Tag Archives: personalized medicine

The history of designer babies

I have a new article up over at Aeon magazine. It’s called “Better Babies: The long and peculiar history of the designer human, from Plato’s citizen breeders to Nobel sperm banks and beyond.”

courtesy Aeon Magazine (www.aeon.co)

After touching upon some of the earliest methods of designing babies, I move through Francis Galton and some of the history of eugenics that should be familiar to Genotopia readers by now. But I take the story up through CRISPR, arguing first that attempts to design our children are all but certain; and second, that they are almost certain to fail. What both the cheerleaders and the hand-wringers fail to take into account is the complexity of the genomics in a species as complex and modulated by culture as ours. Any trait that’s very interesting socially—criminality, sexuality, drug addiction, aggression, etc.—is going to be extraordinarily complex and won’t be reducible to single genes, or even a few.

By all means, new techniques such as CRISPR can and should be applied where they can bring genuine medical benefit. But I caution that high-tech medical benefit comes with social costs—and that high-tech biomedical hype always overreaches real clinical reality.

DNA as Commodity

Here’s a riddle: In the morning I was in the soup. At noon I was in a dish. In the afternoon I was in your gas tank. And at night I am in the bank. What am I?

The answer is DNA. From a natural object emerging, some say, from a primordial soup, to a laboratory object, to a cultural object, it has become data, a special string of computer code endowed with the power to foretell disease, identify criminals, and be leveraged, like software, as a product.

from venturebeat.com

Robert Resta, a genetic counselor and always a reliable source of depressing, ironic, frightening, and amusing stories about heredity and DNA, forwards this piece, by @alexlash, from Xconomy.com on how your DNA is becoming commodified. What’s happening is interesting not for how new it is, but for the way in which the exotic is becoming commonplace. Featuring the San Francisco biotech company Invitae, the piece shows how this small but highly capitalized company is taking on giants such as Illumina, 23andMe, and Myriad in a bid to monetize your sequence—and give you a small cut.

The troubling thing is how commonplace this is all becoming. Nothing Invitae is doing is really new. They want to persuade you to donate your genome to their database, where it can be analyzed to inform you about your health, contribute to research, and be sold to other companies who might use it for anything from curing cancer to targeted advertising. Invitae CEO Randy Scott he is not bringing in new tests–only offering existing ones all in one place, an approach he calls “generic genetics.” (“Generic genomics” would be more accurate–this is about as far from Gregor Mendel as you can get with a double helix.) And he wants to include users in the process, so that if their sequence is bundled into some DNA-based product, you get a tiny royalty. Sort of like allowing ads on your blog.

For some time, historians and sociologists of science have been writing about “biological citizenship,” the idea that we’re coming to base our identity on our biological status rather than our labor. Many people today identify more as a cancer survivor, as living with depression, or as gluten-intolerant than as a carpenter, secretary, or professor.

DNA has been a big part of that shift to biological citizenship. It’s not the only thing, of course, but it’s a big one. DNA, a hypothetical Marxist historian (there are still a few!) might say, came to have “use value.” We hear every day suggestions that our genes make us who we are. Leaving aside for the moment whether they actually do—a challenge for me, as regular readers know—we believe our DNA to be the secret of life. And so, in a sense, it is.

What’s happening now is that use value is being converted into exchange value. DNA is becoming a currency. An investment account we’re all born with. What are you going to do with yours? Hide it under a mattress? Or make it work for you?

One could imagine a day when there’s a new kind of hereditary aristocracy. A group of nouveau riche whose wealth nevertheless was inherited. Those who, through no effort of their own, received a legacy of valuable SNPs (single-nucleotide polymorphisms). But it will take a go-getter to capitalize on that legacy. You’ll have to have ambition, street smarts, and at least a bit of lab smarts.

Marx also said that history was determined by the material reality of the individual. One might now say the molecular reality of the individual. But total self-awareness at the molecular level won’t lead to the end of exploitation of man by man. Indeed, it is only the beginning.

Hope, hype, and $$$ in precision medicine

In the early days of personalized genomic medicine, skeptics wondered how tailored medical care could be profitable. Who would develop a drug for just one or a few people?

Turns out they were looking in the wrong direction. The answer lies in genetic testing more than drug development. A detailed report in today’s New York Times examines how the promise of personalized or precision medicine is being “tainted” by hype. “Across the industry,” they write,

investors are pumping tens of millions of dollars into clinical laboratories that are developing and selling the genetic tests. President Obama recentlycalled on Congress to spend $215 million next year on personalized medicine, calling it “one of the greatest opportunities for new medical breakthroughs that we have ever seen.” A major use of the federal funds would be to create a research group of a million volunteers that would provide scientists with an enormous collection of data.

Doctors and their patients, finding it hard to resist the promise, are being swept up in the excitement. The number of tests has almost doubled in the last few years, creating a $6 billion industry.

While acknowledging that some genetic tests are proving highly valuable–particularly in diagnosing different forms of cancer, which can respond highly specifically to certain drugs depending on the mutation–they note that many genetic tests are doing more to fatten corporate wallets than they are to improve patient care. The tests often run to $1000 or more.

WIth so much at stake, federal regulators are growing concerned about fraud. Turns out some doctors are ordering and charging for tests that people don’t need!

An internal chart reviewed by The New York Times suggests the company was not shy about pointing out that doctors could amass a substantial income by participating. If a doctor enrolled five patients per day and took 110 swabs per month, that physician could earn as much as $125,400 in compensation from the study over a year.

Shock and awe!

An early use of the term “precision medicine”

“Precision medicine” has become a biomedical buzzword, largely replacing “personalized” or “individualized” medicine.  In his 2015 State of the Union Address, President Obama announced a “Precision Medicine Initiative.” I first heard the term in May 2013 as an updating ofThis seems to be about the time its use began to take off. Researching a talk, though, I was surprised to find a much earlier use, from 1979. The sense is the same, but the context very different.

In the first issue of volume 7 of the American Journal of Chinese Medicine, Ling W. Wei, an electrical engineer at the University of Waterloo, Ontario, published an article titled “Scientific advances in acupuncture.”[1] At that time, “alternative” or “comparative” medicine was new enough that he felt the need to define acupuncture as a branch of Chinese traditional medicine. He notes that Richard Nixon’s visit to China in 1972 put acupuncture in the spotlight for Westerners, noting that the scientific community was “aloof and apathetic, if not down right scornful” of the technique. Wei proceeds to evaluate acupuncture as scientific medicine.

There’s much to say about this fascinating paper, but I note here just one passage, on pp. 70-71.

The trend of technological advance in acupuncture holds great promise of promoting medicine in three directions,” he writes. These are what he calls the “three P’s”: preventive medicine, precision medicine, and people medicine.” This is remarkably close to Leroy Hood and colleagues’ “P4” medicine (“personalized, predictive, preventive, participatory”), first discussed in 2010. Wei’s formulation captures all the sense of Hood’s, but more concisely (preventive follows from predictive). But where Hood’s P4 medicine is predicated on reductive genomics, Wei imagines an equally high-tech but image-based approach.

Preventive medicine, writes Wei, “can be realized only with the availability of a simple, non-invasive and thorough physical check-up method. Like a TV screen, it should be able to expose the whole picture of the body’s condition in various colors and patterns.” He then goes on to imagine much more than a TV screen. “Precision medicine,” he continues, “requires similar methodology and, furthermore, a great analytical power in technology. For example, two common diseases of modern times, headache and hypertension, have many causes and the precise origin of the symptom is sometimes very difficult to diagnose.” Acupuncture can help. “Acu-points can serve as alarming outposts in internal organs when sick.” Merging ancient Chinese medicine with futuristic Western technology, he writes,

“If the electrical signals from 365 or a selected number of acu-points of the whole body are successively stored and then fed to a specially designed TV monitor, the pattern of this “holography” could tell us the whole story of the person’s health condition and thereby reveal not only the precise origin of the current illness but also perhaps some hidden signs of developing symptoms. To make the interpretations more precise, this holographical pattern could be fed to a “diagnostic computer” and let it be compared to thousands of standard patterns (in storage) of established causes. If a match or near-match is found, then the cause is said to be pinpointed. A man could take a “holography” anytime or once a year and the film can be as small as the palm. If in the future every drugstore had a terminal link (perhaps through telephone lines) to a central computer, one could simply insert his holography film into the machine and get an instant print-out telling his health condition. That day is not too far off; because the technology in opto-electronics and computers is almost ready for this “diagnostic automat” to be within reach.

The precision required in acupuncture is obvious and material: you have to put the needles in exactly the right place. It’s rather stunning how close Wei’s vision is to what contemporary precision medicine is aiming at, by very different means.

[1] Wei, L. Y. “Scientific Advance in Acupuncture.” Am J Chin Med 7, no. 1 (Spring 1979): 53-75.

Your new genetic test results are here!

McSweeney’s is getting into the genetic satire act. Plenty of room, folks, plenty of room. Funny piece: http://www.mcsweeneys.net/articles/congratulations-your-ineffectual-genetic-test-results-have-arrived

 

 

23andMe, FDA, and the history of hype

Yesterday I and seemingly everyone else interested in genomes posted about the FDA letter ordering the genome diagnostics company 23andMe to stop marketing their saliva test. FDA treats the test as a “medical device, because “it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or is intended to affect the structure or function of the body.” The company first issued a bland, terse statement acknowledging the letter and then company president Anne Wojcicki signed a short post affirming the company’s commitment to providing reliable data, promising cooperation with FDA, and reasserting her faith that “genetic information can lead to better decisions and healthier lives.” (I say she “signed” it because of course we have no way of knowing whether she composed it and she’s no fool: surely the text was vetted by Legal.) In other words, the company followed up with a bland, less-terse response, carefully worded to reassure customers of the company’s ethical stance and core mission. Reactions to the FDA letter range from critics of the company singing “Hallelujah!” to defenders and happy customers are attacking FDA for denying the public the right to their own data. The 23andMe blog is abuzz and, hearteningly, a few sane souls there are trying to dispel misinformation.

I am doing history on the fly here. If journalism is the first draft of history, let’s take a moment to revise that first draft—to use the historian’s tools to clear up misconceptions and set the debate in context as best we can. The history of the present carries its own risks. My and other historians’ views on this will undoubtedly evolve, but I think it’s worth injecting historical perspective into debates such as these as soon as possible.

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We must be clear that the FDA letter does not prohibit 23andMe from selling their test. It demands they stop marketing it. The difference may not amount to much in practice—how much can you sell if you don’t market your product?—but the distinction does help clarify what is actually at stake here. FDA is not attempting to instigate a referendum on the public’s access to their own DNA information. They are challenging the promises 23andMe seems to make. This is, in short, not a dispute about access, but about hype.

The company seems to promise self-knowledge. The ad copy for 23andMe promises to tell you what your genome “says about you.” “The more you know about your DNA,” they trumpet, “the more you know about yourself.” On one level, that’s perfectly, trivially true: your genome does have a lot to do with your metabolism, body structure, how you respond to disease agents, and so forth. The problem is, we as yet know very little about how it all works. The 23andMe marketing exploits a crucial slippage in the concept of “knowledge,” which FDA correctly finds misleading. In short, the marketing implies a colloquial notion of knowledge as a fixed and true fact, while the science behind the test is anything but.

Historians and other scholars of science have thought a lot about the concept of scientific knowledge. In 1934, Ludwik Fleck wrote about the “genesis and development of a scientific fact,” namely the Wasserman test for syphilis. It is a pioneering classic in a now-huge (and still growing) literature on how scientific facts are created. Science claims to gather facts about nature and integrate them into explanations of natural mechanisms. A moment’s reflection reveals that very few scientific facts last forever. Most, perhaps all, undergo revision and many are discarded, overthrown, or reversed. They are historical things, not universal truths. A surprisingly small amount of what I learned in science courses 20 and 30 years ago is still true. As that great philosopher of science John McPhee wrote, “science erases what was previously true” (Oranges, p. 75). Because scientists search for universal, timeless mechanisms, they easily slip into language suggesting that they discover universal, timeless truth. But there is uncertainty, contingency, malleability built into every scientific fact.

This goes double for genome information. The 23andMe product, like every genome test, provides probabilities of risk, not mechanisms. Probabilities are messy and hard to understand. They carry an almost irresistible tendency to be converted into hard facts. If you flip a coin 9 times and it comes up heads every time, you expect the next flip to come up tails. And if you get heads 49 times in a row, the next one has got to be tails, right? Even if you know intellectually that the odds are still 50:50, just like on every previous flip. You can know you have a particular gene variant, but in most cases, neither you nor anyone else knows exactly what that means. Despite the language of probability that dots the 23andMe literature, their overall message—and the one clearly picked up by many of their clientele—is one of knowledge in the colloquial sense. And that is oversell.

Human genetics has always been characterized by overstatement and hype. In the early 1900s, the rediscovery of Mendel’s laws persuaded many that they now understood how heredity works. Although every scientist acknowledged there was still much to learn, prominent students of human heredity believed they knew enough to begin eliminating human defects through marriage and sterilization laws. We now view such eugenic legislation as almost unbelievably naive. Combine that naivete with race, gender, and class prejudice and you obtain a tragically cruel and oppressive eugenics movement that resulted in the coerced sterilization of many thousands, in the US and abroad—including, of course, the Nazi sterilization law of 1933, based on the American “model sterilization law,” which culminated not only in racist forced sterilization but euthanasia.

Human-genetic hype hardly ended with the eugenics movement. In 1960s, as human diseases were finally being mapped to chromosomes, it seemed transparent that if a chromosomal error that produces an individual with an XXY constitution feminizes that individual (which it does), then an extra Y chromosome (XYY) must masculinize. Such “super-males,” data seemed to suggest, were not only taller and hairier than average, but also more aggressive and violent. It was, for a while, a fact that XYY males were prone to violent crime.

The molecular revolution in genetics produced even more hype. When recombinant DNA and gene cloning techniques made it possible to try replacing or augmenting disease genes with healthy ones, DNA cowboys hyped gene therapy far beyond existing knowledge, promising the end of genetic disease. The 1995 Orkin-Motulsky report acknowledged the promise of gene therapy but noted,

Overselling of the results of laboratory and clinical studies by investigators and their sponsors…has led to the mistaken and widespread perception that gene therapy is further developed and more successful than it actually is.[1]

Soon after this report was published, Jesse Gelsinger died unexpectedly in a gene-therapy trial, patients in a French gene-therapy trial for adenosine deaminase (ADA) deficiency unexpectedly developed leukemia, and the gene-therapy pioneer W. French Anderson was arrested, tried, and convicted on charges of child molesting—in other words, abusing and overestimating his power over the children whose health was entrusted to him. The risks of failing to heed warnings about genetic oversell are high.

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Like gene therapy, genome profiling has great promise, but the FDA letter to 23andMe is a stern reprimand to an industry that, like gene therapy and the entire history of human genetics, blurs the line between promise and genuine results.

The current controversy over commercial genome profiling has two qualities that distinguish it as particularly serious. First, unlike previous examples of overselling human genetics, it is profit-driven. The “oversell” is more literal than it has ever been. Although 23andMe presents as a concerned company dedicated to the health of their clientele, they are also—and arguably primarily—dedicated to their stockholders. In a for-profit industry, oversell is a huge temptation and that risk needs to be made transparent to consumers.

Second, the 23andMe test is being sold directly to individuals who may not have any knowledge of genetics. The tendency to convert risks into certainty is higher than ever. The knowledge they sell is a set of probabilities, and further, those probabilities are not stable. The consumer may not—indeed probably doesn’t—appreciate how much we know, how much we don’t know, and how much we don’t even know we don’t know. The company claims to be selling knowledge but in fact they are selling uncertainty.

In a characteristically insightful and clarifying post, the geneticist (and 23andMe board member) Michael Eisen doubts whether the 23andMe test will ever meet FDA’s definition of a “medical device.” It is not an MRI machine or a Wasserman test. It’s something new. Adequate regulation of products such as the 23andMe genome profile will require rethinking of what exactly the company is marketing.

Putting this controversy in context, then, illustrates another critical risk: the risk of failing to acknowledge the uncertainty underlying the science. In some sense, the more we learn, the less we know.

 


[1] Orkin, S. H., and A. Motulsky. Report and Recommendations of the Panel to Assess the NIH Investment in Research on Gene Therapy.  Bethesda, MD: National Institutes of Health, 1995.

A blow for personal genome testing

Hey honey–remember when I accidentally left the chicken coop open and they all flew away? Well I think they’ve come back home to roost!

Last summer, we did an analysis of the 23andMe commercial promoting their genetic testing service and the egotistical identity politics it both taps into and contributes to. The ad was all about how your genes were “You” and knowing about them would enable you to predict your genetic future. Genetic profiling can in some cases give robust statistical estimates of likelihood of certain genetic conditions, but it is safe to say that we rarely know what that means. And it’s presented as though we do.

Now we find that FDA is ordering 23andMe to stop marketing their tests.

The 23andMe saliva sample kit, says FDA, is a “medical device,” “intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or is intended to affect the structure or function of the body.

They cite the company’s claims to allow patients’ genome profiles to help them assess “health risks,” and “drug response,” and specifically as a “first step in prevention” that enables users to “take steps toward mitigating serious diseases” such as diabetes, coronary heart disease, and breast cancer.

23andmescreenshot

This is not a shot over the bow–it’s the last straw. FDA has warned 23andMe repeatedly, going back to July, 2012, that they were making health claims about their product that they couldn’t back up.

The company offers two types of products: a genealogical “panel” or profile, and a health panel. The genealogical panel is popular but is apparently considered a harmless hobby, or at least outside the purview of the Public Health Service. It is not clear whether FDA (which, like the National Institutes of Health and the Centers for Disease Control) falls under the sprawling PHS will have any concerns about genealogical applications of the saliva test, but that would seem unlikely. The problem for 23andMe is that, as shown by the ad we analyzed earlier, they have been pushing the health panel very hard. Family trees are a hobby; health is where the real money is.

Direct-to-consumer medicine trails an appealing democratic, anti-authoritarian perfume that seems to make people slightly drunk. Mild intoxication can be pleasant, need not be dangerous, and sometimes can be a spur to creativity. But it can also impair your judgment. When you’ve gotta drive the kids home, you may need a couple cups of good strong regulatory coffee and a couple hours to sober up before getting behind the wheel.

A good deal of “preventive, participatory, personalized” medicine is profit-driven, and stockholders don’t necessarily have the public’s health foremost in mind. The FDA warning is a good illustration of why it’s important to balance the goal of stimulating innovation and economic growth with the goal of maximizing health. For the former, the free market can be a powerful tool. But for the latter, sometimes you need a little good old-fashioned meritocratic oversight.

h/t Robert Resta, Mark Largent