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What Iran May Be Able to Teach Us About Stem Cells

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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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Why DNA Is So Hard to Visualize
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Picture a strand of DNA and the image you see will likely be similar to the artist’s rendering above. The iconic twisted ladder, or double-helix structure, was first revealed in a photo captured by Rosalind Franklin in the 1950s, but this popular visualization only tells part of the story of DNA. In the video below, It’s Okay to Be Smart explains a more accurate way to imagine the blueprints of life.

Even with sophisticated lab equipment, DNA isn’t easy to study. That’s because a strand of the stuff is just 2 nanometers wide, which is smaller than a wavelength of light. Researchers can use electron microscopes to observe the genetic material or x-rays like Rosalind Franklin did, but even these tools paint a flawed picture. The best method scientists have come up with to visualize DNA as it exists inside our cells is computer modeling.

By rendering a 3D image of a genome on a computer, we can see that DNA isn’t just a bunch of free-floating squiggles. Most of the time the strands sit tightly wound in a well-organized web inside the nucleus. These balls of genes are efficient, packing 2 meters of DNA into a space just 10 millionths of a meter across. So if you ever see a giant sculpture inspired by an elegant double-helix structure, imagine it folded into a space smaller than a shoe box to get closer to the truth.

[h/t It’s Okay to Be Smart]

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Scientists Remove Disease-Causing Mutations from Human Embryos
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Researchers have successfully edited the genes of viable human embryos to repair mutations that cause a dangerous heart condition. The team published their controversial research in the journal Nature.

The versatile gene-editing technique known as CRISPR-Cas9 is no stranger to headlines. Scientists have already used it to breed tiny pigs, detect disease, and even embed GIFs in bacteria. As our understanding of the process grows more advanced and sophisticated, many researchers have wondered how it could be applied to human beings.

For the new study, an international team of researchers fertilized healthy human eggs with sperm from men with a disease called hypertrophic cardiomyopathy, a condition that can lead to sudden death in young people. The mutation responsible for the disease affects a gene called MYBPC3. It’s a dominant mutation, which means that an embryo only needs one bad copy of the gene to develop the disease.

Or, considered another way, this means that scientists could theoretically remove the disease by fixing that one bad copy.

Eighteen hours after fertilizing the eggs, the researchers went back in and used CRISPR-Cas9 to snip out mutated MYBPC3 genes in some of the embryos and replace them with healthy copies. Three days later, they checked back in to see how their subjects—which were, at this point, still microscopic balls of cells—had fared.

The treatment seemed successful. Compared to subjects in the control group, a significant number of edited embryos appeared mutation- and disease-free. The researchers also found no evidence that their intervention had led to any unwanted new mutations, although it is possible that the mutations were there and overlooked.

Our ability to edit human genes is improving by the day. But, many ethicists argue, just because we can do it doesn’t mean that we should. The United States currently prohibits germline editing of human embryos by government-funded researchers. But there’s no law against such experimentation in privately funded projects like this one.

The same day the new study was published, an international committee of genetics experts issued a consensus statement advising against editing any embryo intended for implantation (pregnancy and birth).

"While germline genome editing could theoretically be used to prevent a child being born with a genetic disease, its potential use also raises a multitude of scientific, ethical, and policy questions,” Derek T. Scholes of the American Society of Human Genetics said in a statement. “These questions cannot all be answered by scientists alone, but also need to be debated by society."

Ethicists and sociologists are concerned by the slippery slope of trying to build a better human. Many people with chronic illness and disability live happy, complete lives and report that they’re limited more by discrimination than by any medical issues.

Disability studies expert Lennard Davis of the University of Illinois says we can’t separate scientific decisions from our society’s history of violence against, and oppression of, disabled and sick people.

“A lot of this terrific science and technology has to take into account that the assumption of what life is like for people who are different is based on prejudice against disability,” he told Nature in 2016.

Rosemary Garland-Thomson is co-director of the Disability Studies Initiative at Emory University. Speaking to Nature, she said we are at a cultural and ethical precipice: “At our peril, we are right now trying to decide what ways of being in the world ought to be eliminated.”

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