From the event "Specimen Science: Ethics and Policy Implications," held at Harvard Law School on November 16, 2015. This event is a collaboration between The Center for Child Health and Policy at Case Western Reserve University and University Hospitals Rainbow Babies & Children’s Hospital; the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School; the Multi-Regional Clinical Trials Center of Harvard and Brigham and Women's Hospital; and Harvard Catalyst | The Harvard Clinical and Translational Science Center. It is supported by funding from the National Human Genome Research Institute and the Oswald DeN. Cammann Fund at Harvard University. For more information, visit our website at http://petrieflom.law.harvard.edu/events/details/specimen-science-ethics-and-policy

1. Research with Biospecimens:
A Brief History
Elisa A. Hurley, Kimberly Hensle Lowrance,
and Avery Avrakotos
Specimen Science
Petrie Flom Center, Harvard Law School
November 16, 2015

2. Four Seminal Cases
 Moore v. the Regents of the University
of California
 Havasupai Indian Tribe
 Henrietta Lacks
 Residual newborn bloodspots lawsuits

3. Moore v. the Regents of the University
of California: Tissue Ownership
 1976, John Moore diagnosed with “hairy-cell
leukemia.”
 Treatment at UCLA
 Consented to having his spleen removed; unbeknownst to
him, Dr. Golde keeps his tissue for research
 1983 consent form: “I (do, do not) voluntarily
grant to the University of California all rights I, or
my heirs, may have in any cell line or potential
product which might be developed from the blood
and/or bone marrow obtained from me.”

4. Moore, contd.
 Moore’s lawyer discovers University of
California patent on an immortal cell
line derived from Moore’s tissues
 1984: Moore sues, becoming “the first
person to legally stake a claim to his
own tissue and sue for profits and
damages” (Skloot 2010, 203)

5. Moore court case
CA Supreme Court:
 Once tissue has left a person’s body—
regardless of whether consent provided—it
is no longer owned by that person, and
therefore person cannot control it.
 Thus people have no claim to the
commercial profits that may result from use
of their tissues.

6. NPRM says…
 Where applicable, informed consent
forms must include a statement:
• that the subject’s biospecimens may be
used for commercial profit, and
• whether the subject will or will not share in
that commercial profit.

7. Havasupai Indian Tribe: broad
consent and group harms
 1980s: Havasupai Tribe facing very high rate of
Type 2 Diabetes
 1990: ASU researchers collected blood to look
at DNA
 Inconsistencies in informed consent
 Tribe members believed that the specimens
would only be used for diabetes research

8. Havasupai case, contd.
 200 blood samples taken from the Havasupai shared
extensively for research on schizophrenia,
population migration, and inbreeding
 In 2004: Tribe files a lawsuit against the research
and ASU
 At center of case: “whether the secondary uses of
the Havasupai’s samples fell within the scope
their initial informed consent” (Mello and Wolf
2010).

9. Current regulatory context
 Prospective collection of biospecimens for research
typically constitutes human subjects research, because it
involves an interaction an individual (45 CFR 46.102),
and consent is therefore required.
 However, if a biospecimen was collected for purposes
other than the current research (i.e., for another study or
in a clinical encounter), it is permissible to conduct
research on that biospecimen (“secondary research”)
without consent, as long as the specimen is not
individually identifiable (45 CFR 46.102; OHRP 2008)
• In fact, such an activity does not meet the definition of human
subjects research.

10. Havasupai case and group harms
 Regulations focus on risks of research to individuals
• Risk that we could learn information about an individual
 Implication: if samples are stripped of identifiers,
then there are no risks
 Doesn’t account for group harms:
• When secondary biospecimen research is designed to
study a small population group, it has the potential to result
in stigmatizing findings regarding that group, even if
individual samples are de-identified

11. Havasupai case and broad
consent
 Researchers (in some cases) sought “broad” consent when
they collected the tribe members’ blood (research on the
“causes of behavioral/medical disorders”).
 Tribe members objected when learned the kinds of research
done with their samples.
 Common criticism of broad consent: Doesn’t provide
potential subjects with sufficient information to enable giving
meaningful consent.
 If the NPRM proposals go through, broad consent will be
required for all biospecimen research (identifiable or not).

12. Henrietta Lacks case:
Emerging public consensus about consent
 1951: Henrietta Lacks diagnosed with cervical cancer at
Johns Hopkins
 While under anesthesia, two piece of cervical tissue
taken without her consent
 Using the cells from Lacks’s tumor, George Gey
created the first “immortal” cell line (HeLa)
 HeLa cells are to this day the world’s most commonly
used human cell
 Lacks died in 1951; her family didn’t learn anything
about the use of her cells for over 20 years

13. Lacks case, contd.
 2010: Lacks’s story comes to light in Rebecca
Skloot’s The Immortal Life of Henrietta Lacks
 Widespread condemnation of how the research
establishment treated Lacks and her family.
 Unethical not to have asked permission or at least informed
and educated her family about the existence of her cells and
their uses.
 Though much of what happened to Henrietta
Lacks and her cells is still permitted by the regs

14. Lacks case contd.
 2013: German research team posts genome of a
HeLa cell line on an open-access database, again
without consulting the Lacks family.
• Researchers agree to remove the sequence from the public
database until NIH leadership forge an agreement with the
Lacks family
 Henrietta Lacks becomes flashpoint for emerging
consensus:
• regulations governing research with biospecimens are out
of step with public attitudes
• People should be asked about use of their biospecimens

15. Expanding the Definition of HSR:
Use of Residual Newborn Blood Spots
 Newborn Screening Saves Lives
Reauthorization Act of 2014
 Culmination of recent efforts to bring
secondary research with newborn residual
bloodspots within the scope of human
subjects research regulations, requiring
parental consent.

16. Use of Residual Newborn
Blood Spots, contd.
 Empirical research suggests that parents’
concerns about research with newborn
bloodspots are not primarily about genetic/privacy
risks.
 Rather, a respect for persons concern: object in
principle to the idea that their children’s samples
would be used for research without their
knowledge or permission (Lewis et al 2012).

17. Themes
1. Current regulations are out of step with public
attitudes and emerging norms.
2. Increasing demand from specimen donors that
their interests be recognized and they be seen
as stakeholders in research.
3. Those interests aren’t primarily interests in
protection from privacy risks – rather, about
being asked about use of their biological
tissues for research.

18. References
Botkin,Jeffrey R.,Erin Rothwell,Rebecca Anderson,Louisa Stark,Aaron Goldenberg,Michelle
Lewis,Matthew Burbank,and Bob Wong.2012.Public Attitudes Regarding the Use of
ResidualNewbornScreeningSpecimens forResearch. Pediatrics129.2:231-238.
Couzin-Frankel,Jennifer.2015.NewbornScreeningCollides with Privacy Fears. Science
348.6236:740-741.
Dalton,Rex.2004.When Two Tribes Go to War. Nature 430: 500-502.
Departmentof Health and Human Services (DHHS).2015.Notice of Proposed Rulemaking:
FederalPolicy forthe Protection of Human Subjects. FederalRegister 80 (173):53931-
54061.
Dorney,Maureen S.1990.Moore v. the Regents of the University of California:Balancing the
Need forBiotechnology Innovation againstthe Rightof Informed Consent. Berkeley
TechnologyLaw Journal 5:333-369.
Drabiak-Syed,Katherine.2010.Lessonsfrom HavasupaiTribe v. Arizona State University
Board of Regents:Recognizing Group,Cultural,and Dignitary Harms as Legitimate Risks
Warranting Integrationinto ResearchPractice. JournalofHealth & BiomedicalLaw 6.2:175-
225.
Geetter,JenniferS., and Chelsea M.Rutherford. “The NewbornScreeningSavesLives
ReauthorizationAct:Implications forHuman Subjects Research.”McDermottWill & Emery,
8 April 2015.Web.25 September2015.http://www.mwe.com/The-Newborn-Screening-
Saves-Lives-Reauthorization-Act-Implications-for-Human-Subjects-Research-04-08-2015/
Hudson,Kathy L.and Francis S. Collins.2013.Family Matters. Nature 500: 141-42.
Javitt,Gail. 2010.Why Not Take All of Me? Reflection on The ImmortalLife of Henrietta Lacks
and the Status of Participants in Research Using Human Specimens. MinnesotaJournalof
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19. References, contd.
Kroll, David.2013. “The Henrietta Lacks Genome:Consent,Trust,and Common Decency.”Forbes.
Web.24 March 2013. http://www.forbes.com/sites/davidkroll/2013/03/24/the-henrietta-lacks-
genome-consent-trust-and-common-decency/
Lewis,Michelle Huckaby,MichaelE.Scheurer,RobertC. Green,and Amy L. McGuire.2012.
Research Results:PreservingNewborn Blood Samples. ScienceTranslationalMedicine 4 :1-3.
Mello,Michelle M., and Leslie E. Wolf. 2010.The HavasupaiIndian Tribe Case—Lessons for
Research InvolvingStored Biologic Samples.NEJM 363:204-207
McKie,Robin.“Henrietta Lacks’Cells were Priceless,buther Family Can’t Afford a Hospital.” The
Guardian.Web.3 April 2010. http://www.theguardian.com/world/2010/apr/04/henrietta-lacks-
cancer-cells
Rivera,Suzanne M.2014.ReconsideringPrivacy ProtectionsforHuman Research. HumanSubjects
Research Regulation:Perspectives on the Future.Ed. I. Glenn Cohen and Holly Fernandez
Lynch.Cambridge,MA:MIT Press,251-63.
Rothwell,Erin,Rebecca Anderson,Aaron Goldenberg,Michelle H.Lewis,Louisa Stark,Matthew
Burbank,Bob Wonga,and JeffreyR.Botkin. 2012.AssessingPublic Attitudes on the Retention
and Use of ResidualNewbornScreeningBlood Samples:A Focus Group Study. SocialScience
and Medicine 74.8:1305-1309.
Skloot,Rebecca.2010. The ImmortalLife of Henrietta Lacks.New York: Crown Publishers.
Tilousi,Carletta.“Making Sense of Community:Responsesto Tissue Research.”2010 AER
Conference.PRIM&R.San Diego Convention Center,San Diego,CA.7 December2010.
Zimmer,Carl. “A Family Consentsto a MedicalGift,62 Years Later.” The New York Times.Web. 7
August2013.http://www.nytimes.com/2013/08/08/science/after-decades-of-research-henrietta-
lacks-family-is-asked-for-consent.html?_r=0.