Should Genetic Information About Mental Health Affect Civil Court Cases?
Imagine this scenario: A couple is involved in a heated custody dispute over their only child. As part of the effort to make the case of being a better guardian, one parent goes on a "genetic fishing expedition": this parent obtains a DNA sample from the other parent with the hope that such data will identify some genetic predisposition to a psychiatric condition (e.g., schizophrenia) and tilt the judge's custody decision in his or her favor.
As knowledge of psychiatric genetics is growing, it is likely to be introduced in civil cases, such as child custody disputes and education-related cases, raising a tangle of ethical and legal questions.
This is an example of how "behavioral genetic evidence" -- an umbrella term for information gathered from family history and genetic testing about pathological behaviors, including psychiatric conditions—may in the future be brought by litigants in court proceedings. Such evidence has been discussed primarily when criminal defendants sought to introduce it to make the claim that they are not responsible for their behavior or to justify their request for reduced sentencing and more lenient punishment.
However, civil cases are an emerging frontier for behavioral genetic evidence. It has already been introduced in tort litigation, such as personal injury claims, and as knowledge of psychiatric genetics is growing, it is further likely to be introduced in other civil cases, such as child custody disputes and education-related cases. But the introduction of such evidence raises a tangle of ethical and legal questions that civil courts will need to address. For example: how should such data be obtained? Who should get to present it and under what circumstances? And does the use of such evidence fit with the purposes of administering justice?
How Did We Get Here?
That behavioral genetic evidence is entering courts is unsurprising. Scientific evidence is a common feature of judicial proceedings, and genetic information may reveal relevant findings. For example, genetic evidence may elucidate whether a child's medical condition is due to genetic causes or medical malpractice, and it has been routinely used to identify alleged offenders or putative fathers. But behavioral genetic evidence is different from such other genetic data – it is shades of gray, instead of black and white.
Although efforts to understand the nature and origins of human behavior are ongoing, existing and likely future knowledge about behavioral genetics is limited. Behavioral disorders are highly complex and diverse. They commonly involve not one but multiple genes, each with a relatively small effect. They are impacted by many, yet unknown, interactions between genes, familial, and environmental factors such as poverty and childhood adversity.
And a specific gene variant may be associated with more than one behavioral disorder and be manifested with significantly different symptoms. Thus, biomarkers about "predispositions" for behavioral disorders cannot generally provide a diagnosis or an accurate estimate of whether, when, and at what severity a behavioral disorder will occur. And, unlike genetic testing that can confirm litigants' identity with 99.99% probability, behavioral genetic evidence is far more speculative.
Genetic theft raises questions about whose behavioral data are being obtained, by whom, and with what authority.
Whether judges, jurors, and other experts understand the nuances of behavioral genetics is unclear. Many people over-estimate the deterministic nature of genetics, and under-estimate the role of environments, especially with regards to mental health status. The U.S. individualistic culture of self-reliance and independence may further tilt the judicial scales because litigants in civil courts may be unjustly blamed for their "bad genes" while structural and societal determinants that lead to poor behavioral outcomes are ignored.
These concerns were recently captured in the Netflix series "13 Reasons Why," depicting a negligence lawsuit against a school brought by parents of a high-school student there (Hannah) who committed suicide. The legal tides shifted from the school's negligence in tolerating a culture of bullying to parental responsibility once cross-examination of Hannah's mother revealed a family history of anxiety, and the possibility that Hannah had a predisposition for mental illness, which (arguably) required therapy even in the absence of clear symptoms.
Where Is This Going?
The concerns are exacerbated given the ways in which behavioral genetic evidence may come to court in the future. One way is through "genetic theft," where genetic evidence is obtained from deserted property, such as soft-drink cans. This method is often used for identification purposes such as criminal and paternity proceedings, and it will likely expand to behavioral genetic data once available through "home kits" that are offered by direct-to-consumer companies.
Genetic theft raises questions about whose behavioral data are being obtained, by whom, and with what authority. In the scenario of child-custody dispute, for example, the sequencing of the other parent's DNA will necessarily intrude on the privacy of that parent, even as the scientific value of such information is limited. A parent on a "genetic fishing expedition" can also secretly sequence their child for psychiatric genetic predispositions, arguably, in order to take preventative measures to reduce the child's risk for developing a behavioral disorder. But should a parent be allowed to sequence the child without the other parent's consent, or regardless of whether the results will provide medical benefits to the child?
Similarly, although schools are required, and may be held accountable for failing to identify children with behavioral disabilities and to evaluate their educational needs, some parents may decline their child's evaluation by mental health professionals. Should schools secretly obtain a sample and sequence children for behavioral disorders, regardless of parental consent? My study of parents found that the overwhelming majority opposed imposed genetic testing by school authorities. But should parental preference or the child's best interests be the determinative factor? Alternatively, could schools use secretly obtained genetic data as a defense that they are fulfilling the child-find requirement under the law?
The stigma associated with behavioral disorders may intimidate some people enough that they back down from just claims.
In general, samples obtained through genetic theft may not meet the legal requirements for admissible evidence, and as these examples suggest, they also involve privacy infringement that may be unjustified in civil litigation. But their introduction in courts may influence judicial proceedings. It is hard to disregard such evidence even if decision-makers are told to ignore it.
The costs associated with genetic testing may further intensify power differences among litigants. Because not everyone can pay for DNA sequencing, there is a risk that those with more resources will be "better off" in court proceedings. Simultaneously, the stigma associated with behavioral disorders may intimidate some people enough that they back down from just claims. For example, a good parent may give up a custody claim to avoid disclosure of his or her genetic predispositions for psychiatric conditions. Regulating this area of law is necessary to prevent misuses of scientific technologies and to ensure that powerful actors do not have an unfair advantage over weaker litigants.
Behavioral genetic evidence may also enter the courts through subpoena of data obtained in clinical, research or other commercial genomic settings such as ancestry testing (similar to the genealogy database recently used to identify the Golden State Killer). Although court orders to testify or present evidence are common, their use for obtaining behavioral genetic evidence raises concerns.
One worry is that it may be over-intrusive. Because behavioral genetics are heritable, such data may reveal information not only about the individual litigant but also about other family members who may subsequently be stigmatized as well. And, even if we assume that many people may be willing for their data in genomic databases to be used to identify relatives who committed crimes (e.g., a rapist or a murderer), we can't assume the same for civil litigation, where the public interest in disclosure is far weaker.
Another worry is that it may deter people from participating in activities that society has an interest in advancing, including medical treatment involving genetic testing and genomic research. To address this concern, existing policy provides expanded privacy protections for NIH-funded genomic research by automatically issuing a Certificate of Confidentiality that prohibits disclosure of identifiable information in any Federal, State, or local civil, criminal, and other legal proceedings.
But this policy has limitations. It applies only to specific research settings and does not cover non-NIH funded research or clinical testing. The Certificate's protections can also be waived under certain circumstances. People who volunteer to participate in non-NIH-funded genomic research for the public good may thus find themselves worse-off if embroiled in legal proceedings.
Consider the following: if a parent in a child custody dispute had participated in a genetic study on schizophrenia years earlier, should the genetic results be subpoenaed by the court – and weaponized by the other parent? Public policy should aim to reduce the risks for such individuals. The end of obtaining behavioral genetic evidence cannot, and should not, always justify the means.
Swiss researchers have discovered a third type of brain cell that appears to be a hybrid of the two other primary types — and it could lead to new treatments for many brain disorders.
The challenge: Most of the cells in the brain are either neurons or glial cells. While neurons use electrical and chemical signals to send messages to one another across small gaps called synapses, glial cells exist to support and protect neurons.
Astrocytes are a type of glial cell found near synapses. This close proximity to the place where brain signals are sent and received has led researchers to suspect that astrocytes might play an active role in the transmission of information inside the brain — a.k.a. “neurotransmission” — but no one has been able to prove the theory.
A new brain cell: Researchers at the Wyss Center for Bio and Neuroengineering and the University of Lausanne believe they’ve definitively proven that some astrocytes do actively participate in neurotransmission, making them a sort of hybrid of neurons and glial cells.
According to the researchers, this third type of brain cell, which they call a “glutamatergic astrocyte,” could offer a way to treat Alzheimer’s, Parkinson’s, and other disorders of the nervous system.
“Its discovery opens up immense research prospects,” said study co-director Andrea Volterra.
The study: Neurotransmission starts with a neuron releasing a chemical called a neurotransmitter, so the first thing the researchers did in their study was look at whether astrocytes can release the main neurotransmitter used by neurons: glutamate.
By analyzing astrocytes taken from the brains of mice, they discovered that certain astrocytes in the brain’s hippocampus did include the “molecular machinery” needed to excrete glutamate. They found evidence of the same machinery when they looked at datasets of human glial cells.
Finally, to demonstrate that these hybrid cells are actually playing a role in brain signaling, the researchers suppressed their ability to secrete glutamate in the brains of mice. This caused the rodents to experience memory problems.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Andrea Volterra, University of Lausanne.
But why? The researchers aren’t sure why the brain needs glutamatergic astrocytes when it already has neurons, but Volterra suspects the hybrid brain cells may help with the distribution of signals — a single astrocyte can be in contact with thousands of synapses.
“Often, we have neuronal information that needs to spread to larger ensembles, and neurons are not very good for the coordination of this,” researcher Ludovic Telley told New Scientist.
Looking ahead: More research is needed to see how the new brain cell functions in people, but the discovery that it plays a role in memory in mice suggests it might be a worthwhile target for Alzheimer’s disease treatments.
The researchers also found evidence during their study that the cell might play a role in brain circuits linked to seizures and voluntary movements, meaning it’s also a new lead in the hunt for better epilepsy and Parkinson’s treatments.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Volterra.
Martin Taylor was only 32 when he was diagnosed with Parkinson's, a disease that causes tremors, stiff muscles and slow physical movement - symptoms that steadily get worse as time goes on.
“It's horrible having Parkinson's,” says Taylor, a data analyst, now 41. “It limits my ability to be the dad and husband that I want to be in many cruel and debilitating ways.”
Today, more than 10 million people worldwide live with Parkinson's. Most are diagnosed when they're considerably older than Taylor, after age 60. Although recent research has called into question certain aspects of the disease’s origins, Parkinson’s eventually kills the nerve cells in the brain that produce dopamine, a signaling chemical that carries messages around the body to control movement. Many patients have lost 60 to 80 percent of these cells by the time they are diagnosed.
For years, there's been little improvement in the standard treatment. Patients are typically given the drug levodopa, a chemical that's absorbed by the brain’s nerve cells, or neurons, and converted into dopamine. This drug addresses the symptoms but has no impact on the course of the disease as patients continue to lose dopamine producing neurons. Eventually, the treatment stops working effectively.
BlueRock Therapeutics, a cell therapy company based in Massachusetts, is taking a different approach by focusing on the use of stem cells, which can divide into and generate new specialized cells. The company makes the dopamine-producing cells that patients have lost and inserts these cells into patients' brains. “We have a disease with a high unmet need,” says Ahmed Enayetallah, the senior vice president and head of development at BlueRock. “We know [which] cells…are lost to the disease, and we can make them. So it really came together to use stem cells in Parkinson's.”
In a phase 1 research trial announced late last month, patients reported that their symptoms had improved after a year of treatment. Brain scans also showed an increased number of neurons generating dopamine in patients’ brains.
Increases in dopamine signals
The recent phase 1 trial focused on deploying BlueRock’s cell therapy, called bemdaneprocel, to treat 12 patients suffering from Parkinson’s. The team developed the new nerve cells and implanted them into specific locations on each side of the patient's brain through two small holes in the skull made by a neurosurgeon. “We implant cells into the places in the brain where we think they have the potential to reform the neural networks that are lost to Parkinson's disease,” Enayetallah says. The goal is to restore motor function to patients over the long-term.
Five patients were given a relatively low dose of cells while seven got higher doses. Specialized brain scans showed evidence that the transplanted cells had survived, increasing the overall number of dopamine producing cells. The team compared the baseline number of these cells before surgery to the levels one year later. “The scans tell us there is evidence of increased dopamine signals in the part of the brain affected by Parkinson's,” Enayetallah says. “Normally you’d expect the signal to go down in untreated Parkinson’s patients.”
"I think it has a real chance to reverse motor symptoms, essentially replacing a missing part," says Tilo Kunath, a professor of regenerative neurobiology at the University of Edinburgh.
The team also asked patients to use a specific type of home diary to log the times when symptoms were well controlled and when they prevented normal activity. After a year of treatment, patients taking the higher dose reported symptoms were under control for an average of 2.16 hours per day above their baselines. At the smaller dose, these improvements were significantly lower, 0.72 hours per day. The higher-dose patients reported a corresponding decrease in the amount of time when symptoms were uncontrolled, by an average of 1.91 hours, compared to 0.75 hours for the lower dose. The trial was safe, and patients tolerated the year of immunosuppression needed to make sure their bodies could handle the foreign cells.
Claire Bale, the associate director of research at Parkinson's U.K., sees the promise of BlueRock's approach, while noting the need for more research on a possible placebo effect. The trial participants knew they were getting the active treatment, and placebo effects are known to be a potential factor in Parkinson’s research. Even so, “The results indicate that this therapy produces improvements in symptoms for Parkinson's, which is very encouraging,” Bale says.
Tilo Kunath, a professor of regenerative neurobiology at the University of Edinburgh, also finds the results intriguing. “I think it's excellent,” he says. “I think it has a real chance to reverse motor symptoms, essentially replacing a missing part.” However, it could take time for this therapy to become widely available, Kunath says, and patients in the late stages of the disease may not benefit as much. “Data from cell transplantation with fetal tissue in the 1980s and 90s show that cells did not survive well and release dopamine in these [late-stage] patients.”
Searching for the right approach
There's a long history of using cell therapy as a treatment for Parkinson's. About four decades ago, scientists at the University of Lund in Sweden developed a method in which they transferred parts of fetal brain tissue to patients with Parkinson's so that their nerve cells would produce dopamine. Many benefited, and some were able to stop their medication. However, the use of fetal tissue was highly controversial at that time, and the tissues were difficult to obtain. Later trials in the U.S. showed that people benefited only if a significant amount of the tissue was used, and several patients experienced side effects. Eventually, the work lost momentum.
“Like many in the community, I'm aware of the long history of cell therapy,” says Taylor, the patient living with Parkinson's. “They've long had that cure over the horizon.”
In 2000, Lorenz Studer led a team at the Memorial Sloan Kettering Centre, in New York, to find the chemical signals needed to get stem cells to differentiate into cells that release dopamine. Back then, the team managed to make cells that produced some dopamine, but they led to only limited improvements in animals. About a decade later, in 2011, Studer and his team found the specific signals needed to guide embryonic cells to become the right kind of dopamine producing cells. Their experiments in mice, rats and monkeys showed that their implanted cells had a significant impact, restoring lost movement.
Studer then co-founded BlueRock Therapeutics in 2016. Forming the most effective stem cells has been one of the biggest challenges, says Enayetallah, the BlueRock VP. “It's taken a lot of effort and investment to manufacture and make the cells at the right scale under the right conditions.” The team is now using cells that were first isolated in 1998 at the University of Wisconsin, a major advantage because they’re available in a virtually unlimited supply.
Other efforts underway
In the past several years, University of Lund researchers have begun to collaborate with the University of Cambridge on a project to use embryonic stem cells, similar to BlueRock’s approach. They began clinical trials this year.
A company in Japan called Sumitomo is using a different strategy; instead of stem cells from embryos, they’re reprogramming adults' blood or skin cells into induced pluripotent stem cells - meaning they can turn into any cell type - and then directing them into dopamine producing neurons. Although Sumitomo started clinical trials earlier than BlueRock, they haven’t yet revealed any results.
“It's a rapidly evolving field,” says Emma Lane, a pharmacologist at the University of Cardiff who researches clinical interventions for Parkinson’s. “But BlueRock’s trial is the first full phase 1 trial to report such positive findings with stem cell based therapies.” The company’s upcoming phase 2 research will be critical to show how effectively the therapy can improve disease symptoms, she added.
The cure over the horizon
BlueRock will continue to look at data from patients in the phase 1 trial to monitor the treatment’s effects over a two-year period. Meanwhile, the team is planning the phase 2 trial with more participants, including a placebo group.
For patients with Parkinson’s like Martin Taylor, the therapy offers some hope, though Taylor recognizes that more research is needed.
“Like many in the community, I'm aware of the long history of cell therapy,” he says. “They've long had that cure over the horizon.” His expectations are somewhat guarded, he says, but, “it's certainly positive to see…movement in the field again.”
"If we can demonstrate what we’re seeing today in a more robust study, that would be great,” Enayetallah says. “At the end of the day, we want to address that unmet need in a field that's been waiting for a long time.”