Should Police Detectives Have Total Access to Public Genetic Databases?
This past April, an alleged serial rapist and murderer, who had remained unidentified for over 40 years, was located by comparing a crime scene DNA profile to a public genetic genealogy database designed to identify biological relatives and reconstruct family trees. The so-called "Golden State Killer" had not placed his own profile in the database.
Forensic use of genetic genealogy data is possible thanks to widening public participation in direct-to-consumer recreational genetic testing.
Instead, a number of his distant genetic cousins had, resulting in partial matches between themselves and the forensic profile. Investigators then traced the shared heritage of the relatives to great-great-great-grandparents and using these connections, as well as other public records, narrowed their search to just a handful of individuals, one of whom was found to be an exact genetic match to the crime scene sample.
Forensic use of genetic genealogy data is possible thanks to widening public participation in direct-to-consumer recreational genetic testing. The Federal Bureau of Investigation maintains a national forensic genetic database (which currently contains over 16 million unique profiles, over-representing individuals of non-European ancestry); each profile holds genetic information from only 13 to 20 variable gene regions, just enough to identify a suspect. However, since this database and related forensic databases were established, the nature of genetic profiling has significantly changed: direct-to-consumer genetic tests routinely use whole genome scans involving simultaneous analysis of hundreds of thousands of variants.
With such comprehensive genetic information, it becomes possible to discern more distant genetic relatives. Thus, even though public DNA collections are smaller than most law enforcement databases, the potential to connect a crime scene sample to biological relatives is enhanced. The successful use of one genealogy database (GEDMatch) in the GSK case demonstrates the power of the approach, so much so that the genetic profiles of over 100 similar cold cases are now being run through the same resource. Indeed, in the two months since the GSK case was first reported, 5 other cold cases have been solved using similar methods.
Autonomy in the Genomic Age
While few would disagree with the importance of finally bringing to justice those who commit serious violent offenses, this new forensic genetic application has sparked broad discussion of privacy-related and ethical concerns. Before, the main genetic databases accessible to the police were those containing the profiles of accused or convicted criminals, but now the DNA of many more "innocent bystanders," across multiple generations, are in play.
The genetic services that provide a venue for data sharing typically warn participants that their information can be used for purposes beyond those they intend, but there is no legal prohibition on the use of crowd-sourced public collections for forensic investigation. Some services, such as GEDMatch, now explicitly welcome possible law enforcement use.
The decisions of individuals to contribute their own genetic information inadvertently exposes many others across their family tree.
The implication is that consumers must choose for themselves whether they are willing to bring their genetic information into the public sphere. Many have no problem doing so, seeing value in law enforcement access to such data. But the decisions of individuals to contribute their own genetic information inadvertently exposes many others across their family tree who may not be aware of or interested in their genetic relationships going public.
As one well-known statistical geneticist who predicted forensic uses of public genetic data noted: "You are a beacon who illuminates 300 people around you." By the same token, 300 people, most of whom you do not know and have probably never met, can illuminate your genetic information; indeed a recent analysis has suggested that most in the U.S. are identifiable in this way. There is nothing that you can do about it, no way to opt out. Thus, police interaction with such databases must be addressed as a public policy issue, not left to the informed consent of individual consumers.
When Consent Will Not Suffice
For those concerned by the broader implications of such practices, the simplest solution might be to discourage open access sharing of detailed genetic information. But let's say that we are willing to continue to allow those with an interest in genealogy to make their data readily searchable. What safeguards should we implement to ensure that the family members who don't want to opt in, or who don't have the ability to make that choice, remain unharmed? Their autonomy counts, too.
We might consider regulation similar to the kind that limit law enforcement use of forensic genetic databases of convicted and arrested individuals. For example, in California, familial searches can only be performed using the database of convicted individuals in cases of serious crimes with public safety implications where all other investigatory methods have been exhausted, and where single-source high-quality DNA is available for analysis. Further, California policy separates the genealogical investigative team from local detectives, so as to minimize the impact of incidental findings (such as unexpected non-paternity).
Importantly, the individual apprehended was not the first, or even second, but the third person subjected to enhanced police scrutiny.
No such regulations currently govern law enforcement searches of public genealogical databases, and we know relatively little about the specifics of the GSK investigation. We do not know the methods used to infer genetic relationships, or their likelihood of mistakenly suggesting a relationship where none exists. Nor do we know the level of genetic identity considered relevant for subsequent follow-up. It is also unclear how law enforcement investigators combined the genetic information they received with other public records data. Together, this leaves room for an unknown degree of investigation into an unknown number of individuals.
Why This Matters
What has been revealed is that the GSK search resulted in the identification of 10 to 20 potential distant genetic relatives, which led to the investigation of 25 different family trees, 24 of which did not contain the alleged serial rapist and murderer. While some sources described a pool of 100 possible male suspects identified from this exercise, others imply that the total number of relatives encompassed by the investigation was far larger. One account, for example, suggests that there were roughly 1000 family members in just the one branch of the genealogy that included the alleged perpetrator. Importantly, the individual apprehended was not the first, or even second, but the third person subjected to enhanced police scrutiny: reports describe at least two false leads, including one where a warrant was issued to obtain a DNA sample.
These details, many of which only came to light after intense press coverage, raise a host of concerns about the methods employed and the degree to which they exposed otherwise innocent individuals to harms associated with unjustified privacy intrusions. Only with greater transparency and oversight will we be able to ensure that the interests of people curious about their family tree do not unfairly impinge on those of their mostly law-abiding near and distant genetic relatives.
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.”