Category Archives: Laura Hercher

by | September 21, 2020 · 9:39 AM

JOAN H. MARKS 

In Memoriam

1929-2020

Of all the pioneers who helped shape the field of genetic counseling, it is likely that no one was more influential than Joan H. Marks, who died on September 14th at the age of 91.  In 1972, when Joan took over the 3-year-old program at Sarah Lawrence College that now bears her name, there was no accrediting body, no national society, no Journal of Genetic Counseling.  She stayed for 26 years, a dominating and charismatic presence, often intimidating, often demanding – a fierce advocate for both genetic counselors and their patients, who she insisted deserved more than a lecture on chromosomes and recessive inheritance.  

When your friends and relatives ask you, as they still do, ‘what is a genetic counselor?’ the answer you provide, whether you know it or not, is an echo of Joan’s vision, distilled in a generation of students who went on to define their roles in workplaces across the country, to found NSGC and ABGC, and to serve as teachers and program directors in their turn, passing along the ethos that remains integral to the field.  

I met Joan when I interviewed at Sarah Lawrence in 1999, when she was very much the eminence grise.  “I imagine you’ll get in,” she said to me, looking over my transcript with a practiced air, and I was thrilled – an excitement that was immediately tempered when she mentioned that she would not be sticking around to educate this new class of genetic counselors.  As a charter member of the post-Joan-Marks generation of Sarah Lawrence alums, I can attest to the lingering effects of her legacy.  

Still, devoted former students have told me over the years that I was unlucky not to have known her better.  No doubt this is true (and no offense to Caroline Lieber, who inherited the mantle at Sarah Lawrence and was a great program director in her own right).  So today I would like to invite all of you who knew Joan Marks as a student or a colleague or a friend to treat this post as a sort of an invitation and add your reminiscences here.  

First up, a lovely tribute form Caroline Lieber herself, who talks about her experience filling some very big shoes in the world of genetic counseling.  I hope that many others will fill the comments.

Joan Marks: One of a kind

Caroline Lieber, MS, CGC Director Emeritus, Sarah Lawrence College Joan H Marks Graduate Program in Human Genetics

I met Joan Marks in February 1978.  My then-boyfriend and I flew to New York and then took the train to the Sarah Lawrence campus, two California kids in New York for the first time.  He waited outside of Morrill House while she and I “talked.”  It felt more like she talked and I listened.  After the interview I said, “I am not sure that went so well….” 

But when I called my parents from South America that July to check-in, my father excitedly said, “You got accepted at Sarah Lawrence!” My boyfriend and I packed our meager belongings and headed east. Two California kids in New York for the second time. We arrived two weeks before classes were scheduled to start.  I was going to be a genetic counselor!

Having been undergraduate genetics major, I was comfortable in the science courses. The psychology courses were a different story.  As our instructor for “Issues in Genetic Counseling,” Joan had us read broadly about ethical concerns, the depth of emotional responses to genetic conditions in families, and articles to help identify counseling techniques and how to use them.  She commented in detail on each paper we wrote.  In one paper I found recently, she pointed out some inconsistencies in my thinking.  She further remarked, “But what’s good is that you see yourself as a counselor and you see how tough it can be. I’d like you to reread what you’ve written carefully and try to be objective-aren’t you inserting some biases here and there?” Her critique was not always welcome, but she always made me reflect on each point she made, and to look at it from another view.  I learned to be more empathic in a tough-love way. I am proud of the genetic counselor I became under her direction.

Fast forward to 1998. I discovered that Joan was planning to retire from Sarah Lawrence. I applied for the director position, and went through rigorous interviews.  I recall the pointed questions, some designed to make the interviewee a bit uncomfortable, as a means of gauging responses to tough situations. Even though she wasn’t in the room, it was clear that Joan was part of the process. Fortunately for me, I was selected.

Following in Joan’s footsteps was daunting.  Those early months felt exciting and overwhelming as I learned a whole new landscape.  Not surprisingly, Joan had very definitive ideas about the future of the program and often wanted to share her thoughts.  As my advisor and mentor, I made a point of responding to her calls and emails, listening to her guidance and counsel.  As it was when I was a student, I was not always in sync with her thoughts, but I learned to incorporate many of her suggestions. As I gained confidence in my role, I learned to trust my instincts and experiences to find my own personality in the position.  When in time, Joan told me that I was doing a good job, letting me know that she approved of my leadership, it meant a great deal to me.

During my tenure as program director, our relationship grew on many levels.  Joan and I grew together professionally as we worked on several commemorative events. When the program was renamed in Joan’s honor, it was a proud day for the college and the Joan H Marks Graduate Program in Human Genetics.  After I moved into New York City, we grew closer personally, sharing life outside of the program.  We met for lunch and talked about some of her other interests, including art and gardening. I got to know her softer side.

Joan Marks was the most committed and passionate advocate for the genetic counseling field that I have ever known.  As Laura Hercher said, “I doubt any other single individual did as much to shape the field.”  She put the profession on the map with style, charm, directness and savvy.  It was my privilege to be her student and mentee.  It was my pleasure to be her friend.

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by | December 26, 2019 · 10:45 AM

The List Returns: My Top 10 Stories in Genetics in 2019

2019!!  I’m going to declare it The Year of the Phoenix, with old promises rising from the dead (gene therapy) along with left-for-dead approaches (you came back with a vengeance, polygenic risk scores) and even older fears (remember when we were a post-racial civilization and genetic discrimination –  whew! – didn’t happen?).

Writing about 2019 got me thinking about the end of a decade, and so this year I am offering an end-of-the-decade special: two lists in one.  Here’s my take on the top ten stories in genetics for the 2000-teens (in no particular order):

Clinical use of exome sequencing

The rise of mega-databases

The ancestry-testing craze and the death of genetic privacy

Data sharing becomes the norm (kumbaya awards to gnomAD; ClinVar)

Nanopores! And other forms of heterogeneity in the F2 generation of DNA sequencing

Cell free DNA testing

Polygenic risk scores 2.0

NGS rewrites laws of economics by getting cheaper & better despite Illumina monopoly

Gene therapy rebounds

CRISPR

No surprise, many of these larger trends are reflected in the Top Ten for 2019:

 

  1. DTC: THE TRAIN HAS LEFT THE STATION BUT NOBODY KNOWS WHERE WE ARE HEADED

Can’t talk about genetics in 2019 without a word about DTC testing, as we persist in calling it for lack of a better word (consumer-initiated testing?  Not a better word, though possibly a better phrase…).  The thing is – wait for the irony – you can’t generalize about DTC anymore.  So what’s the biggest DTC story of the year?  I’m going with Ancestry branching out into the health and trait testing business.  This can hardly rate as a giant surprise, as they have hinted at it for years, but the big question was whether or not they would go with a 23andMe Fun Facts approach or something more medical.  Would they try and compete with Invitae or Color and offer a more comprehensive and more expensive CONSUMER-INITIATED, DOCTOR-APPROVED testing?  Seems like this choice would say something about where they see the field going…

And the answer was (drum roll): both.  Take your pick.  This actually does say something about the future, which is to say, we have no idea where the field is headed.  Their two-tiered approach debuts in 2020 and I expect it is more beta testing than market strategy.  I predict they are down to a single product by the time we (please God) inaugurate a new president in 2021.

 

  1. MILASEN

There are so many stories about the success of new treatments in 2019, that it was hard to pick just one.  Trikafta, the new CF combination therapy that will extend effective treatment to over 90% of the cystic fibrosis population?  Studiessuggesting the PCSK9 inhibitor inclisiran may offer a new option for individuals with a genetic predisposition to high cholesterol?

But with all these big stories to talk about, I’m going small: the development of a drug to treat a single individual, reported in October by the New York Times.  This n-of-1 drug was developed for Mila Makovec, a Colorado 8-year-old with an atypical form of Batten’s disease.  The drug, named Milasen, has improved but not cured the little girl, who has gone from 30 seizures a day to something less than 6 on average.  This example of highly personalized medicine was enabled by DNA testing, but also by the 3 million+ dollars Mila’s mother raised via a GoFundMe campaign.  Additionally, as the article points out, the nature of a custom drug is a challenge for regulators, who cannot use data to establish effectiveness or risks associated with treatment.  And without means to get FDA approval, these drugs will operate indefinitely in self-pay mode.

 

  1. FLORIDA MAN AND ACCIDENTAL PHILOSOPHER SELLS BUSINESS AND RETIRES FROM UNPAID ROLE AS ARBITER OF FORENSIC DNA USE BY AMERICAN LAW ENFORCEMENT

In 2010, retired businessman Curtis Rogers and his friend John Olsen founded GEDmatch, a website providing a set of tools to help adoptees find biological relatives.  “Premium members” paid $10 a month, most of which went to offset the cost of servers.  More of a hobby than a business, GEDmatch was staffed by volunteers.

Eight years later, Rogers described himself as shocked and surprised to discover via news reports that his site had been used by law enforcement to locate a suspected serial killer named Joseph DeAngelo, later convicted of a rape/homicide in 1977.  “It took a couple of weeks for me to really wrap my head around what was happening,” said Rogers.  GEDmatch, which was not a testing service like Ancestry or 23andMe, accepted DNA from a variety of sources, making it accessible to profiles derived from crime scene samples, and its DIY set of tools for finding relatives was tailor-made for the new field of forensic genealogy.

Did people who uploaded their DNA for genealogical purposes intend for it to be used by law enforcement?  And did their intentions matter?  Accidentally, this Florida man found himself the arbiters of forensic DNA use in the U.S.  How did he do?  Not bad, considering.  In the wake of the initial Golden State Killer hubbub, Rogers informed law enforcement that they could use GEDmatch only for crimes that included murder or sexual assault.

Then in December 2018, Rogers bent the rules to allow a search for an assault he described as “as close to a homicide as you can get” (an elderly woman playing the organ in church was choked and beaten).  This exception provoked a significant negative reaction from the GEDmatch user community, which in turn caused Rogers to rethink his approach, and in May he announced a new “opt-in” policy, restricting the police searches to those profiles whose users had provided consent.  Overnight, the new policy shrunk law enforcement’s access to GEDmatch to a meaningless fraction of the total database.  While responsive and thoughtful, this sudden about-face illustrated how much the forensic use of genealogical data rested entirely upon the decision-making of one many with no particular expertise and some conflict of interest (Rogers also mused allowed at one point that he might start charging law enforcement to use the site because, why not???).

This status quo held only briefly, with several latte-year events altering the forensic DNA landscape.  In September, the U.S. Department of Justice released interim guidelines for law enforcement that permits them to use DNA databases only for violent crimes like rape and murder, or to identify human remains, and only when traditional investigatory efforts have come up empty.  Two months later, a GEDmatch search occurred for the first time by court order, after a Florida court issued a subpoena.  And in December, Rogers sold the company and his de facto control of forensic DNA use in the U.S. to Virogen, a sequencing company specializing in forensic use of DNA.  Virogen claims it will maintain the opt-in standards set by Rogers even though those standards complicate its core business.  Anyone who takes that promise at face value should contact me; I have a bridge you might be interested in buying.

 

  1. ASCENSION HEALTH PATIENTS, MEET OUR NEW ASSOCIATE, DR. GOOGLE

Maybe they should have called it Project Canary in the Coal Mine.

Ascension Health’s Project Nightingale struck a nerve this November, when the Wall Street Journal reported that they had hired (or, in HIPPA-compliant terms, entered into partnership with..) Google to collect and analyze identifiable health data from the electronic medical records of their patients.  HIPAA forbids the sharing of a patient’s medical information without express consent, but allows for access within a medical system if it is used to improve patient services.  While Google denied any intention to use the data for other purposes or to link it with Google subsidiaries such as Calico (a partner with Ancestry, the largest of the consumer genealogy databases), many skeptical observers pointed out that health data is a valuable commodity in which Google has a previously expressed interest.

Sans accusation, it is fair to say that Project Nightingale raises legitimate concerns about the adequacy of existing privacy regulations in an age when the quantity and richness of data accessible through large health system EMR’s and genomic databases is unprecedented, and there are players like Google potentially capable of connecting the dots between genomic and health outcome data to draw conclusions about individuals and families.  It is unlikely that the architects of HIPAA envisioned the size and scope of Ascension Health (78 hospitals and over 2600 ‘points of care’ according to… Google) and there is no way that HIPAA rules governing internal partnerships were designed with Google in mind.  What could happen?  I don’t know, and neither do you, and that is actually the point.

 

  1. INVITAE INVESTS IN CHATBOTS

If you attended a genetic counseling conference this year, you likely heard a great deal about chatbots, even before reports in November of Invitae’s plans to purchase chatbot pioneer Clear Genomics for $50 million dollars (drinks on you, Shivani Nazareth!!!).  The move represents a clear (no pun intended) double down on Invitae’s other significant 2019 initiative: expanding into the world of consumer-initiated testing.  Chatbots, in this story, play the role of support staff, allowing us to triage questions and concerns that require genetic counseling from those that do not, a crucial step in expanding the use of genetic testing or screening without sacrificing our commitment to informed decision-making and responsible return of results.  In fact, relieved of menial question-answering, the GC staff are able to take more time with those who need it, and practice the sort of personalized and therapeutic relationship-building that characterizes genetic counseling at its best.

Do you sense a *but* coming?  I sense a *but* coming.

But… I have to say that while I buy the potential of chatbots for this purpose, my own view of the future is a bit of a choose-your-adventure story with alternate endings.  In the darker version, institutions and insurers decide, once the automated information-givers are in place, that this system is not intended to enable genetic counseling but to replace it.  So, yes, let’s embrace GC-Siri, but at the same time, let’s double down on producing data to support the value of the (human to human) genetic counseling experience.

 

  1. DATA SHARING HITS A MILESTONE

The clinical value of genomics is based not just on our power to sequence, but on our ability to interpret the variant calls, and for improving interpretation, there is no resource more powerful than past experience – an early-days problem for the nascent field of genomics.  ClinVar, the government-funded repository of variant calls, was developed to provide a way to maximize the value of our collective experience of the relationship between genotype and phenotype.  A real-life exercise in game theory, ClinVar represented an act of trust: hand over your work for the common good and, if enough people participate, everyone will benefit.

The result?  In December 2019, ClinVar announced that the number of shared records has passed one million.  Routinely consulted by clinicians and researchers, ClinVar has become an invaluable resource to the world.  Congrats and thanks to the thousands of volunteers who have organized data, searched records, curated variant calls and worked to promote the gospel of data sharing.

And by the way an example of government doing what private industry cannot, in the service of the public good.

 

  1. CRISPR PRIME PROMISES TO A CURE FOR YOUR GENETIC DISEASE DELIVERED IN TWO DAYS OR LESS

A novel CRISPR technique, reported in an October article in Nature, uses reverse transcriptase to introduce a desired transcript into a DNA strand, without the messiness and unpredictability of CRISPR’s double-stranded breaks.  The technique was widely hailed as a way of improving reliability of the ‘replace’ aspect of CRISPR as a ‘search and replace’ function for DNA.  And called CRISPR prime, so I guess they will give me my money back if it isn’t delivered to the right chromosome in two business days (this joke has fallen flat multiple times but I believe in it and I have the courage of my convictions).

Will CRISPR prime be transformational?  Despite the excitement it is too soon to tell, but here’s what the story represents to me: the incredible pace of technological advancement in the CRISPR era continues unabated.  Prior to 2012 – LESS THAN 8 YEARS AGO – most people excited about CRISPR probably thought of it as an intriguing way to improve yogurt.  In less time than it typically takes to bring a single drug to market, CRISPR has launched a multi-billion dollar industry, with the first CRISPR-mediated therapies approved for human trials (and, less positively, the first CRISPR gene-edited babies already past their first birthday in China).  If CRISPR prime doesn’t deliver, something else will; I’d put an Amazon-sized bet on that.

 

  1. THE UK BIOBANK FUELS A NEW ERA OF POLYGENIC RISK SCORES FOR… EVERYTHING.

Move over, Iceland.  Your collection of genomic and health history information was good but how can a small island nation with a genetically homogenous population compare with the vast genomic richness of… England?

Okay, so 94% of the half million participants in the UK Biobank are white.  But, as papers appear almost daily, it is hard to deny the fundamental impact of the UKB as a research resource.  Funded in 2002, the dataset combines the results of genomic testing with phenotypic measures of more than 2400 traits, and survey data covering everything from sexual history to political preferences.  And with only a handful of restrictions and a $2500 fee for use, UKB data is available to almost everyone, and it has been used to link common genetic variants with everything from depression to obesity to income.

In turn, this mass outpouring of genetic association studies has spawned a sub-genre of “genetics is not deterministic” PSA’s, like this one from Kevin Mitchell, and I’d like to collectively thank you all for your efforts.

Because volume is the message, it is hard to single out a single UKB-themed story, but in the spirit of reductive end-of-year list-making, let me focus on an article on the genetic basis of same sex sexual behavior published in Science in August.  The authors of this study, which reported on a GWAS of data drawn from the UKB and the 23andMe consumer customer database, identified results indicating genetic associations that accounted for 8-25% of the variation between individuals who had participated in same-sex sexual behavior and those who had not.  The authors were extremely careful to explain that a single same-sex experience was not the same thing as homosexual orientation, and in fact further analyses indicated that there were genetic differences between the two.  Additionally, the article made clear that while patterns emerged in a population, individual results were insufficient to indicate likelihood of homosexual behavior on an individual level.  The authors even constructed a website putting this into more user-friendly language, in case anyone found the Science article inaccessible.

So it could come as a surprise to no one that, 6 weeks later, an app called “How Gay Are You?” went up for sale through the DTC gene-testing marketplace Gene Plaza.  Under intense public pressure from the authors of the study among others, this app was removed in November.  Was it only a bit of harmless fun, like the app that claims to identify your inner superhero?  Maybe not says science journalist Emily Mullin, who pointed out on twitter that the person responsible for the app is based in Uganda, where homosexual behavior can get you the death penalty.  Ha ha adorable.

Sure, this example fails to illustrate the medical value and legitimacy of many UKB-based gene tests reported in 2019.  But it says something profound about how quickly the marketplace moves to commercialize genomic associations, and the difficulty of controlling how the information is used – but also (a bit more optimistically) that a response and clear communication from scientists can mitigate misuse.

 

  1. POPULATION SCREENING

The steep fall of the cost of DNA sequencing has transformed genetic research and made exome sequencing a staple of medical management.  It has also opened up the possibility of population-level screening programs, including research programs like the UK Biobank and the U.S. All of Us project and clinical programs like Geisinger Health System’s MyCode.  Is genetic screening of healthy individuals a good idea?  That depends on the circumstances. How about by government decree, without consent, for purposes of tracking a vulnerable and restive minority population?  Hmmm… pretty sure even George Church and David Ledbetter are a hard no on that one.

But a report by the NY Times in February documented that involuntary “free health checks” of a Muslin minority population by Chinese authorities included facial scanning, fingerprinting and a DNA test.  This perversion of health care is even more nefarious in the context of Chinese repression of the Uighars, over a million of whom are rumored to be in ‘re-education camps’ serving indefinite sentences for the crime of belonging to the wrong ethnic group.  Thermo Fisher, the Massachusetts-based company that provided the equipment used for population sequencing, announced that it has ceased sales to China as information on the genetic testing program began to surface in the news.

How do they plan to use DNA sequence data?  Will individuals be tracked using DNA profiles or groups of individuals sorted by genotype?  I doubt even the Chinese know.  But genetics has always had a dark side, and even the most ambitious of early eugenicists could hardly have imagined the power of population-level sequencing programs, and the toxic potential of new-fangled technology and ancient prejudice.

 

  1. ZOLGENSMA AND THE COMPLICATED MORAL MATH OF MIRACLES

There is no bigger story in genetics in 2019 than the success stories in gene therapy, which have brought help to a handful, and hope to many.  Two years removed from the first FDA approvals in 2017 (two immunotherapy drugs and Luxturna, for a rare inherited retinal disease), the 2019 update includes a handful of new market entries and a robust pipeline, with some tantalizing year-end hints about promising results in gene therapy trials for sickle cell disease and beta thalassemia.  Nowhere is the optimism felt more keenly than the SMA community, where parents now have competing options to treat what was until recently a death sentence for their affected children.

But as this story by the Washington Post indicates, access to those options poses a world of new challenges.  Zolgensma, a gene therapy for SMA, made headlines as the world’s most expensive drug at 2.1 million dollars per patient, and that fact means that insurance companies are going to take a long hard look at who qualifies for the treatment.  This article concerns a toddler turned down for the drug because as a type-III SMA patient she is not severely affected enough to qualify – although she has difficulty walking and can anticipate lifelong disabilities.  Since the use of the medication is only approved for children under two, there’s no room for a wait-and-see attitude.

The economics of gene therapy are built on a model of one-and-done treatment that replaces lifelong care, a promise that in these early days is aspirational at best.  But even if it goes according to plan, the model doesn’t account for children like the adorable, moon-faced Daryn Sullivan, whose lifetime medical costs might not be so outrageous as to make 2.1 million up front sound like a bargain.  With other diseases, off label use might include genotypes that are not the best case scenario for use, where we anticipate improvement not cure.  If it’s the best medicine can do, can we pay 2.1 million for anything short of a miracle?

For all these substantial challenges, the biggest translational obstacle may be something more subtle, captured not in the article but in the comments.  Daryn’s parents, it turned out, knew during pregnancy that the child would be born with SMA and chose not to end the pregnancy.  Will our increasing ability to identify and prevent genetic disease make us less willing to fight the hard fight for access to treatment?  “I had the deepest sympathy for the Sullivans,” one reader wrote, “until I read the part where they KNEW their baby was doomed to a terrible wasting disease, but continued the pregnancy anyway.”  A quick review showed about 10% of the 320 comments said something similar: “people create children with disorders and then demand that everybody else pay for their treatment no matter what the cost.  Shameful.”

In the past 10 years, we have addressed many of the technical challenges to gene therapy.  In the next decade, we will have to confront the potentially even more challenging issues of access and empathy.

 

THAT’S IT FOR ME IN 2019!  HAPPY NEW YEAR, EVERYBODY!!!!  GOOD LUCK TO US ALL IN 2020 (WE’LL NEED IT).

 

 

 

 

 

 

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by | December 29, 2017 · 10:17 PM

Top Ten Stories in Genetics in 2017

Mark it in your calendar: 2017 was the year when gene therapy (broadly defined) became something more than hypothetical.  Hard to talk about 2017 as a great year, but that’s the storyline in genetics.  Here’s the countdown:

  1. Ohio Bans Abortions for a Fetus Affected with Down Syndrome

In December 2017, Ohio became the 3rd state to criminalize abortion to avoid the birth of a child with a genetic condition. The first law was passed in North Dakota in 2013 and remains on the books, and a similar measure in Indiana that focuses specifically on Down syndrome was enjoined by court order after an ACLU challenge.

Ohio’s law makes it a felony to perform an abortion if the patient’s motivation is to avoid the birth of a child with Down syndrome. These laws appear unlikely to be enforced: unconstitutional under Roe v Wade, they should not survive a court challenge, and if they did, they would be incredibly difficult to enforce. Still, there are several reasons why it is worth paying attention to what must now officially be called a trend.

First, these laws didn’t pop up organically, and they indicate that therapeutic abortion is on the radar of anti-abortion groups. Expect more of the same, and battles on related fronts, including insurance coverage for prenatal testing.

Second, even if the law is never enforced, it could affect practice. A woman’s motivation is hard to prove, but the motivation of a genetic counselor or a physician discussing termination after a diagnosis of Down syndrome is crystal clear, and could put them at risk. Even a distant and unlikely threat of a felony prosecution is a great disincentive to any clinician. Discouraging counseling may pr may not prevent abortion but it absolutely deprives couples of the good, unbiased information that Down syndrome advocates have been working on for years. And as usual, it increases disparities in care for individuals with fewer resources or less education.

Third, polling suggests that a slim majority of the country believes abortion should be available for pregnant women when the fetus faces cognitive impairment, but it’s emotionally tricky territory and norms may shift to make therapeutic abortion more stigmatized. There’s a reason why the second and third iterations of the law specified Down syndrome: this is a public relations campaign and Down syndrome kids present a sweet and photogenic face. “Every Ohioan deserves a right to life, no matter how many chromosomes they have,” said the head of the Ohio Right to Life, neatly eliminating the difference between a fetus and a child.

Fourth, expect a whole lot more of this if we lose Roe v Wade.

  1. STAT names the Swiss Army Knife the top CRISPR metaphorScreen Shot 2017-12-29 at 7.26.31 PM.png

Bacteria have been using CRISPR for aeons, but humans have only had it in their gene editing toolkit for five years. In that short span, technical advancements have occurred so quickly that 2012 CRISPR is starting to feel a bit old school. Some of these innovations improve the original CRISPR search-and-delete functionality – reducing off target effects, for example, or improving the odds of replacing deleted DNA segments with a scripted sequence delivered via a template. Other advancements add new types of functionality. In 2017, researchers introduced a modified CRISPR system uses the same search function but doesn’t cut; instead, it alters gene expression by changing the elaborate system of packaging that turns gene on or off. In another iteration of CRISPR search-and-don’t-cut functionality, scientists from Harvard and the Broad Institute have pioneered a technique called base editing, which locates a specific spot in the DNA sequence and replaces a single base through a series of chemical reactions without the riskier business of inducing a double-stranded break. In October, researchers from China announced that they had tested base editing in human embryos, and were able to correct a mutation that causes the blood disease beta thalassemia 23% of the time.

The proliferation of CRISPR varietals led writers at STAT to give top honors to “the Swiss army knife” in a ranking of CRISPR metaphors (runner up: “organic photoshop”).

 

  1. Harvard’s George Church opens up the George Church Institute in ChinaScreen Shot 2017-12-10 at 4.37.03 PM.png

Synthetic DNA made significant steps forward this year, starting with an announcement in January that researchers at the Scripps Institute in La Jolla have produced a modified a strain of E coli whose DNA has six rather than the usual four base pairs. The following October, in a story that my be the epitome of 2017, Harvard professor George Church traveled to China to announce the opening of the eponymous George Church Institute of Regenesis. This collaboration with Chinese giant BGI has plans to develop clinical applications of synthetic biology. The investment of substantial resources in artificial life forms and bio-manufacturing is one indication of where we are headed; sadly, the decision by one of America’s great science talents to launch an ambitious project halfway across the world may also prove to be a sign of things to come.

 

  1. Popular Culture Discovers CRISPR

This was the year I read my first sci-fi novel about a world where children (and pets) are routinely gene-edited. Although it was a dystopian vision, I have to admit I was intrigued by the tiger-ized house cat…

CRISPR has definitely captured the imagination of a good part of the universe, and my sense is that the jury is out on whether our new powers of gene editing are going to be viewed as cool or creepy. Meanwhile, here’s some unexpected places where CRISPR popped up in 2017.

On Jeopardy!

Screen Shot 2017-11-25 at 5.24.41 PM.png

In Ashton Kutcher’s twitter feed:

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Graffitied on the mean streets of San Francisco:

Screen Shot 2017-11-25 at 5.24.13 PM.png

This is a sleeper pick at number 7, but I believe it’s important to understand that people are paying attention, because (like the rest of us) they don’t yet know what to think. The early uses of CRISPR will have a great impact on public opinion, and very likely on support for research, development and commercialization of gene editing down the road. It’s something to think about.

 

  1. The FDA Changes Direction on DTC Genetic Testing

The FDA executed a remarkable about-face on direct-to-consumer genetic testing in 2017, beginning in April when the agency approved a new iteration of their SNP scan for liability to disease, 3 ½ years after they shut down sales of the alpha version, claiming it posed a risk to the health of those who bought it. In addition to signing off on testing for 10 complex conditions where the genetic contribution is important but not definitive, the FDA announcement established some ground rules that could be applied to other tests and other companies. First, the decision identified 23andMe as what they called a ‘trusted provider’ and indicated that having been so designated, they would not have to jump through regulatory hoops for every new test, and would be exempt from premarket review. Second, the agency created a category called “genetic health risk (GHR)” tests, as distinct from genetic tests that were diagnostic, which were explicitly excluded from exemption.

Presumably, the agency’s goal was twofold: to remove impediments to the growth of DTC, while carving out some rules for what belonged in that realm, as distinct from what belonged in a clinical setting. In November, the FDA made this explicit, announcing its intention to establish a new regulatory structure for GHR tests which would formalize the ‘trusted provider’ approach through a one-day FDA review, allowing them to introduce non-diagnostic tests and carrier screens without further premarket scrutiny.

This change in governance is likely a response to what is happening in Washington, where anti-regulatory sentiment is rife, and may also be due to changes in the marketplace, with major players like Illumina and Google making sizeable bets on DTC genetic testing ventures. There is little question that the FDA moves have had a big impact, and the fledgling DTC industry appears to have spread its wings and taken off. Strong Christmas sales for both Ancestry.com and 23andMe indicate that consumers are willing to give genetic testing a try; sustained success may be contingent on how that experience goes for the recipients.

 

  1. First RNAi Drugs Show Promise in Human Trials

Many of the early targets of gene therapy are diseases caused by a single missing or defective protein, and the goal in these cases is to introduce a gene that will produce what the body is lacking. Despite the fact that we have not been very successful to date, it is a simple model; often replacing a small fraction of normal production is enough to treat or effectively cure the disease. In some diseases, however, the problem is not the absence of a normal protein but the presence of an abnormal one which disrupts function or damages healthy tissue. In these cases, you can’t simply (‘simply’) replace what you don’t have but must find a way to silence the gene product that is causing all the trouble.

One way to do this is to intercept the RNA messages before they are made into protein via RNA interference – designer RNA’s that find and bind to specific transcripts to prevent translation. Like many other forms of what might broadly be called gene therapy (I’m not into fights about semantics so don’t @ me), RNAi has not fulfilled it’s conceptual promise to date, but that seems to be on the verge of changing. In October Ionis Pharmaceuticals launched the first human trials of a RNAi drug for Huntington’s disease, and in November a Cambridge-based company called Alnylam announced that its RNAi drug for hereditary ATTR amyloidosis was showing success in phase 3 trials and might be up for FDA review in 2018.

 

  1. In Vivo Gene Editing Mitigates Deafness (in Mice)

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In another late entry into the Top Stories of 2017, researchers from the lab of David Liu published a December article in nature describing the use of in vivo gene editing to facilitate hearing in mice bred to exhibit a form of genetic deafness found in humans. Mice injected with CRISPR-Cas9 complexes showed more hair cells and improved response to auditory testing. While it is always good practice to remind ourselves that not everything that works in rodents works in people but… in vivo gene editing is a remarkable technical achievement with incredible potential. Brought to you, by the way, by a co-founder of Editas Medicine, so this maybe this blog post can double as a stock tip. 2017, ladies and gentlemen.

 

  1. A Gene Therapy Ready for Prime Time at Last!

We’ve been talking about gene therapy for so long it seems like old hat, except that this particular old hat has never been thrown into the ring… until now. On December 19th, the FDA approved Luxturna, a gene therapy for blindness. First of its kind, Luxturna introduces a gene into retinal cells by a viral vector and, in cells where uptake of the wildtype variant increases the production of normal protein.

Eyeballs are a uniquely accessible body part, making them low-hanging fruit for gene therapy, but low-hanging fruit is the place to start, and the take-home point here is that the new and improved gene editing technology and gene delivery systems are for real, as is (finally) gene therapy. Coming soon: gene therapies for blood-based diseases such as hemophilia and sickle cell. Still to be determined: how much all of this will cost.

 

  1. Immunotherapy Delivers a One-two Punch

The cancer field has been buzzing about Car-T therapy for years, hopeful that this new class of therapies designed to harness the body’s own immune system would not only expand the range of cancers we could fight, but do so in a targeted fashion that would reduce the toxicity associated with current chemotherapies. Immunotherapy has been through several rounds of hype-and-hate before getting out of the clinical trial phase, as stories about patients rescued from the deathbed have sent up smiley face trial balloons and deaths from unanticipated side effects have popped them.

After all the anticipation, approval of the first two Car-T drugs came only weeks apart, with Kymriah, a drug for pediatric leukemia, approved in August and Yescarta, for some forms of B-call lymphoma, following close behind. All the usual caveats apply – real-world safety and efficacy still to be worked out over time, and price price price price price plus access, but without setting that aside, I want to take a moment to congratulate everyone who worked to create and validate this new and important class of cancer therapies.

 

  1. The Boy who Got New Skin Is Everything You Ever Hoped For in a Stem Cell Success Story

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I was six paragraphs into Ed Yong’s story about a boy with epidermolysis bullosa when I realized it was going to be my top story in genetics for 2017. How many things are there to love about this story? First of all, it’s about a cure for EB, a disease that disrupts the normal structure of the skin, making it fragile, so that it is prone to rupture and blister. In bad cases, people are plagued with open sores that will not heal. It’s a biblical plague of a disease, and this kid was in terrible shape – shape – seven years old, and headed to hospice care.

And they fixed him.  This is also a stem cell success story, joining the list of finally-finally-at last therapeutic success stories in 2017. Doctors removed a small patch of precious intact skin from seven-year-old Hassan and sent it to researchers in Italy, who isolated and corrected skin stem cells, and then used them to grown sheets of skin in which to sheath the dying child. They replaced an astounding 80% of his old skin and – here’s the part from paragraph six – less than a year later he is back in school, playing sports and living the life of a normal child.

I promised myself never to talk about these high tech miracles without discussing cost and access, so here I raise relevant questions: what’s this going to cost, and who will be able to get it?   Honestly, I have no idea.   And for the record, this technique won’t work for all variants of the disease.  But there is a lot to celebrate.

It seems strange to talk about 2017 as a series of victories for humanity, but the year in genetics was full of hope and promise, and nowhere was that contrast more on display than here, in the a story of a global community coming together to save a life. A Syrian child, treated by German doctors together with Italian researchers who were mentored by an American pioneer…  It was the epitome of 2017 in genetics, though sadly not the epitome of 2017 in any other sphere.

 

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by | September 20, 2017 · 5:50 PM

Supporting Our Patients and Their Right to Choose Means Opposing Graham-Cassidy

If you are a genetic counselor supporting the Graham-Cassidy proposal to replace Obamacare, you are a rare bird. Most genetic counselors – most medical professionals – most Americans for that matter – are opposed to this bill, because it compromises our ability to provide basic, essential medical care for people in need. It is not in dispute that millions of American will lose health insurance under this bill. Those with health insurance will generally pay more for less. Many of the changes remove existing protections on which our patients are particularly reliant. Here are some examples:

 

PRE-EXISTING CONDITIONS

The bill will allow states to eliminate regulations on pre-existing conditions, so that people will risk losing coverage if they change or lose their jobs. This is a disaster for individuals with chronic health problems including genetic conditions, and potentially a disaster for individuals who carry susceptibility genes. Although you might make the case that GINA should protect those individuals in theory, in practice it becomes hard to draw the line for what constitutes an existing disease in an at-risk individual. For instance, if a Lynch Syndrome carrier requires special screening and has polyps removed, are they preventing disease or symptomatic? Will a subsequent carrier argue that they already showed signs of Lynch and therefore are not covered for further screening or colon cancer? The fact is that Obamacare arrived before these questions got answered, and there is a very real risk that GINA protections will be eroded when the actual lines between pre-existing and manifest disease are drawn.

 

PRENATAL CARE

The new law allows policies to limit or even eliminate coverage for prenatal care. This logic of this abomination – the disgusting and perverse logic to be voted on by a collection of doddering old men who apparently were not of women born – is that pregnancy is not a disease but a choice, and affects only subset of women, so that others should not be asked to bear the costs. This decision abrogates the most fundamental obligation of civil society, which is to raise the next generation. You have one job, civilization. One job.

 

Every politician who argues that it is not fair to ask everyone to pay for insurance that covers prenatal care should be asked if they believe it is fair to ask women to pay for policies that cover prostate cancer care. Or who it is they believe will care for them in the nursing home, or fight for them in their wars, or protect their streets or teach their grandchildren or write their history books if not the next generation of Americans.

 

But you see here I am getting worked up, and the very righteousness of this anger masks another aspect of this change that has particular resonance for genetic counselors: limiting access to prenatal care limits access to prenatal testing, and limiting access to prenatal testing to those with more money will mean that those genetic diseases and conditions for which we can test will change the essential nature of genetic disease – no longer something that happens to everyone, it will become an affliction of vulnerable individuals. I wrote about this in a recent essay, calling it the Ghettoization of Genetic Disease, and this bill will help make that dystopian prediction a reality in the near term.

 

LIFETIME CAPS AND DISABILITY CARE

The Graham-Cassidy bill eliminates protections on lifetime caps, meaning that many individuals with chronic conditions, including genetic diseases, may end up without coverage. In addition, the cuts to Medicaid and other federally funded programs would radically reduce support for individuals with disabilities.

 

On the surface, flat out, this is heinous and cruel. Beyond that, for the genetics community, this undercuts the promise we make, by implication, to every woman or couple who decides to move forward with a pregnancy affected by or at risk for genetic disease. Supporting choice in reproductive decision-making is not a simple matter of holding someone’s hand through a difficult day. Supporting autonomous decision-making as a field means fighting for those individuals and families to be supported throughout the lifecycle.  The choice to live in a world that offers no support or resources is no choice at all for most people.

 

LET’S TAKE A STAND

It is extremely unfortunate that healthcare, a subject of mutual concern and importance to all Americans, is now held hostage to the ignorant, pettiness of slogans on signs that angry partisans wave at campaign rallies. No professional organization wants to get embroiled in party politics. On the other hand, there are times when everything you believe in is threatened and you have to take a stand. I believe this is one of those times.

 

I’m hardly alone in this. The AMA released a statement yesterday opposing Graham-Cassidy. So have many other groups representing healthcare professionals and patients, a number of them listed here in Jimmy Kimmel’s eloquent denunciation of the bill (comedians must lead when politicians are clowns, I suppose, and what else can he do when our government is beyond satire?).

 

So please, NSGC, make us proud with a statement against this terrible bill. Let’s take a stand for our values and, more importantly, for our patients.

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by | August 5, 2017 · 9:42 AM

Human Germline Editing: our crazy, scary, wonderful future is coming, but not quite yet

Publication this week of a paper by reproductive biologist Shoukrat Mitalipov and others put the subject of editing little baby humans front and center – above the fold news in the NY Times. Universally, the Mitalipov study was recognized as a milestone, and so it appears to be – a milestone on our journey to…wherever it is we are headed.

 

What did they do, and why is it important? Mitalipov improved greatly on previous efforts at germline editing, targeting embryos created using donor eggs and sperm carrying a pathogenic variant in the MYBPC3 gene associated with hypertrophic cardiomyopathy. Modification was successful over 70% percentage of the time, no off-target effects were detected, and only one of the 58 embryos was found to be a mosaic of altered and unaltered cells. While significant safety and efficacy concerns remain to be addressed, this work goes a long way toward validating the idea that, sooner rather than later, clinical use of this technology will be a realistic possibility.

 

The experiment raised hopes, but also some questions. CRISPR is often described as a DNA version of a search-and-replace function in a word processing program, but CRISPR itself only does search-and-remove. The ‘replace’ part leverages the cell’s own machinery for fixing breaks in DNA, and its innate penchant for tidying up any loose ends. Quick to the breach, cells can often be coaxed into using a template for the repair if one is provided along with enzymatic scissors and a guide RNA, allowing us to insert a custom DNA sequence. This bespoke DNA can be anything, but in this case it was meant to be a benign version of the MYBPC3 gene. In a surprising development, the cells preferentially ignored the synthetic template and used the unaffected version on the sister chromosome as a guide instead.

 

This had the desired effect of introducing a functioning wildtype gene, but if it is not overcome as a technical issue, will limit the range of what can be achieved via gene editing. This model doesn’t work at all with recessive disease, where there are two copies of the pathogenic variant. Additionally, it would not allow for the introduction of DNA sequences other than what is carried by a parental allele – a capability which is, I would argue, the truly unique feature of gene editing.

 

Articles about CRISPR may (and usually do) talk about its potential to prevent Mendelian diseases like Huntington’s or sickle cell, but we are already capable of preventing transmission of these diseases using IVF with PGD to identify embryos that are unaffected. Yes, as has been pointed out, this is not foolproof. A round of IVF may produce no unaffected embryos. In rare circumstances, one parent may be homozygous for an autosomal dominant disease. These are non-trivial events when they occur but they are rare and limited circumstances. For the rest, replacing one expensive and complicated technology with another is incremental progress at best, and not the reason why this story was A-1 on the NY Times website. Media interest, let no one be confused, was about the potential of CRISPR to produce what they referred to (inevitably) as designer babies.

 

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Antonio Regalado of the MIT Tech Review decodes media coverage of human genome editing

 

Can the technology produce designer babies? This would be an easier question to answer if designer babies were actually a thing that you could define, but they’re not. Generally, what people mean by ‘designer baby’ is one created through any use of reproductive technology to ensure specific traits, as opposed to using identical technology to avoid diseases. The problem with this is that drawing the distinction is a bit of Impressionistic painting – clear from a distance, but blurring together when you get close. A number of articles this week suggested that designer babies can’t happen because traits are not something that can be manipulated by tweaking a gene or two (here and here). This is comforting but may not hold up. It’s fair to say that you can’t tweak general intelligence – but what about, for example, executive function? And while we’re on it, would that be increasing intelligence (bad) or avoiding ADHD and other mental health problems (good)?

 

But this is leading me into rabbit holes, where we debate what is or might be or could be possible, when just now I want only to say that the potential of gene editing to add an entirely new dimension to what we can currently offer is bound tightly to its ability to introduce DNA sequences that are different from what either parent can contribute. When we are able do that, we can expand the concept of what it means to ‘choose’ a child’s genotype. We can add rare variants that confer some protection or competitive edge. We can even contemplate adding synthetic variants designed in a lab and not borrowed from natural experiments. When move past embryo selection to embryo improvement, we will have our little Gucci baby whose possible existence causes so much consternation.

 

So does this week’s blockbuster paper put us closer to that day? Yes, because the technology has moved forward a giant step. Not that technology ever moves backwards, but the speed with which it has improved is staggering, and while momentum is not going to carry it over the remaining hurdles like a hot wheels car going loop the loop, it does make it easier to assume that all technological barriers will eventually fall. But at the same time, the template surprise reminds us that every step forward reveals another twist in the road.

 

Are we almost there?  Who knows. If 2016 taught me anything, it was to stay out of the prediction game.

 

So what would a wise republic do? Coincidentally, a workgroup under the auspices of the American Society of Human Genetics published a paper yesterday in the AJHG laying out recommendations for public policy on human germline editing. The position statement was approved by ASHG, NSGC and 9 other organizations from six continents (full disclosure: I am one of the co-authors). The take home point is that modification of the human genome (egg, sperm or embryo) would be premature at this time but may be justified in the future, providing that there is a compelling medical rationale, an evidence base to support its use, ethical justification and a transparent public process to solicit and incorporate stakeholder input. In the interim, the organizations encourage governments to permit and to fund work like Mitalipov’s that investigates the potential of human germline engineering.

 

Having been a part of this group, I can attest that we thought long and hard about this aspect of the statement, and that we made it despite our concerns that this technology holds risks for both individuals and society, including the potential to increase existing inequities in health and quality of life. We may try and regulate use and norms such that we get the upside and not the downside, but we must acknowledge that to a large extent the two are inextricable.

 

Speaking only for myself, I can say that I see the allure of a form of intervention that might prevent rather than merely treat sickness and suffering, even as I sympathize with those who worry about the impact of the technology on future generations. If the choice were mine, it would be a difficult choice. But in the end, what I recognize is that we are not given a choice between going backwards and going forwards. The truth is that gene engineering is going to happen.  No one government or individual is going to stop it — the world is too big and the stakes are too large. The questions that sit in front of us are not yes or no, but where, how and under what circumstances. I believe that a thoughtful society should engage with the technology, providing capital and oversight, resources and regulation. To turn our back is to sacrifice whatever leverage we could bring to bear as we establish norms for use, and to cede our leadership role in the scientific community at the dawn of an era, the start of a journey to…wherever.

 

 

 

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by | April 9, 2017 · 7:32 PM

FDA and 23andMe change their Facebook status to ‘in a relationship’

In 2007, 23andMe launched their personal genome scan, a SNP-based test that offered consumers an estimate (some might say a guess) as to how certain elements of their genotype might contribute to their likelihood of having an array of traits and diseases. It was a great success, if success was to be measured in ink and column inches rather than actual dollars. Anne Wojcicki’s company quickly came to represent the embodiment of direct-to-consumer genetic testing, an icon of what was more a movement than an industry.

 

For that reason, six years later, when the FDA surprised 23andMe with a cease and desist order for their genome scan, it could reasonably be taken as a rejection of not only one company but the entire DTC ethos. At the time, many canny observers pointed out that the FDA’s drastic move seemed to have more to do with 23andMe’s attitude than it did with any specific risk posed by testing. As Duke University genetic professor and trenchant observer Misha Angrist was quoted as saying at the time, the FDA missive read “like the letter of a jilted lover…‘We went on fourteen dates! We exchanged all these e-mails! We held hands in the park! Now you’re telling me, “Fuck you,” and kicking me to the curb.’ ”

 

In response, a chastened 23andMe kept a toe in the DTC puddle by offering testing for ancestry and non-medical traits like sleep patterns and eye color while negotiating a slow courtship of the regulatory body. Eventually they got flowers back from the FDA – or rather a single flower, permission to offer just one carrier test, for the aptly named Bloom syndrome. But this blossom, like many others, was freighted with greater significance, and now that they were friends again the FDA decided that other DTC carrier tests would no longer require individual premarket approval, allowing 23andMe to add back a layer of medical testing to their business model.

 

The FDA drew a line between giving out information on carrier status (okay) and giving out information that was diagnostic (not okay). This created the odd situation where 23andMe could tell a customer if he or she had, for example, one CF-causing variant but was forbidden to inform them if they had two, since that was a presumptive diagnosis. Let’s leave aside how confusing this all gets, since sometimes people can have two disease-causing variants and remain healthy, and sometimes carriers can have medical complications. I’m not even going to mention that. See how I didn’t mention that? The bottom line was that 23andMe could inform you of a risk for something that might happen, but only if it was a mere possibility and not if it was certain or highly likely.

 

Two years later, the FDA has come out with another announcement – this time I assume that 23andMe is less surprised than the rest of us – that will expand the universe of what is available through DTC testing. The company will now be allowed to provide testing for susceptibility to 10 diseases and conditions with significant health implications, including late-onset Alzheimers disease, Parkinson’s. celiac, Gaucher’s disease type 1, hemochromatosis, and others. Again, this isn’t just a bouquet of flowers being handed out to a patient suitor. It signifies a change in thinking at the FDA about the value of DTC genetic testing, which they noted in their press release “may help to make decisions about lifestyle choices or to inform discussions with a health care professional.”

 

No but really this is getting embarrassing get a room you two.

 

The FDA announcement indicated that these 10 diseases were merely a beginning. In the future, 23andMe and other trusted practitioners will be able to introduce tests with less regulatory scrutiny. The FDA’s commitment to a streamlined and less burdensome process demonstrates a new interest in making DTC genetic testing widely available.

 

The important thing, emphasized Jeffrey Shuren, director of the FDA’s Center for Devices and Radiological Health, was that consumers did not come away believing that genetics was destiny. “…it is important that people understand that genetic risk is just one piece of the bigger puzzle, it does not mean they will or won’t ultimately develop a disease.” For this reason, the FDA has doubled down on it’s practice of differentiating between susceptibility and diagnosis.

 

Conceptually, this makes sense. Practically, in some cases, it creates a situation where DTC customers can access the sort of probabilistic information that we are generally loathe to give out in a clinical setting – like their chance of getting late-onset Alzheimer’s disease – but are blocked from getting exactly the sort of definitive, actionable information we value the most.

 

Possibly, this might serve to differentiate the realm of DTC testing from the kingdom of clinical medicine. Genetic counselors, often DTC skeptics, might feel more comfortable adopting a live and let live approach if areas central to GC practice like susceptibility for cancer and heart disease were reserved for the clinic. Still, when it comes to ApoE, it is a bit of a paradox that the solution to information deemed too hot to handle by counselors is to give it out with no counseling at all. The impact, I am inclined to believe, will be to speed the integration of probabilistic testing into genetic practice. In the meantime, it will almost certainly herald a period of rapid expansion of health and wellness testing in the DTC space.

 

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by | March 15, 2017 · 4:23 PM

Will H.R. 1313 Allow Wellness Programs to Undermine Your Rights Under GINA? Inquiring Constituents Want to Know…

It’s 2017, and it’s hard to keep track of the reasons to be outraged, but here’s one with special relevance to the genetics community: H.R. 1313, the Preserving Employee Wellness Programs Act (alternatively entitled H.R. 666, the Unfortunate Erosion of GINA Act).

There are two main questions we should be asking about H.R. 1313. One, what does it do? And two, why does it exist? For the first, what the law would do (if passed) is allow so-called wellness programs to circumvent the limitations on data collection by employers set out in the genetic non-discrimination act (GINA) and the Americans with disabilities act (ADA). I say so-called wellness programs because in point of fact they have not generally been demonstrated to make people, shall we say, well-er. Which raises the question of why Congress is so keen to make sure they are maintained, but we will get into that later.

Under GINA, employers are not allowed to purchase, request or require genetic information from their employees. The assumption behind this point of law is that employers who had that information might be tempted to try and reduce their exposure to risk by discriminating against those in their risk pool (or their dependents) with increased susceptibility. Alternatively, they might try and use genetic information as a part of decision-making about promotions or assignments. Some of the people attacking the bill have pointed out that attempts to use predictive genetic information are at present likely to be absurdly ineffective and misguided, but this only makes the acts of discrimination more random, not more (or less) nefarious. If they could do it with pinpoint accuracy, it would still be unfair.

Exceptions for wellness programs already exist under GINA, to allow these programs to ask the participant about genetic conditions or genetic testing. As the law stands, the employee must participate voluntarily, and individual identifying information must be collected by a licensed or certified health professional (including, specifically, a genetic counselor) and cannot be shared with the employer except in the aggregate. As for voluntariness, H.R. 1313 would alter this dynamic by sleight of hand – employers are not allowed to charge people more for insurance if they don’t participate, but they are allowed to offer incentives for employees who do participate, and those incentives can be up to 30-50% of their total healthcare contributions. Got that? We’re not charging you more, people who don’t give us your genetic information, we are simply charging the other people less.

 (Sidebar: perhaps we can get corporations to introduce wellness programs that require employees who participate to vaccinate their kids, while the ones who do not pay thousands of dollars more per year in health insurance costs. Vaccines, after all, are the best validated wellness program that we have. Just a thought.)

 The second and most serious charge that has been made about H.R. 1313 is that it would eliminate privacy protections that exist under GINA, and give your employer access to genetic information about employees and their family members. This has been reported in a number of places (in the NY Times here and in STAT here) but is disputed by the NSGC fact sheet circulated on, forebodingly, the ides of March. The bill doesn’t refer to the issue of sharing genetic information specifically, and it seems reasonable to assume that those protections you have under GINA would be in force unless specifically taken away, HOWEVER, there’s obviously room for doubt, given all the doubt. Take home point: the bill should be amended to include a clear message that genetic information is private and cannot be shared with employers (or, for that matter, sold – as commonly happens with wellness programs today).

Which brings me to my second question: why does this bill exist? Identifying the beneficiaries might shed some light on what it is intended to do. Employers might like the bill, if they see it as allowing them to shift health care costs to non-participants via the incentive system (lower costs for some being alternately described as higher costs for others). If we are being pie-eyed optimists, we could imagine that employers are just determined to see you healthy, although in that case they might be put off by the absence of any compelling evidence that these programs work. If we are being conspiracy theorists, we might wonder if some employers see an opportunity to obtain information on the health and health risks of employees and their dependents to which they are denied access under GINA.

Obviously the law is a boon to the ‘wellness’ industry, which Congress is nurturing with this sack of high quality manure while asking in return only that the wellness program not be “highly suspect” as a method to “promote health or prevent disease.” Ah, the old, ‘not highly suspect’ standard.

Perhaps, say you, another beneficiary of the law is the employee who receives a rebate for being healthier. Yes. I’m all for lower health care costs. But since the wellness programs don’t actually make employees healthier, but may identify employees (and their dependents) with more health risks, their benefits come by chasing people who need insurance out of their insurance pool. Companies could keep their own overall costs the same by dropping everyone’s premiums by some intermediate amount, which would help all employees with the added benefit of not being a human rights violation. Food for thought.

On March 8th, the American Society of Human Genetics (ASHG) came out with a strong statement opposing H.R. 1313, quoting director of science policy Derek Scholes as saying that “If enacted, this bill would force Americans to choose between access to affordable healthcare and keeping their personal genetic and health information private….Employers would be able to coerce employees into providing their genetic and health information and that of their families, even their children.”

The response from NSGC has been more nuanced, prefacing a statement on their concerns about H.R. 1313 with the caveat that “NSGC supports the collection of family health history information.” Without taking an official position on the bill, NSGC has indicated concern about voluntariness and privacy protections, proposing that in its final version, “the bill should explicitly reaffirm the GINA discrimination protections, roll back penalty language altogether, and limit rewards, among others. NSGC would also support further study of the value of wellness programs, and their focus to ensure the programs can indeed positively impact health.

Privately and publicly, I have heard comments from members of the genetic counseling community who are concerned about H.R. 1313. This bill has gathered a fair amount of negative attention and there is a good chance it does not move forward, at least not in its current form. I don’t say this to discourage grass roots activism; in fact it’s the opposite – evidence suggests that public pressure is having an impact. So call your Member of Congress! (we all have our elected representatives on speed dial by now, right?). Here’s a quick summary of three points worth making:

  1. Participation in any program that includes gathering genetic or family health history information on the participant and/or family members should be truly voluntary, and should not be associated with substantial rebates or incentives.
  1. Wellness programs should be explicitly required to conform with the privacy protections for genetic and family health history information that have been established by GINA and the ADA. Congress should pass no laws that erode or diminish these important civil rights protections.
  1. Laws creating special exemptions or accommodations for wellness programs should include a standard for wellness programs based on an objectively assessed, documented record of improved health outcomes.

 

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by | December 27, 2016 · 10:42 AM

TOP TEN STORIES IN GENETICS, 2016: An Adolescent Science Meets the Big World

Clinical genetics is a young science, not yet come of age – a new discipline. It’s early days, say the small group of clinicians and researchers who have watched over its formative years, dreaming like proud parents of a future where genetics and genomics are integral to clinical medicine. And as for many parents, it may sometimes have seemed that the all-consuming, semi-hermetic little laboratory of childhood would go on forever.

But guess what, people? I believe we have entered the teenage years.  I believe baby has borrowed the car keys and taken it out for a spin.  I see a field boasting a few real accomplishments, and on the cusp of so many changes, from therapies for genetic disease and cancer to a suddenly burgeoning DTC marketplace. And like all parents, geneticists are poised to discover the limits of our ability to control what we have nurtured. That’s exciting, more than a little bit scary, and the theme of this year’s top ten.

  1. FDA CANCELS PLANS TO REGULATE LDT’s

Over the past two decades, a single technological advancement has revolutionized the way we practice medicine.

I am talking, of course, about overnight delivery of packages.

Years ago, laboratory testing services were divided into large companies that sold test kits and devices nationwide, and the small labs in hospitals and other clinical settings providing services to their local providers. With limited resources, government regulators focused on the tests that affected more people, and agreed by convention that ‘laboratory-developed tests’ would not be subject to the same scrutiny. Today these distinctions are virtually meaningless, as giant companies like LabCorp and Quest perform tests ‘in-house’ on samples gathered worldwide, tossed in a box and sent overnight. Still laboratory-developed tests (or LDT’s) – a category that includes virtually all genetic tests – remain in regulatory limbo.

In 2010, the FDA announced its intention to address this loophole. In July 2014, they issued draft guidance detailing their plan for a regulatory structure that divided the LDT universe into high, low and medium risk tests. While some professional organizations disputed the FDA’s right to have a role in regulation of LDT’s and threatened legal action, others approved the framework in principle but disagreed on specifics, including how to handle the thorny new territory of exome and genome sequencing. A dialogue ensued with representatives of labs, clinicians and patients that has lasted two years and included multiple workshops and public meetings. That process, it was widely assumed, was nearing its end, with the resulting draft guidance expected to be sent to Congress for approval in the near term.

And then came November 8th and the election of Donald J. Trump, ushering in an executive opposed to regulation on principle, to join a similarly inclined House and Senate. Ten days later, the FDA ran up the white flag, announcing that the agency would not take steps to finalize its existing plan and would instead reopen the discussion with a new administration and a new Congress. What this means precisely is a matter of some interesting speculation, but in general it suggests that an industry that has been struggling for years to avoid too much regulation will have to consider the consequences of living with none at all.

 

  1. IS THIS THE FUTURE? CRISPR EXPERIMENT ADDS RARE PROTECTIVE VARIANTS TO HUMAN EMBRYOS

The second experimental use of CRISPR technology to alter human embryos was reported in May of 2016, again by a group out of China. Again, the embryos used were not viable, and no attempt was made to transfer them for reproductive purposes. While this experiment did not produce the same ethical firestorm as the first, it was in several ways a more significant indicator of both the potential and the peril of human germline engineering using CRISPR.

In the first experiment investigators attempted to alter a gene variant responsible for causing hemoglobinopathy, with limited success – proof in principle that it could be done, but nothing to assure worried observers that it could be done safely. In version 2.0 there were fewer off target effects, but researchers were not able to consistently control the content of changes introduced in place of the edited DNA. This is not inconsistent with what we know so far about CRISPR: if we envision it as a word processing search-and-replace function, it is good at the finding and erasing part, but hit or miss when it comes to  putting in a replacement.

What stands out about the second experiment is that the goal was not to eliminate a disease-causing gene, but to insert a rare and protective one – in this case, the CCR5Δ32 allele that offers the bearer reduced susceptibility to AIDS. Gene editing is often envisioned as a way that individuals whose children are at risk can avoid or change genes that cause disease, but in the vast majority of these cases there are simpler and better established tools such as PGD if the goal is to obtain embryos that do not carry a specific variant associated with some catastrophic risk. Why use technology to substitute out a pathogenic BRCA variant or a double dose of the sickle cell genes when the parents are perfectly capable of producing a healthy embryo themselves? What CRISPR and related technologies can do that is not available through other means is to introduce a gene that neither parent carries. That is a powerful new option, and it is both exciting and scary in the manner of all things powerful and new.

 

8. GENETIC DISCRIMINATION MAKES A CAMEO

Many wise observers have noted that for all our deeply felt concerns about genetic discrimination, to date the examples are few, far between, and usually more clumsy than systemic (looking at you, Burlington Northern Santa Fe Railroad). These arguments, redux, were on display in 2016 as Canada debated and ultimately passed its own national genetic discrimination law. Yes, Globe and Mail Guy, there is little evidence of a big problem, and a look at law suits filed between 2010 and 2015 under GINA, America’s genetic discrimination law, proves the point. But one real unanswered question remains: is the absence of institutionalized discrimination a sign that it is destined to be a bit player in the big picture of genomics, or is it only too soon to tell? Big companies, whether they are offering insurance or providing employment, may not have had an incentive to weather a PR shitstorm in order to use genetic information to limit their exposure to risk when not that many people have been tested, and the reliability of the data is debatable – which it has been in these early days. Genetic discrimination, in other words, may be making an appearance in Act II.

Two stories got some attention in 2016; whether they are one off events or signs of the future – well, that’s crystal ball territory. Are they important? They are something to which we should be paying attention. Attention should be paid.

In January, Stephanie Lee at Buzzfeed published an account of a boy named Colman Chadam who was asked to leave his Palo Alto, CA school because he carried two mutations commonly associated with cystic fibrosis, although he did not have any signs or symptoms of the disease. The results of genetic testing, inappropriately revealed by a teacher at the school, were taken, also inappropriately, as diagnostic. The reason this got him thrown out of school was to avoid contact with another student who did have CF. The emphasis on keeping children with CF apart, which sounds weird if you don’t know much about the disease, was about the only appropriate thing that happened, because individuals with CF are at risk of passing one another dangerous and life-limiting infections.

Although Colman did not have to leave the school, and the Chadam’s lawsuit against the school district has settled, the case continues to raise issues about how genotype as distinct from phenotype can be used under the law. In addition, it may signal the need for measures to protect personal privacy (no such thing, I know, I know) in an age when genetic testing is commonplace.

Three weeks later, Christina Farr wrote an article for Fast Company about a woman who was turned down for life insurance because she had a risk-conferring BRCA1 variant. Unlike the Chadam case, this is not a result of genetic illiteracy, and it is not a violation of any law: GINA does not cover insurance for life or long-term care. It is, in fact, exactly the kind of genetic discrimination that ethicists and patients thinking about genetic testing have worried about over the years, and if systemic, would certainly be an important point for genetic counselors to raise in pretest counseling (if pretest counseling is still something we do, which is an issue unto itself…but related). According to the article, genetic testing for cancer susceptibility is not required by any insurance company, although nothing stops them from doing that, but companies are starting to request to see test results when they exist. Failure to answer questions honestly can invalidate policies if you are caught.

If this becomes the status quo, it may affect uptake of genetic testing. If it is curbed through regulation, genetic testing may change the way the insurance industry operates. Act II is going to be interesting! I am having a couple of stiff drinks and heading back to my seat.

 

7. TYPE II DIABETES: RESISTANT TO INSULIN AND EASY ANSWERS

Genome wide association studies (GWAS), a way of looking at common variants in the gene pool to identify genetic susceptibility to common diseases, have been unable to explain the degree to which liability to these common diseases is inherited, although it clearly is. If you are in genetics and this is news to you, you have not been paying attention.

Many reasons for this have been proposed, and many are likely a part of the answer. One thought was that individually rare variants might be collectively common enough to play a big role in generating risk, which would not be picked up by GWAS, as it traditionally looked only at variants carried by at least 5% of the population (“the population,” as though there was only one!). Looking at rare variants takes a village, but that is what a googleplex of Type II Diabetes researchers did to produce an epic July 2016 paper in Nature.

Okay 300 authors on the paper so close enough.

The report by first author Christian Fuchsberger showed that MEGA*GWAS produced the most GWAS-y result possible: intellectually interesting, informative and ultimately inadequate. Using exome and whole genome data to capture a broader range of variation, the study found significant association to a handful of previously unknown common variants, and then failed to replicate a good chunk of what we thought we knew. Uncommon variation? The researchers found 23 loci that appeared significant, which was meaningful, but nowhere near enough to validate the rare variant hypothesis as the smoking gun in the Mystery of the Missing Heritability. “A comprehensive and extremely well written paper,” said Dan Koboldt at MassGenomics, and you can almost hear him sigh.

 

6. DATABASES: IT’S NOT JUST FOR WHITE PEOPLE ANYMORE

We don’t have enough diversity in our databases. It’s not exactly news, and yet publication of an article called “Genetic Misdiagnoses and the Potential for Health Disparities” in the August issue of the New England Journal of Medicine felt like a slap in the face.

The methodology was not complex. For hypertrophic cardiomyopathy patients, doctors use genotyping to identify individuals and family members at risk for sudden and catastrophic cardiac events. Identification as ‘at risk’ is a traumatic and often life changing event, requiring ongoing medical screening and behavioral modifications. For these families, a lot rides on whether or not a variant is considered pathogenic. One bioinformatics tool is to look at databases, because there are limits on how bad a variant can be if it shows up regularly in healthy individuals. The study checked variants labeled pathogenic against an increasing wealth of exome data available in public databases and found that a number were common in the African-American population. Result: reclassification from pathogenic to benign of multiple variants affecting primarily African-American families.

“Simulations,” said the authors, “showed that the inclusion of even small numbers of black Americans in control cohorts probably would have prevented these misclassifications.

 

5. IMMUNOTHERAPY: A NEW STAR BURNS BRIGHT AND HOT

Earlier this week, my sister-in-law was telling me about a friend with a cancer deemed treatable but not curable. “But if they get it in remission,” she said, “and he has more time, maybe there will be something new.” There it was – the cancer prayer. May There Be Something New. And I thought, has there ever been a moment when those words felt more hopeful than right now?

Hopes have been raised before, by promises that money would bring answers, and we wandered down blind alleys and into mazes waving cash as though the scent of it would draw the answers to us, but this time, progress is lighting the way like street lamps, and money follows hope instead of the other way round. Immunotherapy – engineered cells meant to light the bodies own defenses into a controlled burn that destroys cancer cells and leaves the rest untouched – has burst onto the scene since 2015. Cancer researchers report on progress in Hemingway stories, terse narratives of a few more days, an extra month or two, and that’s a win, but suddenly we are getting Gabriel Garcia-Marquez fables of magic beans and people rising from their deathbed.

So which story is more 2016: Sean Parker’s 250 million dollar cancer institute, connecting Silicon Valley money with Car-T cells that he describes as “little computers,” and presenting to the NIH in comic sans? Or the unexpected lethal immune response that shut down a Car-T trial by Juno Therapeutics in November, after four people died of cerebral edema?

It’s the two in conjunction that tell the tale. Immunotherapy is truly a candle in the wilderness, but it’s a candle that burns rocket fuel. Or perhaps I should say, in the spirit of the season: catch a falling star and put it in your pocket – bet it burns a hole in your ass.

 

4. A NEW DTC GENETICS EMERGES WITH HELIX

In October, Helix announced the first fruit of its partnership with DNA-lifestyle start-up Exploragen and it’s grapes: Vinome, a company that promises to sell you wine tailored to your genetic profile for something like fifty bucks a bottle. I’m not a wine drinker and that sounds like a lot of money but, hey, you do you.

For Helix, the Illumina spinoff that debuted in 2015, this was one of a series of 2016 announcements giving us a more concrete vision of their plans for a sequence-once-access-often platform for DTC genomics. The structure of it is like Apple, if your IPhone didn’t even pretend to be a phone, and existed entirely as a vehicle for apps. With your first purchase, Helix will underwrite the cost of sequencing and storing your entire exome, and then sell it back to you bit by bit in the guise of applications created by partners.

Effectively, the Helix model lowers the barrier of entry for any product based on DNA testing, by spreading out the cost over a myriad of marketing opportunities. Some current players in the DTC universe have signaled their interest in playing in Helix’s playground; Geno 2.0, National Geographic’s version of ancestry testing, is already available on the Helix website. Others may take their toys and stay at home. Daniel MacArthur of the Broad Institute once penned an April Fool’s Day account of a company named Helix Health’s plans for a hostile takeover of 23andMe using Somali pirates, but for real the entry of an Illumina-backed company into the DTC space must have some Mountain View observers concerned that the current industry thought leader might end up the Blockbuster Video of the genomics world.

The uncorking of Vinome raises a few questions that existing partnerships with, say, the Mayo Clinic or the Icahn School of Medicine at Mt Sinai do not. One role that Helix could potentially play is to provide the vetting service much needed in the consumer genomics world, with its mishmash of pharmacogenetics and Warrior Gene testing and supplements designed just for your DNA.

As for Vinome, the eminently quotable Jim Evans called it “silly” in an article by Rebecca Robbins in STAT. “Their motto of ‘A little science and a lot of fun’ would be more accurately put as ‘No science and a lot of fun,’” said Evans — which I guess is true, if paying fifty dollars for a bottle of wine is your idea of fun. But like Apple, Helix is going to have to make some hard decisions about how much it takes responsibility for the quality of the partners it allows to come play in its sandbox.

 

3. GENOMES OF MASS DESTRUCTION

In February, for the first time but probably not the last, the U.S. Director of National Intelligence’s assessment of worldwide threats included genome editing as a weapon of mass destruction. Congratulations, genetics: we’ve made the big time.

The report pointed to the widespread use of new genetic technologies like CRISPR in countries with different regulatory and ethical standards, its low cost and the rapid pace of change as pre-conditions that might lead to intentional or unintentional misuse, though it was vague as to what form they thought the threat might take. More specific concerns were articulated later in the year by the Pentagon’s Defense Advanced Research Projects Agency (called DARPA of course, because…government) in announcing a program called Safe Genes intended to establish a military response to of dangerous uses engineered genes. DARPA, which Scientific American reports has been a major funder of synthetic biology, will support projects that look at ways to remove engineered genes from a variety of habitats and in a variety of circumstances, including those spread through gene drive.

 

2. A BREAKTHROUGH DEFIES CONVENTION AND GEOGRAPHY

On April 6, 2016, a baby was born after the transfer of his mother’s nuclear DNA into an enucleated donor egg in an effort to avoid the mitochondrial disease that killed the couple’s two previous children. The success of mitochondrial transfer therapy itself was not a shock, since earlier experiments had demonstrated good outcomes in animal models and in in vitro human embryos. The circumstances, however, were startling: the procedure was done in Mexico, for Jordanian parents, with the help of a New York-based fertility doctor with no known expertise in mitochondrial disease.

Some have argued that mitochondrial transfer therapy represents a violation of international norms forbidding any germline genetic change, which were meant to provide a clear dividing line between somatic changes associated with gene therapy and genetic engineering with the potential to impact future generations. Pretty clear in theory, but all of these divisions are less clear in reality – there are no guarantees that gene therapy doesn’t affect eggs or sperm, and mitochondrial DNA itself challenges any simple equivalence between the molecular structure of DNA and the intellectual concept of our ‘germline’.

Mitochondrial transfer is illegal in the United States but permitted in Great Britain under a 2015 law, and applications for clinical use have been approved for 2017. Its apparent success – independent sources confirm that the baby appears to have traces of maternal mt DNA associated with Leigh syndrome but no sign of disease – is a cause for celebration for the families whose children are at risk. The step forward is a milestone, but so is the way in which it occurred, which demonstrates the extent to which geography and national laws are no match for money and access in determining what is possible.

Personal note: on my wish list for 2017, can we PLEASE stop cheapening the concept of parenthood by using the term ‘3-parent babies’? If I donated a kidney, that person would have some of my DNA, but it wouldn’t make me their momma.

 

1. WHITE SUPREMACISTS LOVE GENETICS, BUT GENETICS DOES NOT LOVE THEM BACK

Nothing about the year 2016 was more disturbing than the empowerment of the alt right, an all-purpose term for the angry souls that crept out from under rocks to preach hate and division. Here at home and all around the world, narratives of race and ancestry emerged as powerful drivers in political and social movements based on appeals to base and tribal instincts – fear mongering about immigrants, Islamaphobia, white supremacy. In October, Elspeth Reeve at Vice ran a story about white supremacists posting their 23andMe results to prove their whiteness.

This embrace of a science that does not love them back is evident even without a deep dive into the world of Stormfront and 4chan.  Twitter trolls talk about ‘founder effects’ and ‘genetic drift’. A Breitbart tech editor, now barred from twitter, writes gleefully about associations between race, behavior and intelligence, mocking disbelievers as prisoners of an “all-consuming cult of equality.”  The L.A. Times describes the alt-right as “young, web-savvy racists who are trying to intellectualize and mainstream bigotry.”   These viewpoints aren’t mainstream, but their proponents can no longer be dismissed as fringe, with Breitbart’s founder about to be ensconced in the White House as chief strategist, and reports suggesting that the presumptive next National Security Advisor Michael Flynn taking meetings with the head of an Austrian political party founded by former Nazis.

The connection between white nationalism and population genetics is proof once again that genetics as a field is uniquely susceptible to misuse by agenda-driven movements intent on the subjugation of others. Donald Trump ran against political correctness, but his rise has proven the importance of language. As Michelle Obama says, “words matter.” Push back against the misuse of genetics to fuel ‘racialist’ theory. Ancestry sites should think very hard about the manner in which they present their findings, which stress differences without acknowledging the greater than 99% of DNA that we all share. Scientists need to address and refute the ways in which their work can be misconstrued to reinforce prejudice and unsubstantiated visions of racial differences. We all have to be careful not to promote explanations of genetic effects that oversell the determinative power of genes.

Genetics is a science of the future. Let’s not let it be used to drag us back into a tribal past. Peace out, Genetics, and here’s to a better year in 2017.

 

 

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by | November 21, 2016 · 8:23 AM

Summing Up the Consequences of Election 2016: 3 Things That Could Change the Practice of Genetic Counseling

It’s been two weeks, and everyone is sick of hot takes on Life in Trump’s America and What Is the Worst Thing That Could Happen? (um, I’m going with nuclear war, but take your pick). I know, I’m sick of it too. But elections have consequences, and, like climate scientists and immigration lawyers, we need to put some thought into what this could mean for our field.

 

The potential repeal of the Affordable Care Act is a concern for everyone working in health care, as is the threatened dismantling of Medicare. Possibly, critics of the ACA will discover that it is easier to campaign than to govern, and that voting to take away health care from tens of millions of people isn’t as much fun as it was in the good old days when they had the safety net of a presidential veto. But hey I’ve always been a Pollyanna. Too cheerful, that’s me.

 

Point one: prepare to practice in a climate where there is more inequality of access.

 

Chances are, prenatal genetics will be affected by an empowered and emboldened anti-abortion movement.   A president has some limited ability to make access to abortion more difficult through executive orders – President Bush signed regulations that gave everyone in the hospital, including orderlies and cleaning staff, the right to decline to do their job in cases involving abortion – but the main issue is the Supreme Court, where as president Trump will get an opportunity to redefine the balance of right and left if and when any of the reliable supporters of reproductive rights leaves the bench. Ruth Bader Ginsburg turns 84 on March 15th and I know millions of people join me in wishing her a happy birthday and many, many happy returns. The Court’s other octagenarian, Anthony Kennedy, has been behind decisions that chipped away at abortion rights, but has also declined several opportunities to overturn Roe v Wade, and anyone replacing him would almost certainly be more explicitly anti-abortion.

 

When asked last week on Sixty Minutes what would happen if Roe v Wade were overturned, Trump said that control of abortion law would then revert to the states, and that women who wanted an abortion might have to “go to another state.” This is correct (shocking but true) and you can make your own determination about the relative impact that would have on affluent and educated women  versus poor women, and teenagers, and other vulnerable parties.

 

The more complicated truth is that Roe v Wade is not going to disappear overnight, although there is a real and important long term threat. Should further changes create a Supreme Court majority ideologically opposed to abortion, they will have to wait until an appropriate case arises to make any changes. State lawmakers would no doubt be happy to present them with a test case, but making laws takes time, and then there are challenges and lower court decisions and demonstrations and pundits talking on the news before SCOTUS makes an actual decision. Even then, there is the hope that one or another of the anti-abortion faction hesitates to overturn 40+ years of precedent (See? You thought I was joking when I said I was an optimist).

 

A recent Supreme Court decision disallowing TRAP laws (targeted restriction of abortion providers) will stand, and so does the coalition that voided them, at least for now. For the moment, this should limit the chronic deterioration of access to abortion in Southern and Midwestern states that we have seen over the past decade. I believe it remains important to monitor changes that adversely affect our patients’ ability to obtain an abortion related to genetic findings, including decreased coverage, increased cost, logistical obstacles and changes that necessitate travel.

 

Point two: be vigilant about the threat to reproductive rights, but don’t expect dramatic changes in the near term.

 

Here’s something we don’t talk about enough: there is evidence to suggest that prenatal testing itself is likely to be a target of the anti-abortion movement. In fact, it already is. The National Conference of Catholic Bishops issued a directive in 2009 that forbids prenatal diagnosis “if undertaken with the intention of aborting an unborn child with a serious defect.” This decree limits the use of prenatal testing in some Catholic hospitals, a growing segment that includes one in six hospital beds in the country today. Many Catholic institutions including schools and hospitals refuse to pay for insurance plans that cover prenatal testing, restricting availability for all their employees, regardless of their own beliefs.  Other employers with an anti-abortion agenda could do the same thing.

 

More evidence that prenatal testing is on the radar screen of the anti-abortion movement: state laws have been advocated, and in two instances passed, that specifically forbid women from seeking a termination for reasons of genetic defect. These laws don’t get a lot of ink because they are a) unconstitutional (under Roe) and b) virtually impossible to enforce, since they require a prosecutor to prove motivation. This doesn’t mean they are not important. They were written by people whose agenda it is to limit abortion by any means, but they were chosen as a vehicle because they tap into a larger uneasiness about prenatal diagnosis.

 

The laws may not be enforceable, but they are chilling. Abortion is already medicine’s stepchild. Why would doctors or hospital administrators be eager to offer a procedure where they have to think twice about whether or not they could get in legal trouble? And the laws show an intent that could be more fully realized through other means. You may not be able to prove a woman’s intent in seeking an abortion, but you can certainly document a counselor’s intent if he or she offers the option of termination after a prenatal diagnosis. Will we see attempts to limit what can say to our patients? If this seems impossible to you, consider that 35 states currently have script laws detailing what a woman must be told before she can have an abortion, and a number of those require providers to give inaccurate and misleading information. In 6 states, women must be ‘informed’ that personhood begins at conception. In 5 states, women must be ‘informed’ that there is a link between abortion and breast cancer. If they can require us to lie to patients, don’t rule out the possibility that they can forbid us to speak.

 

Advances in prenatal testing are revolutionary.   NIPS is the fastest growing medical test in the history of medical tests. We will continue to see changes that widen the scope of what we can diagnose prenatally and improve our ability to predict outcomes more accurately, and at an earlier phase in pregnancy.  This is going to reduce the incidence of a whole range of genetic conditions — for those who use the  test. But improvements in prenatal diagnosis don’t improve access; in fact, improvements in prenatal diagnosis are fueling the debate over what types of prenatal testing are acceptable. If the courts and the politicians and the public don’t accept the idea that pregnant women have a right to prenatal testing as a part of normal prenatal care, then laws and limits to insurance reimbursement may put it out of reach of many Americans.

 

If prenatal testing is only available people who have enough money, or the right education, or live in certain parts of the country, it is not just unfair to individuals but fundamentally changes the societal impact of offering the tests. The necessary consequence of offering prenatal diagnosis and the option to choose only to some people, is that the birth of a child with a genetic defect or disease will gradually change from being something that can happen to anyone to something that only happens to ‘some people’. Don’t we already see this happening to some extent with Down syndrome? People are right to think hard about the potential consequences of prenatal diagnosis, but restricting prenatal testing so that access is unequal doesn’t limit the harm, it multiplies the harm.

 

Point three: we need to make the case that genetic testing is a part of good prenatal care and that every pregnant woman has a right to it, if she chooses.

 

There are other issues to consider but these three jump out at me as points of concern for genetic counseling practice as we move forward with a new administration. What can we do?  Hope for the best. Make our own spaces – schools, clinics, workplaces – into welcoming and inclusive environments for those who don’t feel safe in the current climate. Be vigilant, and bring changes that affect patient care to public attention. Talk to other counselors. Talk to me; I would love to hear your take and your stories.

 

 

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by | June 8, 2016 · 12:49 PM

Ancestry and the Long Distance Call

These are the days of miracles and wonder

 

I read the science news in 2016 and hear lyrics from that Paul Simon song echoing in my head.

 

These are the days of miracles and wonder

And better variant calls

The way that CRISPR works on everything

The way we sequence it all

 

Perhaps I paraphrase. But these are heady times, when the boy seems poised to burst out of his bubble, and fantasies of a baboon heart turn into dreams of a human heart instead, grown in a lab or in a pig, and we will have no more of slaughtering primates thank you very much.

 

These are the days of promises and phase one trials,

and medicine is magical and magical is art

 

When we cure your disease, I will feed you pancakes with maple syrup and put frosting on your birthday cake, I tell my beloved friend with type I diabetes. We will float Islets of Langerhans in a pouch beneath your skin. We will re-engineer your pancreatic stem cells to be invisible to your immune system.

 

Promises of miracles come with questions. Can we? Should we? How will we pay for it all?

 

We. We use the word freely, but what does it mean? This is a genetics question too, one that we (the purveyors and patrons of genetic technology, the readers of this blog) don’t ask ourselves often enough. Who will benefit from the miracles that are now only twinkles in the eye of brilliant minds?

 

Who is included when we talk about ‘we’? A family, a tribe, a nation, a species? It is one of the ironies of the genomic age that the technological revolution that makes it possible for us to think and act globally has also spawned a growing interest in atavistic concepts like bloodlines. Racism raises its ugly old head on new platforms like Twitter and Facebook. The through-the-roof popularity of ancestry testing both testifies to and nurtures an instinct to tribalism that is ancient beneath the glossy surface of its web-based, consumer-facing interface. A powerful thing, genealogy, beyond the fun and games, with the power to bring us together or tear us apart.

 

Research testifying to this was published earlier this year, in the form of an article called “Living in a Genetic World: How Learning About Interethnic Genetic Similarities and Differences Affects Peace and Conflict”. The authors conducted a series of studies observing how reading a single article about genetic relatedness or the lack thereof altered the response of a Jewish audience toward a hypothetical Arab population, and vice versa. Participants queried after being given a mock BBC article describing Jews and Arabs as genetic cousins expressed a less negative attitude toward individuals of the other ethnicity. Repeating their experiment with populations of Jews of different ages and from different parts of the United States, Sasha Kimel from Harvard and colleagues from the University of Michigan, Europe and Israel found that a suggestion of genetic kinship consistently increased support for peacemaking between Israel and the Palestinians.

 

Now don’t get me wrong, small studies and academic hypotheticals don’t represent a road map to peace in the Middle East. But the discussion points to something we as genetic counselors know from experience: genetic ideation is a powerful force in shaping notions of identity. It helps define ‘we’ for each of us.

 

This is something to think about every time we give out genetic information. For 23andMe and Ancestry.com, it could mean writing a report that puts as much emphasis on what unites us as on what divides us. By convention, we talk about first cousins sharing 12.5% of their DNA.   But we share more of our DNA than that with a banana. Yes, I know that what we mean is that 12.5% of our DNA and our cousin’s DNA is identical by descent. Testing companies give FAQ’s explaining the numerics of relatedness; perhaps the 99.9% we all share ought to merit an asterisk at the very least.

 

It is a strange moment in which we live, full of hope and promise and fear and sadness. A new era builds at our back, with unprecedented tools to diagnose, treat and even prevent disease, while the landscape in front of us is one of increasing income inequality and fitful, angry isolationism. The routine injustice of bigotry and unequal access are far greater threats to the genomic era than the sci-fi horrors of Drs. Frankenstein and Moreau. CRISPR can’t change your zip code.

 

There is no simple solution to this, but the battle begins with how we define ‘we’. Genetics needs to remind us of what we share as often as it tells us how we are different. Many of you are out there every day fighting battles you may not recognize as part of a larger war: battling insurance companies for access, battling to bring diversity to our biobanks and clinical trials, supporting a new vision of family, in which our 99.9% shared DNA is enough, and we are not defined by the fraction that is identical by descent. We are educators in a field that is an agent of change, and so it falls to us to work for an ever more expansive and inclusive definition of ‘we’. Without that, we risk that the amazing technology of the genomic age will be perverted into a tool for doubling down on the things that divide us.

 

These are the days of miracles and wonder

This is the long distance call

The way the camera follows us in slo-mo

The way we look to us all

The way we look to a distant constellation

That’s dying in a corner of the sky

These are the days of miracle and wonder

And don’t cry baby don’t cry

Don’t cry

 

 

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