genetics

RECENT POSTS

Personalized Medicine Distracts From Public Health, 2 Scholars Argue

Personalized medicine is all the rage. President Obama mentioned it in his State of The Union address this year and launched a multimillion-dollar initiative to push a personalized medicine agenda forward. The head of the National Institutes of Health has made it a priority. And really, what’s not to like about the general concept of medicine that’s personalized (it’s also called “precision medicine”) —  an approach that analyzes an individual’s genetics to make medical decisions about diagnosing and treating disease.

Well, two public health scholars argue in the New England Journal of Medicine that the current high-profile fawning over personalized medicine may be a “mistake” that diverts resources away from other public health efforts that could benefit far more people.

Ronald Bayer, Ph.D., a professor at Columbia University’s Mailman School of Public Health, and Dr. Sandro Galea, dean of the Boston University School of Public Health, write in the journal that the great enthusiasm around personalized medicine “derives from the assumption that precision medicine will contribute to clinical practice and thereby advance the health of the public.” But, they note, that may not be the case:

We suggest, however, that this enthusiasm is premature. “What is needed now” is quite different if one views the world from the perspective of the broad pattern of morbidity and mortality, if one is concerned about why the United States has sunk to the bottom of the list of comparable countries in terms of disease experience and life expectancy, or if one is troubled by the steep social gradient that characterizes who becomes sick and who dies. The burgeoning precision-medicine agenda is largely silent on these issues, focusing instead on detecting and curing disease at the individual level…

Without minimizing the possible gains to clinical care from greater realization of precision medicine’s promise, we worry that an unstinting focus on precision medicine by trusted spokespeople for health is a mistake — and a distraction from the goal of producing a healthier population.

I spoke with Dr. Galea about why he and Bayer targeted personalized medicine, in particular. Here, lightly edited, is what he said:

Personalized medicine has become this rallying cry around resource allocation in the health sciences. The president mentioned in the State of the Union. There is a White House precision medicine initiative, and it has dominated much of the NIH agenda…so it seems important to address it directly…

Nobody is arguing that precision medicine does’t have potential, but the number of people who you could point to who have actually benefited from it are very small. And so we are investing in potential — which is fine — but it’s a matter of calibrating our investment. Instead of investing in a untried, untested approach, we should be investing in things that we know make a difference…

We know that macroeconomic taxation on unhealthy substances, on alcohol, for example, can save thousands of lives, early childhood education can make an enormous difference, efforts to increase and improve vaccination rates, efforts to mitigate cycles of violence, one could go on and on….these could improve the lives of hundreds and thousands of people…

Our commentary was a call for a recalibration…I think there’s a feeling in the scientific community that the precision medicine agenda is becoming the overwhelming direction in which we are headed and that we would benefit from discussion and debate and a more careful calibration of the questions we ask and where we invest our resources.

Continue reading

Practicing Restraint In A No-Empathy Zone: At The Cancer Surgeon’s Office With My Son

Cathy Corman
Guest Contributor

I carry a genetic mutation increasing my risk of developing breast and ovarian cancer. My children have a 50 percent chance of inheriting the mutation. My 22-year-old son recently noticed a breast lump and asked me to join him when he met with a surgical oncologist to be evaluated.

The surgeon performed a skillful physical exam but provided neither effective risk assessment nor empathetic counsel. Afterward, I sent an email to friends briefly explaining what had gone wrong during the appointment. “We want to know how you managed not to hit him,” they asked. I did it by practicing restraint: slowly counting backwards from 10 and taking very deep breaths.

Here’s my countdown:

10. I did not correct the icy-blue-eyed surgeon with steel-grey hair and steady hands — 50? 60? — when he dissuaded my son from pursuing genetic testing. The surgeon had shaken my son’s hand, looked him in the eye, and palpated my son’s slender, muscular chest, identifying the small lump under my son’s left nipple. A positive finding of a mutation, the surgeon said, adjusting the top of his surgical scrubs, could expose my son to discrimination in the workplace and in obtaining health insurance. That is, I did not say, “The scenario you describe is illegal in this country.” As of March 23, 2010, with the passage of the Patient Protection and Affordable Care Act (aka “Obamacare”), if anyone were to attempt to discriminate against this young man in the workplace or in the process of applying for health insurance because of a positive finding for a genetic mutation (a pre-existing condition), this person would be subject to a massive lawsuit.

Cathy Corman (Courtesy)

Cathy Corman (Courtesy)

9. When this surgeon used the word “anxiety” for the eighth time to a) describe my son and myself and b) provide his vision of a course of action, I did not refer this man to Leslie Jamison’s collection of essays, “The Empathy Exams.”  “Empathy,” writes Jamison, “isn’t just remembering to say that must really be hard — it’s figuring out how to bring difficulty into the light so it can be seen at all. Empathy isn’t just listening, it’s asking the questions whose answers need to be listened to. Empathy requires inquiry as much as imagination. Empathy requires knowing you know nothing. Empathy means acknowledging a horizon of context that extends perpetually beyond what you can see…”

8.  I did not bring up this statistic: Though men make up only 1 percent of breast cancer diagnoses annually in the U.S., they may be up to 25 percent likelier than women to die from the disease, probably because of lack of awareness and late detection. Nor did I mention that generally male breast cancer presents with a detectable lump and is almost always linked to radiation exposure, unusually high levels of estrogen or a genetic mutation. Surely the surgeon knew these statistics? But my son did not. And I did not want to scare him.

7. I said nothing to this surgeon’s response to my son’s question, “But wouldn’t it be relevant to know if I carry the mutation?” His answer: No, you know you have a family history of breast cancer.

6. I said nothing when this surgeon dodged my son’s question: “If my grandfather didn’t have the mutation,” my son wanted to know, “wouldn’t he not have had breast cancer? And wouldn’t it be important for me to know if I carry the mutation, too, to assess my risk?” The surgeon’s reply: The only way you’ll know if you have cancer is to have the lump removed. The surgeon’s answer, while true, sidestepped the elephant in the room: whether my son carries a mutation elevating his risk of breast cancer.

5. When this surgeon ridiculed an actress whose name he could not remember for publicly disclosing her status as a mutation carrier and for undergoing prophylactic mastectomies, I offered him the actress’s name. Continue reading

Why We Need To Talk Now About The Brave New World Of Editing Genes

Screen shot 2015-05-21 at 7.48.44 PM

(Image: NIH)

It was standing room only in the Harvard Medical School auditorium last week, the atmosphere electric as an audience of hundreds hummed with anticipation — for a highly technical talk by a visiting scientist, Dr. Jennifer Doudna of Berkeley. Near the front sat the medical school’s dean, Dr. Jeffrey Flier.

Dr. Jennifer Doudna (Vimeo screenshot)

Dr. Jennifer Doudna (Vimeo screenshot)

“I don’t believe in my years at Harvard Medical School I’ve ever seen a crowd of this magnitude for a lecture of this kind,” he said.

The draw?

“The draw is, this is one of the most exciting topics in the scene of biology today.”

That buzzworthy biology topic is a revolutionary new method to “edit” DNA that has spread to thousands of labs around the world just in the last couple of years.

Suddenly, it’s no longer purely science fiction that humankind will have the ability to tinker with its own gene pool. But should it?

Learn This Acronym: CRISPR

The hot new gene-editing tool is known by the acronym CRISPR, for “clustered regularly interspaced palindromic repeats.” It acts as a sort of molecular scissors that can be easily targeted to cut and modify specific genes.

(Source: NIH)

(Source: NIH)

CRISPR occurs naturally in bacteria, but scientists are now learning to harness its power to alter DNA for research across the board — cancer, HIV, brain disease — even to make better potatoes. Just this week, the journal Science published a paper on possibly using CRISPR to try to stop female mosquitoes from spreading deadly diseases.

CRISPR looks particularly promising for human diseases that hinge on just one gene, like sickle-cell anemia or cystic fibrosis. Someday, the hope is, CRISPR and gene-editing tools like it will let us cure what are now lifelong diseases by simply deleting and replacing a baby’s “broken” gene. Continue reading

The Complex Interplay Of Genetics And The Placebo Response

Why do some people respond to placebos while others don’t?

One possible answer: genetics.

A provocative new paper introducing the concept of a “placebome” — that is, the complex interplay between genetics and an individual’s response to placebos — raises questions that might ultimately lead to changes in how clinical studies of drugs are evaluated.

Indeed, researchers from Harvard Medical School suggest that genes, and genetic variation, might play a far bigger role in the placebo response than previously thought.

That the placebo effect is an actual physiological response is well established. But the new report, a research review, looks specifically at the placebo response in the context of drug studies, where some participants get the active medication while others get a placebo, or non-active version of the drug.

The new findings, “call into question whether or not the outcomes in a drug treatment arm of a clinical trial are limited to the effect of the drug on the condition,” says Kathryn Hall, an integrative medicine fellow in the Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center, and one of the study authors.

Instant Vantage/flickr

Instant Vantage/flickr

Several neurotransmitters, such as dopamine, appear to be involved in the placebo response, Hall said, and variation in the genes in these pathways appears to change our response to placebo. So different people with different genotypes respond differently to placebos.

But Hall takes it one step further. “When you are in a trial you don’t know if you are getting the drug or the placebo, so not just the people in the placebo arm can have placebo responses. We are curious about the drugs’ effect on the placebo response.”

It’s all a bit tough to wrap your brain around, so I asked Hall to give me an example. Here’s what she said:

In the literature we see several studies in which in the placebo arm one group of people with a certain genotype have a strong placebo response and the other group has a weak placebo response. And when we look at the drug treatment arm, we see the outcomes are reversed, the people who had the strong response in the placebo arm now have a low response and the people who didn’t have a response in the placebo arm now have a strong response. The historical interpretation of these results has been that only one group of people responds to the drug and we’re pointing out that it’s more complicated than that. It’s that one group responded to the placebo and that response is eliminated in the drug treatment arm.

What all this means in the real world is still hard to know. But in their paper published this week in the journal, Trends in Molecular Medicine, the researchers offer these three key takeaways in the abstract:

•The predisposition to respond to placebo treatment may be in part a stable heritable trait.

•Candidate placebo response pathways may interact with drugs to modify outcomes in the drug treatment arms of clinical trials.

•Genomic analysis of randomized placebo and no-treatment controlled trials are needed to fully realize the potential of the placebome.

Continue reading

Biggest Gene Study Finds New Clues To Obesity, Apple Vs. Pear Shapes

(Wikimedia Commons)

(Wikimedia Commons)

You might think the link between genes and weight is simple: Fat tends to run in families, right? But as researchers tease apart the underlying genetics of body weight, it becomes ever clearer that it is a complex trait. Very complex, with ultimately perhaps hundreds of genes involved in what you see when you step on the scale.

Today, the biggest-ever study of the genetics of obesity, involving genetic samples from nearly 350,000 people, reveals dozens of new spots on the human genome that are involved with body weight and body shape, according to two papers (here and here) published in the journal Nature.

My dominant impression: The data tend to implicate the brain as a powerful influence on overall body weight, but point more towards hormones and the fat cells themselves as strong determinants of whether we’re shaped like “apples” — with more upper body fat — or “pears,” with more fat concentrated below the waist.

Dr. Joel Hirschhorn, of Boston Children’s Hospital, the Broad Institute and Harvard Medical School, leads the Genetic Investigation of Anthropometric Traits consortium, or GIANT, the friendly collaborative of hundreds of researchers around the world who contributed to the studies. Our conversation, lightly edited:

How would you sum up the findings that come out in “Nature” today?

We did a very large genetic study looking at two different kinds of obesity: Overall obesity measured by body mass index and central obesity — fat around the belly — measured by waist circumference and hip circumference. And what we found was that there are a lot of genes that influence both types of obesity, but, really interestingly, the types of genes that influence overall obesity are actually quite different than the types of genes that influence where the fat goes on the body.

Interesting. So what does that tell us?

That tells us that even though both types of obesity are bad for your health, that it may be very important to understand what kind of obesity you have, because if the biology is different, that means the way we can treat that obesity, or prevent it effectively, is probably going to be different for the two kinds of obesity.

So it may matter even more than we thought whether you’re shaped like an ‘apple or a ‘pear’?

That’s right. It matters both whether you’re an apple or a pear and it matters just how big you are in general. But the way you get to be big in general is probably different than the way you get to be an apple or a pear.

So it’s different pathways? Perhaps whole different mechanisms at work?

That’s right. The overall obesity seems to have more to do with what’s going on in the brain, maybe controlling appetite or whether you get full or how quickly you get full. And the apple vs. pear seems to have more to do with your fat cells and hormones that your body makes, things like insulin.

So does all this translate into any action points for the general public? Continue reading

Study: Do You Really Need Counseling On Your Alzheimer’s Gene Test?

Today on Radio Boston: A new Brigham and Women’s Hospital study finds that we may not need quite as much genetic counseling as we’d thought. Particularly on relatively cut-and-dried findings, like test results on a common gene that raises the risk of Alzheimer’s disease. Listen to host Anthony Brooks speak with Dr. Robert C. Green in the segment above.

From the Brigham’s press release:

A new study led by researchers at Brigham and Women’s Hospital (BWH) has found that people who received a written brochure instead of time-intensive genetic counseling about their genetic risk for Alzheimer’s disease did not experience greater anxiety or symptoms of depression than their counterparts a year later. The results of the randomized controlled study were published online in the journal Alzheimer’s and Dementia.

“As genetic testing of all kinds becomes commonplace, one of the primary challenges will be determining how to share this information with individuals seeking it in a way that limits the burden on health care providers but still puts the well-being of patients first,” said Robert C. Green, MD, MPH, a medical geneticist and researcher at BWH and Harvard Medical School and lead investigator of the study. “These new results show that for individuals seeking genetic risk information, we can use written material, rather than genetic counseling, to prepare them without causing greater long-term anxiety or distress.” Continue reading

Boston Survey: Most Parents Say Sure, I’d Like To Know My Newborn’s Genes

(Wikimedia Commons)

(Wikimedia Commons)

For years, futurists have foreseen an era when all newborn American babies would be sent home with a supply of self-knowledge: a readout of their full set of genes, with all it may imply about heightened chances for disease or health.

So how would you feel about that, as a new parent? Eager to absorb any possible indicator of your child’s potential future? Or wary that genes are not destiny, and you may spend a lifetime fearing something that never comes to pass?

If you answer, “I’d want to know about my baby’s genetic makeup,” your sentiments are in line with the majority of parents surveyed in the first poll of new parents about genomic screening, just out in the journal Genetics In Medicine. Researchers from Brigham and Women’s Hospital and Boston Children’s Hospital led the study. From the press release:

“Several other studies have measured parents’ interest in newborn genomic screening, but none focused on new parents in the first 48 hours,” said Robert C. Green, MD, MPH, a geneticist and researcher at BWH and Harvard Medical School and senior author of the study. “Since this is when genomic testing would be of the greatest value, it is especially important to study parents’ attitudes immediately post-partum.”

The researchers surveyed 514 parents at the well baby nursery at BWH within 48 hours of their child’s birth. After receiving a brief orientation to the genome and its impacts on human health, including information about what the genome is, what genes are and how they can affect both health and medical care, 82.7 percent of parents reported being somewhat (36 percent), very, (28 percent) or extremely (18 percent) interested in newborn genomic testing. Results were similar regardless of parents’ age, gender, race, ethnicity, level of education, family history of genetic disease, or whether or not the infant was a first-born child. Parents who had experienced concerns about the health of their newborn, however, were less likely to be interested in genomic testing. Continue reading

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