Jamie Metzl, author of Hacking Darwin, shares his views with Leaps.org on the future of genetics, tech, healthcare and more.
In Hacking Darwin, you describe how we may modify the human body with CRISPR technologies, initially to obtain unsurpassed sports performance and then to enhance other human characteristics. What would such power over human biology mean for the future of our civilization?
After nearly four billion years of evolution, our one species suddenly has the increasing ability to read, write, and hack the code of life. This will have massive implications across the board, including in human health and reproduction, plant and animal agriculture, energy and advanced materials, and data storage and computing, just to name a few. My book Hacking Darwin: Genetic Engineering and the Future of Humanity primarly explored how we are currently deploying and will increasingly use our capabilities to transform human life in novel ways. My next book, The Great Biohack: Recasting Life in an Age of Revolutionary Technology, coming out in May 2024, will examine the broader implications for all of life on Earth.
We humans will, over time, use these technologies on ourselves to solve problems and eventually to enhance our capabilities. We need to be extremely conservative, cautious, and careful in doing so, but doing so will almost certainly be part of our future as a species.
In electronics, Moore's law is an established theory that computing power doubles every 18 months. Is there any parallel to be drawn with genetic technologies?
The increase in speed and decrease in costs of genome sequencing have progressed far faster than Moore’s law. It took thirteen years and cost about a billion dollars to sequence the first human genome. Today it takes just a few hours and can cost as little as a hundred dollars to do a far better job. In 2012, Jennifer Doudna and Emmanuel Charpentier published the basic science paper outlining the CRISPR-cas9 genome editing tool that would eventually win them the Nobel prize. Only six years later, the first CRISPR babies were born in China. If it feels like technology is moving ever-faster, that’s because it is.
Let's turn to the topic of aging. Do you think that the field of genetics will advance fast enough to eventually increase maximal lifespan for a child born this year? How about for a person who is currently age 50?
The science of aging is definitely real, but that doesn’t mean we will live forever. Aging is a biological process subject to human manipulation. Decades of animal research shows that. This does not mean we will live forever, but it does me we will be able to do more to expand our healthspans, the period of our lives where we are able to live most vigorously.
The first thing we need to do is make sure everyone on earth has access to the resources necessary to live up to their potential. I live in New York City, and I can take a ten minute subway ride to a neighborhood where the average lifespan is over a decade shorter than in mine. This is true within societies and between countries as well. Secondly, we all can live more like people in the Blue Zones, parts of the world where people live longer, on average, than the rest of us. They get regular exercise, eat healthy foods, have strong social connections, etc. Finally, we will all benefit, over time, from more scientific interventions to extend our healthspan. This may include small molecule drugs like metformin, rapamycin, and NAD+ boosters, blood serum infusions, and many other things.
Science fiction has depicted a future where we will never get sick again, stay young longer or become immortal. Assuming that any of this is remotely possible, should we be afraid of such changes, even if they seem positive in some regards, because we can’t understand the full implications at this point?
Not all of these promises will be realized in full, but we will use these technologies to help us live healthier, longer lives. We will never become immortal becasue nothing lasts forever. We will always get sick, even if the balance of diseases we face shifts over time, as it has always done. It is healthy, and absolutely necessary, that we feel both hope and fear about this future. If we only feel hope, we will blind ourselves to the very real potential downsides. If we only feel fear, we will deny ourselves the very meaningful benefits these technologies have the potential to provide.
A fascinating chapter in Hacking Darwin is entitled The End of Sex. And you see that as a good thing?
We humans will always be a sexually reproducing species, it’s just that we’ll reproduce increasingly less through the physical act of sex. We’re already seeing this with IVF. As the benefits of technology assisted reproduction increase relative to reproduction through the act of sex, many people will come to see assisted reproduction as a better way to reduce risk and, over time, possibly increase benefits. We’ll still have sex for all the other wonderful reasons we have it today, just less for reproduction. There will always be a critical place in our world for Italian romantics!
What are dangers of genetic hackers, perhaps especially if everyone’s DNA is eventually transcribed for medical purposes and available on the internet and in the cloud?
The sky is really the limit for how we can use gentic technologies to do things we may want, and the sky is also the limit for potential harms. It’s quite easy to imagine scenarios in which malevolent actors create synthetic pathogens designed to wreak havoc, or where people steal and abuse other people’s genetic information. It wouldn’t even need to be malevolent actors. Even well-intentioned researchers making unintended mistakes could cause real harm, as we may have seen with COVID-19 if, as appears likely to me, the pandemic stems for a research related incident]. That’s why we need strong governance and regulatory systems to optimize benefits and minimize potential harms. I was honored to have served on the World Health Organization Expert Advisory Committee on Human Genome Editing, were we developed a proposed framework for how this might best be achieved.
You foresee the equivalent of a genetic arms race between the world's most powerful countries. In what sense are genetic technologies similar to weapons?
Genetic technologies could be used to create incredibly powerful bioweapons or to build gene drives with the potential to crash entire ecosystems. That’s why thoughtful regulation is in order. Because the benefits of mastering and deploying these technologies are so great, there’s also a real danger of a genetics arms race. This could be extremely dangerous and will need to be prevented.
In your book, you express concern that states lacking Western conceptions of human rights are especially prone to misusing the science of genetics. Does this same concern apply to private companies? How much can we trust them to control and wield these technologies?
This is a conversation about science and technology but it’s really a conversation about values. If we don’t agree on what core values should be promoted, it will be nearly impossible to agree on what actions do and do not make sense. We need norms, laws, and values frameworks that apply to everyone, including governments, corporations, researchers, healthcare providers, DiY bio hobbyists, and everyone else.
We have co-evolved with our technology for a very long time. Many of our deepest beliefs have formed in that context and will continue to do so. But as we take for ourselves the powers we have attributed to our various gods, many of these beliefs will be challenged. We can not and must not jettison our beliefs in the face of technology, and must instead make sure our most cherished values guide the application of our most powerful technologies.
A conversation on international norms is in full swing in the field of AI, prompted by the release of ChatGPT4 earlier this year. Are there ways in which it’s inefficient, shortsighted or otherwise problematic for these discussions on gene technologies, AI and other advances to be occurring in silos? In addition to more specific guidelines, is there something to be gained from developing a universal set of norms and values that applies more broadly to all innovation?
AI is yet another technology where the potential to do great good is tied to the potential to inflict signifcant harm. It makes no sense that we tend to treat each technology on its own rather than looking at the entire category of challenges. For sure, we need to very rapidly ramp up our efforts with regard to AI norm-setting, regulations, and governance at all levels. But just doing that will be kind of like generating a flu vaccine for each individual flu strain. Far better to build a universal flu vaccine addressing common elements of all flu viruses of concern.
That’s why we also need to be far more deliberate in both building a global operating systems based around the mutual responsibilities of our global interdependence and, under that umbrella, a broader system for helping us govern and regulate revolutionary technologies. Such a process might begin with a large international conference, the equivalent of Rio 1992 for climate change, but then quickly work to establish and share best practices, help build parallel institutions in all countries so people and governamts can talk with each other, and do everything possible to maximize benefits and minimize risks at all levels in an ongoing and dynamic way.
At what point might genetic enhancements lead to a reclassfication of modified humans as another species?
We’ll still all be fellow humans for a very, very long time. We already have lots of variation between us. That is the essence of biology. Will some humans, at some point in the future, leave Earth and spend generations elsewhere? I believe so. In those new environments, humans will evolve, over time, differently than those if us who remain on this planet? This may sound like science fiction, but the sci-fi future is coming at us faster than most people realize.
Is the concept of human being changing?
Yes. It always has and always will.
Another big question raised in your book: what limits should we impose on the freedom to manipulate genetics?
Different societies will come to different conclusion on this critical question. I am sympathetic to the argument that people should have lots of say over their own bodies, which why I support abortion rights even though I recognize that an abortion can be a violent procedure. But it would be insane and self-defeating to say that individuals have an unlimited right to manipulate their own or their future children’s heritable genetics. The future of human life is all of our concern and must be regulated, albeit wisely.
In some cases, such as when we have the ability to prevent a deadly genetic disroder, it might be highly ethical to manipulate other human beings. In other circumstances, the genetic engineering of humans might be highly unethical. The key point is to avoid asking this question in a binary manner. We need to weigh the costs and benefits of each type of intervention. We need societal and global infrastrucutres to do that well. We don’t yet have those but we need them badly.
Can you tell us more about your next book?
The Great Biohack: Recasting Lifee in an Age of Revolutionary Technology, will come out in May 2024. It explores what the intersecting AI, genetics, and biotechnology revolutions will mean for the future of life on earth, including our healthcare, agriculture, industry, computing, and everything else. We are at a transitional moment for life on earth, equivalent to the dawn of agriculture, electricity, and industrialization. The key differentiator between better and worse outcomes is what we do today, at this early stage of this new transformation. The book describes what’s happening, what’s at stake, and what we each and all can and, frankly, must do to build the type of future we’d like to inhabit.
You’ve been a leader of international efforts calling for a full investigation into COVID-19 origins and are the founder of the global movement OneShared.World. What problem are you trying to solve through OneShared.World?
The biggest challenge we face today is the mismatch between the nature of our biggest problems, global and common, and the absence of a sufficient framework for addressing that entire category of challenges. The totally avoidable COVID-19 pandemic is one example of the extremet costs of the status quo. OneShared.World is our effort to fight for an upgrade in our world’s global operating system, based around the mutual responsibilities of interdependence. We’ve had global OS upgrades before after the Thirty Years War and after World War II, but wouldn’t it be better to make the necessary changes now to prevent a crisis of that level stemming from a nuclear war, ecosystem collapse, or deadlier synthetic biology pandemic rather than waiting until after? Revolutionary science is a global issue that must be wisely managed at every level if it is to be wisely managed at all.
How do we ensure that revolutionary technologies benefit humanity instead of undermining it?
That is the essential question. It’s why I’ve written Hacking Darwin, am writing The Great Biohack, and doing the rest of my work. If we want scietific revolutions to help, rather than hurt, us, we must all play a role building that future. This isn’t just a conversation about science, it’s about how we can draw on our most cherished values to guide the optimal development of science and technology for the common good. That must be everyone’s business.
Portions of this interview were first published in Grassia (Italy) and Zen Portugal.
Jamie Metzl is one of the world’s leading technology and healthcare futurists and author of the bestselling book, Hacking Darwin: Genetic Engineering and the Future of Humanity, which has been translated into 15 languages. In 2019, he was appointed to the World Health Organization expert advisory committee on human genome editing. Jamie is a faculty member of Singularity University and NextMed Health, a Senior Fellow of the Atlantic Council, and Founder and Chair of the global social movement, OneShared.World.
Called “the original COVID-19 whistleblower,” his pioneering role advocating for a full investigation into the origins of the COVID-19 pandemic has been featured in 60 Minutes, the New York Times, and most major media across the globe, and he was the lead witness in the first congressional hearings on this topic. Jamie previously served in the U.S. National Security Council, State Department, and Senate Foreign Relations Committee and with the United Nations in Cambodia. Jamie appears regularly on national and international media and his syndicated columns and other writing in science, technology, and global affairs are featured in publications around the world.
Jamie sits on advisory boards for multiple biotechnology and other companies and is Special Strategist to the WisdomTree BioRevolution Exchange Traded Fund. In addition to Hacking Darwin, he is author of a history of the Cambodian genocide, the historical novel The Depths of the Sea, and the genetics sci-fi thrillers Genesis Code and Eternal Sonata. His next book, The Great Biohack: Recasting Life in an age of Revolutionary Technology, will be published by Hachette in May 2024. Jamie holds a Ph.D. from Oxford, a law degree from Harvard, and an undergraduate degree from Brown and is an avid ironman triathlete and ultramarathon runner.
Doctors worry that fungal pathogens may cause the next pandemic.
Although C. auris typically doesn’t sicken healthy people, it afflicts immunocompromised hospital patients and may cause severe infections that can lead to sepsis, a life-threatening condition in which the overwhelmed immune system begins to attack the body’s own organs. Between 30 and 60 percent of patients who contract a C. auris infection die from it, according to the CDC. People who are undergoing stem cell transplants, have catheters or have taken antifungal or antibiotic medicines are at highest risk. “We’re coming to a perfect storm of increasing resistance rates, increasing numbers of immunosuppressed patients worldwide and a bug that is adapting to higher temperatures as the climate changes,” says Prabhavathi Fernandes, chair of the National BioDefense Science Board.
Most Candida species aren’t well-adapted to our body temperatures so they aren’t a threat. C. auris, however, thrives at human body temperatures.
Although medical professionals aren’t concerned at this point about C. auris evolving to affect healthy people, they worry that its presence in hospitals can turn routine surgeries into life-threatening calamities. “It’s coming,” says Fernandes. “It’s just a matter of time.”
An emerging global threat
“Fungi are found in the environment,” explains Fernandes, so Candida spores can easily wind up on people’s skin. In hospitals, they can be transferred from contact with healthcare workers or contaminated surfaces. Most Candida species aren’t well-adapted to our body temperatures so they aren’t a threat. C. auris, however, thrives at human body temperatures. It can enter the body during medical treatments that break the skin—and cause an infection. Overall, fungal infections cost some $48 billion in the U.S. each year. And infection rates are increasing because, in an ironic twist, advanced medical therapies are enabling severely ill patients to live longer and, therefore, be exposed to this pathogen.
The first-ever case of a C. auris infection was reported in Japan in 2009, although an analysis of Candida samples dated the earliest strain to a 1996 sample from South Korea. Since then, five separate varieties – called clades, which are similar to strains among bacteria – developed independently in different geographies: South Asia, East Asia, South Africa, South America and, recently, Iran. So far, C. auris infections have been reported in 35 countries.
In the U.S., the first infection was reported in 2016, and the CDC started tracking it nationally two years later. During that time, 5,654 cases have been reported to the CDC, which only tracks U.S. data.
What’s more notable than the number of cases is their rate of increase. In 2016, new cases increased by 175 percent and, on average, they have approximately doubled every year. From 2016 through 2022, the number of infections jumped from 63 to 2,377, a roughly 37-fold increase.
“This reminds me of what we saw with epidemics from 2013 through 2020… with Ebola, Zika and the COVID-19 pandemic,” says Robin Robinson, CEO of Spriovas and founding director of the Biomedical Advanced Research and Development Authority (BARDA), which is part of the U.S. Department of Health and Human Services. These epidemics started with a hockey stick trajectory, Robinson says—a gradual growth leading to a sharp spike, just like the shape of a hockey stick.
Another challenge is that right now medics don’t have rapid diagnostic tests for fungal infections. Currently, patients are often misdiagnosed because C. auris resembles several other easily treated fungi. Or they are diagnosed long after the infection begins and is harder to treat.
The problem is that existing diagnostics tests can only identify C. auris once it reaches the bloodstream. Yet, because this pathogen infects bodily tissues first, it should be possible to catch it much earlier before it becomes life-threatening. “We have to diagnose it before it reaches the bloodstream,” Walsh says.
The most alarming fact is that some Candida infections no longer respond to standard therapeutics.
“We need to focus on rapid diagnostic tests that do not rely on a positive blood culture,” says John Sperzel, president and CEO of T2 Biosystems, a company specializing in diagnostics solutions. Blood cultures typically take two to three days for the concentration of Candida to become large enough to detect. The company’s novel test detects about 90 percent of Candida species within three to five hours—thanks to its ability to spot minute quantities of the pathogen in blood samples instead of waiting for them to incubate and proliferate.
Unlike other Candida species C. auris thrives at human body temperatures
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Tackling the resistance challenge
The most alarming fact is that some Candida infections no longer respond to standard therapeutics. The number of cases that stopped responding to echinocandin, the first-line therapy for most Candida infections, tripled in 2020, according to a study by the CDC.
Now, each of the first four clades shows varying levels of resistance to all three commonly prescribed classes of antifungal medications, such as azoles, echinocandins, and polyenes. For example, 97 percent of infections from C. auris Clade I are resistant to fluconazole, 54 percent to voriconazole and 30 percent of amphotericin. Nearly half are resistant to multiple antifungal drugs. Even with Clade II fungi, which has the least resistance of all the clades, 11 to 14 percent have become resistant to fluconazole.
Anti-fungal therapies typically target specific chemical compounds present on fungi’s cell membranes, but not on human cells—otherwise the medicine would cause damage to our own tissues. Fluconazole and other azole antifungals target a compound called ergosterol, preventing the fungal cells from replicating. Over the years, however, C. auris evolved to resist it, so existing fungal medications don’t work as well anymore.
A newer class of drugs called echinocandins targets a different part of the fungal cell. “The echinocandins – like caspofungin – inhibit (a part of the fungi) involved in making glucan, which is an essential component of the fungal cell wall and is not found in human cells,” Fernandes says. New antifungal treatments are needed, she adds, but there are only a few magic bullets that will hit just the fungus and not the human cells.
Research to fight infections also has been challenged by a lack of government support. That is changing now that BARDA is requesting proposals to develop novel antifungals. “The scope includes C. auris, as well as antifungals following a radiological/nuclear emergency, says BARDA spokesperson Elleen Kane.
The remaining challenge is the number of patients available to participate in clinical trials. Large numbers are needed, but the available patients are quite sick and often die before trials can be completed. Consequently, few biopharmaceutical companies are developing new treatments for C. auris.
ClinicalTrials.gov reports only two drugs in development for invasive C. auris infections—those than can spread throughout the body rather than localize in one particular area, like throat or vaginal infections: ibrexafungerp by Scynexis, Inc., fosmanogepix, by Pfizer.
Scynexis’ ibrexafungerp appears active against C. auris and other emerging, drug-resistant pathogens. The FDA recently approved it as a therapy for vaginal yeast infections and it is undergoing Phase III clinical trials against invasive candidiasis in an attempt to keep the infection from spreading.
“Ibreafungerp is structurally different from other echinocandins,” Fernandes says, because it targets a different part of the fungus. “We’re lucky it has activity against C. auris.”
Pfizer’s fosmanogepix is in Phase II clinical trials for patients with invasive fungal infections caused by multiple Candida species. Results are showing significantly better survival rates for people taking fosmanogepix.
Although C. auris does pose a serious threat to healthcare worldwide, scientists try to stay optimistic—because they recognized the problem early enough, they might have solutions in place before the perfect storm hits. “There is a bit of hope,” says Robinson. “BARDA has finally been able to fund the development of new antifungal agents and, hopefully, this year we can get several new classes of antifungals into development.”
A space elevator would be cheaper and cleaner than using rockets
This is making space accessible to scientists, startups, and tourists who never could have afforded it previously, but the cheapest way to reach orbit might not be a rocket at all — it could be an elevator.
The space elevator
The seeds for a space elevator were first planted by Russian scientist Konstantin Tsiolkovsky in 1895, who, after visiting the 1,000-foot (305 m) Eiffel Tower, published a paper theorizing about the construction of a structure 22,000 miles (35,400 km) high.
This would provide access to geostationary orbit, an altitude where objects appear to remain fixed above Earth’s surface, but Tsiolkovsky conceded that no material could support the weight of such a tower.
We could then send electrically powered “climber” vehicles up and down the tether to deliver payloads to any Earth orbit.
In 1959, soon after Sputnik, Russian engineer Yuri N. Artsutanov proposed a way around this issue: instead of building a space elevator from the ground up, start at the top. More specifically, he suggested placing a satellite in geostationary orbit and dropping a tether from it down to Earth’s equator. As the tether descended, the satellite would ascend. Once attached to Earth’s surface, the tether would be kept taut, thanks to a combination of gravitational and centrifugal forces.
We could then send electrically powered “climber” vehicles up and down the tether to deliver payloads to any Earth orbit. According to physicist Bradley Edwards, who researched the concept for NASA about 20 years ago, it’d cost $10 billion and take 15 years to build a space elevator, but once operational, the cost of sending a payload to any Earth orbit could be as low as $100 per pound.
“Once you reduce the cost to almost a Fed-Ex kind of level, it opens the doors to lots of people, lots of countries, and lots of companies to get involved in space,” Edwards told Space.com in 2005.
In addition to the economic advantages, a space elevator would also be cleaner than using rockets — there’d be no burning of fuel, no harmful greenhouse emissions — and the new transport system wouldn’t contribute to the problem of space junk to the same degree that expendable rockets do.
So, why don’t we have one yet?
Tether troubles
Edwards wrote in his report for NASA that all of the technology needed to build a space elevator already existed except the material needed to build the tether, which needs to be light but also strong enough to withstand all the huge forces acting upon it.
The good news, according to the report, was that the perfect material — ultra-strong, ultra-tiny “nanotubes” of carbon — would be available in just two years.
“[S]teel is not strong enough, neither is Kevlar, carbon fiber, spider silk, or any other material other than carbon nanotubes,” wrote Edwards. “Fortunately for us, carbon nanotube research is extremely hot right now, and it is progressing quickly to commercial production.”Unfortunately, he misjudged how hard it would be to synthesize carbon nanotubes — to date, no one has been able to grow one longer than 21 inches (53 cm).
Further research into the material revealed that it tends to fray under extreme stress, too, meaning even if we could manufacture carbon nanotubes at the lengths needed, they’d be at risk of snapping, not only destroying the space elevator, but threatening lives on Earth.
Looking ahead
Carbon nanotubes might have been the early frontrunner as the tether material for space elevators, but there are other options, including graphene, an essentially two-dimensional form of carbon that is already easier to scale up than nanotubes (though still not easy).
Contrary to Edwards’ report, Johns Hopkins University researchers Sean Sun and Dan Popescu say Kevlar fibers could work — we would just need to constantly repair the tether, the same way the human body constantly repairs its tendons.
“Using sensors and artificially intelligent software, it would be possible to model the whole tether mathematically so as to predict when, where, and how the fibers would break,” the researchers wrote in Aeon in 2018.
“When they did, speedy robotic climbers patrolling up and down the tether would replace them, adjusting the rate of maintenance and repair as needed — mimicking the sensitivity of biological processes,” they continued.Astronomers from the University of Cambridge and Columbia University also think Kevlar could work for a space elevator — if we built it from the moon, rather than Earth.
They call their concept the Spaceline, and the idea is that a tether attached to the moon’s surface could extend toward Earth’s geostationary orbit, held taut by the pull of our planet’s gravity. We could then use rockets to deliver payloads — and potentially people — to solar-powered climber robots positioned at the end of this 200,000+ mile long tether. The bots could then travel up the line to the moon’s surface.
This wouldn’t eliminate the need for rockets to get into Earth’s orbit, but it would be a cheaper way to get to the moon. The forces acting on a lunar space elevator wouldn’t be as strong as one extending from Earth’s surface, either, according to the researchers, opening up more options for tether materials.
“[T]he necessary strength of the material is much lower than an Earth-based elevator — and thus it could be built from fibers that are already mass-produced … and relatively affordable,” they wrote in a paper shared on the preprint server arXiv.
After riding up the Earth-based space elevator, a capsule would fly to a space station attached to the tether of the moon-based one.
Electrically powered climber capsules could go up down the tether to deliver payloads to any Earth orbit.
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Some Chinese researchers, meanwhile, aren’t giving up on the idea of using carbon nanotubes for a space elevator — in 2018, a team from Tsinghua University revealed that they’d developed nanotubes that they say are strong enough for a tether.
The researchers are still working on the issue of scaling up production, but in 2021, state-owned news outlet Xinhua released a video depicting an in-development concept, called “Sky Ladder,” that would consist of space elevators above Earth and the moon.
After riding up the Earth-based space elevator, a capsule would fly to a space station attached to the tether of the moon-based one. If the project could be pulled off — a huge if — China predicts Sky Ladder could cut the cost of sending people and goods to the moon by 96 percent.
The bottom line
In the 120 years since Tsiolkovsky looked at the Eiffel Tower and thought way bigger, tremendous progress has been made developing materials with the properties needed for a space elevator. At this point, it seems likely we could one day have a material that can be manufactured at the scale needed for a tether — but by the time that happens, the need for a space elevator may have evaporated.
Several aerospace companies are making progress with their own reusable rockets, and as those join the market with SpaceX, competition could cause launch prices to fall further.
California startup SpinLaunch, meanwhile, is developing a massive centrifuge to fling payloads into space, where much smaller rockets can propel them into orbit. If the company succeeds (another one of those big ifs), it says the system would slash the amount of fuel needed to reach orbit by 70 percent.
Even if SpinLaunch doesn’t get off the ground, several groups are developing environmentally friendly rocket fuels that produce far fewer (or no) harmful emissions. More work is needed to efficiently scale up their production, but overcoming that hurdle will likely be far easier than building a 22,000-mile (35,400-km) elevator to space.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
