Having a twin brother could put a woman at a lasting disadvantage, and exposure to his testosterone before birth may play a role, a new study suggests.

Researchers analysed data on 13 800 twin births in Norway between 1967 and 1978. Compared to women with a twin sister, those with a twin brother were 15% less likely to finish high school and nearly 4% less likely to complete college. They had earned almost 9% less by their early 30s.

Biology of sex differences

Their fertility rates were also nearly 6% lower and they were nearly 12% less likely to marry, according to the study published March 18 in the Proceedings of the National Academy of Sciences.

“This is the first study to track people for more than 30 years, from birth through schooling and adulthood, to show that being exposed in utero to a male twin influences important outcomes in their twin sister, including school graduation, wages and fertility rates,” said corresponding author Krzysztof Karbownik. He’s an economist and research associate at Northwestern University’s Institute for Policy Research (IPR) in Evanston, Illinois.

The study supports a theory that females in male-female twin pairs are exposed to more testosterone in the womb through the amniotic fluid or through the mother’s bloodstream, and that this could affect their behaviour.

“This is a story about the biology of sex differences,” study co-author David Figlio said in a university news release. Figlio is an IPR fellow and dean of Northwestern’s School of Education and Social Policy.

During key stages of foetal development, steroids produced by the ovaries and testes, including testosterone, help establish differences between boys and girls. Smaller studies have suggested that exposure to opposite-sex hormones can have lasting effects on behaviour and other traits, though being raised alongside a twin brother might explain any differences, too.

Passive exposure to prenatal testosterone

To address that theory, researchers repeated their analyses focusing only on girls who were raised as singletons, because their twin died shortly after birth. The results were the same, suggesting that the long-term effects stemmed from the womb.

“We are not showing that exposed females are necessarily more ‘male-like’, but our findings are consistent with the idea that passive exposure to prenatal testosterone changes women’s education, labour market, and fertility outcomes,” Figlio explained.

One co-author cautioned that cultural specifics could affect the results of this study.

Christopher Kuzawa, an IPR fellow and Northwestern anthropology professor, said the findings are specific to Norwegian society at one timeframe and may not apply equally across other societies or cultural settings.

“For instance, if gender norms change within a society, acceptance of a wider array of behaviours could minimise later effects on outcomes like school completion or entering a marriage,” he said in the news release.

“Basically we find that there are some very interesting long-term biological effects of being a sister to a twin brother,” Kuzawa said. “But whether we view those effects as ‘positive’ or ‘negative’ may be culturally dependent.”

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Doctors have found a cure for "bubble boy disease," according to research published today in the New England Journal of Medicine.

The inherited immune system disorder is technically called X-linked severe combined immunodeficiency (SCID), and it affects mostly boys. Bubble boy disease is the most common SCID condition, and the frequency of the illness isn't known. However, the National Institutes of Health (NIH) estimates that it affects at last one in every 50,000 to 100,000 babies.

So why is X-linked SCID nicknamed "bubble boy disease"? If a child tests positive for the disease at birth, they can't necessarily do activities that other children can do. A child with X-linked SCID can't fight off infections the way a healthy child can because their immune system doesn't function properly. They have to live inside a "bubble" to keep from coming into contact with germs that wouldn't hurt a healthy person but could kill someone whose immune system doesn't work. For example, David, pictured above, had to live in this plastic "bubble" while doctors searched for a cure for his condition.

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Another example is Ja'Ceon Golden, who was born in 2016 and wasn't able to leave the hospital after he tested positive for the condition. He had to live in isolation to minimize his risk of getting an infection. Golden's aunt and caretaker Dannie Hawkins spoke to CNN about what happened when she heard of her nephew's diagnosis. "At that moment, all kinds of things were going through my mind," she said.

But Golden participated in the trial that led to the newly published research, and the therapy the doctors discovered has cured him. He's now able to go outdoors. Hawkins spoke to CNN about getting to take her nephew outdoors for the first time in his life. "Just to see him look at the cars and just smile: It was a blessing," she said.

Bubble boy disease is caused by mutations in a gene called IL2RG on the X chromosome. "The IL2RG gene provides instructions for making a protein that is critical for normal immune system function. This protein is necessary for the growth and maturation of developing immune system cells called lymphocytes," the NIH explains.

Lymphocytes have three jobs: The first is to protect the body from harmful invaders. They are also in charge of making antibodies, which are blood proteins that identify toxins that need to be destroyed. Lastly, they are tasked with regulating the immune system. "Mutations in the IL2RG gene prevent these cells from developing and functioning normally. Without functional lymphocytes, the body is unable to fight off infections," the NIH says.

In other words, an infection that most of us would be able to survive could kill an infant with bubble boy disease, and this is why children with the illness are kept in isolated areas. Golden's aunt told CNN she got in the habit of constantly cleaning her hands to minimize the risk of exposing her nephew to germs. She also heated the water he would bathe in ahead of bath time so that the water he was in would be sterile.

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The new cure for bubble boy disease is a gene therapy technique that works to reconstruct the immune system. Doctors take stem cells from the bone marrow of a child with the condition, insert a normal IL2RG gene into those cells, then infuse those cells back into the child. The whole process works in about 10 days, lead study author Ewelina Mamcarz, MD, of St. Jude Children's Research Hospital's bone marrow transplant department, tells Health. During those 10 days, the patients are given two low doses of chemotherapy.

Eight infants with bubble boy disease were given the treatment from September 2016 to March 2018. "All the patients were alive and well as outpatients at a median follow-up of 16.4 months and had normal growth with respect to weight and height," the new research says. Dr. Mamcarz and her co-authors are very optimistic about the trail's results. "This approach led to broad immune reconstitution," the report says.

"We were able to fully restore the immune system on most of the patients in this study. That means they recovered all three types of immune cells," Dr. Mamcarz says.

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While the treatment has given babies like Golden improved quality of life, questions remain about the long-term benefits of the cure.

"The question will become: Will it be a durable cure? Will it last 10, 20, 50 years for these children? And only time will tell," James Downing, MD, president of St. Jude Children's Research Hospital, told CNN. "This is the first time we've seen a total reconstruction of the immune system, which has provided the ability for these children to get out of isolation. So we're comfortable, I think, at this point, saying that this is a cure. Only time will say: Will this be a durable, lifelong cure?"

For Hawkins, the cure is nothing less than a remarkable step up from the life her nephew had pre-treatment, a life that meant the closest he got to fresh air was a hospital window. "All he could do was see the cars out the window," she told CNN. "I would put him to the hospital window so he could see people walk and cars go by."

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A little bone scientists thought was being lost to evolution seems to be making a comeback, say experts.

New research sheds light on how a hepatitis B viral protein stimulates the expansion of immune cells that impair antiviral responses, according to a study published April 18 in the open-access journal PLOS Pathogens by Haitao Guo of the Indiana University School of Medicine, Bin Wang and Jiming Zhang of Fudan University, and colleagues. The findings potentially explain how the hepatitis B virus (HBV) establishes and maintains chronic infection, and could lead to the development of novel therapeutic strategies.

Researchers at the University of California, Davis, recently investigated levels of methylmercury in a small sampling of commercial dog foods and found good news for dog owners. Of the 24 diets tested, only three were positive for low concentrations of total mercury, and only one of those contained detectable methylmercury. The study was published in Topics in Companion Animal Medicine.

A powerful computational study of southern California seismic records has revealed detailed information about a plethora of previously undetected small earthquakes, giving a more precise picture about stress in the earth’s crust. A new publicly available catalog of these findings will help seismologists better understand the stresses triggering the larger earthquakes that occasionally rock the region.

They were born without a working germ-fighting system, every infection a threat to their lives. Now eight babies with “bubble boy disease” have had it fixed by a gene therapy made from one of the immune system’s worst enemies – HIV, the virus that causes AIDS.

South Africa’s ‘Bubble Boy’ receives gene therapy in the US

A study out Wednesday details how scientists turned this enemy virus into a savior, altering it so it couldn’t cause disease and then using it to deliver a gene the boys lacked.

“This therapy has cured the patients,” although it will take more time to see if it’s a permanent fix, said Dr Ewelina Mamcarz, one of the study leaders at St. Jude Children’s Research Hospital in Memphis.

Omarion Jordan, who turns 1 later this month, had the therapy in December to treat severe combined immunodeficiency syndrome, or SCID.

“For a long time we didn’t know what was wrong with him. He just kept getting these infections,” said his mother, Kristin Simpson. Learning that he had SCID “was just heartbreaking… I didn’t know what was going to happen to him.”

Omarion now has a normal immune system. “He’s like a normal, healthy baby,” Simpson said. “I think it’s amazing.”

Study results were published by the New England Journal of Medicine. The treatment was pioneered by a St. Jude doctor who recently died, Brian Sorrentino.

Genetic flaw

SCID is caused by a genetic flaw that keeps the bone marrow from making effective versions of blood cells that comprise the immune system. It affects 1 in 200 000 newborns, almost exclusively males. Without treatment, it often kills in the first year or two of life.

“A simple infection like the common cold could be fatal,” Mamcarz said.

The nickname “bubble boy disease” comes from a famous case in the 1970s – a Texas boy who lived for 12 years in a protective plastic bubble to isolate him from germs. A bone marrow transplant from a genetically matched sibling can cure SCID, but most people lack a suitable donor. Transplants also are medically risky – the Texas boy died after one.

Doctors think gene therapy could be a solution. It involves removing some of a patient’s blood cells, using the modified HIV to insert the missing gene, and returning the cells through an IV. Before getting their cells back, patients are given a drug to destroy some of their marrow so the modified cells have more room to grow.

When doctors first tried it 20 years ago, the treatment had unintended effects on other genes, and some patients later developed leukemia. The new therapy has safeguards to lower that risk.

No lasting effects

A small study of older children suggested it was safe. The new study tried it in infants, and doctors are reporting on the first eight who were treated at St. Jude and at UCSF Benioff Children’s Hospital San Francisco.

Within a few months, normal levels of healthy immune system cells developed in seven boys. The eighth needed a second dose of gene therapy but now is well, too. Six to 24 months after treatment, all eight are making all the cell types needed to fight infections, and some have successfully received vaccines to further boost their immunity to disease.

No serious or lasting side effects occurred.

Omarion is the 10th boy treated in the study, which is ongoing. It’s sponsored by the American Lebanese Syrian Associated Charities, the California Institute of Regenerative Medicine, the Assisi Foundation of Memphis and the federal government.

“So far it really looks good,” but patients will have to be studied to see if the results last, said Dr Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, which helped develop the treatment. “To me, this looks promising.”

Rights to it have been licensed by St. Jude to Mustang Bio. Doctors say they have no estimate on what it might cost if it does become an approved treatment. They say they also hope to try it for more common problems such as sickle cell disease.

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A breakthrough study by South African researchers, published in the Journal of Infectious Diseases in November last year, found that one of the country’s most commonly-used injectable contraceptives, Depo-Provera, could increase women’s chances of contracting tuberculosis (TB).

The study, led by Professor Keertan Dheda and Dr Michele Tomasicchio at the University of Cape Town’s (UCT) Centre for Lung Infection and Immunity, recruited women from Cape Town and looked at Depo-Provera and norethisterone enanthate (NET-EN) – two different injectable contraceptives commonly used in South Africa.

They found that Depo-Provera down-regulates immune function genes associated with protection against TB, and up-regulates certain cell types that suppress the immune system. The data also showed that, unlike Depo-Provera, norethisterone does not increase TB pathogenesis.

Injectable contraceptives are widely used across sub-Saharan Africa and are the birth control choice of over 16 million women in the region. According to the World Health Organization (WHO), some of the main reasons for their popularity include “their effectiveness, their simple re-injection schedule every two or three months, depending on the brand, and their sustainability for discreet use”.

Depo-Provera, HIV & TB

The growing concern of this contraceptive stems from a 2018 study of clinical data that found that Depo-Provera may increase women’s chances of contracting HIV by up to 40%. This is because the injection contains the synthetic hormone medroxyprogesterone acetate (MPA), which acts as an immunosuppressant.

The review revealed how MPA could affect the body’s immune system at a molecular and cellular level and increase the risk of acquiring HIV. In this study, NET-EN did, however, not increase women’s risk of contracting HIV.

Professor Dheda and Dr Tomasicchio considered the prevalence of TB in sub-Saharan Africa and the fact that it remains the top infectious disease killer globally, and realised the necessity of investigating whether Depo-Provera could also increase the risk of TB infection.

Policy change needed

Dr Tomasicchio would like to see the study results, along with those of future studies, drive a chance in policy surrounding the use of Depo-Provera in South Africa. “My ultimate aim is to make sure that women are aware of the dangers of using [Depo-Provera], particularly in the context of sub-Saharan Africa,” he said, adding that government clinics in South Africa – and elsewhere – should move over to NET as it is the safer choice. 

On average, injectables are the contraceptive choice in 25% of cases in South Africa, but it is used in up to 85% of KwaZulu-Natal’s rural clinics.

However, despite the studies’ findings, the government is still reluctant to change policies since Depo-Provera is cheaper to manufacture and maintain. It also works on a three-monthly reinjection schedule, while NET-EN must be administered every two months.

Dr Tomasicchio says he plans to pursue this study further to gain a better understanding of why and how MPA actually drives TB pathogenesis. He also hopes that the mounting evidence of these studies will be taken to heart by the South African government and that policy changes will be made sooner rather than later. 

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