In July 2022 Dorlue Schulte of San Diego died at home after a long struggle with Huntington’s disease. To benefit HD research, Dorlue donated her brain to the Harvard Brain Tissue Resource Center (HBTRC) at the nonprofit McLean Hospital in suburban Boston.
“They can get hundreds of samples from one donation, so it’s truly the gift that keeps on giving,” said Dorlue’s husband and main caregiver Doug in a presentation last October at the Huntington’s Disease Society of America (HDSA) San Diego chapter’s “Family is Everything” Education Day.
Doug observed that HD researchers are “coming up with great ways to inspect the brain to learn from them.”
Dorlue Schulte (family photo)
“Scientists now have the ability to look at every cell in the brain and look at the mRNA and the proteins in the cells to see if they are resistant or not resistant to Huntington’s disease and, more importantly, probably, the timing of when (cell) death occurs,” Doug explained. “They’ve got to compare it with a brain that’s not diseased.”
For his outstanding advocacy Doug received the 2021 Woody Guthrie Award at the HDSA national convention. He served on the HDSA-San Diego board from 2019-2022. A retired firefighter, Doug has raised awareness about HD among police officers to make them “a friend, not a foe,” when encountering affected individuals.
You can watch Doug’s 30-minute talk in the video below.
‘Precious’ human data
Besides research on HD mice and many other non-human species, study of HD brains provides “precious” human data in the quest for treatments, in the words of Robert Pacifici, Ph.D., the chief scientific officer of the key, HD-focused CHDI Foundation, Inc.
At meetings like CHDI’s Annual HD Therapeutic Conference scientists discuss the growing body of knowledge coming from these brains.
Doug was inspired to present Dorlue’s story in part by Dr. Pacifici’s statements about the importance of research in humans. Although the huntingtin gene exists in many species, only humans develop HD.
Over 10,000 brains collected
Founded in 1978 and one of the first brain banks in the U.S., Harvard Brain Tissue Resource Center is one of six repositories that are part of the federal National Institutes of Health (NIH) NeuroBioBank, a centralized resource for the collection and distribution of human brain specimens for research.
According to the HBTRC website, it has collected over 10,000 brain donations from across the U.S. and distributed over a hundred thousand samples, both nationally and globally, that have resulted in hundreds of publications. More than 45 different brain disorders are represented in the HBTRC collection, including HD.
HDSA endorses HBTRC. The two have a long-standing collaboration, and HBTRC has one of the largest collections of brains donated by persons diagnosed with HD in the U.S. if not the world.
The HBTRC’s home, McLean Hospital, is the largest psychiatric teaching hospital of Harvard Medical School.
The sole funder of the HBTRC is the federal NIH, HBTRC director Sabina Berretta, M.D., wrote in an e-mail interview with me on July 25. An associate professor of psychiatry at Harvard Medical School, she carries out HD research on the team of investigator Steve McCarroll, Ph.D., whose lab has created precise techniques for measuring the impact of HD on single brain cells.
As Doug pointed out, this type of research is only possible because of brain donations.
The uncertainty of future public funding
Harvard University has sued the federal government to try to block the Trump administration’s freezing of nearly $3 billion in research funds. The government also seeks to eliminate $783 million in NIH funding.
A statement on the NeuroBioBank website reads: “This repository is under review for potential modification in compliance with Administration directives.”
Responding to my questions about this situation, Dr. Berretta wrote that the cuts at Harvard and the NIH have not currently impacted the HBTRC. The government has not flagged current funds, she added. She noted, however, that “we are not sure at the moment” about potential restrictions arising from government concerns about diversity, equity, and inclusion.
Dr. Berretta explained that the HBTRC NIH contract “will end in October 2025. It is not known at this time whether and how the new contract, expected to start in November 2025, will be impacted.”
Dr. Berretta explained that “the current funding uncertainty creates some challenges, particularly for talent retention and long-term planning, both critical to our work.”
“The other 5 brain banks part of the NIH NeuroBioBank are in our same situation,” she added.
Dr. Sabina Berretta (McLean Hospital photo)
A family discussion and a decision
Dorlue was 63 and had been married to Doug for 32 years. After graduating from high school in 1976, she worked for 20 years in a Pacific Bell office. She volunteered at her church, participated in her son Ryan’s school PTA, and enjoyed family camping trips. As a young adult, Ryan tested negative for the HD gene.
Dorlue was remembered as having “a fighting spirit that never wavered in the face of her diagnosis” with HD, including participation in clinical trials in hopes of a cure.
Doug and Dorlue discussed, and then agreed to, donating her brain when she was no longer in “denial” about her disease and learning that Ryan was now free of the disease, Doug said in his presentation. Dorlue registered for the donation in 2012.
“It should be your decision and no one else’s,” Doug emphasized, noting that contemplating a donation can be “very stressful” because of all of the difficulties already involved in HD.
The decision must involve the person’s legal first of kin, who will see through the donation after the person has died.
There are many reasons to donate – or not donate, said Doug, noting that some might have religious reasons against the process.
He recommended that families start conversations about donations “early.”
“You can cancel at any time,” he said of the process. The opportunity to donate is “a blessing,” he added.
A ‘very professional’ organization
A person can pre-register their donation on the HBTRC website or register any time over the phone, even after an individual has died, Doug explained.
Doug spoke several times with Dr. Berretta.
“She’s very compassionate,” he said. “The organization is very professional. I really felt that they understood how difficult it was to go through that process, especially right after your loved one died.”
Doug noted several exclusionary criteria that might prevent a brain from being accepted, such as a delay of more than 24 hours in getting the brain to the bank; a stroke or penetrating head injury; or testing positive for HIV, hepatitis B, or hepatitis C.
Although “it costs a lot of money for the brain to be put on a plane and sent to Harvard,” the only charges covered by the family are the usual funeral costs, such as cremation or embalming, Doug said.
Just 24 hours to get the brain delivered
The 24-hour clock for the donation to be received starts at the moment the last person saw the deceased alive, Doug continued.
Dorlue died at 6 a.m., when a hospice nurse declared her dead. Doug contacted the funeral home, which needed to transport the body to the facility that “harvests” the brain. The funeral home worker took four hours to arrive, Doug said.
“We were ten hours into this before they even took the body out of the house,” he recalled. “I was pretty anxious that we get this thing off.”
The brain is packed in ice for transport and placed in the luggage area of the plane so that it stays cold throughout the flight, Doug explained.
Once it arrives at the HBTRC laboratories, the brain is immediately dissected. Part of it is immediately frozen and kept at minus 80 degrees centrigrade. Another part is immersed in formalin. It is then assessed by a neuropathologist, who generates a neuropathology report. Both preparations are made available to investigators.
Once the brain arrived at Harvard, Doug received a call reassuring him that it had arrived undisturbed and on time. To preserve the integrity of the tissue for research, the brain is ultimately frozen at minus 80 degrees centigrade.
Doug also sent the HBTRC Dorlue’s medical records to assist in their research on her brain.
“That’s a big part of what the scientists look at,” he said. “They compare the brain with the symptoms and see if there’s any similarities or not.”
Crucial work towards a cure
The HBTRC website has an FAQ, donation forms, and phone numbers for making a donation.
This HBTRC does crucial work in the quest for a cure.
Doug has signed up to donate his brain. I will do the same.
As Doug put it, the bank collects brains from around the U.S. and sends samples around the world.
“Who knows who’s going to find a cure,” he said.
