Lecture 6 — Genomics and Enhancement

Part A: Reading Genomes — Prediction, Privacy, and Dual Use

Brendan Shea, PhD

An Introduction to Bioethics.

Would You Sign?

You are a parent on the postpartum floor, twelve hours after a healthy delivery. A research nurse offers to read your newborn’s whole genome at no cost. The report, returned in two weeks, will list gene variants linked to several hundred conditions. Some are treatable in childhood. Some show up only in adulthood. Some are of uncertain meaning. Your partner is leaning yes. You want to ask more questions first.

Write or discuss:

1. Which of those three kinds of result would you want to receive, and which would you rather not know?
2. Does your answer change if the test is offered at the six-year visit instead?
3. Whose decision is this — yours, your partner’s, or the child’s own, twenty years from now?

The question underneath is the time-shape of genetic information: a decision made today binds a person for life.

After You’ve Discussed

Note

• Actionable now — a finding the family can act on in childhood (a treatable metabolic condition).
• Actionable later — a finding that matters in adulthood, when the child can decide for herself whether to know (BRCA1, late-onset Alzheimer’s risk).
• Informative but not actionable — a finding that names a risk no one can act on yet (some Huntington’s variants in a healthy infant).

Today

By the end of Part A, you will be able to:

• Tell the story of the Human Genome Project and the gap between what was promised in 1999 and what arrived.
• Define geneticization and spot it in prenatal testing, ancestry kits, and forensic genealogy.
• Explain ancestry bias in polygenic risk scores.
• Apply Feinberg’s open future to genetic testing of children.
• State the NASEM 2023 rule on race and genetic variation.
• Describe what GINA (2008) covers and what it does not.

The Human Genome Project: Promise and Aftermath

Thirteen Years, Two Teams

• The Human Genome Project was a public, international effort led by the NIH and the Department of Energy, begun in 1990.
• In 1998 a private company, Celera Genomics, run by Craig Venter, said it would finish first with a faster “shotgun” method.
• The race ended in a declared tie at the White House in June 2000. The public group kept the data free; Celera dropped its plan to sell access.

Promised vs. Delivered

Collins predicted by 2010	What 2026 actually has
Routine cheek-swab risk prediction for common diseases	A small set of strong single-gene tests; broad risk prediction still uneven
Drugs dosed by genotype	A few dozen drug-gene pairs in use; far fewer than promised
Twelve common conditions with usable predictive tests	Several, but most predict only modest risk
Genetic privacy laws “fully in place”	GINA 2008 covers health insurance and employment only
Public catching up with the science	Ancestry-kit marketing still routinely overpromises

Francis Collins, the project’s director, made these predictions in 1999 (Collins 1999).

Geneticization

Three Related Pulls

• Geneticization, Abby Lippman’s 1991 term: the tendency to cast human differences, risks, and identities as mostly genetic, and to reach for genetic fixes (Lippman 1991).
• Genetic reductionism: the working assumption that the gene is the right level at which to explain a trait. Sometimes useful; often overshoots.
• Genetic determinism: the stronger claim that genes fix outcomes. Almost no working geneticist believes it; it lives mostly in marketing copy.

Gene × Environment — the Working Picture

• The textbook case is phenylketonuria (PKU). It causes severe intellectual disability, but only if the diet contains phenylalanine.
• Find the gene at birth, change the diet, and the disability never appears. Same DNA, different outcome.
• Diabetes, heart disease, and depression sit closer to the PKU end than popular framing suggests.

Four Words

Term	What it means
Gene	A stretch of DNA that codes for a working product (usually a protein). Humans have about 20,000.
Allele	One of the possible versions of a gene at a given spot. You get one from each parent.
Genome	The full set of DNA in an organism’s cells — about 3.2 billion base pairs in humans.
Variant	Any place where one person’s DNA differs from a reference sequence. Most variants do nothing visible. A few do a lot.

The older word mutation is still used, but variant has largely replaced it. “Mutation” carries an unhelpful hint that the difference is always bad.

Whose Genome Is the Reference?

A Reference Built from Two Men

• When a lab says a patient has “a variant,” it means her DNA differs from the human reference genome, a published sequence everyone is compared against.
• The public reference is roughly 74% from one anonymous man in Buffalo, New York, known as “RP11.” He was paid $50 and never knew he was the main donor.
• Celera’s reference is roughly 71% Craig Venter himself, who quietly added his own DNA to the donor pool.
• For about twenty years, the standard for billions of human genomes was mostly two men (Gannett 2023).

Why It Matters: Ancestry Bias

A genome-wide association study (GWAS) compares the DNA of thousands of people with a trait to thousands without. Who took part, cumulatively, by the mid-2010s:

• ~80% European ancestry
• ~10% Asian ancestry
• ~3% African ancestry
• ~1% Hispanic / Latin American

• A polygenic risk score for coronary disease built on this data is about 4–5× more accurate in people of European ancestry than in people of African ancestry.
• The math is not biased. The training data was.
• The fix is a pangenome: many reference genomes instead of one. The first draft, in 2023, had 47.

(Popejoy and Fullerton 2016)

What Gets Tested, and When

Three Kinds of Genetic Testing

Type	Who is tested	What it tells you
Diagnostic	A patient with symptoms	Whether their disease has a known genetic cause
Predictive	A healthy person at risk	Their chance of developing a disease later
Reproductive	A future parent, fetus, or embryo	Whether a future person is likely to be affected

The same lab test can be used for any of the three. What changes is who is asking, on whose behalf, and what they will do with the answer.

NIPT

• Non-invasive prenatal testing (NIPT) reads fetal DNA floating in the mother’s blood, from about ten weeks.
• It is screening, not diagnosis. A confirming test, usually amniocentesis, is needed before any permanent decision.
• After a confirmed Down syndrome diagnosis, the US termination rate is above 60%; in Denmark and Iceland it is close to 95%. NIPT made that question routine.

Testing Healthy Children for Adult-Onset Conditions

BRCA in a healthy eight-year-old

• The risk is real, but does not become actionable until her twenties or thirties.
• The result will follow her through every insurance form and school record for two decades before she can act on it.
• The American Society of Human Genetics has long advised against testing children for adult-onset conditions with no childhood treatment.

Huntington’s in a healthy eight-year-old

• A near-certain prediction of a fatal brain disease in midlife.
• No treatment. No prevention.
• The professional view is even firmer: do not test.
• Yet some adult Huntington’s patients say they wish they had been told earlier. Others say the opposite.

The same rule, applied twice, gives the same answer for different reasons.

Feinberg’s “Open Future,” Applied to Information

Feinberg’s right to an open future

The legal philosopher Joel Feinberg argued that children hold a class of “rights in trust.” These are autonomy rights they cannot yet use, but which adults must keep open on their behalf. Parental choices that close off a future the child might have chosen are, on this view, a distinct kind of wrong.

The first uses were about things like religion and schooling. Applied to genetic information, the rule is simple: don’t fix the meaning of an adult-onset risk before the future adult can decide whether to know it.

The same adult, twenty years later, can walk into a clinic and ask.

ACMG vs. AAP — Two Positions

	American College of Medical Genetics	American Academy of Pediatrics
Default frame	Sequencing is cheap; expanding the panel of conditions returned is the responsible move	The longstanding rule against testing healthy children should not erode with technology
What to report	A regularly updated list of “medically actionable” findings, including some adult-onset	Conditions with a childhood treatment, by preference
Why	Information delayed is treatments missed	Information returned is futures narrowed
Direction of pressure	Expand the panel	Hold the line

Two mainstream bodies disagree, in public, about the question this lecture opened with.

Consumer Genomics

23andMe

• Founded 2006; cleared by the FDA as a home health test in 2017. About 14 million customers by 2023, most for ancestry rather than health.
• 2023: attackers reused leaked passwords to break into accounts. Through the “DNA Relatives” feature, each broken account exposed relatives who were never hacked. About 6.9 million users were affected.
• 2025: the company filed for bankruptcy, and its genetic database was sold as an asset for $305 million to a nonprofit led by its own co-founder (23andMe 2025).
• Bankruptcy law, not medical-privacy law, decided who would hold 14 million people’s DNA.

What happens to your DNA if the company goes under? For years the standard privacy worry about consumer genomics was hypothetical: what happens to your DNA if the company goes under? In 2025 we found out.

23andMe entered Chapter 11, and its genetic database went to auction like any other asset. After competing bids — including one from the pharmaceutical company Regeneron — the winner was TTAM Research Institute, a nonprofit founded and led by Anne Wojcicki, 23andMe’s own co-founder, for $305 million. The sale closed in July 2025, and the service continues to operate (23andMe 2025).

The outcome was comparatively benign: a nonprofit with privacy commitments rather than a data broker or an insurer. But notice what the process established regardless of who won. Your genome, once handed to a company, is property on a balance sheet. Bankruptcy law, not medical-privacy law, determined who ended up holding 14 million people’s DNA — and the customers were creditors’ collateral, not parties to the decision. Consent given to one company in 2015 transferred to a different legal entity a decade later.

Write or discuss: You consented to research with Company A. Company A is liquidated and your data goes to Entity B. Is your original consent still valid? What would a consent form have to say up front for the answer to be clearly yes — and would anyone sign it?

NASEM 2023 — The Headline Rule

Important

Recommendation 1. “Researchers should not use race as a proxy for human genetic variation. In particular, researchers should not assign genetic ancestry group labels to individuals or sets of individuals based on their race, whether self-identified or not.”

— National Academies of Sciences, Engineering, and Medicine, Using Population Descriptors in Genetics and Genomics Research (2023), Summary, Rec. 1.

• Race is a social-political category that shifts by country and era. Human genetic variation is continuous, not discrete.
• An ancestry kit’s “23% Italian” has a precision the science does not support.
• The report also retires Caucasian, a term coined in 1795 by Blumenbach to rank a skull he found beautiful (National Academies of Sciences, Engineering, and Medicine 2023).

Forensics and Discrimination

GEDmatch and the Golden State Killer

Important

Joseph James DeAngelo, 2018

Between 1973 and 1986, one offender committed at least 13 murders and dozens of rapes across California. The case went cold for thirty years. In 2018, a Sacramento team uploaded a DNA profile from a 1980 crime scene to GEDmatch, an open genealogy site used mostly by hobbyist family-tree researchers.

The profile matched several of DeAngelo’s distant cousins. None of them had any idea their saliva tubes could finger a relative for murder. Investigators built family trees from the matches, narrowed to DeAngelo, picked up DNA from his car door handle, and arrested him.

He pleaded guilty in 2020.

With a few million users in a database, some third or fourth cousin of almost any American is in it. Staying out yourself does not keep you out of the searches it enables.

Thought Question — Whose Consent?

Your second cousin — someone you have met twice in your life — uploads her saliva to a genealogy site. Six years later, investigators use her upload to identify you as a suspect in a thirty-year-old assault case. They are right; you did it. You are arrested, charged, and convicted.

Write or discuss.

1. Did you have a privacy interest that was violated, given that your own DNA was never tested?
2. Does the answer change if you are innocent and were briefly a suspect before being cleared?
3. Does it change if the crime is a serial murder vs. a thirty-year-old simple assault?

GINA (2008) and Its Gaps

The Genetic Information Nondiscrimination Act is the federal floor against genetic discrimination. It covers two things only.

	Covered by GINA?
Health insurance	Yes
Employers with 15 or more workers	Yes
Life, disability, and long-term-care insurance	No: insurers may ask for genetic results and price on them
Smaller employers	No
US military	No

In 2020 Florida became the first state to extend protection to life, disability, and long-term-care insurance.

Geneticization, Five Times Over

Where it shows up	What gets read as genetic	What gets read out
NIPT + the >90% question	Fetal trisomy	What life with Down syndrome actually looks like
23andMe ancestry	“23% Italian” — discrete national identities	The continuous geographic gradients beneath the labels
Polygenic risk scores	Disease risk as a number	The training-data ancestry that set how accurate the number is
Race in research	Genetic variation as racial-group difference	The environment and history that track race in the US
Forensic genealogy	A suspect’s identity from distant-cousin matches	The non-suspect relatives whose DNA was searched without consent

Review Questions

Write a brief answer to each, or use them as discussion prompts.

Recall

Define geneticization in your own words. Then explain why polygenic risk scores work better for people of European ancestry than for everyone else.

Apply

A 34-year-old whose mother died of ovarian cancer brings a 23andMe report flagging two BRCA1 variants. What should her care team do before any discussion of preventive surgery? Which of those steps is the one a 23andMe report cannot replace?

Debate

Should police need a warrant before searching genealogy databases for a suspect’s relatives? Take a side, then name the strongest argument on the other side.

Key Terms

• Geneticization — Lippman’s term for the cultural tendency to explain human differences, risks, and identities primarily in genetic terms, and to favor genetic interventions as the preferred solution to health problems.
• Genetic determinism — the strong claim that genes fix outcomes — that DNA is destiny — regardless of environment; almost no working geneticist defends it in this form, but it persists in popular and marketing framings.
• Germline vs. somatic — germline changes occur in reproductive cells and are inherited by every descendant; somatic changes occur in non-reproductive tissue of one person and die with that person.
• Genome-wide association study (GWAS) — a research method that scans the DNA of thousands of people with and without a trait to identify variants statistically linked to it; results work best in the ancestry group the study was run on.
• Polygenic risk score — a number calculated by adding up the small effects of thousands of variants across the genome to estimate an individual’s risk for a complex trait; accuracy depends heavily on whether the training population matches the person being scored.

• NIPT — non-invasive prenatal testing; reads fragments of fetal DNA floating in the mother’s blood from about ten weeks of pregnancy to screen for chromosomal conditions like trisomy 21; a screening result, not a diagnosis, and requires confirmatory testing before any permanent decision.
• Open future (Feinberg) — Feinberg’s principle that children hold autonomy rights “in trust”; adults must keep those futures open rather than foreclosing choices — including the choice of whether to know one’s genetic risks — before the child can make them herself.
• Population descriptor (NASEM) — a label used to group people in genetics research; the 2023 NASEM report recommends using geographic ancestry or genetic similarity rather than race as a stand-in for genetic variation, since race is a social-political category, not a biological one.
• Investigative genetic genealogy — a forensic technique that uploads a crime-scene DNA profile to a consumer genealogy database, identifies distant-cousin matches among users, and builds a family tree to narrow to a suspect; used to solve the Golden State Killer case in 2018.
• GINA — the Genetic Information Nondiscrimination Act (2008); bars health insurers and employers from using genetic information against people, but does not cover life, disability, or long-term-care insurance, or the US military.

References

23andMe. 2025. 23andMe Receives Court Approval for Sale to TTAM Research Institute, a Nonprofit Public Benefit Corporation. 23andMe Media Center. https://mediacenter.23andme.com/press-releases/23andme-receives-court-approval-sale-ttam-research-institute/.

Collins, Francis S. 1999. “Shattuck Lecture — Medical and Societal Consequences of the Human Genome Project.” New England Journal of Medicine 341 (1): 28–37. https://doi.org/10.1056/NEJM199907013410106.

Gannett, Lisa. 2023. The Human Genome Project. The Stanford Encyclopedia of Philosophy (Fall 2023 Edition), Edward N. Zalta and Uri Nodelman (eds.). https://plato.stanford.edu/archives/fall2023/entries/human-genome/.

Lippman, Abby. 1991. “Prenatal Genetic Testing and Screening: Constructing Needs and Reinforcing Inequities.” American Journal of Law & Medicine 17 (1–2): 15–50.

National Academies of Sciences, Engineering, and Medicine. 2023. Using Population Descriptors in Genetics and Genomics Research: A New Framework for an Evolving Field. The National Academies Press. https://doi.org/10.17226/26902.

Popejoy, Alice B., and Stephanie M. Fullerton. 2016. “Genomics Is Failing on Diversity.” Nature 538 (7624): 161–64. https://doi.org/10.1038/538161a.