Viruses are known to use the genetic machinery of the human cells they invade to make copies of themselves. As part of the process, viruses leave behind remnants throughout the genetic material (genomes) of humans. The virus-like insertions, called “transposable elements,” are snippets of genetic material even simpler than viruses that also use host cell machinery to replicate.
Nearly all these inserted elements have been silenced by our cells’ defense mechanisms over time, but a few, nicknamed “jumping genes,” can still move around the human genome like viruses. Just one, called long interspersed nuclear element 1 (LINE-1), can still move by itself.
As an element type that behaves like the retrovirus HIV, the LINE-1 “retrotransposon” is first copied into a molecule of RNA, the genetic material that partners with DNA, and then the RNA LINE-1 copy is converted back into DNA in a new place in the genome. In this way, retrotransposons add code to the human genome every time they move, which explains why 500,000 LINE-1 repeats now represent a “staggering” 20 percent of the human genome. These repeats drive genome evolution, but can also cause neurological diseases, cancer, and aging when LINE-1 randomly jumps into essential genes, or triggers an immune response like a virus to cause inflammation.
To copy itself, however, LINE-1 must enter each cell’s nucleus, the inner barrier that houses DNA. Now a new study, published online May 2 in the journal Science Advances, reveals that LINE-1 binds to cellular DNA during the brief periods when nuclei break open as cells continually divide in two, creating replacements to keep tissues viable as we age. The research team found that LINE-1 RNA takes advantage of these moments, assembling into clusters with one of the two proteins it encodes, ORF1p, to hold tightly to DNA until the nucleus reforms after cell division.
Led by researchers at NYU Langone Health and the Munich Gene Center at Ludwig-Maximilians-Universität (LMU) München in Germany, the work revealed specifically that LINE-1 can only bind to DNA when ORF1p — which can bind to RNA, DNA, and itself in linked copies called multimers — accumulates into clusters of hundreds of molecules called condensates. As more ORF1p molecules build up, they eventually envelop the LINE-1 RNA, which makes more binding sites available for the entire cluster to attach to DNA.
“Our study provides crucial insight into how a genetic element that has come to make up a large part of human DNA can successfully invade the nucleus to copy itself, said Liam J. Holt, PhD., associate professor in the Department of Biochemistry and Molecular Pharmacology, and the Institute for Systems Genetics, at NYU Grossman School of Medicine.”These findings on the precise mechanisms behind LINE-1 insertion lay the foundations for the design of future therapies to prevent LINE-1 replication.”
The work also suggests that the LINE-1 condensate acts as a delivery vehicle to bring its RNA into proximity of the right sequences (rich in the DNA bases adenine and thymine) on DNA where the retrotransposon tends to insert, say the study authors. Packaged in its condensates, LINE-1 is thought to evade mechanisms that exclude large particles from the nucleus during mitosis as a cellular defense against viruses.
“LINE-1 condensates have a remarkable feature in that their DNA binding ability emerges only when the ratio of ORF1p copies to RNA is high enough in the condensates,” added Dr. Holt. “Moving forward we will be looking to see if other condensates undergo functional changes as the ratios between their components change.”
Along with Dr. Holt, the first study authors were graduate student Farida Ettefa at NYU Grossman School of Medicine and its Institutes for Systems Genetics; and Sarah Zernia of Gene Center Munich at Ludwig-Maximilians-Universität (LMU) München in Germany. Also study authors were Cas Koeman, Joëlle Deplazes-Lauber, Marvin Freitag, and co-senior author Johannes Stigler from Ludwig-Maximilians-Universität München. The study was supported by the LMU-NYU Research Cooperation Program.
Researchers at the University of Minnesota have completed a first-in-human clinical trial testing a CRISPR/Cas9 gene-editing technique to help the immune system fight advanced gastrointestinal (GI) cancers. The results, recently published in Lancet Oncology, show encouraging signs of safety and potential effectiveness of the treatment.
“Despite many advances in understanding the genomic drivers and other factors causing cancer, with few exceptions, stage IV colorectal cancer remains a largely incurable disease,” said Emil Lou, MD, PhD, a gastrointestinal oncologist with the University of Minnesota Medical School, Masonic Cancer Center and M Health Fairview, and clinical principal investigator for the trial. “This trial brings a new approach from our research labs into the clinic and shows potential for improving outcomes in patients with late-stage disease.”
In the study, researchers used CRISPR/Cas9 gene-editing to modify a type of immune cell called tumor-infiltrating lymphocytes (TILs). By deactivating a gene called CISH, the researchers found that modified TILs were better able to recognize and attack cancer cells.
The treatment was tested in 12 highly metastatic, end-stage patients and found to be generally safe, with no serious side effects from the gene editing. Several patients in the trial saw the growth of their cancer halt, and one patient had a complete response, meaning that in this patient, the metastatic tumors disappeared over the course of several months and have not returned in over two years.
“We believe that CISH is a key factor preventing T cells from recognizing and eliminating tumors,” said Branden Moriarity, PhD, associate professor at the University of Minnesota Medical School, Masonic Cancer Center researcher and co-director of the Center for Genome Engineering. “Because it acts inside the cell, it couldn’t be blocked using traditional methods, so we turned to CRISPR-based genetic engineering.”
Unlike other cancer therapies that require ongoing doses, this gene edit is permanent and built into the T cells from the start.
“With our gene-editing approach, the checkpoint inhibition is accomplished in one step and is permanently hardwired into the T cells,” said Beau Webber, PhD, associate professor at the University of Minnesota Medical School and Masonic Cancer Center researcher.
The research team delivered more than 10 billion engineered TIL without adverse side effects, demonstrating the feasibility of genetically engineering TIL without sacrificing the ability to grow them to large numbers in the lab in a clinically compliant environment, which has never been done before.
While the results are promising, the process remains costly and complex. Efforts are underway to streamline production and better understand why the therapy worked so effectively in the patient with a complete response in order to improve the approach in future trials.
The Haenyeo, a group of all-female divers from the Korean island of Jeju, are renowned for their ability to dive in frigid waters without the aid of breathing equipment — even while pregnant. A study publishing on May 2 in the Cell Press journal Cell Reports shows that the divers’ remarkable abilities are due to both training and genetic adaptation, including gene variants associated with cold tolerance and decreased blood pressure. The divers also showed pronounced bradycardia, or slowing of the heart rate, when they dived, but this trait is likely due to a lifetime of training, not genetics.
“The Haenyeo are amazing, and their incredible ability is written in their genes,” says geneticist Melissa Ilardo of the University of Utah. “The fact that women are diving through their pregnancy, which is a really tough thing to do, has actually influenced an entire island’s people.”
The Haenyeo, or “women of the sea,” dive year-round in social collectives to harvest food for their communities. They begin training at around age ten and continue for their whole lives. Inspired by the Haenyeo’s remarkable diving abilities, the researchers wanted to know whether they have distinguishable physiological traits that help them cope with the strain of diving, and if so, whether these traits are due to genetic adaptation or training.
To find out, the team compared the physiological traits and genomes of 30 Haenyeo divers to 30 non-Haenyeo people from Jeju, as well as 31 people from mainland Korea. To match the age of the divers, the average age of all participants was 65. The researchers compared the participants’ heart rate and blood pressure at rest and during “simulated dives” where the participants held their breath while submerging their faces in cold water.
“If you hold your breath and put your face in a bowl full of cold water, your body responds as if you’re diving,” says Ilardo. “A lot of the same processes happen in your body that would happen if you were to jump in the ocean, but it’s done in a way that’s safe for people with no diving experience.”
The team’s genomic analysis showed that Jeju residents — both Haenyeo and non-Haenyeo — were distinct from individuals from mainland Korea, suggesting that all Jeju residents are descended from the same ancestral population.
“We can essentially think of everyone from Jeju as either ‘diving Haenyeo’ or ‘non-diving Haenyeo,’ because their genetics are the same,” says Ilardo.
The genomic analysis also revealed two gene variants in the Haenyeo that may help them cope with the pressures of diving, making the Haenyeo the second known population of traditional breath-hold divers that has evolved for diving. One gene is associated with cold tolerance, which could make the divers less vulnerable to hypothermia. The other gene is associated with decreased diastolic blood pressure (i.e., blood pressure in between heart contractions). The variant was found in 33% of participants from Jeju but only 7% of mainland participants.
“This association may reflect natural selection to mitigate the complications of diastolic hypertension experienced by female divers while diving through pregnancy,” says Ilardo. “Since Bajau women also dive while they’re pregnant, we wonder whether pregnancy is actually driving a lot of the genetic changes in these diving populations.”
During the simulated dives, all of the participants showed decreased heart rates, but the Haenyeo’s heart rates dropped significantly more than those of either control group. On average, the divers’ heart rates decreased by 18.8 beats per minute (bpm) compared to a decrease of 12.6 bpm in the Jeju non-divers. A lowered heart rate during diving is beneficial because it saves energy and conserves oxygen. Since their genomic analysis indicated that Haenyeo and non-diving Jeju are genetically members of the same population, the researchers concluded that this feature is likely due to the divers’ training.
“Because the Haenyeo have been diving for a very long time, their heart rate has been trained to drop more,” says Ilardo. “This was something we could actually visually see — we had one diver whose heart rate dropped by over 40 beats per minute in less than 15 seconds.”
The researchers say that these findings highlight the potential of studying traditional diving populations to better understand human genetic and physiological adaptation.
“We’re really excited to learn more about how these genetic changes may be affecting the health of the broader population of Jeju,” says Ilardo. “If we can more deeply characterize how those changes affect physiology, it could inspire the development of therapeutics to treat different conditions, such as hypertensive disorders of pregnancy and stroke.”
This research was supported by the Office of Naval Research, the National Institutes of Health, and the National Science Foundation.
By using antibodies from a human donor with a self-induced hyper-immunity to snake venom, scientists have developed the most broadly effective antivenom to date, which is protective against the likes of the black mamba, king cobra, and tiger snakes in mouse trials. Described May 2 in the Cell Press journal Cell, the antivenom combines protective antibodies and a small molecule inhibitor and opens a path toward a universal antiserum.
How we make antivenom has not changed much over the past century. Typically, it involves immunizing horses or sheep with venom from single snake species and collecting the antibodies produced. While effective, this process could result in adverse reactions to the non-human antibodies, and treatments tend to be species and region-specific.
While exploring ways to improve this process, scientists stumbled upon someone hyper-immune to the effects of snake neurotoxins. “The donor, for a period of nearly 18 years, had undertaken hundreds of bites and self-immunizations with escalating doses from 16 species of very lethal snakes that would normally a kill a horse,” says first author Jacob Glanville, CEO of Centivax, Inc.
After the donor, Tim Friede, agreed to participate in the study, researchers found that by exposing himself to the venom of various snakes over several years, he had generated antibodies that were effective against several snake neurotoxins at once.
“What was exciting about the donor was his once-in-a-lifetime unique immune history,” says Glanville. “Not only did he potentially create these broadly neutralizing antibodies, in this case, it could give rise to a broad-spectrum or universal antivenom.”
To build the antivenom, the team first created a testing panel with 19 of the World Health Organization’s category 1 and 2 deadliest snakes across the elapid family, a group which contains roughly half of all venomous species, including coral snakes, mambas, cobras, taipans, and kraits. Next, researchers isolated target antibodies from the donor’s blood that reacted with neurotoxins found within the snake species tested. One by one, the antibodies were tested in mice envenomated from each species included in the panel. In this way, scientists could systematically build a cocktail comprising a minimum but sufficient number of components to render all the venoms ineffective.
The team formulated a mixture comprising three major components: two antibodies isolated from the donor and a small molecule. The first donor antibody, called LNX-D09, protected mice from a lethal dose of whole venom from six of the snake species present in the panel. To strengthen the antiserum further, the team added the small molecule varespladib, a known toxin inhibitor, which granted protection against an additional three species. Finally, they added a second antibody isolated from the donor, called SNX-B03, which extended protection across the full panel.
“By the time we reached 3 components, we had a dramatically unparalleled breadth of full protection for 13 of the 19 species and then partial protection for the remaining that we looked at,” says Glanville. “We were looking down at our list and thought, ‘what’s that fourth agent’? And if we could neutralize that, do we get further protection?” Even without a fourth agent, their results suggest that the three-part cocktail could be effective against many other, if not most, elapid snakes not tested in this study.
With the antivenom cocktail proving effective in mouse models, the team now looks to test its efficacy out in the field, beginning by providing the antivenom to dogs brought into veterinary clinics for snake bites in Australia. Further, they wish to develop an antivenom targeting the other major snake family, the vipers.
“We’re turning the crank now, setting up reagents to go through this iterative process of saying what’s the minimum sufficient cocktail to provide broad protection against venom from the viperids,” says lead author Peter Kwong, Richard J. Stock professor of medical sciences at Columbia University Vagelos College of Physicians and Surgeons and formerly of the National Institutes of Health. “The final contemplated product would be a single, pan-antivenom cocktail or we potentially would make two: one that is for the elapids and another that is for the viperids because some areas of the world only have one or the other.”
The other major goal is to approach philanthropic foundations, governments, and pharmaceutical companies to support the manufacturing and clinical development of the broad-spectrum antivenom. “This is critical, because although there are millions of snake envenomations per year, the majority of those are in the developing world, disproportionately affecting rural communities,” Glanville says.
This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, the National Institutes of Health Small Business Innovation Research program, and the US Department of Energy.
A watched pot never boils, goes the old saying, but many of us have at least kept an eye on the pot, waiting for the bubbling to start. It’s satisfying to finally see the rolling boil, behind which complex physical mechanisms are at play.
When this happens, the bubbles that form continuously change in shape and size. These dynamic movements influence the surrounding fluid flow, thereby affecting the efficiency of heat transfer from the heat source to the water.
Manipulating small amounts of liquid at high speeds and frequencies is essential for processing large numbers of samples in medical and chemical fields, such as in cell sorting. Microbubble vibrations can create flows and sound waves, aiding in liquid manipulation. However, the collective behavior and interactions of multiple bubbles is poorly understood, so their applications have been limited.
Motivated to better understand bubble behavior, a team of researchers at Kyoto University has developed an experimental setup to precisely adjust the distance between microbubbles, employing laser light to photothermally heat degassed water.
“We were able to establish a new method to fundamentally alter the liquid flow by simply adjusting the arrangement of bubbles,” says first author Xuanwei Zhang.
The team successfully generated two bubbles measuring about 10 micrometers in diameter that spontaneously vibrate at sub-megahertz frequencies, investigating how their vibrations affect each other. Using this apparatus, the researchers were able to precisely control the fast movements of bubbles at sub-megahertz frequencies as well as the surrounding flow.
After comparing the results with theoretical equations, the team found that the pressure generated by each bubble’s vibration accounts for the interactions between bubbles. They discovered that neighboring bubbles synchronize their vibrations, and that changing the distance between bubbles by just 10 micrometers altered their vibration frequency by more than 50%.
“We did not expect to observe such clear vibrational coupling between two oscillating bubbles, but the vibrations of the bubbles we generated were very stable over time and highly reproducible,” says corresponding author Kyoko Namura. These characteristics enabled the team to capture changes in the vibrations of the two bubbles when their relative positions were even slightly adjusted.
The results of this study provide a new fluid control tool for the medical and chemical fields, where faster analysis and data collection are indispensable. Though the research team used degassed water, similar effects can be achieved with water-alcohol mixtures, rendering this method applicable to a wide range of applications.
In the future, the team plans to explore ways to actively select bubble vibration frequencies and modes, control larger arrays of bubbles, and analyze the sound waves and flows generated around them.
Scientists at the University of East Anglia (UEA) have developed a revolutionary new way of uncovering the ‘true age’ of your heart using MRI.
Research published today shows how an MRI scan can reveal your heart’s functional age — and how unhealthy lifestyles can dramatically accelerate this figure.
It is hoped that the findings could transform how heart disease is diagnosed — offering a lifeline to millions by catching problems before they become deadly.
The team say their cutting-edge technique is a “game changer.”
Lead researcher Dr Pankaj Garg, from UEA’s Norwich Medical School and a consultant cardiologist at the Norfolk and Norwich University Hospital, said: “Imagine finding out that your heart is ‘older’ than you are. For people with conditions like high blood pressure, diabetes, or obesity, this is often the case.
“Our new MRI approach doesn’t just count your birthdays — it measures how well your heart is holding up.”
Led by UEA, the research team collaborated with hospitals in the UK, Spain, and Singapore. They studied MRI scans from 557 people — 191 healthy individuals and 366 with conditions like high blood pressure, diabetes, or obesity.
Using advanced imaging, they measured things like the size and strength of the heart’s chambers. Then, they built a formula to calculate the heart’s ‘functional age’ and checked it against healthy hearts to make sure it was accurate.
Dr Garg said: “We found that an MRI scan can reveal your heart’s ‘functional age’ — how old it acts, not how old you are.
“In healthy people, we found that heart age was similar to chronological age. But for patients with things like diabetes, hypertension, obesity, and atrial fibrillation — their functional heart age was significantly higher.
“For example, a 50-year-old with high blood pressure might have a heart that works like it’s 55.
“People with health issues like diabetes or obesity often have hearts that are aging faster than they should — sometimes by decades. So, this could help doctors step in early to stop heart disease in its tracks.
“This is a game-changer for keeping hearts healthier, longer.
“Heart disease is one of the world’s biggest killers. Our new MRI method gives doctors a powerful tool to look inside the heart like never before and spot trouble early — before symptoms even start.
“By knowing your heart’s true age, patients could get advice or treatments to slow down the aging process, potentially preventing heart attacks or strokes.
“It could also be the wake-up call people need to take better care of themselves — whether that’s eating healthier, exercising more, or following their doctor’s advice. It’s about giving people a fighting chance against heart disease,” he added.
PhD Student Hosam Assadi, also from UEA’s Norwich Medical School, said: “It’s thrilling to see how this MRI technique could change lives. We’ve found a way to spot hearts that are aging too fast, and that could mean catching problems early enough to fix them. I hope this could become a standard check-up for hearts in the future.”
This research was led by UEA in collaboration with the Norfolk and Norwich University Hospitals NHS Foundation Trust, the National Heart Research Institute Singapore, the University of Sheffield, the Hospital San Juan de Dios (Spain), Barts Health NHS Trust, Leiden University Medical Center (The Netherlands), the University of Leeds, and the National University of Singapore.
Today (May 1st) is the final day to decide to join us for Year 9 in Conscious Growth Club, and I felt inspired to share some insights about where I see the club flowing in Year 9 and beyond.
Every year the club evolves. This transition from Year 8 to Year 9 is a big advancement with some very powerful shifts opening up.
Leadership Dojo
Many members in CGC have been evolving in the direction of leadership. This has been showing up differently for everyone, but it’s fair to say that it’s not the stale old corporate or hierarchical version of leadership. It’s a much more personal and internal form of leadership. At least that’s where it begins.
This is about leading from within – knowing yourself, standing strong in your core essence, and radiating your light into the world around you, like I shared in this video several months ago: Fill Your Reality With Your Light.
When you step up and take charge of your own life powerful, other people are likely to notice. Those who appreciate similar values to yours will likely feel drawn to you. They’ll be attracted to your centeredness, your resolve, your clarity, and your sense of ease, lightness, and flow. You may end up attracting some sort of following without really trying.
For some members this shows up as a desire to build communities or their own, online or offline. A lot of members have been going through meaningful transformations of their social lives. They no longer feel in tune with their old circles, and it’s important to them to draw more people into their lives who really align with who they are now and who they’re becoming.
One reason this happens is that CGC itself is a model for this kind of social alignment. It’s a community centered around growth, self-development, and truly embodying our best selves. People who value this will find lots of like-minded people inside to connect with. Once they experience how delightful it is to make and have so many friends like this in one place, it can reveal a difficult contrast with their other social circles, which may not feel adequate anymore. Thus begins the journey into assuming more autonomy over one’s social life, and this eventually flows into some kind of leadership experience.
Seeing this aspect of CGC emerging over time has encouraged me to give it more attention and to invite new members into the club who see themselves flowing into an emerging leadership role. So this year I made that a key part of the invite.
That’s yet another reason we don’t invite Trump supporters to join us in CGC. That’s been our policy for years. Trump supporters carry follower vibes by definition. That’s the opposite of our direction in CGC.
There are lots of ways to step into leadership. In CGC we really focus on the inner journey, which involves getting clear about what we want to create and then advancing it into being.
Note that at the beginning of 2017, CGC was just an idea. I began sharing about the idea on my blog back then, inviting people to comment on it and share their feedback. Later that year we opened the doors with an early access phase while we were developing it. Today we’re starting our 9th year together, the club is thriving inside, and we clearly have a bright future together as we continue to advance together. This all began with a decision to step up and make it happen. Many hundreds of other decisions followed – and are still following – as the club continues to evolve.
Relating to People as Their Strong Selves
Since I have a lot of experience watching people grow and seeing how they evolve over time, I often pick up patterns in what’s unfolding for people before they see what’s emerging within themselves. I like to meet people where they are, but I also love to relate to them based on where they appear to be heading.
The better I get to know someone who’s very growth-oriented, the more I can help to hold the vision and the vibes of the stronger and more capable version of them that’s emerging.
For instance, I may interact with someone who’s a bit camera shy, but I can also see that they’re working on it, which may help me see that they’ll eventually get past it altogether. So I can start relating to them as the person they’re becoming, not who they’ve been.
Or I may be talking with a very head-based person, but I can also see they’re making good progress in developing their intuitive side and opening their heart, so I can meet in the the land of emotional expressiveness and keep relating to them as their emerging future self.
Sometimes this surprises people because they’ve never had anyone treat them as the person they’re becoming. Others have usually been treating them as who they’ve been in the past (or some skewed version of that).
I love doing this for people, but it’s definitely best when I get to know someone, so I gain a more specific understanding of where they’re heading.
Holding stronger visions of each other – and for each other – is becoming woven into the fabric of CGC. As more members bear witness to each other’s growth, they’re helping hold those new visions of themselves. That’s really lovely to see.
If you’ve never been in a social circle that holds you in high regard and begins treating you as your stronger and more capable future self, I sense you’d really love and appreciate this aspect of CGC.
Don’t think it’s easy though. The old parts of you may rise up to reject your new self-image – at first – so it can take some time to work through those old limits and release them.
Feeding and Fueling Our Strong Selves
As members have continued to invest in CGC, they’re clearly gotten stronger and more capable. More possibilities are opening up for them. There’s a sense of strength and stability in the core of the club, which is fertile soil for encouraging even more to emerge.
Back in 2018 when I first created the Deep Abundance Integration course, my motivation was largely driven by compassion for people who were struggling with scarcity. I wanted to provide a helpful resource to immerse people in abundance vibes, so they could really lock onto it and transition over, much like I learned to do back in 1999 (the year I went bankrupt).
In the early years of CGC, there was a lot of this helping-people-who-were-struggling mentality in the club too. That fit with the old coaching model, and many coaching calls involved helping people with various forms of stuckness. Today we are way beyond that old mindset and old approach.
Struggles can be endless and cyclical, especially if people keep recreating the same conditions that lead to struggle. Now we’re better at stepping back and inviting those weaker energies to depart, so something stronger and more engaging can emerge.
When this kind of powerful energy surges, many old struggles vanish. Either they become easy to solve because we become stronger, or they’re no longer seen as problems, or we stop creating the conditions that give rise to them. One way or another, CGCers learn to opt out of living in perpetual crisis mode.
Today’s CGC isn’t a good match for people who are mired in distracting problems. It’s a much better fit for people who want to engage with their lives from their core – their strong selves. Then keep building from there.
I like to think of this stronger part of me as my higher self. That’s the version of me that’s fearless, wise, caring, kind, creative, generous, and more. These days my own path of self-development is mainly about coming into greater alignment with this core version of me. I do my best to channel my deepest wellspring of insight and energy into my decisions and actions. That’s been working really well.
Even when I have mundane problems to deal with, I find that I can easily shred them when I’m attuned to my core strengths. Then I can be as patient, methodical, rational, and courageous as needed to solve problems definitively. These kinds of solutions are very satisfying, both during the solution process and afterwards. I know I did my best, so there are no regrets.
This kind of energy is emerging very strongly in the club now. I sense it will be a big part of Year 9 and beyond.
One specific way we’re supporting this energy is with the new Sense & Solve call format that we’re introducing this CGC year. We’re running it the first time on May 15.
High Trust and Intimate Teamwork
CGC is a very kind, intimate, caring group inside. It took some work to get there though, and I’m very protective of this aspect of our culture. In our early years, we attracted some members who were only into self-development for themselves – some prima donna types if you know what I mean. They came to CGC for the content and for their own gains and didn’t participate much in the community aspects, except for their own validation now and then.
We still did our best to serve those members, but I soon realized that we were better off without them. What we do in CGC really is a team effort, and we grow stronger by attracting good team players. So I’ve deliberately positioned the club to make it less palatable to people who aren’t interested in the team aspect.
We’ve come a long way since then, really focusing on attracting more genuine team players and serving them well. CGC has become a space where the givers tend to gain the most. Those who show up and participate and share their growth journeys surely learn a lot more and make bigger strides.
I see us investing even further in this teamwork direction in Year 9 and beyond. That includes involving other members in the live event we’ll be co-creating for April 2026.
All of our calls for Year 9 involve some form of interaction. They’re really not content-based. They’re all designed as group experiences that we share in and create together.
This morning, for example, we had our monthly Intention Infusion call. The call was very well-attended, with lots of members sharing all throughout. This included sharing our individual intentions for the month and also co-creating a group intention. The group intention we chose was limitless vitality, so we’re all pooling our collective intentional energy to intend limitless vitality for each other. This has been a normal rhythm in CGC for the past two years now. Every month we all hold positive intentions for each other’s well-being and advancement.
The core of this community is trust. When people open up and trust more, they tend to thrive in CGC. It’s not like sharing about your life on social media and wondering who will judge you for it.
It usually takes a bit of time for people to get used to a community like this. They come in with their well-developed masks from years of social media engagement. Then they gradually drop those old facades and let us see more of their real selves. That’s where they’re met with so much love, understanding, and connection.
Life really is different when you learn and grow as part of a kind and caring community that has your back. If you don’t get that from CGC, please find some place to get it – a space where you can fully open up and show all parts of the real you and be seen and acknowledged as the beautiful being you are. This includes letting others see your beauty even when you’re not seeing it yet yourself.
This kind of work really lights me up inside. Even after 8 years of serving CGC, I’m still abundantly enthusiastic about it. As I’ve said many times before, this is my forever project. That’s something I learned from Walt Disney because Disneyland was his forever project. The benefit of a forever project is that you have lots of time to keep improving it and optimizing it. You know to be extra thoughtful in making each decision because you’re thinking about how it might ripple out over decades.
Playfulness
I love that we’re so playful in CGC. I really resonate with making self-development lively and fun. I feel we’re landed in a really good range there. We take self-development seriously, and we have serious fun working on it together.
We often crack jokes on the live calls, but we also do our best to keep them light. I really think we bond very well through shared humor. Some members are really great at anchoring humor vibes into the club, and I would love to see even more people like this join us inside because we so appreciate what they bring to the experience.
We already have some great abundance in this area, but I say let’s keep going. Why limit ourselves? Good-natured humor folds really well into our group energy and values.
I sense that this light-hearted playfulness that so many of us share in CGC will be infused into our April 2026 gathering as well, which makes me look forward to it even more.
Range and Variety
I know of no other self-development group that covers as much range and variety as CGC does. We really do cover all aspects of self-development and more.
Take a look at our call types for Year 9. We have 18 different formats now, up from 14 last CGC year. And even within a given format, no two calls are the same. Each call is a unique experience.
In Bear Care we work on boundaries and self-care. In Contribution Café we focus on purpose and service. In Story Lab we use the lens of story to fuse the objective and subjective aspects of our lives into a cohesive plot that’s unfolding. Courage Forge’s theme ought to be pretty obvious. Same goes with Pure Imagination. Mating Call is a new format we’ve added this year to improve our sex lives. And Moonglow is all about receiving and allowing (and not blocking life’s gifts).
I actually drew a significant amount of inspiration from theme parks, particularly Disneyland itself, in designing and evolving CGC’s core structure. I’ve personally spent at least 100 days of my life at Disneyland, including going there with Rachelle for 30 days in a row, six months before we opened CGC. So you can definitely think of CGC as being like a self-development theme park. While our core focus is on self-development, the calls are all designed to be lively, entertaining, and enjoyable as well. I never want the experience for our members to become stale or boring.
The vast majority of our live calls are unrecorded too (only Reflections & Revelations is recorded), so that helps people open up and be more candid as well. I really noticed a positive shift in participation when we shifted from recorded to unrecorded calls a while back. I love that we have so many years to keep tinkering and fine-tuning to discover what works best for our members.
Learning From Each Other’s Growth Journeys
With the CGC forums as part of the experience, there’s even more variety because members can share and discuss anything of interest to them.
I especially love that our discussions and explorations are so focused on helping each other advance. There really isn’t much debating in CGC for the sake of debating. Politics and current events don’t have a big presence in the group. That’s all fair game for discussion, but most CGCers would rather not discuss that sort of thing, especially since they can do that elsewhere on social media all day long if they want.
In CGC the conversations are mainly about personal experiences and explorations as well as how members are figuring out solutions. People discuss their goals, action steps, and their progress a lot. They share the emotional side too, like how life is going and how they’re being affected.
Because we have our own private, members-only spaces, members are a lot more candid, and the shares are often deeper and more detailed than what you’d find elsewhere on the Internet. People share a certain depth in CGC that they wouldn’t trust to Instagram, Facebook, etc.
This is true for me too. While I’ve been very open about my life from 20+ years of blogging and also YouTubing, I share even more depth and detail in CGC. Most of what I share about my ongoing explorations these days is posted in CGC, not outside of it. I just feel drawn to share certain details more with the people I’ve come to know and trust very well. I’m still into sharing openly outside of the group, but with CGC as such a huge part of my life, I don’t feel drawn to share as much outside the club.
I maintain a progress log in the club myself and update it often. It looks like this in the forums and has hundreds of posts. It’s very interactive too since members can ask me anything about the various explorations I’m doing at any given time. Usually I update it multiple times per week. There is so much I’ve shared there that I haven’t shared outside of CGC, such as details about the 3-night ayahuasca ceremony I did in March and how it affected me – it was very powerful.
One experience that’s coming up this month is my first-ever San Pedro ceremony. I’ve never done it before and have been wanting to sit with it for years. I probably won’t blog about it, but I’ll surely share about what it was like in CGC.
Other members maintain progress logs in the club too, and this has consistently been a great way for us to keep tabs on what we’re all doing and how we’re progressing.
A High-Vibe Approach to Self-Development
When I first got into self-development many years ago, my mindset was very objective. I focused on productivity and time management a lot. I thought very algorithmically much of the time, always looking for useful processes and step-by-step approaches. Some of my favorite authors were Brian Tracy and David Allen – both very deliberate and methodical but also immensely head-based.
That was interesting and helpful for some years, but I soon ran into limits with that approach, especially with respect to certain types of goals and lifestyle desires. Some goals just would not budge.
I was able to use that old mindset to have some cool achievements though, such as running a marathon. That was all about showing up, putting in the training time, and being very methodical and tenacious till I crossed the finish line and got my finisher’s medal – done and checked off my bucket list.
But my most interesting breakthroughs did not arise from that type of programmer mindset. For that I really needed to stretch myself to explore more limitless ways of relating to life and reality. I documented that alternative approach very well in the Submersion course, which is based on relating to life far more subjectively. Since then I’ve layered in even more robust and expansive approaches to keep advancing in ways where an overly objective approach falls flat.
I’d say my #1 favorite gift from opening up and pursuing a different self-development path is my relationship with Rachelle. We’ve been together for 15+ years now, married for more than 7 years. She and I host the CGC calls together. I adore her deeply, and I love the life we share together. I also really love that she and I get to serve and support CGC together. We attracted each other from different countries (she’s Canadian) and flowed into a beautiful yet unconventional relationship. I don’t see anyway a relationship like this could have flowed into my life if I’d been stuck in an overly objective mindset. That old limit had to go, so I could open myself to new forms of allowing, inviting, and surrendering.
This type of energy is strongly infused into CGC. I’ve stopped being an apologist about it, and I’ve really gone all-in with a vibrational-first approach – because it works! It takes time for some people to warm up to it, but what keeps them engaged is that this gets results, especially in areas where an objective approach just isn’t moving the needle much.
The objective aspects of life are still important, and objective problem-solving tools are still useful, so we haven’t thrown that out. We do a tremendous amount of fusion in CGC, and that YES-AND approach woven into many of our group calls as well. Our problem-solving methods are part vibrational, part physical. They involve getting into harmony with the solution space and feeling our way into it to ramp up motivation and inspiration. Then we devise practical action steps and flow into them with greater ease.
In recent months I’ve been sharing in the club about using this approach to do various DIY plumbing and electrical projects around the house. I got clear about how I wanted to solve each problem on a vibrational level first, including how I wanted to feel throughout the experience and afterwards. As I locked onto those feelings, I flowing through a compelling action sequence that included watching how-to videos on YouTube, acquiring the needed parts and tools, and doing all the steps to get to completion.
This really taught me a lot about my own best pathways through problems I might otherwise put off. I didn’t want to deal with certain problems because I didn’t understand them well enough, and I didn’t feel very trusting about the prospect of hiring someone to do those projects for me. So I went to the vibe level first and crafted the solution there. For instance, I knew that education could solve the understanding problem, so I resolved to educate myself thoroughly first. I also saw solutions to the trust issue, so I worked through how to find a contractor I could genuinely trust, and I found and hired a fabulous plumber to do some bigger jobs. It all flowed beautifully at the action level once I solved these problems first at the vibrational level.
I can tell this kind of vibrational-physical fusion will be a big part of CGC Year 9 and beyond – again because it works. Problems are much easier to solve when we engage not just our minds but our hearts and spirits as well.
Lightness & Happiness
The energy in some earlier CGC years felt heavier to me. Today it’s a lot lighter feeling inside. There’s more happiness and optimism inside the club these days – and some genuine excitement too, especially since we’re starting a whole new year together starting today.
Years ago, some people were initially drawn to approach CGC like a therapy container – a space for working through unresolved trauma.
I gave it a lot of thought and took concrete steps to move the club well away from that direction. I know this bothered some people, but I’m certain that it was the correct decision. Even back then I knew we needed to move away from that.
I’m not a therapist, and I don’t intend to become one. I really don’t want to meet people in their misery and delve into the ache with them.
I know some great people who do work in the space of trauma, healing, PTSD, etc. Most of them work with plant medicines because that really moves the needle when nothing else will. I’ve seen a tremendous amount of positive changes unfolding for people who need to process and release old trauma.
But that isn’t my path. I know this. I’m not here to serve people while they’re still enmeshed in their trauma. I’m meant to work and live in limitless land. That’s very clear to me.
I’ve done multiple plant medicine journeys where I’ve looked into that space – with ayahuasca, mushrooms, and more – and they all tell me the same thing. I’m not traumatized and never have been, and I’m not here to help people with their trauma. One journey revealed a fun way of framing this, revealing that when I incarnated as a human in this life, I looked at the box to select my trauma for my human character, and I wrote in “Fuck no!” And so that wish was granted.
I’ve had plenty of challenges to deal with in this life, but none have ever traumatized me. That isn’t what I’m here to experience. And it isn’t how I aim to serve.
I am the opposite of traumatized. I’m ridiculously happy, and I thrive when working with other people who are at least pretty happy with their lives, and they want to unfold even more richness.
I work best with people who want to let go of old limits and stretch themselves. They want to grow stronger and become even more capable. They may not be traumatized, but letting go of old limits is still a great challenge, and this is where I most enjoy serving people.
This has also become a big aspect of CGC as well. We’re not here to meet you in your pain. We’re here to help you advance beyond old limits. If you have a lot of unresolved pain to work through first that’s holding you back from even focusing on richer and more expansive forms of self-development, I feel for you, but there are much better teachers and communities that focus on that. I have tremendous respect for them, and I’m friends with some great people in that space, but I definitely don’t aspire to be one of them. I’ve found where I belong and what I’m good at, and I do sense that this is a limit I want to keep because it serves me well, and it opens into a beautiful outlet for serving others very well too.
CGC’s energy is much lighter than what you’d find in trauma-informed spaces. The energy inside is typically very positive, encouraging, optimistic, and expansive. Members are usually very engaged with interesting projects and working on stretching themselves in various ways.
Even when someone is going through a major challenge, they’re met with positive support, not commiseration. This helps people remember their strong selves, which they can use to meet any problem.
Stepping Into Your Limitless Self
Hopefully this run-through gives you a clearer picture of what CGC is like inside now and how we’re continuing to evolve.
I’d say that our limitless vitality intention for May is a good container for our upcoming year in the club as well. This month we’re inviting more energy to flow through our bodies and our lives, so we can enjoy more capacity to investing in what we find most engaging.
If CGC appeals to you, I invite you to join us. There’s still time to come aboard and join us for Year 9 if you sign up today. Otherwise you’ll have to wait till April 2026 for another chance.
I’d recommend perusing the CGC FAQ, and then read through the CGC invite page as you reflect upon the decision (sign-up button is at the bottom of that page.
Lastly, feel free to drop me a message via my contact form if you have any further questions. We always see a lot of people join on the last day – even in the final hours – so I’m used to that!
Bad habits such as smoking, heavy drinking and lack of exercise must be tackled as early as possible to boost the odds of a happy and healthy old age.
That is the message of a new peer-reviewed study, published in the Annals of Medicine (Elevate), that found smoking and other vices are associated with declines in health in people as young as 36.
The impact is even greater when these bad habits are indulged in over the long-term, state experts whose study tracked the mental and physical health of hundreds of people for more than 30 years.
Previous research has followed people from middle-age, typically for around 20 years. Studies to-date have shown that smoking and other aspects of a healthy lifestyle are adapted before the age of 30. However, in this new study a research team from Finland wanted to track people from a younger age — and to unpick, at the same time, the effect of unhealthy habits on mental health.
Using a long-running longitudinal study, in which hundreds of children who were born in the Finnish city of Jyväskylä in 1959 were followed from childhood until their early 60s, the team analyzed participants’ mental and physical health via data that was collected from surveys and medicals when they were 27 years old (326 participants) and again at age 36, 42, 50 and 61 (206 participants).
Mental health was assessed via surveys on symptoms of depression and on psychological wellbeing. Physical health was assessed by creating a metabolic risk score based on blood pressure, waist size and levels of blood sugar, cholesterol and other blood fats.
Self-health was assessed by asking the participants to rate the state of their health over the past year.
Three risky behaviours were also assessed at each point in time: smoking, heavy drinking (defined as consuming at least 7,000g/875 units of alcohol a year for women and 10,000g/1,250 units a year for men) and physical inactivity (exercising less than once a week).
Analysis of the results showed that if an individual had all three unhealthy habits — they smoked, drank heavily and were inactive — at a given point in time, their mental and physical health were poorer than if they didn’t have any of these risky behaviours.
Depressive symptoms rose by 0.1 points, metabolic risk score rose by 0.53 points, psychological wellbeing fell by 0.1 point and self-rated health fell by 0.45 points. Depressive symptoms and psychological wellbeing was measured on a scale of 1-4; self-rated health was measured on a scale of 1-5; and metabolic risk was scored from 0-5.
Having all three unhealthy behaviours long-term was even more strongly associated with poor health. Depressive symptoms rose by 0.38 points, metabolic risk score rose by 1.49 points, psychological wellbeing fell by 0.14 points and self-rated health fell by 0.45 points.
Lack of exercise was particularly linked to poor physical health, smoking was mainly linked to poor mental health and heavy alcohol consumption was associated with declines in both mental and physical health.
Crucially, the effects were apparent by the time the participants were in their mid-30s.
“Non-communicable diseases such as heart disease and cancer cause almost three-quarters of deaths worldwide,” says lead author Dr Tiia Kekäläinen, a health scientist who has a particular interest in aging. “But by following a healthy lifestyle, an individual can cut their risk of developing these illnesses and reduce their odds of an early death.
“Our findings highlight the importance of tackling risky health behaviours, such as smoking, heavy drinking and physical inactivity, as early as possible to prevent the damage they do to from building up over the years, culminating in poor mental and physical health later in later life.
“However, it is never too late to change to healthier habits. Adopting healthier habits in midlife also has benefits for older age.”
The authors note that the study was observational and so couldn’t establish that the risky behaviours were fuelling ill health, rather than vice versa.
They say that the relationship is likely two-way. For example, someone who is stressed may drink heavily to help them cope. This could then cause problems with family and friends that lead to poorer mental well-being.
They add that the results are likely to apply to people born in Finland and other Western countries in late 1950s and in the 1960s. However, they may not be as relevant to younger generations, owing to cultural and societal changes, and partly different risky behaviors occurring nowadays.
The study’s limitations include rating each of the three habits as being equally damaging to health, instead of weighting them.
The authors also acknowledge that they only looked at three types of behaviour and say that other factors, such as diet, should be included in future studies.
