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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

Aging, Ethics, Medicine and Society, Research, Science, Stanford News

Golden years? Researcher explores longevity research and the companies banking on its success

Golden years? Researcher explores longevity research and the companies banking on its success

Elderly Japanese woman for Scott blog postAlthough I haven’t had a birthday yet this year, the transition to writing 2015 on all my checks (whoops, did I just date myself there? ahem) has made me feel older. Coincidentally, I’ve also been working on an article for an upcoming issue of Stanford Medicine magazine about aging and longevity. So, yeah. I’ve been thinking a lot about the passage of time.

That’s why I was really interested to learn that Stanford bioethicist Christopher Scott, PhD, teamed up with Nature Biotechnology senior editor Laura DeFrancesco to c0-author a feature article examining the commercialization of longevity research. The article layers research advances with the rise and fall (and rise again) of companies and organizations that have tossed their hats into the anti-aging ring since the 1990s. With it, Scott and DeFrancesco paint a picture of a dynamic field on the brink of something big. As Scott explained in an email to me:

Aging research, as we knew it in the 1990s and 2000’s, is being abandoned in favor of something much more ambitious. The central features of longevity research include an embrace of big data, a pivot away from studies hoping to find aging genes, a recognition that aging is best thought of a collection of diseases, not just one disease.

I’m fascinated by how quickly this new direction has taken off, especially since classic aging research yielded so little, and became saddled with hype. Longevity research has that same feel to it, and from an ethics and policy perspective one question is whether the promise of healthy lifespans will outrun the reality of the science.

And there’s the rub. As Scott points out, it’s not enough to just live long. No one wants a prolonged, but unhealthy, old age. We need to live long and well. The concept that gained ground is “healthspan” rather than “lifespan.” And from Google’s Calico to Craig Venter’s Human Longevity, Inc , there are a lot of bright minds (and plenty of $) focused on this problem. But there’s a lot at stake.

As Scott explained:

These are highly consequential decisions (funding research, creating new companies, establishing new scientific disciplines), technological inventions, and social changes that are being pursued on the tacit assumption that such decisions, inventions, and changes do lead to a healthier, longer life and the promise of a better future. In ethics, I think these assumptions are largely unexplored and unacknowledged.

The article is a fascinating cross-section of a rapidly growing field, but, as Scott points out, there are still many questions that scientists haven’t addressed. It’s well worth the time to read, whether you’re a writer on a deadline or just a person trying to figure out how to gracefully change that “4” into a “5” on …all your paperwork.

Previously: Exploring the value of longevity with bioethicist Ezekiel Emanuel , Tick tock goes the clock – is aging the biggest illness of all? and Researchers aim to extend how long – and how well – we live
Photo by Maya Stone

Aging, Chronic Disease, Ethics, Health Policy

Exploring the value of longevity with bioethicist Ezekiel Emanuel

baby hand in old hand - big

In a popular article in the Atlantic published this past fall, Ezekiel Emanuel, MD, bioethicist and prominent federal policy adviser, made a controversial case against longevity. Just before the recent holidays, the USC Annenberg School for Communication & Journalism sponsored a webinar during which Emanuel explained and elaborated on his message. It’s not that he “hopes to die at 75,” as the title chosen by the Atlantic suggested, but he wants a life at 75 focused on living, not on living longer.

Emanuel essentially argues for quality of life over quantity of years, and he claims that American society is becoming obsessed by the latter. I listened in on his December talk, which began with an ad from the AARP that glorifies “going on forever” – a value he says is reflected in both the medical system and our contemporary culture.

He directed his scientific criticism against the idea of the “compression of morbidity” – the belief that with enough medical advances, disabilities will go away and people will live in good health until, more or less suddenly, they die. He calls this the “rectangularization” of life: falling off a cliff instead of rolling down a gradual decline. The idea is immensely popular and money-making, but while some research claims to prove it, far more proves the opposite. There is, in fact, an expansion of morbidity as people live longer, an elongated and more gradual decline with more disabilities and less and less creativity.

Given this, Emanuel’s hope and recommendation is two-fold: that people will consider what makes their life meaningful and spend their energy cultivating that, and that medical resources will be redirected from prolonging life to improving its quality at the outset – by reducing the country’s exceptionally high rate of premature births, for example.

American life expectancy is at an all-time high at nearly 80 years, but are octogenarians living meaningfully? Last month in the New York Times, David Brooks argued against Emanuel’s earlier piece by saying that the “happiest people” are ages 82-85; in the webinar, Emanuel says this misses the point. It’s much easier to measure happiness than meaningfulness, yet the latter is the real aim of life (and, furthermore, Brooks didn’t account for the perspectives of those in nursing homes, assisted living, or suffering from dementia). Emanuel talked of patients who say cancer was “the best thing that happened to me” because it made them focus on what was meaningful in their life. The end of life is important to think about, as it helps us see what we want from life now.

“Contorting life around living as long as possible seems to me to be counter-productive,” he said. “What we should be focusing our life on is what’s meaningful, how we enrich other people and contribute to our families and society.”

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Ethics, Health Policy, In the News, Medicine and Society, Research

Watching your spouse die on a TV reality show: De-identification as a myth, in death and life

Watching your spouse die on a TV reality show: De-identification as a myth, in death and life

Much biomedical research relies on the idea of “de-identification.” The Common Rule, the federal regulation on human subjects research, applies, as a general matter, if the researchers make some kind of intervention with the research subject or if they use “identifiable private information” about the research subject. But the “Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects.”

De-identification doesn’t mean that no one will recognize the research subjects’ identity. Federal regulation says the researchers must not be able to ascertain it readily.

If the private information was not collected by the researcher (it comes from someone’s medical record or was collected as part of someone else’s research) and the research subject’s identity is not known to and cannot “readily be ascertained” by the researcher, it doesn’t count. No consent is required, no IRB review is required – it isn’t “human subjects research.”

And why should it be? If no one knows it is you, you cannot be hurt, or so the argument goes.

[Last Friday], the New York Times published an extraordinary article entitled “Dying in the E.R., and on TV Without His Family’s Consent” by Charles Ornstein, a reporter for ProPublica. It recounted how Anita Chanko, a 75-year-old widow, watching an ABC reality television show, NYMed, suddenly realized that she was watching her husband’s death in the emergency room. More than a year earlier, the 83-year-old man had been hit by a garbage truck while crossing the street and had died in the NewYork-Presbyterian hospital. The televised version blurred his face, but not the face of the surgeon, the description of the accident, or the sound of her late husband’s voice, asking “Does my wife know I’m here?”

At no time were any of the family told  that Mr. Chanko’s treatment was being filmed or asked their consent to its use on television.

The dead man’s widow and children were traumatized. One of their sons wrote in a complaint “I had to unnecessarily relive my father’s death at your hospital a second time, while knowing that the public at large was able to — and continues to be able to — watch my father’s passing, for the purposes of what can only be described as drive-by voyeuristic ‘entertainment.’ ”

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Ethics, Health Policy, In the News, Medicine and Society, Transplants

Moving the needle on organ donation

Moving the needle on organ donation

For the thousands of people on organ donation lists, news of an available heart, or lungs, or liver can’t come soon enough. But many don’t get that call in time. According to a new feature on The Atlantic’s website, 21 people die waiting for a transplant every day. That works out to more than 7,600 patients every year.

Unfortunately unless you’re personally touched by the issue… you don’t really think about it

Although many people say they support organ donation, in many countries, only a minority actually register as organ donors. (“Unfortunately unless you’re personally touched by the issue, unless you have a child that gets a virus and suddenly needs a new heart, you don’t really think about it,” one expert says in the piece.) It’s a paradox many people in the field are trying to unravel. The reasons they’ve uncovered so far include mistrust of medical professionals: Some people believe that if a medical team finds out that you’re an organ donor, they won’t work as hard to save your life, in order to harvest your organs. And how much TV a person watches can influence how much he or she trusts doctors. One study found that people who watched more of the TV series Grey’s Anatomy were more likely to mistrust doctors and nurses.

Religion also influences the picture, probably because of concepts of bodily integrity in the afterlife. Catholics are less likely to donate their organs, even though the Vatican officially supports organ donation.

So what can be done about the organ shortage? Some groups are working on solutions, as highlighted in the piece:

“What we’re trying to do in New York is move the cultural needle on the issue,” says Aisha Tator, executive director of the New York Alliance for Donation. “Organized tissue donation should be a cultural norm like we did with bike helmet and seatbelt interventions.” Her organization isn’t the only one. Throughout the United States there have been a smattering of recent educational campaigns and studies on their efficacy. Campaigns have targeted the young, the oldnursesDMV employees, and ethnic minorities who tend to donate less than white Americans or white Brits.

Another, more drastic change is to shift the U.S.’s current opt-in system to one that requires people to opt-out. Many experts point to Spain, which has an opt-out system – and one of the highest rates of organ donation. But the logistics of such a system would probably be difficult, best, to implement.

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Ethics, FDA, Health Policy, In the News, Stanford News

Stanford experts weigh in on spate of "right to try" laws for the terminally ill

Stanford experts weigh in on spate of "right to try" laws for the terminally ill

4286759185_f958aedc10_zTerminally ill patients should be able to access medication that could help them, regardless of how far along that drug might be in the FDA‘s in-depth approval process, right? Yes, some states such as Colorado, Missouri and Lousiana have said. They’ve adopted so-called “right-to-try” laws that gives dying patients access to drugs that have passed only the first stage of the FDA approval process.

Yet these laws — which are modeled on a policy from the libertarian Goldwater Institute — are ultimately useless given that federal law trumps state law, according to Stanford scholars Patricia Zettler, JD, and Henry Greely, JD, in an opinion piece published recently in JAMA Internal Medicine. In addition, the laws are redundant, they write:

Since the late 1980s, patients with serious and terminal conditions have been treated with unapproved medical products. Following sharp criticism from AIDS access about blocking access to potentially effective, but unproved, treatments, as well as congressional intent, the FDA issued regulations that are intended to provide patients with faster access to novel drugs for life-threatening conditions… Although satisfying the agency’s requirements may, at first glance, seem onerous, in practice the FDA very rarely rejects requests for expanded access.

Zettler, who formerly worked for the FDA, pointed out a link that is telling: During fiscal year 2012-2013, the FDA received 977 requests for “expanded access” (these requests may include more than one patient, Zettler said). It approved 974 of them.

None of the state or federal laws require a drug company to provide experimental drugs, and Zettler said she knows of only one – NeuralStem, Inc., a Maryland-based company that is developing therapies for central nervous system disorders –  that intends to provide drugs under these laws. By skipping the FDA’s process, the companies risk angering the FDA, whose favor they need for their drug approval, Zettler told me.

Why then these laws, which are currently also being considered in Michigan, Nevada and Arizona?

Well, Zettler told me, they’re political no-brainers. Imagine the political rants: “So-and-so made my mom die faster,” or “Joe Baloozabum opposes dying patients” – nope, that doesn’t fly inside any Beltway. Many state politicians are also motivated by a “good faith desire to help people,” Zettler said.

But she doubts that states have the expert staff needed to evaluate drug applications. And they don’t have the legal green-light either, she said, pointing out a recent ruling blocking Massachusetts’ attempt to ban a long-acting opiod.

Zettler said the state-based debates simply add a new wrinkle to a discussion that’s been percolating for decades.

Previously: No one wants to talk about dying, but we all need to and Asking the hardest questions: Talking with doctors while terminally ill
Photo by Melanie Tata

Clinical Trials, Ethics, Genetics, NIH, Pediatrics

The promise and peril of genome sequencing newborns

NICUEven though doctors and researchers have made great strides in caring for patients in the past few decades, there are still many illnesses that are difficult to diagnose, let alone treat. Among the most heartbreaking cases are those newborns who come down with mysterious illnesses that defy medical expertise. But in recent years, doctors have turned to genetic sequencing in some of these cases to identify the culprit causes of the illnesses.

Last year, the National Institutes of Health funded four pilot projects looking into the efficacy and ethics of genetic screening for otherwise inexplicable illnesses in newborns. The first of the trials will begin next week at Children’s Mercy Hospital in Kansas City, Missouri, as reported in a recent story from Nature. The trial at Children’s Mercy Hospital will focus on rapid genome sequencing with a 24-hour turn-around. Genetic sequencing normally takes weeks, but some of these infants don’t survive that long. Doctors have used similar rapid genome sequencing to diagnose an infant with cardiac defects at Lucile Packard Children’s Hospital Stanford.

Earlier this year, I had the opportunity to report on a rare genetic mutation that leads young infants to develop inflammatory bowel disease. I spoke with some parents of children with the mutation, which was identified by sequencing the children’s exome – just the protein-producing part of the genome – as part of a new project (separate from the NIH trials) at the University of Toronto in Canada. As I explain in the piece, getting a bone marrow transplant early enough can help alleviate symptoms and save the child’s life.

The parents were uniformly grateful for the sequencing technology that made it possible to understand what was causing their baby’s illness, even in cases where the child didn’t survive long after diagnosis. One mother mentioned that realizing some of the best doctors in the country didn’t know what was ailing her daughter made the experience even more frightening. After months of worried confusion about their young children’s deteriorating health, for these parents to have an answer was a relief.

But because the technique is so new, several ethical details still need clarification – which the NIH study hopes to answer. From the Nature news story:

Misha Angrist, a genomic-policy expert at Duke University in Durham, North Carolina, says that although the 24-hour genome process is impressive, it is not clear whether genomic sequencing of newborns will soon become standard practice. Many questions remain about who will pay for sequencing, who should have access to the data and how far clinicians should go in extracting genome information that is unrelated to the disease at hand. Then there is the question of how informative the process is. “I think it’s really important that we do these experiments so that we start to see what that yield is,” Angrist says.

All four teams will include an ethicist who will be responsible for dealing with questions like the ones Angrist raises. The other three trials at Boston Children’s Hospital, the University of North Carolina in Chapel Hill, and at the University of California, San Francisco are still awaiting approval from the Federal Drug Adminstration.

Previously: Stanford patient on having her genome sequenced: “This is the right thing to do for our family” When ten days = a lifetime: Rapid whole-genome sequencing helps critically ill newborn Assessing the challenges and opportunities when bringing whole-genome sequencing to the bedside Whole genome sequencing: The known knowns and the unknown unknowns
Photo by kqedquest

Clinical Trials, Ethics, Health Policy, Stanford News, Videos

Video explains why doctors don’t always know best

Video explains why doctors don’t always know best

“Over 85 percent of our major medical guideline recommendations are not based on high-quality evidence,” said Robert Califf, MD, director of the Duke Translational Medicine Institute, in an article I recently wrote for Inside Stanford Medicine.

This was the inconvenient truth that Stanford bioethicist David Magnus, PhD, had to explain to patients during focus groups, as he began developing policy recommendations for conducting ethical comparative-effectiveness research within physician practices.

“We had to dispel the myth that doctors always know which treatments are most effective for individual patients,” Magnus told me. “The truth is, in the absence of good evidence, these choices are often influenced by advertising, insurance coverage and local preferences.”

Gathering better treatment evidence is a key objective of the Affordable Care Act’s health-care reform mandate. It provides incentives for medical practices to continually evaluate the relative effectiveness of competing medical interventions as a way of delivering better, less costly care to more people. The widespread adoption of electronic medical records is enabling researchers to conduct these head-to-head comparisons in more automated ways, reducing the time and expense associated with the highly controlled clinical trials used to evaluate new drugs and devices.

A communications challenge with these new approaches, however, is how to explain the risks and rewards of participation to patients. In focus groups, Magnus found that no meaningful discussions could take place until his research team had educated patients on some fundamental concepts of medical research, such as standards-of-care, randomization and informed consent. To help with this process, his team produced three short, animated videos that would rapidly get everyone up to the same level of understanding. Magnus and his collaborators are making these videos available to all for educational purposes.

The first video, “Which Medication is Best?,” explores the influences and uncertainty associated with physicians’ prescribing preferences. “Research on Medical Practices” explains medical record reviews, study randomization and randomization of clinics and hospitals; and “Informing or Asking” describes ways to explain study participation to patients.

Magnus and his bioethicist collaborators from the Seattle Children’s Research Institute and University of Washington expect to publish their final ethics policy recommendations later this year.

Previously: Bioethicists say criticisms of preemie oxygen study could have “chilling effect” on clinical researchStanford biomedical ethicist discusses Choosing Wisely Initiative and Will new guidelines lead to massive statin use?
Videos by Booster Shot Media

Ethics, Genetics, Medicine and Society

Film documents rise and fall of a genome matching service – and poses tough ethical questions

Film documents rise and fall of a genome matching service - and poses tough ethical questions

Jesse_01When I think of “science fiction,” I picture three-eyed aliens with purple-and-gold tentacles — not the disturbing demise of a man, and a company, depicted in the film “The Perfect 46.”

Nor do I expect to ponder the ethics of a company that strives to produce genetically “pure” children.

Yet this is precisely the type of science fiction filmmaker Brett Ryan Bonowicz dished up to a sold-out Stanford crowd last week. Following the film, an all-star panel of genetics experts fielded questions.

The film’s premise is simple, and alluring. People can send their sequenced genome, along with their partner’s,  in to a company called The Perfect 46 and allow its proprietary algorithm to figure out if their children will be born genetic-defect free — or not.

“Jesse [Darden, the company’s CEO] wasn’t going to cure the diseases, he would just breed them out. It made a lot of people uncomfortable,” said one of the characters in the film.

So uncomfortable, in fact, that the company, and its leader Jesse Darden, played with a standout performance by actor Whit Hertford, unravels quite thoroughly – with Darden’s painful personal and professional demise forming the meat of “The Perfect 46’s” somewhat-tortured plot.

For me, the ethical quandary is a no-brainer: perfect – what fun is that? My husband and I are both far from perfect, and if we had a perfect child, it certainly wouldn’t be anything like us.

More seriously, however, the film poses thorny questions about the future of consumer genetics, a boom-and-bust field that’s both promising and terrifying. “The Perfect 46” doesn’t answer these questions, but the post-screening panelists delved into some of them.

During the talk, the experts made  it clear the technology featured in the film isn’t there – yet. Right now, if scientists sequence a genome , they don’t know the meaning of the many versions, or allele , of the gene that pop up. “Often, we don’t know if it’s disease-causing or not,” said panel member Michael Snyder, PhD, Stanford professor and chair of genetics.

Although the film takes place in the “near future,” corporations that provide basic genetic screening are already available, the experts said. And corporations may not be providing adequate counseling for potential parents, panel member Sandra Lee, PhD, a senior researcher at the Stanford Center for Biomedical Ethics, pointed out.

The Stanford-heavy audience seemed to dig the movie, but I thought the film would be more effective if its lessons were a little subtler and its pace a bit quicker.

Still, the questions it asks are real, even pressing, and not science-fictiony at all.

Becky Bach is a former park ranger who now spends her time writing, exploring, or practicing yoga. She’s currently a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously:Stanford patient on having her genome sequenced: “This is the right thing to do for our family”, Stanford geneticist discusses genomics and medicine in TEDMED talk, New recommendations for genetic disclosure released and A conversation about the benefits and limitations of direct-to-consumer genetic tests
Screenshot of movie courtesy of Clindar

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Ethics, Events, Health Policy, Medicine and Society, Public Health, Transplants

Stanford Health Policy forum on organ-donation crisis now available online

Stanford Health Policy forum on organ-donation crisis now available online

The latest Stanford Health Policy Forum, which focused on ways to end our country’s organ-donor shortage, is now available online. More than 100,000 Americans currently need organ transplants, and the panelists discussed a variety of solutions for solving the problem. Among the ideas brought to the table was a compensation system for donors – an option that was also the focus of an article in today’s San Francisco Chronicle.

Previously: At Stanford Health Policy Forum, panelists dig into the issue of organ donationHow can we end the donor organ shortage?, Stanford visiting professor and founder of kidney-exchange program wins Nobel economics prize and One gift saves three young lives 

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