ANNE-CHRISTINE POUJOULAT/AFP/Getty Images
ANNE-CHRISTINE POUJOULAT/AFP/Getty Images

What Iran May Be Able to Teach Us About Stem Cells

ANNE-CHRISTINE POUJOULAT/AFP/Getty Images
ANNE-CHRISTINE POUJOULAT/AFP/Getty Images

In 2002, Iranian supreme leader Ayatollah Ali Khamenei issued a religious ruling, a fatwa, declaring embryonic stem cell research acceptable under Islamic law. American scientists at that time were stuck in an epic political debate over the cells’ use, but Iranian researchers had a green light to launch various experiments, develop cell lines, and invent novel therapies.

In the 14 years since, they’ve made great strides in stem cell research. And now that Iran is losing its pariah-state status after sanctions were lifted in mid-January, there are opportunities for collaborations with non-Iranian scientists—which has Ali Brivanlou, who leads the Stem Cell Biology and Molecular Embryology lab at The Rockefeller University, intrigued about the possibilities. 

Brivanlou discussed the state of stem cell research in Iran—and what other scientists might learn from that research—during a recent presentation at the American Association for the Advancement of Science's annual meeting in Washington, D.C. Born in Tehran, Brivanlou did his post-doctoral research at the University of California, Berkeley, and continued his career in the United States. When sanctions were lifted, he visited Tehran again. “After 36 years, I was quite impressed with what I saw,” he said during his talk. “Iran is certainly at the cutting edge of stem cell research, in terms of basic knowledge and in terms of application platforms.” 

Brivanlou later spoke to mental_floss about the potential benefits of collaborating with Iranian scientists. So too did panel organizer Richard Stone, who oversees international coverage at the journal Science. Stone noted to mental_floss that before the sanctions were lifted, there were too many constraints for any American-Iranian scientific collaborations to really work. “That turned scientists off,” Stone said. Now new possibilities are opening up. 

THE SCIENCE—AND POLITICS—OF STEM CELL RESEARCH IN THE U.S.

Derived from a fertilized human egg, embryonic stem cells are pluripotent—under the right conditions, they can develop into any of the 200 cell types present in the body of an adult. Under certain other conditions, they can keep replicating themselves forever. All these unique qualities make embryonic stem cells extremely valuable not only for basic research, but also for a gamut of medical cures—from regenerative medicine to tissue replacement therapies to treating genetic diseases.

But because embryonic stem cell usage implies that, at some point, some embryo had been destroyed to harvest its cells, this research spawned a great deal of controversy in the Western world.

When the Bush administration placed various restrictions on the cells’ usage and funding in 2001, American embryonic stem cell researchers found themselves in the crosshairs of ethical, religious, and funding wars. For the next several years, politicians, lawyers, and advocacy groups wrote letters, signed petitions, and composed bills—some in favor of the practice, others against it. Bills were passed by Congress and vetoed by President George W. Bush, until in 2009 President Obama lifted the restrictions, expanding the number of stem cell lines that qualified for federally funded research. 

THE SCIENCE—AND POLITICS—OF STEM CELL RESEARCH IN IRAN

Meanwhile, the Royan Institute in Tehran, a city of nearly 9 million people on the slopes of the Shemiran Mountains, was an embryonic research safe haven. (Royan means "embryo" in Farsi.) Iran didn’t view stem cell research as problematic because under Islamic law life is defined not at conception, but when one can distinguish a heartbeat, Brivanlou explained in his talk.

Royan scientists began operating embryonic cell lines in 2003, and now have over 40 different lines in clinical trials, Brivanlou told mental_floss. In 2006, they successfully cloned a sheep, naming it Royana, and last year they cloned an endangered animal—an Isfahan mouflon (a wild sheep). “This was their tour de force,” he said at the conference. “It was a nucleus of a mouflon grown inside a sheep.”

While the world scrutinized Iranian nuclear advances, the country’s stem cell embryonic research had risen to the scientific forefront.

FROM 12 TO 362 STEM CELL LINES SINCE 2004   

For the past few years, stem cell research in the U.S. has made a lot of progress, David Schaffer, director of the Berkeley Stem Cell Center, told mental_floss. Schaffer studies stem cell bioengineering and its applications in regenerative medicine. “We now have 362 lines on the federal registry compared to something like a dozen in 2004,” he said.

Scientists in the U.S., often in collaboration with researchers in Europe and Japan, have managed to grow muscles, bones, kidneys, intestines, and liver and heart tissue from stem cells, aiming to treat disease or alleviate the shortage of donor organs. There are clinical trials underway to treat degenerative eye disease with retinal cells derived from stem cells. The goal of another trial is to alleviate spinal cord injuries by growing myelinated cells, which serve as neuron insulators. Schaffer’s lab is looking into the possibilities of regenerating brain cells that die off in Parkinson’s disease. 

Partnering with Iranian colleagues offers many advantages, Brivanlou said. The Iranian scientists, who worked in isolation from the rest of the world, experimented in different research areas—such as cloning endangered species to prevent their extinction. (Besides the mouflon, they’re also working on potentially cloning an endangered white tiger that lives in the mountains of Iran.) They focused on finding ways to treat region-specific infectious diseases and genetic disorders caused by inbreeding. They also focused on producing antidotes to local venomous snakes such as cobras. These technologies can help countries neighboring Iran, which face similar medical and environmental challenges but aren’t as advanced.

LIMITED RESOURCES LED TO SCIENTIFIC CREATIVITY

It’s important to note, Brivanlou said, how much Iranian scientists were able to achieve with the rudimentary tools they had. He likens it to building a car without having hammers and screwdrivers at hand. Bioreactors that grow stem cells are complex pieces of equipment— computer-controlled to feed nutrients to cells, remove cellular waste, and keep cultures at precise temperature. Reagents used to grow cells are specific chemical solutions that Western labs buy from companies that make them.

Sequencing DNA, which is part of stem cell research, requires high-end robotics and various chemical solutions. Brivanlou’s lab can order a dozen reagents from around the world and they get shipped by FedEx the next day. But many Western biochemical companies couldn’t sell products to Iran, and there’s still no FedEx delivery, so Iranian scientists have had to make everything from scratch.

A bioreactor Brivanlou saw in Iran looked as if it was made in someone’s garage. “It was just a metal chamber with a couple of tubes and a burning candle underneath to keep it at the right temperature—but it worked and it grew cells,” Brivanlou recalled. “An experiment that takes me a week to make would take an Iranian scientist a year. Imagine what they could accomplish if they had the same access we do.”

Stone also said that because Iranian scientists had to play by tougher rules, they learned to think about every little detail of a study or experiment. Repeating experiments was difficult and costly, so they learned to anticipate what a paper reviewer might ask for—and plan for it. “That allowed them to be competitive in a very tough research field,” Stone said. “It made them better scientists.”

Joining forces in research would unlock the untapped potential the Iranian stem cell scientists hold, Brivanlou said. It would also allow Western and Iranian scientists to share and exchange research materials, allowing for greater genetic diversity in experiments.

Brivanlou hopes to begin collaborating soon, starting by Skype and expanding to other venues: “My dream is to have universities in the United States, such as The Rockefeller University, and institutes in Iran, such as the Royan Institute, to be engaged in a double exchange program as soon as possible,” he said at the conference. 

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Uncombable Hair Syndrome Is a Real—and Very Rare—Genetic Condition
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Keystone/Getty Images

Everyone has bad hair days from time to time, but for roughly 100 people around the world, unmanageable hair is an actual medical condition.

Uncombable hair syndrome, also known as spun glass hair syndrome, is a rare condition caused by a genetic mutation that affects the formation and shape of hair shafts, BuzzFeed reports. People with the condition tend to have dry, unruly hair that can't be combed flat. It grows slower than normal and is typically silver, blond, or straw-colored. For some people, the symptoms disappear with age.

A diagram of a hair follicle
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Although there have been only about 100 documented cases worldwide, one of the world's leading researchers on the condition, Regina Betz, of Germany's University of Bonn, believes there could be thousands of others who have it but have not been diagnosed. Some have speculated that Einstein had the condition, but without a genetic test, it's impossible to know for sure.

An 18-month-old American girl named Taylor McGowan is one of the few people with this syndrome. Her parents sent blood samples to Betz to see if they were carriers of the gene mutation, and the results came back positive for variations of PADI3, one of three genes responsible for the syndrome. According to IFL Science, the condition is recessive, meaning that it "only presents when individuals receive mutant gene copies from both parents." Hence it's so uncommon.

Taylor's parents have embraced their daughter's unique 'do, creating a Facebook page called Baby Einstein 2.0 to share Taylor's story and educate others about the condition.

"It's what makes her look ever so special, just like Albert Einstein," Taylor's mom, Cara, says in a video uploaded to YouTube by SWNS TV. "We wanted to share her story with the world in hopes of spreading awareness."

[h/t BuzzFeed]

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13 Things to Know About DNA Testing Kits
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iStock

The search for our identities—where we came from, what we're made of—is a unifying human experience, and our collective fascination with ourselves as individuals has fueled a booming industry around personal DNA testing. More than 12 million people have had their DNA tested by services like 23andMe and AncestryDNA, and that number is expected to grow substantially in the next few years. But can DNA tests really reveal the nuanced information about ancestry and health that many of us seek? Here are 13 things to know about these personal testing kits.

1. PERSONAL DNA TESTING IS SIMPLE—ALL IT TAKES IS A LITTLE SPIT.

Typically, all you have to do is collect some of your saliva or swab the inside of your cheek, then seal the sample in a container and mail it to the lab in a pre-labeled envelope or box. Six to eight weeks later, you can see the results online.

Most personal DNA tests are relatively affordable: Kits from industry leaders like 23andMe, AncestryDNA, Family Tree DNA, MyHeritage DNA, and Living DNA range from $69 to $199. In some cases, the price depends on which genetic reports a customer opts to receive: For 23andMe, for instance, a test that only aims to analyze your ancestry is cheaper than one that also includes health information. Check out this Wiki chart from the International Society of Genetic Genealogy to compare companies' offerings.

2. THE KITS LOOK FOR GENETIC VARIATIONS CALLED SINGLE NUCLEOTIDE POLYMORPHISMS.

After extracting DNA from your cheek swab or saliva sample, DNA testing companies search your DNA for certain genetic variants. The building blocks of DNA are chemical bases called nucleotides, which come in four varieties—A, T, C, and G (adenine, thymine, cytosine, and guanine, respectively). We have 3 billion pairs of these bases, so 6 billion letters in all, strung together in a sequence. Altogether, this genetic information is called your genome.

DNA testing companies determine which of the four letters is present at many locations in your genome. Much of the sequence is shared among humans, so the companies focus on specific letters that vary from person to person, known as single nucleotide polymorphisms (SNPs). Many SNPs have some biological relevance. For example, having one variant of a specific SNP near the gene OCA2, which codes for a protein believed to be involved in producing the dark pigment melanin, makes it much more likely you’ll have blue or green eyes. Other traits and even some diseases are also associated with certain SNPs, some more strongly than others.

3. KIT ACCURACY CAN VARY BASED ON TESTING METHODS.

According to company spokesperson Scott Hadly, 23andMe can identify SNPs with 99.9 percent accuracy, which is in a plausible range for the methods they use. Since many other major companies use similar techniques, their accuracy may be about equivalent—but not all tests meet the same standards. Recently, one test failed to recognize that a purportedly human DNA sample actually came from a golden retriever named Bailey. It did recommend, though, that based on her genetics, Bailey should take up cycling and basketball. The canine’s results came from the lighthearted Superhero DNA Test, which claims to tell customers about their strength, speed, and intelligence. It only tests for four genetic variants, while the pricier kits can include tens of thousands of variants. (It's also worth noting that no matter how many variants a kit tests for, it can't predict complex traits like intelligence, which are influenced by many different genes and environmental factors.)

You should steer clear of companies that offer dubious predictions about your optimal diet, what sports you'll be good at, and other questionable tips. Experts say using DNA tests to extrapolate this information is at best premature and at worst pseudoscience, especially because the recommendations are often based on just a handful of studies on specific groups of people, commonly white men. "The results that have been acquired in one population are not always generalizable to other populations," Jason Rosenbaum, an assistant professor at the University of Pennsylvania's medical school, tells Mental Floss.

4. DNA CAN REVEAL GENETIC CONNECTIONS—BUT INFORMATION ON SOME POPULATIONS IS LIMITED.

Companies use various methods to determine ancestry, but the tests generally involve comparing the customer's DNA to reference DNA meant to represent populations from different geographical regions. Since most people have at least somewhat mixed heritage, ancestry is often represented in percentages: 26 percent Polish, 14 percent Greek, and so on.

These tests aren’t able to guarantee where your ancestors actually lived—they can’t directly compare your data to DNA from people who lived hundreds of years ago, as Adam Rutherford, a British geneticist, pointed out to Gizmodo. And not all groups of people are equally represented in the reference populations, which can impact how precise your results are. People with European backgrounds are overrepresented in the reference data, while there are fewer references relevant to those whose roots lie in the Middle East or Asia, for example. But as research is done on a more diverse range of people, companies are tweaking their analyses to provide more detailed ancestry information to people from all over the world.

5. SOME HINT AT YOUR DNA'S DISTANT HISTORY—INCLUDING NEANDERTHAL HERITAGE.

All humans alive today can trace their mitochondrial lineage back to one woman nicknamed Mitochondrial Eve, who may have lived in Africa about 150,000–200,000 years ago (although this is a source of perennial debate). She wasn't the first modern human woman or the only woman living at the time; other women from her time also have descendants today. They just don’t have an unbroken line of female descendants like Mitochondrial Eve does.

We inherit our mitochondria—the parts of our cells that make energy—from our mothers. Some companies offer a mitochondrial DNA test that allows you to find your maternal haplogroup, which includes people who all share a maternal ancestor thousands or tens of thousands of years ago.

Men can learn about their paternal line through the Y chromosome, which is passed from father to son; certain SNPs on the Y chromosome can be used to determine a person's paternal haplogroup. (Women can find their paternal haplogroup through their biological father or brother.) There’s a "Y-chromosomal Adam," too, although scientists disagree about whether he lived around the same time as Mitochondrial Eve.

A home DNA test might even tell you that you're a little bit Neanderthal, which is especially common in Caucasian and Asian people. Don't worry about Neanderthals' reputation as dull brutes. We now know they were intelligent, used tools, and had their own complex culture.

6. YOU COULD FIND RELATIVES YOU DIDN'T KNOW YOU HAD.

Many DNA testing services allow customers to see whether other users of the same service are biologically related. This can be a boon for anyone assembling a detailed family tree, as well as any adoptees wondering about their biological families. Several people have discovered siblings they never knew they had through these services. In one case, two women—one adopted through an agency and another adopted by a family who found her in the woods as a baby—realized they were long-lost sisters.

Not everyone is pleased to uncover family secrets, though, and you should proceed with caution before you allow a company to match you with new relatives.

7. DNA TESTS CAN REVEAL HEALTH INFORMATION …

While genetic testing might reveal your inability to detect the unique odor of asparagus pee, most people are seeking deeper information, such as whether they have genetic variants associated with diseases like Alzheimer's or breast cancer.

Genetic risk is all about probability. For example, it may be frightening to learn you have an SNP associated with a tenfold increase in risk for a disease—but if that disease only affects 0.01 percent of people, your risk is still just 0.1 percent. Even if you have a SNP strongly associated with a more common illness and show signs of having it, you should see a doctor to get a proper evaluation.

And having a disease-associated SNP isn't a diagnosis. Rare variants are especially likely to lead to false positives: if a variant is only found in one in a million people, it’s more likely that the positive test result is an error than it would be with a more common variant. Some companies report on genetic variants that doctors and scientists haven't deemed medically useful to test for—which is why combing over every SNP is of dubious use. Shoumita Dasgupta, an associate professor in the biomedical genetics program at Boston University, tells Mental Floss that healthcare providers often don't order tests for these SNPs "because professionals have come to the conclusion that the predictive value of these tests is limited."

8. … INCLUDING YOUR RISK OF CERTAIN KINDS OF CANCER.

In March 2018, the FDA granted 23andMe permission to give customers information about certain mutations in the genes BRCA1 and BRCA2 that dramatically increase the risk for breast and ovarian cancer. Some people with a faulty BRCA gene take precautions to prevent or detect cancer early, including undergoing preventive double mastectomies, as Angelina Jolie famously did in 2013.

An important caveat: This test only screens for three SNPs in the BRCA genes that are connected to a dramatic increase in the risk of developing cancer. A positive result merits a consultation with doctor, but a negative result doesn't necessarily mean you're free from the risk of cancer, hereditary or not.

9. SOME DNA TESTING KITS ARE PRESCRIPTION ONLY.

GeneSight is designed to reveal what psychiatric medications will work best for a particular patient. Fertilome aims to show whether a person has genetic markers associated with increased risk of fertility problems, and is intended to help people make reproductive decisions such as whether to freeze eggs or try another round of in vitro fertilization. However, both Fertilome and GeneSight have faced criticism from experts who say there's not enough evidence that the tests are clinically valuable. They're also expensive: Fertilome costs $950, while GeneSight can cost several hundred dollars (though the price can drop to zero with certain insurance plans).

10. MORE DATA ISN'T ALWAYS BETTER.

With the price of DNA analysis falling rapidly, some companies are offering to analyze the order of all the letters of a customer's DNA—what's called sequencing—rather than just looking at SNPs. Sequencing is important in research and medicine: Dasgupta says she now sees some physicians ordering full sequences of multiple genes or even whole exomes (the protein-coding sequences in the genome) for patients.

Exome sequencing is useful to doctors and scientists because it allows them to look for genetic variants beyond the commonly tested SNPs. But every test has a risk of generating false positives, so excessive testing means an increased risk that a person will receive an incorrect diagnosis. Rosenbaum likens it to MRIs. "It's one reason why we don't just give MRIs to everyone, because you're going to turn up things that lead you to believe there's disease where there isn't disease," he explains.

11. YOUR DNA RESULTS COULD CONTRIBUTE TO RESEARCH.

Some home DNA testing companies ask customers to participate in research, answering questions about everything from their sleep habits to their personalities. The goal is to discover previously unknown associations between genetic variants and specific traits. "The way many genetic studies are designed, the more people who are recruited to the study, the more likely the study will be able to identify genetic factors that impact the trait or condition being studied," Dasgupta says.

Personal DNA testing companies potentially have access to the genetic data of millions of users, giving them a huge opportunity to make these connections. Using customer-provided data, 23andMe has already reported some preliminary discoveries on genetic variants linked to detached earlobes, the risk of Parkinson's disease, and more. Studies based on self-reported information always come with caveats, but they’re common in many fields of research and especially useful when collecting objective data isn't practical or possible. Future research spurred by these observations will reveal whether crowdsourced research like 23andMe's has potential to become part of geneticists' repertoire.

12. YOU COULD POTENTIALLY EARN MONEY FROM YOUR DNA.

One company, Genos, charges $499 to sequence a customer's entire exome, and then offers to connect them with genetic researchers. Participating research partners can offer $50 to $250 to Genos users for completing a study intended to find links between their genetic information and any trait or condition the researchers are studying, including dementia, cancer, and infectious disease. Meanwhile, the newly formed company Nebula proposes to sequence customers' genomes, secure them with blockchain technology, and allow customers to control the data—including selling it to biotech and pharmaceutical companies in exchange for Bitcoin-like cryptocurrency. There’s still potential for privacy issues, however, since there’s no guarantee companies that rent or purchase genetic data will keep it secure.

13. YOUR DNA MIGHT ONE DAY HELP TO CATCH A CRIMINAL.

Recently, police investigators in California arrested a man suspected to be the Golden State Killer, thought to be responsible for dozens of rapes and burglaries and at least 12 murders in California from 1976 to 1986. The suspect left DNA behind at the scene of a 1980 murder; after having the DNA analyzed, the investigators created a fake profile on the genealogy website GEDMatch and uploaded the data, hoping it would turn up some of the killer's relatives. It did—and with the help of genealogy experts, the investigators followed the genetic trail to the Sacramento home of 72-year-old Joseph James DeAngelo, who was a cop during the first several years of the deadly crime spree.

The case has raised ethical and privacy concerns for some experts. Genetic data can be stored indefinitely, and it’s possible to use a person's DNA to make inferences about biological relatives who haven’t even taken DNA tests.

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