As Professor of Pediatrics and Population Health Sciences at the University
of Wisconsin School of Medicine and Public Health, Dr. Farrell concentrates
his efforts on cystic
fibrosis (CF) newborn screening and population health promotion.
His activities include:
Leading the Wisconsin
Cystic Fibrosis Neonatal Screening Project as
the principal investigator on an National Institutes of Health-funded
epidemiologic research study.
This study, which includes collaborative research with
France, demonstrates the medical benefits of early diagnosis
CF through neonatal screening. A related study, supported
by a grant from the US
Cystic Fibrosis Foundation (CFF),
psychosocial outcomes after newborn screening.
Collaborating with the Centers
for Disease Control on process improvement
for CF newborn screening. This collaboration
works to develop: a national repository of transmembrane conductance
regulator (CFTR) mutations; a best practices protocol for
CF newborn screening to be used throughout North America
and Europe; and a
CF newborn screening quality assurance (QA) program.
This multiyear, evidence-based project on infant mortality, or more specifically, the disparity of outcomes between white and African-American babies, addresses one of the most critical health problems facing Wisconsin.
Although Wisconsin is a leader among states for its low white infant mortality rate (number of infant deaths per 1,000 live births), the infant mortality rate for African-Americans in Wisconsin is the worst in the nation.
In 2004, infants born to African-American mothers in Wisconsin were more than four times likely to die before their first birthday than infants born to white mothers (19.3 deaths per 1,000 live births for blacks compared to 4.5 deaths per 1,000 live births for whites).
Dr. Farrell has extended his role in the WPP’s Oversight and Advisory Committee to chair the steering committee of this innovative program, which incorporates best practice public health and self-sustaining community-based interventions to produce better African-American birth outcomes.
Agencies in four Wisconsin communities—Milwaukee, Beloit, Racine, and Kenosha—are currently applying for Community Action Planning Grants through the Lifecourse Initiative. We expect that they will also apply for funds to implement projects designed to lower infant mortality rates in their respective communities.
Cystic fibrosis (CF) is the most common life-threatening autosomal recessive genetic disease among Caucasians. It is most frequently associated with the F508del allele, which was the first mutation discovered. This 3 base pair (bp) deletion allele generally accounts for ~70% of CF chromosomes in Europeans and Euro-Americans, but in Denmark, a higher frequency—namely >85%—has been documented.
In the Western World, about half of CF patients are homozygous for F508del and another 40% have one F508del and another mutation. Thus, the relatively high incidence and prevalence of this disease are largely attributable to F508del, and about 1 in 30 of current, native Europeans are estimated to be CF/F508del heterozygote carriers.
The basis of this high frequency is unknown, although available data suggest a combination of a founder effect and a selective advantage of some unknown nature in the heterozygote. This gap in knowledge has led to great challenges for clinical programs that offer newborn screening for CF using the common IRT/DNA method because it identifies CF heterozygote carrier infants. (In 2009, approximately 8 million babies were screened for this disease.)
In an effort that might referred to as archaeological genetics applied to evolutionary medicine, we are investigating the following hypotheses:
The F508del mutation was present in Europe during the Iron Age with an incidence at least as high as the current heterozygote carrier rate (~1:30);
F508del was disseminated throughout central and western Europe by large-scale population movements and migrations in the Pre-Roman Iron Age; and
The presumed selective advantage for F508del heterozygotes is attributable to protection from endemic environmental exposures related to diet and/or heavy metal toxicity, rather than to infectious diseases, as some researchers have speculated.
The rationale for the final element relates to the supposable lack of endemic infectious disease, evidence that suggests long-term exposure of prehistoric Europeans to lead and arsenic, and some recent indications that the CFTR gene is influenced by arsenic.
Our archaeological genetics work thus far has enabled us to:
Develop reliable aDNA methods with excellent quality control; and
Identify the principal cystic fibrosis mutation, F508del, in ancient DNA that we extracted from teeth of individuals buried near the Danube River during the LaTène period of the Celtic culture (~400 BC).
However, Bronze Age specimens from the same cemetery, presumably an ancestral population, analyzed by the same methods, have been negative for F508del allele.
In addition to DNA analyses, we are analyzing bone specimens for toxic trace elements such as arsenic and lead. These same samples are also used for AMS-radiocarbon dating and stable isotope determinations that allow us to reconstruct paleodietary habits.
Such analyses have enabled us to determine that high levels of arsenic were apparently common during the Iron Age and subsequently in Romano-Britons of Londinium (Roman London during 100-200 AD).
on Cystic Fibrosis
Cystic fibrosis newborn screening was recommended
by CDC in an historic publication that also recommended that “Newborn
screening systems should ensure parental and provider education…” (Grosse
SD, Boyle CA, Botkin JR, et al. Newborn
for cystic fibrosis: evaluation of benefits and risks and recommendations
for state newborn screening programs. MMWR Recomm Rep. 2004;53(RR-13):1–36).
component of CF screening has proved to be difficult for a
reasons. In fact, the understanding of health care providers
and the lay
public regarding all newborn screening activities in the USA
leaves much to
be desired, despite four decades of PKU testing.
Dr. Farrell has worked intensively since 2005 on the development
of continuing medical education programs covering both the
early diagnosis of cystic fibrosis through newborn screening and
of providing care to keep patients and their parents healthy.
serving for nearly 12 years as Dean of the University of Wisconsin
Medical School (now the School of Medicine and Public Health), and
for the 10 prior years as Chair of the University of Wisconsin Department
of Pediatrics, Dr. Farrell acquired unique
knowledge and leadership
skills in academic
medical center development.
have been slow to advance toward integrated, synergistic groups
of specialists focussed on a common, unifying vision/mission.
Indeed, the autonomous, independent nature of physicians and scientists
medical faculty and their departments extremely challenging
when essential changes must be accomplished in a reasonable
time frame (usually 1–3 years).
Using leadership methods and coaching
techniques that proved very successful at UW-Madison, Dr. Farrell
academic medical center leaders on a variety of innovations
Academic facilities development;
Clinical programs reengineering; and
education combined with public health training.
His work as an academic
consultant is provided as an extension of Philip M. Farrell
After 12 years as Dean of the University of Wisconsin Medical
School (now the School of Medicine and Public Health), Dr.
Farrell continues to serve the school through numerous of leadership,
fund-raising, and educational activities. These include:
advice for a variety of academic, clinical, and research programs
at the UW SMPH, including the Master
of Public Health program and the Morris Institute for Respiratory