November 30 Research Roundup: CRISPR Embryos, Brain-Computer Interface, ADHD Genetic Variants and More
There are plenty of great scientific research stories out this week. Here’s a look at just a few of them. Although most readers will already be aware of it, the biggest story, perhaps the biggest story of the year—certainly the most controversial—involves a Chinese researcher who used CRISPR to modify embryos to be resistant to HIV, and the recent birth of a set of twins.
CRISPR Embryo Research Generates Global Controversy
Chinese researcher He Jiankui reported at the Second International Summit on Human Genome Editing held at the University of Hong Kong that a set of twins had been born who underwent CRISPR gene editing as fetuses. He followed up this extremely controversial statement that another one of the seven couples he experimented on is pregnant, although it is still early.
He Jiankui is affiliated with the Southern University of Science and Technology of China. He’s research has not been published in a peer-reviewed scientific journal yet. The details of the research were met with widespread condemnation and criticism by researchers globally. He was assisted by Michael Deem, a professor at Rice University in Houston. Both Southern University, the Chinese government, and Rice University have launched investigations.
More than 100 Chinese researchers signed a letter calling the research “crazy” and the bioethics approval “insufficient.” Other ethicists and researchers called it “monstrous,” “unconscionable” and “a grave abuse of human rights.”
The Summit ended with an official but restrained rebuke and criticism of He’s work and called for guidelines related to clinical trials on heritable germline CRISPR research.
He and Deems used CRISPR gene editing during in vitro fertilization (IVF) procedures. All the men in the couples had under-control HIV infection. Their sperm was “washed” to separate it from the semen, where the HIV is present. A single sperm was inserted into a single egg to create an embryo. They then used CRISPR-Cas9 gene editing to disable a gene called CCR5. CCR5 creates a protein that allows HIV to enter a cell. The goal was to modify the embryos’ genomes to make them resistant to HIV infection.
Of the twins born, this was only partially successful. In one of the twins, He reported, both copies of the CCR5 gene were disabled; in the other, only a single copy was disabled. How much—if any—immunity this will provide is unknown (and ethically untestable). It is also unknown if there were any negative side effects.
Successful Brain-Computer Interface in Paralyzed Patients
BrainGate, a collaboration between Brown University’s Carney Institute for Brain Science, the Providence Veterans Affairs Medical Center (PVAMC), Massachusetts General Hospital and Stanford University published research in PLOS ONE describing a successful implanted brain-computer interface (BCI). The technology allowed individuals with quadriplegia to operate electronic devices using thoughts.
Three patients with quadriplegia were implanted with the BrainGate BCI, a sensor about the size of a baby aspirin. It can detect signals in the motor cortex. These were decoded and routed to a Bluetooth device that acts as a wireless mouse.
They then used the mouse to surf the web, send emails, and stream audio/video. One participant used the device to play Beethoven’s “Ode to Joy” on a digital piano.
Senior author and Stanford neurosurgeon Jaimie Henderson told Forbes, “For years, the BrainGate collaboration has been working to develop the neuroscience and neuroengineering know-how to enable people who have lost motor abilities to control external devices just by thinking about the movement of their own arm or hand. In this study, we’ve harnessed the know-how to restore people’s ability to control the exact same everyday technologies they were using before the onset of their illnesses.”
How the Brain Predicts the Future
There is something in people called “anticipatory timing.” You experience it, for example, when you step on the gas just before the light changes. Researchers at the University of California, Berkeley (CAL) have identified the two parts of the brain involved in this. One part relies on memories from past experience while another part is based on rhythm. They published their work in the Proceedings of the National Academy of Sciences.
“Whether it’s sports, music, speech or even allocating attention, our study suggests that timing is not a unified process, but that there are two distinct ways in which we make temporal predictions and these depend on different parts of the brain,” stated lead author Assaf Breska, a postdoctoral researcher in neuroscience.
They researched the anticipatory timing strengths and deficits in Parkinson’s patients and in people with cerebellar degeneration. The rhythmic timing was related to the basal ganglia and interval timing to the cerebellum. Both are regions associated with movement and cognition.
“Together, these brain systems allow us to not just exist in the moment, but to also actively anticipate the future,” stated senior author Richard Ivry, a UC Berkeley neuroscientist. “Our study identifies not only the anticipatory contexts in which these neurological patients are impaired, but also the contexts in which they have no difficulty, suggesting we could modify their environments to make it easier for them to interact with the world in face of their symptoms.”
Epigenetic Drugs Could Cause More Problems than they Fix
Researchers at The Institute for Research in Biomedicine in Barcelona, Spain, published work in the journal Nature Cell Biology that studied whether the opening of chromatin is the cause of higher mutation rates in certain areas of the genome.
Specific areas of chromosomes have more mutations than others. These regions are more prevalent in causing cancer. Chromatin is a combination of DNA and proteins. Their work looked at whether the opening of chromatin was a factor in creating more or fewer mutations in these regions. And they concluded that drugs that are used to inhibit epigenetic factors may change the pattern and number of mutations that could, they stated, “even be detrimental for patients.”
“We are not saying that this is going to happen in every case, but it is something that needs to be studied in greater depth before deciding whether drugs targeting epigenetic factors should be used in clinical practice or not,” stated Salvador Aznar Benitah, head of the Stem Cell and Cancer Laboratory at IRB Barcelona.
Some of these drugs, HDAC inhibitors or HDI and DNA-demethylating agents are being investigated and used as adjunct therapy in cancer therapy.
Restoring Breathing and Limb Function After Spinal Cord Injuries
Every year there are a quarter million to half a million chronic spinal cord injuries worldwide. Mostly they come from car crashes or falls. The worst can cause paralysis, and more than half impair breathing. Researchers with Case Western Reserve University were able to restore breathing and partial forelimb function in rats with spinal cord injuries. They published their research in the journal Nature Communications.
The group used an enzyme called chondroitinase, which breaks down inhibitory proteoglycan molecules. These proteoglycans normally inhibit the growth of new axon branches from a sub-population of nerve cells. They found it didn’t work all that well immediately after injury, but a one-time injection long after the injury did. The results, in injured rats, was new nerve extensions that helped restore diaphragm function and some use of their forelimbs.
“For the first time we have permanently restored both breathing and some arm function in a form of high cervical, chronic spinal cord injury-induced paralysis,” stated Jerry Silver, professor of neurosciences at Case Western. “The complete recovery, especially of breathing, occurs rapidly after a near lifetime of paralysis in a rodent model.”
Genetic Variants Linked to ADHD
Scientists from a consortium of prominent research institutions studied the entire genomes of more than 20,000 people with attention-deficit/hyperactivity disorder (ADHD) and compared them to the genomes of 35,000 who did not have ADHD. They identified 12 genetic variants in the ADHD group, suggesting an increased risk of ADHD compared to those without the variants.
The consortium has researchers from the Danish iPSYCH project, the Broad Institute of Harvard University and the Massachusetts Institute of Technology, Massachusetts General Hospital, SUNY Upstate Medical University, and the Psychiatric Genomics Consortium. The research was published in the journal Nature Genetics.
“The large amount of data enabled us to find, for the first time, locations in the genome where people with ADHD stand out from those who are healthy,” stated Ditte Demontis, associate professor with Aarhus University in Denmark, and co-lead author of the study. “The search for such genetic risk variants for ADHD has spanned decades but without obtaining robust results.”
The variants identified are widespread in the overall population. However, the more you have, the higher the tendency towards AHDH-like characteristics, as well as a higher risk of developing ADHD. The research also found a positive connection between ADHD and obesity, increased BMI and Type 2 diabetes. In other words, the variants that increase ADHD risk also increase the risk of being overweight and having Type 2 diabetes.