The Road to Discovery
Medical Research Today
PROJECT MEDICAL EDUCATION
America’s medical schools and teaching hospitals
working together to inform Congress, policymakers, and opinion leaders about medical
education for the benefit of all Americans.
Association of
American Medical Colleges
This publication was adapted from the Road to Discovery brochure on biomedical research originally produced by the office of
marketing and communications at University of Iowa Health Care in Iowa City, Iowa.
Now more than ever, medical research is
being woven into the fabric of our daily lives.
Headlines regularly trumpet the latest
findings emerging from fields such as
genetics, nutrition, and diagnostic imaging.
Health sites on the Internet connect patients
with researchers studying innovative
treatments. People are living longer and better
lives because of greater knowledge about how
the body works, and how to prevent,
diagnose, and treat disease.
Behind these headlines, breakthroughs, and
hopes for the future are people who have
dedicated their careers to medical research—
laboratory scientists, physicians, nurses,
engineers, statisticians, and many others.
Medical research is a team effort, and much of
it takes place at academic medical centers.
These centers typically include a medical
school and a teaching hospital, along with
schools dedicated to other health fields, such
as dentistry, nursing, pharmacy, and public
health.
But how many of us know how medical
research works? What are its different
application and career fields? How are
research results tested and communicated?
What are some of the ethical dilemmas
involved with medical research?
These pages will provide answers to these
questions as well as examine how research
enhances the other core missions of medical
schools and teaching hospitals—patient care,
the education of new generations of health
professionals, and community service.
Basic Research
In biomedical science, basic research refers to
the study of living systems, from humans
down to single-cell organisms and even
subcellular or molecular components.
Scientists not only want to learn how living
systems function normally, but also how and
why normal processes fail and cause disease.
This type of work represents what many
people picture when they think of scientific
research. Typically occurring in a laboratory, it
usually does not involve human volunteers as
study subjects, but it may use human tissue or
fluids. Such research may focus on a particular
cellular substance or function, or a system in
the body. Its goal alternatively may be to find a
better understanding of a specific disease.
The medical treatments that benefit us today
come from years—often decades—of research
that began with scientists drawn to intriguing
biological phenomena. Studying these
phenomena often leads to understanding
their role in the progression of specific
diseases. For example, learning about how
normal cells divide sheds light on the
progression of cancer, where the normal
2
process goes awry. Eventually, this work may
lead to developing new treatments.
To perform basic research, scientists often
experiment on model systems. Cell
cultures—human or animal cells grown
under controlled conditions—offer a way to
study specific cellular events. Other model
systems may include simple organisms like
fruit flies or yeast, or higher animals like mice
and rats. Although humans seem far removed
from these creatures, we actually share many
traits with them.
Basic research seeks answers to countless
questions in many different scientific fields,
but genetics has emerged in the past few
decades as a particularly important area of
study. Genes guide the production of
proteins, the building blocks of life. The sum
of all genes within a particular organism is
called the genome. The human genome is
yielding new knowledge about how the body
works and how to treat disease. Genetic
research offers a powerful example of how the
most fundamental discoveries may have
dramatic implications for health.
Association of American Medical Colleges
Basic science disciplines
The following are examples of basic science disciplines and the topics associated with them.
Many disciplines are related, and all have roots in the sciences of biology, chemistry, or physics.
Anatomy: The identification and description of body structures in living things. Gross anatomy
typically refers to the study of human body structures large enough to be seen without magnification, while other forms of anatomy look to smaller structures.
Biochemistry: The study of chemical substances and processes that occur in living things, or the
chemistry of life.
Biophysics: The application of principles from physics to solve biological problems.
Cell biology: The analysis of cells as the fundamental units of living things.
Genetics: The focus on heredity, particularly genes, their functions, and how they are transmitted
from parents to offspring. Molecular genetics concerns molecules in cells that store genetic
information.
Microbiology: The exploration around the structure, function, and classification of microorganisms like bacteria, viruses, molds, algae, and protozoans.
Molecular biology: The study of the molecular basis for biological processes, particularly as they
involve proteins, nucleic acids, enzymes, and the transfer of genetic information.
Neuroscience: The analysis of the central and peripheral nervous system of biological organisms.
Pharmacology: The investigation of drugs and their effects, particularly therapeutic uses.
Physiology: The examination of how living things and their cells, tissues, and systems function.
3
Clinical Research
Clinical research is the disease-oriented,
often patient-centered, component of medical
research involving human subjects who
volunteer to take part in scientific studies. It
takes scientific knowledge from the
laboratory into hospitals, doctors’ offices, and
communities. Clinical research can validate
new treatments or disprove old ones, chart
the course of disease, identify health risk
factors, and improve health care delivery.
Clinical research is complex and often very
expensive. Studies must be designed to ensure
that their results are valid and can be
replicated by other researchers. The most
reliable trials require large samples of
carefully screened volunteers and often are
conducted simultaneously at multiple
research centers. Testing a new drug or device
through clinical trials may require several
years and tens of millions of dollars.
Clinical research may be observational or
experimental. In observational studies,
physicians look at how a disease changes over
time and the possible effects due to
medications, lifestyle adjustments, or other
interventions. Experimental research involves
studies specially designed to answer a
question, often to determine the effectiveness
of a new medication, procedure, or device.
These studies are called clinical trials.
In addition to evaluating new treatments,
clinical researchers design projects that
examine disease prevention and diagnosis.
They also explore factors that can ease
discomfort or improve quality of life for sick
patients and their families.
Clinical trials often are conducted using two
or more groups of volunteers with similar
backgrounds and health status. The “test
group” receives the treatment being studied;
the “control group” receives an older
treatment or a placebo (a mock drug or
procedure). Researchers compare results from
the two groups to determine the efficacy of
the treatment being tested.
Within clinical research, the field of
epidemiology studies groups of people.
Epidemiologic research looks at the distribution of disease among human populations
and the factors that influence that distribution.
It may involve studying contemporary
populations or looking back at historical
records to discern disease patterns. Epidemiologic research may be descriptive, using
surveys to collect data on a disease and how it
has changed over time. Or it may be analytic,
involving experiments that divide participants
into groups to observe, for example, whether
changes in a disease appear linked to factors
like diet or smoking, or the environment.
Researchers often assign volunteers at
random to either the test group or control
group. Randomized trials are designed to
prevent selection and other biases from
skewing the results. In “doubleblind” trials,
neither researchers nor volunteers know who
received what treatment until the study’s end.
4
Association of American Medical Colleges
Research Funding
The cost of conducting research increases as
science becomes more complex and technologically sophisticated. Medical schools and
teaching hospitals receive funding for medical
research from federal and state agencies,
industry, philanthropic efforts, and institutional funds.
Federal support for research by medical
institutions largely stems from the extramural
funds of the National Institutes of Health
(NIH), the predominant funding source for
medical research in this country. For more
than 60 years, the partnership between the
NIH and scientists at the nation’s universities,
medical schools, teaching hospitals, and
research institutes has pioneered many of
medicine’s most remarkable advances,
including life-saving vaccines, new and better
treatments for cancer, heart disease, and
diabetes; and new medical technologies that
improve quality of life.
U.S. medical schools and teaching hospitals
are awarded more than half of all extramural
funding. Physicians and scientists (known as
“principal investigators”) seeking financial
support for a research project at their
institution may apply for NIH funding, which
is awarded in the form of grants, cooperative
agreements, or research contracts. Grants, the
largest category of funding, are available for
one to five years. Nearly 50,000 funding
applications are submitted to the NIH each
year. Unfortunately, NIH funding levels have
not kept pace with the rise in applications.
This has resulted in fewer awards to young
investigators. Applications are subject to a
peer-review process, as mandated by law. A
national pool of research scientists helps the
NIH select which applications will be
approved for funding. The review of grant
applications is done on the basis of scientific
and technical merit, and in consideration of
the sponsoring NIH institute’s program goals
and available funds.
with Veterans Affairs (VA) medical centers and
the VA research supported by the Department
of Veterans Affairs.
Industry-sponsored research accounts for
more than half of the nation’s total medical
research and development, with about onequarter of industry-sponsored research
supporting the conduct of clinical trials.
The Percentage of Traditional NIH Grants Awarded to
Young Investigators Has Steadily Declined
100%
Over 55 years old
80%
46-55 years old
60%
40%
In addition to the NIH, other federal agencies
that support medical research are the Centers
for Disease Control and Prevention (CDC),
the Department of Defense (DOD), and the
Agency for Healthcare Research and Quality
(AHRQ). Medical schools and teaching
hospitals also benefit from strong relationships
5
36-45 years old
20%
35 years old and younger
0
1980
1984
1988
1992
1996
Source: NIH
Association of American Medical Colleges
2001
2006
Research facilities
Much medical research demands specialized
facilities, whether laboratories equipped with
high-tech tools or clinics outfitted with the
latest apparatus for making medical
diagnoses. New technology speeds medical
advances. Today, investigators can look deep
inside the body with techniques like magnetic
resonance imaging (MRI) or positron emission
tomography (PET). They also can use
technology to create detailed images of
molecules and chart movement of atoms.
Increasingly powerful computers help them
process, store, and share information more
quickly.
Investments in research facilities ensure that
investigators have the tools they need to carry
on their work. New facilities help to recruit
and retain talented and successful investigators who can win grants for their research
activities. Private donations, state and local
government assistance, and debt financing
enable institutions to pay for new
construction projects. At the same time,
renovations of older facilities must keep pace
with developments in technology and
research practices. While laws and regulations
can mandate renovations, only a small
amount of direct federal support is allotted
each year for construction, repair, and
modernization of research facilities.
Philanthropy too has long been an important
source of support. Medical schools and
teaching hospitals with research programs are
the beneficiaries of many large private gifts
and endowments.
Also essential to medical exploration is
unsponsored research, which includes
institutionally funded and faculty-supported
research activities. This research often leads to
important discoveries, as well as to other
grant awards and publications.
With restrictive caps on federal extramural
research support and the need to allocate
research resources for unsponsored research,
medical schools and teaching hospitals must
be prepared to share in the cost burden for
sustaining the nation’s research enterprise.
These costs include those necessary for
complying with diverse federal, state, and
local regulations; reimbursing investigator
salaries; recruiting new investigations; and
continually expanding and reinvesting in
necessary facilities and equipment.
6
To maintain and improve deteriorating
research facilities, medical schools have
typically turned to fundraising, endowment
earnings, and net income from the delivery of
clinical services. Schools often rely on risky
debt financing to pay for new construction
projects with the justification that new facilities
will help recruit talented and successful investigators who can win research grants. To
succeed in the research environment, medical
schools and teaching hospitals must focus on
strengthening their organizational and
management infrastructure, exploring new
opportunities for research support, and
promoting faculty development.
Research Ethics
Each research proposal submitted for federal
funding by medical schools and teaching
hospitals must be certified by the university to
ensure compliance with regulations dealing
with misconduct, conflict of interest, drug
abuse, hazardous materials, occupational
health and safety, age discrimination, equal
opportunity, and other matters. Laboratories
and administrators often must abide by
complex systems of local, state, and federal
regulations.
Because clinical research involves real
people—including those facing serious
illnesses—ethical issues are a top priority for
researchers and their institutions. By law,
clinical investigators must obtain informed
consent from study participants, meaning
that volunteers must be fully aware of what
could happen during a study, including any
known risks. They must be told about any
proven treatments that exist for their
condition and must be assured that they can
leave the study at any time. If a study involves
children or those with impaired decisionmaking ability, parents or guardians must
provide informed consent.
To ensure that scientists conduct sound and
ethical clinical research, institutions establish
Institutional Review Boards (IRBs) that
evaluate all studies using human participants.
IRBs consist of scientists, faculty members,
and lay people from within and outside the
universities that conduct research. These
review boards take their mission very
seriously.
Long before a clinical research project begins,
an IRB carefully reviews a written proposal
from the project’s lead investigator. Lengthy
debates and suggestions from committee
members about how to improve the study
and enhance informed consent procedures
often occur. At research institutions, full-time
staff assist IRB members and researchers.
IRBs report to the highest levels within
universities and no research involving human
subjects takes place at institutions without
IRB approval. All federally funded research
involving human subjects must also meet
national regulations mandated by the Office
of Human Research Protection. Regulations
protecting human subjects strictly applies to
research that is federally funded or under
7
jurisdiction of the federal Food and Drug
Administration (FDA).
Another committee pays special attention to
any research involving radiation or
radioactive materials, X-rays, or lasers,
ensuring that studies conform to current
radiation protection regulations and
practices. Research projects involving animals
also are strictly controlled by federal law and
monitored by various agencies as well as
research institutions themselves. To ensure
that their research programs meet the highest
levels, many schools participate in rigorous
animal research and human subject accreditation programs.
The realm of research ethics extends to
information about participants gathered
during clinical trials. With new forms of
electronic information storage and retrieval,
attention to privacy and confidentiality is
more important than ever. Research participants’ identities must be protected, and
information about their health histories and
status kept strictly confidential.
Association of American Medical Colleges
The clinical trials process
The controlled clinical trial has become the
standard for testing new drugs and medical
devices. In the United States, a new drug
that has been studied in the laboratory and
in animals must pass through three phases
of clinical trials in people to gain approval
from the FDA.
Phase I clinical trials use human volunteers
to determine safety. Once this is established,
the drug may enter a phase II trial, in which
it is given to a group of people who have the
disease that the drug is designed to treat.
Investigators study whether the drug affects
the disease and whether any additional side
effects emerge. Finally, a phase III trial uses
a larger number of people and compares the
drug to other treatments or placebo.
In addition to the clinical trials of new drugs,
pharmaceutical manufacturers may sponsor
studies that compare a drug to related
products or assess its comparative
effectiveness. Other projects, known as
adjuvant studies, look at whether combining
a drug with surgery or other therapy
improves patients’ health.
Other ethical concerns within medical
research include the appropriate representation of women and minorities among
research subjects, the need to assess new
treatments in children as well as adults, and
the involvement of mentally impaired
individuals in research. Public misunderstanding of clinical research creates additional
challenges, as potential volunteers may see
clinical trials as a way to receive yet-unproven
therapies that may be their last chance for
help. Some patients with life-threatening
diseases may be reluctant to take part in trials
knowing they may receive a placebo or older
drug rather than a new treatment. Individual
researchers, medical schools, teaching
hospitals, patient advocacy groups, and
government oversight agencies strive to
address ethical concerns to ensure that all
research is safe, reliable, and fair.
influences can undermine trust. Conflicts of
interest are situations in which financial or
other personal considerations can potentially
compromise the professional judgment of
faculty conducting research. A system that
oversees and manages such conflicts ensures
transparency, public accountability, and
responsible stewardship of federal resources.
U.S. medical schools and teaching hospitals
are implementing stronger conflict-of-interest
policies to ensure that its missions of
education and research remain viable and that
public trust in research is maintained.
Conflict-of-interest policies too need to be
considered by researchers and institutions
when industry support of a project is involved.
Although industry support of our nation’s
health-related research is needed, industry
8
Association of American Medical Colleges
Communicating results
As they work, medical researchers keep meticulous records to help them report exactly
what they observed. When they feel they have acquired enough data, they begin the
process of reporting their findings to peers and the public. Most of their work ends
up published in scientific journals or shared at professional conferences.
Publishers of scientific journals want to ensure that the work they publish meets strict
standards, and only a small fraction of the articles submitted to top journals are
published. Literally hundreds of journals are currently being published, many of them very
specialized. The most prestigious medical journals include Science, Nature, Cell, the
Journal of the American Medical Association, and the New England Journal of Medicine.
The first step toward publication involves drafting a paper to submit to a journal for peer
review, an essential “quality-control” method in modern science. The journal distributes
the paper to experts familiar with the type of work being reported, asking that they
carefully review the study’s design and results. These experts almost always ask the
paper’s authors to clarify details or expand parts of their article before it can be published.
Some research results are presented at conferences before peer review and publication.
The Internet is changing the way early research results are communicated, allowing online
conferences where scientists share results without traveling away from home. More
articles and data are being published online, bringing researchers together faster than
ever before.
9
Medical Research Careers
Medical research requires teams drawn from
different backgrounds and specialties, most
with education beyond the four-year college
degree. A strong grounding in science
including basic education in biology,
chemistry, and physics is good preparation for
any career in biomedical research, allowing
individuals to specialize in different fields
depending on their strengths or interests.
Most basic scientists hold doctor of
philosophy (Ph.D.) degrees, also referred to
as doctorates, in scientific disciplines. Ph.D.
programs at universities can take four or
more years to finish and usually follow
completion of a bachelor’s degree. After
receiving their Ph.D. degrees, many scientists
elect to pursue additional training to gain
more experience or further specialize in their
chosen field. They may go on to work in a
university, industry, or other setting.
Many medical researchers, particularly those
who perform clinical research, are physicians
with doctor of medicine (M.D.) degrees. The
M.D. degree, along with additional training
and state licensure, permits such individuals
to treat patients while doing research. A
10
relatively small number of researchers hold
both Ph.D. and M.D. degrees, having been
trained in both medicine and a basic science
discipline. They often are referred to as
physician-scientists.
Professionals from fields such as dentistry,
nursing, pharmacy, and public health also
conduct biomedical research. They usually
hold professional or graduate degrees of some
kind, such as the doctor of dental surgery
(D.D.S.) degree for dentists or the doctor of
pharmacy (Pharm.D.). Some hold master’s
degrees—graduate degrees that precede the
Ph.D.—like the master’s in public health
(M.P.H.) degree, or a master’s degree required
for a career as a physical therapist.
Some individuals train to become laboratory
professionals, assisting lead investigators on
research projects or heading studies of their
own. Professionals from fields such as
engineering, statistics, information
technology, social work, and the social
sciences also take part in medical research, as
do some individuals with business or
humanities backgrounds.
Association of American Medical Colleges
Multiple Missions
Medical research cannot be separated from
the education and service missions of
academic medical centers—medical schools
and teaching hospitals. Research is about
much more than just advancing human
knowledge. It is about teaching tomorrow’s
scientists and health professionals, fighting
disease, and improving quality of life.
of opportunities for students—
undergraduates, graduate students, and
professional students alike—to conduct
research alongside top faculty mentors. Even
those students who do not go on to become
researchers gain essential problem-solving
skills, familiarity with scientific methods, and
often a drive to keep asking “Why?”
Many of the nation’s medical schools are
home to strong research programs. Faculty
members who conduct research are among
those best able to help students discover how
the human body works. Schools offer a range
Academic medical centers dominate lists of
the best teaching hospitals, primarily because
they are the places where discoveries move
from the laboratory to the bedside, putting
new knowledge into practice. They attract
physicians and scholars who are leaders in
their fields. For this reason, academic medical
centers are where other doctors turn when
faced with scientific riddles.
The medical discoveries that make headlines
come from many individuals working
together, including patients who turn to
academic medicine when faced with an
illness. Patients who participate in research
are essential members of the research team;
their contributions today may improve life for
others tomorrow.
Photo Credit
Additional Resources
Association of American Medical Colleges
(AAMC)
www.aamc.org
Council of Academic Societies
http://www.aamc.org/members/cas/start.htm
Financial Conflicts of Interest in Medical
Research Press Kit
http://www.aamc.org/newsroom/presskits/coi.htm
Fulfilling the Promise Campaign
http://www.aamc.org/research/ftp/start.htm
Project Medical Education
www.aamc.org/pme
Other Resources
Agency for Healthcare Research and
Quality
http://www.ahrq.gov/
Association for Assessment and
Accreditation of Laboratory Animal Care
International (AAALAC)
http://www.aaalac.org/
Centers for Disease Control and Prevention
http://www.cdc.gov/
Food and Drug Administration
Clinical Trials
http://www.fda.gov/oashi/clinicaltrials/
default.htm
National Institutes of Health
http://www.nih.gov/
Office for Human Research Protections
http://www.hhs.gov/ohrp/education/
United States Department of
Veterans Affairs Office of Research and
Development
http://www.research.va.gov/
Association for the Accreditation of
Human Research Protection Programs, Inc.
(AAHRPP)
http://www.aahrpp.org/www.aspx
12
Front Cover, pages 1, 3, 11
Lee P. Thomas, University of Kentucky
College of Medicine © 2007-2008
Page 2
Washington University School of Medicine in
St. Louis © 2004
Page 9
Jim Ziv, Northwestern University © 2008
Page 10
Robert Boston, Washington University
School of Medicine in St. Louis © 2007
This document was produced by the AAMC’s Project Medical Education, a focused educational program for members of Congress,
congressional staff, as well as other policymakers, influential stakeholders, community leaders, and board members. Its goal is to
provide an increased understanding of the U.S. medical education process and the role that our medical schools and teaching hospitals
play in producing the world’s greatest doctors.
Project Medical Education attendees visit a medical campus and assume the roles of a medical student, resident physician and faculty
physician. By doing so, attendees are provided a hands-on experience of what it takes to become a doctor and the challenges that face
our nation’s medical schools and teaching hospitals.
The model is flexible offering institutions the ability to tailor the program to fit their particular goals and issues. A successful program
will touch upon the major areas of medical education financing, tuition and debt, research funding and how research is conducted, as
well as community service and caring for the uninsured, among others.
The program is extremely interactive and has grown increasingly popular. Since the project’s initiation in 1998, nearly 900 state and
federal policymakers have attended a program at leading medical institutions across the country.
If you are interested in learning more about attending or hosting a program, please contact:
Sallyann C. Bergh, M.P.A.
Senior Communications Specialist
Project Medical Education
AAMC
2450 N Street, N.W.
Washington, D.C. 20037
Phone: 202-862-6289
Fax: 202-828-1123
E-mail: [email protected]