Using optogenetic techniques, which relied on laser light to activate the cancer cells in mice implanted with human gliomas, the researchers demonstrated that increasing electrical signals into the tumors caused more tumor growth. Proliferation of the tumors was largely prevented when glioma cells expressed a gene that blocked transmission of the electrical signals.

Existing drugs that block electrical currents also reduced growth of high-grade gliomas, the research found. A seizure medication called perampanel, which blocks activity of neurotransmitter receptors on the receiving end of a synapse, reduced proliferation of pediatric gliomas implanted into mice by 50%. Meclofenamate, a drug that blocks the action of gap junctions, resulted in a similar decrease in tumor proliferation.

Monjes team plans to continue investigating whether blocking electrical signaling within tumors could help people with high-grade gliomas. Its a really hopeful new direction, and as a clinician Im quite excited about it, she said.

Other Stanford co-authors of the paper are staff scientist Wade Morishita, PhD; postdoctoral scholars Anna Geraghty, PhD, Marlene Arzt, MD, and Kathryn Taylor, PhD; graduate student Shawn Gillespie; medical student Lydia Tam; staff scientist Cedric Espenel, PhD; research assistants Anitha Ponnuswami, Lijun Ni and Pamelyn Woo; Hannes Vogel, MD, professor of pathology and of pediatrics; and Robert Malenka, MD, PhD, professor of psychiatry and behavioral sciences.

Monje is a member of Stanford Bio-X, the Stanford Institute for Stem Cell Biology and Regenerative Medicine, the Stanford Maternal & Child Health Research Institute, the Stanford Cancer Institute and the Wu Tsai Neurosciences Institute at Stanford.

Scientists from Massachusetts General Hospital, Harvard Medical School, the Massachusetts Institute of Technology, Johns Hopkins University, the University of Michigan and the University of California-San Francisco also contributed to the research.

The research was funded by the National Institutes of Health (grant DP1 NS111132), the National Institute of Neurological Disorders and Stroke (grant NINDS R01NS092597), the National Cancer Institute (grant F31CA200273), the Michael Mosier Defeat DIPG Foundation, the ChadTough Foundation, the V Foundation, Ians Friends Foundation, the Department of Defense, the Mckenna Claire Foundation, Alexs Lemonade Stand Foundation, The Cure Starts Now Foundation and DIPG Collaborative, the Lyla Nsouli Foundation, Unravel Pediatric Cancer, the California Institute for Regenerative Medicine, the Joey Fabus Childhood Cancer Foundation, the N8 Foundation, the Sam Jeffers Foundation, Cancer Research UK, the Virginia and D.K. Ludwig Fund for Cancer Research, and the Stanford Maternal & Child Health Research Institutes Anne T. and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and Blood Diseases.

Stanfords Department of Neurology and Neurological Sciences also supported the work.

A second paper showing similar findings by another team of researchers was published simultaneously in Nature.

See more here:
Brain tumors form synapses with healthy neurons, Stanford-led study finds - Stanford Medical Center Report

Share this Article

You are free to share this article under the Attribution 4.0 International license.

To survive chemotherapy, some cancer cells eat their neighboring tumor cells, a new study shows.

The findings suggest that this act of cannibalism gives the cancer cells the energy they need to stay alive and initiate tumor relapse after the course of treatment is completed.

Chemotherapy drugs such as doxorubicin damage cancer cells DNA to kill them, but cells that survive initial treatment can soon give rise to relapsed tumors. This is a particular problem in breast cancers that retain a normal copy of a gene called TP53. Instead of dying in response to chemotherapy-induced DNA damage, these cancer cells generally just stop proliferating and enter a dormant but metabolically active state known as senescence.

In addition to surviving chemotherapy, these senescent cancer cells produce large amounts of inflammatory molecules and other factors that can promote the tumors regrowth. Chemotherapy-treated breast cancer patients with normal TP53 genes are therefore prone to relapse and have poor survival rates.

Understanding the properties of these senescent cancer cells that allow their survival after chemotherapy treatment is extremely important, says Crystal A. Tonnessen-Murray, a postdoctoral research fellow in James G. Jacksons laboratory at the Tulane University School of Medicine.

Researchers discovered that, after exposure to doxorubicin or other chemotherapy drugs, breast cancer cells that become senescent frequently engulf neighboring cancer cells. They observed this surprising behavior not only in cancer cells grown in the lab, but also in tumors growing in mice. Lung and bone cancer cells are also capable of engulfing their neighbors after becoming senescent, the researchers discovered.

As reported in the Journal of Cell Biology, senescent cancer cells activate a group of genes that are normally active in white blood cells that engulf invading microbes or cellular debris. After eating their neighbors, senescent cancer cells digested them by delivering them to lysosomes, acidic cellular structures that are also highly active in senescent cells.

Senescent cancer cells that engulfed a neighboring cell survived in culture for longer than senescent cancer cells that didnt. The researchers suspect that consuming their neighbors may provide senescent cancer cells with the energy and materials they need to survive and produce the factors that drive tumor relapse.

Inhibiting this process may provide new therapeutic opportunities, because we know that it is the breast cancer patients with tumors that undergo TP53-mediated senescence in response to chemotherapy that have poor response and poor survival rates, Jackson says.

Source: Tulane University

Original Study DOI: 10.1083/jcb.201904051

Read more here:
Some cancer cells turn cannibal to survive chemotherapy - Futurity: Research News

An international team of scientists from Gero Discovery LLC, the Institute of Biomedical Research of Salamanca, and Nanosyn, Inc. has found a potential drug that may prevent neuronal death through glucose metabolism modification in stressed neurons. The positive results obtained in mice are promising for future use in humans. The new drug could be advantageous in neurological conditions ranging from amyotrophic lateral sclerosis, Alzheimers and Huntingtons diseases, to traumatic brain injury and ischemic stroke. The results have been published in the Scientific Reports Journal.Brain injuries and neurological disorders are among the most significant causes of death worldwide. According to WHO, stroke is the second most common cause of mortality, and more than a third of people who have survived a stroke will have a severe disability.What is more, as the population ages, millions more people are at risk of developing Alzheimers or Parkinsons diseases in the near future. However, there are no efficient drugs for major neurodegenerative diseases. It is thus critically important to understand the biology of these diseases and to identify new drugs capable of improving quality of life, survival, and, in the best-case scenario, curing the disease completely.

In most tissues in the body, glycolysis is considered an essential metabolic pathway for cell survival since it meets the cells energy needs in case of intensive energy consumption. However, in brain tissue, the situation is quite different - individual cell types show distinct glucose metabolism patterns. In neurons, only a small portion of glucose is consumed via the glycolysis pathway. At the same time, astrocytes provide nutrients to neurons and utilize glycolysis to metabolize glucose. These differences are mostly due to a specialized protein called PFKFB3, which is normally absent in neurons and is active in astrocytes. In the case of certain neurological diseases, stroke being one of them, the amount of active PFKFB3 increases in neurons, which is highly stressful for these cells and leads to cell death.

An international team of researchers led by Peter Fedichev, a scientist and biotech entrepreneur from Gero Discovery, and professor Juan P. Bolaos from the University of Salamanca, suggested and further confirmed in in vivo experiments that a small molecule, an inhibitor of PFKFB3, may prevent cell death in the case of ischemia injury. In experiments using mouse cell cultures, it was shown that the PFKFB3 inhibitor protected neurons from the amyloid-beta peptide, the main component of the amyloid plaques found in the brains of Alzheimers disease patients. Subsequent in vivo testing showed that inhibition of PFKFB3 improves motor coordination of mice after stroke and reduced brain infarct volume.

Bolaos commented, Excitotoxicity is a hallmark of various neurological diseases, stroke being one of them. Our group has previously established a link between this pathological condition and high activity of PFKFB3 enzyme in neurons, which leads to severe oxidative stress and neuronal death.

We are glad that our hypothesis that pharmacological inhibition of PFKFB3 can be beneficial in an excitotoxicity-related condition, such as stroke, was confirmed. I would like to note that in our work, we used a known molecule to demonstrate that PFKFB3 blockage has a therapeutic effect. But we have also performed the same experiments with other proprietary small molecule designed in our company and showed that it had a similar effect. There is, of course, still much work to do. We are currently investigating the efficacy of our compounds in models of orphan excitotoxicity-related neurological diseases. We have already obtained good safety results in mice and believe that we will be successful in our future investigations said Olga Burmistrova, director of preclinical development in Gero Discovery.

The Gero Discovery team is planning to proceed with preclinical trials and to move into clinical trials soon. These promising results bring hope to dozens of millions of patients suffering from life-threatening neurological diseases. We have started communicating with potential investors and co-development partners and invite interested parties to collaborate on the further development of this breakthrough medicine through the preclinical and early clinical stage said Maksim Kholin, the Gero Discovery Co-Founder and Business Development Director.

Reference:http://dx.doi.org/10.1038/s41598-019-48196-z

See original here:
Glycolysis Inhibitor Could Prevent Cell Death and Excitotoxic Brain Disease - Technology Networks

Ancient Greek philosopher Aristotle made what may be the first known attempt to define life. He said that something is alive if it grows, is animated and nourishes itself. A more recent definition suggests the important characteristics being the capacity for growth, reproduction, functional activity and continual change preceding death.

There are other attempts, but they all fail in some way. Both of these definitions, for example, would consider fire to be alive and mules, which are born sterile, not to be alive. All that said, most of us have an instinctive understanding of what it means to be alive. If you see a bug or a bird or even an amoeba, you are certain it possesses life.

None of this, however, tells us anything about how life first started or whence it came. Again, there are countless thoughts about this, such as life resulting from a stroke of lightning zapping just the right elements at the right time. Some believe radiation was the instigator, and some suggest that early life forms arrived on Earth aboard rocks from outer space. No one knows for sure.

However, there is research that shows the possibility of creating the basic building blocks of life, amino acids and proteins, from basic inorganic compounds by simulating the conditions that must have prevailed at Earths beginning. And research in cell biology has established some remarkably likely facts about how we became human.

Its all about cells?

A cell is the smallest functional unit of every living thing; we are made from trillions of them. The cell has a jelly-like liquid called cytoplasm enclosed in a membrane. Within the cytoplasm are structures with functions similar to our organs, and they are called organelles, or little organs, with names like mitochondria, lysosomes and others. With these, the cell can perform for itself all the same functions that we need for life: respiration, reproduction, waste removal, energy conversion and more.

Some cells have an organelle called the nucleus inside the membrane, as well. These are called eukaryotes, meaning to have a true (eu) nucleus (kary). A nucleus is important, as it contains most of the cells genes that are part of its DNA molecules; DNA is packaged in the form of chromosomes in order to fit into the nucleus. Other cells are called prokaryotes, meaning to exist before (pro) a nucleus occurs; bacteria are prokaryotes. They, too, have DNA, but its located directly in the cytoplasm.

The organelles are like computer programs, apps, in that they can perform specific functions, but they have to be started by a brain. The important fact is that cells are intelligent, and their brain is the cell membrane. The membrane includes tens of thousands of IMPs (integral membrane proteins) that receive and send signals from and to their environment, directing the organelles to do their thing and so create the complex behavior of a living cell.

A brief timeline

Earth was created about 41/2 billion years ago, but it wasnt until 3.8 billion years ago that single-cell prokaryotes appeared. That is, the bacteria have been here a seriously long time.

The eukaryotes evolved from prokaryotes, appearing about 21/2 billion years ago, and the kind of life forms we experience today are only about 600 million years old. There were no mammals until about 200 million years ago, and we, Homo sapiens, have been around for a mere 200,000 years. So, what happened to get from the first eukaryotes to us?

Community building

For the first 3 billion years that there was life on Earth, it consisted of independent single cells, monads. They were bacteria, they were algae, they were protozoans and some fungi. It was long thought that they were solitary.

Research has shown, however, that the signals they use to organize their own physiology can be released into their environment, creating a kind of long-distance communication. For example, amoebas consuming food release a particular molecule that informs other amoebas of a supply of food to which many are then drawn. Other signal molecules like hormones were in use by these single-cell critters, as well.

As time passed, monads learned to increase the number of IMPs in their membrane and started to assemble themselves into close-knit cellular communities for survival. As the size and complexity of these multicellular communities grew, they became highly organized and parceled out specific functions to specialized groups of cells: forming body tissues and organs, building nervous and immune systems, etc. And so there evolved the complex organisms we recognize as plants and animals.

As the more complex animals evolved, there were specialized cells that became responsible for monitoring and regulating the flow of signaling among other cells. This central information processor became the brain that controls the overall interaction and behavior of all the cells in the body. We commonly believe that our mind is the same as our brain and is located our head. However, neuroscientist and pharmacologist Candace Perts elegant experiments showed that the mind is distributed throughout the body.

We as humans, and, in fact, all mammals and some others, are an advanced stage of this kind of community organization. Of special interest is the development of a region of the brain called the prefrontal cortex. In this, we find the capacity for thinking, planning and decision-making, as well as the seat of self-consciousness.

And so ...

Cellular communities continue to evolve, giving new perspectives on what it means to be alive.

Bob Keller maintains a holistic practice in Newburyport. He offers medical massage therapy for pain relief, as well as psychological counseling, dream work and spiritual direction. Many patients call him Dr. Bob and accuse him of doing miracles, but he is not a medical doctor nor a divinity. His expertise is medical massage therapy, understanding this miracle we call the human being. He can be reached at 978-465-5111 or rk2name@gmail.com.

The rest is here:
Making Sense of Medicine: The meaning of life | Lifestyles - The Daily News of Newburyport

Share this Article

You are free to share this article under the Attribution 4.0 International license.

The CRISPR gene editing technique may provide the means for lifelong correction of the genetic mutation responsible for Duchenne muscular dystrophy, a new study with mice shows.

Duchenne muscular dystrophy (DMD), a rare but devastating genetic disorder, causes muscle loss and physical impairment. Children with DMD have a gene mutation that interrupts the production of a protein known as dystrophin. Without it, muscle cells weaken and eventually die. Many children lose the ability to walk, and muscles essential for breathing and heart function ultimately stop working.

Research has shown that CRISPR can be used to edit out the mutation that causes the early death of muscle cells in an animal model, says Dongsheng Duan, professor in medical research in the molecular microbiology and immunology department at the University of Missouri School of Medicine and senior author of the paper in Molecular Therapy.

However, there is a major concern of relapse because these gene-edited muscle cells wear out over time. If we can correct the mutation in muscle stem cells, then cells regenerated from the edited stem cells will no longer carry the mutation. A one-time treatment of the muscle stem cells with CRISPR could result in continuous dystrophin expression in regenerated muscle cells.

For the study, researchers explored whether they could efficiently edit muscle stem cells from mice. They first delivered the gene editing tools to normal mouse muscle through AAV9, a virus that the US Food and Drug Administration recently approved to treat spinal muscular atrophy.

We transplanted AAV9 treated muscle into an immune-deficient mouse, says lead author Michael Nance, a MD-PhD program student in Duans lab. The transplanted muscle died first then regenerated from its stem cells. If the stem cells were successfully edited, the regenerated muscle cells should also carry the edited gene.

The researchers reasoning was correctthey found abundant edited cells in the regenerated muscle. They then tested if they could use CRISPR to edit muscle stem cells in a mouse model of DMD. Similar to what they found in normal muscle, the stem cells in the diseased muscle were also edited. Cells regenerated from these edited cells successfully produced dystrophin.

This finding suggests that CRISPR gene editing may provide a method for lifelong correction of the genetic mutation in DMD and potentially other muscle diseases, Duan says.

Our research shows that CRISPR can be used to effectively edit the stem cells responsible for muscle regeneration. The ability to treat the stem cells that are responsible for maintaining muscle growth may pave the way for a one-time treatment that can provide a source of gene-edited cells throughout a patients life.

With more study, the researchers hope this stem cell-targeted CRISPR approach may one day lead to long-lasting therapies for children with DMD.

Additional coauthors are from the University of Missouri, the National Center for Advancing Translational Sciences, Johns Hopkins School of Medicine, and Duke University. The National Institutes of Health, the Department of Defense, the Jackson Freel DMD Research Fund, Hope for Javier, and the Intramural Research Program of the National Center for Advancing Translational Sciences funded the work.

Source: University of Missouri

See original here:
CRISPR fix in mice may lead to muscular dystrophy therapy - Futurity: Research News

Several recent studies in high-profile journals reported to have genetically engineered neurons to become responsive to magnetic fields. In doing so, the authors could remotely control the activity of particular neurons in the brain, and even animal behaviorpromising huge advances in neuroscientific research and speculation for applications even in medicine. We envision a new age of magnetogenetics is coming, one 2015 study read.

But now, two independent teams of scientists bring those results into question. In studies recently posted as preprints to bioRxiv,the researchers couldnt replicate those earlier findings.

Both studies . . . appear quite meticulously executed from a biological standpointmultiple tests were performed across multiple biological testbeds, writes Polina Anikeeva, a materials and cognitive scientist at MIT, to The Scientist in an email. I applaud the authors for investing their valuable time and resources into trying to reproduce the results of their colleagues.

Being able to use small-scale magnetic fields to control cells or entire organisms would have enormous potential for research and medical therapies. It would be a less invasive method than optogenetics, which requires the insertion of optical fibers to transmit light pulses to specific groups of neurons, and would provide a more rapid means of inducing neural activity than chemogenetics, which sparks biochemical reactions that can take several seconds to stimulate neurons.

In a 2016 study in Nature, geneticist Jeffrey Friedman from Rockefeller University and colleagues reported to have stimulated neural activity in glucose-sensing neurons in the mouse hypothalamus. Those neurons fired when the animals were exposed to a magnetic field, causing blood glucose concentrations to rise and insulin levels to fall. Ultimately, the mice ate more.

What I find most impressive about these reports . . . is just the level of care and effort that has gone into this.

Markus Meister, Caltech

The researchers did so by genetically engineering a construct to be expressed specifically in those neurons. The introduced sequences coded for the iron-based blood cell protein ferritin coupled to the TRPV1 membrane channel, a temperature-sensitive protein that allows positively charged ions such as calcium to enter cells. Stimulation of ferritins iron through a magnetic field was thought to prompt TRPV1 to open, although the precise mechanism is unclear.

In a different 2016 study in Nature Neuroscience,neuroscientist Ali Gler of the University of Virginia and colleagues used a similar construct they named Magnetothis time coupling ferritin to the TRPV4 membrane protein, sensitive to mechanical forces as well as temperature changes. Expressing this in dopamine-receptor neurons in the mouse striatum caused the rodents to preferentially spend time in a magnetized area of their cage.

The year prior, researchers of Tsinghua University in Beijing had expressed the gene for a different iron proteinmembrane channel construct, dubbed MAR, in specific sensory neurons of the nematode worm Caenorhabditis elegans. Applying a magnetic field resulted in changes to the worms movement, they reported in Science Bulletin. All three research groups presented multiple lines of evidence to back up their claims, such as electrophysiologic techniques to monitor the activity of individual neurons in brain slices and in vitro calcium imaging assays, in addition to the behavioral studies.

The studies received a mix reception from the scientific community. Some, like Boston neuroscientist Steve Ramirez, were enthusiastic, calling the work badass on Twitter, while others were skeptical, critiquing the findings in journals and on blogs. That latter includes Markus Meister, a physicist-turned neuroscientist at Caltech, who says hes aware of several research groups that had difficulties replicating some of the findingsspurring some to conduct lengthy, systematic investigations of the function of these constructs.

The new replication studies used a range of methods to investigate whether the constructs work as described in earlier research. In one study, neurophysiologist Tansu Celikel of Radboud University in the Netherlands and his colleagues focused their research on the Magneto construct used in Glers study.

Like Glers group, they used a virus to deliver DNA encoding Magneto to neurons in the mouse cortex and waited two weeks for the cells there to express the construct. Using permanently implanted microelectrodes, they recorded cortical neural activity as they exposed the animals to a magnetic field. The stimulus didnt change the rate of action potentials in those neurons, they observed, and the same was true for in vitro experiments. We argue that the utility of Magneto to control neural activity in vivo is not warranted, the authors write in the preprint.

In the second study, neuroscientist Julius Zhu of the University of Virginia and his team conducted a systematic investigation of all three constructs that had been used in previous studies: Magneto, the TRPV1-ferritin complex developed by the Rockefeller group, and the MAR construct. (Gler, who is also at Virginia provided some materials for the experiments, but the two labs did not collaborate.)

Were anxious to understand what the basis for the differences between his results and ours are.

Jeffrey Friedman, Rockefeller University

Similar to Celikels findings, they observed that magnetic fields did not induce an electrical current in Magneto-expressing mouse hippocampal cells in culture, when the construct was delivered either with a plasmid or a virus. They did note, however, that both Magneto-expressing neurons as well as control cells that lacked the construct frequently displayed spontaneous changes in current that sometimes triggered the cells to fire an action potential. Based on this, they suggest that Glers reportedly magnetically triggered action potentials are likely to represent mismatched spontaneous firings.

The team appears to have had difficulties getting the construct expressed in cells at all. They used a plasmid encoding the Magneto construct to express it human kidney cells in culture, and made electrophysiological recordings of the cells. Neither a magnetic field nor the addition of a protein that stimulates TRPV4 elicited significant electrical currents in the cells. Interestingly, they did observe a current when they repeated these experiments with kidney cells that expressed the wildtype, unaltered version of the gene for TRPV4 expressed separately with ferritins gene. Together with other observations, this suggested that Magneto doesnt form a functional ion channel or incorporate into the plasma membrane, the authors suggest. The construct lacks a portion of the TRPV4 protein considered necessary for its placement in cellular membranes, the researchers note.

In testing the other constructs, Zhus group used viruses to express MAR in neurons from cultured rat hippocampal slices, and the TRPV1-ferritin construct in hypothalamic neurons in intact mouse brains. Again, electrophysiologic recordings did not detect a change in action potentials in any of the genetically modified cells when they were exposed to a magnetic field, although the cells did exhibit frequent spontaneous action potentials. Together, these results support the theoretical conclusion that Magneto, [MAR] and [the ferritin-TRPV1 construct] are incapable of controlling neuronal activity by producing magnetically-evoked action potentials, they write in the preprint. The senior authors of both studies both declined to comment out of concern it would interfere with the publication of their research in a peer-reviewed journal.

What I find most impressive about these reports . . . is just the level of care and effort that has gone into this, remarks Meister. Neither he nor Anikeeva are surprised by the new findings; both have previously critiqued earlier studies. By now, if it worked as advertised, you would expect a small industry of people doing this and using it for all kinds of purposes, Meister says.

Neither have a good alternative explanation for the observations reported in earlier studies. Meister suggests it may boil down to human error, while Anikeeva speculates that tethering ferritin, a relatively bulky protein, to TRPV proteins might possibly make the channels leaky and lower the threshold for action potential firing.

Gler, who developed the Magneto construct, points out several differences between his study and the two preprints that may account for the contradictory results. The groups used different viruses to introduce the constructs to cells, and for the most part, didnt allow as much time for them to be expressed in neurons as Glers group did, which may be why they didnt achieve full presentation in the cellular membranes. For some experiments, they also didnt verify that the viruses were actually expressing the constructs before they introduced them into cells, he adds. Some batches will not work, and you have to systematically make sure that your tools are up to par, he tells The Scientist.

We acknowledge that the system we have developed is a little finnicky in that it requires a lot of optimization to get it to work, he adds. I think that is where the setback is: everybody wants to have something that works immediately. Magnetogenetics techniques will take some time to refine until they are reliable, he says.

Friedman, the senior author of the Nature study, is similarly puzzled why Zhus team couldnt replicate his findings. We take the Zhu paper seriously and . . . were anxious to understand what the basis for the differences between his results and ours are, he says. Zhus team expressed the construct indiscriminately into all neurons in the hypothalamus rather than selectively in a subset of cells, as Friedman did. Some hypothalamic neurons are more easily excitable than others, he explains. Its possible that by restricting the cells we were recording from, we may have gotten a cell type that . . . seems to be more rather than less responsive.

Friedman stresses that his team did multiple experiments as part of their study to ensure that they werent mistakenly attributing spontaneous neural activity to a magnetic effect. For instance, in the same Nature study they repeated their experiments with an altered version of the TRPV1 channel that acts as a chloride channel rather than a calcium channel. Whereas calcium influx would excite a neuron, chloride flux would inhibit it, Friedman explains. We get opposite effects when we use the inhibitory version of the construct instead of the activating one, he says. We wouldnt see that if it was spontaneous activity.

Both Gler and Friedman note there are three additional studies that report having successfully used similar genetic techniques to excite neurons under magnetic fields. In 2017, a team of researchers engineered a construct made of the genes for ferritin and the heat-sensitive channelseither TRPV1 or TRPV4into neural crest cells of chick embryos, claiming to have stimulated the neurons with electromagnetic fields. In 2018, another group combined the TRPV1-ferritin construct with a protein involved in cell migration, and showed that human kidney cells expressing the introduced genes had an unusual migration pattern when under a magnetic field. And earlier this year, a third set of researchers replicated Glers findings by expressing a TRPV4-ferritin construct in a human kidney cell line to better understand its function, also observing a response to magnetic stimulation.

Its not quite clear how these constructs might work. One possibility is that magnetic fields cause the iron atoms in the ferritin to flip periodically, generating heat that causes the temperature-sensitive TRPV1 channel to open. Another option is that the stimulated ferritin would tug open the central pore of the membrane channels. The group that was able to replicate Glers results in kidney cells suggested that the magnetic sensitivity of the TRPV4 channel has more to do with thermal energy than with mechanical force.

Meister has argued that these proposed mechanisms conflict with basic laws of physics, on the grounds that ferritin doesnt have the characteristics necessary to prompt a mechanical stimulus under a magnetic field. In several back-of-the-envelope calculations outlined in his 2016 eLife paper, Meister shows that magnetic interactions between ferritin and a magnetic field would be between five and ten orders of magnitude too weak to generate the mechanical force to cause a membrane channel to open.

The core of ferritin consists not of a truly magnetic substance, but ferrihydrite, which is only weakly paramagnetic at room temperature. This means that the molecule requires a more powerful magnetic field to induce a magnetic momentthat is, to align all iron atoms with the magnetic fieldthan those used in previous studies. Even if the iron ferritin was truly magnetic, the forces would still be too small to account for the proposed mechanisms, notes Anikeeva, who made similar arguments in a separate eLife paper.

Those biophysical arguments could be overcome if physicist Mladen Barbic of the Howard Hughes Medical Institutes Janelia research campus is right. Earlier this year in eLifehe proposed several new alternative mechanisms whereby magnetic stimulation of ferritin could open an ion channel. One, for instance, is based on the Einstein-de-Haas effect, by which iron oxide particles would rotate under a magnetic field, producing energy which could perhaps cause the ion channel to open. Other groups are exploring the possibility of a chemical mechanism through the release of free iron, Friedman says. I think all these are on the table, he says.

The lure of a non-invasive method to control neural activity has kept scholars in pursuit of a reliable method of magnetogenetics, including those that arent based on ferritin. For instance, Anikeevas group has shown that its possible to open TRPV1 and stimulate neuronal activity with synthetic nanoparticles made of the iron oxide magnetite. The particles are known to dissipate heat, and that opens the channels, she explains. However, these particles cant be genetically expressed because they are synthetic. Rather, they have to be injected into the brain.

Another route is to look at organisms in nature that have already evolved systems that respond to magnetic fields. Magnetotactic bacteria, for instance, produce particles similar to the ones Annikeeva synthesized in her lab, she writes. Scientists could also examine the mechanisms that migratory organisms such as pigeons, butterflies, and fish use to sense magnetic fields to navigate, she suggests.

What may help speed these efforts along, and help untangle the controversies around magnetogenetics, is better communication between physics and neuroscience, Anikeeva notes. There should be more interaction between physical and biological sciences, especially in the context of training of both biologists and engineers in each others disciplines and vocabularies.

Katarina Zimmeris a New Yorkbased freelance journalist. Find her on Twitter@katarinazimmer.

Continued here:
Two Studies Fail to Replicate Magnetogenetics Research - The Scientist

The news that Formula One legend Michael Schumacher was moved to a hospital in Paris last week for pioneering stem cell therapy has provoked a fever of hope and speculation among fans that his condition could be improved.

After suffering devastating head injuries in a ski accident almost six years ago, Schumacher was placed in a coma for six months and has been receiving treatment at his home in Switzerland. He has not been seen in public since the accident.

His privacy is closely guarded and, while it is understood he cannot walk or stand, and, according to former Ferrari manager, Jean Todt, he may still have trouble communicating, nothing has been confirmed officially.

No wonder then that fans have been so excited to hear Schumacher is now under the care of world-renowned cardiac surgeon Philippe Menasch, described as a "pioneer in cell surgery" at the Georges-Pompidou hospital in Paris.

READ MORE:* Schumacher 'conscious' after treatment*Corinna Schumacher provides rare update*Schumacher 'struggles' to communicate*Mick Schumacher trying to emulate his dad

Stem cells are cells that can differentiate or change into other types of cell, opening the possibility of replacing damaged cells with healthy ones. Scientists have been looking into their use since the Sixties, most successfully so far in cases of cancers of the blood or bone marrow. More than 26,000 patients are treated with blood stem cells in Europe each year.

And since the Eighties, skin stem cells have been used to grow skin grafts for patients with life-threatening burns; most recently, a new stem cell-based treatment to repair damage to the cornea (the surface of the eye) after an injury like a chemical burn, has received conditional approval in Europe.

But their flexibility offers hope for lots of illnesses and conditions including heart disease, MS and macular degeneration and clinical trials are progressing in all these areas. Chronic spinal cord injury is being researched with some promise, thanks to the Christopher & Dana Reeve Foundation, set up after actor Christopher Reeve was paralysed in a riding accident.

Crucially, for cases such as Schumacher, stem cells are also being explored for neurodegenerative diseases like Parkinson's and Alzheimer's and traumatic brain injuries like the one he suffered in a skiing accident in December 2013.

Head injuries are difficult to treat as brain damage cannot be undone and each case is different. Asked for comment by The Daily Telegraph, the hospital responded that they could neither confirm nor deny the presence of Schumacher.

However, if he is under the care of Menasch, it is likely he will have had stem cells delivered by an IV to the area of the body where it is felt they could work best - whether that is his head or heart.

CHRISTOPHE ENA/AP

Paris' Georges-Pompidou Hospital, where Michael Schumacher is reportedly a patient.

In a recent interview online, Menasch explained that stem cell treatment for cardiac conditions - his particular area of expertise - is in its infancy. "Nobody really knows how stem cells are working," he said. "They do not permanently transplant into the myocardium [the muscular tissue of the heart] - after a couple of days or weeks, they just disappear.

"But you still may have a functional benefit as during their transient stay in the heart," he explains in the Future Tech podcast, "as the cells release molecules into the tissue. The hypothesis is that the repair comes from the heart itself, stimulated by these molecules."

Should the stem cells have been intended for Schumacher's brain injury, research suggests that the treatment has potential. A University of Plymouth study published in the journal Cell Reports in June found that neural stem cells could be used to "wake up" and produce new neurons (nerve cells) and surrounding glial cells in the brain.

The research is in its infancy, says lead author Dr Claudia Barros, from the Institute of Translational and Stratified Medicine at the University of Plymouth, who acknowledges there is still a long way to go until such findings can be translated into human treatments.

"We are working to expand our findings, to bring us closer to the day when human neural stem cells can be controlled and efficiently used to facilitate brain damage repair, or even prevent brain cancer growth that is fuelled by stem-like cells," she says.

A Chinese study published last month in the journal Frontiers in Cellular Neuroscience examined the current state of progress into the effects of stem cell therapy on traumatic brain injury. But the researchers from Zhejiang University, Hangzhou warned much more work was needed: "Although a large number of basic studies have confirmed that stem cells have good effect in the craniocerebral injury," they said, "the safety of stem cells, the route of injection, the time of injection and the specific mechanism are all factors that affect the clinical application of stem cells, and are the important research point in the future study."

PREMA TEAM

Mick Schumacher doesn't mind the comparisons with his seven-time F1 champion father Michael.

In the UK, some applications of stem cell medicine are already available privately, although tightly controlled by the Human Tissue Authority and not in the brain.

Simon Checkley, CEO at the Regenerative Clinic in Brighton, explains: "It is possible to get stem cells from sources outside your body, like the umbilical cord or Wharton's jelly [the vitreous humour in the eyeball], but in the UK we can only take stem cells from our own bodies.

"It is possible to get them donated, but it is safer to use your own."

In some countries, stem cells can then be manipulated in a laboratory but that is illegal in the UK, says Checkley. "There is a concern with cultured stem cells which have been bred in a Petri dish that they may keep proliferating after you transplant them into a body. That, having triggered their growth, you can't stop it and no one knows what might happen."

At the Regenerative Clinic, stem cells are taken from adipose fat, where they are plentiful, and then injected back into the area to be treated - mostly arthritic joints.

"We are seeing fantastic results," Checkley says, "with reduced pain and improved mobility for 80 per cent of patients." He is considering a clinical trial which could see the treatment pass through the National Institute for Health and Care Excellence (NICE) and become available on the NHS.

The therapy is still only four years old, he emphasises. "We have treated 1000 patients so far and around the world, it's about 40,000. We need longer-term studies."

LUCA BRUNO/AP

Michael Schumacher has not been seen in public since suffering a serious brain injury in a skiing accident nearly six years ago.

This type of stem cell treatment is also offered in the UK for post-menopause vaginal atrophy and stress incontinence, Checkley says, plus the genital skin condition lichen sclerosis. In all these cases, he says, the mechanism is the same: the stem cells are not replicating dead or dying cells but acting as signalling devices, alerting the body that this is an area where healing is needed.

For stem cells to work in more complex conditions, they would need to be manipulated, Checkley says. In cases of brain injury or disease, that would mean altering stem cells so that they could be targeted more precisely. But he believes the role would be similar: "The idea is they would go to the area of greatest damage and signal the body to regrow tissue there."

Cost would be a huge factor, he points out. A treatment for arthritis costs about 6000 (NZ$11,700) at the Regenerative Clinic but an IV-led treatment for brain injury with manipulated stem cells could cost up to 50,000 (NZ$98,000). But then what price recovery from a traumatic brain injury? Full recovery thanks to stem cells would be a prize beyond value.

Go here to read the rest:
Reported stem cell treatment could give hope to Michael Schumacher - Stuff.co.nz

(Reuters) - For Jessica Lescault there is no question that her 6-year old English bulldog Moose deserves cutting-edge biotechnology cancer treatment as much as any human patient.

Pets are your loved ones, pets should be your family, pets are not something you keep on a chain in the backyard, the intensive-care nurse from Somers, Connecticut, said.

Lescault, 43, who enrolled Moose in a clinical trial of an experimental drug designed to help his immune system fight his cancer, represents the type of pet lover that has spurred animal health companies around the globe to invest in developing complex new treatments previously reserved for humans.

Biotechnology, which produces medicines from living cells, revolutionized the drug industry more than a quarter century ago with breakthrough medicines at prices that now run as high as hundreds of thousands of dollars a year.

In recent years, the cost of genetic testing and biotech drug production has fallen sharply, making biotechnology for pets financially viable at much lower prices, industry experts said. For a FACTBOX, click

Sector leader Zoetis (ZTS.N) and others say animal drug development is faster, less expensive and more predictable than drugs for people.

Its not nearly as common for pivotal studies to fail in animal health as it is in human medicine. Most of them are successful, said Cheryl London, professor in comparative oncology at Cummings School of Veterinary Medicine at Tufts University in Massachusetts.

Biotech drugs for pets, if proven safe and effective, would be a boon to a $44 billion veterinary medicines market currently dominated by vaccines, flea and tick repellents and anti-infectives.

A recent product launch has galvanized the industry.

Cytopoint for canine itch relief sold by Zoetis reached blockbuster status by animal health standards in its second year on the market. Launched in late 2016, Cytopoint generated 2018 sales of $129 million, and first-quarter 2019 sales jumped 65% from a year earlier.

Produced from cloned genetically engineered hamster cells over at least eight bio-processing steps, the monoclonal antibody is no less complex than comparable therapeutic proteins used in human medicine. But the cost to consumers is far less.

Like many biotech drugs, dose and cost is determined by weight. Zoetis declined to disclose its prices. But an animal hospital in Stamford, Connecticut, for example, charges $104 for a 40-pound (18 kg) dog. For much smaller dogs, a Cytopoint injection, which lasts about four to eight weeks, costs about $35 to $50. To keep a large dog from scratching itself raw could run $140 per shot.

The cost of a highly effective new anti-itch biotech drug to treat severe atopic dermatitis in humans can run about $30,000 a year.

Cytopoint was a turning point that has made it clear that (biotech drugs) can be successful in this space, London said. Now there are an estimated five to ten companies developing antibodies for the veterinary market.

That has created increased business for related services.

Its a big challenge for us to keep up with the pace of demand growth, said Klaus Hellmann, managing director at Munich-based Klifovet AG, Europes largest contractor for late-stage clinical trials of veterinary drugs.

While Cytopoint sparked investment interest in biotech treatments for animals, drug development still comes with inherent risks and uncertainty.

Aratana Therapeutics Incs canine lymphoma drug, Blontress, was launched in 2015, but later withdrawn after scientific data led the company to determine it was unlikely to be a financial success.

Declining costs has mitigated some of the risk.

Over the past several years, human health has been able to advance the technology to improve efficiency of their cell production systems, said Rob Polzer, head of global therapeutics research for Zoetis.

Zoetis can repurpose and optimize existing procedures, mechanisms of action and technologies, it said.

The company is seeking approval for a biotech medicine to treat osteoarthritic pain in cats, with plans for a 2021 market launch and a similar product for dogs thereafter.

Others have jumped on the bandwagon.

German start-up Adivo was spun out of biotech firm Morphosys (MORG.DE) in March 2018 out of frustration by its founders that scientific advances for humans were not translating into better treatment options for their dogs.

It has since struck a global collaboration deal with Bayers (BAYGn.DE) animal health unit for its early-stage research platform for animal-specific monoclonal antibodies - the backbone of biotechnology.

Over the last few years, the veterinary market has seen an incredibly dynamic development, said Adivo co-founder Kathrin Ladetzki-Baehs.

This could prove a lifesaver for Moose, the bulldog in the oncology drug trial.

In early August, Lescault discovered a mass on Mooses throat, soon followed by deteriorating health and a diagnosis of canine B-cell lymphoma. Moose was given one to two months to live without treatment or about a year with 25 weeks of punishing chemotherapy.

Lescaults local vet suggested the Tufts trial testing an experimental protein that could help advance the current immuno-oncology craze into the animal health arena.

Tufts declined to disclose the compound or the studys sponsor. But more than three weeks into the trial, Mooses cough and labored breathing has disappeared and he is back to his playful and boisterous self, Lescault said.

While treatment in a clinical trial is free, Lescault said she would not hesitate to pay thousands of dollars for a safe and effective drug to save Moose. I wouldnt blink an eye, she said.

That is exactly what drug companies are banking on.

Additional reporting by Katherine Taylor in Boston; editing by Bill Berkrot

Continue reading here:
Biotech is going to the dogs - and big profits await - Reuters

One scientist recently suggested cannibalism might be the way that humanity can survive climate change. We suspect satire, but it seems some of the cells in our bodies are way ahead. Unfortunately, it's the cells we don't want to survive. New research suggests eating other cells could be the secret that allows certain cancer cells to survive the most powerful drugs modern medicine can throw at them.

The side effects of chemotherapy are brutal, but it's an exceptionally effective way to destroy cancer cells while keeping the essential organs of the body alive. Sometimes, however, a small portion of cancer cells manage to evade the chemicals that kill most of their brethren, allowing them to come back, usually with fatal consequences.

Understanding how they do this is key to finding ways to prevent it and saving millions of lives. It's a complex process because not all resistant cancer cells use the same method and we're just starting to understand the diversity of approaches. Dr Crystal Tonnessen-Murray of Tulane University in Louisianna has identified a particularly gory path some breast cancer cells use, which is also adopted by some other cancers.

Despite the great strides that have been made in treating many forms of breast cancer, some have proven more obstinate, including those that have a normal TP53 gene. A normal version of a gene sounds good, particularly considering TP53 codes for a protein that suppresses tumors, and 70 percent of cancers involve mutations in this one gene. However, the other 30 percent of cancers include some with the worst survival rates.

The types of breast cancer Tonnessen-Murray is studying include cells that enter a form of dormancy when exposed to chemotherapy, preventing them from dying, and bounce back when the treatment stops. In the Journal of Cell Biology Tonnessen-Murray reveals that during this stage, known as senescence, the tumor cells often swallow neighboring non-senescent cancer cells.

Tonnessen-Murray has witnessed this occurring in cultured human breast cancer cells, mouse mammary tumors, and certain lung and bone cancers, indicating it could be quite a widespread trait.

The capacity to engulf other cells is an adaptation of processes used by white blood cells to absorb threats such as bacteria for disposal. The consumption of neighbors is associated with longer survival times for these cells, presumably because it provides nutrients to power the cells through the period where normal feeding is interrupted, like lost explorers eating their companions to survive a long winter, and then reboot when the opportunity presents.

"Understanding the properties of these senescent cancer cells that allow their survival after chemotherapy treatment is extremely important," Tonnessen-Murray said in a statement. Exactly how this insight can be used to help those suffering from chemo-resistant tumors remains to be seen, but only by learning these miniature Hannibal Lecters' secrets will we discover how to overcome them.

Visit link:
Cancer Cells Survive Chemotherapy By Turning Into Cannibals - IFLScience

Indian-American oncologist and author Dr Siddhartha Mukherjee, Biocon chairperson Kiran Mazumdar Shaw and Kush Parmar, managing partner at 5AM Ventures, are bringing the innovative Chimeric Antigen Receptor (CAR) T-cell therapy to cancer patients in India. Cell therapies are therapies in which your own body cells are used as drugs to fight cancer. In CAR T-cell therapy, immunological cell is derived from the patients body and weaponised to kill cancer cells in the body.

In an interview to CNBC TV-18, Dr Siddhartha Mukherjee touches upon the affordability of this therapy and the other challenges facing cancer research and treatment in India.

Edited excerpts:

I want to talk to you about your visit to India. There is an announcement you are making with Kiran Mazumdar-Shaw. So tell me a little bit more about that.

We are announcing the formation and launch of a company that will deliver cell therapies in India. Cell therapies are therapies in which cells your own body cells are used as drugs to fight cancer.

One example of this is a so-called CAR T-cell. The name stands for a kind of immune cell, immunological cell that is derived from your own body and is engineered, weaponised to go and kill cancer cells in your body.

This therapy has been in development in many countries for several years but was finally launched as an FDA-approved drug a couple of years ago against certain cancer zones. Different ones work for different cancers but it was not available in India at all. So we, Kiran, Kush Parmar and I partnered up and our goal is to deliver the first in human cellular therapy in India for cancer.

When are we going to be seeing this commercialised?

So, these are extraordinarily complicated. They are called living drugs. They are drugs but they are alive. So you can imagine that producing them, making them available is an extraordinarily complicated process. Also, you have to be extremely careful because it is not like manufacturing aspirin or penicillin. It is taking cells, weaponising them, usually with a virus, and then re-injecting them into the body. So the whole process to develop this, we are hoping, will take about six to eight months. We hope to be in human patients in India within eight months.

Do you have all the regulatory clearances here in India?

A completely new regulatory framework needs to be created so that it is not just free for all as it were because these are toxic therapies, they are reserved for cancer patients, you have to know how to use them. These are living drugs, these are living things. You can imagine that if you dont control them properly, they can go out of control. So you require not just the scientific framework, which is important, but also the regulatory framework. What are the circumstances that an individual hospital or a medical centre can be allowed to use them, what are the safety precautions.

We dont have that yet in India?

We have the broad framework, but it has to be made specific for the use of cellular therapies. India has a very powerful regulatory framework for the use of drugs, but for living drugs, there are some special things that need to be addressed; safety needs to be addressed, you can get contamination. So you cannot just decontaminate a living drug like you decontaminate a chemical.

For instance, just to give you a very practical example, imagine if I am growing a patients T-cells in an incubator and that incubator gets infected with a bacteria or a virus, that whole batch has to be destroyed, the whole incubator has to be cleaned. Maybe the entire facility has to be cleaned to ensure that the next one doesnt get infected. So it is a very different process. It fits under the broad umbrella but it is fundamentally a different process.

It is all going to happen out of Bangalore. How is this going to work?

Kiran and I have had extensive discussions. The best way to do this is to do it at one facility to start with. The closest analogy that we have to living drugs is drug made out of living cells, insulin being one of them. So we decided to start off with a facility where we could have exquisite control. We need to have exquisite control so that we can deliver the therapy to the first needy patients. These are extraordinarily effective drugs, we wouldnt be doing this if these werent extraordinarily effective drugs for particular cancers.

Would these be affordable and accessible?

The challenge is affordability. Just to give you a sense of what the numbers are in the US, there are two T-cell drugs that are now approved in the US and the ticket price for them they are called Yescarta and Kymriah is around $400,000 per person. Part of the problem is that they are intrinsically expensive to make. It is not like making aspirin, it is not like making insulin, it is not like making penicillin. You have to take the cells out of someones body, weaponise them with a virus, grow them in incubators, ensure the safety and then return them back into patients. So I think that the real trick and the real advantage is we will be taking advantage of the ingenuity of Indian engineers and Indian bio-engineers.

We are pretty convinced, we have done very detailed analysis of this. This is my fourth visit and we are confident that we can reduce that $400,000 price tenfold. Even that lies beyond affordability, but it is on the order of a bone marrow transplant in most countries outside the West.

The goal is to make it affordable but this is never going to be an insulin or a penicillin or an aspirin, this is reserved for patients who are very needy, very desperate. We will almost certainly have programmes for the most needy and the most desperate that will allow them to afford it. These are intrinsically very difficult to make.

I want to pick up this latest collaboration that you have with Kiran who is part of the healthcare system in India. You have also got a similar venture where Johnson & Johnson is an investor and that venture you started around three years ago. Do you see more of these collaborations picking up pace? Global pharma has tried to reinvent itself post the backlash that it faced a few years ago. That backlash has now shifted to the technology companies. So do you see more of a collaborative approach being taken and what does it mean for research and development (R&D) going forward?

There is no other option. The maturation of a living drug, the natural cycle is exactly this. So usually drugs are born in laboratories; I am a laboratory investigator, I am a research scientist. I own the patterns that lead to the companies called Vor. I have another one called Myeloid, there are about 6-7 of them. These originate in my ideas or in the ideas of very young investigators who are really driven to solve this problem.

How do you fight cancer with cell or with other therapies? But that is their skillset. Now to convert that into a real therapy, to run a human study to be able to deliver that therapy, safely, effectively to humans, you have to collaborate.

So the way we collaborate now is that we form a biotech company. This company is ceded by investors, its ceded on the basis of science. These investors are extremely savvy, they are extremely thoughtful. Before making an investment, they will make deep analysis of the product itself; is it viable, is it effective, what data do we provide etc. And then you form that company and at that stage you begin to attract companies like Johnson & Johnson, Novartis and open your asset to them, open what you have invented and ask the question would you partner with us in bringing this thing which is just an idea to becoming a real medicine. This is a tried and tested process and this is what is happening.

I know that your research approach has been to understand the micro environment as you call it, to understand cause and co-relation. So given the approach that you have taken and with the likes of Johnson & Johnson, Novartis, Biocon etc. partnering with you, what could it mean for costs? Do you see this becoming more accessible and hence affordable for a country like India?

There is a pipeline process. Part of the reason that I began to collaborate with Kiran was that if we can have one of those most viable telecom and software sectors on the planet, we should be able to make cellular therapies; we should be able to make Chimeric Antigen Receptor (CAR) T-cell, T-cell. There is no fundamental reason that Indian engineers and Indian scientists, and of course, ultimately Indian patients cannot get access to these therapies. This is not like rocket science.

We have mastered that too

We have almost mastered that, but it requires that kind of effort. It requires a certain sense of audacity, it requires an ambition but that is what we are in for. We know the challenges but we have a kind of deep confidence that we can reduce the cost 5-10 fold and still deliver effective therapies. The engineers that I have met here, the scientists that I have met here, the board that we formed is of the bluest chip quality. They involve some of the inventors of these therapies in the United States and in the UK. There is no lack of quality and determination. Operationalising it, making sure that the government partners with us in an appropriate way. Those are the challenges that we are facing right now and we will solve them.

I want to ask you this because you meet people who are backing or funding healthcare. You talk to regulators, you talk to governments around the world. What is the priority, for instance, for the government of India at this point in time? How do you deal with the cancer problem? It is a crisis that this country is also dealing with? What will it take for the government to prioritise it or how should they prioritise it?

The problem of cancer or the crisis of cancer is in some ways the side effect or cross effect of a population that is living longer thats one reason; in India that is compounded by the fact that smoking is still a major problem; cigarette smoking, and pollution is a major problem. We are not effectively vaccinating for cancer such as cervical cancer thats caused by human papillomavirus. Vaccine is available. So there are many arenas in which you could handle the cancer problem but for a government to handle cancer, that strategy is built on a pyramid. The bottom of the pyramid is prevention and that is the deep bottom pyramid.

And that is where there isnt enough attention?

That requires a vast amount of attention and prevention. I gave you some examples, thats why I used those examples first. I used the example of stopping of cigarette and tobacco, the effects of various pollutants particularly in the air and water, and finally vaccination against cancers that can be vaccinated against.

The second layer of that is early detection. This would include finding cancer at the earliest possible phases. The very effective ones are Pap smearing, colonoscopy, less so mammography but still effective to find breast cancer, and in general cancer health screening. The final layer of the pyramid is of course cancer treatments, therapies, including chemotherapy, things like Tamoxifen, which is actually quite inexpensive. Tamoxifen is an inexpensive drug and very effective for breast cancer.

Its important to realise that this pyramid is part of an ecosystem. It feeds back on itself. So you begin with prevention. There is early detection and there is final treatment. You only create a strategy against cancer by creating this entire ecosystem. You dont slice out one piece of it and you certainly dont slice out the most expensive piece of it, which is treatment. Cancer treatment is at the top of the pyramid, the narrowest edge of the pyramid. The base, as far as the government is concerned, is to focus on prevention and that is an important idea for the Indian government and all other governments to internalise. It has done that to some extent. There are now finally anti-smoking, anti-pollution and vaccination campaigns all across India.

But do you see that happening at a pace that will ensure that we are being able to deal with this issue?

So for schizophrenia and depression that process has happened. We now understand very well that schizophrenia is not just a kind of random madness but rather is a genetic disease that has an environmental component to it but has a genes and environment component to it so that is one example.

For schizophrenia, in fact, some of the genes are now being identified and we are trying to understand the circuits, the mental circuits that interact with the environment and thereby cause schizophrenia. We are beginning to understand similarly for depression.

In some cases, it has to do with the destigmatisation of things that were called illnesses, but in fact are not illnesses at all. Homosexuality is one of them. Around 50-70 years ago, a mental health handbook would define homosexuality as a mental illness. It has been a striking mark of progress to understand that that is not the case.

So we have seen a lot of this happen already in many countries. We are seeing that happening in India and it was a very proud moment for the Indian courts to recognise this fact, to recognise that there is biology behind all sorts of health and some things that were called illnesses 20 years ago are really not illnesses, they are states of human behaviour.

What is it that is exciting you in the work that you are doing or the research that you are doing today?

We are doing a lot of work on gene therapy. We have a completely exciting new programme to try to cure a previously incurable form of leukaemia and we are going to run that first in human study next year.

We have invented a new way to try to cure leukaemia, it is the most exciting thing I have ever done in my life and I am basically so anxious to get this study off the ground. It will be the first time that we will get a gene therapy linked cure for leukaemia.

We have a lot of work that we are doing on stem cells. We identified a stem cell that contributes to osteoarthritis, one of the most common diseases of women around the world but also men.

We are doing a lot of work on pancreatic cancer and breast cancer, finding new medicines and again going through this process. I think of myself as an inventor. I invent drugs, all the programmes in my laboratory are now focused on making human medicines. If you are working in my laboratory and you cannot tell me how your work relates to the development of a new human medicine, for me it is a failure. Everything in my laboratory is directed towards absorbing the research from others but trying to make new human medicines.

I was reading this interview that you had done a few years ago where you spoke of how research that was done for prostate cancer came up with ideas on how to deal with breast cancer. So how much of that kind of cross-pollination are you seeing happen?

It is among the richest arenas of cross-pollination going on right now. The word for a person like me is translational scientist. I am a translator. I take insights from basic researchers, people who work on enzymes, bacteria, genes and genetics. I take those insights and ask the question how can I make a human medicine out of that? I take that all the way into a human clinical trial or human clinical study, the invention of the new drug. This can only happen if there is very deep cross-pollination.

Is more of that happening today? Are the two camps more aligned?

The camps have decided to become more aligned because there is no other choice. This is the only way that we know to make medicine move forward. There is a third camp, clinicians, but it is more like a relay race. There is a handoff between the basic scientists of insights to the translation researchers who then hand off that towards the clinicians. Now all of this process has to come together and requires governments to provide regulations. It requires philanthropists. Of course, it requires patients, it requires venture funds. It is a risk-taking process, but nothing moves in the world of science without risk. So all of this has to come together and that is the only way it moves forward.

As you try to get this ecosystem to work together, what is the biggest challenge that you foresee today? Do you see people now reacting differently to the needs of healthcare and putting more money behind research?

We are sort of in that middle of the road and this is the time that requires the most energy because the middle of the road is when people get the most tired. Bill Gates and I have had many conversations together in Seattle, in Davos and other places. The challenges of global health are extraordinarily acute today. They include a vast spectrum from arenas that the Gate Foundation has focused traditionally on, which are contagious or infectious diseases, all the way to chronic non-infectious disease such as hypertension, diabetes, obesity and of cancer.

So, the challenges are great, they are not solved. We are living longer as a population, we now also need to learn to live healthier and we need to learn to live more fulfilling, robust and ultimately more dignified life.

If you are in a particular country in the African continent, maybe your crisis is Ebola. If you are in Seattle, may be you are facing down breast cancer, but the spectrum of disease is vast and is turning out to be quite universal. One interesting statistic which you may not know, and has not been talked about is that in countries where we think most of the deaths are from infectious diseases are slowly turning around. Countries like Tanzania are seeing trends in which the number of deaths from infectious diseases is fewer than the number of deaths from hypertensions or from diabetes or from kidney diseases. So the entire world is experiencing spectra of diseases that range from things that we thought would be sort of flames in one corner but in fact are across the entire world.

Do you see more venture-backed funding, especially when we talk about new therapies, new research?

Biotech has been in the United States, now one of the most attractive arenas, recently. We looked enviously at the tech industry, at the software tech industry and at social media. I have to say, personally I barely use social media, and I have to say social media might have created more ills than it solved. Now it has left biotech to solve those ills or medicines to solve those ills.

I think there has been resurgence of interest in ventures in the biotech world. Medicine has been historically regulated. We have very strong ethical boundaries that we have to abide by and for good reasons because we in the past have violated those ethical boundaries. I think that similar ethical boundaries should have been drawn for all technologies, including social media.

Why are you not on social media at all?

I am on Twitter. It is the only social media that I use and I use it quite sparingly. I dont find using anything less particularly inspiring. I like to talk to people directly. If you very carefully curate as a scientist or a writer, if you very carefully curate who you follow on Twitter, it can be very useful because you can get news. But I like traditional news. I like the long form news and I have never found that joy that some people find in connecting through social media.

Is there another book in the works?

There are two books in the works. Very broadly speaking, one of them will address the history of medicine and the other will address questions of immortality, our search for immortality - digital, social and other.

Has the writing process for you changed? I know that you had rules about how to structure your chapters and so on and so forth? Has it changed over the years?

It has been very much the same. My writing process begins with a lot of research and reading. It begins in a very close space. I need silence, I need a lot of time to think and then it comes out as a work.

How much time do you spend writing every day?

I try to spend at least a couple of hours writing every day, but the writing can be diverse, and they interlock with each other.

You are working on both the books at the same time?

No, but it might involve writing a long letter to a regulator about a clinical study that I am excited about and then switch to the book. Now you could say those are two completely different parts of your brain, but they are not. You see, if every experience that I have becomes fuel for the writing, this interview might find its way into a book. The clinical study that we are doing in leukaemia will almost certainly become a book. What is interesting is that even if it fails, it will become a book. It will become a book about failure. So nothing is off the record in some ways to me in my brain.

What is the one thing that gives you the most hope as we look ahead and what is the one thing that worries you the most?

I think the most hopeful thing is the community of thinkers that exists around the world. I think a vibrant community of thinkers has arisen in India asking vibrant questions.

The more we resist the temptation of groupthink, the more likely we contribute to the world of ideas that is inspiring for me. What is worrisome is just the opposite. What is worrisome is the descent into groupthink.

Recent political developments around the world have not given much hope. People are retiring backwards, towards nostalgic isms driven by fear typically. So what worries me the most is that in 2019 we are living at the end of a cycle of innovation and invention which has been unprecedented in history. If we were to take all these isms and put them on national stages, these isms will inevitably stop the cycle of innovation that we are inheriting. We will not pass it on to our children, we will deny them a generation of invention and innovation and that is a very sad thing. We should be very careful about it.

Get the best of News18 delivered to your inbox - subscribe to News18 Daybreak. Follow News18.com on Twitter, Instagram, Facebook, Telegram, TikTok and on YouTube, and stay in the know with what's happening in the world around you in real time.

See the original post here:
CAR T-Cell Therapy May be Available to Cancer Patients in India Next Year: Dr Siddhartha Mukherjee - News18