Barriers or Filters?

 

Both good and bad can be said about Direct to Consumer (DTC) genetic testing. Some of the tests offered are probably better labeled Dreck To Consumer. Please, somebody, issue a cease and desist order for MTHFR testing. Or better yet, make it a criminal offense, punishable by sentencing to hard time at the Clockwork Orange Folic Acid Supplementation Rehabilitation and Penal Colony.

On the other hand, I am betting that established labs that currently offer clinically useful genetic testing will be migrating toward a greater presence in some form in the DTC market. This trend will be driven, by among other things, the demand on the part of some patients because of the convenience factor, the increasing uptake of BRCA testing by unaffected women, and by the potential income source it would create for labs. Whether clinicians like it or not, some form of DTC testing will probably play an increasing role in patient care in the near future. We will need to adapt to it, even if it makes some of us feel uneasy. My prediction is that we will initially see the most significant inroads in the area of DTC germline testing for cancer predisposition gene panels that include BRCA, Lynch, and their kindred.

Another  factor that could drive DTC testing is that genetic counselors are sometimes viewed by clinicians, labs, and consumers as barriers to genetic testing. For patients, just finding the time in their busy lives for an hour long appointment and verifying insurance coverage for the consultation is no mean feat. Then there is the genetic counseling ethos of nondirectiveness and genetic counselors’ obsessive urge to (over?)educate patients, which can result in some patients coming out of the session saying No Thank You to genetic testing for now, much to the chagrin of their referring care providers. Not to mention the lack of genetic counseling manpower in some parts of the country. From this perspective, you start to understand why some critics claim there can be a reduced uptake of genetic testing when a genetic counselor is an intermediary between patient and laboratory.

Genetic counselors might cringe at the thought of patients entering the genetic testing pathway without having worked through the emotional implications, and possibly partially blind to the clinical and personal implications of positive, negative, and uncertain results. We somewhat paternalistically view ourselves as guardians of our patients’ medical and emotional well being. While genetic testing may be important for patients, at least for unaffected patients genetic testing is rarely an urgent matter. It can take place today, next week, a few months, next year, or at some point in the vague future. Perhaps that is not so terrible because a test result delivered at the wrong moment might backfire by causing the patient to go into a psychological tailspin and possibly wind up avoiding risk reducing and screening strategies. In this way, genetic counselors are more like filters than barriers, helping ensure that nobody takes a deep dive into their gene pool without first pausing and taking a deep breath.

This response may be partially and subconsciously influenced by the fact that our jobs depend on the steady stream of patients seeking genetic testing. DTC also takes away some of the “gatekeeper” power inherent in our positions. Conflict of interest affects us in ways that can make us too uncomfortable to acknowledge that it might it shape our beliefs and attitudes.

Enter DTC into this drama, stage right. If you are a patient who has a few hundred bucks to spare, you can avoid carving a chunk of precious time out of your busy schedule to set up a genetic counseling appointment (and maybe 2 or 3 appointments, depending on the provider’s policy of requiring separate appointments for counseling, test, and results disclosure), avoid those incomprehensible (non)explanations of benefits from health insurers, and with saliva testing skip the unpleasantness of a blood draw (although saliva collection has its own icky issues). Those forward-thinking online genetic counseling services that are unaffiliated with specific labs may help mitigate some of these perceived barriers, but maybe not enough for the majority of patients. DTC labs make it pretty easy to sign up for genetic testing, no muss, no fuss, never needs ironing. If I am honest with myself, in some situations – and maybe more often than I am willing to acknowledge – the “hassles” of genetic counseling may very well serve to discourage a goodly number of patients from undergoing genetic testing.

One concern about DTC is the way that labs may try to portray their tests to patients. Labs typically strive to act in patients’ best interests and try to make sure that patients get the genetic testing they need. By and large I find them to be just as committed as I am to providing excellent patient care. But at the end of the day they are businesses, and even if they have noble aspirations, it is in their best interests for as many patients as possible to undergo genetic testing. This can subtly influence their advertising under the rubrics of patient education and patient empowerment.

The best example I can think of to illustrate this point is the websites of many labs that offer cancer genetic testing, DTC or otherwise, which often cite the high end of disease risks in hereditary cancer syndromes. Labs aren’t lying to patients when they quote 80-90% lifetime breast cancer risks or whatever. But it certainly makes their genetic tests look more clinically critical than, say, the 40-50% risks found in some studies. It’s not that the 40-50% risk is necessarily closer to the “true” risk than 80-90%. The point is that there a range of risk estimates out there and which risks one chooses to present can be influenced by many factors.

Here is one lesson I have learned from ~34 years of genetic counseling with about a jillion patients: Nobody undergoes genetic testing until they are emotionally ready. Sometimes that readiness is thrust upon the patient, such as when a patient is diagnosed with cancer and has to make treatment choices fairly quickly. But for unaffected patients, some emotional triggering event(s) needs to occur before they make a genetic counseling appointment. Examples of triggering events might include reaching an age when the patient’s own parent was diagnosed with cancer or when their own child reaches the age the patient was when the patient’s parent was diagnosed; having a false positive “scare” on a mammogram; a recent cancer diagnosis in a loved one; a media celebrity such as Angelina Jolie sharing a personal cancer story; reaching a certain stage in life where, as one patient put it, “It was time to start acting like an adult” (which I suspect for many people is the incipient stages of facing their own mortality); having a grandchild; or gazing at your child one day and realizing that you might want to be around for your kindergartener’s college graduation.

If my observation about what leads patients to genetic testing is correct, it will be interesting to see if affordable, convenient, DTC genetic testing will itself become the trigger event that nudges patients into undergoing genetic testing. Would this be good or bad? Will we see a rapid proliferation of genetic testing for hereditary cancer or other syndromes if DTC testing becomes widely available? Will this translate into clinical gains that are also economically cost effective, such as increased uptake of risk-reducing surgery and high risk screening? Who will watchdog labs to assure that they offer a quality, uniform, and trustworthy product that patients can depend on without first doing in depth research about depth of coverage, variant calls, and the other arcana of genetic testing? If recent calls for cancer genetic testing for essentially everyone, such as the proposal by Dr. Mary-Claire King or Canada’s Screen Project, become widely embraced, will DTC be the most efficient way to deliver the service? Will life insurers start requiring genetic testing before a consumer is eligible for a policy? How often will untrained care providers and patients misinterpret test results? Will it turn out that genetic counselors are barriers to genetic testing or are they filters who help ensure that the appropriate patients get the appropriate testing at the appropriate time in their lives? Will genetic counselors wind up largely becoming, as I have predicted for years, phenotype counselors who meet with patients after genetic testing?

Nobody knows the answer to these questions, although a lack of data has never been a barrier to strong opinions. This is the time to plan research studies that can help address them. The genetic counseling profession needs to continuously adapt and evolve. But it needs to do so without losing its soul.

 

Thanks again to Emily Singh for help with realizing the graphics.

 

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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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Am I Man Or Am I A Microbe?

For several decades, it was commonly believed that bacterial cells constituted ~90% of the cells in the human body. You could casually slip this eyebrow-raising fact into a dinner party conversation or a philosophical debate about human identity and the discussion would pause while everyone chewed over that attention-grabber. If we are 90% bacteria then you could argue that humans are basically a minor evolutionary appendage to a seething microbial mass. It was humbling and downright embarrassing, from a species pride viewpoint.

However, about a year ago, researchers from the Weizmann Institute of Science in Israel re-evaluated the data and assumptions behind this eyebrow-raising factoid and poured a pitcher of cold water on it when they concluded that the number bacterial cells in our bodies was only ~30% greater than the number of human cells. Stripping this fact of most of its dignity, the authors pointed out that about 25-30% of bacteria are lost with an average bowel movement, or as they wryly commented “Indeed, the numbers are similar enough that each defecation event may flip the ratio to favor human cells over bacteria.” If that is true then I was at my most human when I underwent a colonoscopy.

But a half-human/half-bacteria hybrid evokes an image of a cheesy monster from a 1950s Grade B sci-fi movie forbidden planet that orbited around my developing childhood psyche. It was a blow to my pride in my species. I am a human, damn it, and I have my biological dignity. I am not some primitive blobby affair that obtains its food by absorbing dead organic material or some thermophile sucking sulfur from a deep Pacific hydrothermal vent. I go to a supermarket to hunt and gather my food like a man! Yeah! That’s what I’m talkin’ about! No foreign species is going to dominate my body!

The lying left wing scientific media got it wrong again. So I pondered how I might further trivialize my bacterial component and fully regain pride in my species. How could I write a scientifically based executive order using alternative biological facts that could ban all foreign species from my native body? And then I hit on the right-in-front-of-me-all-the-time ruby slippers solution: click my heels together three times for DNA, the very currency of evolution! There’s no species like Homo, there’s no species like Homo, there’s no species like Homo. So I asked myself “Hey Bob, you Wizard of Odds genetics specialist, tell me, how much bacterial DNA does the human body contain compared to human DNA?”

The Assumptions

  • The analysis of the Weizmann Institute paper is reasonably accurate.
  • I used Ecoli K-12 as the model organism. Several hundred types of bacteria reside in the human body and some have more or less DNA than E. coli, but E. coli is the predominant bacterial strain in humans.
  • The total number of non-bacterial organisms  in human – viruses, archaea, fungi – are several orders of magnitude less common than bacteria and are essentially a rounding error of the human microbial makeup.
  • The E. coli genome is fairly compact, containing little in the way of introns or non-coding DNA.
  • Each E. coli bacterium contains 4,377 genes and 4,639,221 base pairs, which I rounded off to 4.4×103, amid ~4.6×106 DNA base pairs.
  • The reference person is a 170cm tall male who weighs 70 kg (Sorry for the sexist bias here, but this is the model used in the published papers. Proportionally though, the ratios here probably apply to all genders, whichever bathroom they choose to use, except in North Carolina).
  • Per the updated estimates, the human body contains ~4×1013 bacteria.
  • Our bodies contain ~3×1013 human cells. However, per the Weizmann Institute paper, about 90% of those cells are enucleated blood cells. Thus the vast majority of cells in an adult do not contain nuclear or mitochondrial DNA. Ergo, the total number of human cells that contain DNA is on the order of ~3×1012.
  • Each nucleated diploid human cell has about 20,000 genes (2×104) and 6,000,000 (6×109) DNA base pairs (though see Addendum below). The number of haploid sperm and egg cells are small enough to ignore for these calculations.
  • The total amount of mitochondrial genes and DNA in humans is minor compared to nuclear DNA and can also be ignored for these calculations.
  • Unlike bacterial DNA, the vast majority of human DNA is non-coding, resulting in a far higher ratio of DNA to gene in humans compared to bacteria.

 

The Calculations^

What is the total number of bacterial genes in the human body?

This is calculated by multiplying the number of genes in each bacterium by the number of bacteria in the human body:

(4.4×103) x (4×1013) ≅ 1.7×1017 bacterial genes in the human body

 

What is the total amount of bacterial DNA in the human body?

This is calculated by multiplying the number of DNA base pairs in each bacterium by the total number of bacteria in the human body:

(4.6×106) x (4×1013) ≅ 1.8×1020 base pairs of bacterial DNA in the human body

 

What is the total number of human genes in the human body?

This is calculated by multiplying the number of genes in the human body by the number of nucleated cells:

(2×104) x (3×1012) ≅ 6×1016 genes in the human body

 

What is the total amount of human DNA in the human body?

This is calculated by multiplying the number of DNA base pairs per cell by the total number of nucleated cells:

(6×109) x (3×1012) ≅ 1.8×1022 DNA base pairs in the human body

 

So to summarize:

Organism Total Number of Genes In Human Body Total Number of Base Pairs in Human Body
Bacteria ~1.7×1017 ~1.8×1020
Human ~6×1016 ~1.8×1022

 

This analysis demonstrates that there are far more bacterial genes in the human body than human genes. The preponderance of bacterial genes is not significantly altered by a “defecation event” or even a colonoscopy prep. The best I can say is that any genetic superiority humans might have over bacteria comes from our “junk” DNA. Not much solace there.

To throw a little salt in the psychic wound, the human genome contains about 150 non-human genes that have insinuated themselves into our double helices. Even some of our human genes ain’t so human. A bit less than 1% of the total, but enough to strike a symbolic blow to the human ego. Homo bacteriensis, I guess. Bacteria rule.

Addendum (Added 3/19/2017)

Actually, in thinking about this for a few more days, I realized that the number of human genes in each diploid cell is ~40,000 since each cell has ~20,000 maternal genes and ~20,000 paternal genes, so the number of human genes in the body is (4×104) x (3×1012) = 1.2×1017. This is getting closer to the number of bacterial genes in the human body, give or take a few quadrillion genes. Likewise, the amount of human DNA in each diploid cell is actually (1.2×1010) x (3×1012) ≅ 3.6×1022 DNA base pairs in the human body. Bacteria, being haploid organisms, only have a single copy of each gene, except just prior to binary fission when their DNA content is doubled. So the bacteria/human differences are greater if you limit the assumption to the number of human genes, not the number of human alleles.

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Thanks to my good friend Tom Wolfe for pointing out to me the revised estimates of bacterial and human cells.

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^ – I freely admit that these calculations and assumptions may not be error free. I ran them several times and kept coming up with different answers. It has been a long time since I multiplied and added exponents. Please check my calculations .

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Are We Ready For This?

Recent advances in genetic testing technology have us poised on the brink of a new paradigm of prenatal diagnosis – prenatal screening for all genetic and chromosomal conditions. Okay, not all disorders, but lots. Non-invasive Prenatal Testing (NIPT), whole exome sequencing, and expanded carrier screening are close to being available and affordable to a large proportion of the population. This is the culmination of a trend that began with the introduction of amniocentesis in the late 1960s, followed by ultrasonography, maternal serum screening, microarrays, and cell free placental DNA in maternal serum. From a strictly technical standpoint, each technology, while far from perfect, was an improvement on its predecessors in terms of accuracy, detection, false positive rates, and the range of  detectable genetic conditions.

On the surface, this sounds like progress, and it is, in many ways. These technologies can contribute to the reduction of the incidence genetic conditions, some of which are pretty serious, a long-standing goal of medical genetics since its inception, as Nathaniel Comfort has pointed out. But technological advances often outstrip the ethical and social means with which to appropriately assess, modify, and utilize them in fair, just, and meaningful ways. So I ask these questions of the sage and thoughtful readers of The DNA Exchange: Just because we can perform prenatal screening for nearly everything genetic, should we? Who should be making this decision?

There are many competing and intertwined narratives about the history of prenatal diagnosis. Let me offer one such narrative to provide ethical and historical angles. During the 1970s and early 1980s, amniocentesis was primarily offered to women of “advanced maternal age” because of the well-documented increase in the incidence of trisomy with maternal age. At the time, in the US women 35 and older represented about 5% of the pregnant population, and this group accounted for about 20% of pregnancies with Down syndrome (this statistic has since changed considerably). While such a policy could be viewed as discriminatory and prejudicial against people with disabilities, the goal of the policy did not seem to be the elimination of genetic disability. Rather, the effect and likely the intent of the policy was to level the reproductive playing field for “older” mothers. During the 1970s, women made great strides in expanding their social and economic opportunities and in taking some measure of control over their reproductive lives with birth control and the availability of safe, legal abortion. Women could now readily attend most colleges and graduate schools, had more career opportunities, and did not feel as much social pressure to retire to motherhood after high school. However, one of the perceived obstacles for delayed childbearing was the greater risk of Down syndrome and other trisomies. Amniocentesis removed this perceived obstacle and consequently women felt freer to delay childbearing until such time as they felt that they and their partners were ready.

Over the decades, mission creep worked its way into prenatal screening. With the gradual incorporation of ultrasound and maternal serum screening into most pregnancies, regardless of maternal age, the detection rate for Down syndrome increased, and critics of prenatal diagnosis raised the specter of the theoretical elimination of all people with Down syndrome. While such an outcome never seemed likely for a variety of social, cultural, individual, and economic reasons, that could be viewed as the intent of prenatal screening. But still, aneuploidy represents only a small portion of all genetic and congenital disorders.

But it is a qualitatively different ethical story with universal NIPT and the expanding number of conditions it can screen for, the prospect of carrier screening for hundreds of genetic conditions for all couples, and talk of whole exome screening of fetuses. That is making quite a profound statement to and about people with a wide range of physical and developmental abilities.

We tacitly assume that the majority of pregnant women want such screening at the same time that we offer it to them. Many patients will  assume that because we are offering it, it must be a good thing. Because genetic counselors’ jobs can depend on the offer and uptake of such services, it affects our views and actions in ways that we often cannot fully appreciate or grasp. To some extent, we offer new testing because labs are offering it and because genetic counselors tend to be early adopters of new genetic tests. As much as we like to think that we are objective assessors of genetic technology who always put the best interests of patients first, the complicated human psyche makes for a messier reality. Our perspectives are distorted by being in the center of the storm. Go ahead and disagree with me if you want, but you are by and large wrong. That’s not me trying to sound superior; motivated blindness is a basic foundational principal of human psychology.

Psychological complexity aside, think of this. The medical profession is already doing a less than stellar job of presenting a realistic and unbiased picture of Down syndrome to parents. Remember, too, that more and more prenatal genetic testing happens without the involvement of a board certified genetic counselor and that parents are often not educated about these conditions until after they have received an abnormal test result. Not exactly the best time to seek out and weigh complicated information. Add a few hundred more conditions less common and familiar than Down syndrome, and you can see the makings of a goddamn mess.

So can there ever be an ethical justification for universal prenatal screening of (theoretically) all genetic and chromosomal diseases? Let me offer some suggestions that could serve as a starting point to address this question. One can argue that this framework or one like it should have been in place decades ago. I agree, it should have. I recognize that for people who are opposed to termination of pregnancy under any condition or for some of the staunchest disability advocates, prenatal screening will never be acceptable unless it somehow improves the lives of people with different abilities and their families. But I ask all sides to at least hear me out.

First, many parties should be involved in the discussion about wide scale prenatal testing, à la Cyprus and thalassemia screening. Prospective users, clinicians, labs, ethicists, religious leaders, legal experts, legislators, and most especially the community of people who are affected directly by the conditions in question (let me add “and others” since no doubt I am forgetting some important stakeholders). You will never get everyone to agree on all of the details, but there should be at least broad consensus about the most critical issues among the majority.

Second, more resources need to be devoted to improving the lives of people with genetic conditions and their families. Every newborn should  be able to live full, rewarding, loving, and enjoyable lives as much as humanly possible. This involves large-scale medical, technological, and social innovations and changes. Improving the social attitudes toward disability is a long, slow, frustrating journey but that should not deter us.

Third, related to the above, prenatal genetic testing should also offer some benefit people with the conditions in questions and their families, other than letting them have the same option as everyone else to terminate pregnancies. Right now, people with disabilities and their families get essentially zero benefit from prenatal screening. Or more accurately, very little research has been done to show any benefits.

Fourth, any new technology or test needs to be vetted by those who do not have a vested professional, financial, or personal interest in the technology or test. Intellectual, research, and financial conflicts of interest have ways of distorting our views in subtle ways that we are incapable of appreciating. This is extraordinarily difficult for us to understand and acknowledge (vide supra motivated blindness).

Fifth, better resources need to be developed for parents to become educated about the medical implications of genetic diagnoses, the range of developmental outcomes, the resources available to manage the condition, and the impact on families, particularly in lower socio-economic populations.

Sixth, this information needs to be provided to parents before they decide to enter the cascade of prenatal screening, not after they receive an abnormal test result. Parents have to carefully decide which if any condition(s) is important to their reproductive and family planning.

If all of these recommendations are in place, this will allow parents to make informed choices about whether or not they wish to go down the prenatal screening pathway and for which conditions. For parents who would never consider a termination under any conditions, they should have the option of screening only for those conditions for which prenatal knowledge can help the child and family, with better medical, psychological, or adaptational outcomes. For parents who have carefully weighed these issues and feel that there are certain conditions that they will choose to avoid if they can, then they should be supported in their decisions with safe, legal, and non-judgmental abortion services. For parents who are not interested in prenatal screening, they should be supported in their decision rather than being made to feel like they are sub-standard parents.

We can ignore my plea, just sit back and see what happens. But this would be a big mistake. Although genetic counselors obviously cannot address this issue by themselves, we are in the ideal position to take the lead in organizing, coordinating, and spearheading the discussion. We owe it to ourselves and to our patients.

 

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No Great Shakes

Cooties. That dread disease for which there is no effective vaccination. A microbe resistant to all known antibiotics and antivirals. A fourth biological domain – archaea, bacteria, eukarya, and cootia. Cootiensis trumpii, in formal Linnaean taxonomy, is the sole representative of this branch of life. A highly contagious cause of a wide range of medical, social, and psychological ills. The Dreaded Lurgi, to our UK colleagues and Spike Milligan fans. Etymologically, cootie may be derived from kutu, a term for a biting insect in the Austronesian language family, attesting to its pandemic nature. Cooties appear to thrive in certain foods, icky substances like mystery spills on hospital floors, and dropped food not picked up for a few dangerous seconds too long. In the sometimes cruel world of childhood, an unfortunate socially awkward child may be super-infected. During my pre-pubescent years, I was fairly certain that most girls my age were cootie hosts. My sisters sure thought I was a cootie reservoir.

cootie2

Two virulent strains of Cootiensis trumpii, viewed through an electron microscope.

Cooties may be as old as humanity. Some paleoanthropologists believe that the hand impressions common in many Paleolithic caves actually represent ritual attempts to purify the hands of cooties acquired by the ancestors of modern humans after they interacted with Neanderthals and Denisovans, who in fact may have been wiped out by a devastating cootie plague rather than having been out-competed by our early ancestors (Okay, I admit I just made that up about paleocooties and early humans. But nowadays it is apparently okay to make up facts, just as long as they serve one’s agenda.).

Paleolithic cootie purification rituals?

Paleolithic cootie purification rituals?

All of which brings me to how I greet patients at my cancer genetics clinic. About a decade ago it dawned on me that many of my patients are immunocompromised from their cancer treatment. The last thing they need is to acquire an infectious disease from me. Handshakes have long been known to be a source of microbe transfer between people. So I decided that I would stop shaking hands with my patients when I greeted them in the waiting room. After all, we are supposed to make them healthier, not sicker.

No, I don’t know the likelihood of passing along infectious disease cooties via handshake in an outpatient setting but it is probably not trivial. Yes, I use a hand gel sanitizer but many people use them inadequately. Besides, I bet all that hand sanitizing is selecting for super-resistant cootie strains. Evolution is far more resourceful and clever than we can ever hope to be. Soap and water may be more effective than alcohol gels in eliminating microbes but, honestly, how many of us will sing “Happy Birthday” twice while thoroughly soaping up between genetic counseling sessions? No, I am not a germophobe. Regular exposure to microbial organisms is a good way of keeping my immune system cocked and loaded. Yes, my hospital has policies on minimizing contagion in out-patient settings. For example, the plants in my office must be a minimum distance from patients.

The potential cootie host in my office.

Which is why it strikes me as odd that guidelines do not include a hand-shaking ban; my guess is that hand clasping is at least as likely a source of nosocomial infection as the big old plant in my office. On top of that, many employees come in to work when they are sick with some crud, trying to be conscientious, not inconvenience co-workers, and not screw up patient schedules. “Oh, it’s just a cold and I am past the infectious stage, I am sure” they will unconvincingly say between coughing fits. The road to an office-wide flu epidemic is paved with their good intentions. And not uncommonly there are unstated conflicting tensions between hospital policies encouraging employees to use their sick days and the attitudes of mid-level management who seem to view sick days as abuse of a privilege bestowed by God and only to be used when you are near death or beyond.

I recognize the social importance of the handshake in establishing a trusting relationship between strangers. So I have replaced it with a simple wave and a pleasant smile, which is probably at least as socially effective and friendly as a handshake. Some patients look at me quizzically when I state my no handshaking policy. However, the vast majority become very appreciative of the policy once I explain its basis and most people say “That’s a good idea. I wonder why most healthcare providers don’t do it?” Good question. I think it actually enhances the trust between provider and patient, and communicates that I care about them far more concretely than those hospital advertising slogans that proclaim patients always come first. And for patients who still think I am peculiar after my explanation, well, tough noogies, as we used to say when I was a kid (extreme situations called for the more forceful “Tough noogies on your boogies!”).

Call me old-fashioned, but other forms of greeting, like the fist bump or its two-knuckle modified version called a cruise tap, seem inappropriate in the hospital setting and still involve some degree of skin-to-skin contact. Wearing gloves to shake hands would be just plain old wrong. There are other greetings that do not involve skin contact – the wai in Thailand, eyebrow flashing, sticking out your tongue (Tibet), the Japanese bow, the namaskar of India, the  jumping greeting dance of the Maasai, or particularly among men in Western cultures, that barely perceptible slightly angled up-tilt of the head between two bro’s who sort of recognize each other. But unless you work primarily with specialized patient populations, the regular use of such greetings will probably only lead to awkward misunderstandings between clinicians and patients.

images-1

Inspector Clouseau (wanting to know if your dog bites) and Professor Quincy Adams Wagstaff (addressing the faculty of Huxley College) were both frequent users of the flashed eyebrow greeting.

I admit that it felt odd when I first started my no-handshake policy. I sometimes held my hands behind my back to fight the instinctive urge to shake hands. Deeply embedded cultural practices don’t disappear overnight. But after a few months, it became quite natural and I found myself recoiling in concerned surprise when I would see other providers shaking hands with patients. I have even begun minimizing handshaking outside of work; there is always “that bug that’s going around” that I prefer to avoid if I can. The no-handshake policy should not be limited to the cancer clinic. We need to minimize the risk that any patient will get sick from a visit to a medical office, whether or not they might be immunocompromised. No one deserves the cooties!

no-germs

Thanks yet again to Emily Singh for help with graphics

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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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Open Reading Frame – The Books That Caught Genetic Counselors’ Attention in 2016

I have never seen a formal study on the topic, but I am pretty sure that many genetic counselors are voracious readers. Despite the daunting task of trying to stay current with the unending torrent of professional articles fire-hosing at us from all directions, we manage to carve out time to read books of our own choosing. There is deep intellectual and emotional satisfaction in immersing yourself in a book that opens up a whole new way of looking at your professional or personal philosophies, values, and opinions.  Well-constructed, beautifully worded sentences sing off the page and you catch yourself saying “Man, I wish I could write a sentence like that.” How did that writer get inside my head, understand me, and open up parts of myself I didn’t know about? It can be a psychotherapeutic experience.

I occasionally use an e-reader and appreciate its practical qualities. But the physical pleasures of holding a book, moving my book mark around, flipping back and forth between pages, studying the front and back covers, the crisp pristine quality of a brand new hardcover, the wrinkled front cover pages falling out old much read paperback that looks like it has been through several wars all touch some pleasure center in my psyche that no doubt would require psychoanalysis to decipher. I try to keep a book in mint condition so that you can’t even tell it has been read. My wife, on the other hand, attacks a book like a terrier going after a rat, bending the spine, folding pages and otherwise beating the life out of it. Despite 30 years of interventions, I have yet to be able to cure her of this disease.

What do genetic counselors like to read? I decided to find out by asking subscribers to the NSGC general forum what book(s) they read in 2016 that made them say “Hey I bet my colleagues would love this book!” I was going to restrict it only to books published this year, but then I thought, why be so limiting? So the list below includes older and new books, along with comments from the genetic counselors who recommended them. This is just in time to buy a gift for yourself or your favorite colleagues for the holidays or just because we sometimes deserve a gift out of the blue. Want to add a personal favorite? Just add it in the Comments section.

The first four books are my personal recommendations.

Life Histories of Genetic Disease by Andrew Hogan. 2016 Johns Hopkins University Press. Andy Hogan, a superb historian of medical genetics who teaches at Creighton University in Nebraska, explores the historical arc of three genetic diseases – Prader-Willi, fragile X, and DiGeorge or CATCH-all DiShprintzen-Velo-22q or whatever you call it these days – and how their definitions continued to evolve with new genetic testing technologies. These stories are told within the framework of the history, ethos, and goals of the field of Medical Genetics. I particularly enjoyed how he delineates the way that the graphic of the ideogram of the g-banded human karyotype continued to influence the way clinicians and researchers think about genetic diseases even after chromosomal studies began playing a less prominent role in genetic diagnosis.  In my view, the chromosonal ideogram is like the pedigree – the other genetics graphic that shapes how our minds think about hereditary diseases.

The Undoing Project: A Friendship That Changed Our Minds by Michael Lewis. 2017. W.W. Norton and Company. You might start to question why I chose this book when you read the first chapter, which is about how the Houston Rockets basketball team assess the talents and potential of their players. But this clever ploy leads quickly to an exploration of the profound insights into human behavioral psychology developed by the work of the psychologists Amos Tversky and Daniel Kahneman. Just as interesting is the intense, complex relationship between the two men. Their work has had a significant influence in many areas, not the least of which is genetic counseling research into decision-making and coping with risk. Michael Lewis, the author of Moneyball and The Big Short, has a knack for storytelling and beautifully explaining complicated topics.

Orphan – The Quest to Save Children With Rare Genetic Disorders by Philip J. Reilly. 2015. Cold Spring Harbor Laboratory Press. Phil Reilly, the author of The Surgical Solution and other genetics related books, gives us an insider’s view of commercial and research labs that are working on treatments and cures for rare genetic diseases, and most importantly, the day-to-day lives of  people and families coping with the diseases. By the end of the book even a curmudgeon like me found myself wondering what it would be like to work in such a lab and come up with a treatment that makes patient makes even a little bit of difference in patients’ lives. See my full review in The American Journal of Medical Genetics – http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.37585/full

Blame by Tony Holzman. 2016. Cloud Splitter Press. This novel, by the retired Director for the Genetics and Public Policy Center at Johns Hopkins, examines how a gene therapy trial for Alzheimer’s disease goes terribly awry with the death of an African American woman participating in the trial. The characters are thinly drawn making it confusing to understand their arcs, and the dialogue can be a bit wooden, but they exist mostly to drive the plot. We genetic counselors love to perseverate about the issues that the book raises – complicated workings of IRBs, university politics, conflict of interest, for-profit research, race relations, sexual harassment, poorly interpreted genetic tests, and a HIPAA violation thrown in for good measure.

 

The following are recommendations gleaned from my informal survey on the NSGC General Forum, along with the submitters’ thoughts on why they chose the particular book.

The Gene – An Intimate History by Siddhartha Mukherjee. 2016. Scribner. Like almost everyone I know, I thoroughly enjoyed Siddhartha Mukherjee’s gem, which made the world of genetics lively, complicated, and very, very human. We all know the stories, but they become page-turners through his story-telling lens, campfire ghost stories beautifully crafted and hauntingly memorable. I went around recounting them in a “he tells it so much better” way for days and days afterward. – submitted by  Karlla W. Brigatti, Clinic for Special Children, Strasburg Pennsylvania

Lab Girl by Hope Jahren. 2016. Alfred A. Knopf. This book is an exceptional memoir of a woman’s experience in establishing herself as a scientist, in this case, botany. Ms. Jahren writes eloquently and with humor about her efforts to fund her lab in various universities and the opposition she encounters all along the way. In addition, chapters alternate with scientific discussions of the life cycle of trees, climate change, research initiatives and problems, and her description of her own eccentricities as well as her unusual co-worker’s idiosyncrasies. Everyone I know who has read it has found it fascinating. – submitted by Judy Widmann, retired Genetic Counselor.

News of The World by Paulette Jiles. 2016. William Morrow. The book has nothing to do with science but it is an extraordinary, beautifully written novel.  I don’t remember underlining a book of fiction since college, but I underlined passages in this one. The story takes place in post-Civil War Texas. An elderly gentleman travels to small towns buying up newspapers from around the world. He then rents a hall and reads the news to the townspeople, each customer paying him a dime to listen. Along the way, he is given charge of a 10 year-old white girl who has lived among the Kiowa Indians, having been abducted by the tribe at age 6 after her family was killed. He is to return her to her aunt and uncle in the south of Texas, a journey of several hundred miles. The relationship between these two characters gives the novel its center and significance. – submitted by Judy Widmann, retired genetic counselor.

Far From The Tree – Parents, Children, and The Search for Identity. by Andrew Solomon. 2012. Simon and Schuster. My nomination for any GC’s must-read list is Far from the Tree by Andrew Solomon. This book had me at the intro:
“There is no such thing as reproduction. When two people decide to have a baby, they engage in an act of production, and the widespread use of the work reproduction for this activity, with its implication that two people are but braiding themselves together is at best a euphemism to comfort prospective parents before they get in over their heads.”

What I truly love about genetic counseling is the opportunity to hear people’s stories. Solomon weaves the true shared experiences – good, bad and ugly – of individuals with children who are different with historical context, insights from philosophy and sociology, and personal insights. It’s not always sweet and it’s not always pretty but it is real.

This may not be the most shocking or surprising choice, given that Dr. Solomon was a keynote speaker at NSGC in 2014, but I feel this choice is not without controversy. There are chapters titled “Down Syndrome” and “Prodigies” nestled alongside “Rape” and “Crime.” There is even a chapter titled “Dwarfs” (yuck). I was gently told that trying to assign this 900+ page book to our genetic counseling students was lunacy. But this is a book that I have read, and re-read, and expect to read throughout my life cycle as a genetic counselor. It informs my soul and my work. – submitted by Christine G. Spaeth, Cincinnati Children’s, Cincinnati, Ohio

Small Great Things by Jodi Picoult. Random House. 2016. I’ve always been a fan of Jodi Picoult. In her most recent book, she helps the reader confront issues that permeate the headlines today – prejudice, race, and how the legal system works. Don’t worry, there’s a few genetics-related twists and turns included too! – submitted by Alyson Krokosky, Walter Reed National Military Medical Center, Bethesda, Maryland

Are We Smart Enough To Know How Smart Animals Are?  by Frans de Waal. W. Norton & Company. 2016. Frans de Waal, a leading primatologist, explains how social, smart and altruistic animals are if we only design the correct social experiments to bring out their behavior. I first became interested in Dr. de Waal’s work because he wrote about his observations of a captive Rhesus monkey with Trisomy 18 born in 1988. This monkey was born to a 22 year old G12P11 mother, elderly for this species, where menopause typically occurs at around age 20-25. The mother did not reject her. She was not kicked out of the troop or savagely beaten. Her older sisters helped her forage for food on the ground, until she was euthanized at age 32 months due to intractable seizures. – submitted by Laila Rhee, UC Davis Health System, Department of OB/GYN, Sacramento, California

A Cancer In The Family by Theodora Ross, MD, PhD. 2016. Avery. How do you talk to relatives about family history, especially if they have been reluctant to share in the past? This book gives great how-to’s. The author also praises and recommends working with GC’s. Interestingly the advice she gives about talking to relatives is very similar to what I’m learning from the genealogy community. Genealogists use techniques like those in this book to elicit family stories, starting with oldest relatives first. Since more and more of my patients tell me about their molecular genealogy results, I find this a fascinating tie-in to our profession. – submitted by Kate Crow, MS, CGC, Hereditary Cancer Service, Southern Colorado Centura, Colorado Springs, Colorado

Life, Animated: A Story of Sidekicks, Heroes, and Autism by Ron Suskind. 2014. Kingswell. I really enjoyed the story about how the Suskind family found that Disney movies were being used by their son with autism as a model for how to interact in the real world. submitted by Susan L. Sell, Hershey Medical Center, Department of Pediatrics, Division of Genetics, Hershey, Pennsylvania

Mapping Fate : A Memoir of Family, Risk, and Genetic Research by Nancy Wexler.1996. Univerity of California Press. I’m a little bit late to the game, but I finally read [this book] this year and really enjoyed it.  Alice Wexler tells the story of a thrilling chase to find the Huntington disease gene, which once discovered, would allow for predictive genetic testing of unaffected individuals (unleashing an entire field of gene ethics). She unveils the eventual breakthrough discovery of the gene as the culmination of daring bets and novel scientific approaches. Now, more than 10 years since the Human Genome Project’s completion, with genetic services extending to every rare disease, it is breathtaking to realize how little we knew in 1979, and how far we’ve come today.

As a genetic counselor, I am most moved by Wexler’s deeply personal account of her connection to – and identity in – the Huntington disease world. She allows the reader to experience all the unfinished edges in her story – her contentious relationship with her father, who has a personal and scientific investment in Huntington research; her frustrations with her passive, 1950s-housewife mother; her personal struggle with relationships and infertility in the context of being at-risk. I appreciate that she did not “hero-ify” every character in her memoir, as some do when eulogizing. – submitted by Weiyi Mu, Johns Hopkins University, Institute of Genetic Medicine, Baltimore, MD

Beggars In Spain by Nancy Kress. 1993. William Morrow and Company. Written in 1993, [this book] is surprisingly relevant in the age of CRISPR/Cas9 which has led us to dust off old hopes of treating genetic disease at the source and old fears of taking gene editing too far. The book is based on a society where genetic modifications is available for those who can afford it. A group of children, called Sleepless, do not require sleep to survive. Sleeplessness is associated with other traits such as improved survival and intelligence. Divisions between the sleepless and the sleepers lead to societal divides and touches on the moral questions of what an individual owes to society, what we owe to each other, and what parents owe to their children. – submitted by Rebecca Tryon, Pediatric Blood & Marrow Transplant, Minneapolis

Evicted: Poverty and Profit in the American City by Matthew Desmond. 2016. Crown. I cannot recommend [this book]  highly enough and feel should be required reading for every American citizen who has known nothing but stable housing during their own lifetimes. Equal parts compelling, eye-opening, and heartbreaking, this book illuminates the daily lives of those who struggle to exist within urban poverty at a level that is likely unimaginable to most genetic counselors. What does housing and eviction have to do with genetics you might ask? After more than a decade and a half practicing as a pediatric genetic counselor, I could not even begin to count of the number of no-shows or last-minute cancellations that were disproportionately for children with government healthcare insurance. Although it is just one small storyline in a book of great depth and complexity, an incident is recounted in which a single mother living in poverty and the chaos of eviction with her two sons has to make a decision about getting treatment when one of the boys has an asthma attack. This book depicts with great humanity how complicated and overwhelming even seemingly simple decisions can become when one feels helpless and without hope as the earth seems to be constantly shifting beneath one’s feet. This book offers a powerful and disturbing insight into a plight that is under the national radar, and for me, the insight relevant to children and healthcare was a striking additional nuance. Perhaps “happy reading!” would not be the right sentiment, but I cannot think of a book that is more worthy of reading. – submitted by Stefanie Dugan, Blood Center of Wisconsin, Milwaukee

 

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