Genetic screening: Evolving science, evolving ethics

John D. Lantos M.D., Director

Children’s Mercy Bioethics Center

Children’s Mercy Hospital, KCMO

COPYRIGHT 2012

A new era in genomics and medicine?

• Human genome project

• Direct-to-consumer genomics

• Intellectual property disputes– Moore– Catalona – Myriad Genetics– Henrietta Lacks

• Personal Genome Project

Past fears

• Eugenics– Nazi abuses – Racial stereotypes/profiles – Bell Curve

• Compulsory sterilization

• Genetic determinism

• The 20th century saw horrific genocides inspired by Nazi pseudoscience about genetics and race. It also saw horrific genocides inspired by Marxist pseudoscience about the malleability of human nature. Two of the groups who were historically most victimized by racial pseudoscience — Jews and African-Americans — are among the most avid consumers of information about their genes.

– Steven Pinker

Fears seem to be receding

Is genetic information different?

• My family history

• My blood pressure and cholesterol level

• My psychiatric history

• The meds in my medicine cabinet

• My tax returns

• Records of my web searches

Who should have access?

• Only doctors

• Doctors and patients

• Family members

• Researchers

• Insurance companies

• The world

Key ethical questions

• Can laws, rules, and morals be imported from other domains to “cover” genomics?

Personal Genome Project

• Ten individuals agree to make their genome and their health records public.

• “volunteers…willing to share their genome sequence and many types of personal information with the research community and the general public, so that together we will be better able to advance our understanding of genetic and environmental contributions to human traits.”

To encourage the development of personal genomics technology and practices that:

- are effective, informative, and responsible; - yield identifiable and improvable benefits at manageable levels of risk; and- are broadly available for the good of the general public

MISSION

Three people wrote about being participants in the PGP

Misha Angrist

Steven Pinker

Richard Powers

Personal Genome Project

• Harvard IRB:– All subjects must have Masters in genetics– Subjects told that there would be no privacy– Subjects agree to disclose health information

Informed Consent

• Your posted genomic and medical information could be used to: – Infer paternity– Claim statistical evidence that could affect your

employment or insurability– Claim your relatedness to infamous villains– Synthesize DNA and plant it at a crime scene– Reveal propensity for a disease

• “Did I really want my genome to be available to everyone via a mouse click when I clearly didn’t feel that way about other aspects of my life…My therapist speculated that maybe my whole foray into the land of public genomes was just another form of acting out.”

• Misha Angrist

Risks

Risks

• There are risks of misunderstandings, but there are also risks in much of the flimflam we tolerate in alternative medicine, and in the hunches and folklore that many doctors prefer to evidence-based medicine.

– Pinker

Risks

• “Personal genomics is just too much fun.”– Pinker

Risks

• Curiosity may be just suspicion co-opted by endorphins. I had no idea what I was blundering into. But I figured I could start learning now about privacy and public good, research and entrepreneurship, risk and susceptibility—all the dangers of knowing the full story—or I could bump up against them later, along with the rest of unwitting humanity.

– Richard Powers

Complexity

• Assessing risks from genomic data is not like using a pregnancy test kit. It’s more like writing a term paper on a topic with a huge and chaotic research literature. You are whipsawed by contradictory studies with different sample sizes, ages, sexes, ethnicities, selection criteria and levels of statistical significance.

– Steven Pinker

Life-changing?

• “In the end, this journey of self-exploration had turned out to be more of a speculative intellectual exercise than a life-changing clinical one.”

• “My own genome was no longer an abstraction for me, but neither was it an immediate revelation.”

– Misha Angrist

Genes and identity

• I soon realized that I was using my knowledge of myself to make sense of the genetic readout, not the other way around.

– Steven Pinker

Dealing with bad news

• We know what happens to people who do get the worst news. They don’t sink into despair or throw themselves off bridges; they handle it perfectly well. Most of us cope using some combination of denial, resignation and religion.

– Steven Pinker

• People who have grown up with the democratization of information will not tolerate paternalistic regulations that keep them from their own genomes.

– Steven Pinker

The Future

Genotype and phenotype

• When the connection between the ACTN3 gene and muscle type was discovered, parents and coaches started swabbing the cheeks of children so they could steer the ones with the fast-twitch variant into sprinting and football.

– Steven Pinker

Genotype and phenotype

• Carl Foster, one of the scientists, had a better idea: “Just line them up with their classmates for a race and see which ones are the fastest.”

– Steven Pinker

• If you want to know whether you are at risk for high cholesterol, have your cholesterol measured; if you want to know whether you are good at math, take a math test.

– Pinker

Genotype and phenotype

• If you really want to know yourself, consider the suggestion of François La Rochefoucauld: “Our enemies’ opinion of us comes closer to the truth than our own.”

– Pinker

Genotype and phenotype

The Experimental Man Project

Online and Book

First Step: Visit My Internist

Prognosis after routine check-up: • Healthy• Borderline high cholesterol• Heart attack risk: 4 percent risk 10 years

The ExperimentThe Experiment

• Number of labs, companies: ~250

• Amount of blood drawn, in liters: ~2

• Hours spent in an MRI: 22

• Number of chemical toxins tested for: 320

• Gene markers tested, in millions: 7 – 10

• Gigabytes of data produced: ~100

• Cost: ~$150,000

GENESGENES

Blood, Spit, and Swabs

ENVIRONMENTENVIRONMENTENVIRONMENTENVIRONMENT

Labs: Axyss Analytical, Quest Diagnostics

Chemicals Tested: 320Detected: 165 Cost: $15,000

Chemical Report Card

Duncan D.E.,National Geographic, 2006

BRAINBRAIN

BODYBODY

Copyright 2008 Entelos, Inc.

Scans: Ultrasound and CTCarotid and Chest(Part of a full-body scan)

Still going… more tests

My Proteomic Scan

Microbial Scan (Coming)

Conclusion

• “I ought to lose 10 pounds…”

• I’m flooded with the memory of the books:– Madame Bovary, with its subplot of private

medical research gone horribly wrong.– Middlemarch, with its search for the Key to All

Mythologies. – The Magic Mountain, whose hero, convinced

that the newly discovered X-rays are a glimpse inside people’s souls, carries around an X-ray photograph of his beloved as a kind of erotic fetish.

– Richard Powers

Nothing new

• A few years from now, people may carry around their loved ones’ personal genomes on USB key fobs.

– Powers

The Future

• “Just like with personal computing, until there are some compelling stories involving real products, the only people who are going to get what’s happening are the ones who can imagine things that aren’t yet there.”

– George Church

The Future

• Most hunters and gatherers would never have been able to wrap their heads around the concept of a supermarket. The naysayers would have insisted that landing food was always going to remain probabilistic, that no amount of technology would ever make the satisfaction of hunger anything more than a matter of chance. “But the naysayers were wrong.”

– Richard Powers, on George Church

Why?

• Personal genomic medicine is not merely about saving lives; it’s a more complicated, ambiguous story, one dating back to the start of technological time: the gradual replacement of luck with control. Once upon a time, we were dealt a hand by Fate, God, or the Unreliable Narrator, and the task of life was to deal with that hand. Now the task is to improve the deal.

– Richard Powers

Personalized Genomics

• A vague sense of promise

• Ambiguous benefits

• Vague (and mostly unrealized) fears

• A technology in search of an application

Ethics Too soon for

conclusions New ideas about self,

privacy, medicine, and freedom.

Evidence-based ethics

• Ethics should reflect human values and human experience

• Crucial to understanding the meaning of the new genetics to the people who want it, need it, and use it.

• Ethics should shape technology, but only with good feedback loops.

Money

• There seems to be no end of money that might be made from the molecularization of human health.

– Richard Powers