Peter believes “we owe the next generation” what he calls “AI-powered education.” He explains how it can already work using the example of Khan Academy and the personal story of a young woman from Afghanistan named Sultana. It’s a great story!
Alongside healthcare, I can’t think of another field more in need of reinvention than education. Some teachers and schools have come out saying that using generative AI tools is a form of cheating, and others have banned them altogether. But as Stability AI CEO Emad Mostaque notes:
“Education isn’t about competition. We made it a competition. It’s about actuation.”
An alternative vision of education powered by AI is about the learning process becoming more personalized and effective.
Imagine a future where every student has their own personalized AI that is customized for them and looks out for them. Are you a visual learner? Do you learn best through listening? Are you dyslexic?
Imagine an AI that uses an iPad’s forward-looking camera to study a student’s facial expressions as a lesson is being delivered. If the student looks confused or bored, the AI can change tack, adjusting the lesson accordingly from a different point of view, or at a different level of complexity.
Imagine a future where a teacher’s AI assistant adapts to each student’s learning style and pace, offering personalized education, and incorporating a student’s favourite sports stars or movie stars into the curriculum. It can track a given student’s progress, identify trouble areas, and optimize on the fly.
Beyond AI alone, the combination of AI and VR together promises to make learning “experiential” and “immersive,” delivering lessons that are unforgettable and hyper-personalized.
I remember as a child going to Greek School to learn about my heritage, and then at MIT taking a course on ancient cultures covering Socrates, Plato, and Aristotle. Whatever way you cut it, reading historical textbooks about philosophy is difficult at best. Imagine instead, entering an interactive VR world set in ancient Greece, surrounded by a vibrant Agora, encircled by bustling crowds, lively debates, and the grand architecture of a flourishing city-state at the pinnacle of its cultural and intellectual achievements.
As you traverse the cobblestone pathways, an arresting figure captures your attention. Seated on a marble plinth, an elderly man exudes an air of wisdom. His physique is draped in the unadorned elegance of a white toga, a white beard frames his gaze. With a graceful rise, he beckons you forward and extends his hand. “Greetings, traveller,” he proclaims with a genial smile, “I am Socrates, your guide here in Athens. May I show you around and answer your questions?” Embracing his invitation, you find yourself wandering alongside the philosopher, meandering through the vibrant streets. As you walk, Socrates, with a storyteller’s flair, illustrates the daily routines of Athenian life, while recounting local politics and recent history. He guides you towards the Acropolis that rises like a crown above the city and introduces you to his many friends and pupils as you walk.
The generative AI imagery and experience are so immersive and compelling that you forget you’re in VR. It feels more like a real-life experience. Perhaps most importantly, everything this AI version of Socrates says and does is driven by a fully validated large language model (LLM) built upon historical consensus.
In this fashion, AI in partnership with VR will allow us to experience the greatest moments in human history ranging from the signing of the Declaration of Independence alongside Thomas Jefferson and John Adams to walking on the surface of the Moon with Neil Armstrong and Buzz Aldrin.
When I think about digitizing, dematerializing, demonetizing, and democratizing education, one of the most impactful stories I’ve ever heard was told to me by Sal Khan, Founder and CEO of Khan Academy.
Sometimes a single individual’s story can best exemplify the power of a new technology to transform a field. This is one such story about a young girl in Afghanistan named Sultana who used Khan Academy to educate herself and change the course of her life. Sultana grew up in Afghanistan, and when the Taliban took over her town, they forbade all the young girls from going to school. Khan Academy became her lifeline. She studied everything from elementary school math to algebra and trigonometry, eventually moving on to physics, chemistry, and other subjects. Without access to school or teachers, she used Khan Academy’s free online lessons and courses, all from the safety of her home.
Here’s how Sultana later described the experience in a 2021 article in The Economist:
“Armed with an iPad, the internet and a free education website called Khan Academy, I taught myself English. And philosophy. And math. And science. And history. I wanted to understand the world in every way possible, and my place in it. Solving math problems gave structure to the uncertain world I was living in, even if just in my head. I felt liberated when I first learned to make a graph of a linear equation. On the page, drawing a two-dimensional coordinate plane and graphing an equation, the world was in my control.”
Sultana then decided that she wanted to be a theoretical physicist in the United States. So, she smuggled herself into Pakistan to take the SAT because the test wasn’t offered in Afghanistan. She passed. Soon after, she was admitted to Arizona State University, graduating with honours!
Where’s Sultana now? She’s currently a member of the research faculty at Tufts University studying quantum computing.
Since Sultana’s success, the Khan Academy has super-charged its platform using generative AI powered by GPT-4 from OpenAI. The new product is called Khanmigo, an AI-powered teaching assistant, that can amplify the power to educate and ultimately help humanity enable many more Sultanas in our future.
Announced in March 2023, Khanmigo adopts an AI-powered Socratic, narrative-driven approach to engage students. It promises to make learning easier and more efficient, functioning as a personal tutor that engages students interactively, assisting with meaningful exercises, diagnosing mistakes and encouraging understanding over memorization.
Khanmigo is designed to understand students’ reasoning, a departure from traditional rote methods of learning. It contextualizes learning to a student’s interest, asking probing questions to reveal practical applications of academic concepts.
Khanmigo’s integration into the educational process is showcased through interactive features such as reading comprehension aids, AI memory for ongoing interactions, and narrative progress reports. Future updates will soon include voice interaction and multi-user activities.
Khanmigo is not a replacement for human teachers. Instead, it serves as an assistant to educators, allowing them to focus on fostering critical human skills such as judgment and creativity. It also provides recorded AI conversations for review, while supporting grading, lesson planning, and providing personalized guidance, aiming to reduce teacher workload.
Given how fast everything is changing, we need to keep the world from revolting at the rate of disruption. This means giving people access to high-quality education and helping them believe that they have a future that is compelling and abundant. AI in education creates a compelling way to teach and learn, independent of where you live and how wealthy you are. If that’s not democratization in learning, what is?
]]>Peter Diamandis has his take on how AI will positively disrupt medical practice. Peter is both a medical doctor and an engineer. He is convinced that AI is the answer to much of what is currently wrong in the state of medicine.
He writes that doctors today are overworked and drowning in data. He quotes data from a 2017 report that stated 30% of physicians spent between 17 and 24 minutes with a patient, and that 29% spent less time, between 13 and 16 minutes per patient. So the majority of patients who wait an average of 26 days to see their family doctor, end up with a face-to-face visit between 13 and 24 minutes.
Why? One of the reasons is the fallout from COVID-19 which has witnessed since 2020 a large number of doctors, particularly general practitioners, retiring. In 2021, 20% of healthcare workers resigned with 117,000 physicians in the United States leaving. That same year only 40,000 got their medical license.
Another reason for physicians drowning in data is the sheer volume of medical information being published today. It is a wonder that doctors can keep up with the 28,000 peer-reviewed medical journals that publish more than 1.8 million articles per year, or roughly 5,000 new papers every day.
Then there is the paperwork and patient record keeping. Patient diagnostic testing results, consult reports, patient visit notes, prescriptions, phone calls to referring specialists, and more fill a doctor’s daily workload. The billing and other administrative tasks of a medical practice add even more to this.
As a patient, you have to ask, can my family physician keep up-to-date in the face of this incoming and outgoing information overload?
Should doctors feel threatened by the arrival of AI in their profession? Some may feel that their expertise is not to be trifled with. AI algorithms, some believe, are committing systematic theft on a mass scale using physicians’ online records in the large datasets that AIs use for training.
Others, however, welcome AI for its enhanced capability, speed, consistency, and accuracy in diagnoses. AI algorithms can consume images, test results, case notes and more and do it with blinding speed. An AI can train on hundreds of thousands if not millions of cases. A physician, even a specialist, will only have knowledge and exposure to a fraction of that number.
AIs see subtle patterns that humans miss. AIs can think outside the box and make associated links among data that indicate a disease may be starting. A physician may never see the links at all.
Some physicians fear that dependence on medical AIs will decrease the knowledge possessed by doctors and other health professionals and that the AI black box will take over. A Viewpoint article on the JAMA Network last month entitled “AI’s Threat to the Medical Profession,” notes that fear:
“Most of today’s knowledge on disease mechanisms will be forgotten and we will be ruled by systems that only focus on intervention strategies that will provide the best possible outcome. This era will show a decrease in intellectual debates among colleagues.”
Peter Diamandis argues that knowledge, nor methodologies, will not be forgotten when a medical AI starts working with a general practitioner or specialist. He states the transformation to a partnership between physician and AI co-pilot is to be celebrated and not feared.
Along with the arrival of the Internet-of-Things (IoT) and the proliferation of smart connected sensors and medical devices, medicine is entering a transformative moment with the patient being a partner in achieving healthy outcomes.
I’ll give you an example. When COVID-19 infected my heart I developed arrhythmias (rhythm disturbances) that in my case were considered life-threatening. I bought a Kardiamobile, a device that I could use at home to test my heart. Whether I felt a change or not, the use of this device once a day gave me a 30-second electrocardiogram that I could share with my doctor. I didn’t need an appointment or a lab requisition for me to know my heart’s status, and for my doctor to be kept informed.
The arrival of medical AI and this sensory revolution of medical devices means that wait time issues will no longer be all that relevant. Instead, medical AIs will continually monitor the sensors a patient has on hand and the data produced to assist a doctor without being intrusive.
Peter writes:
“Rather than waiting a month to book your annual medical checkup, sensors on your body, in your body, and your environment (bedroom, bathroom, office, and car) will be constantly monitoring your physiology and uploading data to your medical AI.”
Continuous monitoring will catch diseases at their earliest stages, allow for rapid intervention, and forego medical appointments, hospital visits, or prolonged hospital stays.
Medical AIs will fill the gap created by retired and missing healthcare workers. It will give physicians the means to provide continuous healthcare without being overwhelmed.
]]>He cites three AI milestones that occurred in 2022 and 2023:
All these developments happened coincidentally with the release of Open AI’s ChatGPT. Imagine then what is likely to happen in the next two or three years. Will AI eliminate the need for human programmers? Or, rather than eliminate coders in using AI-based tools, become software coders? Have large-language modelling AIs permanently changed the world of software? I’ll let Peter explain.
In a future where generative AI does coding, anyone can express what they want in natural language which then an AI will convert into code. NVIDIA’s CEO Jensen Huang noted in a recent call: “We’ve democratized computer programming for everyone … who could explain in human language a particular task to be performed.” Eliminating barriers that once blocked creativity means anyone can build systems that solve problems and create value for society.
These are called “no-code” and “low-code” platforms that empower individuals with little to no programming skills to develop new applications. No-code platforms have user-friendly interfaces, and facilitate rapid application development for those with domain-specific understanding to solve a business problem but who have no or limited coding skills. IT professionals are taking to low-code platforms requiring a rudimentary understanding of coding but offering higher degrees of customization and integration. “Citizen developers” are taking to no-code platforms.
In this new environment, does it still make sense to learn how to code? Should your kids continue to learn Python or another programming language? While your first reaction may be to say “No,” Steve Brown, my Chief AI Officer, has a different opinion:
“Coding is not about a particular computer language or even about writing programs per se. It’s about cultivating a mindset of computational thinking: enhancing your ability to break down complex problems into manageable components, devising logical solutions, and thinking critically.”
This skill will become increasingly important.
While it is true that AI has enabled machines to speak English, if you want to collaborate with AI and harness its power, learning the native language of AI will give you a distinct advantage. It’s how you will go from being a naive end-user to becoming a creative partner, problem solver, and critical thinker.
Technology has always allowed individuals to do more, faster. Robotic farm equipment has increased the output of farmhands 1,000-fold, while computers have empowered investors, scientists, and digital artists by orders of magnitude. Now AI, in a somewhat recursive manner, is enabling our best programmers to amplify their skills and programming prowess 100-fold.
AI-enabled programming is a superpower for both the novice and the experienced coder. AI tools such as Replit and GitHub Copilot are helping developers automate redundant workflows, learn faster, write code faster and with fewer bugs, work more efficiently, and scale their productivity.
For example, researchers at Microsoft have found that software developers using AI assistants complete tasks 55% faster than those not using them. An MIT study shows that the top 5% of programmers performed orders of magnitude better while partnering with AI.
The best coders soon or already are hybrids: humans working with AI assistants. This development is democratizing humanity’s ability to code and magnifying the abilities of the best coders 100-fold. We are super-charging our future.
At the same time, AI is learning how to code by itself and improve its performance and capabilities. Without question, the rate of technological advancement is accelerating. While this may scare many, it is important to recognize that these improved tools will enable entrepreneurs to address and defeat many of humanity’s grand challenges. These tools are enabling individuals and small teams to take on challenges previously only addressable by governments or large corporations. That’s why I stated previously that we are through a marriage of humans and AI democratizing our ability to solve the biggest problems.
]]>Meta’s Chief AI Scientist is Yann LeCun. He is a graduate of The Sorbonne and a professor at NYU. He developed AI capable of recognizing handwriting and was a past winner of the Turing Award.
LeCun argues that “intelligence doesn’t necessarily equate to a desire for domination.” Is this human trait to use superior intellect the only way we act?
LeCun points out that not all humans use their intelligence this way and often act oppositely, He states, “The most intellectually gifted among us aren’t necessarily those seeking power. This phenomenon can be observed in various arenas, from international politics to local communities. It’s believed that those who aren’t as intellectually endowed might feel a greater need to influence others, perhaps as a compensatory mechanism. In contrast, those with higher intelligence can often navigate life relying on their skills and knowledge.” LeCun reflects on his own experience in leading a research laboratory, stating, “The most rewarding hires were those who brought more intellect to the table than myself. Working with individuals who display superior intellect can be enriching and elevating.”
Similarly, our future interactions with AGI assistants envisioned to be more intelligent than us will likely enhance our capabilities rather than diminish them. It won’t overthrow us but will rather serve to augment us. This relationship is analogous to a mentor and apprentice, where the AGI will play the role of a supportive and enlightening guide.
The notion of AGI’s desire for dominance stems from our understanding of social animals where hierarchical structures prevail. We exhibit this characteristic. But a better animal species to emulate, states LeCun, would be the orangutan.
Orangutans are nearly as intelligent as us. They can operate machinery and use our tools as you can see from the above image. Yet they lack any notable desire to dominate because of their non-social and solitary nature.
So we can design our AGI to be like the orangutan by giving it no inherent ambition to dominate. LeCun says, “It is we, the humans, who will define the objectives for AI systems. These intelligent systems will then create subgoals to achieve these primary goals. However, the method to ensure that AI aligns its subgoals with our intended outcomes is a technical challenge yet to be fully resolved.” This area of AI research needs further development to ensure none of the concerns described above become the norm.
Imagine an AI that is a more interactive, knowledgeable version of Wikipedia, a platform that not only stores information but also infers, learns, and assists. This AI needs to be open and accessible to all and not controlled by a few private entities, A concern LeCun raises is that a small number of companies could end up controlling super-intelligent AI systems and, “They could potentially influence public opinion, culture, and more, leading to an imbalance of power and control.” That’s why from his Meta pulpit LeCun is advocating for AI systems to be open source much the way the Internet is today. This will allow for global contributions and oversight and ensure that AI becomes the repository of our collective knowledge shaped by inputs that span the globe.
]]>What were the top 22 breakthroughs of 2022? And how do they compare to the top breakthroughs of 1922, 100 years ago? Back in 1922 in the United States and the rest of the world, we were just emerging from the aftermath of the Spanish flu. In that year, the United States had:
The top breakthrough inventions of 1922 included:
Now compare that to the top 22 breakthroughs of 2022 covering space, energy, health, food, robotics, quantum computing, and artificial intelligence.
The #1 breakthrough in my book is The James Webb Space Telescope (JWST). Its successful launch and deployment represent the most sophisticated and complex observatory ever constructed. At a cost exceeding $10 billion, JWST is an infrared observatory orbiting the Sun about 1 million miles from Earth. Its primary mirror is 21.3 feet (6.5 meters) across and can image objects 9x fainter than its predecessor, the Hubble Telescope.
JWST was designed to study the most distant objects in the universe, including the first stars and galaxies that formed after the Big Bang. Its mission will unveil unprecedented details about the Universe’s origins and lead us to new cosmological discoveries, and even help to search for signs of life on other worlds. Scientists can now see the Universe as it appeared mere 100 million years after the Big Bang
The #2 breakthrough was DART, the Double Asteroid Redirection Test which deliberately smashed a spacecraft into a 160-metre-wide moonlet accompanying a larger asteroid. The impact velocity was 22,500 kilometres (14,000 miles) per hour causing the moonlet to alter its orbit significantly. The mission was deemed a great success for future planetary defence with the Earth in constant danger of being impacted by an asteroid. A 1903 event, the Tunguska Incident, levelled 1,000 square kilometres (400 square miles) of Siberian forest back then with a 12 Megaton blast. With Tunguska-sized events happening about once every thousand years, and 5-kiloton air bursts about once per year, the threat to Earth from an impactor is very real. And astronomers only have detected about 40% of the estimated 25,000 near-Earth asteroids that pose a threat. The DART mission, however, demonstrated a viable defence.
The #3 breakthrough occurred this month with net positive fusion output achieved. Scientists at California’s National Ignition Facility at the Lawrence Livermore National Laboratory announced a net energy gain in a fusion reactor for the first time. Fusion research has been pursued for decades. While this particular form of fusion will require a lot more work to reach commercial utility, it inspires us to show what is possible in the future. It is worth noting that there are currently 37 privately funded fusion companies working on commercializing various forms of fusion. One example is Commonwealth Fusion Systems, spun out of MIT in 2017, which is building a tokamak the size of a tennis court, backed with $250 million in private capital.
Fusion reactors require very small amounts of hydrogen. The hydrogen in a glass of water could provide enough energy for a lifetime. Fusion creates no radioactive waste. With the U.S. pledged to eliminate all carbon dioxide emissions from the electricity sector by 2035, adding fusion to solar, wind, hydropower, and mini-fission nuclear reactors would help achieve this audacious goal. And nuclear fusion would be a far superior solution to provide abundant clean energy.
The #4 breakthrough is small modular reactors (SMR) achieving U.S. Nuclear Regulatory Commission approval. The first of these to be built in the United States is the NuScale Power Module. At less than 25 metres (80 feet) tall, this SMR will generate enough clean electricity to power a city of 60,000 homes. It is expected to be completed in Utah and running by the end of the decade and should operate continuously for 60 years without any major overhaul.
In shrinking reactors, the nuclear industry is making them safer, cheaper, and faster to implement. The NuScale reactors will be manufactured off-site and will have lower operating costs than traditional reactors. Globally, nuclear power supplies just 11% of electrical power, down from approximately 18% in 1996. NuScale’s SMR will take up 1% of the space of a conventional reactor, which will allow for SMRs to be stacked side-by-side and efficiently minimize space while maximizing power production. It is hoped that these SMRs, being smaller, cheaper, and safer will allow nuclear power to increase its footprint in global energy production.
Stay tuned for Part Two when we look at the health breakthroughs of 2022.
]]>Peter goes on to describe how this seamlessly impossible capability is much closer to reality as he discusses work by two different research teams working with synthetic mouse embryos created from stem calls rather than eggs and sperm, and about keeping the embryos alive for almost the gestational period for mice using artificial wombs. These embryos developed beating hearts and brain stems.
The question of why researchers are doing this is fundamental to Peter’s enthusiasm for this work. He sees it as giving us new medical insights into embryology, an alternative to infertility in parents trying to conceive, and the potential to grow organs that would not be rejected in transplants.
What follows are Peter’s words with a few edits from me. I’d be interested in hearing back from readers about this new scientific endeavour.
How life evolves from a single fertilized cell to an organism with hundreds of billions or trillions of differentiated cells is a fundamental question scientists are only just beginning to understand. Developmental biologists have made significant progress studying animals whose young develop in transparent eggs, such as zebrafish and frogs. But mammalian development is harder to observe because it takes place inside a uterus. Ethical concerns and tight regulations complicate research on human embryos even further.
In recent years, there has been progress coaxing embryonic stem cells into structures resembling blastocysts, the precursor of embryos, which provide an essential model for early human development that sidesteps some of these issues. But without the supportive environment of the womb, there’s only so far these so-called “blastoids” can survive, and have the chance to develop into the later stages of embryonic development.
In August of 2022, a pair of papers published by two separate groups shook the scientific world as each demonstrated the use of an artificial womb to keep mouse embryos (derived from embryonic stem cells) alive for 8.5 days. Central to both papers was a complex contraption designed to mimic the environment of the uterus, designed by Jacob Hanna, from the Weizmann Institute of Science in Israel, who led one of the teams. It combines rotating glass vials filled with blood serum and a ventilation system that maintains pressure and oxygen levels.
But the artificial womb wasn’t the only innovation. In 2018, Magdalena Zernicka-Goetz, who has dual appointments at Caltech and the University of Cambridge and led the other team, discovered that embryonic stem cells developed further when combined with stem cells from two structures key to early development: the placenta and yolk sack.
By combining these two breakthroughs, the two teams were able to create synthetic mouse embryos that developed to the stage where the basic body plan starts to emerge. This included complex structures including beating hearts, primitive brains, and the beginnings of a gut.
The most obvious impact these advanced synthetic embryos could have is helping scientists crack the underlying code of development. This underpins all kinds of critical capabilities such as regeneration, reproduction, and tissue specialization that have significant implications for medicine.
The team led by Zernicka-Goetz is particularly interested in understanding why some pregnancies fail at the earliest stages, and she says that this new model could provide an unprecedented window into these processes.
One of the beauties of this synthetic embryo model is that it should be possible to genetically engineer the stem cells used to build them. This could allow researchers to identify how specific genes contribute to the developmental process.
The other group led by Hanna has even grander ambitions. They have created a startup called Renewal Bio that plans to create synthetic embryos from patients’ cells, whose tissues could be harvested for transplantation. While there’s been significant progress in the ability to grow simple tissues like skin and cartilage, organs with complex 3D structures and vasculature have been more challenging. Hanna believes that relying on the body’s own developmental processes might be a better approach. “We view the embryo as the best 3D bioprinter,” he told MIT Technology Review. “It’s the best entity to make organs and proper tissue.”
Among the potential applications are collecting blood cells from embryos and transfusing them into patients to rejuvenate their immune systems, or using cells from rudimentary ovaries to help women extend their fertility later in life.
Efforts to reinvent human biology inevitably raise thorny ethical challenges. While guidelines vary among countries, human embryos are typically not allowed to develop beyond 14 days, which is the point at which they start to develop from an amorphous blob of cells into something resembling a body.
Renewal Bio envisages developing its embryos to 40-day or 50-day equivalents to gestation in pregnancies. While there is still the question of these entities being viable, the further along the developmental pathway the murkier the ethical implications. One potential solution suggested by Hanna is to genetically engineer the precursor stem cells so that the embryo never develops a brain and head, avoiding any concerns about experimenting on a potentially conscious being.
Other researchers have argued that the concerns about synthetic embryos with no potential to develop into living beings do not outweigh the concrete benefits to people on organ donor waiting lists.
But while these ethical challenges are considerable, experts say the technical ones are probably a more pressing concern. The efficiency with which stem cells can be coaxed into embryo-like structures is still very low, with less than 1% of all cell cultures doing so successfully. And even when they do, the synthetic embryos feature many defects that raise questions about whether they are truly useful models for development. And moving from mouse stem cells to human ones is not a trivial step, not least because it takes considerably longer for human embryos to reach a similar stage of development.
We remain a long way from the feasibility of the technology to combat aging or the regeneration of organs on demand, but it’s important not to understate its potential. Despite these cautious assessments of what lies ahead, experts liken these latest developments to the time when the first cloned sheep, Dolly, was born in 1997.
]]>About fifteen years ago bloodwork ordered by my family doctor indicated my cholesterol levels were a little above high normal. My doctor prescribed a statin which I continue to take a minimal dose each day. It took awhile for me to adjust to a side effect – lower back pain, but by adding CoQ10 to my daily intake I have had no problems.
High cholesterol levels in the blood are a potential heart disease threat because an excess can cause fatty deposits to grow on the walls of blood vessels which over time can lead to blockages, a stroke, or a heart attack.
High cholesterol can be an inherited condition. It can also occur from an unhealthy diet, other medications, or a lack of exercise. The prevalence of high cholesterol in North American populations has had some in the medical profession suggesting that statins should be added to the drinking water, just like fluoride used to prevent tooth decay.
Cholesterol in combination with proteins expressed through genetic instructions produces a substance called lipoproteins. There are two versions: low-density lipoprotein (LDL) and high-density lipoprotein (HDL). It is LDL that causes fatty deposits. HDL is seen as good because it removes excess cholesterol from the bloodstream.
Taking statins targets LDL and in some studies is seen as increasing HDL levels in blood plasma. But it is still unclear whether statins impact HDL effectiveness.
But what if we didn’t need statins and could end high cholesterol by altering a specific gene associated with blood cholesterol levels? In Peter Diamandis’ latest musings he describes what appears to be a biomedical game changer. A therapy that permanently alters one gene responsible for a protein that produces LDL and HDL.
I have edited Peter’s work and hope you find what follows to be an interesting read.
Heart disease accounts for roughly 16% of total deaths globally each year. It costs the US economy roughly $219 billion annually. High levels of cholesterol in the bloodstream is one of the main causes. That’s why more than 200 million people worldwide regularly take statins, the leading medication for lowering cholesterol levels. These drugs have proved effective, but require consistent use and can result in side-effects.
Scientists have identified a link between the PCSK9 gene and a protein for which it is responsible that plays a role in regulating cholesterol levels in the blood.
Research at the University of Texas Southwestern Medical Center in the mid-2000s established the role of the PCSK9 gene in heart health. The researchers identified people with a genetic mutation that inhibited it from producing a protein had lower LDL levels in their bloodstreams.
The PCSK9 gene-produced protein was seen as preventing the recycling of receptors in the liver responsible for filtering LDL from the bloodstream. Where the PCSK9 gene produced high levels of the protein the overall number of receptors dropped and cholesterol levels rose. The impact of the amount of protein produced by the PCSK9 gene was associated with 15 to 28% reductions in LDL levels and a 47 to 88% lower risk of heart disease.
Finding a drug that could target the protein has proven challenging. Monoclonal antibodies that target PCSK9 called alirocumab and evolocumab have been produced to cut the risk of cardiovascular events by half. But these drugs are more expensive than statins.
The Texas Southwestern researchers thought that a more promising approach would be to tackle the errant gene rather than the protein it produces. From the patients they identified that had mutations and low LDL levels, it seemed possible to genetically replicate a resistance to heart disease by changing all PCSK9 genes to express less protein.
The tool of choice for this project was CRISPR. The emergence of the CRISPR-Cas9 system has revolutionized our ability to tweak genes. There are issues however that have limited its applicability in biomedicine. That’s because the Cas9 protein produced by CRISPR cuts both strands of DNA at a target site before relying on the cell’s internal repair system to stitch the DNA together. Experience has shown that the process isn’t always perfect leading to unintended edits that reduce efficacy and can potentially introduce harmful mutations.
An emerging approach known as base editing gets around the problem by using a modified Cas9 protein to break only one of the DNA strands. This is spliced to another protein to convert one DNA letter to another. The approach only makes single letter edits but is much more precise for use in medical applications. And by a remarkable stroke of luck, it turns out that the PCSK9 gene can be altered to deal with the errant protein through a simple one-letter edit. This is a big deal because diseases caused by a single-point mutation like this are relatively uncommon.
A company called Verve Therapeutics has designed a base editor to switch out a single letter in the stretch of DNA encoding for PCSK9 to essentially turn the gene off. Last year, they reported when they injected the therapy into the livers of monkeys it reduced their LDL levels by 60%.
The first human trial began this month with the first to receive the therapy a New Zealand volunteer. The plan is to treat 40 people who have an inherited condition called familial hypercholesterolemia (FH) which occurs in 1 in 250 and produces extremely high levels of LDL. Those with FH are at higher risk for heart disease. If successful the treatment can become a standard approach to dealing with FH and other high cholesterol risks. Stated Sekar Kathiresan, CEO of Verve, in a recent MIT Technology Review article, “If this works and is safe, this is the answer to heart attack—this is the cure.”
The therapy is a one-and-done treatment unlike being on statins or taking monoclonal antibodies. It will make a permanent change to liver cells and stop them from producing the PCSK9 protein. The edits will pass on to the next generation of cells when they divide. That means that even if the therapy is initially expensive, the lifetime cost should prove to be comparable if not lower than current alternatives.
The therapy is delivered to the liver cells in lipid nanoparticles, the same technology being used by mRNA Covid-19 vaccines. The pandemic has created manufacturing capacity for this type of therapeutic delivery which is helping to lower costs.
A successful clinical trial doesn’t lead right away to adoption throughout the medical profession. It is likely there will be many more trials, and a number of years before Verve has enough data to convince regulators to approve the treatment for run-of-the-mill high cholesterol. If it turns out to become the new treatment standard, however, it will be one of the most transformational innovations in human healthcare to be seen in decades.
Beyond the potential to cure heart disease, this news is an exciting milestone in the use of genetic engineering in clinical application. Current base editing technology is capable of tackling about 60% of single-point mutations associated with diseases and this could widen the scope for its use.
Beam Therapeutics is another company working with base editing technology that is about to start human clinical trials designed to treat the genetic blood disorder sickle-cell anemia. It is using base editors to make multiple single letter changes for more complex genetic repairs.
Then there is Wave Life Sciences that is experimenting with base editors to modify RNA rather than DNA to make it possible for transient changes to how genes are expressed rather than permanent alterations to the genome.
Most excitingly, the researcher who first developed base editing, David Liu from the Broad Institute of MIT and Harvard, has continued innovating. In 2019, he and his colleagues outlined a new approach called prime editing in the journal Nature, which dramatically increased the scope of potential edits. Base and prime editing are being used by the team at CureHeart to tackle cardiomyopathies. You can read what I recently wrote about their work on this blog site. Like base editing, prime only breaks a single DNA strand, but in addition makes edits to individual letters or entire stretches of genetic sequences. It is believed that up to 89% of mutations associated with diseases in humans can be treated this way.
In his missive, Peter talks about Matt Ridley, a zoologist, who wrote and published The Rational Optimist in 2010. The book takes a profoundly optimistic view of human progress, a counterblast to the prevailing pessimism of our day. Ridley coined the phrase “moaning pessimism” to describe the current state.
The following summarizes Peter’s talking points joined by some editorializing on my part. I welcome your optimism, less so your pessimism in any comments you wish to share with my subscribers and casual visitors and readers.
Is there any reason for optimism today asks Peter? A glance at current headlines is enough to set anybody on edge. And with an endless media stream of bad press that includes online and hard copy, it’s hard to be optimistic. What makes all of this worse is that evolution has shaped us to be acutely aware of danger so the bad gets larger mindshare than anything good and our ability to appreciate the positive that is happening is compromised.
Peter is the author of an intriguing book called Abundance: The Future is Better Than You Think, which I highly recommend you read. It describes what is an abundance mindset, one that shifts from cynicism to hope, and from pessimism to optimism. This mindset shift is especially important when tackling challenging problems.
Peter cites Matt Ridley in his email blast. Matt is an award-winning author of a book called The Rational Optimist. He’s an Oxford-trained zoologist and science writer. He specializes in the origins and evolution of human behaviour.
Ridley describes how we are obsessed with the bad when he states, “It’s incredible, this moaning pessimism, this knee-jerk, things-are-going-downhill reaction from people living amid luxury and security that their ancestors would have died for. The tendency to see the emptiness of every glass is pervasive. It’s almost as if people cling to bad news like a comfort blanket.”
Ridley blames our cognitive biases and evolutionary psychology for this mindset. He identifies cognitive bias as “loss aversion,” a tendency for people to regret a loss more than a similar gain. Loss aversion is often what keeps people stuck in ruts. It’s an unwillingness to change bad habits for fear that the change will leave them in a worse place than before.
But loss aversion isn’t the only thing Ridley contends. He notes “there could be an evolutionary psychology component. We might be gloomy because gloomy people managed to avoid getting eaten by lions in the Pleistocene.”
Ridley believes that this divorce from reality is doing us more harm than good. So he sees the need for us to fight back as he states, “It’s become a habit now for me to challenge such remarks [bad news]. Whenever somebody says something grumpy about the world, I just try to think of the other side of the argument and—after examining the facts—again and again, I find they have it the wrong way round.”
This conversion to positive thinking doesn’t happen overnight for anyone. The answer states Ridley is to look at the data and the science to counter the glum future argument.
About 25 years ago, Ridley noticed that the issue of acid rain had doom experts predicting forests would be decimated in the near future. Acid rain was once considered the planet’s most dire environmental threat. It was caused by the burning of fossil fuels, particularly coal, causing large amounts of sulphur dioxide and nitrogen oxides to accumulate in the atmosphere causing an acidic shift in the pH balance of precipitation. Hence the name.
First described by Robert Angus Smith, a British scientist, in 1852, acid rain went from a curiosity to a catastrophe. By the late 1970s, it was seen as an existential threat described by a member of the Canadian cabinet as “one of the most devastating forms of pollution imaginable, an insidious malaria of the biosphere.” Back then, Ridley agreed with this opinion. But as the decades passed, he noted that data wasn’t supporting this predicted outcome. He writes, “It wasn’t just that the trees weren’t dying, it was that they never had been dying—not in any unusual numbers and not because of acid rain. Forests that were supposed to have vanished altogether were healthier than ever.”
It should be noted that human innovation played a role in averting an acid rain disaster. Amendments to the US Clean Air Act were adopted, Cars and trucks got catalytic converters. The end result was a 94% reduction in sulphur dioxide emissions from 31 million tons in 1970 to just 1.8 million in 2021. Nitrogen oxide emissions also declined from over 27 million tons to 7.6 million during the same period.
Ridley’s observation was about aid rain damaging forests. It clearly was not. This made him look for other dark prophecies being pronounced in the public forum. For example, he noted cancer rates weren’t rising even though stories in the press suggested otherwise. In reality cancer rates were steadily falling. He then found other headlines predicting a dire future that were unsupported by the evidence despite the media’s profound and gloomy pessimism. This led Ridley to wonder if the really negative predictions weren’t coming true, was the assumption that the world was getting worse absolutely wrong? He began examining global trends looking at the economy, health, the environment and more. And that’s how The Rational Optimist was born with its argument of optimism over pessimism.
The last few years have felt chaotic, unpredictable, and downright scary at times. But pause and zoom out to take a broader perspective, and it becomes clearer that we are living in a most exciting period in human history. Why is this true? Because exponential technologies are giving us unparalleled access to knowledge, experts, and global communications at little-to-no cost.
One of the best ways to see this is to look at how the Internet has grown. In 2010, under 2 billion people were connected to it. Now the number has surpassed 5 billion, and by 2030 will rise to 7.5 billion or almost 90% of us on the planet.
Coupled with human participants on the Internet is a growing population of technology in the form of sensors, artificial intelligence (AI) tools, robots, and more. The Internet is making it possible to create an intelligent brain for the entire planet. It is this intelligence layer that is enabling us to solve global problems. It helps to mobilize resources across the globe. And this is the core of the abundance mindset, the idea that our human progress will bring us more abundance each and every year as the future unfolds.
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An Afterword:
When I began Techso Mogro back in 2009, I was driven by a love of history, science, and technology. I believe that history provides a guide to better understand where we are going in the future. Even though collectively humanity has experienced numerous bumps on our path to progress, there is a record of how our curiosity and ability to problem solve makes it possible to overcome the profound challenges we encounter on our path to the future.
A good example is the COVID-19 pandemic. Two-and-a-half years ago this virus spread around the world at lightning speed facilitated by our interconnectedness. So one aspect of our technological prowess fueled the crisis. But at the same time another technological advancement led us to biomedical breakthroughs as vaccines emerged in months rather than years because we could read the genetic information of almost every living thing on our planet including this virus. Advances in genetics have not only created the means to save billions of lives through rapid vaccine development, but this technology also is going to help to achieve a future of food security for the billions who come after us.
Peter in talking about Ridley’s acid rain example didn’t include the positive story of human ingenuity coming to the rescue of our lakes although he mentioned catalytic converters. What he could have described were the development of smokestack scrubbers to remove acid-rain-creating materials and chemicals from the air. Today, modified versions of that technology is helping us to capture CO2 from smokestack emissions to reduce climate change impacts.
The current existential threat that produces gloom and doom headlines is climate change. In some respect I am as guilty as many others in spreading the dire warnings. But I also believe we cannot afford to wallow in the woe, but rather should take heart and watch how leading inventive and curious minds are developing solutions to help the planet and ensure a sustainable future for all its inhabitants.
I know Peter calls this positivism an abundance mindset. But others have described it as the power of positive thinking.
]]>These include augmented human longevity, the surging smart economy, AI-human collaboration, urbanized cellular agriculture, and high-bandwidth brain-computer interfaces to name just a few.
So welcome to a new era of runaway technological booms and watershed disruptive moments that will lead to extraordinary future abundance.
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And just as I was finishing it Peter Diamandis sent one of his missives about robots as friends and employees. Robots and artificial intelligence are finding their way into both our personal and business lives. Peter sees them as entities not to be feared and has provided the following to reinforce his argument. I hope you enjoy the read.
Camel racing is a centuries-old tradition in the Middle East—think the Kentucky Derby for sheikhs—and it’s one of the richest sports on Earth. However, it’s the jockeys who have changed the most.
Twenty years ago, camels were ridden by children—the lightest possible riders—but general principle, injury, and death led to a humanitarian outcry. So, both the UAE and Qatar banned the practice, replacing children with an even lighter saddle occupant: the robot jockey.
Today, in camel racing, robot jockeys are the norm. Exactly like traditional jockeys, these robotic replacements sit on a saddle, steer with the reins, and prod with a whip. The jockeys are small, about a foot high, and light, weighing between five and eight pounds, with skinny hinged arms.
Of course, my point isn’t that there’s a bevy of entrepreneurial possibilities in camel racing. It’s that robotics, another exponential technology long mired in deception, is now heading for disruption.
According to a report by the Littler Workplace Policy Institute: “Robotics is the fastest growing industry in the world, poised to become the largest in the next decade.” Which is to say, robot jockeys are just the beginning.
Consider Moxie, the brainchild of NASA roboticist Paolo Pirjanian, Co-founder of Embodied, Inc. Moxie is a small, Pixar-like robot with large eyes and a cute, dynamic virtual face. Moxie converses with children in a natural, lifelike manner, becoming a personalized companion to them. You can continuously talk to Moxie (as opposed to simply saying “Hi, Alexa”), and the AI knows to take its turn allowing for a fluid conversation and storytelling.
Importantly, Moxie doesn’t try to be too human or perfect—in fact, that’s where many other robotics companies have failed. Instead, Moxie has a key human-like element: it makes mistakes and learns.
Rather than a full prebuilt chatbot, Moxie has an actual personality and learns over the course of multiple interactions which “unlock” new content and behaviours, further engaging a child in a goal-oriented manner. (If you have young kids, or kids with learning disabilities, please check out Moxie at https://embodied.com/.)
Besides human-like, user-friendly robots, we’re also seeing exponential progress in robotic agility, mobility, and diversity.
Enabled by a new generation of sensors and actuators, and driven by near-unlimited computing and artificial intelligence, there’s a Cambrian explosion in robotics, with species of all sizes, shapes, and modes of mobility crawling out of the muck of the lab and onto the terra firma of the marketplace.
Of course, what is driving the current robotics revolution is the convergence of exponential advances in computation and machine learning using neural networks. A lot of what today’s amazing walking, flying, dancing and talking robots can do is simply a result of cheaper, faster and more ubiquitous computation driving artificial intelligence. The second exponential advance is 3D printing, which is allowing researchers and tinkerers to design, build and test robotic parts faster. Finally, it’s all about advances in networks and sensors to collect and feed data to a robot’s algorithms.
Festo, for one example, has created a robot that flies like a bird. Boston Dynamics makes robots that climb, crawl, jump, and hop, and all while carrying heavy loads. Some of their bots can carry more than a hundred kilogram load. And recently Boston Dynamics put out a video showing their robots making really cool dance moves which seems to be even more impressive than watching them unpack boxes from the back of an 18-wheeler.
Incredible companies like Chef Robotics are putting robots to work in the food industry. The National Restaurant Association reported that in 2017, 37% of its members listed labour recruitment as their top challenge, up from 15% in 2015. This means long lines for you, food deserts with little fresh food, and inconsistent orders (aka not enough guacamole). Chef Robotics believes robots are the best solution to this problem.
What’s the allure of robots? Robots don’t unionize, don’t show up late, and don’t take lunch, and they can work on an assembly line for just a few dollars an hour. And as the cost of labour continues to increase there will come a crossover point when robots will be cheaper and better suited for certain jobs.
Indeed, the market for industrial robots has seen double-digit growth annually since 2013, and is expected to continue to grow 12,3% annually through to 2026.
A 2017 report by the McKinsey Global Institute concludes that almost 50% of tasks done by employees today are at high risk of being taken over by computers (AI and robots). Among these are data collection and processing, representing 51% of the activity in the American economy.
In China, Foxconn, the Chinese electronics manufacturer that builds Apple’s iPhone, made news back in 2013 when the skyrocketing demand for cell phones led to labour disputes, reports of harsh working conditions, even riots and suicides. In the aftermath of these reports, Foxconn has moved to automate 30% of its workforce, cutting 60,000 jobs in 2016 and replacing them with robots, a trend accelerated by the coronavirus pandemic.
Besides replacing blue-collar workforces, robots are invading many more fields. Consider the effect autonomous driving will have on the trucking industry, or surgical robots in healthcare, and companion robots for therapy and eldercare.
“If I were an exponential entrepreneur looking to create tremendous value,” says robotics expert Dan Barry, “I’d look for those jobs that are least enjoyable for humans to do … Given that the global market for unskilled labor is worth many trillions of dollars, I would say this is a huge opportunity.”
Startup infrastructure dedicated specifically to robotics continues to grow—the recent announcement of the Founder Institute partnering with the NASA Ames Research Center and MassRobotics to launch an AI and Robotics-focused accelerator is just one example.
At the same time, the continued exponential growth of AI, robotics, and other technologies, along with our improving understanding of human nature, are moving us to a world of true robotic colleagues and friends.
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