Jenner
On Trial
Tom
Kerns
Introduction
Human experiments to test the efficacy
of preventive AIDS vaccines will probably begin before the end
of the millennium. The World Health Organization has approved
the first such trials to be done within the next year or two,
probably in Thailand, and perhaps in other lesser developed nations
such as Uganda or Brazil. Efficacy trials will not, in all likelihood,
be done in the US for at least another year or two (or perhaps
much longer) following that.
The ethical quandaries raised by these HIV vaccine efficacy trials
will be at least as complex as, and probably more difficult than,
any that have been faced by vaccine researchers in the past.
The Nazi doctors did numerous vaccine trials in Buchenwald and
Natzweiler concentration camps in the early 1940s, and the design
of these experiments was conceptually simple and straightforward:
inject 100 subjects with an experimental typhus vaccine, then
wait for some weeks for an immune response to develop. After the
weeks have passed, assemble all 100 experimental subjects, as
well as an additional 100 control subjects, and then directly
challenge (i.e., infect) all 200 of them with virulent typhus.
If the experimental vaccine works, then most of those who received
it will be protected and will not contract typhus, but the controls
will. If the experimental vaccine does not work, then all 200
subjects get typhus, and most of them die.
This method of testing by direct challenge, the method of testing
also used by Edward Jenner in his first vaccination experiments,
was clearly unethical, or at least it was when the Nazi's did
it. The Nuremberg Code, one of the earliest statements of the
ethics of medical research involving human subjects, was developed
as a result of the doctors' trials at Nuremberg, and has served
as a basis for medical-ethical decision-making ever since. The
recent WHO/CIOMS International Ethical Guidelines for Biomedical
Research Involving Human Subjects, published by the World Health
Organization in November of 1993, also traces its history back
to The Nuremberg Code.
A brief sampling of some of the difficult questions entailed in
the planning and design of these HIV vaccine trials would include
the following:
How will researchers be able to execute an ethically adequate
informed consent procedure when the amount of information necessary
for subjects to understand is so great and the nature of it so
complicated? How will researchers be able to provide information
about the nature of vaccines and immune responses to persons (in
developing nations) who may hold conceptions of disease and disease-causality
that are quite different from the conceptions of disease held
by the researchers? How can research sponsors properly assess
whether prospective subjects have understood enough information
so that they are able to give adequately informed consent? How
can research counselors effectively counsel subjects to not engage
in risk behaviors when they themselves, at some level, realize
that the research protocol itself requires that subjects do engage
in those risk behaviors? What are some of the potential harms
that might reasonably be expected to accrue to subjects who participate
in these trials, and what are some benefits they might theoretically
expect which could counterbalance the risks they could be taking?
What is to be done about protecting volunteers' confidentiality,
and how can these volunteers be protected against unfair discrimination
based on their new serostatus which will (often) result from their
participation in the studies?
And underlying all these specific questions is the deeper meta-question:
Should the main operative ethical principles in this international
vaccine research be different in different countries, varying
according to the different mores and different cultural standards
in each country, or should there be a set of common, agreed-upon
international ethical standards for the protection of research
subjects, applicable to all research sponsors regardless of the
country in which the research is conducted?
These questions, and numerous others related to them, will not
be easy to deal with, nor will the answers to them be simple.
This book does not deal directly
with these questions about AIDS vaccines (for that see my recent
book, Ethical Issues in HIV Vaccine Trials ), but it will be quite
instructive to look instead at some of the first (scientifically
designed) medical research ever done on human subjects. This earliest
research too was built on the concept of testing the efficacy
of a preventive vaccine, an experimental inoculation that would,
Edward Jenner hoped, protect people against the most dreaded plague
of the age: smallpox.
In many respects the disease of smallpox will turn out to be a
fruitful analog for understanding today's AIDS and HIV disease,
or at least for understanding some aspects of our battle against
them. Smallpox is almost certainly a better model for understanding
AIDS than is the (sometimes suggested) Black Death, which was
seldom endemic, but rather came in great blows, struck down upon
a people by no-one-knew what agency (the word plague being from
the Greek plege, meaning a stroke, or blow.) AIDS, by contrast,
looks as if it will be more endemic, and probably with us for
some years (probably even some generations) to come. If Professor
Alan Brandt showed us that the 19th century epidemics of the Great
Pox (syphilis) can be intriguing and fruitful as an analog for
understanding our attempts to control the spread of AIDS, in this
study we will discover that the Small Pox, as an analog, will
also be able to provide us with insights into today's research
on prevention technologies for AIDS.
Jenner
homepage and Table of Contents
preface | Introduction | chp
1 | chp
2 | chp
3 | chp
4
cchp 5 | chp
6 | chp
7 | chp 8 |
App I | App
II
Ethical
Issues in HIV Vaccine Trials