I was adopted, I know the trauma it can inflict

On Wednesday, as the Supreme Court heard oral arguments from state attorneys seeking to uphold Mississippi’s 15-week abortion ban, Justice Amy Coney Barrett kept getting at one question: Why was abortion necessary, when women who do not want to be mothers can simply give their babies up for adoption?

As an adoptee myself, I was floored by Justice Barrett’s assumption that adoption is an accessible and desirable alternative for women who find themselves unexpectedly pregnant. She may not realize it, but what she is suggesting is that women don’t need access to abortion because they can simply go do a thing that is infinitely more difficult, expensive, dangerous and potentially traumatic than terminating a pregnancy during its early stages.

As an adoptive mother herself, Justice Barrett should have some inkling of the complexities of adoption and the toll it can inflict on children, as well as birth mothers. But she speaks as if adoption is some kind of idyllic fairy tale. My own adoption actually was what many would consider idyllic. I was raised by two adoptive parents, Alice and Terry, from the time I was an infant, and grew up in a home where I knew every day that I was loved. A few years ago, I found my biological mother, Maria, and three siblings I didn’t know I had via a DNA test and Facebook.

The first time I spoke to Maria on the phone — she lives in Alabama, not too far from my parents, and I live in Brooklyn — she apologized repeatedly for giving me up and told me she loved me and that I would always be family. “You are blood,” she would say later. I told her, and continue to tell her, every time she brings it up, that the apology is unnecessary. I had a wonderful childhood and I believe she had made the right decision. But she remains heartbroken about the years we missed together.

Damon Winter/The New York Times

Both Maria and my mom, Alice, oppose abortion on religious grounds. My mom is white and Southern Baptist; Maria is Hispanic and Pentecostal. Both like to point to me to justify their beliefs, saying that had Maria gotten an abortion, I would not exist. It’s a familiar argument: The anti-abortion movement likes to invoke Nobel Prize winners who might never have materialized, or potential adoptees who might have cured cancer, if they hadn’t been aborted at eight weeks.

I’m no Nobel Prize winner, but I still resent being used as a political football by the right. I believe that abortion is a form of health care, and that every woman should have access to it if she needs it. But perhaps more than that, I resent the suggestion by people like Justice Barrett that adoption is a simple solution, and I resent it on behalf of Maria, who found the choice she made traumatizing and still feels that pain, 44 years later. Even when an adoption works out well, as it did in my case, it is still fraught.

When I echo Maria in saying that she “gave me up,” the language always rankles adoptive parents, because it introduces an unpleasant complexity — implying that my birth mother was not completely happy with her choice. Or worse, that it made her miserable. But that is sometimes the case, even when adoption is the best option for all involved. Adoption is not always an unalloyed good. It’s a complicated choice in a situation that has no right or wrong answer.

If the court overturns Roe v. Wade, many women will be forced to give birth to children they did not want or did not feel that they could afford to support. While pregnant, they will undergo the bonding with a child that happens by biological design as an embryo develops into a living, breathing, conscious human. And then that child will be taken away.

The right likes to suggest that abortion is a traumatic experience for women — a last resort, a painful memory. But adoption is often just as traumatic as the right thinks abortion is, if not more so, as a woman has to relinquish not a lump of cells but a fully formed baby she has lived with for nine months.

I’m a mother myself, to an adorable 6-year-old self-proclaimed Fortnite expert, and as is often the case, I did not know I was pregnant with him until the usual symptoms appeared a few weeks into the pregnancy. As anyone who has gestated a human will tell you, there is a vast difference between the fourth week of pregnancy and the 40th. By the 40th, you’re familiar with your baby’s regular rhythms of kicking and moving. When I awoke, my son would wake up shortly after and I’d feel him turning and stretching, or less pleasantly, jamming his precious little foot into what felt like my cervix. This is one of the paradoxes of pregnancy: Something alien is usurping your body and sapping you of nutrition and energy, but you’re programmed to gleefully enable it and you become desperately protective of it. It’s a kind of biological brainwashing. And this often happens whether you want to be a parent or not.

Justice Barrett is well aware of the kind of biological brainwashing that occurs during pregnancy; she gave birth to five children. And yet she blithely seems to assume that a mother can simply choose not to bond with the child she’s gestating solely on the basis that she is not ready to be a mother or believes that she is unable to provide for the child. She assumes that the mother will be supported financially and otherwise, throughout the pregnancy, even in a country where maternal mortality statistics are abysmal. And she assumes that children surrendered for adoption will find a home, and not a bed in the foster care system. She probably assumes these things because she cannot fathom being in this position herself. These are assumptions that stem from the privilege of being financially secure, having never needed an abortion, and perhaps the assumption that women who do have done something wrong and must face the consequences.

In my experience, some on the right believe that the trauma adoption inflicts is a consequence of irresponsibility. But unexpected pregnancy is not a de facto function of bad decision making. It can be a failure of contraception, the product of a rape, a mistaken belief that a woman is infertile. There is no justifiable reason to inflict harm on women and the babies they might produce in any of these situations, regardless of judgment.

The trauma doesn’t just affect mothers, either. Researchers have a term for what children who are adopted, even as infants, may suffer from later in life: relinquishment trauma. The premise is that babies bond with their mothers in utero and become familiar with their behaviors. When their first caretaker is not the biological mother, they register the difference and the stress of it has lasting effects.

I probably got off easy in that respect, in part because I did spend a few months with my biological mother before I was adopted, but that had the unintended effect of traumatizing my older siblings, who remember me as a baby who was there, and then suddenly was gone. This was driven home to me by my older sister Bobbi, whose first encounter with me was over Facebook. “All I can say is I remember you,” she wrote. “I have loved you and missed you my entire life.”

What Justice Barrett and others are suggesting women do in lieu of abortion is not a small thing. It is life changing, irrevocable, and not to be taken lightly. It often causes trauma, even when things work out, and it’s a disservice to adoptees and their families, biological and adopted, to pretend otherwise in service of a neat political narrative.

(Source: NYT)

Did you know that a coronavirus epidemic hit 20,000 years ago?

Scientists say that a few dozen human genes rapidly evolved in ancient East Asia to thwart coronavirus infections. Those genes could be crucial to today’s pandemic.

Researchers have found evidence that a coronavirus epidemic swept East Asia some 20,000 years ago and was devastating enough to leave an evolutionary imprint on the DNA of people alive today.

The new study suggests that an ancient coronavirus plagued the region for many years, researchers say. The finding could have dire implications for the COVID-19 pandemic if it is not brought under control soon through vaccination.

“It should make us worry,” said David Enard, an evolutionary biologist at the University of Arizona who led the study, which was published on Thursday in the journal Current Biology. “What is going on right now might be going on for generations and generations.”

Until now, researchers could not look back very far into the history of this family of pathogens. Over the past 20 years, three coronaviruses have adapted to infect humans and cause severe respiratory disease: COVID-19, SARS and MERS. Studies on each of these coronaviruses indicate that they jumped into our species from bats or other mammals.

Over the past 20 years, three coronaviruses have adapted to infect humans and cause severe respiratory disease: COVID-19, SARS and MERS. (Photo: AP)

Four other coronaviruses can also infect people, but they usually cause only mild colds. Scientists did not directly observe these coronaviruses becoming human pathogens, so they have relied on indirect clues to estimate when the jumps happened. Coronaviruses gain new mutations at a roughly regular rate, and so comparing their genetic variation makes it possible to determine when they diverged from a common ancestor.

The most recent of these mild coronaviruses, called HCoV-HKU1, crossed the species barrier in the 1950s. The oldest, called HCoV-NL63, may date back as far as 820 years.

But before that point, the coronavirus trail went cold – until Enard and his colleagues applied a new method to the search. Instead of looking at the genes of the coronaviruses, the researchers looked at the effects on the DNA of their human hosts.

Over generations, viruses drive enormous amounts of change in the human genome. A mutation that protects against a viral infection may well mean the difference between life and death, and it will be passed down to offspring. A lifesaving mutation, for example, might allow people to chop apart a virus’s proteins.

But viruses can evolve, too. Their proteins can change shape to overcome a host’s defences. And those changes might spur the host to evolve even more counteroffensives, leading to more mutations.

When a random new mutation happens to provide resistance to a virus, it can swiftly become more common from one generation to the next. And other versions of that gene, in turn, become rarer. So if one version of a gene dominates all others in large groups of people, scientists know that is most likely a signature of rapid evolution in the past.

In recent years, Enard and his colleagues have searched the human genome for these patterns of genetic variation in order to reconstruct the history of an array of viruses. When the pandemic struck, he wondered whether ancient coronaviruses had left a distinctive mark of their own.

He and his colleagues compared the DNA of thousands of people across 26 different populations around the world, looking at a combination of genes known to be crucial for coronaviruses but not other kinds of pathogens. In East Asian populations, the scientists found that 42 of these genes had a dominant version. That was a strong signal that people in East Asia had adapted to an ancient coronavirus.

But whatever happened in East Asia seemed to have been limited to that region. “When we compared them to populations around the world, we couldn’t find the signal,” said Yassine Souilmi, a postdoctoral researcher at the University of Adelaide in Australia and a co-author of the new study.

The scientists then tried to estimate how long ago East Asians had adapted to a coronavirus. They took advantage of the fact that once a dominant version of a gene starts being passed down through the generations, it can gain harmless random mutations. As more time passes, more of those mutations accumulate.

Enard and his colleagues found that the 42 genes all had about the same number of mutations. That meant that they had all rapidly evolved at about the same time. “This is a signal we should absolutely not expect by chance,” Enard said.

They estimated that all of those genes evolved their antiviral mutations sometime between 20,000 and 25,000 years ago, most likely over the course of a few centuries. It’s a surprising finding, since East Asians at the time were not living in dense communities but instead formed small bands of hunter-gatherers.

Aida Andres, an evolutionary geneticist at the University College London who was not involved in the new study, said she found the work compelling. “I’m quite convinced there’s something there,” she said.

Still, she didn’t think it was possible yet to make a firm estimate of how long ago the ancient epidemic took place. “The timing is a complicated thing,” she said. “Whether that happened a few thousand years before or after – I personally think it’s something that we cannot be as confident of.”

Scientists looking for drugs to fight the new coronavirus might want to scrutinize the 42 genes that evolved in response to the ancient epidemic, Souilmi said. “It’s actually pointing us to molecular knobs to adjust the immune response to the virus,” he said.

Anders agreed, saying that the genes identified in the new study should get special attention as targets for drugs. “You know that they’re important,” she said. “That’s the nice thing about evolution.”

By Carl Zimmer © The New York Times

This article originally appeared in The New York Times.

(Source: CNA Lifestyle)

Neanderthal genes increase risk of serious Covid-19, study claims

 Strand of DNA inherited by modern humans is linked to likelihood of falling severely ill

Modern humans and Neanderthals could be forgiven for having other issues on their minds when they interbred in the stone age. But according to researchers, those ancient couplings laid a grim foundation for deaths around the world today.

Scientists have claimed that a strand of DNA that triples the risk of developing severe Covid-19 was passed on from Neanderthals to modern humans. The genetic endowment, a legacy from more than 50,000 years ago, has left about 16% of Europeans and half of south Asians today carrying these genes.

The origins of the risk genes came to light when scientists in Sweden and Germany compared the DNA of very sick Covid-19 patients with that from Neanderthals and their mysterious sister group, the Denisovans. The stretch of DNA that makes patients more likely to fall seriously ill closely matched that collected from a Neanderthal in Croatia.

“I almost fell off my chair because the segment of DNA was exactly the same as in the Neanderthal genome,” Hugo Zeberg, an assistant professor at the Karolinska Institute in Stockholm, told the Guardian.

An exhibit at the Neanderthal museum in Krapina, Croatia. A strand of DNA increasing the risk of developing severe Covid-19 has been inherited from the Neanderthals, scientists believe. Photograph: Nikola Solic/Reuters/Corbis

Zeberg and his co-author, Svante Pääbo, director of the Max Planck Institute of Evolutionary Anthropology in Leipzig, suspect the Neanderthal genes have persisted in modern humans because they were once beneficial, perhaps helping to fight off other infections. Only now – when faced with a new infection – has their downside been exposed.

It is unclear how the genes may worsen Covid-19, but one gene plays a role in the immune response and another has been linked to the mechanism the virus uses to invade human cells. “We are trying to pinpoint which gene is the key player, or if there are several key players, but the honest answer is that we don’t know which are critical in Covid-19,” Zeberg said.

According to the study, published in Nature, the cluster of genes on chromosome three are most commonly found in Bangladesh, where 63% of the population carry at least one copy of the DNA sequence.

“The genes in this region may well have protected the Neanderthals against some other infectious diseases that are not around today. And now, when we are faced with the novel coronavirus these Neanderthal genes have these tragic consequences,” Pääbo said.

The researcher, who led the international team that first deciphered the Neanderthal genome in 2010, said his “rough estimate” was that about 100,000 “additional” people have died so far in the current pandemic due to the genetic contribution from Neanderthals.

Beyond the Covid-19 risk genes, the Neanderthals have bequeathed other genes to modern humans. Some increase sensitivity to pain, while others reduce the risk of miscarriages. “Some are beneficial and some are detrimental,” Zeberg said. “This has been a double-edged sword.”

But Mark Maslin, a professor at UCL and author of the book The Cradle of Humanity, cautioned that the work risked oversimplifying the causes and impact of the pandemic. “Covid-19 is a complex disease, the severity of which has been linked to age, gender, ethnicity, obesity, health, virus load among other things,” he said.

“This paper links genes inherited from Neanderthals with a higher risk of Covid-19 hospitalisation and severe complications. But as Covid-19 spreads around the world it is clear that lots of different populations are being severely affected, many of which do not have any Neanderthal genes.

“We must avoid simplifying the causes and impact of Covid-19, as ultimately a person’s response to the disease is about contact and then the body’s immunity response, which is influenced by many environmental, health and genetic factors.”

(Source: The Guardian)

A letter to… my daughter who has 47 chromosomes

‘You say little, but your presence is immense. You reinforce the essential simplicities of life’

Almost 30 years ago, you exploded into our lives. Exploded is an appropriate term because we had no warning about your condition. It is fair to say that I was devastated. I felt I had been catapulted into a world in which I did not want to belong.

My early memories of that time are painful. I remember a nursing assistant in the hospital picking you up from your cot without permission and announcing, “Ooh, I love Down’s babies!” Well-wishers looked at me pitifully as they asked, “Didn’t you have the test?”

They were dark times and it was not an easy transition, but your older sister, who was two when you were born, welcomed and adored you. Your younger brother was born two years later and then, after three more years, there was another sister for you. Family life was chaotic. There were a lot of fun times, but also embarrassment and frustration, such as the time you took off your clothes in a department store, or flushed your sister’s makeup down the toilet.

 ‘My early memories of that time are painful.’ Image posed by models. Illustration: Guardian Design/Getty

Your learning disability is such that you have no spontaneous language and require 24-hour supervision and support. Your additional needs demand a rigid structure and routine.

Your brother and sisters have now grown up and live in their own homes. Your dad and I got divorced, an unfortunate casualty, in part, of the pressures of raising a disabled child. You are living with me, still enjoying Postman Pat and Disney.

I wonder how you make sense of all the changes? I know your quiet acceptance masks a much deeper understanding of human nature than any of us could hope to achieve. Your dad and I enjoy a good relationship now and he continues to be a big part of your life. Your siblings are always popping in for an audience, and an essential hug from you. You say little, but your presence is immense. You are their counsellor and their mentor. For them, you reinforce the essential simplicities of life, things we often lose in the chaos and mundanity of everyday existence.

The positive contribution you have brought to our lives is immeasurable, and that extra chromosome I so despised in the early days of your life is now revered, with gratitude, as an integral feature of the wonderful person to whom it belongs: you.

You are the glue that binds our unique, amazing family together. I feel privileged to be your mum.

(Source: The Guardian)

First human-monkey chimera raises concern among scientists

Researchers reprogrammed human cells before injecting them in the monkey embryo

Efforts to create human-animal chimeras have rebooted an ethical debate after reports emerged that scientists have produced monkey embryos containing human cells.

A chimera is an organism whose cells come from two or more “individuals”, with recent work looking at combinations from different species. The word comes from a beast from Greek mythology which was said to be part lion, part goat and part snake.

The latest report, published in the Spanish newspaper El País, claims a team of researchers led by Prof Juan Carlos Izpisúa Belmonte from the Salk Institute in the US have produced monkey-human chimeras. The research was conducted in China “to avoid legal issues”, according to the report.

Chimeras are seen as a potential way to address the lack of organs for transplantation, as well as problems of organ rejection. Scientists believe organs genetically matched to a particular human recipient could one day be grown inside animals. The approach is based on taking cells from an adult human and reprogramming them to become stem cells, which can give rise to any type of cell in the body. They are then introduced into the embryo of another species.

Izpisúa Belmonte and other scientists have previously managed to produce both pig embryos and sheep embryos which contain human cells, although the proportions are tiny: in the latter case, researchers estimate that only one cell in 10,000 was human. Pig-human and sheep-human chimeras are attractive in part because pigs and sheep have organs about the right size for transplantation into humans.

 The human-monkey chimeras have reportedly only been allowed to develop for a few weeks. Photograph: Xinhua/Barcroft Images

Details of the work reported this week are scarce: Izpisúa Belmonte and colleagues did not respond to requests for comment.

However Alejandro De Los Angeles, from the department of psychiatry at Yale University, said it was likely monkey-human chimeras were being developed to explore how to improve the proportion of human cells in such organisms. “Making human-monkey chimeras could teach us how to make human-pig chimeras with the hope of making organs for transplantation,” he said. “It could teach us which types of stem cells we should be using, or other ways of enhancing what’s called ‘human chimerism levels’ inside pigs.”

De Los Angeles pointed out that, as with previous work in pigs and sheep, the human-monkey chimeras have reportedly only been allowed to develop for a few weeks – ie before organs actually form.

Prof Robin Lovell-Badge, a developmental biologist from London’s Francis Crick Institute, agreed. “I don’t think it is particularly concerning in terms of the ethics, because you are not taking them far enough to have a nervous system or develop in any way – it’s just really a ball of cells,” he said.

But Lovell-Badge added that if chimeras were allowed to develop further, it could raise concerns. “How do you restrict the contribution of the human cells just to the organ that you want to make?” he said. “If that is a pancreas or a heart or something, or kidney, then that is fine if you manage to do that. [But] if you allow these animals to go all the way through and be born, if you have a big contribution to the central nervous system from the human cells, then that obviously becomes a concern.”

The news of the monkey-human chimeras comes shortly after it was reported Japanese researchers such as Prof Hiromitsu Nakauchi received government support to create mouse-human chimeras.

In March Japan lifted a ban on allowing such embryos to develop beyond 14 days and being implanted in a uterus, meaning these chimeras can, if permission for an experiment is granted, be brought to term. Nakauchi has said he does not plan to bring the human-mouse chimeras to term yet.

Lovell-Badge said it is very unlikely the animals, if brought to term, would take on human-like behaviour, but said the animals might not behave like “normal” rodents.

“So there are some animal welfare issues as well as the ‘yuck-factor’ ethical issues from making something more human,” he said. “Clearly if any animal born had aspects of human appearance, their faces, their hands, their skin, then I suspect, while scientifically very interesting, people might get a little upset with that.”

De Los Angeles and colleagues have suggested monkey-human chimeras could, in theory, provide new ways to study neurological and psychiatric diseases in humans.

“In theory, for diseases where primate models are not good enough, making human-monkey chimeras could provide a better model of brain diseases,” he told the Guardian, adding that in the case of Alzheimer’s more than 150 trials have failed in 20 years, possibly because of a lack of a good disease model.

One possible approach for brain research is that a monkey embryo could be genetically altered and then injected with human stem cells so that part of the brain, for example the hippocampus, is composed only of human cells. A similar approach has previously been used by Izpisúa Belmonte and colleagues to grow a rat pancreas inside a mouse.

“If you just swap the hippocampus, it doesn’t mean you are now going to have a human-functioning brain,” said Lovell-Badge. “It might have perhaps slightly better memories or slightly different memories … but they are not going to have a human cortex, which is what actually makes us human.”

But such proposals walk straight into the ethical arena others have been at pains to dodge: the possibility of human cells ending up in monkey brains, a development some fear could result in the creatures being human-like. Researchers have previously said they are able to prevent human cells ending up in chimeras’ brains or sex organs.

De Los Angeles said there is still a long way to go before human-monkey chimeras are brought to term.

“The evolutionary distance between humans and monkeys spans 30-40 million years, so it is unclear if this is even possible,” he said. “This difference is greater than 10 million years between mice and rats, and even the efficiency of making mouse-rat chimeras is already quite low.”

While making monkey brains more human is a red line for some, in some ways it has already been crossed. In April scientists in China published a study in which they claimed to have introduced a human brain gene into monkeys, with the animals showing features including better short-term memory and shorter reaction times. These animals are not chimeras, but it is clear that new boundaries are being pushed.

Lovell-Badge said he thought it possible that the development of human-monkey chimeras to study a part of the central nervous system could gain approval, but that it would take a while.

“In the UK, any proposal to make human-monkey chimeras would have to be very well justified, and it would have to get through a very tough review process,” he said. “I am sure that any proposal to go straight to live born chimeras would not get approval in the UK and probably not also in Japan.”

(Source: The Guardian)

70% of the world’s macadamia nuts came from one tree in Australia

Call it the Genghis Khan of macadamias.

LAST WEEK, A SHOCKING DISCOVERY rattled the relatively stagnant field of commercial macadamia nut research. The vast majority of the world’s commercial macadamia crops originated from a single 19th-century tree in the tiny town of Gympie in Queensland, Australia, according to a new study in Frontiers in Plant Science. It’s basically the Genghis Khan of macadamia nut trees, progeny-wise.

The researchers collected hundreds of DNA samples from macadamia trees in the trees’ native habitat in Queensland and compared them to samples of commercially grown trees from Hawaiʻi, which produces 70 percent of the world’s macadamia varieties. This comparison revealed that all of Hawaiʻi’s macadamias share distinctive markers with a tiny wild grouping of trees in Gympie, suggesting that all of the state’s modern crops were likely cloned out of a single Australian tree. In other words, 70 percent of the world’s macadamia varieties can be sourced back to a single tree or a couple of trees in Gympie, according to a statement from Craig Hardner, a horticulturalist at the University of Queensland and one of the researchers leading the study.

“A small collection of seeds were taken to Hawaiʻi at the end of the 19th century and historical records suggest that there was maybe six trees grown from that sample of nuts that were taken by Robert Jordan and planted in his brothers’ backyard in the suburbs of Honolulu in 1896,” Hardner told ABC News.

A grove of macadamia trees in Queensland, Australia. JENNY BROWN/CC BY 2.0

Macadamias are no small affair for Queensland. In the 1860s, King Jacky, the Aboriginal elder of the Logan River Clan and the world’s first “macadamia nut entrepreneur,” was the first to commercially market the nut to settlers. The world’s oldest known cultivated macadamia nut tree, planted in 1858, still grows in Brisbane’s botanic gardens. In 2017, the nuts comprised 14 percent of the Australia’s horticultural exports, according to The Guardian. Queensland has paid fitting tribute to its nut-spreading legacy in the form of the Big Macadamia Nut. The nut, which stands 52 feet tall, is one of Australia’s 50 Big Things, which include other fruits such as a Big Bunch of Bananas and a Big Avocado.

Of the four wild macadamia species living in Queensland today, three are threatened and one is endangered, the study notes. While collecting samples, the researchers stumbled upon one tree grown in Hawaiʻi that they were unable to trace back to the wild. So they’ve asked local, would-be nut-spotters to get involved in identifying old, wild macadamia nut trees that could hold this missing genetic diversity. So if you happen by Queensland anytime soon and spot the telltale strands of green nuts hanging from a tree, send a leaf sample here and you may help preserve Australia’s fattiest wild nuts.

(Source: Atlas Obscura)

Gene-silencing: 'New class' of medicine reverses disease porphyria

Doctors have used a new type of medicine called "gene silencing" to reverse a disease that leaves people in crippling pain.

The condition, acute intermittent porphyria, also causes paralysis and is fatal in some cases.

The novel approach fine-tunes the genetic instructions locked in our DNA.

Doctors say they are "genuinely surprised" how successful it is and that the same approach could be used in previously untreatable diseases.

Sue Burrell no longer has severe bouts of pain.

How bad is porphyria?
Sue Burrell, from Norfolk, has endured pain few could imagine and needed to take strong opioid painkillers every day.

At one point her porphyria was causing severe attacks every couple of weeks and needed hospital treatment.

But even then morphine did not stop the pain.

She told the BBC it was worse than child-birth, saying: "It's so intense - so strong it's in your legs, in your back, and it just resonates everywhere. It's really, really unbearable."

Her sister was affected even more severely and was completely paralysed in hospital for two years.

What is porphyria?
There are several types of porphyria, but each is caused by the body being unable to produce enough of a substance called haem.

Haem is a key component of the haemoglobin in red blood cells that transport oxygen around the body.

Problems in the body's haem manufacturing process can lead to a build up of toxic proteins.

These cause the attacks of physical pain in Sue's form of the disease. In other porphyrias the proteins can cause skin problems.

There is some speculation King George III had porphyria.

But the new treatment worked?
Sue was one of the patients on the trial and is now taking the drug.

She says her life has been transformed.

Sue no longer needs daily painkillers

"I've had pain for 10 years, I didn't expect that could go away. I'm seeing friends and they're [asking] 'you're not taking any painkillers?' and I was [saying] 'no!'."

A clinical trial on 94 people across 18 countries was presented at the International Liver Congress in Vienna.

The therapy cut the number of severe attacks by 74%.

And 50% of patients were completely clear of attacks that needed hospital treatment, compared to 16% given a dummy treatment.

One person dropped out of the study due to side effects.

So how does it work?
The treatment uses an approach called gene silencing.

A gene is part of our DNA that contains the blueprint for making proteins, such as hormones, enzymes or raw building materials.

But our DNA is locked away inside a cell's nucleus and kept apart from a cell's protein-making factories.

So our bodies use a short strand of genetic code, called messenger RNA, to bridge the gap and carry the instructions.

This drug, called givosiran, kills the messenger in a process known as RNA interference.

In acute intermittent porphyria it lowers the levels of an enzyme involved in haem production and prevents the build-up of toxic proteins.

Is this a big deal?
Prof David Rees, from King's College London, treated patients taking part in the trial in the UK.

He told the BBC: "This is a really important treatment - it's innovative. Porphyria is one of the first conditions it has been used in successfully.

"I'm genuinely surprised how well it works in this condition and I think it offers a lot of hope for the future."

Could this treat other diseases?
Potentially yes, but it is still very early days.

Gene silencing has been used to treat a genetic disease that causes nerve damage and the US Food and Drug Administration said such medicines "have the potential to transform medicine".

A similar approach is also being investigated in Huntington's disease, which is caused by a toxic protein that kills brain cells.

Researchers are also looking into it as an alternative to statins for lowering cholesterol.

Barry Greene, the president of Alnylam, which developed the porphyria drug, told the BBC the latest findings were "heralding a brand new class of medicine".

Are people excited?
The field of gene silencing has been around for a long time.

The Nobel Prize in Physiology or Medicine in 2006 went to the researchers who discovered RNA interference, which occurs naturally in our cells.

But the field is now getting to the point where it can be harnessed to help some patients.

Dr Alena Pance, from the Wellcome Sanger Institute, told the BBC News website: "I get excited about this, because targeting the messenger RNA allows the fine-tuning of the proteins that are involved in certain diseases.

"And therefore, perhaps for the first time, [it can] offer a tool to be able to control those diseases to very accurate levels.

"There are diseases that are very difficult to find treatment for, that with this technology might be possible to tackle."

Is this like gene therapy?
Kind of.

Gene therapy permanently alters the hard copy of the genetic instructions in DNA.

Your DNA contains the instructions for building the human body

This can be beneficial as it means you need treatment only once, but could also be more risky. If anything goes wrong, such as accidentally editing the wrong part of the genetic code, it cannot be undone.

Gene silencing leaves the original DNA alone, but targets the instructions that it sends out into the cell.

The downside is you need to keep taking the treatment for the therapy to work.

The two approaches are likely to have roles in different diseases.

Gene therapy has greater potential in diseases like Duchenne muscular dystrophy where a vital protein for keeping muscles intact is missing.

Gene silencing has more potential where tweaking levels of a protein will affect the course of a disease.

Will anybody be able to afford it?
This is the million dollar question, almost literally, as so far genetic medicines have been expensive.

A recent gene therapy for a rare form of blindness was priced at $850,000 (£650,000) for the one-off treatment.

How much the monthly injections of givosiran will be is still unknown.

The hope will be that as the field develops, the costs will eventually come down.

(Source: BBC)

DNA tests prove disgraced fertility doctor used own sperm to secretly father 49 children

Suspicions were partially raised because so many donor offspring looked alike

A fertility doctor accused of illegally using his own sperm to inseminate patients has been found to be the father of at least 49 children.

Jan Karbaat, who died two years ago, impregnated their mothers at his clinic near Rotterdam, in the Netherlands.

None of the women were aware he was using his own semen in the operations.

The mass deception, which the doctor always denied, was revealed on Friday after DNA tests were made public by a Dutch court.

DNA tests to determine if fertility clinic doctor fathered 200 children with his own sperm ( EPA )

It followed a two-year legal battle instigated by dozens of the children – most of who are now in their 30s – after suspicions grew they were related.

One of the apparent giveaways, an early court hearing was told, was that several donor child had such close physical resemblances.

Items were seized from the doctor’s home after his death, aged 89, in April 2017. DNA was then extracted from a toothbrush.

Tests carried out subsequently proved Dr Karbaat was the father of the 49 – although it is now thought he may have sired even more offspring.

Martijn van Halen, one of the doctor’s children, told Dutch news website nrc.nl: "It's nice to know for sure. It gives peace."

He added that he and many of his newly confirmed half-siblings had become friends through their legal fight and would be staying in touch.

The clinic itself was closed in 2009 - after being open for decades - amid allegations of falsified data, and systematic exceeding of the permitted number of six children per donor.

(Source: Independent)

Damaged sperm could be to blame for repeated miscarriages

Imperial College scientists find DNA damage in sperm could be undetected cause

Men should undergo tests when couples suffer repeated miscarriages, according to researchers who say the health of the man’s sperm may sometimes be a factor.

The focus is usually on the woman’s body when multiple pregnancies fail, with tests usually looking for immune system problems or infection. But a small government-funded study by scientists at Imperial College London suggests miscarriage could also be a result of male issues, particularly if they are not routinely tested.

“Traditionally, doctors have focused attention on women when looking for the causes of recurrent miscarriage. The men’s health – and the health of their sperm – wasn’t analysed,” said Dr Channa Jayasena, the lead author of the research, from Imperial’s department of medicine.

“However, this research adds to a growing body of evidence that suggests sperm health dictates the health of a pregnancy. For instance, previous research suggests sperm has an important role in the formation of the placenta, which is crucial for oxygen and nutrient supply to the foetus.”

The team tested 50 men whose partners had suffered recurrent miscarriages, defined as the loss of three consecutive pregnancies before 20 weeks’ gestation. All were patients at St Mary’s hospital, in London. The scientists analysed their sperm and compared the results with those of 60 similar male volunteers.

The sperm of the men in the miscarriage group had twice as much DNA damage as that in the control group, Imperial College scientists found. Photograph: Alamy

The sperm of the men in the miscarriage group had twice as much DNA damage as that in the control group, they found. The researchers, writing in the journal Clinical Chemistry, say this could be down to reactive oxygen species – molecules formed by cells in semen to protect sperm from bacteria and infection. In high enough concentrations, the molecules can cause significant damage to sperm cells.

The results from the study revealed sperm from men whose partners had suffered miscarriage had four times more of these molecules compared to the control group. The scientists are now investigating the cause.

“Although none of the men in the trial had any ongoing infection such as chlamydia, which we know can affect sperm health, it is possible there may be other bacteria from previous infections lingering in the prostate gland, which makes semen. This may lead to permanently high levels of reactive oxygen species,” said Jayasena.

Obesity can also cause fertility problems. Higher fat levels in the body could trigger an increase in reactive oxygen species.

The men whose partners had suffered miscarriage were older than the other group, with an average age of 37 compared to 30, and were slightly more overweight. The team is now investigating whether these factors may have affected the levels of reactive oxygen species.

Dr Kevin McEleny of the British Fertility Society said: “This is an interesting study that illustrates the importance of research into sperm quality. The results agree with some of the previous research into a link between DNA damage in sperm and miscarriage.

“We know that the partners of older men are more likely to suffer miscarriage. The study group was generally older than the control group, which might go some way to explain the results.

“The study picked up small differences in hormone levels; it is not clear if these findings are of clinical relevance, because the average hormone levels of all groups were well within normal range. Minor differences in sperm quality were observed but the significance of that isn’t clear.”

Jayasena concluded: “Although this is a small study, it gives us clues to follow. If we confirm in further work that high levels of reactive oxygen species in semen increase the risk of miscarriage, we could try to develop treatments that lower these levels and increase the chance of a healthy pregnancy.

“It has taken medicine a long time to realise sperm health has a role to play in miscarriage and that the cause doesn’t lie solely with women. Now we realise both partners contribute to recurrent miscarriage, we can hopefully get a clearer picture of the problem and start to look for ways of ensuring more pregnancies result in a healthy baby.”

(Source: The Guardian)

World's first genetically altered babies born in China, scientist claims

Leading scientists described the work as ‘monstrous’ and ‘far too premature’

A Chinese scientist claims he has helped create the world’s first genetically edited babies.

In research that would be illegal if carried out in most countries, Professor He Jiankui and his team said they altered the embryos of seven couples undergoing fertility treatment.

One successful pregnancy resulting from this treatment resulted in twin girls born earlier this month that the scientists claimed were naturally resistant to HIV.

Scientists have lined up to criticise the research which, if it turns out to be true, would represent a profound leap of science and ethics.

A US scientist also confirmed that he took part in the work in China, but this kind of gene editing is banned in his home country because the DNA changes can pass to future generations and risk harming other genes.

Many mainstream scientists therefore think it is too unsafe to try, and some denounced the experiment as “monstrous” human experimentation.

Professor He said his goal was not to cure or prevent an inherited disease, but to try to bestow a trait that few people naturally have: an ability to resist possible future infection with HIV, the Aids virus.

He said the parents involved declined to be identified or interviewed, and he would not say where they live or where the work was done.

There is no independent confirmation of the claim, and it has not been published in a journal, where it would be vetted by other experts. He revealed it on Monday in Hong Kong to one of the organisers of an international conference on gene editing that is set to begin on Tuesday, and earlier in exclusive interviews with the Associated Press.

“I feel a strong responsibility that it’s not just to make a first, but also make it an example,” he told AP. “Society will decide what to do next” in terms of allowing or forbidding such science.

Professor Julian Savulescu, an ethicist at the University of Oxford, said considering the effective ways to prevent HIV in healthy individuals and to treat those suffering from the disease, the work undertaken in China was indefensible.

“If true, this experiment is monstrous,” he said.

“Gene editing itself is experimental and is still associated with off-target mutations, capable of causing genetic problems early and later in life, including the development of cancer.”

Dr Eric Topol, who heads the Scripps Research Translational Institute in California, agreed that the research was “far too premature” given the current status of gene editing research.

“We’re dealing with the operating instructions of a human being. It’s a big deal,” he said.

However, one famed geneticist, Harvard University’s Professor George Church, defended attempting gene editing for HIV, which he called “a major and growing public health threat”.

“I think this is justifiable,” Professor Church said of that goal.

In recent years scientists have discovered a relatively easy way to edit genes, the strands of DNA that govern the body, using a tool that makes it possible to supply a needed gene or disable one that’s causing problems.

It’s only recently been tried in adults to treat deadly diseases, and the changes are confined to that person. Editing sperm, eggs or embryos is different – the changes can be inherited.

While this is outlawed in the US and the UK, China outlaws human cloning but not specifically gene editing.

Profesor He studied at Rice and Stanford universities in the US before opening a lab at the Southern University of Science and Technology in Shenzhen, where he also has two genetics companies.

The US scientist who worked with him on this project after Professor He returned to China was physics and bioengineering professor Michael Deem, who was his adviser at Rice. Professor Deem also holds what he called “a small stake” in and serves on the scientific advisory boards of Professor He’s two companies.

The Chinese scientist said he chose to try embryo gene editing for HIV because those infections are a big problem in China. He sought to disable a gene called CCR5 that allows HIV to enter a cell.

All the men in the project had HIV and all the women did not, but the gene editing was not aimed at preventing the small risk of transmission, Professor He said. The fathers had their infections deeply suppressed by standard HIV medicines and there are simple ways to keep them from infecting offspring.

Instead, the appeal was to offer couples affected by HIV a chance to have a child that might be protected from a similar fate.

He said the gene editing occurred during IVF, or lab dish fertilisation. First, sperm was “washed” to separate it from semen, the fluid where HIV can lurk. A single sperm was placed into a single egg to create an embryo. Then the gene editing tool was used.

When the embryos were three to five days old, a few cells were removed and checked for editing. Couples could choose whether to use edited or unedited embryos for pregnancy attempts. Eleven embryos were used in six attempts before the twin pregnancy was achieved, Professor He said.

Tests suggest that one twin had both copies of the intended gene altered and the other twin had just one altered, with no evidence of harm to other genes, he said. People with one copy can still get HIV.

Several scientists reviewed materials that Professor He provided to AP and said tests so far are insufficient to draw conclusions.

It’s unclear whether participants fully understood the purpose and potential risks and benefits. For example, consent forms called the project an “Aids vaccine development” programme.

The study participants are not ethicists, Professor He said, but “are as much authorities on what is correct and what is wrong because it’s their life on the line”.

“I believe this is going to help the families and their children,” he said. If it causes unwanted side effects or harm, “I would feel the same pain as they do and it’s going to be my own responsibility”.

Other researchers said that whatever the ultimate conclusions, Professor He’s experiments should serve as a warning of what is to come.

“It was inevitable that someone trying to reach the limelight would likely try this. However it is often better to be safe than to be first,” said Professor Peter Braude, a reproductive health specialist at King’s College London.

Dr Yalda Jamshidi, a human genetics expert at St George’s, University of London, added: “Whether the results stand up to scrutiny or not we need as a society to think hard and fast about when and where we are willing to take the risks that come with any new therapeutic treatment, particularly ones that could affect future generations.”

(Source: The Independent)

Child abuse leaves molecular ‘scars' in DNA of victims’ sperm: Study

'We already know there are a lot of behavioural mechanisms by which trauma has negative effects on the next generation... This is another possible pathway'

Child abuse may leave marks that go even deeper than psychological trauma by physically etching itself into people’s DNA, according to a new Harvard study.

Research based on a small sample of men found differences in chemical marks within the genetic code of those who have experienced abuse as children.

The scientists examined a chemical process termed methylation in DNA from sperm samples, and found noticeable differences that appeared to distinguish victims and non-victims.

Scientists found that childhood abuse was linked with changes in DNA of victims' sperm ( Getty Images )

Not only do these findings suggest a long-term physical impact of trauma, the presence of these changes in sperm cells suggests its legacy may even be passed between generations.

“We already know there are a lot of behavioural mechanisms by which trauma has negative effects on the next generation,” Harvard scientist Dr Andrea Roberts told The Independent.

“Trauma obviously really affects the behaviour of people traumatised. It often makes them depressed, it gives them post-traumatic stress disorder, and those mental health conditions affect their parenting and affect the kids.

“This is another possible pathway.”

Methylation is a process by which a structure termed a methyl group is added to a strand of DNA, and it can act as a “dimmer switch” on genes.

Though research into this process is still in its infancy, scientists think it is influenced by conditions such as life experiences and physical environment.

While methylation marks on DNA have been described as “molecular scars” by some commentators, Dr Roberts said the truth is that the impact – positive or negative – of this process is still largely mysterious in humans.

However, extensive experiments in mice have suggested that when it strikes sperm cells methylation can transmit health problems to offspring.

“Some very good findings from mice have shown that early life stressors affect the marks on the sperm, and then in turn those affect the health of the offspring in particular creating a kind of anxious behaviour,” said Dr Roberts.

In their sample of 34 men, all of which were taking part in a long-term study coordinated by Harvard's TH Chan School of Public Health, 22 had suffered some kind of abuse as children.

Within those samples they identified 12 areas of DNA that had been consistently struck by some degree of methylation “dimming” in the abuse victims.

If this effect is consistently seen in larger studies and can be explained in greater detail, the scientists suggest it could have practical applications in a legal setting.

"Methylation is starting to be viewed as a potentially useful tool in criminal investigations – for example, by providing investigators with an approximate age of a person who left behind a sample of their DNA," said Dr Michael Kobor of the University of British Columbia, senior author of the Translational Psychiatry study.

"So it's conceivable that the correlations we found between methylation and child abuse might provide a percentage probability that abuse had occurred."

However, this vision is still a long way from reality, and the process of conception adds further complications as it reshuffles lots of the fathers’ genetic material and potentially erases many of the changes that occurred previously.

Dr Roberts said there is a need to replicate their findings, but described this as a step towards establishing a long-term impact of abuse that can transcend generations.

(Source: The Independent)

4500-year-old DNA from Rakhigarhi reveals evidence that will unsettle Hindutva nationalists

The 'petrous bone' is an inelegant but useful chunk of the human skull -- basically it protects your inner ear. But that's not all it protects. In recent years, genetic scientists working to extract DNA from ancient skeletons have discovered that, thanks to the extreme density of a particular region of the petrous bone (the bit shielding the cochlea, since you ask), they could sometimes harvest 100 times more DNA from it than from any other remaining tissue.

Now this somewhat macabre innovation may well resolve one of the most heated debates about the history of India.

As the dust of the petrous bones of a 4,500-year-old skeleton from Rakhigarhi, Haryana, settles, we may have the answer to a few questions that have vexed some of the best minds in history and science -- and a lot of politicians along the way:

Q: Were the people of the Harappan civilisation the original source of the Sanskritic language and culture of Vedic Hinduism? A: No.

Q: Do their genes survive as a significant component in India's current population? A: Most definitely.

Q: Were they closer to popular perceptions of 'Aryans' or of 'Dravidians'? A: Dravidians.

Q: Were they more akin to the South Indians or North Indians of today? A: South Indians.

All loaded questions, of course. A paper suggesting these conclusions is likely to be online in September and later published in the journal Science.

These revelations are part of the long-awaited and much-postponed results of an excavation conducted in 2015 by a team led by Dr Vasant Shinde, an archaeologist and vice chancellor of Pune's Deccan College.

Why did it take so long? One answer was on offer exactly a year ago when this writer spoke to Shinde who was then holding out the promise of publishing the findings in September 2017. "It's a very politically sensitive issue," he said.

NOT THE SAME: The Indus Valley people lacked the steppe and ancestry that marks many North Indian high castes today (Photograph by Bandeep Singh, for representational purpose only)

The archaeologist was referring to the fact that any research dealing with the Harappan civilisation would have to confront the Hindutva agenda of the government of India -- whose politics demands a genuflection to Vedic Hinduism as the origin of Indian civilisation.

For historians or anyone working on the Harappan or Indus Valley Civilisation, this is a complication. Indeed, when the Indus Valley Civilisation was first 'discovered' in the 1920s, colonial archaeologists quickly identified it as evidence of a pre-Vedic culture, which, they theorised, had been utterly destroyed by the advent of 'Aryan' invaders from the Northwest who represented the dawn of Hindu India.

In later years, most mainstream historians have discarded the 'Aryan invasion theory' or 'AIT' as an oversimplification -- while retaining a chronology that places the Vedic civilisation as a successor to the Indus Valley Civilisation.

And the Aryan invasion theory continues to rankle Hindutva nationalists even as it has taken root in South India as the core narrative of a popular politics which sees the Indus Valley Civilisation as a Dravidian culture that has survived 'Brahminical' invaders only south of the Vindhyas.

GREAT EXPECTATIONS
Meanwhile, the reality of who the Indus Valley Civilisation people were has remained a mystery. Shinde knows all too well the incongruous burden of expectations that has now settled on a 4,500-year-old resident (classified as 'I4411') of Rakhigarhi, a ramshackle village in the dusty khadar or floodplain of an almost extinguished river.

You may know of Rakhigarhi too: over the last decade-and-a-half, the name has become a staple of school textbooks, tourism pamphlets and journalism-invoked as the largest Harappan/Indus Valley site in India. In fact, since 2014, it has been regularly cited as 'even larger than Mohenjo-Daro' -- the archaeological site in Sindh, Pakistan, first excavated in the 1920s.

Despite the element of hyperbole, excavations here -- conducted intermittently since the late 1960s -- have established its significance as an extensive and enduring urban settlement with its beginnings arguably as early as the 7th millennium BCE.

Most importantly, the village with its seven teelas or mounds has produced enough evidence to identify it as the site of a 'mature' Harappan settlement of the 2nd and 3rd millennium BCE. In other words, a town that witnessed the rise and -- more than 4,000 years ago -- the mysterious fall, of India's first urban civilisation.

If the 'rewriting of Indian history' was lurching ahead on the Hindutva fringe of academia, science was steadily advancing in another direction
On the face of it, the single most startling revelation of the Rakhigarhi research may be what it doesn't talk about: the complete absence of any reference to the genetic marker R1a1 in the ancient DNA retrieved from the site.

This is significant because R1a1, often loosely called 'the 'Aryan gene', is now understood to have originated in a population of Bronze Age pastoralists who dispersed from a homeland in the Central Asian 'Pontic steppe' (the grasslands sprawling between the Black Sea and the Caspian) some 4,000 years ago. The genetic impact of their migrations has left a particularly strong and 'sex-biased', (i.e. male-driven) imprint on the populations of two geographically distant but linguistically related parts of the world: Northern India and Northern Europe.

"We are not discussing R1a," says Niraj Rai, the lead genetic researcher on the Rakhigarhi DNA project. "R1a is not there." The admission came wrapped in some prevarication but was all the more telling given that the Rakhigarhi data presented in this paper are derived primarily from the genetic material of 'I4411', a male individual -- R1a is a mutation seen only in samples of the male Y chromosome.

The absence of this genetic imprint in the first genome sample of an individual from the Indus Valley culture will bolster what is already a consensus among genetic scientists, historians and philologists: that the Indus Valley culture preceded and was distinct from this population of cattle-herding, horse-rearing, chariot-driving, battle-axe-wielding, proto-Sanskrit-speaking migrants whose ancestry is most evident in high-caste North Indian communities today.

Rai points out that the fact that haplogroup R1a did not show up in the Rakhigarhi sample could be attributed to the limited amount of genetic data retrieved. Or it could be because it's just not there. "We do not have much coverage of the Y chromosome regions [of the genome]," Rai says, revealing that they had retrieved more data from the mitochondrial and autosomal DNA in their sample (mitochondrial DNA reflects maternal descent and autosomal tests reveal genetic information inherited from both parents).

However, he was emphatic in acknowledging that while "a mass movement of Central Asians happened and significantly changed the South Asian genetic make-up", the inhabitants of ancient Rakhigarhi "do not have any affinity with the Central Asians". In other words, while the citizens of the Indus Valley Civilisation had none of this ancestry, you, dear average Indian reader, owe 17.5 per cent of your male lineage to people from the Steppe.

It's worth noting that this genetic footprint is of an entirely more impressive order than the relatively inconsequential biological legacy of Islamic or European colonial invasions that often preoccupy the political imagination in India.

So much for what we have now learned about who our 4,500-year-old ancestor 'I4411' was not. What about who he was? The short answer, says Rai, is that I4411 "has more affinity with South Indian tribal populations". Notably, the Irula in the Nilgiri highlands.

A draft of the paper argues that this individual could be modelled as part of a clade [a group sharing descent from a common ancestor] with the Irula but not with groups with higher proportions of West Eurasian related ancestry such as Punjabis, and goes on to suggest that the inhabitants of Rakhigarhi probably spoke an early Dravidian language.

Most mainstream historians have discarded the 'Aryan invasion theory' or 'AIT' as an oversimplification
However, the results also show clear evidence of mixing with another population from outside the subcontinent, labelled 'Iranian agriculturalist'. This is a population that had been identified in earlier studies of ancient DNA and is consistent with the hypothesis that some agricultural technologies were introduced to the subcontinent through contact with the 'fertile crescent' in West Asia, widely regarded as one of the birthplaces of Eurasian agriculture in the 5th-8th millennium BC.

For an older generation of Indians, the Rakhigarhi results may sound like a reboot of half-remembered schoolbooks: 'Dravidian' Harappans followed by Vedic horsemen from the Steppe. And for anyone who has been following more recent developments in population genetics too, the latest findings will sound familiar.

Meanwhile, in the popular press, coverage of recent discoveries in the archaeology or genetics of Harappan India has been obsessively and distractingly focused on the 'Aryan invasion theory'. What gives? And why does it matter? The answer has to do with the fact that recent years have been a very busy time in ancient Indian history. And modern Indian politics.

SKULDUGGERY
In the months preceding the news of the Rakhigarhi findings, anticipation was high, and fuelled by a series of related research papers and their journalistic glosses, an amusing if acrimonious debate erupted in the social media and the blogosphere. Shinde for his part was given to dropping broad hints that the Rakhigarhi results would point to a 'continuity' between the population of the ancient town and its present-day inhabitants (predominantly Jats, a population marked by pronounced R1a Steppe ancestry).

Perhaps it should be no surprise, in these fractious times, that fake news would be deployed as a weapon in the civil war that has consumed ancient Indian history. In January this year, a Hindi newspaper carried an article purportedly based on an interview with Rai, asserting that the Rakhigarhi DNA was, in fact, a close match for North Indian Brahmins and that the findings would establish that India was the 'native place' of the Indo-European language family.

"Utter crud!" was the reaction of David Wesolowski, host of the Eurogenes blog-well regarded by some of the world's leading geneticists as a go-to site for the latest debate. Wesolowski's site witnessed frequent arguments over the likelihood that Rakhigarhi DNA would turn up the R1a1 marker.

Here, extended and nuanced discussions of the finer points of molecular evidence would often conclude with kiss-offs along the lines of "you're an idiot" or "you're going to need psychiatric help when the results are out". In the event, Wesolowski's own prediction, "Expect no R1a in Harappa but a lot of ASI [Ancestral South Indian]", would prove to be spot on.

The single most startling revelation of the Rakhigarhi research may be the complete absence of any reference to the genetic marker R1a1, often loosely called 'the 'Aryan gene'
Behind the surly invective and the journalistic misdirection were rumours and whispers of a face-off between a rising tide of scientific evidence and the political pressures of nativist, Hindutva sentiments.

The saga of 'Hindutvist history' is by now another familiar tale, with its origins in early Hindu nationalist reaction to colonial archaeology and linguistics, a monomaniacal obsession with refuting the 'Aryan invasion theory'.

It is perhaps most clearly expressed in an irate passage from former RSS sarsanghchalak M.S. Golwalkar's screed Bunch of Thoughts (1966): "It was the wily foreigner, the Britisher, who carried on the insidious propaganda that we were never one nation, that we were never the children of the soil but mere upstarts having no better claim than the foreign hordes of Muslims or the British over this country."

In recent years, this resentful impulse has focused particularly intently on asserting the wishful conclusion that the Indus Valley Civilisation itself must be 'Vedic'. This has understandably gained traction in the popular imagination in tandem with the political rise of Hindutva. In 2013, Amish Tripathi, a bestselling author of 'Hinduistical fantasy' novels, gave vent to the keening desire for a 'Vedic IVC' in a short fiction in which future archaeologists discover clinching evidence "that the Indus Valley Civilisation and the Vedic-erroneously called Aryan-civilisation were one and the same." The story is poignantly titled, 'Science Validates Vedic History'.

Inevitably, the advent of a BJP majority government in the general elections of 2014 has given new energy -- and funding-to the self-gratifying urges of Hindutvist history.

The Rakhigarhi findings build on earlier work by some of the same researchers revealing the story of population migrations from the Eurasian steppe at the close of the Indus Valley Civilisation. What emerges is a remarkable parallel in the prehistory of South Asia and Northern Europe as populations from the steppe advanced into both subcontinents. The migrations produce the population mixes that now inhabit both areas and help explain the linguistic connections between them.

The charge has been led by the Union minister for culture Mahesh Sharma, who has prioritised the project of 'rewriting Indian history', whether by appointing a pliant obscurantist as head of the Indian Council of Historical Research or promoting the 'research' of para-scientific outfits such as I-SERVE (Institute of Scientific Research on Vedas) and a former customs officer who uses hobby astronomy software to establish that "thus Shri Ram was born on 10th January in 5114 BC...around 12 to 1 noontime [in Ayodhya]".

In March this year a Reuters report revealed details of a meeting of a 'history committee' convened by Sharma at the office of the Director General of the Archaeological Survey of India in January 2017. Its task, according to the committee chairman K.N. Dixit, was "to present a report that will help the government rewrite certain aspects of ancient history".

The minutes of the meeting apparently "set out its aims: to use evidence such as archaeological finds and DNA to prove that today's Hindus are directly descended from the land's first inhabitants many thousands of years ago, and make the case that ancient Hindu scriptures are fact, not myth".

Yet, if the 'rewriting of Indian history' was lurching ahead on the Hindutva fringe of academia, mainstream science was steadily advancing in quite another direction.

In March this year, the Harvard population geneticist David Reich published an overview of the state of research in his field, the surprise bestseller Who We Are and How We Got Here, including an account of how the extreme sensitivity of leading Indian scientists about earlier evidence suggesting an ancient migration of Eurasian people from the Northwest into the subcontinent had nearly scuppered an important scientific collaboration in 2008.

The Indian scientists Lalji Singh and K. Thangaraj "implied that the suggestion of a migration would be politically explosive", Reich writes. The issue was ultimately resolved by means of a terminological sleight-of-hand -- using the nomenclature 'Ancestral South Indian' (ASI) and 'Ancestral North Indian' (ANI) to obscure the revelation that ANI represented a population with a significant genetic contribution from outside the subcontinent.

But the same dynamic appears to have emerged this year around a paper involving both Reich and his team at Harvard on the one hand and the scientists leading the Rakhigarhi project on the other. Entitled, rather flatly, The Genomic Formation of South and Central Asia, this paper (usually referred to by the shorthand 'M Narasimhan et al') -- made public as a 'pre print' in April -- would make headlines in the Indian press and social media and reveal some more of the political pressures that colour research on ancient Indian history today.

Shinde said that he had complained to Reich about an earlier draft of that paper, and insisted that any reference to 'migrations' into South Asia be avoided. Or else. He suggested the more ambivalent term 'interaction' be used instead.

As the results of the Rakhigarhi study leak steadily into the public domain, a political backlash seems inevitable
Given that Shinde controlled access to the Rakhigarhi samples which Reich was keen to work on, this would have been a potent threat, and indeed the paper manages to eschew the term 'migration' entirely while ultimately making more potent statements about the impact of post-Harappan 'Middle to Late Bronze Age' (MLBA) Steppe populations on the Indian gene pool.

However, the timing of the paper remains curious to say the least, given that it would have benefitted from the Rakhigarhi data which it seemed to pre-empt -- despite the fact that several of its co-authors, including Rai, Shinde, Thangaraj, Narasimhan and Reich now share credit for the mysteriously delayed paper.

The official word on this was that the Rakhigarhi research was behind schedule due to the 'contamination of one sample', but at the time the geneticist community was abuzz with rumours that the slowdown was because of the Indian team's discomfort with politically inconvenient results.

According to one US-based researcher, who prefers to remain anonymous, "It was common knowledge through the grapevine that the Harvard team became impatient and eventually pushed to release their preprint before Indian colleagues were totally comfortable. Some samples [read 'Rakhigarhi'] were removed because of disagreements between collaborators."

In more recent conversations with this writer, Shinde seemed intent on dissembling the results of his team's paper, offering that the results showed that Rakhigarhi's inhabitants were "just like the locals with some contact with South Indian tribals". Peculiarly, in a recent magazine interview, Shinde is convinced that the ancient people of Rakhigarhi were "tall and sharp-featured like the modern Haryanvis", leading his interviewer to label Wazir Chand Saroae, a prominent local historian of Rakhigarhi and a self-identified Dalit, as a 'Sirohi Jat'.

However, Shinde is no geneticist, and from what we now know, the Rakhigarhi study endorses the findings of the Narasimhan paper -- indeed, it can be seen as a companion piece to that earlier work of the common authors.

Significantly, while Narasimhan and others predicted a model of the Harappan genome using samples of DNA from ancient skeletons of apparent Indus Valley 'visitors' found in sites that were in trading contact with the Harappans, as well as remains of post-Harappan (1200-BC-1 CE) individuals from Swat, the Rakhigarhi paper suggests that this model was accurate. It recommends that the Narasimhan paper's tentative label of 'Indus Valley periphery' for this model is a significant match for I4411 of Rakhigarhi and this genetic cluster should now be recognised as the 'Harappan cline'.

IT'S STILL COMPLICATED
As the results of the Rakhigarhi study leak steadily into the public domain, a political backlash seems inevitable -- and largely predictable: some exultation from Dravidianists and the legion of anti-Hindutva Indians for many of whom the fall of Delhi in the 2014 election is seen as a calamitous replay of that fabled 'Vedic Aryan invasion'.

And we can expect sullen scepticism from the saffron right. Intriguingly, some of the strongest reservations about the Rakhigarhi project have already been expressed from an unexpected quarter: established historians.

Romila Thapar, always a name to reckon with in ancient Indian history and a perennial target of Hindutva polemic, has followed the genetics story keenly, but expressed her reservations about this new science.

As it turns out, the Rakhigarhi research was not without glitches -- apparently, a misleading 'East Asian' signal in the early data is the reason why the Korean scientists who first worked on the samples may not be credited in the final paper.

Meanwhile, another respected historian, Nayanjot Lahiri, declared complete disinterest in the work on 'Harappan DNA', voicing impatience at the obsession with the 'Aryan' question and scepticism about the narrow sampling of ancient genetic material. "As far as the whole question of Aryans and the Vedic component in the Indus Valley Civilisation goes, until the Harappan script is deciphered, it's not decided," she says.

While such responses may be unduly harsh -- even small genetic samples can reveal considerable demographic depth and geneticists are in any case expanding the range of samples at an impressive rate -- some cold water is not amiss.

Certainly any triumphalism or despair on the basis of the emerging genetic profile of the 'Harappan Indians' would be misplaced.

While the evidence does point convincingly to the Indus Valley Civilisation being a distinct population from the 'post-Vedic' population infused with MLBA Steppe genes that stamp India's population to this day, it's also the case that the Indus Valley Civilisation's population represents "the single most important source of ancestry in South Asia" today (as the Narasimhan paper puts it).

Similarly, any impulse to equate the apparent Dravidian affinities of ancient Indus Valley people with the culture and people of South India today or to cast the latter as the 'original inhabitants' of the subcontinent would be an exaggeration.

India is composed of a large number of small populations
- Geneticist David Reich
Quite apart from the fact that the people and cultures across the subcontinent today display evidence of having mixed with each other (and populations beyond the borders of present day India) over millennia, there is also no population in the region that can claim to represent a 'pure' lineage of ancient Indians.

Not even the Irula or any other South Indian or 'Adivasi' group. Nor should the evidence of the deeply intertwined genetic history of Indian communities lull anyone into a cosy fable of Indic cosmopolitanism.

What our DNA tells us instead is that while India witnessed phases of extensive genetic mixing for a millennium after the collapse of the Indus Valley Civilisation, this was followed by a long period of deep endogamy -- which has been a uniquely unhealthy stamp of the subcontinent.

Reich summed it up in his recent book: "People tend to think of India, with its more than 1.3 billion people, as having a tremendously large population. But genetically, this is an incorrect way to view the situation. The Han Chinese are truly a large population. They have been mixing freely for thousands of years The truth is that India is composed of a large number of small populations."

UNEARTHING ANCIENT ORIGINS The researchers took extra care to reduce sample contamination to the minimum

If this sounds complicated, that's because it is. And the more we discover about India's past, the more complicated it is likely to become. One of the more intriguing asides in the Rakhigarhi study, is a suggestion that while the Indus Valley Civilisation population was evidently multi-ethnic, a persistent genetic 'substructure' also indicates that the Harappan civilisation may have been characterised by 'high within-group endogamy'.

Such teasers indicate that there is still much work to be done; they are reminders not to jump to conclusions or project modern fantasies onto an ancient civilisation we still know so little about. In truth, this has been a pathology of the 'liberal' imagination in India as much as it has been of the 'Hindutvist'.

In that foundational text of Indian nationalism, The Discovery of India, Jawaharlal Nehru could not resist a moment of secularist rapture when he first set eyes on Mohenjo-Daro. "What was the secret of this strength? Where did it come from?" he wondered. "It was, surprisingly enough, a predominantly secular civilisation, and the religious element, though present, did not dominate the scene."

At the end of the day, Nehru's vision too is a modern nationalist fantasy. In the years to come, we are certain to discover much more about the enduringly mysterious civilisation of the Harappans and what elements of culture and social behaviour they bequeathed us -- along with their genes. For now, miraculously, their ears are speaking. We would do well to listen for a while.

(Source: India Today)