While vital for understanding a host of other diseases including schizophrenia, traumatic brain injury, and Alzheimer’s disease, studying human brains is no easy task. Immediate expenses of collecting, preserving, and taking a detailed history of a donor places the cost of one human brain at $10,000 to $30,000. Then there’s the added costs of storing the organs, not to mention later sampling and preparing tissue to do the actual research.
Brains that have been well preserved from known donors are scarce. Investigators from universities, other brain banks, and disease advocacy groups are constantly requesting brain tissue. Each request requires careful review because providing samples for each such study can deplete banked tissues faster than they can be replenished.
Because of the softness of the tissue, brains are very difficult to preserve. The quality of incoming tissue can vary greatly due to cause of death and time since death. Brains need to be processed quickly to preserve RNA and proteins, the products of gene expression. It’s partly by studying gene expression that scientists can understand how brains work and why the brains of people with mental illness function differently.
The first scientific studies of human brains began back in the 1500s with Belgian physician Andreas Vesalius, who noted many structural characteristics of the brain while dissecting human cadavers. Around this same time, Leonardo da Vinci sketched parts of the human brain. But it was not until 1889 that a scientist at Cornell University started the first brain collection to learn about psychology and human brain anatomy.
Today, there are around 136 brain collections around the world, and they remain vital for research. However, subtle differences can arise in collections, such as manner of collection, age, socioeconomic background, or race.
There are four major national brain repositories devoted to mental illness. The first was started in 1977 by Joel Kleinman, a visionary physician at the federal government’s National Institute of Mental Health. This collection is still operating and draws donors from Northern Virginia and the District of Columbia, so that around half of the donors are Caucasian, while the other half are African American. Donors also tend to be young, substance abusers, victims of suicide, and are thought to have more extreme cases of mental illness.
In contrast, a US government supported collection located at Harvard is much different, with donors tending to be mostly White, and with low frequency of drug abuse. And because donors in this collection tend to die of natural causes, the samples are skewed toward older people and are thought to have less severe forms of mental illness.
A third collection was started in 1986 at the Mount Sinai School of Medicine, which focuses on schizophrenia and Alzheimer’s disease. Mount Sinai is unique in reaching out to potential donors while they are still living. This allows researchers to collect much more information about the donor’s psychiatric history and other potential health problems. However, this extra work is labor intensive and drives up collection costs. Accordingly, their collection has fewer specimens than otherwise would be possible.
At the Lieber Institute for Brain Development (LIBD), we have perhaps the most carefully curated and characterized collection of human brains for the study of developmental brain disorders in the world, and the largest collection of confirmed cases of PTSD brains for research. At LIBD, all brains are processed, diagnosed and dissected by the same team of individuals. Our donors have come primarily from the Chief Medical Examiners in Maryland, and in Kalamazoo, Michigan, meaning the repository has few Latinos or Asians. In Kalamazoo this month, Congressman Fred Upton championed the effort underway to collect and process brains. Because of this, we are now working with the Chief Medical Examiner in Santa Clara County, California to increase the number of Asian brains, and we are working to begin a collection site in North Dakota where around 10% of donors will be Native American.
Researchers at LIBD have used postmortem human brains from their repository to discover several insights into developmental brain disorders and identify potential novel drug targets. The study of human brain across development, from early life to old age, has clarified the developmental origins of schizophrenia, led to the discovery of a gene for violent suicide, and elucidated how PTSD influences brain function at a molecular level. With more donors, and sufficient resources to draw from different populations across the country, we can move forward with research into the some of the most difficult challenges in mental health and solve many of the problems plaguing our country.