Personalized Medicine’s Problem of Meaning
Personalized Medicine’s Problem of Meaning
--Hannah Arendt, The Human Condition
What is the route between the technological ingenuity that brings us ever expanding genomic and other – omic data – data that is at the heart of the promised personalized medicine – and meaningful knowledge that might foster life and human understanding? This question of meaning – the question of the uses, significance and value of the human genome sequence – marks what I call the postgenomic condition. While efforts to forge answers to important questions about privacy, property and consent will continue to be important to advancing personalized medicine, my contention is that the field will not make meaningful progress unless it grapples with the fundamental questions about value and worth created in the wake of sequencing human genome sequence: We can sequence all those As, Cs, Gs, and Ts, but what do they mean? While the genome was described as the secret of life, will it lead to important new biological knowledge? (Note: this question addressed in Hallam Steven’s and Sarah Richardson’s and Prainsack’s books: hairballs; what knowledge is gained and lost). People talk about genomics being a revolution in biology, but I think we need to start with the more basic question, what is biology and is genomics a part of it? Is it an important thing around which we should gather? Note the etymology of thing. Recall, as the French theorist of science and technology Bruno Latour reminds us, the word thing derives from the Old English word “ding”, which means a meeting or assembly.[ii] A thing, or a gathering, arises around a matter of concern.
In an age of historic inequalities, dwindling natural resources and growing polarization, what should be a thing around which we gather? Should a genome be such a thing? Should personalized medicine? How can we constitute the collectives – the we’s – that can credibly answer these fundamental questions about what ought to exist and who we are, questions that are at the heart of collective life and of justice?
I am, of course, not the first person to raise these questions about meaning and genetics/genomics. Nor is it surprising that I would. My father was a Jesuit priest. He was one of the Washington DC Catholic priests known as the Washington Dissidents disciplined by Cardinal O’Boyle for opposing John Paul VI’s teaching on birth control in John Paul VI’s 1968 encyclical, Humanae Vitae. Birth control, of course, is now one of many biotechnologies that the Church has grappled with. I grew up hearing from my father about these debates about how to interpret their meaning in the light of theology. It is also from my father that I learned of the work of Bob Brungs and the Institute for Theological Encounter with Science and Technology he co-founded. It is from my father that I am in possession of several of the ITEST bulletins, including this one that published the proceedings of the October 1996 ITEST Workshop, “Patenting of Biological Entities”. While, remarkably, we have not talked much about ownership or patenting at this meeting, at this workshop 20 years ago it was the main topic of concern. Jeremy Rifkin had just called for a ban on patenting life, and many Church leaders has joined him. Brungs, however, questioned whether patenting should be the main concern. Indeed, he questioned the utility of any kind of line drawing between ethical and unethical, use and abuse. As he explained:
Are we certain that lines should be drawn where we would at present draw them? The problem we face is not ethical; it is ontological, if I may use that word. Our issues and challenges are at the level of meaning. Ethical discourse is necessary, but it is in no way sufficient.
He went on to cite a portion of the civil engineer Harry Boardman’s address delivered in 1976 to the AAAS (which had the great title “Some Reflections on Science and Society: A Terrain of Mostly Clichés and Nonsense, Relieved by the Sanity of Whitehead”):
But far too pervasively, these endless biomedical-science-value discussions manifest a deplorable blindness which seems to proceed from a hypnotic fascination with appliances and appliance-makers. … The central concern is not science or scientists, but with the whole of knowledge – its benefits, the price it extracts, and its special province; that of ideas.
“In other words”, Brungs explains, “Boardman is calling for less attention to techniques (and to issues like patenting) and more concern about the meaning of these new powers”.
I would argue, similar to Brungs and Boardman, that to address questions of meaning we must turn our attention to fundamental questions about the constitution of knowledge, questions that are inextricably bound up with questions of justice. Yet it is here that Brungs and I depart, although I think the departure will be illuminating, and will speak to my main point. Brungs was interested in understanding what bioengineering “looked like in the light of the Revelation and of the future of the Kingdom of God”. I am interested in what it looks like in the light of justice.
This makes me undoubtedly a product of my times, and of genomics. As John Rawls pointed out in his enormously influential Theory of Justice, justice brings us back to first principles and virtues. We live in times where people across the globe are questioning the first principles of institutions, whether it is right to concentrate wealth on Wall Street, whether the Freedom of Movement should be fundamental to a free Europe, whether a union between a man and a woman is fundamental to the institution of marriage. Rawls argues that no matter how efficient or well-ordered laws and practices may be, if they are unjust they must be redone.
At the end of the last millennium, the human genome sequence became an emblem of just one struggle for justice. It promised to be a part of the fall of the Cold War, and to unite the world – the first principle of our collective living is that we are not divided, we are one (One genome, one world). This is what originally attracted me to genomics. Of course, I quickly learned the reality was far more complicated and contentious. At the very same time, right at the height of the HGP, genomics also became an emblem of public, open science. Leaders of the public effort to sequence the HGP fought off efforts to patent the human genome. They framed their effort as an epic fight of the good (public HGP) against evil, the privately funded Craig Venter. Jeremy Rifkin and the Protestants and Buddhists and indeed some Catholics came to their side. However, Brungs did not. Instead, he organized the ITEST meeting to question the emerging moral consensus that patenting life was wrong.
At the same time Merck decided to fund the work of Bob Waterston. Waterston’s lab was one of the two main labs that produced the final sequence of the human genome. The other was John Sulston’s Lab at Sanger. Waterston and Sanger were deeply committed to keeping the sequence in the public domain. Merck also sought to keep human genome data in the open, and supported their efforts. Brungs (who was at St. Louis University) invited Waterston (from the neighboring Washington University) to attend the meeting. At the meeting, Waterston said he’d rather not speculate about why Merck was supporting him.
Merck came to us because they had made the corporate decision that they wanted to sponsor a project that would put on the Web human DNA sequence of the same kind that Incyte and Human Genome Sciences were producing. They wanted to sponsor projects with equivalent information out in the public domain. The reasons they wanted to do this, they never told us. I can only speculate and I would rather not. I think it is basically that they wanted to level the playing field.
The fact of Merck’s support was tricky. Obviously it blurred the bright line some in the HGP were trying to draw between the evil corporate world and the good public one. Yet it made Brung’s point: simple line drawing – between private and public, good and evil – will not work.
If the situation was murky back in 1996, it has only gotten murkier. Genomics is no longer primarily supported by public institutions. Rather, it is fueled by large investments made by private philanthropists, venture capitalists, start-ups, and major pharmaceutical companies. Turning a profit has become a primary concern, if not responsibility, of many, including Atul Butte, chief data scientists of UC Health. How to align genomics with the cause of justice under these conditions is far from clear.
Genomics has helped to create a world in which its data may be accessible, but medical treatments resulting from it may not. Medicines arising from genomics are the most expensive ever produced. Spark, for example, just released the gene therapy Luxturna to treat retinal degeneration at a cost of $425,000 per eye, or $850,000 per person.[iii] These extraordinary price tags add new strains on already taxed healthcare systems, and place the new gene therapies out of the reach of the many worldwide.
In the wake of the completion of the human genome sequence, today worries that investments in genomics might aggravate inequalities in access to healthcare are a defining concern. Where I live in San Francisco, residents recently asked leaders of the University of California, San Francisco how they could invest so much money in the new Mission Bay campus, a hub for precision medicine research where billionaires are financing half-billion dollar buildings devoted to their areas of interest, while closing the last full-service reproductive health clinic serving poor Black and Latino youth in San Francisco. As a petition posted to the Color of Change website put it: “The message the city of San Francisco and the University of California San Francisco are sending is blatant: money matters, not Black and Brown lives”.[iv]
These new bioeconomies today being built in the Bay Area are transforming a visit to a UCSF doctor into a contractual transaction. At a routine physical check-up in 2013, I received a Terms and Conditions of Access (TACOS) form that informed me that reception of medical care was dependent on agreeing that UCSF could share my data and tissues with researchers and I possessed no rights to any useful commercial products that resulted. When I asked my doctors what they might want to do with my data and tissues, the first use they mentioned was genomic research. When I published an account of this encounter in the San Francisco Chronicle, I heard from others who said they were in fights with their medical providers over this very issue.[v] One had a rare disease, and did not want this disclosed to others. Struggles like these are further eroding trust in doctors and medical systems and raising questions about ultimate ends and goals: or first virtues, to refer back to Rawls. Who is this system for? Me or researchers? Me or industry?
While market forces and contractual arrangements today powerfully combine to produce access to the tissues and data needed to propel the personalized medicine revolution, they do so at the risk of aggravating already existing problems of trust that may ultimately contravene the field’s promises of health and wealth. Consider the proposed clinical trial using CRISPR to treat sickle cell. After years of proportionately low research dollars flowing to this disease that primarily affects African Americans (sickle cell trait affects 1 in 13 AA, and sickle cell disease 1 in 365), now the spotlight is on sickle cell. This is because it is a disease that targets a specific cell type, and so is considered ideal for CRISPR gene therapy. However, will researchers be able to recruit enough people to sign up for the trial? Historic and ongoing mistrust of the biomedical research community, mistrust partially created by legacies of eugenics and sterilization, poses questions about the ultimate meaning and value of advances like CRISPR.[vi]
It is, I suggest, possible that today we sit on top of a biomedical bubble produced by celebrating technical prowess while sidelining fundamental questions of trust and truth, justice and knowledge. Under these conditions. the value of genomics and of personalized medicine could collapse under the weight of these mounting concerns.
I should say that I think that those in this field are aware of these issues. Indeed, I think many had hoped that after the HGP scientists would return to the task of focusing on creating meaningful insights about life. However, it soon became clear that advances in sequencing technology would continue to generate the most money and excitement. The premier sequencing project – the Human Genome Project – might be complete, but influential thought leaders argued that medical breakthroughs required radically decreasing the cost and increasing the speed of DNA sequencing. NIH invested two hundred and thirty million dollars of seed money to spur innovation in sequencing; venture capital (VC) funding and an X prize followed.[vii] DNA sequencing companies became the darling of the tech world, exploding Intel co-founder Gordon Moore’s law that computing power doubles every two years. Sequencing powers increased five times as fast, doubling every three months.[viii] Despite the initial post-HGP efforts to return focus to fundamental questions of biology and medicine, this startling demonstration of technological prowess captured the limelight and VC dollars, and created a powerful force that few could resist.
Some prominent genome scientists understood the threat such large sums of money posed to the communal and democratic ethos propounded by leaders of the HGP. Indeed, they resolved to fight the forces of capitalist accumulation, and to help ensure that the resources that flowed to sequencing did so in a more equitable fashion. NIH distributed grant funding to companies who could complete with ABI and break their monopoly.
ABI did falter. However, the DNA sequencing monopoly did not. Today, one powerful company again dominates: not Applied Biosystems, but Illumina. In 2015, Illumina was valued at twenty-eight billion dollars, and produced more that 90 percent of all DNA data.[ix] In 2017, its share price increased 71%. Today the company is valued at 46.2 billion dollars, and is positioned to grow dramatically.[x] This is because it seeks not just to sequence DNA, but to own the means of interpreting it. A look at the company’s home page provides a glimpse into its aspirations to dominate all aspects of postgenomics, from forensics to the microbiome to oncology to reproductive health.[xi] While many hoped that in the era after the Human Genome Project the field would diversify not only the genomes sequenced, but also genome sequencers and its interpreters, it is here that we have arrived: a genomics in which one powerful corporation and its machines lie at the center.
The postgenomic condition is future-oriented now strongly shaped by this past in which the Human Genome Project’s effort to create the machines to sequence took precedence over the effort to interpret that sequence. There was a moment in which some – including the leader of the private effort, Craig Venter – urged devoting resources to interpretation. However, James Watson, leader of the public effort, urged “sequence now, interpret later”. The result: today there exist powerful capacities to sequence, but not robust institutions that can interpret and responsibly govern.
Addressing this critical lacuna will require moving beyond the traditional bounds of bioethics – circumscribed by concerns about privacy, consent and property – to ask more fundamental questions. Around what can we gather to create collective life? What principles and practices will engender trust and produce credible knowledge that can guide our decisions? Recall that decision derives from the Latin root cis, meaning to cut or kill. Not all forms of life or uses of genomic data can be supported. Some live and prosper. Others fail to gain support and die. A judgment must be made. The question is not whether to judge, but how. As Arendt reminds us, there is perhaps no question more fundamental to political life than this one. On what grounds will we judge? Who are “we”? These are the urgent questions that today all of us – whether we are a scientist in the lab, a leader in government, or a VP of a corporation – must confront if the global financial collapse is not to be followed by a global political collapse and a global scientific collapse.
Perhaps it should not surprise that in this moment in which the credibility and authority of so many institutions are in question – from the media to medicine from the courts to the classroom – genomics has emerged as a new ground for attempting to order life. As some astute political commentators recently have observed, genomics and high tech biomedicine are among the few things left around which divided nations gather.[xii] Genomics still promises to transcend partisan politics and to unite humanity through its offer of miracle cures. Yet recent events should contravene this dangerously simple interpretation. Elizabeth Warren’s effort to resolve questions about why she checked a box claiming she was Native American decades ago did not reveal the truth. Instead, it revealed all too limited capacities to understand the scientific and political questions at stake when citizens and their leaders attempt to speak about differences among human beings at the genomic level. Can ancestry be parsed from race? Can locating differences in our genome help us to locate our place in society? Who decides and how? By treating genomics as the all-powerful secret of life – by granting it too much meaning – we have failed to grasp and respond to its actual meaning, and its role in fundamental activities of ordering natural and social order.
Thus, today it is all too easy for extreme views to fill the void. As a recent set of articles by Amy Harmon of the New York Times revealed, we live in a moment in which white supremacists invoke genomics to support their beliefs in racial purity and superiority, and engender few critical responses.[xiii] Harmon struggled to find any geneticists willing to go on the record to comment on these white supremacist invocations of genomics. Powers to sequence may have grown exponentially, but powers of speech and of response have dangerously eroded. We systematically – over several decades – have built an ir-response-able genomics – that is, a genomics with the power to sequence, but not the power to respond and speak about these new constitutional powers. The grave consequences of this are now beginning to be felt.
How can we respond?
First, we must recognize that the genome is quickly becoming a powerful institution in our society: it is becoming a routinized set of practices and ideas by which we order. Second, we must take responsibility for this fact and invest in genomics as a moral institution with the capacity to reflect upon and speak about its constitutional powers. We must build institutions that enable ‘us’ to ask – and answer – fundamental questions: Who lives and dies and how? Or as Brungs provocatively asked, what is our bodied future? If Jesus were to ascend today, would he bring his banked stem cells with him to heaven?
Finally, we must work across historic divides. At my own university, our Science and Justice Training Program, for example, trains science and engineering graduate students alongside social science, humanities and arts graduate students to ensure that justice is part of the conversation. While our focus is on training our students, to make this possible we have had to learn how to train our institution to work in new ways too. For our natural scientists and engineers this means recognizing that reflective work counts as ‘science’ and is not a distraction from the hard work of the lab. For our social scientists and humanists, it means walking away from assumptions that as soon as you introduce a sequencing machine you might be producing a reductionist, determinist vision of humanity.
We all hope for a future of personalized medicine that achieves its promises: new cures; longer and better lives. However, for that to come to pass, we must begin with the simple task of cultivating meaningful speech among us, where we ask who we are and who we ought to be. Who is not represented around this venerable table today? And whatever ‘we’s’ we can muster must endeavor to speak about that which genomics does today – not the future – and to develop the ability to respond to it. A response-able personalized medicine should be our next milestone.
 For ideas far afield from science and technology may be the most lethal. Inspiration to man’s action lies not in appliances – as much as they may encourage or inhibit it – but in the spell of ideas and the conviction of mind and heart they generate.
[i] The quote continues: “In this case, it would be as though our brain, which constitutes the physical, material condition of our thoughts, were unable to follow what we do, so that from now on we would indeed need artificial machines to do our thinking and speaking. …Wherever the relevance of speech is at stake, matters become political by definition, for speech is what makes man a political being. If we would follow the advice, so frequently urged upon us, to adjust our cultural attitudes to the present status of scientific achievement, we would in all earnest adopt a way of life in which speech is no longer meaningful. For the sciences today have been forced to adopt a ‘language’ of mathematical symbols, though it was originally meant only as an abbreviation for spoken statements, now contains statements that in no way can be translated back into speech” (Arendt 1958, 3-4).
[ii] Latour andWeibel, eds, Making Things Public: Atmospheres of Democracy.
[iii] See https://www.cnn.com/2018/01/03/health/luxturna-price-blindness-drug-bn/index.html. Accessed October 15, 2018.
[iv]Barros, “UCSF Plans to Shutter Clinic Serving Minority Youth”.
[v] See https://www.sfgate.com/opinion/article/Should-patients-understand-that-they-are-research-4321242.php
[vi] See http://www.sideeffectspublicmedia.org/post/black-communitys-troubled-history-could-make-sickle-cell-crispr-editing-hard-sell
[vii] Angrist, Here Is a Human Being: At the Dawn of Personal Genomics, 78-80.
[viii] Hayden, “Technology: The $1,000 Genome”.
[ix] See “Illumnia Enterprise Value”, YCharts, accessed October 16, 2016, https://ycharts.com/companies/ILMN/enterprise_value
[x] See “Illumnia Enterprise Value”, YCharts, accessed October 15, 2018, https://ycharts.com/companies/ILMN/enterprise_value
[xi] Hayden, “Technology: The $1,000 Genome”, Regaldo, “Illumina Says 228,000 Human Genomes Will Be Sequenced This Year”, Timmerman, “DNA Sequencing Market Will Exceed $20 Billion, Says Illumina Ceo Jay Flatley”.
[xii] Pear, Robert. 2018. “Medical Research? Congress Cheers. Medical Care? Congress Brawls”. New York Times January 6.
[xiii] Harmon, Amy. 2018. Why White Supremacists Are Chugging Milk (And Why Geneticists Are Alarmed). New York Times. October 17. https://www.nytimes.com/2018/10/17/us/white-supremacists-science-dna.html