Let’s put this number into perspective.
In August 2020, researchers at University College London set a new record for internet speed at the time: 178 terabits per second. This means that they could download Netflix’s entire catalog in 1 second. So, a year later, the NICT team has nearly doubled that record and halved the amount of time it would take to download the Netflix catalog. HOW THE NICT TEAM BROKE THE RECORD The fastest internet signals are made up of data converted to pulses of light and sent flying down bundles of hair-like glass strands called fiber optics. Fiber optic cables enable far faster data transmission with less loss than traditional copper wires. Millions of miles of fiber now crisscross continents and traverse oceans. This is the web in its most literal sense. With all that infrastructure in place, researchers are trying to figure out how to jam more and more data into the same basic design—that is, keep things more or less compatible but improve the number of Netflix libraries per second we can download. They can do that in a few ways. First, light has wave-like properties. Like a wave on water, you can think of a light wave as a series of peaks and troughs moving through space. The distance between peaks (or troughs) is its wavelength. In visible light, shorter wavelengths correspond to bluer colors and longer wavelengths to redder colors. The internet runs on infrared pulses of light that are a bit longer than those in the visible band. We can code information in different wavelengths—like assigning a different “color” of light for each packet of information—and transmit them simultaneously. Expand the number of wavelengths available and you increase the amount of data you can send at the same time. This is called wavelength division multiplexing. That’s the first thing the team did: They expanded the selection of “colors” available by adding a whole band of wavelengths (the S-band) that had only been demonstrated for short-range communication previously. In the study, they showed reliable transmission including the S-band over a distance of 3,001 kilometers (nearly 2,000 miles). The trick to going the distance was two-fold. Fiber cables need amplifiers every so often to propagate the signal over long distances. To accommodate the S-band, the team doped—that is, they introduced new substances to change the material’s properties—two amplifiers, one with the element erbium, the other with thulium. These, combined with a technique called Raman amplification, which shoots a laser backwards down the line to boost signal strength along its length, kept the signals going over the long haul. While standard long-distance fiber contains only a single fiber core, the cable here has four cores for increased data flow. The team split data into 552 channels (or “colors”), each channel transmitting an average 580 gigabits per second over the four cores. Crucially, though, the total diameter of the cable is the same as today’s widely used single-core cabling, so it could be plugged into existing infrastructure. Next steps include further increasing the sheer amount of data their system can transmit and lengthening its range to trans-oceanic distances. FINAL THOUGHTS: IMPLICATIONS FOR THE FUTURE OF THE INTERNET This kind of research is only a first step to experimentally show what’s possible—as opposed to a final step showing what’s practical. It’s worth noting that although the speeds achieved by the NICT team could fit into existing infrastructure, we would need to replace existing cables. The prior UCL work, which added S-band wavelengths over shorter distances, focused on maximizing the capacity of existing fiber cables by updating just the transmitters, amplifiers, and receivers. Indeed, that record was set on fiber that first hit the market in 2007. In terms of cost, this strategy would be a good first step. Eventually, though, old fiber will need replacing as it approaches its limits. Which is when a more complete system, like the one that NICT is investigating, would come in. As rapidly-evolving exponential technologies continue to converge, faster internet speeds will be a key aspect of global gigabit connectivity connecting everyone and everything, everywhere—at ultra-low cost. Bringing online an additional 3 billion individuals will drive tens of trillions of dollars into the global economy. How will you take advantage of this coming wave? © PHD Ventures, 800 Corporate Pointe, Culver City, California, 90230, United States Photo by Thomas Jensen on Unsplash
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CRISPR gene editing technology is revolutionizing healthcare as we know it.
The technology, which earned two of its discoverers a Nobel Prize in 2020, can target and edit genes more easily and more precisely than its predecessors. Yet as promising as CRISPR has been over the past several years, it’s mostly been developed in the lab. Thankfully, that is now changing as a growing number of clinical trials are beginning to test gene therapies in humans. Early CRISPR trials have focused on hereditary blindness and diseases of the blood, including cancer and sickle cell anemia. The problem is that although cutting-edge, these therapies can be costly and intense. For example, in one trial for sickle cell anemia, doctors remove cells from the body, edit them in a dish, and then infuse them back into the patient. Such a complicated approach won’t work as readily for other diseases. What we need is a general delivery method for CRISPR, so that it can be used like any other medication. Participants in the trial suffer from a condition called hereditary transthyretin amyloidosis, in which a mutated gene produces a malformed protein (transthyretin) that builds up in and damages the heart and nerves. The disease is eventually fatal. Patients received a single infusion of a CRISPR-based therapy into their bloodstream. Blood carried the therapy to the liver, where it switched off the mutated gene and curtailed production of the errant protein. Though the Phase 1 trial was small, the approach had strong results relative to existing options. And it hints at the possibility other genetic diseases may be treated in a similar fashion in the future. The University of California, Berkeley’s Jennifer Doudna, who shared the Nobel Prize for CRISPR, cofounded Intellia, the company that, alongside fellow biotech company Regeneron, developed the treatment (NTLA-2001) used in the UCL trial. “This is a major milestone for patients,” Doudna said. “While these are early data, they show us that we can overcome one of the biggest challenges with applying CRISPR clinically so far, which is being able to deliver it systemically and get it to the right place.” HOW THE THERAPY WORKS: A THREE-PART PUNCH The therapy is made up of three parts. A tiny bubble of fat, called a lipid nanoparticle, carries a payload of CRISPR machinery: a strand of guide RNA and a sequence of mRNA coding for the Cas9 protein. Billions of these CRISPR-carrying nanoparticles are infused into the bloodstream, making their way to the liver, the source of the dysfunctional protein. The mRNA instructs the cells to produce the Cas9 protein (CRISPR’s genetic ‘scissors’) which then links up with the guide RNA, seeks out the target gene, and snips it. The cell repairs the DNA at the site of the break, but imperfectly, switching the gene off and shutting down production of the problematic protein. Interim trial results, recently reported in the New England Journal of Medicine, were very encouraging. The UCL trial’s six patients, who received either a low or high dose, reported no serious side effects. Meanwhile, production of the target protein declined by up to 96 percent (and an average of 87 percent) in those given the high dose. ONE AND DONE? The disease, which affects roughly 50,000 people worldwide, was untreatable until recently. Existing drugs, approved by the FDA in 2018, silence the mRNA that produces the malformed transthyretin protein, instead of altering its gene. They reduce protein production about 80 percent and keep people alive longer, but don’t work for everyone and require ongoing treatment. The CRISPR approach, if successful, would be a one-time treatment. That is, by targeting the genes themselves, the protein is permanently silenced. Patrick Doherty, a trial participant, told NPR he jumped at the opportunity. Doherty, an avid trekker and hiker, was diagnosed with transthyretin amyloidosis—which had killed his father—after noticing symptoms, like tingling fingers and toes and breathlessness on walks. “It’s [a] terrible prognosis,” he said. “This is a condition that deteriorates very rapidly. It’s just dreadful.” Doherty started feeling better a few weeks after the treatment and said improvements have continued. “A one-hit wonder,” he called it. “A two-hour process, and that’s it for the rest of your life.” SO, WHAT’S NEXT? Although the results are promising, there’s reason to temper expectations. The trial, as noted, was small, and focused on safety. Future work will further test safety and efficacy in larger groups, which—as is apparent from recent experience with COVID-19—can reveal rare side effects or prove disappointing despite early success. Researchers will likely also look out for off-target “snips” in the liver or other cells. A benefit of this approach, however, is the cells break down the mRNA after they’ve made the Cas9 protein. In other words, the gene-editing system doesn’t persist long. It also remains to be seen whether the approach would work as well in other diseases. The liver was a prime target for the trial because it greedily soaks up foreign substances. Other organs and tissues may not be as amenable to a general infusion of the therapy. If the trial ultimately proves successful, however, researchers will want to know if they can reach any organ or target tissue with a general infusion. And can genes also be edited in vivo? Instead of merely knocking out a faulty gene, can we safely correct it? FINAL THOUGHTS It’s critical to remember that as we aim for personalized, effective medicine it isn’t about any one technique or technology—whether CRISPR, gene therapy, or stem cells, among others. It’s the combined power of all these techniques—their convergence—that holds the most potential. Perhaps the biggest consequence of this convergence will be individually customized medicine, or what’s called “N-of-1 medicine.” In N-of-1 medicine, every treatment you receive has been specifically designed for you—your genome, transcriptome, proteome, microbiome, and all the rest. It’s a level of preventative care never seen before. You’ll know which foods, supplements, and exercise regimens are best suited to your genetic code. You’ll understand which microbes inhabit your gut, and what diet sustains healthy microbiome diversity. You’ll know which diseases you’re most likely to develop and be able to take steps to prevent them. It’s an era of incredibly personalized medical care, wherein the tools of life have become tools for the preservation of life, and many of the diseases that plagued earlier generations have begun to fade from memory. © PHD Ventures, 800 Corporate Pointe, Culver City, California, 90230, United States Photo by Birmingham Museums Trust on Unsplash Viome was founded in 2016 on a fascinating insight.
While most researchers and scientists at the time were focused on looking at your genome (your DNA and genes) for clues to better fight disease, Naveen and his team knew that DNA doesn’t change. What does change is your gene expression: which genes are expressed (turned on for transcription into mRNA and thereafter proteins), how they are expressed, and how the expression of these genes change over time. Knowing the DNA of a particular organism allows you to identify that specific organism, but it doesn’t tell you which of its genes are actually turned on. You need to look beyond DNA to messenger RNA (mRNA) to understand which part of the organism’s DNA is actually transcribed, which genes are being “expressed”—then you can understand what it’s doing. So, what if we could measure gene expression? And not only of your human genes. What if you could measure the gene expression of the 100 trillion bacteria in your gut microbiome, which transform our food into fuel, and how these microbial genes impact your health? Viome does this using a process called meta-transcriptome sequencing to look at what mRNA and proteins the microbes in your gut are producing. We’ve heard about the microbiome for nearly a decade, but we’re just now starting to realize just how impactful it is on our mood, our diet, and our overall health. As Naveen puts it, by simply analyzing your microbiome and then adjusting your diet and nutrition, and taking steps to understand what supplements you need, you can vastly improve your health while reducing your risk of disease. For example, is vitamin B3 (Niacin) good for everyone? Not necessarily. If your body has high production levels of uric acid, then you shouldn’t be taking vitamin B3 because it could be harmful. It’s giving you this kind of accurate picture of your unique health that Viome does so well. HOW EXACTLY DOES VIOME WORK? Viome’s core service is its Health Intelligence Test, and the first step in the process is to take a few drops of blood and a stool sample (an at home, easy-to-use process). The results of the Health Intelligence Test include a range of key metrics including: (i) your immune health; (ii) your biological age; (iii) your cellular health; and, (iv) the health of your gut. Based on these findings and insights, Viome will recommend which foods you should eat and which ones to avoid and why, which nutrients and supplements you need, and so on. Viome then makes recommendations of food extracts, vitamins, probiotics, prebiotics, minerals, herbs, etc. that are all personalized for you. And importantly, the platform and its recommendations are dynamic: as your body changes over time, so will the recommendations. The company will soon include another test, Health Intelligence Test Plus, based on saliva samples that will add yet another layer of analysis and insights. DATA DOESN’T LIE Viome recently did a study of 10,000 people to measure the effects of receiving Viome’s recommendations of supplements over a period of 4 months. Here are some of the findings:
Viome then used a machine learning model that analyzed microbial activity, which was able to actually predict the glycemic response of different foods: if you eat this food, then this will be your body’s sugar response in your blood. SO, WHAT’S NEXT? Viome is now using its platform for early detection, and perhaps eventually prevention, of certain types of cancer. The FDA recently awarded the company “Breakthrough Device Designation” for its mRNA technology and AI platform to detect oral and throat cancer. They will soon be publishing a series of scientific papers on how its technology can detect those cancers using only a saliva-based test. And Viome isn’t stopping there. The company’s analyses of the human microbiome are now leading to a new understanding of the mechanisms that lead to the formation of different cancers. These findings are already surfacing new insights on the treatment of colorectal cancer, and they are charting a path to eventually treat other cancers, including pancreatic, breast, and ovarian cancers. Viome is even starting to look at how its technology can be used to treat mental health issues, including anxiety, depression, and even Alzheimer’s diseases. In success, Viome may be able to detect diseases like cancers, autoimmune, and mental health conditions far earlier than what is possible today. Finally, we’ll know exactly how to increase and decrease microbial strains and their activities—the production of enzymes and amino acids—with pinpoint accuracy. And that means that we will also get one step closer to what Viome envisions: a world where “illness is optional.” CLOSING THOUGHTS The microbiome is an open frontier ripe for innovation and a chance to make a massive difference in our health by optimizing every person’s unique biological makeup. Now is truly an exciting time to understand how to improve our health in ways we previously couldn’t have even imagined. And Viome is leading the way to harness this new knowledge to detect and prevent diseases much earlier, and to more precisely inform personal lifestyle and nutritional decisions that will help us live longer, healthier, and more productive lives. © PHD Ventures, 800 Corporate Pointe, Culver City, California, 90230, United States Photo by Karolina Kołodziejczak on Unsplash n the 1980s, Paul Ehrlich released a book, The Population Bomb, that incited a worldwide fear of overpopulation. He said that too many people, packed into too-tight spaces, would take too much from the Earth. Unless humanity cut down its numbers, all of us would face “mass starvation” on “a dying planet.”
Now, let’s take a closer look at the UN Population Division and disprove that. Total fertility rate (TFR) is a metric that demographers use to measure the number of offspring per parent. The population replacement rate, which is the average number of children per family for each generation to exactly replace itself, is roughly 2.1. It was different 70 years ago: As you can see in the above chart, the global average fertility rate was 5.05. Several countries, such as Rwanda, Kenya, and the Philippines, had a fertility rate higher than 7 children per woman. China had a fertility rate just over 6, while India was just below 6. Only one country in the world had a fertility rate below 2: Luxembourg. The United States had a TFR of 3.03 in 1950, which increased to a maximum of 3.6 in 1957. But a lot has changed since then. Today is VERY different: As of 2020, the global average fertility rate has more than halved to 2.44. What is the reason for this unprecedented decline? In short, there are three major reasons: the empowerment of women, declining child mortality, and a rising cost of raising children. Today, roughly 80% of the world’s population lives in countries with a fertility rate below 3. Only 10% live in countries where women, on average, have more than 5 children. For example, while China and India previously had total fertility rates above 5, each country has sharply declined rates around 2 today. Africa, on average, remains high but has more recently begun to rapidly decline. Several countries now have a fertility rate that is significantly below the replacement level. The TFR in the United States is currently 1.77. And women in countries such as Iran and Thailand have just 1.6 children on average. And the COVID-19 pandemic seems to have accelerated this trend toward underpopulation. Historically, there’s been a spike in births nine months after disasters and some people are wondering whether there will be a COVID baby boom. But it’s more complicated than that. Many people are now more unsure of their financial safety. Childcare during the pandemic has been difficult. Parents are cut off from extended family, who would have been part of a newborn’s upbringing. And the numbers reflect these trends. Clinics are reporting an increase in requests for birth control prescriptions and abortion medications. The pandemic has changed the way the world thinks about having children—it might even bring the world closer to underpopulation sooner than we think. Back in April 2021, when I interviewed Elon Musk for the launch of the $100M XPRIZE Carbon Removal, I asked him about his concern of underpopulation. He shook his head and said, “Earth is going to face a massive population collapse over the next 20 to 30 years… this would be civilization’s way of dying with a whimper.” AGE REVERSAL AND LONGEVITY When I speak publicly about longevity and age reversal, one of the routine arguments against this work is public concern for “overpopulation”. As demonstrated above, the reality is that the world is facing a threat of underpopulation, and increasing healthspan by a decade or two may be a critical step in maintaining increased abundance for humanity. More than ever, we need to increase our productive and healthy lifespan. Not only will this allow us to spend more time with loved ones and fulfill our bucket list dreams—it also has the potential for enormous economic value. Researchers from Harvard, Oxford, and London Business School recently demonstrated just how much increasing healthy lifespan is worth in dollars. Slowing aging by only one year is worth +$38 trillion to the global economy. That is just one year. Imagine the societal benefits and economic value of increasing healthy lifespan by 10-20 years. Here are some of the technologies that will get us there: (1) Improvements in diagnostic medicine will change “sick-care” to healthcare. We practice reactive medicine, when it should be preventive medicine. This is crucial to increasing longevity. Cancer is still one of the most feared words in medicine. But what if we could diagnose cancer early? A stage I cancer is infinitely easier to treat than a metastatic stage IV. The number one thing you can do to fight and survive cancer is to find it early. GRAIL is one of the most promising diagnostic breakthroughs of the decade. It’s a liquid biopsy––a blood test that can detect most major types of cancer at an early stage. It searches for tiny fragments of DNA and RNA that have been released into the bloodstream by a tumor that reflect the tumor’s genomic features. It’s so sensitive it can detect even a faint signal that an early tumor exists. Its ultimate mission is to offer one test that can simultaneously scan for every type of cancer. (2) CRISPR and gene therapy. Single point gene mutations make up roughly two-thirds of known human genetic variants associated with disease. This is where the revolutionary gene-editing technology CRISPR comes in. Its “molecular scissors” are able to snip a stretch of DNA and either disable the affected sequence or replace it with a new, correct one. The allure of this kind of therapy is that it’s a one-time treatment that cures the disease. The possibilities that CRISPR have opened up are endless. The most recent landmark CRISPR trial from June 2021 showed its effectiveness against a form of amyloidosis, an incurable disease that involves misfolded proteins depositing in and destroying organs. These advancements in genome editing can also be used to increase your healthy lifespan. Dr. David Sinclair of Harvard Medical School has engineered a virus to deliver a combination of three Yamanaka genes. These genes are responsible for creating induced pluripotent stem cells. When these viruses were injected into the eyes of mice, their eyes became younger. In the case of glaucoma and aging, all the mice got their vision back. The hypothesis is that this technology can be applied to other parts of the body. Imagine a rejuvenation of our aging bodies. (3) Organ regeneration. As our organs begin to tire and age, finding a way to regenerate them will be vital to increasing healthy lifespan. Dr. Deepak Srivastava, President of the Gladstone Institutes, is using gene therapy to repair heart damage with an approach we personally like to call cellular alchemy. He’s reprogramming scar tissue to become a new heart cell. After injecting these genes into the heart after a heart attack, they were able to change the fate of the scar cells, turning them into beating hearts. No need to GATTACA clone humans to provide an extra set of organs. We can regrow our own organs from within us. MY CONCLUSIONS—WHAT DO YOU THINK? Contrary to popular belief, the world is facing the threat of underpopulation as a result of the sharp decline in global reproductive rates. On top of that, an increasing proportion of our world is likely to face one of the most crippling and major causes of physical suffering: a disease called aging. This calls for increasing not just lifespan, but healthy and productive lifespan. Thankfully, due to the convergence of AI and medically related exponential technologies, advancements in age reversal are already happening at an accelerated rate. There is a reason the longevity industry has been named the biggest and most complex industry in human history. On the bright side, this has become a massive opportunity for innovation. At XPRIZE, we are working to fund and launch a $100M Age Reversal XPRIZE with the goal of demonstrating a 25% lifespan “age reversal” (more details on this as the guidelines and funding are solidified). In the meantime, our goal (yours, mine, and everyone in our global community) should be to live long enough to intercept the next bridge of technology, and the next one, and so on. While it sounds next to impossible and almost too sci-fi for our imaginations to grasp, I ensure you that many brilliant minds are working to crack this challenge. And, without question, age reversal will be one of the biggest business opportunities on Earth and economic benefits for humanity. |
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