Author Archives: Robert Resta

Genetic Counseling ≠ Genetic Testing

I know that I am old and curmudgeonly. I acknowledge that my musical tastes and my concept of genetic counseling are hopelessly stuck in the 20th century. I sense in a frighteningly helpless way that my generation of genetic counselors is becoming increasingly irrelevant to the profession. It is like watching the air slowly leak out of my inflatable raft in the middle of a swift flowing river and realizing I don’t have a lifejacket. If you press me on it and buy me a few drinks, I will let slip out an admission that DNA analysis technologies like ion semiconductor sequencing and pyrosequencing are incomprehensible magic to me. I feel like I have become a visitor in my home country and I can barely speak the native tongue anymore.

So this paradox might sound like a useless warning flare fired from a sinking vessel before it goes under, a futile attempt to alert my younger upstream genetic counseling colleagues who are new to navigating these tricky waters: I love genetic testing; I hate genetic testing.

Genetic counselors and genetic testing have grown hand in hand since the early 1970s. At least in the US, one would not have flourished without the other. Amniocentesis, CVS, carrier screening, maternal serum screening, ultrasound, DNA sequencing, microarrays, and other genetic testing advances have all been ushered into medical practice by the genetic counseling profession. The tests generated a need for our unique skill sets along with the security of employment and the financial wherewithal to support our positions. Without genetic testing, we wouldn’t be where we are today. So what’s to complain about, even for a complainer like me?

Well, I have two related complaints. My first complaint is the ever-expanding list of genetic tests that we feel obliged to offer our patients in prenatal, oncology, and other settings. Don’t get me wrong – I think genetic testing can be incredibly valuable from both a medical and a psychological perspective. But I wind up spending way too much valuable counseling time highlighting the differences between Panel A and Panel B and the relative merits of this lab versus that lab. And, oh, by the way, many of the genes included on these panels are largely irrelevant to your particular clinical concerns. I hear similar plaints from some of my colleagues in prenatal – this carrier test for 75 conditions or that one for 200 conditions, or this prenatal screen versus that prenatal screen.

It is often not clear to me why some of these tests are part of clinical practice to begin with. Probably a variety of forces are behind it – the push from labs to offer more tests and to compete with other labs; the common trait of genetic counselors to be early adopters of new technologies; trying to show that we are at the cutting edge of genetics; our obsession with offering ALL options to ALL comers; demands from patients and referring physicians; worry that if we don’t offer the shiniest, newest products our patient population will go shopping at the next medical center down the road, or Heaven forbid, shop online; and a nagging fear of being sued or at the very least of providing sub-standard care. As I have written about previously, sometimes genetic tests became standard of care before they were thoroughly vetted, evaluated, and debated.

Which leads me to my second complaint. There is a tendency, sometimes overtly and sometimes silently, to conflate genetic testing and genetic counseling. Yeah, sure, genetic testing is an important part of what many of us do, but my job title says counselor, not tester. For some genetic counselors, testing is not even part of their job. We educate, provide clinical expertise to other care providers, and participate in research. There are other services we provide to our patients, not the least of which should be an intense psychological, personal, and occasionally angst-filled exploration of why patients might even want testing to begin with, never mind which test they want. We are there to support and work with them when no testing was done, when testing is irrelevant, or when testing was done in the past and we are helping them adapt to their new medical and emotional status. Let’s look at what your worries and fears are, and why you are in my office to begin with. What has it meant for your life that you or your child or your sister have this condition? What resources do you need? How have your loved ones been supportive or not of you? What are your health care and life goals? Or bigger picture questions such as what are the medical, economic, and social impacts of genetic disease?

At times I think that genetic counseling for psychiatric conditions is the last pure form of genetic counseling – reliable genetic testing is not available for most psychiatric conditions, so you are “forced” to rely on your counseling and clinical skills. Okay, so perhaps I exaggerate a bit, but you catch my drift. I remember my long time colleague Vickie Venne once saying to me that cancer genetic counseling became a lot less interesting to her once BRCA testing became available. While not denying the many benefits of BRCA testing and how it has helped save lives, there is a measure of wisdom in Vickie’s statement.

As a profession, we should extol and support our role in ordering and interpreting genetic testing. But we, or at least I, don’t want testing to be our defining activity. Yes, as one of our skill sets, we are pretty damn good at it. But let’s not forget that it is a counseling session, not an Informed Consent session or a sales pitch. We should boast more about our abilities to help patients make sense of genetic disease for their lives in a psychologically meaningful way, and testing is only one means of achieving this goal. Genetic counselors are not Genetic Testers; Genetic Counseling is not Genetic Testing.

 

 

 

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Euphemisms, Chucklers, Pet Peeves, And Wincers: Thoughts On Our Professional Vocabulary

Words are the clothes thoughts wear.

– Samuel Beckett

I struggle with words. I struggle when I counsel patients to find just the right words to explain genetic complexity while also trying to engage them in a counseling relationship. I sometimes catch myself silently groaning at the stream of what sounds like the absolutely wrong choice of words pouring out of my mouth. I wind up feeling like the voice of the parents in those Charlie Brown cartoon specials; just Wah-Wah-Wah, nonsense utterances that have no meaning or relevance to the central characters. I struggle to understand the psychological meaning of the words patients use to express their thoughts, fears, anxieties, understandings, and misunderstandings. I agonize over these blog postings, repeatedly re-working them until they have the right tone and tenor but still I always feel slightly dissatisfied with some detail of the never-quite-finished product. A close friend says that for him the wrong word is like a flat note in a musical composition. One jarring note and it takes a while for your ear to re-adjust.

So yes, I confess that I am overly obsessed with words. It is yet one more of those Devil-and-Angel aspects of my personality. Good and bad must co-exist else neither exists at all. That obsession is the impetus for this blog posting – exploring the deeper meanings, ramifications, and implications of the vocabulary of genetics, medicine, and reproduction.

I start with words that make me wince. I have previously written about products of conception, habitual aborter, and mutant. Let me add incompetent cervix and birth defect to that list. Even though these words are not used with dark intent, they say a lot about underlying unconscious attitudes and biases. Incompetent cervix is clearly a term created by men for women. Would a man who has difficulty attaining or maintaining an erection ever be said to have an incompetent penis? Birth defect is no better, though in all honesty I catch myself using it from time to time. Just another malfunctioning piece of machinery, a mistake, a reject, an inferior product of conception. And don’t get me started on crack babies. These are all judgmental and harmful words, weaponized to induce blame, shame, and guilt.

In some contexts, benign words can be manipulative, such as high risk. Every patient has a unique and flexible definition of high. But when professionals say high risk it can create a disproportional sense of worry and anxiety. For example, it is often said women 35 and older are at high risk of having a baby with Down syndrome. You can try to soften that by saying higher but the patient mostly hears the high part of that word. In fact, though, the chance that a 38-year-old woman will not have a baby with an aneuploidy is 99%. Those are pretty good odds in my book. But the presumably unconscious and unstated attitude of health care providers is that aneuploidy is an unacceptable outcome – a risk, not a probability – when they show a woman a graph or table displaying age related odds without an objective reference point to put the numbers in context. That is a lot scarier than reframing it as barely 1%, as well as sounding like an unstated scolding – “Well, if you hadn’t waited so long to have a baby, you wouldn’t have this problem.”

Some words are euphemisms. Family balancing – using reproductive technologies to choose the sex of a baby for non-medical reasons – comes to mind. It is fine and normal to want a baby of a particular gender. There are also different cultural imperatives and norms, and complicated psychological reasons why a particular gender is strongly desired.Calling it balancing glosses over the darker implications of reinforcing, and profiting from, sexism. And it implies that a family of all girls, all boys, or varying gender mixes might be out of balance.

Family balancing is a cousin to gender swaying. At first I honestly thought it referred to someone like David Bowie who seemed to fluidly float along the gender spectrum. As I have come to learn, gender swaying describes the practice of trying to increase the odds of having a baby of a particular gender by using folk methods and pseudoscientific techniques, like ovulation timing, cervical PH, and, my personal favorite, positive and negative ions in the air that can be affected by artificial lighting (just why would artificial lighting be found, uh, “down there”?). Somehow it seems more ethically innocuous than family balancing, maybe because the success rate is usually not statistically significantly greater than 50%. But family balancing and gender swaying are on the same moral spectrum. Another euphemistic term is fetal reduction, which neutrally smooths over the rougher ethical edges when a medical procedure transforms a quadruplet pregnancy into a twin pregnancy.

In genetic counseling, we try to reciprocally engage our patients to make the experience more counseling than lecturing. But there is still an underlying power dynamic that can sneak between the cracks and that can remind the patient who is in charge. An example is when we say that we take a family history. Although it is not how we intend to use the word, taking implies that I have the power to assume ownership of story that belongs to the patient, a story that is deeply personal. And by taking it, I now own this intimate knowledge and transform it into something that I reframe into a medical context that gives me power by “interpreting” it for the patient. The message can be “I know what you think about your family history, but let me tell you what it really means.” Perhaps too this power differential  underlies some of the unease many genetic counselors have about Direct To Consumer genetic testing – it diminishes our gatekeeper role of controlling access to genetic testing.

Along those lines, think of the power relationship implied by medical consultation notes that state that the patient denies a family history of genetic disease or drug use or certain symptoms. Denies? Like they are suspected of lying or a criminal activity, and I am the Grand Inquisitor trying to drag the truth out of them? Were these patients ever expecting the Spanish Inquisition?

Not all of my vocabulary pondering is dark. Some reflect my personal pet peeves on usage. I am not a Language Fascist who tries to enforce arbitrary grammatical rules because, dammit, that’s the right way. On the contrary, I love language for its variety, constant evolution, playfulness, and wonderfully creative adaptability. But a few words rub me the wrong way. Pre-existing condition is an ear-sore for me. How can something be pre- to existing? Either something exists or it doesn’t. They are existing conditions. Of course, this mild upset is nothing compared to the outrage I feel at the pig-headed, uninformed, downright nasty views about pre-existing conditions expressed by the President of the United States and his lackey Director of the Office of Management and Budget, they who are too shameful to be named. Now there’s a pair of bad hombres you’d love to rope with Wonder Woman’s Lasso of Truth. Another “earitation” is when someone writes “The patient was told to return in 3 weeks time.” In that sentence, the word time belongs in the Department of Redundancy Department; the same information is communicated if the word is omitted. For my internal ear, it is a jarring note.

Another, perhaps more justifiable, pet peeve is when an author or speaker says something along the lines of “there was a 500% reduction in disease occurrence following this intervention” or “a five fold reduction in occurrence.” Sorry, just flat out impossible. Nothing can be reduced by more than 100% or 1 fold. After that, it ceases to exist (unless of course it were pre-existing) or it becomes an imaginary number*. If the number of cases of a disease decreases from 500 patients to 100 patients, that is an 80% reduction. Or there are one fifth of the number of cases that occurred prior to the intervention. And I don’t believe I am being a kvetcher here. Accuracy in statistical analysis and interpretation is at the very core of the scientific process and discourse, so it is critical to use the right words to describe research results.

There are some words that make me smile when I hear them, such as Captain Underpants’ arch-nemesis Professor Pippy Pee-Pee Poopypants or HMS Boaty McBoatface (okay, they have nothing to do with genetic counseling but even if your inner mind is not permanently mired like mine in the 8 year old boy phase, these names make you chuckle). Similarly, I smile when I hear surgeons describe large breasts as generous. How nice that someone has generous breasts! It almost sounds like a description of a wet nurse. A long time favorite is Instant Baby Formula, which I first encountered 45 years ago when I was a stock clerk at a Brooklyn grocery store. Just add water, and Voila! You have a baby. What could be simpler? None of the icky bother of 9 months of pregnancy or the agonies of labor.

I would love to hear from the Good Readers of The DNA Exchange about their thoughts on the vocabulary of genetics and medicine. What in our professional lexicon makes you irritated, raises your moral hackles, induces euphemistic groans, or you just enjoy? Given the widespread employment of genetic  counselors in laboratories, is there some new Lab Vocab starting to emerge?

As Raymond Carver once wrote in a NY Times piece, “That’s all we have, finally, the words, and they better be the right ones.” So let us make sure we think carefully about them, choose and use them wisely, never weaponize them, and remember to enjoy them.


  • – Yes, I know that this is not technically an imaginary number. I am just employing poetic license.

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Why Me?

“We tell ourselves stories in order to live.” – Joan Didion

Even after decades of clinical experience I am still struck by the sometimes random and sometimes cruel nature of the occurrence of genetic and congenital conditions. You meet a family with 3 successive children with a profoundly serious recessive condition and the next carrier couple that you see have 6 unaffected children. A grandmother watches her husband, son, and grandchildren die from Li-Fraumeni cancers, and then you encounter a TP53 mutation in a young woman with breast cancer and a family history devoid of other cancers. A gene panel reveals that a woman has dodged a BRCA1 mutation in a pedigree overflowing with breast cancer – but she has a pathogenic APC mutation and not a single relative with colon cancer or polyposis. An adopted woman learns she is pregnant the same day she is contacted for the first time by her biological family and told that her biological father just died of Huntington disease.

We consult the Codex of OMIM or the Oracle of Bayes, and then tell scientific stories of skewed mendelian ratios or stochastic processes (Literal translation: Shit happens), stories as much for ourselves as for our patients. My favorite (non)explanatory story is “a multifactorial combination of genetic and environmental factors.” Come on, please. What human trait is not the result of a combination of genetic and environmental factors? We can wind up committing the original sin of genetic counseling – responding only with cold, meaningless facts to patients’ cris de coeur for comfort, validation and acknowledgment of their emotional states, their quest for a psychologically meaningful understanding and acceptance of their situation, and the need to make sense of their suddenly upturned lives. We should be forgiven though. Genetic counselors are only human and who among us is without sin? None of us were immaculately conceived.**

Patients will fill this void with their own stories. It was that stress in my life. They used to spray insecticide all the time in my neighborhood and now every house on my block has someone with cancer. Then there are the somewhat morally judgmental plaints – I am a vegan, I exercise daily, and put no poisons in my body; my sister eats only fast food, smokes, drinks, and has a new boyfriend every weekend, but I am the one who gets cancer and it’s just not fair. Or it must have been the manufacturing plant down the road with that awful chemical smell (How come no one ever lays the blame on pleasing aromas like cinnamon buns in the oven, freshly roasted coffee, or the sensual curry infused scent of an Indian kitchen?).

If Joseph Campbell was right, mythopoesis is as innate as erythropoiesis. Our minds can’t help but tell stories like our marrow can’t help but make blood. So let me offer my own mythological explanation of the epidemiology and distribution of genetic and congenital disorders – Pedigrus Rex, the god and ruler of pedigrees. Pedigrus is definitely  in the classic Greco-Roman tradition of a powerful god ready to unleash his power at a mere whim or perception of insult, without the slightest thought to consequences. As much Zeus as Trickster.

Pedigrus rex

Sometimes he is benevolent. Let’s see, I will render that woman pregnant after she has given up, exhausted from years of unsuccessful fertility treatments. Sometimes he is terribly unkind (Pedigrus Wrecks?). Hmmm, I think I will give a tetralogy of Fallot to that baby with severe ichthyosis. Hey, why not introduce yet another common mutation in another gene to the Ashkenazim? Sometimes he is astonishingly trivial in his malevolence, like making my pedigree software malfunction after having entered a hugely complex family history. Usually, though, he is emotionally indifferent, just going about his business of indiscriminately sowing the seeds of sadness, joy, shock, and love into the soil of human reproduction. We may try to appease him with sacrifices in our temples or try to understand his motives by consulting seers and prophets in our clinics. Mostly, though, he is beyond comprehension and placation.

This is not to lessen the importance of providing medical and scientific explanations. Many patients want technical information and often that is why they come to us. The beam of knowledge sheds some light for them but does not fully illuminate. They will integrate the scientific story into their own narrative – but on their own terms. It is only part of what they are seeking. Our duty to patients is not discharged once we have given them a recurrence risk or a name to their child’s condition. We need to help them create a psychologically meaningful narrative, a life story, that helps them cope and adapt to their situations, to grow and move on.

The Greek tragedies teach us that we have the ability transform sadness into love, shock into acceptance, fragility into strength, denial into hope. Suffering (pathos) turns into recognition (anagnorisis) and reversal (peripeteia). Humanity trumps divinity by telling stories that work emotional miracles. We can all be greater than gods.

“Mythology, in other words, is psychology misread as biography, history, and cosmology.”
― Joseph Campbell, The Hero With a Thousand Faces

Thanks to Emily Singh for help with the graphics.


** Let me digress here and correct a common “mythconception” about the term Immaculate Conception. Most people use the term to describe a conception that occurred without the benefit of sexual intercourse. This is quite incorrect; this is confusing Immaculate Conception with Divine Conception. Immaculate Conception refers to Mary, the mother of Jesus, and not to the conception of Jesus. In Roman Catholic doctrine, Mary, who was the product of conjugal relations between her parents Joachim and Anne after years of infertility, was the only human ever conceived without Original Sin on her soul, i.e., she was immaculately conceived. Jesus, on the other hand, was the product of Divine Conception by the Holy Spirit. He could not have been conceived in the usual style because that would have tainted him with Original Sin, a trait he would have inherited from Mary’ s husband Joseph. Mary learned of her pregnancy at The Annunciation, traditionally 9 months before Christmas on March 25th, when the Angel Gabriel announced to her that “the Holy Spirit would come upon thee” resulting in the miracle of divine conception in Mary’s virginal womb that was unblemished by sin or sex, and without Joseph’s, er, assistance (Joseph had his own visit from an angel who sort of explained the situation to him. So you  might understand why Joseph was deserving of sainthood.).

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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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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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