How It Works
“The whole idea originally came from a conversation I had with General Norman Schwarzkopf, a supposedly brilliant military strategist,” says David Baskin, professor of neurosurgery and leader of the effort at Houston Methodist. “I asked him what is the secret to your success and he said, ‘Energy. Take out the power grid and the enemy can't communicate.’ So I thought about what supplies [energy to] cancer, especially brain cancer.”
Baskin came up with the idea of targeting the mitochondria, which process and produce energy for cancer cells.
"This is the most exciting thing in glioblastoma treatment I've seen since I've been a neurosurgeon, but it is very preliminary,” Baskin says.
The magnetic helmet creates a powerful oscillating magnetic field. At a set range of frequencies and timings, it disrupts the flow of electrons in the mitochondria of cancer cells. This leads to a release of certain chemicals called Reactive Oxygen Species, or ROS. In normal cells, this excess ROS is much lower, and it's neutralized by other chemicals called antioxidants.
However, cancer cells already have more ROS: they grow rapidly and uncontrollably, so their mitochondria need to produce more energy which in turn generates more ROS. By using the powerful magnetic field, levels of ROS get so high that the malignant cells are torn apart.
The biggest challenge was working out the specific range of frequencies and timing parameters they needed to use to kill cancer cells. It took skill, intuition, luck and lots of experiments. The helmet could theoretically be used to treat all types of glioblastoma.
Developing the magnetic helmet was a collaborative process. Santosh Helekar is a neuroscientist at Houston Methodist Research Institute and the director of oncomagnetics (magnetic cancer therapies) at the Peak Center in Houston Methodist Hospital. His previous invention with colleagues gave the team a starting point to build on. “About 7 years back I developed a portable brain magnetic stimulation device to conduct brain research,” Helekar says. “We [then] conducted a pilot clinical trial in stroke patients. The results were promising.”
Helekar presented his findings to neurosurgeons including Baskin. They decided to collaborate. With a team of scientists behind them, they modified the device to kill cancer cells.
The magnetic helmet studied for treatment of glioblastoma
Dr. David Baskin
Initial Results
After success in the lab, the team got FDA approval to conduct a compassionate trial in a 53-year-old man with end-stage glioblastoma. He had tried every other treatment available. But within 30 days of using the magnetic helmet his tumor shrank by 31%.
Sadly, 36 days into the treatment, the patient had an unrelated head injury due to a fall. The treatment was paused and he later died of the injury. Autopsy results of his brain highlighted the dramatic reduction in tumor cells.
Baskin says, “This is the most exciting thing in glioblastoma treatment I've seen since I've been a neurosurgeon, but it is very preliminary.”
The helmet is part of a growing number of non-invasive cancer treatments. One device that is currently being used by glioblastoma patients is Optune. It uses electric fields called tumor treating fields to slow down cell division and has been through a successful phase 3 clinical trial.
The magnetic helmet has the promise to be another useful non-invasive treatment according to Professor Gabriel Zada, a neurosurgeon and director of the USC Brain Tumor Center. “We're learning that various electromagnetic fields and tumor treating fields appear to play a role in glioblastoma. So there is some precedent for this though the tumor treating fields work a little differently. I think there is major potential for it to be effective but of course it will require some trials.”
Professor Jonathan Sherman, a neurosurgeon and director of neuro-oncology at West Virginia University, reiterates the need for further testing. “It sounds interesting but it’s too early to tell what kind of long-term efficacy you get. We do not have enough data. Also if you’re disrupting [the magnetic field] you could negatively impact a patient. You could be affecting the normal conduction of electromagnetic activity in the brain.”
The team is currently extending their research. They are now testing the treatment in two other patients with end-stage glioblastoma. The immediate challenge is getting FDA approval for those at an earlier stage of the disease who are more likely to benefit.
The Future
Baskin and the team are designing a clinical trial in the U.S., .U.K. and Germany. After positive results in cell cultures, they’re in negotiations to collaborate with other researchers in using the technology for lung and breast cancer. With breast cancer, the soft tissue is easier to access so a magnetic device could be worn over the breast.
“My hope is to develop a treatment to treat and hopefully cure glioblastoma without radiation or chemotherapy,” Baskin says. “We're onto a strategy that could make a huge difference for patients with this disease and probably for patients with many other forms of cancer.”
The test tubes contain tiny DNA/enzyme-based circuits, which comprise TRUMPET, a new type of electronic device, smaller than a cell.
While a computer gives these inputs in binary code or "bits," such as a 0 or 1, biocomputing uses DNA strands as inputs, whether double or single-stranded, and often uses fluorescent RNA as an output.
Adamala’s research focuses on developing such biocomputing systems using DNA, RNA, proteins, and lipids. Using these molecules in the biocomputing systems allows the latter to be biocompatible with the human body, resulting in a natural healing process. In a recent Nature Communications study, Adamala and her team created a new biocomputing platform called TRUMPET (Transcriptional RNA Universal Multi-Purpose GatE PlaTform) which acts like a DNA-powered computer chip. “These biological systems can heal if you design them correctly,” adds Adamala. “So you can imagine a computer that will eventually heal itself.”
The basics of biocomputing
Biocomputing and regular computing have many similarities. Like regular computing, biocomputing works by running information through a series of gates, usually logic gates. A logic gate works as a fork in the road for an electronic circuit. The input will travel one way or another, giving two different outputs. An example logic gate is the AND gate, which has two inputs (A and B) and two different results. If both A and B are 1, the AND gate output will be 1. If only A is 1 and B is 0, the output will be 0 and vice versa. If both A and B are 0, the result will be 0. While a computer gives these inputs in binary code or "bits," such as a 0 or 1, biocomputing uses DNA strands as inputs, whether double or single-stranded, and often uses fluorescent RNA as an output. In this case, the DNA enters the logic gate as a single or double strand.
If the DNA is double-stranded, the system “digests” the DNA or destroys it, which results in non-fluorescence or “0” output. Conversely, if the DNA is single-stranded, it won’t be digested and instead will be copied by several enzymes in the biocomputing system, resulting in fluorescent RNA or a “1” output. And the output for this type of binary system can be expanded beyond fluorescence or not. For example, a “1” output might be the production of the enzyme insulin, while a “0” may be that no insulin is produced. “This kind of synergy between biology and computation is the essence of biocomputing,” says Stephanie Forrest, a professor and the director of the Biodesign Center for Biocomputing, Security and Society at Arizona State University.
Biocomputing circles are made of DNA, RNA, proteins and even bacteria.
Evgeny Katz
The TRUMPET’s promise
Depending on whether the biocomputing system is placed directly inside a cell within the human body, or run in a test-tube, different environmental factors play a role. When an output is produced inside a cell, the cell's natural processes can amplify this output (for example, a specific protein or DNA strand), creating a solid signal. However, these cells can also be very leaky. “You want the cells to do the thing you ask them to do before they finish whatever their businesses, which is to grow, replicate, metabolize,” Adamala explains. “However, often the gate may be triggered without the right inputs, creating a false positive signal. So that's why natural logic gates are often leaky." While biocomputing outside a cell in a test tube can allow for tighter control over the logic gates, the outputs or signals cannot be amplified by a cell and are less potent.
TRUMPET, which is smaller than a cell, taps into both cellular and non-cellular biocomputing benefits. “At its core, it is a nonliving logic gate system,” Adamala states, “It's a DNA-based logic gate system. But because we use enzymes, and the readout is enzymatic [where an enzyme replicates the fluorescent RNA], we end up with signal amplification." This readout means that the output from the TRUMPET system, a fluorescent RNA strand, can be replicated by nearby enzymes in the platform, making the light signal stronger. "So it combines the best of both worlds,” Adamala adds.
These organic-based systems could detect cancer cells or low insulin levels inside a patient’s body.
The TRUMPET biocomputing process is relatively straightforward. “If the DNA [input] shows up as single-stranded, it will not be digested [by the logic gate], and you get this nice fluorescent output as the RNA is made from the single-stranded DNA, and that's a 1,” Adamala explains. "And if the DNA input is double-stranded, it gets digested by the enzymes in the logic gate, and there is no RNA created from the DNA, so there is no fluorescence, and the output is 0." On the story's leading image above, if the tube is "lit" with a purple color, that is a binary 1 signal for computing. If it's "off" it is a 0.
While still in research, TRUMPET and other biocomputing systems promise significant benefits to personalized healthcare and medicine. These organic-based systems could detect cancer cells or low insulin levels inside a patient’s body. The study’s lead author and graduate student Judee Sharon is already beginning to research TRUMPET's ability for earlier cancer diagnoses. Because the inputs for TRUMPET are single or double-stranded DNA, any mutated or cancerous DNA could theoretically be detected from the platform through the biocomputing process. Theoretically, devices like TRUMPET could be used to detect cancer and other diseases earlier.
Adamala sees TRUMPET not only as a detection system but also as a potential cancer drug delivery system. “Ideally, you would like the drug only to turn on when it senses the presence of a cancer cell. And that's how we use the logic gates, which work in response to inputs like cancerous DNA. Then the output can be the production of a small molecule or the release of a small molecule that can then go and kill what needs killing, in this case, a cancer cell. So we would like to develop applications that use this technology to control the logic gate response of a drug’s delivery to a cell.”
Although platforms like TRUMPET are making progress, a lot more work must be done before they can be used commercially. “The process of translating mechanisms and architecture from biology to computing and vice versa is still an art rather than a science,” says Forrest. “It requires deep computer science and biology knowledge,” she adds. “Some people have compared interdisciplinary science to fusion restaurants—not all combinations are successful, but when they are, the results are remarkable.”
Crickets are low on fat, high on protein, and can be farmed sustainably. They are also crunchy.
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Further reading:
More info on Bicky Nguyen
https://yseali.fulbright.edu.vn/en/faculty/bicky-n...
The environmental footprint of beef production
https://www.earthsave.org/environment.htm
https://www.watercalculator.org/news/articles/beef-king-big-water-footprints/
https://www.frontiersin.org/articles/10.3389/fsufs.2019.00005/full
https://ourworldindata.org/carbon-footprint-food-methane
Insect farming as a source of sustainable protein
https://www.insectgourmet.com/insect-farming-growing-bugs-for-protein/
https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/insect-farming
Cricket flour is taking the world by storm
https://www.cricketflours.com/
https://talk-commerce.com/blog/what-brands-use-cricket-flour-and-why/
