A New Web Could be Coming. Will It Improve Human Health?
A number of emerging technologies are in the mix to define Web3, the next era of the digital age. They could contribute to our overall health and well-being.
The Web has provided numerous benefits over the years, but users have also experienced issues related to privacy, cybersecurity, income inequality, and addiction which negatively impact their quality of life. In important ways, the Web has yet to meet its potential to support human health.
Now, engineers are in the process of developing a new version of the Web, called Web3, which would seek to address the Web’s current shortcomings through a mix of new technologies.
It could also create new problems. Industrial revolutions, including new versions of the Web, have trade-offs. While many activists tend to focus on the negative aspects of Web3 technologies, they overlook some of the potential benefits to health and the environment that aren’t as easily quantifiable such as less stressful lives, fewer hours required for work, and a higher standard of living. What emerging technologies are in the mix to define the new era of the digital age, and how will they contribute to our overall health and well-being?
In order to answer these questions, I have identified three major trends that may help define the future landscape of Web3. These include more powerful machine intelligence that could drive improvements in healthcare, decentralized banking systems that allow consumers to bypass middlemen, and self-driving cars with potential to reduce pollution. However, it is the successes of the enabling technologies that support these goals—improvements in AI, blockchain and smart contracts, and fog computing—that will ultimately define Web3.
Machine Intelligence and Diagnosing Diseases
While the internet is the physical network equipment and computers that keep the world connected, the Web is one of the services that run on the internet. In 1989, British scientist Tim Berners-Lee invented the World Wide Web and, when Web1 went live in 1991, it consisted of pages of text connected by hyperlinks. It remained that way until 2004 with the introduction of Web2, which provided social media websites and let users generate content in addition to consuming it passively.
The Semantic Web could expand the impact of new cognitive skills for machines by feeding data to AI in more readily accessible formats. This will make machines better at solving hard problems such as diagnosing and treating complex diseases.
For the most part, Web2 is what we still have today but, from the beginning, Berners-Lee, now an MIT professor, envisaged a much more sophisticated version of the Web. Known as the Semantic Web, it would not only store data, but actually know what it means. The goal is to make all information on the Internet “machine-readable,” so it can be easily processed by computers, like an Excel sheet full of numbers as opposed to human language. We are now in the early stages of the Semantic Web, which incorporates his vision. For example, there is already a cloud of datasets that links thousands of servers without any form of centralized control. However, due to the costs and technological hurdles related to converting human language into something that computers can understand, the Semantic Web remains an ongoing project.
Currently, AI is only able to perform certain tasks, but it can already make healthcare business practices more efficient by leveraging deep learning to analyze data in supply chains. DeepMind, the company that developed AI for defeating chess masters, has also made huge advances in figuring out protein folding and misfolding, which is responsible for some diseases. Currently, AI is not that useful for diagnosing and treating many complex diseases. This is because deep learning is probabilistic, not causal. So, it is able to understand correlation, but not cause and effect.
Like the Web, though, AI is evolving, and the limitations of deep learning could be overcome in the foreseeable future. A number of government programs and private initiatives are dedicated to better understanding human brain complexity and equipping machines with reasoning, common sense, and the ability to understand cause and effect. The Semantic Web could expand the impact of these new cognitive skills by feeding data to AI in more readily accessible formats. This will make machines better at solving hard problems such as diagnosing and treating complex diseases, which involve genetic, lifestyle, and environment factors. These powerful AIs in the realm of healthcare could become an enduring and important feature of Web3.
Blockchain, Smart Contracts and Income Inequality
The Web2 version of the digital age was certainly impactful in altering our lifestyle both positively and negatively. This is predominately because of the business model used by companies such as Meta (formerly Facebook) and Google. By providing useful products like search engines, these companies have lured consumers into giving away their personal data for free, and the companies use this information to detect buying patterns in order to sell advertising. The digital economy made high tech companies billions of dollars while many users became underemployed or jobless.
In recent years, a similar model has been emerging in the realm of genetics. Personalized genomic companies charge a relatively small fee to analyze a fraction of our genes and provide probabilities of having specific medical conditions. While individual data is not valuable, cumulative data is helpful for deep learning. So, these companies can sell the anonymous DNA data to pharmaceutical companies for millions of dollars.
As these companies improve their ability to collect even more data about our genetic vulnerabilities, the technologies of Web3 could protect consumers from giving it away for free. An emerging technology called blockchain is able to provide a Web-based ledger of financial transactions with checks and balances to ensure that its records cannot be faked or altered. It has yet to reach mass adoption by the public, but the computer scientist Jaron Lanier has proposed storing our genomes and electronic health records in blockchain, utilizing electronic smart contracts between individuals and pharma healthcare industry. Micropayments could then be made to individuals for their data, using cryptocurrency.
These individual payments could become more lucrative in the coming years especially as researchers learn how to fully interpret and apply a person’s genetic data. In this way, blockchain could lead to improvements in income inequality, which currently drives health problems and other challenges for many. A number of start-ups are using this business model which has secure data and eliminates middlemen who don’t create any value, while compensating and protecting the privacy of individuals who contribute their health data.
Autonomous Vehicles, Fog Computing and Pollution
A number of trends indicate that modernizing the transportation industry would address a myriad of problems with public health, productivity and the environment. Autonomous vehicles (AVs) could help usher in this new era of transportation, and these AVs would need to be supported by Web3 technologies.
Automobile accidents are the second leading cause of death worldwide, with roughly 1.3 million fatalities annually, according to the World Health Organization. Some estimates suggest that replacing human drivers with AVs could eliminate as many as a million global fatalities annually. Shared AVs would help to reduce traffic congestion that wastes time and fuel, and electric vehicles would help minimize greenhouse gases.
To reap the benefits from replacing gas vehicles with electric, societies will need an infrastructure that enables self-driving cars to communicate with each other. Most data processing in computers is performed using von Neumann architecture, where the data memory and the processor are in two different places. Today, that typically means cloud computing. With self-driving cars, when cameras and sensors generate data to detect objects on the roads, processors will need to rapidly analyze the data and make real-time decisions regarding acceleration, braking, and steering. However, cloud computing is susceptible to latency issues.
One solution to latency is moving processing and data storage closer to where it is needed to improve response times. Edge computing, for example, places the processor at the site where the data is generated. Most new human-driven vehicles contain anywhere from 30 to 100 electronic control units (ECUs) that process data and control electrical systems in vehicles. These embedded systems, typically in the dashboard, control different applications such as airbags, steering, brakes, etc. ECUs process data generated by cameras and sensors in AVs and make crucial decisions on how they operate.
Self-driving cars can benefit by communicating with each other for navigation in the same way that bacteria and animals use swarm intelligence for tasks involving groups. Researchers are currently investigating fog computing which utilizes servers along highways for faster and more reliable navigation and for communicating data analytics among driverless cars.
The Future Landscape of Web3 is Uncertain
The future of Web3 has many possibilities. However, there is no guarantee that blockchain, smart contracts, and fog computing will achieve public acceptance and market saturation or prevail over other technologies or the status quo of Web2. It is also uncertain if or when the breakthroughs in AI will occur that could eradicate complex diseases through Web3.
An example of this uncertainty is the metaverse, which combines blockchain with virtual reality. Currently, the metaverse is primarily used for gaming and recreational use until its infrastructure is further developed. Researchers are interested in the long-term mental health effects of virtual reality, both positive and negative. Using avatars, or virtual representations of humans, in the metaverse, users have greater control of their environment and chosen identities. But, it is unclear what negative mental health effects will occur. As far as regulations, the metaverse is still in the Wild West stage, and bullying or even murder will likely take place. Also, there will be a point where virtual worlds like the metaverse will become so immersive that we won't want to leave them, according to Meta’s Zuckerberg.
The metaverse would rely on virtual reality technology that was developed many years ago, and adoption has been slower than some experts predicted. But most emerging technologies, including other examples related to Web3, follow a similar, nonlinear pattern of development that Gartner has represented in graphical form using the S-curve. To develop a technology forecast for Web3, you can follow the progress along the curve from proof of concept to a particular goal. After a series of successes and failures, entrepreneurs will continue to improve their products until each emerging technology fails or achieves mainstream adoption by the public.
What mix of emerging technologies ultimately defines Web3 will likely be determined by the benefits they provide to society—including whether and how they improve health—how they stimulate the digital economy, and how they address the significant shortcomings of Web2.
Pioneering XPRIZEs, Longevity and Mindset with Dr. Peter Diamandis
XPRIZE founder and chairman Peter Diamandis launches XPRIZE Healthspan at an event on November 29.
A new competition by the XPRIZE Foundation is offering $101 million to researchers who discover therapies that give a boost to people aged 65-80 so their bodies perform more like when they were middle-aged.
For today’s podcast episode, I talked with Dr. Peter Diamandis, XPRIZE’s founder and executive chairman. Under Peter’s leadership, XPRIZE has launched 27 previous competitions with over $300 million in prize purses. The latest contest aims to enhance healthspan, or the period of life when older people can play with their grandkids without any restriction, disability or disease. Such breakthroughs could help prevent chronic diseases that are closely linked to aging. These illnesses are costly to manage and threaten to overwhelm the healthcare system, as the number of Americans over age 65 is rising fast.
In this competition, called XPRIZE Healthspan, multiple awards are available, depending on what’s achieved, with support from the nonprofit Hevolution Foundation and Chip Wilson, the founder of Lululemon and nonprofit SOLVE FSHD. The biggest prize, $81 million, is for improvements in cognition, muscle and immunity by 20 years. An improvement of 15 years will net $71 million, and 10 years will net $61 million.
In our conversation for this episode, Peter talks about his plans for XPRIZE Healthspan and why exponential technologies make the current era - even with all of its challenges - the most exciting time in human history. We discuss the best mental outlook that supports a person in becoming truly innovative, as well as the downsides of too much risk aversion. We talk about how to overcome the negativity bias in ourselves and in mainstream media, how Peter has shifted his own mindset to become more positive over the years, how to inspire a culture of innovation, Peter’s personal recommendations for lifestyle strategies to live longer and healthier, the innovations we can expect in various fields by 2030, the future of education and the importance of democratizing tech and innovation.
In addition to Peter’s pioneering leadership of XPRIZE, he is also the Executive Founder of Singularity University. In 2014, he was named by Fortune as one of the “World’s 50 Greatest Leaders.” As an entrepreneur, he’s started over 25 companies in the areas of health-tech, space, venture capital and education. He’s Co-founder and Vice-Chairman of two public companies, Celularity and Vaxxinity, plus being Co-founder & Chairman of Fountain Life, a fully-integrated platform delivering predictive, preventative, personalized and data-driven health. He also serves as Co-founder of BOLD Capital Partners, a venture fund with a half-billion dollars under management being invested in exponential technologies and longevity companies. Peter is a New York Times Bestselling author of four books, noted during our conversation and in the show notes of this episode. He has degrees in molecular genetics and aerospace engineering from MIT and holds an M.D. from Harvard Medical School.
Show links
- Peter Diamandis bio
- New XPRIZE Healthspan
- Peter Diamandis books
- 27 XPRIZE competitions and counting
- Life Force by Peter Diamandis and Tony Robbins
- Peter Diamandis Twitter
- Longevity Insider newsletter – AI identifies the news
- Peter Diamandis Longevity Handbook
- Hevolution funding for longevity
XPRIZE Founder Peter Diamandis speaks with Mehmoud Khan, CEO of Hevolution Foundation, at the launch of XPRIZE Healthspan.
Hevolution Foundation
Matt Fuchs is the editor-in-chief of Leaps.org and Making Sense of Science. He is also a contributing reporter to the Washington Post and has written for the New York Times, Time Magazine, WIRED and the Washington Post Magazine, among other outlets. Follow him @fuchswriter.
Important findings are starting to emerge from research on how genes shape the human response to the Covid virus.
From infections with no symptoms to why men are more likely to be hospitalized in the ICU and die of COVID-19, new research shows that your genes play a significant role
Early in the pandemic, genetic research focused on the virus because it was readily available. Plus, the virus contains only 30,000 bases in a dozen functional genes, so it's relatively easy and affordable to sequence. Additionally, the rapid mutation of the virus and its ability to escape antibody control fueled waves of different variants and provided a reason to follow viral genetics.
In comparison, there are many more genes of the human immune system and cellular functions that affect viral replication, with about 3.2 billion base pairs. Human studies require samples from large numbers of people, the analysis of each sample is vastly more complex, and sophisticated computer analysis often is required to make sense of the raw data. All of this takes time and large amounts of money, but important findings are beginning to emerge.
Asymptomatics
About half the people exposed to SARS-CoV-2, the virus that causes the COVID-19 disease, never develop symptoms of this disease, or their symptoms are so mild they often go unnoticed. One piece of understanding the phenomena came when researchers showed that exposure to OC43, a common coronavirus that results in symptoms of a cold, generates immune system T cells that also help protect against SARS-CoV-2.
Jill Hollenbach, an immunologist at the University of California at San Francisco, sought to identify the gene behind that immune protection. Most COVID-19 genetic studies are done with the most seriously ill patients because they are hospitalized and thus available. “But 99 percent of people who get it will never see the inside of a hospital for COVID-19,” she says. “They are home, they are not interacting with the health care system.”
Early in the pandemic, when most labs were shut down, she tapped into the National Bone Marrow Donor Program database. It contains detailed information on donor human leukocyte antigens (HLAs), key genes in the immune system that must match up between donor and recipient for successful transplants of marrow or organs. Each HLA can contain alleles, slight molecular differences in the DNA of the HLA, which can affect its function. Potential HLA combinations can number in the tens of thousands across the world, says Hollenbach, but each person has a smaller number of those possible variants.
She teamed up with the COVID-19 Citizen Science Study a smartphone-based study to track COVID-19 symptoms and outcomes, to ask persons in the bone marrow donor registry about COVID-19. The study enlisted more than 30,000 volunteers. Those volunteers already had their HLAs annotated by the registry, and 1,428 tested positive for the virus.
Analyzing five key HLAs, she found an allele in the gene HLA-B*15:01 that was significantly overrepresented in people who didn’t have any symptoms. The effect was even stronger if a person had inherited the allele from both parents; these persons were “more than eight times more likely to remain asymptomatic than persons who did not carry the genetic variant,” she says. Altogether this HLA was present in about 10 percent of the general European population but double that percentage in the asymptomatic group. Hollenbach and her colleagues were able confirm this in other different groups of patients.
What made the allele so potent against SARS-CoV-2? Part of the answer came from x-ray crystallography. A key element was the molecular shape of parts of the cold virus OC43 and SARS-CoV-2. They were virtually identical, and the allele could bind very tightly to them, present their molecular antigens to T cells, and generate an extremely potent T cell response to the viruses. And “for whatever reasons that generated a lot of memory T cells that are going to stick around for a long time,” says Hollenbach. “This T cell response is very early in infection and ramps up very quickly, even before the antibody response.”
Understanding the genetics of the immune response to SARS-CoV-2 is important because it provides clues into the conditions of T cells and antigens that support a response without any symptoms, she says. “It gives us an opportunity to think about whether this might be a vaccine design strategy.”
Dead men
A researcher at the Leibniz Institute of Virology in Hamburg Germany, Guelsah Gabriel, was drawn to a question at the other end of the COVID-19 spectrum: why men more likely to be hospitalized and die from the infection. It wasn't that men were any more likely to be exposed to the virus but more likely, how their immune system reacted to it
Several studies had noted that testosterone levels were significantly lower in men hospitalized with COVID-19. And, in general, the lower the testosterone, the worse the prognosis. A year after recovery, about 30 percent of men still had lower than normal levels of testosterone, a condition known as hypogonadism. Most of the men also had elevated levels of estradiol, a female hormone (https://pubmed.ncbi.nlm.nih.gov/34402750/).
Every cell has a sex, expressing receptors for male and female hormones on their surface. Hormones docking with these receptors affect the cells' internal function and the signals they send to other cells. The number and role of these receptors varies from tissue to tissue.
Gabriel began her search by examining whole exome sequences, the protein-coding part of the genome, for key enzymes involved in the metabolism of sex hormones. The research team quickly zeroed in on CYP19A1, an enzyme that converts testosterone to estradiol. The gene that produces this enzyme has a number of different alleles, the molecular variants that affect the enzyme's rate of metabolizing the sex hormones. One genetic variant, CYP19A1 (Thr201Met), is typically found in 6.2 percent of all people, both men and women, but remarkably, they found it in 68.7 percent of men who were hospitalized with COVID-19.
Lung surprise
Lungs are the tissue most affected in COVID-19 disease. Gabriel wondered if the virus might be affecting expression of their target gene in the lung so that it produces more of the enzyme that converts testosterone to estradiol. Studying cells in a petri dish, they saw no change in gene expression when they infected cells of lung tissue with influenza and the original SARS-CoV viruses that caused the SARS outbreak in 2002. But exposure to SARS-CoV-2, the virus responsible for COVID-19, increased gene expression up to 40-fold, Gabriel says.
Did the same thing happen in humans? Autopsy examination of patients in three different cites found that “CYP19A1 was abundantly expressed in the lungs of COVID-19 males but not those who died of other respiratory infections,” says Gabriel. This increased enzyme production led likely to higher levels of estradiol in the lungs of men, which “is highly inflammatory, damages the tissue, and can result in fibrosis or scarring that inhibits lung function and repair long after the virus itself has disappeared.” Somehow the virus had acquired the capacity to upregulate expression of CYP19A1.
Only two COVID-19 positive females showed increased expression of this gene. The menopause status of these women, or whether they were on hormone replacement therapy was not known. That could be important because female hormones have a protective effect for cardiovascular disease, which women often lose after going through menopause, especially if they don’t start hormone replacement therapy. That sex-specific protection might also extend to COVID-19 and merits further study.
The team was able to confirm their findings in golden hamsters, the animal model of choice for studying COVID-19. Testosterone levels in male animals dropped 5-fold three days after infection and began to recover as viral levels declined. CYP19A1 transcription increased up to 15-fold in the lungs of the male but not the females. The study authors wrote, “Virus replication in the male lungs was negatively associated with testosterone levels.”
The medical community studying COVID-19 has slowly come to recognize the importance of adipose tissue, or fat cells. They are known to express abundant levels of CYP19A1 and play a significant role as metabolic tissue in COVID-19. Gabriel adds, “One of the key findings of our study is that upon SARS-CoV-2 infection, the lung suddenly turns into a metabolic organ by highly expressing” CYP19A1.
She also found evidence that SARS-CoV-2 can infect the gonads of hamsters, thereby likely depressing circulating levels of sex hormones. The researchers did not have autopsy samples to confirm this in humans, but others have shown that the virus can replicate in those tissues.
A possible treatment
Back in the lab, substituting low and high doses of testosterone in SARS-COV-2 infected male hamsters had opposite effects depending on testosterone dosage used. Gabriel says that hormone levels can vary so much, depending on health status and age and even may change throughout the day, that “it probably is much better to inhibit the enzyme” produced by CYP19A1 than try to balance the hormones.
Results were better with letrozole, a drug approved to treat hypogonadism in males, which reduces estradiol levels. The drug also showed benefit in male hamsters in terms of less severe disease and faster recovery. She says more details need to be worked out in using letrozole to treat COVID-19, but they are talking with hospitals about clinical trials of the drug.
Gabriel has proposed a four hit explanation of how COVID-19 can be so deadly for men: the metabolic quartet. First is the genetic risk factor of CYP19A1 (Thr201Met), then comes SARS-CoV-2 infection that induces even greater expression of this gene and the deleterious increase of estradiol in the lung. Age-related hypogonadism and the heightened inflammation of obesity, known to affect CYP19A1 activity, are contributing factors in this deadly perfect storm of events.
Studying host genetics, says Gabriel, can reveal new mechanisms that yield promising avenues for further study. It’s also uniting different fields of science into a new, collaborative approach they’re calling “infection endocrinology,” she says.