Abstract: By 2001, two years after approval, the new MassGeneral Institute for Neurodegenerative Disease (MIND) building was designed, built and opened. About 30 independent faculty laboratory heads occupied the laboratory floors. Each lab head had 5–15 people in their lab and in total about 300 people worked on the two main floors. Anne’s lab and office moved to MIND. Early on, she was still very depressed about Jack’s death and needed help to continue her research. Without Jack, Anne didn’t have enthusiasm or ambition. Zane Hollingsworth and Anne’s previous trainees, Jang-Ho Cha and David Standaert, helped Anne with her students, postdocs, technicians and grants. Anne was elected president of the American Neurological Association and then president of the Society for Neuroscience. Six years after Jack died, Anne received an email from her old eighth-grade and sometimes high school boyfriend, Stetson Ames. He was coming to Boston in May and asked Anne if she would like to meet. She and Stets eventually married. Anne inherited $2 million when her mother died, a million of which she donated to Mass General. Nancy Wexler began showing signs of Huntington’s disease. It was undeniable, but neither Anne nor Nancy could face the devastating possibility.

Abstract: Anne’s first years at Mass General were very exciting scientifically. Faculty members Rudy Tanzi, Jim Gusella and their collaborators found the gene for one form of Alzheimer’s disease and Robert Brown found another gene for one form of amyotrophic lateral sclerosis (ALS). Finally, ten years after finding the marker, the project paid off. At the end of February 1993, Marcy MacDonald and Jim Gusella told Nancy and Anne that they had found the actual mutation in the gene for Huntington’s disease. Now they knew that the HD gene mutation was composed of an abnormal number of repeated sequences in the DNA, which was keeping with what other research scientists had already found to be the cause of several other neurologic diseases. The identification of the gene mutation allowed for many new experiments to be done. The identification of the gene mutation also made possible a simple blood test that allowed people to determine whether they had inherited HD. At first, there was some enthusiasm for getting tested. However, it soon became clear by the relative few who signed up for the test that many people would rather live with ambiguity than know they would definitely develop a deadly, incurable disease sometime in the future.

Anne Young, a neurologist at Harvard and Mass General, experiences a traumatic life change when her husband, a neurologist and collaborator in her field, returns from a week of neuroscience meetings in Aspen, Colorado, complaining of pain in his throat and dies suddenly in his sleep from a heart attack. Anne tries to be strong for her daughters, Jessie and Ellen. She gains comfort from friends in her field and family, who give her the strength to cope. Most of all, Anne is comforted by Nancy Wexler, a dear friend who is like a second mother to her daughters. Having Nancy by her side lightens the burden and impossibility of caring for herself and her daughters while experiencing an unbearable loss. Nancy accompanies Anne to the Ether Dome for Neurology Grand Rounds for a presentation on organ donation. It is an opportunity for Anne to thank her colleagues and friends during this terrible time and tell them how she donated as many of Jack’s organs as she could for research. The courageous steps she takes to express herself are cathartic, yet, in times of desperation and loneliness, she doesn’t know how her future will unfold.

Abstract: As they continued to work together, Anne and Nancy Wexler became closer friends. Anne, Jack, Jessie, Ellen and Nancy traveled to Peru to conduct more research along with other Venezuela-trip veterans such as Graciela Penschensadeh (an Argentinian), Maria Ramos (a Spanish geneticist), Ira Shoulson and Fidela Gomez (an Argentinian nurse). They arrived in Lima in the middle of the night and Dr. Cuba (the Lima neurologist who knew the HD families) met us at the airport and took us to the Hilton Hotel. The next day, they rented two Toyota pickup trucks. They traveled south to the Cañété Valley where they found a hotel. They spent two weeks going up and down the valley, from town to town and house to house finding, questioning and examining families affected by Huntington’s disease. To keep Jessie and Ellen busy, Anne gave them the job of photographing people in the HD families and writing their names on the back. They had just received Polaroid cameras for Christmas that they used. By the end of their trip, Anne and the rest of the team discovered that their hotel was a money-laundering operation complete with four-star rooms, restaurant, pool and laundry.

Abstract: Medicine improved since the beginning of Anne’s career. Therapies improved for neurological illnesses such as Parkinson’s disease, epilepsy, multiple sclerosis, myasthenia gravis and others. Improvements can be made in the time doctors have to spend on paperwork and extensive documentation required by insurance companies that leave less time for actual patient interactions. There are still challenges for women, such as their promotion to the highest academic and leadership levels. Anne describes the advances since her early studies in Sol’s lab. By 2015, it was becoming impossible for Anne to deny Nancy’s signs of HD. Anne wanted so much to help her. Nancy’s sister, Alice, became a close friend and they both hoped Nancy would join a clinical trial. Several promising therapies were being tested and Nancy agreed to join one. Before she was able to actually join the trial, however, it was suddenly stopped as it was making people worse. Over weekly Zoom calls with Anne and Alice, Nancy was excited that her Hereditary Disease Foundation (HDF) was going to fund three large and extremely innovative research grants that promise the application of novel approaches to find HD therapies.

Abstract: At Ann Arbor, Anne applied for grants from the National Institutes of Health (NIH) and the National Institute of Neurological Disorders and Stroke, which she received. Sid Gilman suggested Anne speak with her health science administrator (HSA) Nancy Wexler for advice. Wexler told Anne her grant proposal was accepted. With the grants, Anne and Jack could spend 80 percent of their time in the laboratory and 20 percent of their time seeing patients (one day a week). The experiments Anne proposed turned out to be complete failures. She decided that it was not worth pursuing further. Instead, Anne and Jack used their time to study the main pathways of the motor system. Jack did the surgery, made and evaluated the lesions and Anne conducted the biochemical experiments. They proposed the idea of a Movement Disorders Clinic to Sid. They hoped to focus on Parkinson’s disease, Huntington’s disease and related disorders. Movement disorders fascinated both Anne and Jack because it was a subspecialty relying on direct patient observation. With the stability provided by the grants, Anne and Jack decided to have another child, Ellen. Anne met Nancy Wexler at the Society for Neuroscience meeting in Atlanta after Ellen was born.

Abstract: Anne became more familiar with Nancy Wexler. Nancy was at risk for Huntington’s because her mother had had it. Wexler was a founding member of the Michigan Chapter of the Committee to Combat Huntington’s Disease. Anne was invited to attend a workshop at the Hereditary Disease Foundation (HDF). The HDF was founded by Nancy’s father, Milton Wexler, a psychoanalyst. In 1981, Nancy invited Anne to Maracaibo, Venezuela, to pursue studies of the families that she had presented two years before at Michigan. Anne would examine the family in which two parents with HD had together birthed 14 children, all of whom were living. Anne had never been out of the country without Jack; she got his approval, but she could tell he was jealous. At the Maracaibo airport, she met the team, such as Steve Uzzell (a photographer), who she’d be working alongside. She knew Ira Shoulson, a neurologist and HD expert; they overlapped for a day. Nancy’s goal was to put together a detailed family tree of all the HD families, take blood and skin samples from each family member and examine each person neurologically and cognitively. The team went to Lagunetas, a remote stilt village to examine the family.