao Paolo also claim to have made sperm and eggs from male mouse ESCs, and are currently starting to take the work into human cells. The research brings hope to people dealing with infertility, a problem that affects one in six couples, although scientists say the process is still in its infancy and treatments are a long way off.
There is also potential to use 'induced pluripotent stem cells', stem cells derived from human skin cells, as a starting point for the process. This could enable gay men to donate skin cells that would be used to create stem cells from which eggs could be formed. The eggs could then be fertilised using sperm from his partner, and placed in a surrogate mother.
Greg Aharonian, a patent analyst in the US, is trying to patent the technology behind 'female' sperm and 'male' eggs. A self-proclaimed 'troublemaker', he wants to undermine the argument that marriage should remain heterosexual because its main purpose is procreation.
The controversial developments have provoked mixed responses in the UK and US. Mike Judge from the Christian Institute faith group says that 'children need male and a female role models'. Many religious groups still oppose gay marriage. Josephine Quintavalle, from the pro-life lobby group Comment on Reproductive Ethics, says: 'we are looking at absurd solutions to very obscure situations and not addressing the main issue. Nobody is interested in looking at what is causing infertility - social reasons such as obesity, smoking and age'.

Less Dud, More Stud Sperms

The University of Michigan's sperm sorter consists of a penny-size silicon chip divided into two channels. Semen is dripped onto one side, a saline solution on the other. Where the channels meet, the healthy, or motile, sperm swim over to the saline channel, leaving the dead or slow sperm behind. The healthy sperm are then collected for in vitro fertilization. University of Michigan scientists have developed a new technique to sort out the swimmers from the duds in semen, which could lead to a more efficient way for men who suffer from low sperm counts to make babies.

Current methods use centrifugation, which spins the sperm at very high speed. But the technique isn't efficient because live sperm are pelted with dead ones, causing a significant number of viable sperm to die in the separation. "We can harvest motile sperm from samples where there is a low number without causing any damage to the sperm," said team member Dr. Gary Smith, associate professor of obstetrics and gynecology at the University of Michigan Health System.

In men with healthy sperm counts, each ejaculation contains about 200 million to 400 million sperm. For these men, in vitro fertilization using centrifugal separation is relatively easy because it only takes 10 million to 20 million motile sperm to fertilize an egg in a petri dish. But men with low sperm counts have had less success. "For men with very low sperm count, these other techniques are often unable to recover any motile sperm," said Shuichi Takayama, assistant professor in the Biomedical Engineering program at the University of Michigan, where the new sorter is being developed. Other methods to pinpoint live sperm in a low sperm sample require a microscope and a lot of patience. The new sperm sorter may put an end to this laborious hand sorting. "It may mean that instead of having a well-trained technician, you could have one that is not so well-trained," said Dr. Mark Surrey, of the Southern California Reproductive Center in Beverly Hills.

So far the sorter has fared well in trials. In one test the team used a sample in which only 44 percent of the sperm was motile. After going through the sorter, the count of motile sperm went up to 98 percent. The sorter employs microfluidics, a branch of physics and biotechnology that examines the microscopic flow of fluids. Within the device everything is pushed downstream by gravity and surface tension. The Michigan team notes, however, that more tests are needed before the sorter becomes a mainstay in doctors' offices. Smith said he expects it will be ready for clinical use in one to two years.

Swiss experts say individuals with undetectable viral load and no STI cannot transmit HIV during sex

Swiss HIV experts have produced the first-ever consensus statement to say that HIV-positive individuals on effective antiretroviral therapy and without sexually transmitted infections (STIs) are sexually non-infectious. The statement is published in this week’s Bulletin of Swiss Medicine (Bulletin des médecins suisses). The statement also discusses the implications for doctors; for HIV-positive people; for HIV prevention; and the legal system.

The statement’s headline statement says that “after review of the medical literature and extensive discussion,” the Swiss Federal Commission for HIV / AIDS resolves that, “An HIV-infected person on antiretroviral therapy with completely suppressed viraemia (“effective ART”) is not sexually infectious, i.e. cannot transmit HIV through sexual contact.”

It goes on to say that this statement is valid as long as: the person adheres to antiretroviral therapy, the effects of which must be evaluated regularly by the treating physician, and the viral load has been suppressed (< 40 copies/ml) for at least six months, and there are no other sexually transmitted infections.

The article begins by stating that the Commission “realises that medical and biologic data available today do not permit proof that HIV-infection during effective antiretroviral therapy is impossible, because the non-occurrence of an improbable event cannot be proven. If no transmission events were observed among 100 couples followed for two years, for instance, there might still be some such events if 10,000 couples are followed for ten years. The situation is analogous to 1986, when the statement ‘HIV cannot be transmitted by kissing’ was publicised. This statement has not been proven, but after 20 years’ experience its accuracy appears highly plausible.”

For example, they note, Quinn and colleagues found that in sero-discordant couples the risk of transmission depended on the viral load of the HIV-positive partner, and refer also to a prospective study of 393 heterosexual sero-discordant couples from Castilla and colleagues found that there were no infections among partners of persons on antiretroviral therapy, compared to a rate of transmission of 8.6% among partners of untreated patients. They also note that transmission from mother to newborn also depends on the maternal viral load, and can be avoided by taking antiretroviral therapy.

They go on to assert that effective antiretroviral therapy eliminates HIV from genital secretions. They say that HIV RNA, measured in sperm, declines below the limits of detection on antiretroviral therapy, and that HIV RNA is also below the limits of female genital secretions is, as a rule, during effective antiretroviral therapy. “As a rule,” they write, “it rises after, not before, an increase in plasma viral load.” They also assert that although cell-associated viral genomes are present in genital secretions, even on antiretroviral therapy, these are not infectious virions since “HIV-containing cells in sperm lack markers of viral proliferations such as circular LTR-DNA.”

They note that the concentration of HIV RNA in sperm correlates with the risk of transmission and that “transmission risk declines towards zero with falling sperm viral load. These data indicate that the risk of transmission is greatly decreased by antiretroviral therapy.”

They add, however, several exceptions and caveats to the above statements:
After a few days or weeks of discontinuation of antiretroviral therapy, plasma viral load rises rapidly. There is at least one case report of transmission during this rebound.

In patients not on treatment, STIs such as urethritis or genital ulcer disease increase the genital viral load; it falls again after the STI is treated.

In a patient with urethritis, sperm viral load can rise slightly even while the patient is receiving effective treatment. This rise is small, however, much smaller that the rise observed in patients not on treatment.

They conclude the scientific part of the article by saying that: “During effective antiretroviral therapy, free virus is absent from blood and genital secretions. Epidemiologic and biologic data indicate that during such treatment, there is no relevant risk of transmission. Residual risk can not be scientifically excluded, but is, in the judgment of the Commission, negligibly small.”

Implications for doctors
The Commission then discusses the implications for doctor-patient discussions. It says, "the following information aims to communicate to doctors criteria allowing them to establish whether or not a patient can sexually transmit HIV.

HIV cannot be transmitted sexually if:
The HIV-positive individual takes antiretroviral therapy consistently and as prescribed and is regularly followed by his/her doctor.

Viral load is ‘undetectable’ and has been so for at least six months

The HIV-positive individual does not have any STIs."


Implications for HIV-positive people
The Commission states that an HIV-positive person in a stable relationship with an HIV-negative partner, who follows their antiretroviral treatment consistently and as prescribed and who does not have an STI, is "not putting their partner at risk of transmission by sexual contact."

"Couples must understand," they write, "that adherence will become omnipresent in their relationship when they decide not to use protection, and due to the importance of STIs, rules must be defined for sexual contacts outside of relationship."

"The same goes for people who are not in a stable relationship," they add. However due to the importance of STIs, use of condoms is still recommended.

They add that heterosexual women will have to consider eventual interactions between contraceptives and antiretrovirals before considering stopping using condoms.

They also say that insemination via sperm washing is no longer indicated when "antiretroviral treatment is efficient."

Implications for HIV prevention
The Commission says that it "is not for the time being, considering recommendations that HIV-positive individuals start treatment purely for preventative measures." Aside from the cost involved, they argue, it cannot be certain that HIV-positive people would be sufficiently motivated to follow, and apply to the letter, antiretroviral treatment on a long-term basis without medical indications. They note that poor adherence is likely to facilitate the development of resistance, and that, therefore, antiretroviral therapy as prevention is indicated only in "exceptional circumstances for extremely motivated patients."

The Commission also says that their statement should not change prevention strategies currently taking place in Switzerland. With the exception of stable HIV-positive couples where HIV-positivity and the efficacy of antiretroviral therapy can be established, measures to protect oneself must be followed at all times. "People who are not in a stable relationship must protect themselves," they note, "as they would not be able to verify whether their partner is positive or on efficient antiretroviral therapy."

Honour for creator of Dolly the sheep ‘is insult to science’

Former colleagues of Sir Ian Wilmut, the scientist widely credited as the creator of Dolly the cloned sheep, have called for the Queen to revoke his knighthood, describing the honour as an insult.

In a petition to Buckingham Palace, four former employees of the Roslin Institute, near Edinburgh, allege that Sir Ian is a “self-confessed charlatan” who “apparently lacks adequate scientific understanding”. The petition urges the Queen to “withhold, recall or reduce the Royal Assent from the knighthood of Professor Ian Wilmut”.

A letter adds: “We do feel very bitter that not only has our own work not been fully recognised but we appear to have been used . . . Wilmut’s knighthood is seen as the crowning insult to honest endeavour.”

Sir Ian, 63, who won global acclaim after being credited in 1996 with creating Dolly, the first mammal to be cloned from an adult cell, was knighted in the New Year Honours for services to science. His former colleagues claim that their objections to the knighthood are shared by numerous others. They add: “Roslin, the University of Edinburgh and Scotland are all tarnished with this grant. We beg reconsideration.”

The petition is signed by Prim Singh, a molecular biologist with a history of conflict with Sir Ian; Jeremy Brown, a former research scientist at Roslin; Pauline Ward, a former bio-informatician at the institute; and Douglas Currie, managing director of Roslin Nutrition, a private research company.

At an employment tribunal in 2006, Dr Singh claimed that he had been racially discriminated against by Professor Wilmut because he was Asian. Although he lost that claim, the tribunal found that he had been unfairly dismissed as head of nuclear programming at Roslin. All his allegations against Sir Ian personally were dismissed and are the subject of an appeal. During the hearing, Professor Wilmut was asked whether the statement “I did not create Dolly” was accurate; he said it was. He said he had appeared as lead author on the paper because of an arrangment with his colleague Keith Campbell, whom he said deserved “66 per cent” of the credit.

Dr Singh told Times Higher Education yesterday: “He has admitted he isn’t the brains behind Dolly, and to then go on and award him a knighthood reflects very badly on Scottish science.”

Sir Ian, who is now director of the Scottish Centre for Regenerative Medicine at Edinburgh University, said yesterday: “I am aware of the terms of the correspondence . . . I am aware also that the Queen’s Private Secretary has indicated that this is a matter in which her Majesty would not intervene.” In a letter to Dr Singh, the Queen’s Private Secretary said that recommendations for honours were the Prime Minister’s responsibility and the petition had been referred to the Cabinet Office.

Chimera embryos have right to life, say bishops

Human-animal hybrid embryos conceived in the laboratory - so-called “chimeras” - should be regarded as human and their mothers should be allowed to give birth to them, the Roman Catholic Church said yesterday. Under draft UK Government legislation to be debated by Parliament later this year, scientists will be given permission for the first time to create such embryos for research as long as they destroy them within two weeks. But the Catholic bishops of England and Wales, in a submission to the Parliamentary joint committee scrutinising the draft legislation, said that the genetic mothers of “chimeras” should be able to raise them as their own children if they wished.The bishops said that they did not see why these “interspecies” embryos should be treated any differently than others.

The wide-ranging draft Human Tissue and Embryo Bill, which aims to overhaul the laws on fertility treatment, will include sections on test tube babies, embryo research and abortion. Ministers say that the creation of animal-human embryos - created by injecting animal cells or DNA into human embryos or human cells into animal eggs - will be heavily regulated.They insist that it will be against the law to implant “chimeras” - named after the mythical creature that was half man and half animal - into a woman’s womb. The bishops, who believe that life begins at conception, said that they opposed the creation of any embryo solely for research, but they were also anxious to limit the destruction of such life once it had been brought into existence.

In their submission to the committee, they said: “At the very least, embryos with a preponderance of human genes should be assumed to be embryonic human beings, and should be treated accordingly.

“In particular, it should not be a crime to transfer them, or other human embryos, to the body of the woman providing the ovum, in cases where a human ovum has been used to create them.

“Such a woman is the genetic mother, or partial mother, of the embryo; should she have a change of heart and wish to carry her child to term, she should not be prevented from doing so.”

The draft Bill will also allow the screening of embryos for genetic or chromosomal abnormalities that might lead to serious medical conditions, disabilities, or miscarriage. It will permit doctors to check whether an embryo could provide a suitable tissue match for a sibling suffering from a life-threatening illness.

The Bill would abolish the requirement for fertility clinics to consider the need for a father when deciding on treatment. This means clinics will no longer be able to deny treatment to lesbians and single mothers.

The Catholic bishops said that most of the procedures covered by the Bill “should not be licensed under any circumstances”, principally on the grounds that they violate human rights.

Ooplasmic Transfer

Ooplasmic transfer is an experimental fertility technique that involves injecting a small amount of ooplasm from eggs of fertile women into eggs of women whose fertility is compromised. The modified egg is then fertilized with sperm and implanted in the uterus of the woman attempting to achieve pregnancy.

Children born from this procedure have been reported to possess cytoplasmic organelles called mitochondria from both their biological mother and the ooplasmic donor, a condition referred to as mitochondrial heteroplasmy. Because mitochondria carry their own sets of genes that are passed on to succeeding generations, the mixing of parent and cytoplasmic donor mitochondria might be considered to be a form of germline modification. However, the technique does not involve modification of particular genes and could not be used as part of any procedure to create "designer babies."

In 2001, researchers at St. Barnabas Hospital in New Jersey announced that they had used ooplasmic transfer to enable several women with impaired fertility to bear children. They described their work to the press as "the first case of human germline modification."

However, ooplasmic transfer is not germline genetic modification, or inheritable genetic modification (IGM), in the usual sense. It cannot be used to modify genes housed in the cell nucleus, which influence all traits except for those regulated by mitochondrial genes. But the procedure might be considered a form of IGM in that the mixed mitochondrial DNA would be passed on to all future generations.

On the other hand, some advocates of IGM have identified ooplasmic transfer as a technology whose development and use could be used to help erode popular resistance to IGM. Following the St. Barnabas announcement, the FDA notified all US fertility clinics known to be offering the procedure that further ooplasm transfer protocols could not proceed without FDA approval.

The FDA expressed concerns about this "de facto germ line gene transfer" technique, citing its potential to alter the germline, the medical risks associated with mitochondrial heteroplasmy, the high incidence of Turner's syndrome in fetuses reported in one study (2 of 13 reported pregnancies), and the paucity of animal studies and other pre-clinical data. A general consensus was reached at the meeting that more preclinical data would be necessary before FDA would allow further clinical trials involving ooplasm transfer to proceed.

Tainted Drugs Tied to Maker of Abortion Pill

A huge state-owned Chinese pharmaceutical company that exports to dozens of countries, including the United States, is at the center of a nationwide drug scandal after nearly 200 Chinese cancer patients were paralyzed or otherwise harmed last summer by contaminated leukemia drugs.

Chinese drug regulators have accused the manufacturer of the tainted drugs of a cover-up and have closed the factory that produced them. In December, China’s Food and Drug Administration said that the Shanghai police had begun a criminal investigation and that two officials, including the head of the plant, had been detained.

The drug maker, Shanghai Hualian, is the sole supplier to the United States of the abortion pill, mifepristone, known as RU-486. It is made at a factory different from the one that produced the tainted cancer drugs, about an hour’s drive away.

The United States Food and Drug Administration declined to answer questions about Shanghai Hualian, because of security concerns stemming from the sometimes violent opposition to abortion. But in a statement, the agency said the RU-486 plant had passed an F.D.A. inspection in May. “F.D.A. is not aware of any evidence to suggest the issue that occurred at the leukemia drug facility is linked in any way with the facility that manufactures the mifepristone,” the statement said.

When told of Shanghai Hualian’s troubles, Dr. Sidney M. Wolfe, a leading consumer advocate and frequent F.D.A. critic, said American regulators ought to be concerned because of accusations that serious health risks had been covered up there. “Every one of these plants should be immediately inspected,” he said.

The director of the Chinese F.D.A.’s drug safety control unit in Shanghai, Zhou Qun, said her agency had inspected the factory that produced mifepristone three times in recent months and found it in compliance. “It is natural to worry,” Ms. Zhou said, “but these two plants are in two different places and have different quality-assurance people.”

The investigation of the contaminated cancer drugs comes as China is trying to restore confidence in its tattered regulatory system. In the last two years, scores of people around the world have died after ingesting contaminated drugs and drug ingredients produced in China. Last year, China executed its top drug safety official for accepting bribes to approve drugs.

Shanghai Hualian is a division of one of China’s largest pharmaceutical companies, the Shanghai Pharmaceutical Group, which owns dozens of factories. Neither Shanghai Hualian nor its parent company would comment on the tainted medicine.

Last week, The New York Times asked the F.D.A. whether the Shanghai Pharmaceutical Group exported to the United States any drugs or pharmaceutical ingredients other than the abortion pill. But after repeated requests, the agency declined to provide that information; it did not cite a reason.

On at least two occasions in 2002, Shanghai Hualian had shipments of drugs stopped at the United States border, F.D.A. records show. One shipment was an unapproved antibiotic and the other a diuretic that had “false or misleading labeling.” Records also show that another unit of Shanghai Pharmaceutical Group has filed papers declaring its intention to sell at least five active pharmaceutical ingredients to manufacturers for sale in the United States.

One major pharmaceutical company, Pfizer, declined to buy drug ingredients from Shanghai Pharmaceutical Group because of quality-related issues, said Christopher Loder, a Pfizer spokesman. In 2006, Pfizer agreed to evaluate Shanghai Pharmaceutical Group’s “capabilities” as an ingredient supplier, but so far the company “has not met the standards required by Pfizer,” Mr. Loder said in a statement.

Because of opposition from the anti-abortion movement, the F.D.A. has never publicly identified the maker of the abortion pill for the American market. The pill was first manufactured in France, and since its approval by the F.D.A. in 2000 it has been distributed in the United States by Danco Laboratories. Danco, which does not list a street address on its Web site, did not return two telephone calls seeking comment.

Problems with the cancer drugs first surfaced last summer after leukemia patients received injections of one cancer drug, methotrexate. Afterward, patients experienced leg pain and, in some cases, paralysis. At the People’s Liberation Army No. 307 Hospital in Beijing, a 26-year-old patient, Miao Yuguang, was unable to stand up five days after being injected in the spine with the drug. “We were already unlucky to have this illness,” her father, Miao Futian, said of the leukemia. “Then we ran into this fake drug.”

The authorities recalled two batches of the drug, but issued only mild warnings because the cause of the problem was unclear. Officials with Shanghai Pharmaceutical Group stood by their products, saying that drug regulators investigating the plant had found no problems. But when another cancer drug made in the same factory — cytarabin hydrochloride — also began causing adverse reactions, investigators suspected contamination.

In September, health and drug officials announced that they had found that the two drugs were contaminated with vincristine sulfate, a third cancer drug, during production. After issuing a nationwide alert, the government announced a wider recall, and Shanghai’s drug agency sealed manufacturing units at the plant.

“Many people thought there was a problem with the hospitals,” said Zheng Qiang, director of the Center for Pharmaceutical Information and Engineering Research at Peking University. “It wasn’t until later that they discovered the problem was with the medicine.”

Chinese media attention on the case has surged, after a terse statement by China’s drug agency in December, accusing Hualian company officials of a systematic cover-up of violations at the facility that made the drugs.

Family members at the No. 307 hospital have counted 53 victims in Beijing, and say they were told that there were least 193 victims nationwide. It is unclear how many were paralyzed, because the authorities have not released an official figure. Relatives have joined to share information and advocate for the victims. Based on interviews with several families in Beijing and Shanghai, it appears that about half of those injected still cannot walk.

Wu Jianhua said his daughter, Wu Xi, 15, collapsed on her way to school after an injection in August. “We thought she was tired,” Mr. Wu said. Doctors now say she may never walk without a cane, he said.

Last week, on a window near the gate of the closed plant was a notice from the Shanghai Food and Drug Administration, dated Sept. 8, accusing the plant of “producing substandard medicine that poses major risks of causing serious harm to human health.” It identified a company official, Gu Yaoming, as the “person responsible” for the plant.

Records show Mr. Gu also met with the United States F.D.A. inspectors last May as part of the routine inspection of the plant that makes RU-486.

Reached by telephone, Mr. Gu declined to describe his role at the two plants. “I cannot answer your questions,” he said.

A spokeswoman for China’s Food and Drug Administration, Yan Jiangying, said that Shanghai Hualian had been stripped of its license to produce antitumor drugs, but that this action did not affect RU-486.

Hualian is the latest in a string of tainted medicine cases that have undermined confidence in the safety of drugs here. In 2006, at least 18 Chinese died after an intravenous drug used to treat liver disease, Armillarisin A, was laced with diethylene glycol, a toxic chemical used in some antifreeze. Also in 2006, at least 14 Chinese died after taking a Chinese antibiotic, Xinfu, which was not properly sterilized during production. And more than a hundred people died in Panama after taking cold medicine containing a mislabeled and toxic chemical from China.

In each of these cases, the manufacturer failed to follow good manufacturing practices to ensure the final product was safe.

Describing the cover-up at the factory, Ms. Zhou, the regulator who led the investigation, said workers did not tell investigators that vincristine sulfate — a drug too toxic for use in spinal injections — had been stored in a refrigerator with materials for other drugs.

“At the time, we didn’t think they had lied to us,” Ms. Zhou said. The deception sent investigators on a two-month hunt for other possible causes of the adverse reactions. “If they had been open about the vincristine sulfate in the beginning, maybe fewer people would have been harmed,” she added.

While regulators have accused factory employees of a systematic cover-up of violations in production, they have not said whether superiors at Shanghai Pharmaceutical were aware of it. “We’ll have to wait until the police investigation is finished” to make more details public, said Ms. Yan, the drug agency spokeswoman.

Mr. Zheng at Peking University said that producing multiple drugs in a single workshop was risky, but that some Chinese companies saw it as a way to save money. “It was an accident,” he said of the Hualian case. “But it was bound to happen.”