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Bioengineering, Ethics, Fertility, Genetics, In the News, Parenting, Pregnancy

And baby makes four? KQED Forum guests discuss approval of three-parent IVF in UK

And baby makes four? KQED Forum guests discuss approval of three-parent IVF in UK

newborn feet Scope BlogLast week, the U.K. House of Commons voted to legalize a controversial in vitro fertilization technique called mitochondrial donation, popularly known as the “three-parent baby” technique. The technique is intended for mothers who have an inherited genetic defect in their mitochondria – the fuel compartments that power our cells – and can help them from passing on the incurable disease that often entails years of suffering and ends in premature death.

Doctors replace the DNA from a donor egg with the mother’s DNA, use sperm from the father to fertilize it, then implant it into the mother’s uterus via IVF technology. The donor egg’s cytoplasm contains defect-free mitochondria and DNA from both parents. Proponents say the technique gives parents with mitochondrial disease the chance to have disease-free children, but critics say it brings us one step closer to the reality of genetically modified “designer babies.”

On Friday, Stanford law professor and biotechnology ethicist Hank Greely, JD, was among the guests on KQED’s Forum broadcast to discuss the issue. He’s in favor of the procedure, noting that when looking at genetic modifications, “the purpose, the nature, [and] the safety” should be considered. “There are some things that I think shouldn’t be done,” he said, adding that “things like this, which gives women who have defective mitochondrial DNA their only chance to have genetic children of their own… if the safety proves up… seems to be a good use.”

Previously:  Daddy, mommy and ? Stanford legal expert weighs in about “three parent” embryos and Extraordinary Measures: a film about metabolic disease
Photo by Sean Drelinger

Genetics, Science, Stanford News, Technology

Major genomics exhibit, staffed with Stanford volunteers, now open in San Jose

Major genomics exhibit, staffed with Stanford volunteers, now open in San Jose

Abbey Thompson, a Stanford PhD candidate, gives tour of Genome exhibit at the The Tech Museum of Innovation in San Jose on Wednesday, February 4, 2015. ( Norbert von der Groeben/Stanford School of Medicine )

Last week I checked out the museum exhibit “Genome: Unlocking Life’s Code,” which just arrived at the Tech Museum of Innovation in San Jose.

Created to honor the 10-year anniversary of the completion of the Human Genome Project by the National Institutes of Health and the Smithsonian Institution, the exhibit’s goal is to demystify the science of genetics. It includes demonstrations of the equipment used in sequencing the human genome, videos about the practical and ethical implications of having your own genome sequences, and interactive exhibits that let you explore which genetically-determined characteristics — like hair color or even being lactose intolerant — you might have. There is a section devoted to determining ancestry from your DNA; it turns out that we humans all hail from east Africa.

The part of exhibit I can’t get out of my mind was made up of transparent cylinders filled with sand. It was a comparison of the genomes of different species. We humans are, of course, a complex species and so is our genome, with 20,000 genes. But amoebas and barley (yes, the grain) have bigger genomes than we do!

Volunteer docents, many from the Stanford genetics community, are ready to answer questions from visitors of all ages. Michael Cherry, PhD, professor of genetics, has trained as a docent for the exhibit. Members of his lab team have volunteered, too.

“It is good for us to learn how to communicate our science to the general public — to explain things that seem basic to us,” Cherry said in an Inside Stanford Medicine article I wrote on the exhibit. “Visitors tell us what is important to them; they stimulate us.”

The Tech Museum and Stanford’s Genetics Department have a long-term relationship. For more than a decade, the department has sponsored Stanford at the Tech, a program that aims to explain the science of genetics to the general public.

“It is so critical that we reach the public,” Michael Snyder, PhD, professor and chair of genetics told me. “We are undergoing a genetics revolution, where everyone can get their DNA sequence determined, and it will transform the way medicine is practiced.”

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Genetics, Neuroscience, Stanford News

“The uncertainty was killing me”: A student’s tale of genetic testing for Huntington’s disease

"The uncertainty was killing me": A student's tale of genetic testing for Huntington’s disease

happyImagine you had a 50 percent chance of being diagnosed with a disease that progressively breaks down the nerve cells of your brain, and that as early as your 30s or 40s you could begin exhibiting a range of symptoms of including involuntary movements, emotional problems and cognitive impairment. Such was the fate of Stanford student Kristen Powers.

Powers was three years old when her mother began experiencing symptoms of an incurable neurodegenerative disorder called Huntington’s disease, which claimed her mother’s life in 2011 at the age of 45. By the time she was 11, Powers became fully aware that she and her brother, Nate, had a 50/50 chance of someday developing the disease. Not long after, she learned that a genetic test could tell her if she carried the gene mutation that causes Huntington’s. The only problem was, she had to be 18 in order to take the test.

“The uncertainty was killing me,” said Powers, who was recently named one of the “15 incredibly impressive students at Stanford” by Business Insider. “I was constantly thinking about this ‘What if?’ scenario and it was very consuming in terms of my thoughts and conversations with my best friend. It was getting very tiresome.”

But rather than letting frustration and anxiety dominate her life, Powers channeled her energy into producing a documentary film, titled Twitch, about her experience growing up with her mother’s illness and the potential of carrying the Huntington’s gene.

“My film helped prepare me a lot because it gave me a sense of control in a process that was, very much, out of my control,” she said. “I could distract myself constructively and positively. My film was also a very important process for preparing for the results.”

Distraction came in the form of learning the documentary film business before she was barely old enough to drive a car. Powers had to pitch the idea of potential investors, raise money, hire a film crew, learn about film rights and copyright laws, work with attorneys to draft contracts, and make sure the production didn’t go broke.

To fund the film, she launched a crowdfunding campaign on Indiegogo. “I had decided that if the fundraising campaign was a failure I would take it as sign that I shouldn’t make the film,” she said.

But in the end she raised $18,025, 80 percent more than the goal amount. “I was so surprised. I had never raised more than $300. Within the first night we hit $1,000 and we hit our goal amount on the one-year anniversary of my mom’s passing,” said Powers.

On May 18, 2012, the long-awaited day finally arrived. Accompanied by her family and best friend, Powers took the test that, in her mind, would dictate major life decisions such as if she would have children. When the test results came back two weeks later, she learned the good news: She tested negative.

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Applied Biotechnology, Biomed Bites, Genetics, History, Research, Videos

Basic research underlies effort to thwart “greatest threat to face humanity”

Basic research underlies effort to thwart "greatest threat to face humanity"

Welcome to this week’s Biomed Bites, a weekly feature that introduces readers to Stanford’s most innovative researchers. 

Stanley Cohen, MD, isn’t a household name. But it probably should be. The Stanford geneticist was instrumental in the discovery of DNA cloning – the technology that underlies innumerable advances in biotechnology and medicine, and led to the founding of biotech giant Genentech.

It wasn’t always thought possible to snip out a gene, stitch it into a new stretch of DNA – often in a different organism – and have it produce a desired protein.

In the video above, Cohen emphasizes that striving to achieve a concrete – and profitable – goal didn’t enable the discovery of gene cloning. First, researchers had to work to understand the basic biological processes. “In order to apply knowledge, it’s necessary to get that knowledge somehow.”

These days, Cohen isn’t resting on his laurels. Instead, he’s striving to thwart what he considers perhaps the “greatest threat to humanity,” drug-resistent microbes.

“My lab is still interested in understanding microbial drug resistance and the way in which microbes exploit host genes to carry out microbial functions such as entering cells, reproducing in cells and exiting from cells,” he said. Scientists need that basic knowledge to develop strategies to thwart the process, he added.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: The history of biotech in seven bite-sized chunks, The dawn of DNA cloning: Reflections on the 40th anniversary and Why basic research is the venture capital of the biomedical world

Aging, Genetics, Immunology, Infectious Disease, Research, Stanford News

In human defenses against disease, environment beats heredity, study of twins shows

In human defenses against disease, environment beats heredity, study of twins shows

Pfc. Lane Higson and Pfc. Casey Higson, identical twins serving in Iraq with the Enhanced Combat Aviation Brigade, 1st Infantry Division. The twins, natives of Myrtle Beach, S.C., joined the Army together and have not separated since.I’m one of those people who’ve paid to have their genomes analyzed for the purpose of getting a handle on susceptibility to this or that disease as time goes by. So it was with great interest that I came across a new study of twins conducted by immunologist Mark Davis, PhD, and fellow Stanford investigators. The study, published in CELL, shows that our environment, more than our heredity, plays the starring role in determining the state of our immune system, the body’s primary defense against disease. This is especially true as we age.

Improving gene-sequencing technologies have focused attention on the role of genes in diseases. But the finding that the environment is an even greater factor in shaping our immune response should give pause to anyone who thinks a whole-genome test is going to predict the course of their health status over a lifetime.

“The idea in some circles has been that if you sequence someone’s genome, you can tell what diseases they’re going to have 50 years later,” Davis told me when I interviewed him for a news release I wrote on the study. But, he noted, the immune system has to be tremendously adaptable in order to cope with unpredictable episodes of infection, injury and tumor formation.

Davis, who heads Stanford’s Institute for Immunity, Transplantation and Infection, is worth taking seriously. He’s made a number of major contributions to the field of immunology over the last 30 years or so.  (Not long ago, I wrote an article about one of those exploits for Stanford Medicine.)

To find out whether the tremendous differences observed between different people’s immune systems reflec tunderlying genetic differences or something else, Davis and his colleagues compared members of twin pairs to one another. Identical twins inherit the same genome, while fraternal twin pairs are no more alike genetically than regular siblings, on average sharing 50 percent of their genes. (Little-known fun factoid: The percentage can vary from 0 to 100, in principle, depending on the roll of the chromosomal dice. But it typically hovers pretty close to 50 percent, just as rolling real dice gives you a preponderance of 6s, 7s, and 8s. Think of a Bell curve.)

Because both types of twins share the same in utero environment and, usually, pretty close to the same childhood environment as well, they make great subjects for contrasting hereditary versus environmental influence. (If members of identical-twin pairs are found to be no more alike than members of fraternal-twin pairs with respect to the presence of some trait, that trait is considered to lack any genetic influence.)

In all, the researchers recruited 78 identical-twin pairs and 27 pairs of fraternal twins and drew blood from both members of each twin pair. That blood was hustled over to Stanford’s Human Monitoring Center, which houses the latest immune-sleuthing technology under a single roof. There, the Stanford team applied sophisticated laboratory methods to the blood samples to measure more than 200 distinct immune-system cell types, substances and activities.

Said Davis: “We found that in most cases – including your reaction to a standard influenza vaccine and other types of immune responsiveness – there is little or no genetic influence at work, and most likely the environment and your exposure to innumerable microbes is the major driver.”

It makes sense. A healthy human immune system has to continually adapt to its encounters with hostile pathogens, friendly gut microbes, nutritional components and more.

“The immune system has to think on its feet,” Davis said.

Previously: Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology’s Holy Grail, Deja vu: Adults’ immune systems “remember” microscopic monsters they’ve never seen before and Immunology escapes from the mouse trap
Photo by DVIDSHUB

Genetics, Research, Science, Stanford News

Show-off! Protein upstages DNA by ordering amino-acid add-ons

Show-off! Protein upstages DNA by ordering amino-acid add-ons

Show-offEvery living cell is a metropolis in which the vast bulk of work is performed by phenomenally productive laborers called proteins. Proteins work so hard – and the work that must be done in a cell changes so rapidly – that turnover in the labor force is immense. To maintain the brisk pace of life inside a cell, new proteins must constantly be assembled.

The machines responsible for that assembly are called ribosomes – as many as 10 million of them within a single mammalian cell, each capable of stapling together up to 200 amino acids (the building blocks of proteins) per second. The resulting amino-acid strings immediately fold themselves into characteristic structures reflecting their precise composition.

There are about 20 different varieties of amino acids, so the number of possible combinations a ribosome can make, in theory, is mind-boggling. But a ribosome doesn’t just piece together whatever protein suits its passing fancy. It carefully heeds instructions stored on lengthy strands of DNA inside the cell’s nucleus, in a massive library known as the genome: a gigantic set of genes (the recipes for proteins), written in a ribosome-readable chemical code. But genes never leave the nucleus, and ribosomes never enter it.

Bridging that physical gap is a substance called messenger RNA, chemically similar to DNA but physically far more flexible and athletic. Like couriers carrying copies of a royal edict, messenger RNA molecules constantly exit the nucleus, where they were produced as portable copies of one gene or another. They head for the watery suburbs of the cell where protein construction takes place. And there, they find a ribosome, climb in, are fed through the ribosome’s molecular machinery, and get spit out like spent ticker tape once the ribosome has finished reading the recipe and assembling the specified protein product.

Under ordinary circumstances, ribosomes faithfully follow genetic instructions. But with all that whirling and whirring, sometimes things go wrong: The mRNA molecule or the ribosome is defective or, for some other reason, the protein-in-the-making is faulty.

Misspelled or misfolded proteins can wreak havoc. Happily, cells have “quality control” teams that can pick apart poorly produced proteins, tear up malfunctioning messenger RNA and retire rotten ribosomes.

In exploring that process, Stanford biochemist Onn Brandman, PhD, and colleagues at the University of California and University of Utah may have turned molecular-biological dogma on its head. In a new study in Science, Brandman and his associates report that they’ve identified a member of the quality-control squad, a protein called rqc2, that gloms onto stalled ribosomes – and then does something no protein has ever previously been shown to do: call out for the delivery of two particular amino acids, which get attached in random sequences to the aberrant protein under construction.

“Our results defy textbook science, showing for the first time that the building blocks of a protein, amino acids, can be assembled without the standard blueprints,” Brandman told me. “In the case we observed, neither DNA nor messenger RNA but a protein directs that a pair of amino acids be randomly added, in small stretches, to the ends of proteins that have stalled mid-synthesis. The function of these ‘tails’  isn’t known. But in yeast, elevated levels are correlated with proteotoxic stress, a condition that in humans may be involved in disorders such as Alzheimer’s, Parkinson’s and Huntington’s disease.”

Previously: Key to naked mole rat longevity may be related to their body’s ability to make proteins accurately and Night of the living dead gene: Pseudogene wakes up, puts chill on inflammation
Photo by Iain Farrell

Biomed Bites, Genetics, Research, Videos

Gene regulation controls identity – and health

Gene regulation controls identity - and health

Welcome to the first Biomed Bites of 2015. We’ll be continuing this series this year — check each Thursday to meet more of Stanford’s most innovative biomedical researchers.

Push play and prepare to blow away many of your preconceptions about genetics. ‘Cause gene aren’t the thing these days. At least not for Michael Snyder, PhD. He leads Stanford’s genetics department and directs the Stanford Center for Genomics and Personalized Medicine. Here’s Snyder:

One of the things we’ve found is that our DNA has a lot more regulatory elements than people previously appreciated. In fact, there are more regulatory elements for genes than the genes themselves.

And that’s not all. What makes you you, is, in fact, your regulatory elements, not so much your genes, which really aren’t that different from those of a chimpanzee or that next-door neighbor you dislike.

Your health may also be governed by these regulatory elements, Snyder says:

This is going to be very, very powerful in a world where many people are getting their human genome sequences and trying to understand what diseases they might be at risk for or what diseases they have and what the underlying causes are.

This knowledge might lead to swifter diagnoses, or even prevent the disease from emerging at all.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Of mice and men: Stanford researchers compare mammals’ genomes to aid human clinical research, Personal molecular profiling detects diseases earlier and  You say “protein interactions,” I say “mosh pit”: New insights on the dynamics of gene expression

Genetics, In the News, NIH, Public Health, Research

The genomics revolution and the rise of the “molecular stethoscope”

The genomics revolution and the rise of the “molecular stethoscope”

ATCGBack in 2012, Stanford bioengineer Stephan Quake, PhD, and colleagues sequenced the genome of a fetus using only a maternal blood sample for the first time. Technology Review later recognized the work as one of the “10 Breakthrough Technologies 2013.”

In a recently published opinion piece (subscription required) in the Wall Street Journal, Quake and Eric Topol, MD, a professor of genomics at the Scripps Research Institute, discuss the method and how it exemplifies the potential of the genomics revolution to provide scientists and clinicians with a new type of stethoscope that allows one to see “inside the body at the molecular level.” They write:

The prenatal molecular stethoscope is the first truly widespread clinical application to result from the human-genome project. The National Institutes of Health has an opportunity to build on this new knowledge of “alien” DNA in healthy individuals, and determine whether it may change their clinical course—the molecular-stethoscope approach. Meanwhile, whole genome sequencing of the germ-line, or native, DNA from populations is under way, with seven ongoing world-wide projects, each sequencing the native DNA from 100,000 or more individuals. It’s projected that nearly two million people will be sequenced by 2017.

Already, the scientific literature is brimming with new applications of the molecular stethoscope. Two studies in the New England Journal of Medicine in December showed that more than 10% of healthy people over age 65 carried so-called somatic mutations in their blood cells, and that these individuals had more than a tenfold increased risk of subsequently developing a blood-based cancer.

Previously: Stanford-developed eye implant could work with smartphone to improve glaucoma treatmentsA simple blood test may unearth the earliest signs of heart transplant rejection and Step away from the DNA? Circulating *RNA* in blood gives dynamic information about pregnancy, health
Photo by Stefano

Autism, Genetics, Research, Stanford News

Unlocking autism’s secrets: Stanford researchers point fingers at a brain cell dark horse

Unlocking autism’s secrets: Stanford researchers point fingers at a brain cell dark horse

Snyder smilingGeneticist Michael Snyder, PhD, has a thing for ‘omes.’ He’s studied genomes, transcriptomes, proteomes and microbiomes. Each term represents looking at something (DNA, RNA, proteins or microorganisms on a grand scale, throughout an entire organism). Most recently he’s been known for combining omics information to generate a dynamic picture of his own changing health over time (he termed the analysis a “integrative personal omics profile, or iPOP, but really, the siren call of “the Snyder-ome” is almost too great to resist).

Now he and postdoctoral scholar Jingjing Li, PhD, have turned their attention to the human “interactome,” a database that includes information about more than 69,000 protein interactions. They’ve used sophisticated algorithms to identify who in the brain is playing nicely with whom, and identified a particular group that seems to play an important role in the development of autism in a part of the brain called the corpus callosum. Importantly, the analysis points a finger at a new cell type in the brain — the oligodendrocytes. These serve as kind of a pit crew for the neurons, coating them in an insulating material to keep electrical signals between cells running smoothly. They’ve published their work today in Molecular Systems Biology.

As Snyder explained in our release:

This is our first glimpse of autism’s underlying biological framework, and it implicates a cell type and region of the brain that have not been extensively studied in this disease. Until now, we’ve suspected that autism could be the result of defects in the neurons themselves. Now it appears that the oligodendrocytes can contribute to the problem by inhibiting neuronal signaling through poor cellular differentiation and myelination.

Snyder, who also directs Stanford’s Center for Genomics and Personalized Medicine, and Li hope that the finding will allow researchers to broaden their net to the corpus callosum, which helps the two halves of the brain communicate with one another. As psychiatrist and study co-author, Joachim Hallmayer, MD, commented:

Autism is an extremely heterogeneous disease. Many genes have been implicated, but environment also plays a role. This study suggests a possible way to subdivide patients into smaller, more homogenous populations based on which genes are mutated. Some of these may be very easy to treat, based on their mechanism, while others may be much more difficult. For those in this category, it’s possible we could one day find a way to train or improve the connection between the brain’s hemispheres.

It will be fascinating to see where this research goes next. In the meantime, here’s hoping the New Year-ome treats you and yours well!

Previously: New imaging analysis reveals distinct features of the autistic brain, Omics’ profiling coming soon to a doctor’s office near you? and A conversation with autism activist and animal behavior expert Temple Grandin
Photo of Snyder by Steve Fisch

Cancer, Genetics, Stanford News, Videos, Women's Health

Stanford specialists discuss latest advancements in breast cancer screening and treatment

Stanford specialists discuss latest advancements in breast cancer screening and treatment

Invasive breast cancer will affect one in eight women in the United States during their lifetime. Many women, and men, may believe that if they don’t have a family history of breast cancer, then they’re not at risk of developing the disease. However, this is a common myth: About 90 percent of patients diagnosed with the disease have no family history of breast cancer.

But the good news is that breast cancer detected in the early stages can be very effectively treated. Additionally, breast-cancer death rates have been falling over the past 25 years as a result of increased awareness, improvements in treatments and earlier detection.

During a recent Stanford Health Library talk, captured in the above video, breast-cancer specialists discussed the latest advancements in genetic testing, diagnostic imaging, reconstructive surgery and treatments and adjunct therapies to surgery.

Previously: Don’t hide from breast cancer – facing it early is key, Despite genetic advances, detection still key in breast cancer and Ask Stanford Med: Radiologist responds to your questions about breast cancer screening

Stanford Medicine Resources: