Roger Williams MD: a friend, role model and tireless champion for FH patients

I met Dr. Roger Williams in 1985 when I visited the University of Utah from Rockefeller University, where I was a post-doctoral fellow in Jan Breslow’s laboratory. Jan arranged for me to learn Southern blotting with Ray White and Jean-Marc Lalouel at the Howard Hughes Medical Institute. Jean-Marc was just starting to collaborate with Roger on his large Mormon FH families. I was absolutely amazed when I first saw the pedigree diagrams showing hundreds of family members, some with 10 or more generations. In New York, a couple with two children was considered to be a large family; the Utah family trees in contrast filled scores of taped-together legal-sized pages filed in binders.

For a human geneticist, the Utah FH kindreds were a breathtaking resource, painstakingly assembled by Roger and his marvelous clinical and scientific team, including Paul Hopkins, Steve Hunt, Sandy Hasstedt and Lily Wu, among many others. Two years later, I moved to Salt Lake City to continue my post-doctoral training at the U, and was privileged to collaborate with Roger on several projects, including the early application of DNA in FH diagnosis 1.

Roger’s Utah kindreds enabled our group to pursue many projects. We devised a PCR-based method for APOE genotyping 2, mapped the LPA locus to chromosome 6q26 adjacent to the gene for plasminogen 3, and demonstrated that certain FH patients had extremely high Lp(a) levels 4. Some fascinating FH families had various gene mutations segregating independently, for instance an APOB hypobetalipoproteinemia mutation that cancelled out the lipid effects of an LDLR FH mutation 5. In another family, interaction of a heterozygous FH mutation and the APOE E2 allele was associated with expression of type 3 hyperlipidemia 6. Most importantly, Paul and Roger spearheaded development of the MED-PED FH diagnostic criteria, which are still cited a quarter century later 7.

Roger kindly wrote letters of reference both for my first faculty position and my first grant application. I was fortunate to inaugurate the first Canadian MED-PED FH site at St. Michael’s Hospital in Toronto, and later at the Robarts Research Institute in London, Ontario. In my clinic, we’ve since performed next generation DNA sequencing to diagnose >700 heterozygous FH patients, most of them under my care. I’m also involved in the care of five FH homozygotes. I was privileged to be among the first in Canada to use several medications in clinical trials involving FH patients. My FH patients are the foundation of my clinical practice and my engagement with FH traces back directly to Roger’s influence.

Working with Roger and MED-PED FH led to many memorable scientific and personal encounters. I attended several investigator meetings with international colleagues, many of whom are still friends and collaborators. Roger headed the first WHO consultation on FH in Paris in 1993. Later that year, Roger and I both spoke at a conference in Jerusalem, and then together toured the historic sites of Capernaum, Nazareth and Cana, ending with a boat ride on the Sea of Galilee. Roger and I sat together when the results of the 4S study were first presented in 1994. I have many more deep professional and personal memories of this remarkable man.

On September 2, 1998 I was en route to WHO headquarters in Geneva for a two-day conference comprised of a WHO workshop on FH, followed by the international MED-PED FH investigators’ meeting. When I arrived in Geneva the next day, I was shocked to learn that my friend – our group’s leader – had perished the previous evening in tragic airplane crash.

The rest of us continued in Roger’s absence; we dedicated the second workshop and proceedings to his memory. It was a sad and surreal time. We supported each other and tried to do what Roger would have expected. The two WHO consultation proceedings on FH are wonderful documents that stand the test of time. The consultations were the brainchildren of Roger and Dr. Victor Boulyjenkov, and I believe they are among the first WHO public health documents on a non-communicable genetic illness.

After the meetings were finished, I attended an ecumenical memorial service at the old town Zurich cathedral for the victims of Swissair flight 111. That memory is imprinted in my brain. Roger has been on my mind constantly since that time. In 2003, I visited the Swissair flight 111 memorials at Peggy’s Cove and Bayswater, Nova Scotia, and then again in 2014. I wept both times as I scanned the terrible but beautiful North Atlantic Ocean.

Many things impressed me about Roger. First and foremost were his clinical skill, acumen and humanity that gave depth and dimension to his scientific excellence. He was absolutely committed to the well-being of his patients and their families, and I’ve tried to emulate this in my own career.

Roger always had his eye on how science and technology might benefit his patients; what today we call “translational medicine”. Roger never wavered in his view that patients were the centerpiece of biomedical research. Science and technology, while gratifying and academically fascinating, ultimately existed to serve the greater good of patients and their families. I’ve never forgotten this lesson and have tried to organize my career to reflect Roger’s standards and outlook.

Roger was a visionary in so many ways. He was committed to the clinical issues facing FH patients at a time when most of the scientific interest in FH was in its molecular biology. He was ahead of his time in establishing biobanks and family registries. The Inherited High Cholesterol Foundation and MED-PED FH stand as his enduring scientific monuments; they are achievements never to be forgotten. MED-PED has been directly responsible for the identification of thousands of FH patients around the world. It serves as a model for contemporary registry and cascade screening initiatives.

We must use this occasion to remember Roger’s devotion to FH patients and to follow his example as we move forward to confront the future challenges of this vital public health issue. 

Rob Hegele, MD, FRCPC, FACP
Distinguished University Professor of Medicine and Biochemistry
Schulich School of Medicine and Dentistry
University of Western Ontario
London, Ontario, Canada

1) Hegele RA, Emi M, Wu LL, Hopkins PN, Williams RR, Lalouel JM. Clinical application of deoxyribonucleic acid markers in a Utah family with hypercholesterolemia. Am J Cardiol 1989; 63:109-12.
2) Emi M, Wu LL, Robertson MA, Myers RL, Hegele RA, Williams RR, White R, Lalouel JM. Genotyping and sequence analysis of apolipoprotein E isoforms. Genomics 1988; 3:373-9.
3) Drayna DT, Hegele RA, Hass PE, Emi M, Wu LL, Eaton DL, Lawn RM, Williams RR, White RL, Lalouel JM. Genetic linkage between lipoprotein(a) phenotype and a DNA polymorphism in the plasminogen gene. Genomics 1988; 3:230-6.
4) Hegele RA, Sutherland S, Robertson M, Wu L, Emi M, Hopkins PN, Williams RR, Lalouel JM. The effect of genetic determinants of low density lipoprotein levels on lipoprotein (a). Clin Invest Med 1991; 14:146-52.
5) Emi M, Hegele RA, Hopkins PN, Wu LL, Plaetke R, Williams RR, Lalouel JM. Effects of three genetic loci in a pedigree with multiple lipoprotein phenotypes. Arterioscler Thromb. 1991; 11(5):1349-55.
6) Hopkins PN, Wu LL, Schumacher MC, Emi M, Hegele RA, Hunt SC, Lalouel JM, Williams RR. Type III dyslipoproteinemia in patients heterozygous for familial hypercholesterolemia and apolipoprotein E2. Evidence for a gene-gene interaction. Arterioscler Thromb 1991; 11:1137-46.
7) Williams RR, Hunt SC, Schumacher MC, Hegele RA, Leppert MF, Ludwig EH, Hopkins PN. Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am J Cardiol 1993; 72:171-6.


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