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When Muscular Dystrophy Is Personal — And Global

Chris Chege (courtesy Romana Vysatova)

Chris Chege (courtesy Romana Vysatova)

By Fred Thys
Guest Contributor

Every once in a while, I’m grateful I live in such a medically-minded town, with many deep thinkers trying to figure out treatments and cures for some very tough diseases.

I felt this way over the summer, at a conference in Boston on Facioscapulohumeral Muscular Dystrophy, a genetic disorder that affects 1 in 8,333 people and has no treatment. I did not attend the meeting due to some theoretical interest in the topic; for me, it’s personal.

My mother and grandmother suffered from the condition, and so does my brother. It causes gradual loss of muscle function, notably in the face, and in the muscles that mobilize the shoulder blades and the upper arm, but also in the legs.

My brother first developed symptoms when he was 15, and found that he could no longer run as fast as his high school soccer teammates. Since the age of 43, he has been confined to a wheelchair or scooter, unable to walk or stand.

But at the conference in August, I also realized that this illness with such a profound impact on my family, also has a global reach. Indeed, in regions like Africa, the condition is only just beginning to be acknowledged.

Enter: Chris Chege

I first saw Chege sitting on a tall stool at the back of the room with his wife. Their presence proved that the condition affects Africans, too, something that isn’t widely acknowledged. Chege and his wife had traveled to Boston from their home in Thika, in central Kenya, 30 miles Northeast of Nairobi.

An interview with Chege pointed to one possible reason that conference room was full, mainly, of white people: most people with the condition in Africa may not have been diagnosed with it yet.

But Chege said he sees others with FSHD in Kenya. He said he can tell.”By the way they walk,” he said. “I see them on national television when journalists go to their homes to interview them.” Continue reading

Please Discuss: ‘Gene Drives,’ Sci-Fi Scary Or Cool Leap Forward?

Scientists say new "gene drive" technology could help fight malaria by affecting the mosquitoes that carry it. (Wikimedia Commons)

Scientists say new “gene drive” technology could help fight malaria by affecting the mosquitoes that carry it. (Wikimedia Commons)

Perhaps you’ve followed that teeny tiny controversy around genetically modified foods, the “GMO” debate. Or you watched the fierce back-and-forth over whether it was a good idea to modify a strain of avian flu in the lab to make it spread more easily, in order to study it.

If this is your kind of spectator sport, it’s time to learn about gene drives, a powerful new genetic technology that basically flips Charles Darwin on his head, allowing a sort of artificial selection to help chosen genes come to dominate in a population.

A paper just out in the journal eLife outlines a way to use gene drives to spread just about any altered gene through wild populations that use sex to reproduce. And a related paper just out in the journal Science calls for greater oversight and a public discourse about the potential risks and benefits of gene drive technology — now, while it’s still in early stages and confined to labs.

I can already imagine the “pro” side of the debate: “This could eradicate malaria. Reduce the use of pesticides. Bolster agriculture for a crowded planet.” And the “con” side: “But what if it goes wrong out in the wild? Have you read no science fiction?”

I spoke with two of the paper’s co-authors: Kevin Esvelt, a technology development fellow at the Wyss Institute for Biologically Inspired Engineering and Harvard Medical School, who is also the lead author of the eLife paper; and Kenneth Oye, Professor in Engineering Systems and Political Science at MIT and director of policy and practices of the National Science Foundation’s Synthetic Biology Engineering Research Center. Our conversation, edited:

CG: So what exactly is a gene drive and why are we talking about it now?

Kevin Esvelt: A gene drive is a potential new technology that may let us alter the traits of wild populations but only over many generations. We think that gene drives have the potential to fix a lot of the problems that we’re currently facing, and that natural ecosystems are facing, because it allows us to alter wild populations in a way that we could never do before.

We would really like to start a public conversation about how we can develop it and use it responsibly, because we all depend on healthy ecosystems and share a responsibility to pass them on to future generations.

So how do they work? The reason we haven’t been able to alter wild populations to date is natural selection. When you say natural selection, you think, ‘How many organisms survive and reproduce?’ And that’s pretty much how it works. The more likely you are to survive and reproduce, then the more copies of your genes there are going to be. So genes that help an organism reproduce more often are going to be favored.

The problem is, when we want to alter a species, the way we want to alter it usually doesn’t help it survive and reproduce in nature. But that’s not the only way that a gene can reproduce. We have two copies of each gene, and when organisms have children, each of the offspring has a 50% chance of getting either copy. But you can imagine that a gene could gain an advantage if it could stack the deck — if it could ensure that it, rather than the alternate version, was inherited 70%, 80%, 90%, or 99% of the time.

How gene drives affect which genes are passed down (Courtesy Kevin Esvelt)

How gene drives affect which genes are passed down (Courtesy Kevin Esvelt)

There are a lot of genes in nature that do exactly this; they’ve figured out an incredible variety of ways of doing that. Almost every species in nature has what we would call an ‘inheritance-biasing gene drive’ somewhere in its genome, or at the very least the broken remnants of one. They’re actually all over the place in nature.

The idea that we could harness these to spread our alterations through populations has actually been around for a long time. Continue reading

Tinkering With Baby’s Genes: FDA Reviews Controversial Fertility Technique

By Karen Weintraub
Guest Contributor

FDA hearings in Washington this week have raised an ethical quandary: If we have the scientific power to help a sick woman give birth to healthy children, should we do it? Even if it requires us to cross an ethical line in the sand drawn decades ago by hundreds of nations worldwide?

A reproductive biologist from the Oregon Health and Science University in Beaverton, Shoukhrat Mitalipov, has asked the federal government for permission to test an unprecedented gene replacement technique in people. If he succeeds, women with mitochondrial diseases will be able to have their own, biological children, without passing on their disease.

But some others worry that this research will open up an ethical Pandora’s Box, legitimizing human genome manipulation. Plus, they say, the science is premature. This technique has only been tested in a handful of monkeys and it’s way too early to try in people, they say.

At root is some pretty technical science in an area that’s not yet well understood.
Mitochondrial disease is driven by mistakes in the 37 genes that drive the mitochondria — which, as you might remember from freshman biology, provide every cell with energy. Mitochondria is passed down from mother to child; the father’s mitochondria dies with him.

Mitalipov wants to get rid of the mother’s flawed mitochondria and replace them with a healthy donor’s. He would take the nucleus of an egg cell from the sick woman and implant it in an egg cell from a healthy donor, after the donor’s nucleus has been removed. When the egg is fertilized, the 20,000 genes in the mother’s nuclear genome will mix with the same number from the father’s, plus 37 healthy genes from the mitochondria of the donor. The result, Mitalipov says, will be a normal child.

Not everyone agrees with that last point. Even if the child appears healthy, it’s possible that it will have genetic problems during development, later in life or that will only appear when that child has children.

Sharon and Alana Aaarinen/Photo: Karen Weintraub

Sharon and Alana Aaarinen/Photo: Karen Weintraub

One potential problem: some of the mother’s unhealthy mitochondria will survive the transfer and show up in the child, unnoticed perhaps for generations, before another descendent gets sick. Mitalipov says this is impossible, that his technique promises nearly 100 percent swap of mitochondria, but some scientists remain unconvinced.

Mixing mitochondria from two “mothers” can put mice at higher risk for diabetes, stroke and heart disease, according to research.

Continue reading

The New Fertility Frontier: A Child With Three Biological Parents

Sharon and Alana Aaarinen (Karen Weintraub)

Sharon and Alana Aaarinen (Karen Weintraub)

Don’t miss this fascinating story by CommonHealth contributor Karen Weintraub detailing an ethically questionable new fertility treatment that involves three biological parents in order to avoid a rare but devastating mitochondrial disease.

Here’s the top of the piece, published in today’s New York Times:

Alana Saarinen sat at the piano, playing smoothly and with feeling. Behind her, plastic toys shared floor space with a book of plays she’d been writing. Her mother beamed.

Alana is apparently a normal, well-adjusted 13-year-old. But there is something extraordinary about her — every cell in her body is different in a way that is nearly unprecedented.

Alana was conceived with genetic material from three parents: Sharon and Paul Saarinen, who provided the egg and sperm, and a second woman who contributed genes to Alana’s mitochondria, the tiny power plants that fuel every cell.

The experimental technique making this possible — a cytoplasmic transfer, in Alana’s case — was halted by the Food and Drug Administration in 2001. Now, despite uncertainties about its safety, scientists in the United States and the United Kingdom are urging legalization of a more targeted version. Critics say it hasn’t been adequately studied and crosses the line into genetic engineering.

The story also explores the origins of the experimental cytoplasmic transfer and explains how the technique is being improved. Karen adds this in an email:

Researchers never followed the children born in the late 1990s and 2000s of this cytoplasm transfer technique, so it’s not clear what the risks are of this form of conception. Continue reading

The Genetics Of Autism: Inside The Brains Of The Supple Boys

Don’t miss Lynn Jolicoeur’s excellent piece on WBUR this morning about the genetics of autism and the two young Natick boys, Tommy and Stuart Supple, whose gene mutations are the focus of research by Stanford neuroscientist Dr. Thomas Sudhof.

(Jesse Costa/WBUR)

(Jesse Costa/WBUR)

From Lynn’s story:

…The Stanford University neuroscientist — who this year shared the Nobel Prize in medicine for his decades of study into how brain cells communicate — has been studying Tommy and Stuart’s genes, specifically an alteration in one gene, for five years. The Supples hosted Sudhof Wednesday night at a Boston fundraiser in support of his research into the functioning of brain synapses in autism…

According to the Supples, Sudhof’s work is helping conquer the “defeatism” surrounding the neurocognitive disorder.

“He doesn’t think this is unknowable at all. He thinks that it’s very knowable,” Kate Supple said. “We all put so much time and effort into dealing with the symptoms of autism. But you also have to look to deal with the underlying disease.”

For many parents of children with autism, the disorder is a mystery. They have no idea what caused it and focus on therapies to help address the symptoms. But after the blow of both boys being diagnosed before their 2nd birthdays, the Supples sought out private genetic testing without the encouragement of their doctors. Continue reading

Growing Up Genomic: What Happens When You Know All A Baby’s Genes?

DNA

How would it change your life if you knew all your genes from the get-go? I mean, not just a little foray onto 23andMe when you’re 23 and curious, but a full sequencing of all your significant DNA at birth? Would you grow up with some deeply different ideas about yourself and your future than you would have otherwise? If, say, you knew you were at high risk for cancer or Alzheimer’s?

This is not just a thought experiment. Boston-based researchers have just announced that they will be seeking subjects for a $6-million study called BabySeq that involves sequencing more than 200 babies’ full sets of genes at birth, then following them to see how that genetic knowledge affects their lives and medical care. To which I say: Darn. This genomic future keeps arriving even faster than I expect.

The press release is below — Boston parents-to-be, take note: Recruitment is expected to begin early next year.  I spoke with Dr. Robert C. Green, one of the lead researchers; our conversation, lightly edited:

So what is the question that this research project seeks to answer?

RCG: This is a research project at Brigham and Women’s Hospital and Boston Children’s Hospital, led by myself and Alan Beggs, that asks the question: What happens when you sequence newborn babies? What happens when you sequence healthy newborn babies and what happens when you sequence ill newborn babies?

The philopsophy with which we’ve started this project is that sequencing is here,  it’s getting cheaper and cheaper, and more accessible. And everyone thinks that this is going to be a great boon to your health; it’s going to tell you about diseases and conditions that are going on, and it’s going to warn you about diseases and conditions to come. And we’d like to find out how this really plays out in these two very different situations.

If you have access to the reference book of life, and you  can open it to any page you want, what do you get to read there, and how does it influence you?

In other words, if you have access to the reference book of life, and you  can open it to any page you want, what do you get to read there, and how does it influence what your doctor does with you, what your doctor says to you, what your parent-and-child bonding is like? These are tremendously controversial issues, they’re issue we simply don’t know the answers to because the technology is so new, but it’s hurtling down the track at such speed that we must ask these questions as soon as we can, and as scientifically as we can, so that we understand the answers as the technology is being rolled out, not after it’s rolled out.

How many babies will be sequenced in this ‘BabySeq’ project?

There will be 480 babies enrolled, of whom half — or 240 — would be sequenced. It’s designed as a randomized, controlled trial. Continue reading

For $9,000, Your Personal Genome Sequenced

Updated at 10:52 AM, August 28th, 2013

If you’ve got $9,000 handy and a hankering to learn more about your genetic roadmap, here’s your chance.

Partners Healthcare, the largest hospital system in Massachusetts, announced yesterday that complete genomic sequencing is now available to patients. The full test would take 16 weeks, said spokesman Rich Copp, and insurance coverage would be determined on a case by case basis.

greyloch/flickr

greyloch/flickr

Formerly a technique limited to the laboratory, complete genome sequencing maps the 3 billion pairs of DNA in a human’s genome. In recent years, scientific and technical advances have made genetic sequencing available for clinical use.

That’s a far cry from 2006, when scientists were still diagnosing a “market failure” in providing “rapid, low-cost medical grade genomes.” It was enough to spur the creation of the Archon Genomics X-Prize, which promised a $10 million prize to a team that could sequence 100 genomes in 30 days for less than $10,000 per genome. The X-Prize team ultimately called off the competition, citing commercial interests making the prize incentive superfluous:

What we realized is that genome sequencing technology is plummeting in cost and increasing in speed independent of our competition. Today, companies can do this for less than $5,000 per genome, in a few days or less – and are moving quickly towards the goals we set for the prize. – Peter Diamandis, chairman of X-Prize Committee

But where, exactly, will your new $9,000 map lead you? Shortly after he was diagnosed with cancer, Steve Jobs spent $100,000 on getting his genome completely sequenced. Continue reading

Imagining Gene Therapy For Girls With Rare Rett Syndrome

By Karen Weintraub
Guest Contributor

Imagine your daughter has a debilitating genetic disease — a disorder that will plague her for the rest of her life. Now imagine hearing about a treatment that might improve her condition dramatically.

{EHPhoto}/flickr

{EHPhoto}/flickr

That the kind of brimming-with-hope feeling many parents had six years ago when Scottish researcher Adrian Bird announced that he had reversed a genetic condition called Rett Syndrome in adult mice.

Of course everyone who heard about the study understood that curing a mouse is not the same as helping a person, but the improvements stunned researchers who had assumed that a mouse would never be able to recover from the restricted mobility, tremors and unusual brain activity that characterize the mouse version of the disease.

The parents of girls with Rett Syndrome – which occurs mainly in females, because males with the genetic mutation usually die before birth – suddenly had hope that their children might someday be able to talk, run, wave or blow them a kiss. Continue reading

Mom’s Rich, Fatty Diet May Trigger Taste For Drugs In Offspring

Yesterday, we reported on a powerful link between kids who gulp down sweet, sugar-laden drinks and their increased risk of becoming obese. Here’s a sad, what-goes-around-comes-around postscript to that story:

sugarMothers (at least mother rats) fed high-fat, high-sugar diets while pregnant may have kids with a “taste” for alcohol and a sensitivity to drugs, according to research presented at an annual meeting of the American Psychological Association.

Here’s some of the APA news release:

Vulnerability to alcohol and drug abuse may begin in the womb and be linked to how much fatty and sugary foods a mother eats during pregnancy, according to findings from animal lab experiments presented at APA’s 121st Annual Convention.

“The majority of women in the U.S. at child-bearing age are overweight, and this is most likely due to overeating the tasty, high-fat, high-sugar foods you find everywhere in our society. The rise in prenatal and childhood obesity and the rise in number of youths abusing alcohol and drugs merits looking into all the possible roots of these growing problems,” said Nicole Avena, PhD, a research neuroscientist with the University of Florida’s McKnight Brain Institute.

Compared to pups of rats that ate regular rodent chow, the offspring of rats that ate high-fat or high-sugar diets while pregnant weighed more as adults and drank more alcohol, and those on high-sugar diets also had stronger responses to commonly abused drugs such as amphetamine, Avena said. Her presentation examined experiments from three studies, each lasting about three months and involving three to four adult female rats and 10 to 12 offspring in each dietary condition.

Researchers compared weight and drug-taking behavior between the offspring of rats fed diets rich in fats, sucrose or high-fructose corn syrup with the offspring of rats fed regular rodent chow during gestation or nursing. They tested both sucrose and high-fructose corn syrup because they are chemically different and could cause different outcomes, Avena said. Sucrose occurs naturally and is commonly processed from sugar cane or sugar beets into table sugar, whereas high-fructose corn syrup is synthesized from corn.

To determine effects of the mothers’ diets during gestation, the offspring of rats fed the high-fat, high-sucrose or high- fructose corn syrup diets were nursed by mother rats that were eating regular chow. To determine the effects of the mothers’ diets on the offspring during nursing, the pups with mothers that had eaten regular chow were nursed by mother rats that were eating either the high-fat, high-sucrose or high-fructose corn syrup diets.

The pregnant rats’ high-fat diet contained 50 percent fat, Continue reading

Breaking: Supreme Court Says Genes Cannot Be Patented

DNA

Readers, we’ll be discussing this on Radio Boston today at 3 p.m.; any particular comments or questions to be mentioned on air? Please write them in the Comments below.

From the New York Times here:

Human genes may not be patented, the Supreme Court ruled on Thursday.

“A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated,” Justice Clarence Thomas wrote for a unanimous court. But manipulating a gene to create something not found in nature is an invention eligible for patent protection.

The case concerned patents held by Myriad Genetics, a Utah company, on genes that correlate with increased risk of hereditary breast and ovarian cancer.

The central question for the justices in the case, Association for Molecular Pathology v. Myriad Genetics, No. 12-398, was whether isolated genes are “products of nature” that may not be patented or “human-made inventions” eligible for patent protection.

And its take on the implications:

The court’s ruling will shape the course of scientific research and medical testing, and it may alter the willingness of businesses to invest in the expensive work of isolating and understanding genetic material.

From The Wall Street Journal:

The court was handing down one of its most significant rulings in the age of molecular medicine, deciding who may own the fundamental building blocks of life.

The case involved Myriad Genetics Inc., MYGN +10.29%which holds patents related to two genes, known as BRCA1 and BRCA2, that can indicate whether a woman has a heightened risk of developing breast cancer or ovarian cancer.

Justice Clarence Thomas, writing for the court, said the genes Myriad isolated are products of nature, which aren’t eligible for patents.

“Myriad did not create anything,” Justice Thomas wrote in an 18-page opinion. “To be sure, it found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention.”

Even if a discovery is brilliant or groundbreaking, that doesn’t necessarily mean it’s patentable, the court said.

However, the ruling wasn’t a complete loss for Myriad. The court said that DNA molecules synthesized in a laboratory were eligible for patent protection. Myriad’s shares soared after the court’s ruling.

Further reading: Continue reading