Chicago, Illinois, United States
|Fig 1. Left to right: 2 Aspirin+2 Tylenol®+ 1 can of Coca-Cola®+ 2 Sudafed®; Excedrin® + Sudafed®; Imitrex® capsule; Excedrin® + Caffeinated Coffee; 1 Maxalt-MLT® + 4 Aleve®; Imitrex® by injection Sinnott Family Collection|
A reporter doing a story on migraines asked me about my family’s tendencies toward them.1 With a bit of dark humor, I pointed to a family picture and said, instead of identifying them by name, that I would identify them by the treatments they use at a migraine’s onset. Left to right: 2 Aspirin+2 Tylenol®+ 1 can of Coca-Cola®+ 2 Sudafed®; Excedrin® + Sudafed®; Imitrex® capsule; Excedrin® + Caffeinated Coffee; 1 Maxalt-MLT® + 4 Aleve®; Imitrex® by injection. The treatments, some prescribed and some personal trial and error, were as diverse as our susceptibility to individual migraine triggers and the timing of migraine’s intrusion into our lives. (Note: Doctor’s orders banned the use of the Sudafed “cocktail.”)
Four out of five migraine sufferers have a family history of migraines. If one parent has a history of migraines, the child has a 50% chance of developing migraines, and if both parents have a history of migraines, the risk jumps to 75%.2 In my family, both parents, my grandfather, two aunts and an uncle on my father’s side and my great grandmother and two aunts on my mother’s side had migraines. All of my siblings, my two nephews and one great nephew have migraines.
The recognition of a link to heredity and migraine is relatively new. This is due, in part, to evolving medical and scientific research methods as well as technological advancements. To explore the genetics of migraine, one must look at the beginning of the field of genetics. Gregor Mendel’s landmark work was published in 1866. Based on his pea plant studies, Mendel concluded that traits are inheritable. “Mendel had discovered what later scientists called ‘dominant’ and ‘recessive’ alleles3” (“An allele is one of the alternative versions of a gene at a given location (locus) along a chromosome”).4 In hindsight, this discovery was monumental, however, the impact was not immediate. It wasn’t until 1901 that Mendel’s theories were verified and generally accepted. Confirmation of Mendel’s findings coupled with improved equipment, such as microscopes, accelerated genetic research.
On a personal level, the early 1900s was also the time that migraines were first documented in my family. “I bathed my feet and drank hot whiskey to sweat to try to bring on my monthlies… Sunday I came unwell and of course I felt very bad I was sick all afternoon and all day monday and w monday night…and such a headache.”5 That was written on December 9, 1902, in a letter sent to my maternal great grandfather from my maternal great grandmother. It is, I believe, the first written documentation of my family’s migraines. Also at this time, the oral history of my family’s migraines began with the story of my fraternal Aunt Margaret, who in 1914 at age seven, had a horrific migraine on her First Communion day, a milestone in a Catholic‘s life. She was so sick that her father, known to have migraines that left him bedridden for days, had to carry her to church to receive the sacrament.6
|Fig 2. Margaret Sinnott c. 1914|
Sinnott Family Collection
A major advancement in genetic research came about in 1910 and 1911 when Thomas Hunt Morgan published his chromosomal theory of heredity based on his studies of fruit flies. “Thomas Hunt Morgan, proposed that each chromosome contains a collection of small units called genes…with different genes having specific locations along specific chromosomes.”7 His theory lead to further investigation using fruit flies, confident that they could produce a greater understanding of heredity. In spite of these advancements, it took almost another 100 years for the direct link of specific chromosomes and migraine disease to be discovered and confirmed.
In the interim, my family’s chronicle of migraines continued. Rose Mary, Aunt Margaret’s and my father’s sister, described a migraine she had while in nursing school in the 1930s. She awoke with an extremely bad headache and asked her dorm mate to bring her some aspirin and said that if she was asleep, just to leave them on her nightstand. The next morning, my aunt awakened quite refreshed. Curiously, though, there were two aspirins on her nightstand, but her starched nurses cap pearl buttons/studs were missing. So, she always recommended taking two buttons. Yes, our family often uses humor to help buffer the pain. Was it a placebo effect? We will never know. Later, Rose Mary became a proponent of a very basic form of biofeedback and taught it to me giving some relief.
In the 1940s, the study of a possible vascular component to migraine continued to be explored. “It was proposed that a migraine begins with a spasm…of the arteries leading to the main part of the brain (cerebrum). The first spasm decreases the blood supply to part of the brain, which causes the aura…that some people experience. These same arteries then become too relaxed, which increase blood flow and causes pain.”8 “Triggers,” psychological, dietary and/or environmental elements that seemed to cause migraines in susceptible sufferers, were also being studied. Some believed that triggers caused migraines; others thought triggers were just one factor of many that might induce migraines. In migraine sufferers within the same family, each one’s triggers are as individual as the family members themselves.
In the mid 20th century, heredity regarding migraines was not the major focus of studies. While practitioners were often treating several migraine sufferers within families, noting such by clinical observance, there was not yet the science and technology available to verify how the disease was acquired and if heredity was truly a factor. That changed in the 1950s with two genetic research breakthroughs. In 1952, Alfred Hershey and Martha Chase confirmed, “that DNA is the molecule that mediates heredity.”9 In April, 1953, another milestone occurred in the “scientific paper where James Watson and Francis Crick presented the structure of the DNA-helix, the molecule that carries genetic information from one generation to the other.”10
|Fig 3. Rose Mary Sinnott c. 1935|
Sinnott Family Collection
In regards to my family, the 1960s were when migraine manifested itself among my siblings. When my brother was a youngster, he would get migraines, typically on a Saturday night. He would go to his room and lie under a pile of blankets, bedspreads, afghans etc. in order to block out any light or sound. A trusty wastebasket stood by in case of severe nausea. My mother eventually realized that he always got these headaches on Saturday nights when hotdogs were for dinner—yes, “hotdogs” were his “trigger.” Evidence to further support her claim was my brother being brought home from Boys’ Scout Camp after becoming violently ill during a hotdog cookout. My mother believed that red dye was the culprit. Some in the medical community thought that nitrates in hotdogs were triggers. Regardless, abstaining from hotdogs reduced the number of headaches my brother suffered. In the late 1960s, my teenaged sisters began getting hormonal migraines. In later years, a variety of triggers affected my sisters who experienced auras and light and sound sensitivity. Again, triggers seemed to be a component of migraine, but were they the cause?
In 1966, the genetic code was deciphered, now scientists knew how “DNA’s code is used by cells to build proteins.”11 In 1977, Fred Sanger produced sequencing technology “used to determine the nucleotide sequence of DNA (deoxyribonucleic acid)…It is the blueprint that contains the instructions for building an organism, and no understanding of genetic function or evolution could be complete without obtaining this information.” 12 These discoveries gave migraine researchers more pieces of the migraine puzzle.
Also during this time, serotonin and dopamine levels were seen to be factors in migraines. This approach coupled with the vascular theory of migraine “came to be known as the neurovascular theory of migraine.”13 In many ways, I was fortunate to begin my migraines at this time. They started in the late 1980s and were hormonal in nature, but later turned into a variety of trigger-related occurrences. With the acceptance of the neurovascular theory, medications based on triptans were developed. My siblings and I benefited greatly from these medications.
In the 1990s, heredity in migraines was being studied through genetic research and twin studies. In 1999, J Med Genet published “The inheritance of migraine with aura estimated by means of structural equation modeling” which studied twins to understand the roles of genetics and environment in the inheritance of migraine with aura.14 In 2001, the human genome was sequenced which meant that researchers now had the science and technology to relate specific genes present in specific diseases, including migraine. This greatly accelerated studies in regards to migraine and heredity.
In 2003, results from the “Genetic and environmental influences on migraine: a twin study across six countries” resulted in a heritability range from 34% to 57%.”152003 was also the year that chromosome 11q24 was linked directly to migraine with aura.16 2012 brought the confirmation that there was a chromosomal link to migraine without aura.17The United States National Institute of Neurological Disorders and Strokes (NINDS) recognizes research regarding the genetic component. It states that “Researchers believe that migraine is the result of fundamental neurological abnormalities caused by genetic mutations at work in the brain.”18
In the area of genetics, only one of my siblings has been tested. My sister was found to have the genetic variation MTHFR. As for myself, when there are treatments related to the findings, then I will proceed with tests. However, we all still trade notes on treatments as they have changed as have our migraines through the years. Looking at that family picture now, left to right are: “Excedrin with Diet Coke; Excedrin®;Relpax®; Maxalt MLT®; Relpax®; Migranal Nasal Spray®.” I’m looking forward to the day that those descriptions no longer come to mind and that we’re just, left to right: Nancy, Joe, Terri, Chris, Leslie, Linn. Migraines are our legacy, a legacy that we wouldn’t wish on anyone.
- The New York Times “Is There Such A Thing as a ‘Mini-Migraine’?” Consults New York Times Blog July 23, 2010 http://consults.blogs.nytimes.com/2010/07/23/is-there-such-a-thing-as-mini-migraines/.
- Cleveland Clinic. “Diseases and Conditions Migraine Headaches.” Last modified December 11, 2011. Accessed January 2, 2014. http://my.clevelandclinic.org/disorders/migraine_headache/hic_migraine_headaches.aspx.
- University of California Museum of Paleontology, Berkeley. “Understanding Evolution: Discrete Genes Are Inherited: Gregor Mendel.” Accessed January 16, 2014. http://evolution.berkeley.edu/evolibrary/article/history_13.
- Genetics Home Reference. “Allele.” Last modified February 18, 2014. Accessed February 22, 2014. http://ghr.nlm.nih.gov/glossary=allele.
- 1902 correspondence of Theresa and Edwin Brouillette. John Mize Collection.
- Nancy Egierski, oral interview with author, 2013.
- Eric R. Kandel. “Genes, Chromosomes, and the Origins of Modern Biology.” Columbia Magazine Living Legacies Series. http://www.columbia.edu/cu/alumni/Magazine/Morgan/morgan.html.
- emedicine health. “Causes and Treatments of Migraine Headaches.” Accessed January 12, 2014. http://www.emedicinehealth.com/script/main/art.asp?articlekey=59066&pf=3&page=2.
- Department of Biology Davidson College. “Timeline of the History of Genetics.” Last modified August 27, 2009. Accessed January 21, 2014. http://www.bio.davidson.edu/people/kahales/301genetics/timeline.html.
- Nobel Prize. “The Discovery of the Molecular Structure of DNA-The Double Helix A Scientific Breakthrough.” Accessed January 21, 2014. http://www.nobelprize.org/educational/medicine/dna_double_helix/readmore.html.
- University of California Museum of Paleontology, Berkeley. “Understanding Evolution: Chromosomes.” Accessed January 21, 2014. http://evolution.berkeley.edu/evolibrary/article/0_0_0/history_18; and Department of Biology Davidson College “History of Genetics.” Accessed January 21, 2014. http://www.bio.davidson.edu/people/kahales/301genetics/timeline.html.
- Encyclopedia Britannica. “DNA sequencing.” Last modified July 5, 2012. Accessed January 21, 2014. http://www.britannica.com/EBchecked/topic/422006/DNA-sequencing.
- emedicine health. “Migraine Headaches.” http://www.emedicinehealth.com/script/main/art.asp?articlekey=59066&pf=3&page=2.
- Vibeke Ulrich et.al. “The inheritance of migraine with aura estimated by means of structural equation modelling,” J Med Genet, 1999; 36:225-227. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1734315/pdf/v036p00225.pdf.
- E.J. Mulder et.al. “Genetic and environmental influences on migraine: a twin study across six countries,” Abstract :win Res. 2003 Oct;6(5):422-3114624726[PubMed – indexed for MEDLINE]. http://www.ncbi.nlm.nih.gov/pubmed/14624726.
- Zameel M. Cader et. al. “Significant linkage to migraine with aura on chromosome 11q24,” Human Molecular Genetics, 2003, Vol. 12, No. 19, 2511. Copyright Oxford University Press 2003. DOI: 10.1093/hmg/ddg252 2511-2517.
- Tobias Freilinger et.al. “Genome-wide association analysis identifies susceptibility loci for migraine without aura,” Abstract Nature Genetics 2012; 44; 7;777-82. http://www.ncbi.nlm.nih.gov/pubmed/22683712. Nature Genetics 44, 777-782 doi:10.1038/ng.2307. http://www.nature.com/search/executeSearch?sp-q-1=NG&sp-q=migraine+without+aura&sp-c=25&sp-m=0&sp-s=&sp-a=sp1001702d&sp-sfvl-field=subject|ujournal&sp-x-1=ujournal&sp-p-1=phrase&sp-p=all&submit=go .
- National Institute of Neurological Disorders and Stroke. “Migraine Information Page: What research is being done?” Last modified February 7, 2014. Accessed February 22, 2014. http://www.ninds.nih.gov/disorders/migraine/migraine.htm
TERRI SINNOTT, MA, is a museum consultant with over 25 years experience in museum project management and exhibit development, in both non-profit and corporate museums, including Chicago’s Museum of Science and Industry, Motorola’s Museum of Electronics, and Motorola’s Beijing Gallery. Ms. Sinnott holds a BA in history from the University of Notre Dame, MA in history museum studies from the Cooperstown Graduate Program/SUNY, and a Masters Certificate in project management from George Washington University. She also developed and taught a museum management class as adjunct-faculty in the Public History Department at Loyola University.