Mapping Fate:: A Family at Risk Confronts a Fatal Disease

by Alice Wexler

Wexler tells two stories, the one of her family's emotional odyssey after her mother was diagnosed with Huntington's disease, and the relentless efforts to find the gene and a cure, and the news that she had a 50/50 chance of getting it also. This book comes from her unique position of being both reporter of how scientists sought a cure and someone who could be saved by it.

Genres: Nonfiction, Science, Genetics, Memoir, Medical, Biography, History

294 pages, Hardcover

First published January 1, 1995

About the author

Alice Wexler received a Ph.D. in history from Indiana University in 1972. She has taught at UC Riverside, the California Institute of Technology, Claremont Graduate School, Occidental College and UCLA. She has been a Research Scholar at UCLA's Center for the Study of Women since 1994.

Reviews

[Nancy · Rating 4 out of 5]

Posted at Shelf Inflicted

“The ambiguous condition of 50% risk is extremely difficult to maintain in one’s mind, if not impossible. In practice, a 50-50 risk translates to a 100% certainty that one will or will not develop the disease.”
― Nancy Wexler, Genetic Russian Roulette

Before reading this book, I was aware that singer-songwriter Woody Guthrie died of Huntington’s disease in 1967. What I didn’t realize until after I read this book was how cruel this disease is. Symptoms usually develop between 30 and 50 years of age. In the early stages, patients may experience mild cognitive symptoms and psychiatric changes. Later on, they experience chorea, or abnormal involuntary movements, in different areas of the body. In later stages of the disease, individuals may have difficulty walking, speaking, and swallowing. Pneumonia and heart disease are the leading causes of death for people with Huntington’s disease.

Daniel Mundy’s (1976-2014) battle with Huntington’s disease:
https://www.youtube.com/watch?v=JzAPh...

This scientific memoir is utterly fascinating, despite the fact that some of the science went over my head. Still, I feel that Alice Wexler did an admirable job writing a compelling story about family, living with the risk of disease, and the innovation and efforts by her father, her sister, Nancy, and the scientific community that led to the discovery of a genetic marker for Huntington’s in 1983.

Alice’s mother, Leonore Sabin, was 53 in 1968 when she was diagnosed with the disease. Her father and three brothers had already died. Her husband, Milton, started the Hereditary Disease Foundation, and dedicated his efforts to inspiring researchers and caring for his sick ex-wife.

Nancy’s work with the foundation took her to the fishing villages near Lake Maracaibo in Venezuela, where about 1 in 10 people have Huntington’s disease.

Despite the grim subject matter, I found this very hopeful and optimistic. Even though there is still no cure for Huntington’s disease, there are drugs that can help alleviate certain symptoms and the option for those at risk to undergo genetic testing to find out whether they will develop HD in the future.

[Reece Smith · Rating 5 out of 5]

An incredibly well-written account of the efforts to find the Huntington’s disease gene in the 1980s by somebody who was personally affected and whose family was at the forefront of the project. Wexler skilfully weaves this narrative along with a memoir of sorts in order to discuss living with embodied risk

[Barron Lerner · Rating 4 out of 5]

I can understand why some of the reviews for this book are fairly low. Wexler tries to an awful lot of things in this book and, at times, her agenda may not seem clear. First, the book is a social history of Huntington's disease, the devastating genetic neurological condition that strikes healthy people in middle age and leads to a gruesome death. Second, the book is a tutorial about the science of Huntington's and the researchers who have studied it. The level of detail here may numb the casual reader. Third, and most important, "Mapping Fate" is a memoir about a family devastated by the disease, and its simultaneous efforts to deal with personal tragedy and help scientists conquer it. Wexler's mother and many relatives died of Huntington's but, as in many families, the whole topic was shrouded in shame and secrecy. Meanwhile, Wexler and her sister Nancy needed to decide whether or not to undergo the genetic test that would reveal if they would eventually become ill. But the book's complexity is also what makes it so important. It is an outstanding example of how our understandings of disease, while seemingly a story of scientific progress, have all to do with politics, funding, the media and--within families--how the ill and their loved ones process issues such as infirmity, stigma and, ultimately, death. All families should aspire to the Wexlers' example.

[Linda · Rating 4 out of 5]

At 54, your mother began not being "herself." She seemed to forget how to do things, simple things, like planning dinner. Then she started stumbling and tripping when there was nothing there to trip on. Finally, your father takes you aside and explains: your mother has an incurable disease that will slowly wreck her body and possibly her mind as well. And you have a 50% chance of having it too. And, if you have children, they are at risk too.

Now there is a test. It can tell you for sure whether you will develop this disease, which usually only begins its rampage around age 35. Will you take the test?

This was the dilemma facing Alice Wexler. Her mother died of Huntington's disease. Her maternal grandfather did, too. Her mother either did or did not (he didn't seem to be sure about it) mention it to your father before they had children. Her father, her sister, and to a lesser extent she, herself, began the hunt for the gene responsible almost as soon as their mother was diagnosed and began her noticeable decline.

And it was a success. Through a foundation her father began and her sister participated in until her career gave her a better opportunity to organize studies of the disease, scientists were found that became fascinated and dedicated to finding the gene, families were located to help with research, and an incredible community in Ecuador that had several generations living in proximity, many with Huntington's, and, eventually, the gene itself was isolated.

A test was developed that would tell potential sufferers if they had the gene and remove all doubt. Would they do it? Wexler and her sister decided not to. Some people did and the results were interesting. Some who were sure they would get HD were surprised that they did not have the gene and were angry that they had put their lives on hold, no marriage, no children, no dedication to a profession, because they were sure they would develop it. Others, who had been sure they would get the disease were confirmed and found that, now that they knew for sure, they were unsure what to do with the information and realized that they, maybe, hadn't been so sure after all.

The book is fascinating from two points: the hunt for the gene involved a lot of coordination, many different theories and actually succeeded because scientists began to truly collaborate - going to workshops where they actually tossed around ideas, building on each other at the moment, rather than waiting for formal publications and refusing the competitiveness of trying to find the answer alone; and then of course there is the fact that the author is a potential sufferer. And, most importantly, that it was her family that is responsible for finding the gene.


So, if you were at risk for a disease that wouldn't appear until after you had children and was incurable, destroying your body and mind slowly but inexorably and terribly, would YOU take the test?

[Farah Bader · Rating 4 out of 5]

In the past, if asked whether I would want to be tested for HD if I had a family history of it, I would have said "yes, a thousand times yes" but after reading Wexler's personal memoir's I'm beginning to see that it's not a simple black and white issue, particularly with no cure in the horizon. After being privy to the author's emotional pain resulting from watching her mother's conditions deteriorate with the progression of HD, I now realize the ramifications on other family members if one person decides to be tested and others do not. Pay attention to the relationship between the daughers and the father in this book. As the unaffected parent, he appears to be a frustrating character but his efforts to advance HD research and unearth the genetic origins of HD are commendable and his reluctance in allowing his daughters to be tested just humanizes him even more.

[Chrissie]

I think this book could be very interesting. I think it will cover both the scientific side of Huntington's disease, the implications of genetic testing and also the emotional impact a hereditary disease, not just Huntingtons, has within a family. And I liked the text, the way the author expressed herself in the book's first pages visible at Amazon. Thank you Lynne for bringing this book to my attention.

[Penny Zang · Rating 4 out of 5]

I somehow read this book in two days despite my busy schedule and confusion over all the biology/genetic "stuff" (which is also endlessly fascinating). I may have a biased interest because of my family's history with Huntington's, but it so far the most insightful text I've read on the subject. And, needless to say, terrifying. But how it could it not be?

[Kim Potvin · Rating 2 out of 5]

The subject matter is fascinating but the author is inconsistent. She will get very granular with scientific information as though it is a journalistic piece and then throw in some arbitrary information about herself. If given the option I would prefer to read a straight non-fiction book on Huntington's Disease.

[Lauren · Rating 2 out of 5]

a story about the search for the huntington's disease (hd) gene by the sister of one of the lead researchers. the two sisters also happen to be at risk of hd as their mother died of it. an interesting blend of personal and professional writing.

[Pat · Rating 4 out of 5]

An insightful view into the complex issues that face families of genitic diseases. Chapters devoted to research may be a bit detailed for readers outside the Huntington's Disease circle but overall well worth the read.

[Kate · Rating 2 out of 5]

This wasn't what I was looking for. It was too sciency to be a memoir and too memoirish to be a science book. It sounds like a great combo, but it didn't work for me. I gave up halfway through after renewing it about 9 times at the library.

[Erin · Rating 3 out of 5]

Frightening, thought-provoking.

[Allison · Rating 3 out of 5]

A great book for those interested in medicine, genetics, or Huntington's disease in particular. Probably a bit dry for others.

[Karen · Rating 5 out of 5]

Very moving and important story. Poignantly told. Extremely useful book for understanding so many different aspects of HD. I'd recommend this one first off to a friend or family member.

[Patrick · Rating 3 out of 5]

I liked the personal account of Alice Wexler's quest into finding the gene responsible for Huntington's disease so for that I give this book 3 stars.

Having Huntingtons suck b/c not only is ones body effected but also ones mind. While some members of the family consider Huntingtons to be part of their identity, other members think it ought to be kept inside the family. The book is living with the risk of an incurable disease. Like XDP, patients with Huntingtons can live productive lives as long as they have the necessary support system to allow them to have independent productive lives.

Wexler whose mother is smart graduating the top of her class and pursuing a masters degree @ Columbia got Huntingtons and did not tell her husband before he married her. She belonged to a family of professionals though her mother actively discouraged her from pursuing PhD for fear she would not be marriage material. In her family, Huntingtons carried a heavy stigma of a curse in the family line. Alice's paternal grandfather was a womanizer and "Willy Loman" type of real estate magnate. Her dad was a failed lawyer b/c it seemed to him that it was less about justice than it was about arguing the best way possible. So her dad quit being a lawyer to do a PHD in Pychology and began a psychotherapy practice b/c he loved human character and its multiple permutations. Although their mother was highly intelligent, she was not a rebel so she was okay with being in a traditional female role.

I like how Wexler characterizes the shock she and her family must have experienced knowing that her mother and daughters can get it too. Their mother felt shyness and sadder knowing the possibility of disease. Alice did not like the passivity that her mother possessed. Like all teenagers, she was obsessed with the feelings of popularity though she also liked thinking about death and sex (goth preoccupations). Alice was mad at the betrayal of her father divorcing her mother after her father's long term affair with a colleague. Her father's and mother's divorce precipitated a renaissance in both their lives but her mother's renaissance came to an abrupt end when she started exhibiting symptoms of Huntingtons.

Dr. Huntingtons was the first physician who described Huntington's. In the early 20th century, the anti-immigrant movt funded studies to sterilize Huntington patient but the study also found that Huntingtons is an autosomal dominant disease. Huntingtons disproportionately effects the Caudate nucleus of the Basal Ganglia in which 1/3 of the brain cells seem to die. They found that the younger patient is the more severe the symptoms will be and the more it will progress to death b/w 7-8 years versus the usual 10-20 yrs of an older patient. They also grew stiffer as opposed to the chorea movts of older Huntingtons. Like XDP, Huntingtons' symptoms of uncontrollable movements disappeared when a person is asleep and they also become emaciated. The question becomes why is the person emaciated is it b/c of increased Basal movement or secondary to basal ganglia metabolic influences. The social component of seeing what happens to a parent with Huntingtons could be debilitating and the guilt that a parent passes on to their child is also severe. Mother's Huntington symptoms made her more fearful and uncertain which also increased her loneliness. Alice became depressed b/c she found the love of her life only to think she was not deserving of that love since she came with Huntingtons, meanwhile, Nancy decided never to have children in order to stop the progression of Huntingtons disease.

Just as Huntington's came with a 7X increase in suicide rate, especially in their earlier years, their mother tried to commit suicide knowing what had happened to her brothers and father. The children tried to convince their mother not to take her life b/c of the disease. The disease strained Alice's relationship with her father which she felt was filled with recriminations for not being

more vigilant in finding out the past of the woman she was marrying while strengthening her bond with her sister and the feminist movement. Meanwhile, her father and his mistress became her mother's primary caretaker.

Mendel thought of the law of independent assortment that is, each gene, is transmitted separately from the other genes of a given trait. But certain traits are inherited in batches which scientist termed as linkages. But in certain people, traits that were previously linked becomes unlinked in the process of recombinant DNA during meiosis. So what previously was a gene from the mother gets switch to the father genetic material. While giving L-Dopa eased the Parkinsonian symptoms, it made Huntington's symptoms worse. So the hypothesis is that while the lack of dopamine made Parkinson disease worse too much dopamine makes Parkinson better.

Their father and Mayline became instrumental partners in fighting the disease. Wexler the father was instrumental in building a foundation dedicated in finding a cure. So they had a Huntingtons scientist come to try to find a cure. Whereas clinicians wanted people who were smarter, scientist wanted people who were younger who knew the latest methods but were not influenced yet by any hypothesis and thus remained open minded. Their father believed in free-association in creating interdisciplinary ideas in order to create new solutions to solving old problems. He believed thinking creatively was best achieved in an informal setting in which everyone involved felt safe, relaxed, and playful. He invited only scientist who were confident and open to interacting with other scientist from other fields in "corridor talk". Since science is inherently organized, a workshop that encouraged free thinking in an intimate setting of 15-17 people was great.

Nancy feared the stigma of having a genetic disease that affected her mind could possibly affect how people in her field saw her. Will telling people that she might have a terminal illness lead people to wonder about her capabilities to the job. It is young untested post-docs that come up with the best ideas for breakthroughs. While Mr. Wexler thought basic research was the most important piece of the puzzle (XDP Foundation), Mrs. Guthrie thought that grass-roots organizing, education, and patient care were the most important piece of the puzzle.

Nancy became the head of the commission trying to put the Huntington picture in the US together.

In Venezuela, Dr. Negrette diagnosed people with Huntington's. He described their loneliness and isolation. The isolation they felt made them constantly think about death. At least, they realized that the disease is hereditary and not a curse from God and they realized that they are all in the same boat. Once Nancy was placed as head of NIH head, she went to Venezuela in search of the famous homozygous Huntington. She was pleasantly surprised how willing the local population helped in them with the research and how well they were integrated into the community. Venezuela was key in that everyone descended from a common ancestor which limits the number of variables, which is called the founder's effect. They lived in proximity to each other, had large offspring with both effected and non-effected members.

Nancy wanted to gain the trust of the Venezuelans so she told them she had the disease which led them to trust her so that she could get blood from them. Young shows how staging the disease is

important in later curing it, if a cure materializes. Alice tries to trace the ancestral lines of Huntingtons disease in Venezuela.

They first found the genetic marker of Huntingtons by using RLFP technology although the G8 marker was neither sensitive nor specific. The question then becomes, does one want to know if they have a terminal illness during the presymptomatic phase. Familial emotions flare b/c a positive result will effect the whole family not just the person getting tested. The only reason to take a presymptomatic test is if one was thinking about having children or if there was a cure for the disease. Alice states living with doubt that one may get the disease undermines confidence b/c one does not know whether the normal setbacks of life is due to the disease or not. Having Huntingtons means a lose of identity. People who like having control usually have the test done though the anxiety for those who have a positive result never goes away. Even if the results are negative, the patients lose their identity as @risk Huntington which causes them to lose their sense of self briefly. Presymptomatic testing effects both the patient as well as his family so it has wide ranging repercussions.

In '86, it was determined that the homozygous for the Huntington gene was not clinically more significant than the heterozygous. The Huntington's disease collaborative group was the prototype of a collaborative effort for scientists and on their way in solving Huntingtons they discovered new scientific technologies. They solved the question of authorship by signing it the HD collaborative research group and have the PI decide the order of the participants. Those who stayed in the group tended to be unusually self-confident and cooperative people, willing to expose themselves to group scrutiny and to give up individual fame for collective achievement. It was essential of the importance of troubleshooting competitive issues and to remind people that this is not about the fame and glory. The collaborative research team was led by Nancy Wexler presence along with the family atmosphere of the workshops which led each research group to focus on the collective victory. On Feb 24, 1993, the Huntington gene was found on the short arm of chromosome 4 which codes for the Huntingtin protein.

Medical genetics testing is a family affair. But they realize that being positive on the genetic test leads one to not plan for a future. Wexler makes the case that predictive testing for a lethal disease like Huntingtons is never innocuous and always carries the potential for negative repercussions not only to the patient but also to the family too. Wexler states the people who do not want to get their genetic test done do so b/c there is an absence of an effective cure, the potential loss of health insurance (pre-Obamacare), financial cost of testing, the degree which being fired is a danger, and the inability to undo the knowledge once it is known.

[Evelyn]

I had very personal reasons for reading this book. Someone very close to me had his life changed in a multitude of ways due to his proximity to someone one who was a possible carrier of the Huntington gene. Huntington’s disease has been described as the most horrific genetic disease ever discovered. It is like haveing Parkinson’s, schizophrenia, dementia and ALS all at once, and it strikes in the prime of life. Any child of a parent with the disease has a fifty percent chance of inheriting it. There is no effective treatment or cure.

This is the story of the Wexler family who devoted their lives to pinpointing the Huntington gene and later developing a test that would allow an at risk person to find out if they did have the gene.

This is not just a story about the science, but also about being a family at risk. The Wexler matriarch died of this disease which inspired her daughters and husband to search for answers amid their fear. This story is filly with determination, perseverance and hope.

[Anne · Rating 4 out of 5]

A memoir about a daughter's experience watching her mother die of Huntington's, a disease that she has a 50% chance of inheriting. It's a particularly difficult disease to watch progress, as it results in all sorts of personality changes, inability to control muscle movement, and so forth.

This is also an account of how the scientific community came together to find the gene responsible for Huntington's. It's interesting that even now, decades after this book was published, there still is no cure for Huntington's. There are only diagnostic tests--so what do we do with that? Up for us to decide...

[Sabrina Harris · Rating 2 out of 5]

Informative and educational, but definitely for the
'higher level' individuals with a scientific mind who can easier comprehend the delve into the scientific specifics. I struggled to maintain interest and had to power thru as I got lost and had to do a lot of re-reading of the thick science areas.

[Lkn99goodread · Rating 4 out of 5]

A fascinating story on the Wexler family’s efforts to help to find the genetic clue to Hungtington’s disease. Touching and candid, sometimes embarrassingly so. A very good read.

[Wendy · Rating 4 out of 5]

In the fields of genetics and genomics today, we take classical Mendelian disorders like Huntington disease for granted, forgetting that at the time, no disease gene had been identified without knowing what the gene did, or where the gene was. Alice Wexler tells the story of a thrilling chase to find the Huntington disease gene, which once discovered, would allow for predictive genetic testing of unaffected individuals (unleashing an entire field of gene ethics). She unveils the eventual breakthrough discovery of the gene as the culmination of daring bets and novel scientific approaches. Now, more than 10 years since the Human Genome Project's completion, with genetic services extending to every rare disease, it is breathtaking to realize how little we knew in 1979, and how far we've come today.

As a genetic counselor, I am most moved by Wexler's deeply personal account of her connection to - and identity in - the Huntington disease world. She allows the reader to experience all the unfinished edges in her story - her contentious relationship with her father, who has a personal and scientific investment in Huntington research; her frustrations with her passive, 1950s-housewife mother; her personal struggle with relationships and infertility in the context of being at-risk. I appreciate that she did not heroify every character in her memoir, as some do when eulogizing.

One facet I found most fascinating was that Wexler describes Huntington disease as a direct threat to her womanhood. In the days before prenatal and preconception genetic testing, being at risk meant (to Wexler and her sister) that a woman could not in good conscience marry and become pregnant without the chance of passing the disease to the next generation. I only wish she wrote more of how her personal journey, such as why she decided to try for a pregnancy despite the risks (a decision never fully explored in the book), and what soul-searching discussions she must have had with her partner on the subject.

What is especially interesting to me is Wexler's experience of being an at-risk person, prior to and after the availability of predictive genetic testing. The clear climax of the novel was the chapter "Testing Fate." Once the HD gene was finally mapped, what were the protagonists going to do with this information? As it turns out, after all those decades of pining for the certainty that a genetic test could bring, both sisters decided to defer genetic testing. I admire and agree how Wexler emphasizes that the decision to not test is no less "brave" than the decision to test. Each sister realized that uncertainty would remain, even if they knew their disease status. That's the real punchline - at the end of the day, we cannot escape uncertainty; we must each cope with it.

Wexler's memoir is a moving periscope into the Huntington gene-finding saga. Her chapters jump back and forth in style - at times abruptly - among diary, science journalism, and biology textbook. She attempts to use a fish metaphor as a connecting theme, perhaps a bit unconvincingly, but it did bookend the story well. Readers with an interest in scientific discovery stories, as well as personal illness experience, will find this a story of resilience and hope in the face of inescapable fate.

[Crosby · Rating 3 out of 5]

It is almost impossible to imagine how stressful it must be to live with a 50% chance that you will die with an incurable, hereditary disorder in mid-life. For that unlucky half it is not enough to know that death is certain but the terrible way that one will die is so devastating that many choose to end their own lives. Despite that, some have conceived children who will also inevitably be faced with the same distressing odds of death. Huntington disease is the killer. It runs through families as a dominant trait meaning all children born to a parent with the disease, have a 50% chance of also dying of the disease when they hit midlife. The Wexler sisters, Alice and Nancy, were children of a mother who died of the disease. This book is the story of these siblings and how they lived their lives in the face of such daunting odds. Rather than accept their fate, these two highly intelligent women made history by studying the disease at a scientific, social and historical level. Alice (the historian) describes the role of her father and sister in this book as they developed the framework for studying the disease that ultimately led to her sister assuming a leadership role in the scientific investigation of the disease. The strength of the book lies in a first hand narration of what it is like to spend one's life knowing that she and her sister are at risk for the disease that had such a devastating effect on their mother and uncles. Another strength is that it does an excellent job of describing how the new advances (at the time-1978-84)in molecular biology were incorporated into discovering the location of the gene for the disease (however, readers who have no science background might get lost in some of the detail). I also enjoyed the details describing how a family history (pedigree) of 14,000 plus was constructed on site in Venezuela by the Wexler team (in fact, it filled in some of the details that I lacked when I discuss this disease in my genetics classes). Weaknesses include the last couple of chapters. The discovery of the gene is just out of the blue announced without any specifics and then not discussed much beyond that ---almost as an afterthought. The last chapter discusses the social and psychological impact of having a test available that could tell one whether they have the gene or not ---although important, a whole chapter discussing surveys was another tedious section to read. There were also many loose ends that Wexler never returned to after introducing them earlier in the book. For example, how did they discover the gene was a triplet repeat; what did she and her sister decide to do once a test based on the gene was discovered;did she continue to try to have children and if she conceived what was she going to do if the child tested positive, etc. A unique book and one that will be on my recommended list for my medical genetics class.

[Madison VanEpps · Rating 1 out of 5]

In the second half of this trimester I read " Mapping Fate: A Memoir of Family, Risk, and Genetic Research" by Alice Wexler. This book is about a family with a disease in their genes called Huntington's. Basically the book talks about their family, memories, and genetic research to clear the disease from their name. I would not recommend this book to anyone. If you like non fiction, then you might like this, but it's a long book. It's not long so much in pages, but the speed you have to read it at makes it seem longer. Basically to sum it up, I was not a fan of this book at all, and I would not recommend it to anyone who likes fictional books more than nonfiction books.