Lost in “Translation”

Eric T. Juengst, Ph.D.Eric T. Juengst, Ph.D.Center for BioethicsCenter for Bioethics

University of North Carolina at Chapel HillUniversity of North Carolina at Chapel Hill

Translation in Healthcare ConferenceOxford University

June 23, 2015

Three Senses of “Translation”:

1. Elijah’s translation to heaven

Features:

SpontaneousMiraculousBased on virtue

Challenges:

Faith-basedTemptation risksUnreliable

Three Senses of “Translation”:

2. DNA’s translation into protein

Features:

SpontaneousMechanicalBased on necessary conditions

Challenges:

ResourcesSpeedMistakes

Three Senses of Translation

3. Translation of ideas between languages

Features:

IntentionalImperfectBased in negotiation

Challenges:

MisunderstandingsConnotationsPolitics/Ethics/Etiquette

PreviewPreview

““Personalized” to “Precision”Personalized” to “Precision”

Tailored therapy to risk stratificationTailored therapy to risk stratification

Coincidental trends, marked and masked:Coincidental trends, marked and masked:– Patient empowerment to expert gatekeepingPatient empowerment to expert gatekeeping– Individual to population research frameIndividual to population research frame– Elective to expected research participationElective to expected research participation

Two examples for discussionTwo examples for discussion

Reinterpreting “personalized medicine” as Reinterpreting “personalized medicine” as “precision medicine”.“precision medicine”.

Reinterpreting “intellectual property” as Reinterpreting “intellectual property” as “genomic soveriegnty”.“genomic soveriegnty”.

 

“We are on the leading edge of a true revolution in medicine, one that promises to transform the traditional “one size fits all” approach into a much more powerful strategy that considers each individual as unique and as having special characteristics that should guide an approach to staying healthy”

(Collins 2010: xxiv). 

“Personalized medicine” may be thought of as tailoring medical treatment to the individual characteristics, needs, and preferences of each patient” p.4.

PredictivePredictive– Proactive, through risk profiling and forecastingProactive, through risk profiling and forecasting

PreventivePreventive– Pre-emptive, through early detection and Pre-emptive, through early detection and

interventionintervention

PersonalizedPersonalized– Precisely-targeted, “individualized” via molecular Precisely-targeted, “individualized” via molecular

identityidentity

ParticipatoryParticipatory– Patient-centered, empowering patients to Patient-centered, empowering patients to

become actively involved in carebecome actively involved in care

As the Personalized Medicine Coalition stresses in describing PHC, “it is proactive and participatory, engaging patients in lifestyle choices and active health maintenance to compensate for genetic susceptibilities.”

(PMC 2009: 2)

“Patient empowerment” as a cardinal virtue of participatory PGM

“The success of personalized medicine will come about only when we each take responsibility for our health. Health care providers can help, but they cannot drive your bus. Each chapter of this book has concluded with a list of things you can do now to take full advantage of the potential for personal empowerment. If you follow these recommendations, you will truly be on the leading edge of this new revolution. But the edge will keep moving, and so it will be essential to upgrade your own knowledge base periodically.”

(Collins 2010: 278)

“Personalized medicine” refers to the tailoring of medical treatment to the individual characteristics of each patient. It does not literally mean the creation of drugs or medical devices that are unique to a patient, but rather the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment.” PCAST, 2008

The limitation in trying to reach the goal of having a unique medicine for every individual for every disease is that it is simply not practical. It’s not practical from a research perspective nor is it practical from a pharmaceutical or diagnostic perspective.

The reality of how patients behave is that they do respond differently, and these responses can be organized into groups. The first step to improving healthcare is to identify what those groups look like, how to cluster individuals within a group and then manage the behavior in terms of the clinical response of that group both for diagnosis and treatment.

If we can’t get to treating patients in groups, then the hope of driving it even further into a personalized – completely personalized type of medication is going to be well beyond our reach.

In the UK: “Strategic” or “Stratified” Medicine

“I think “personalized medicine” was perhaps a useful rubric with which to launch this activity, but it sends a misleading message – actually both to ourselves and the broader community” Maynard Olson, Nov., 2012

“With the term “precision medicine” we are trying to convey a more precise classification of disease into subgroups that in the past were lumped together because there wasn’t a clear way to discriminate between them.” Charles Sawyer, IOM committee co-chair

2012: Personalized Medicine is Dead! Viva Precision Medicine!

NAS/IOM report, 2011 starts a rebranding trend

PredictivePredictive– Proactive, through risk profiling and forecastingProactive, through risk profiling and forecasting

PreventivePreventive– Pre-emptive, through early detection and Pre-emptive, through early detection and

interventionintervention

Personalized?Personalized?– Precisely-targeted, “individualized” via molecular Precisely-targeted, “individualized” via molecular

identityidentity

ParticipatoryParticipatory– Patient-centered, empowering patients to become actively Patient-centered, empowering patients to become actively

involved in careinvolved in care

3

I.e., “3P Medicine,”

The fine print in PGMThe fine print in PGM

–““allowing healthcare allowing healthcare professionals to customize professionals to customize your treatment for what your treatment for what works best for you” so that works best for you” so that “your physician can treat “your physician can treat you with greater precision, you with greater precision, fewer side effects and with fewer side effects and with better results” better results”

“Medicine is, at least to some extent, an inherently paternalistic endeavor simply because of an inevitable asymmetry in knowledge and because those who practice medicine pledge to avoid causing harm”.

Jim Evans and Jonathan Berg, “Next Generation DNA Sequencing, Regulation, and the Limits of Paternalism” Genetics in Medicine, 2011.

““The application of comprehensive genotype and The application of comprehensive genotype and functional genomic measurements across the functional genomic measurements across the general population is likely to yield unexpected general population is likely to yield unexpected incidental findings for nearly everyone.incidental findings for nearly everyone.””

Kohane, Masys, Altman, Kohane, Masys, Altman, ““The Incidentalome: A Threat to The Incidentalome: A Threat to Genomic Medicine” Genomic Medicine” JAMAJAMA 296(2006):212 296(2006):212

PredictivePredictive– Proactive, through risk profiling and forecastingProactive, through risk profiling and forecasting

PreventivePreventive– Pre-emptive, through early detection and Pre-emptive, through early detection and

interventionintervention

Personalized?Personalized?– Precisely-targeted, “individualized” via molecular Precisely-targeted, “individualized” via molecular

identityidentity

Participatory?Participatory?– Patient-centered, empowering patients to become actively Patient-centered, empowering patients to become actively

involved in careinvolved in care

2

Comparative Population Genomics as the lensComparative Population Genomics as the lens

““Variation mapping” to identify biological differences (environmental Variation mapping” to identify biological differences (environmental adaptations and common susceptibilities) between human groups adaptations and common susceptibilities) between human groups and trace population historyand trace population history– via haplotype mapping and sequence comparisionsvia haplotype mapping and sequence comparisions– Traditionally: in order to facilitate public health planning Traditionally: in order to facilitate public health planning

(“genetic epidemiology”) and advance understanding of how (“genetic epidemiology”) and advance understanding of how groups are related (“molecular anthropology”)groups are related (“molecular anthropology”)

– Now: for clues to drug discovery and comparative outcomes Now: for clues to drug discovery and comparative outcomes across genotypesacross genotypes

“The hope of course here is that we’ll be able to subcategorize people into ever smaller groups that can be more targeted in terms of how a diagnosis is done, what a diagnosis means, what treatment would apply, what side effects that subgroup might experience. … The day will likely never come when each individual has something specificially done for them, but I think these groups or subgroups will get increasinlgy smaller as we learn and have higher resolution genomic information” --genomic scientist

As a result… more genomic research framed in terms of social groups

Mexico and India embrace concept of Mexico and India embrace concept of “genomic sovereignty” to regulate export “genomic sovereignty” to regulate export and ownership of biobank samples.and ownership of biobank samples.– ““Genetic Sovereignty Amendment to Health Law: “Mexican-Genetic Sovereignty Amendment to Health Law: “Mexican-

derived human genome data are property of Mexico’s derived human genome data are property of Mexico’s government and prohibits its collection, use and export without government and prohibits its collection, use and export without prior government approval” prior government approval”

Achieving the goals of precision medicine will also require advancing the nation's regulatory frameworks. To unleash the power of people to participate in research in innovative ways, the NIH is working with the Department of Health and Human Services to bring the Common Rule, a decades-old rule originally designed to protect research participants,5 more in line with participants' desire to be active partners in modern science. To help speed the translation of such discoveries, the Food and Drug Administration is working with the scientific community to make sure its oversight of genomic technology supports innovation, while ensuring that the public can be confident that the technology is safe and effective.

https://www.whitehouse.gov/blog/2015/01/30/precision-medicine-initiative-data-driven-treatments-unique-your-own-body

The real The real ““paradigm shiftparadigm shift”” from genomics?from genomics?

““We must dispense with old models of research support and regulatory We must dispense with old models of research support and regulatory guidance designed for the pre-Human Genome Project worldguidance designed for the pre-Human Genome Project world””

– Kathy Hudson, Kathy Hudson, ““The Health benefits of genomics: Out with the old, in The Health benefits of genomics: Out with the old, in with the newwith the new”” Health Affairs 27(2008): 1612-1615. Health Affairs 27(2008): 1612-1615.

““We cannot assume that all social goals will be met through a lemming-like We cannot assume that all social goals will be met through a lemming-like coincidence of universal consent. We must address consentcoincidence of universal consent. We must address consent’’s conflicts with s conflicts with other values, even as we try to maximize both autonomy and social goods.other values, even as we try to maximize both autonomy and social goods.””

– Patrick Taylor, Patrick Taylor, ““When consent gets in the wayWhen consent gets in the way”” Nature 456(2008): 32- Nature 456(2008): 32-33.33.

““Participation in research is a critical way to support an important public Participation in research is a critical way to support an important public good. Consequently, all have a duty to participategood. Consequently, all have a duty to participate””

– Shaefer, Emanuel, Wertheimer, Shaefer, Emanuel, Wertheimer, ““The Obligation to parrticipate in The Obligation to parrticipate in biomedical researchbiomedical research”” JAMA 302 (2009): 67-72. JAMA 302 (2009): 67-72.

In Conclusion:

The weakness of “personalized medicine” as a promissory label for the new paradigm genomics brings to health case is that it promises more than genomics can actually deliver: increased patient empowerment and participation.

“Precision medicine” correctly takes the focus of genomic medicine off of the patient, but in the process flags other emerging concerns. To the extent that it connotes “precision equipment” and privileges medical expertise, it encourages professional claims to authority and threatens the ethos of shared decision-making. To the extent that it echoes “precision bombing” and targets human groups as the key units of analysis for genomic medicine, it encourages a socially risky essentialism, and encourages genomic nationalism.

Both of these trends of visible in current debates over the governance of genomic medicine and translational genomic research.