Rare Diseases, Stigma, and Animal Models: Key Concepts and Legislation

Rare diseases

Diseases affecting fewer than 200,000 people in the U.S.; about 10,000 exist; ~30 million Americans affected; most genetic; few treatments.

Rare disease definition and statistics

U.S. definition <200,000 people; EU <1 in 2,000; ~80% genetic; <5% have treatment; many affect children.

Meaning of rare disease to patients

Delayed diagnosis, misdiagnosis, few specialists, high cost, limited treatment, emotional burden.

Paradox of rarity

Each rare disease is uncommon, but together rare diseases affect millions.

Orphan Drug Act (1983)

Law encouraging development of drugs for rare diseases using tax credits, research grants, and 7-year exclusivity.

Purpose of ODA incentives

Make rare disease drug development profitable.

NORD

National Organization for Rare Disorders; advocacy group that helped pass ODA.

Quincy M.E.

TV show episode helped raise awareness for rare diseases and support the ODA.

Impact of ODA

Large increase in orphan drugs approved after 1983.

Rare Diseases Act (2002)

Expanded federal rare disease research and created NIH programs.

Office of Rare Diseases Research

NIH office coordinating rare disease research; now Division of Rare Diseases Research Innovation.

National Center for Advancing Translational Sciences

NIH center that helps move research to treatments.

RDCRN

Rare Diseases Clinical Research Network; research groups studying rare diseases.

RDCRN Consortia

Groups focused on specific rare diseases.

RaDaR

Rare Diseases Registry Program; collects patient data.

GARD

Genetic and Rare Diseases Information Center; provides info to public and doctors.

Raising awareness of rare disorders

Advocacy, campaigns, patient groups, social media.

EURORDIS

European rare disease advocacy organization.

Rare Disease Day

Awareness day on last day of February.

Zebra symbol

Symbol of rare diseases from "think horses not zebras."

Rare diseases and social media

Used for support, awareness, advocacy, fundraising.

Disease stigma

Negative social labeling causing discrimination.

Definition of stigma

Social disapproval based on disease or condition.

Disease-avoidance model

Stigma may come from instinct to avoid infection.

Disease avoidance in animals

Animals avoid sick individuals to reduce disease spread.

Visible/contagious stigma

Disease seen and infectious (ex: smallpox).

Visible/non-contagious stigma

Visible but not infectious (ex: scars).

Label/contagious stigma

Not visible but infectious (ex: HIV).

Label/non-contagious stigma

Not visible, not infectious (ex: genetic disease).

Combatting stigma

Education, awareness, contact, accurate information.

Stigma and COVID-19

Fear caused discrimination and blaming.

Stigma and Hansen's disease

Long history of extreme stigma and isolation.

Mycobacterium leprae

Bacterium that causes Hansen's disease.

Different names for leprosy

Leprosy (stigmatized), Hansen's disease (preferred), separating sickness, disease you do not name.

Lazarettes / Lazar houses

Isolation places for people with leprosy in Middle Ages.

Leprosaria

Hospitals/colonies for Hansen's disease patients.

Kalaupapa

Isolation colony in Hawaii started 1866; forced relocation; mostly Native Hawaiian; isolation until 1969.

Carville

U.S. national leprosarium in Louisiana; U.S. Marine Hospital No. 66.

Daughters of Charity

Nuns who provided care at Carville.

Unjust conditions at Carville

Loss of rights, forced name change, no marriage, no voting, family separation.

Positive aspects of Carville

Community, medical care, research, advocacy.

Miracle of Carville

Promin and later dapsone treatment for Hansen's disease.

Challenges combatting Hansen's disease

Stigma, late diagnosis, poverty, limited vaccine, neglected disease.

Guinea pigs

Used in research; similar biology to humans; cannot make vitamin C.

Why guinea pigs useful

Similar hearing, vitamin C metabolism, used in nutrition and allergy research.

Duncan-Hartley

Common lab guinea pig strain.

Ethics of animal testing

Must minimize harm and justify use.

Three R's

Replacement, Reduction, Refinement.

Beyond three R's

Sanctuaries, adoption, better housing, memorials.

Professional guinea pigs

People paid to participate in research.

Phase I clinical trials

First human testing; safety; small group; often healthy volunteers.

Exploitation concerns

Poor people may take risk for money.

Placebo

Inactive treatment used as control.

Single-blind

Subject does not know treatment.

Double-blind

Subject and researcher do not know treatment.

Placebo effect

Improvement due to belief in treatment.

Mechanisms of placebo

Expectation, brain response, stress reduction, endorphins.

Ethics of placebo

Allowed in trials if no treatment exists; controversial in practice

Nazi medical atrocities

Unethical human experiments during WWII without consent causing suffering and death.

Dachau hypothermia experiments

Nazi experiments exposing prisoners to extreme cold to study survival.

Eduard Pernkopf atlas

Anatomy atlas made using bodies of executed prisoners; raises ethical concerns.

Ethics of using Nazi data

Debate about using knowledge obtained through unethical experiments.

Nuremberg Doctors' Trial

Post-WWII trial of Nazi doctors for unethical experiments.

Nuremberg Code

Rules for ethical research requiring voluntary consent and protection of subjects.

Key principle of Nuremberg Code

Voluntary informed consent required.

Tuskegee Syphilis Study

U.S. study (1932-1972) where Black men with syphilis were not treated to observe disease progression.

Why Tuskegee unethical

No consent, deception, treatment withheld, racism, harm to subjects.

National Research Act

Law creating rules for human research after Tuskegee.

Belmont Report

Ethical guidelines for research on humans.

Respect for persons

Informed consent and voluntary participation.

Beneficence

Minimize harm, maximize benefit.

Justice

Fair selection of research subjects.

IRBs

Institutional Review Boards that review research ethics.

Tuskegee apology

U.S. government apology in 1997.

Effects of Tuskegee

Distrust of medicine, especially in Black communities.

Quarantine

Separation of people exposed but not sick.

Isolation

Separation of people who are sick.

Origin of quarantine

40-day isolation for ships; from Italian "quaranta."

US quarantine laws

Federal and state governments can isolate people to prevent disease spread.

Examples of quarantine laws

Used for TB, Ebola, COVID, etc.

Salmonella Typhi

Bacterium causing typhoid fever.

Salmonella Paratyphi

Causes paratyphoid fever.

Asymptomatic carrier

Person infected but without symptoms who can spread disease.

Carrier and typhoid

Healthy carriers can spread bacteria through food.

Fecal-oral transmission

Disease spread through contaminated food or water.

Chlorination of water

Disinfection that helped stop typhoid spread.

Mary Mallon

Cook who was a healthy carrier of typhoid fever.

Typhoid Mary first quarantine

Isolated after causing outbreaks.

Typhoid Mary release

Released after promising not to cook.

Typhoid Mary second quarantine

Returned to cooking; caused more cases; isolated for life.

North Brother Island

Quarantine site in New York.

Riverside Hospital

Hospital for quarantined patients on North Brother Island.

Typhoid Mary debate

Conflict between personal freedom and public safety.

Personal autonomy vs social responsibility

Individual rights vs protection of society.

Disease eradication

Permanent worldwide removal of disease.

Disease elimination

Removal of disease in a specific region.

Diseases easier to eradicate

No animal reservoir, effective vaccine, clear symptoms, human-only infection.

Variola virus

Virus that causes smallpox.

Smallpox characteristics for eradication

Human only, visible symptoms, vaccine available, no carriers.

Variolation

Early method of smallpox protection using infected material.