A RACE TO THE BOTTOM
Most people first hear about nanotechnology through cinema. Science fiction screenwriters lean heavily on the concept to explain away some of the more far-fetched undertakings seen on screen. The mass-murdering robot in Terminator II used nanotechnology to shapeshift, Star Trek’s evil Borg civilization relies on nanobots to assimilate its victims, and various Marvel superheroes have utilized the technology to keep themselves alive long enough to sell more merchandise. In film and TV, nanotechnology represents the future, a far-flung place where cars fly, aliens invade, and—sometimes—people live forever. But in fact, nanotechnology has been used here in the real world for a very long time.
The Romans developed technology way ahead of their time. They built transport infrastructure, water delivery systems, and even heated baths, all considered advanced for a civilization of that era. Astonishingly, they also dabbled in nanotechnology. The Lycurgus Cup, named after the king depicted tangled in vines in the vessel’s glass, has some fascinating properties. When light shines through the front of the cup, it appears jade green. But when the cup is turned around, it glows a blood red. The British Museum acquired the artefact in the 1950s,[1] and it baffled scientists for decades. In 1990, researchers took broken fragments of the chalice and put them under extremely powerful microscopes. What they found was incredible. The Roman artists who created the cup had impregnated the glass with tiny particles of silver and gold, which were ground down until they were just fifty nanometers in diameter. To achieve the color-shifting effect, the mix of particles—which were less than one-thousandth the size of a grain of salt—needed to be exact. The complexity proved the Romans had mastered the art of infusing nanoparticles into objects, even if they probably didn’t know exactly how it worked.[2]
The Romans weren’t the only early civilization known to use nanotechnology. The windows of late medieval churches were found to display the same properties. They shone a magnificent luminous red and yellow as the sun passed through them thanks to the gold and silver nanoparticles meticulously placed inside the glass.[3] But the coolest early use of the technology came from the Middle East. Europeans were first introduced to Damascus Steel when the Crusaders attempted to retake the Holy Lands, beginning in the eleventh century. Swords made of this material could slice a silk scarf floating to the ground. They were extraordinarily strong, and flexible enough to bend from hilt to tip. Many of the Crusaders learned this the hard way—it was often them being cleaved in two midair instead of a piece of clothing.
The swords were immediately recognizable by watery, wavy marks in the steel, and any Crusader close enough to see it was already at risk of losing a limb.[4] Armorers from across the region, including Persia, closely guarded the secrets of Damascus steel, and many legends and myths emerged speculating on how the swords were made. Most focused on the way the metal was quenched, the process of cooling it rapidly after heating it to extreme temperatures. Some of the rumors were wild. One suggested the swords were quenched in dragon blood, while a person in Pakistan, who said they’d had a sword in their family for generations, insisted its makers in Afghanistan cooled it in donkey urine. Medieval smiths in Europe believed the urine of either a red-haired boy or a three-year-old goat fed only ferns for three days were the secret ingredient. Writing found in Asia Minor told a grislier tale. It said to temper a Damascus sword, the blade must be heated until it glows “like the sun rising in the desert,” then cooled until it was royal purple by plunging it into the body of a muscular slave so their strength was transferred to the steel. It seems the red-haired boys got off lightly.[5]
The popularity of the swords eventually died out in the eighteenth century, some say because of the rise of firearms, and no European smith was ever able to fully replicate their method of production. But in 2006, the mystery was finally solved when Marianne Reibold and colleagues at the University of Dresden discovered the smiths were inadvertently using nanotechnology.
All Damascus swords were forged from the same small cakes of steel which originated in India and were labeled “wootz.” Steel is made from iron and carbon. Typically, there will only be a tiny amount of carbon to strengthen the metal. If the carbon content reaches 1–2 percent, the steel becomes a lot harder but is also brittle enough to shatter easily. Wootz had an abnormally high carbon content of around 1.5 percent, so really should have been useless for swords. Even so, the Damascus swords were both malleable and tough.
Reibold and her team analyzed a Damascus sabre created by a famous blacksmith named Assad Ullah in the seventeenth century. They dissolved a tiny part of the weapon in hydrochloric acid and used an electron microscope to take a closer look. The steel contained carbon nanotubes, one of the strongest materials known to humanity, each one slightly larger than half a nanometer. It isn’t clear how blacksmiths produced the nanotubes, but the research team believed it was partly due to the quenching, as the legends had stated. The wootz contained small traces of different metals, and alternating hot and cold phases during the manufacture of the steel caused these impurities to segregate and become catalysts for the formation of the carbon nanotubes. The nanotubes then formed cementite nanowires, which formed along the planes of the steel, explaining the wavy bands that were the hallmark of Damascus swords. [6]
While all of the smiths, armorers, and artists who mastered these techniques produced amazing art and weaponry, it’s almost impossible that they understood what was going on. Researchers were only able to get a grasp of that understanding as microscopes became increasingly powerful. Right at the turn of the twentieth century, Max Planck and Albert Einstein produced theoretical evidence that a range of tiny particles existed which obeyed their own laws but weren’t visible using the apparatus of the time. Improvements in those tools proved the pair correct—and spawned a whole new world of scientific study.[7]
Nanotechnology research was first predicted by the physicist and Nobel Prize–winner Richard P. Feynman in 1959. His paper, “There’s Plenty of Room at the Bottom: An invitation to enter a new field of physics,” talked about the production and control of tiny machines through quantum mechanics and foresaw that the development of microscopes would enable scientists to arrange atoms any way they wanted them. The paper makes no mention of the word nanotechnology but is still seen as the founding text of the field.[8]
“It would be interesting in surgery if you could swallow the surgeon. You put the mechanical surgeon inside the blood vessel and it goes into the heart and ‘looks’ around…It finds out which valve is the faulty one and takes a little knife and slices it out. Other small machines might be permanently incorporated in the body to assist some inadequately-functioning organ,” Feynman wrote. [9]
His paper piqued the interest of the scientific world, and a new field of research was born. Two schools of thought emerged on how to make his ideas reality. The first was to shrink existing machines and instruments. The second, far-more-sensible-sounding approach was to build complex nanostructures atom by atom. The latter was popularized by one of the most important books on the subject by a man considered one of the godfathers of nanotechnology.[10]
In the 1970s, K. Eric Drexler spent most evenings as an MIT undergraduate studying the latest research in genetic engineering. He began to wonder if it would be possible to mimic the role cells play in the body with mechanical replacements. If you could recreate the functions of DNA and proteins with tiny machines, he thought, you could do anything that biology does, and a whole lot more. This theory took inspiration from genetic engineering but was in fact molecular engineering, a technology with the potential to change the world. In 1977 this led him to an incredible idea—a host of minuscule robots that could move around molecules so quickly and precisely they could produce almost any substance in the world with basic ingredients. In Drexler’s theory, you would feed these robots a few cheap chemicals and they would produce gasoline, diamonds, or anything you wanted. If you were to put these miniature bots into the bloodstream, they could fight off disease. Put them in the air and they’d clean it of pollution.
Two years later, Drexler read Feynman’s paper and realized he wasn’t alone in his thinking, but he struggled to get the idea taken seriously at MIT, partly because he was seen as something of an outcast. In the 1980s he was known to organize retreats with his wife where students could discuss topics including cryonics and immortality. Regardless, he was able to publish his first book in 1986, Engines of Creation, which popularized the term nanotechnology. The book explained all the potential benefits of this molecular manufacturing he intended to invent, but it also highlighted the dangers. Chief among those was the gray goo scenario: the prospect of self-reproducing assemblers escaping a lab and eating up anything in their path, turning the Earth into a blob of gray goo.[11]
Drexler’s writing inspired scientists eager to make the jump into a new field (it also fascinated science fiction writers). Drexler earned his PhD in 1991, receiving the first ever degree in molecular nanotechnology from MIT. The following year he took his theories to Congress, telling the Senate Subcommittee on Science, Technology, and Space this new field could lead to “new technologies for a sustainable world.” Al Gore, the subcommittee chair, declared his support and wanted exploratory research funded. Drexler published his masterpiece the same year—a 550-page paper laying out a molecular manufacturing system in detail. “Nanosystems: Molecular Machinery, Manufacturing and Computation” used illustration, charts, and equations to show objects could be built from the molecules up. But the paper did not receive the kind of recognition Drexler hoped for, perhaps partly because it was neither one scientific discipline or another; it was a mix of different fields. [12]
Over the next decade, doubts began to emerge not just over the feasibility of molecular manufacturing, but whether we should do it at all. Prominent scientists suggested nanotechnology could easily be weaponized and used for military purposes, so should be left in the metaphorical box with the lid firmly shut. When the author Michael Crichton read about the gray goo theory, he depicted such a catastrophe in his bestselling novel Prey. In the book, a cloud of nanoparticles is released from a lab and quickly reproduces, evolves intelligence, and causes mayhem in the Nevada desert. Crichton prefaced the story with an introduction that claimed although the events in the book were made up, the technology behind it was a very real possibility. The book played into the hands of a growing group of scientists who believed Drexler was peddling nonsense. At the head of that group was Richard Smalley, a chemist from Rice University and a Nobel Prize winner. [13]
In 2004, Chemical and Engineering News published a series of letters exchanged between Smalley and Drexler in which the former expressed his doubts that molecular manufacturing was even possible. “Chemistry of the complexity, richness, and precision needed to come anywhere close to making a molecular assembler—let alone a self-replicating assembler—cannot be done simply by mushing two molecular objects together,” he wrote. But Smalley wasn’t done there. He also accused Drexler of terrorizing the world with the concept of gray goo. “You and people around you have scared our children,” the letter read. “I don’t expect you to stop, but I hope others in the chemical community will join with me in turning on the light and showing our children that, while our future in the real world will be challenging and there are real risks, there will be no such monster as the self-replicating mechanical nanobot of your dreams.”
Two days later, Drexler’s hopes of establishing molecular manufacturing as a recognized field of research were dealt a further blow. That day, President George Bush signed the 21st Century Nanotechnology Research and Development Act, which earmarked $3.7 billion for molecular-scale technologies. In the run-up to the signing of the bill, Drexler had expected the announcement to catapult his research to the next level, putting it at the forefront of the nation’s scientific agenda. But no money was allocated to molecular manufacturing as he imagined it, and almost all of it was instead put aside for projects using the technology to attempt to develop new materials. Drexler, the godfather of nanotechnology, had been sidelined from the field he established.[14]
In the aftermath, the young field of nanotechnology was divided. Drexler stood on one side with his molecular assembly theory, something he still hasn’t been able to master. On the other was Smalley and the vast majority of scientists, who saw nanotechnology as any work carried out at the nanoscale. Immortalists like Aubrey de Grey see Drexler as not just one of their own, but also believe he’ll end up on the right side of history.[15] The science community has another view. Kostas Kostarelos, a professor of nanomedicine at the University of Manchester in the United Kingdom, sees Drexler as a fringe actor in a field he’s been a significant part of since its inception.[16]
Kostarelos, born and raised in Athens, Greece, started research at the nanoscale in 1990, studying double-stranded DNA at the University of Leeds before he moved to Imperial College London in the chemical engineering department. He was tasked with working on delivery systems, tiny man-made methods to carry chemicals, vitamins, and medical treatments. He worked with liposomes to create fatty molecular envelopes—later referred to as lipid nanoparticles. While colleagues in his department accepted lucrative jobs in the petrochemicals industry in the Middle East, Kostarelos moved to the United States, where he was paid just $40,000 a year to continue his study of liposomes at medical school at the University of California, San Francisco. By 1994, the liposome research area was beginning to boom. They were used to deliver a vaccine in Switzerland and approved by the FDA in the United States for the treatment of Kaposi’s sarcoma in AIDS patients. The field was called colloidal chemistry, physical chemistry, formation chemistry, but never nanotechnology, despite scientists working at nanoscale.
Kostarelos later moved to the East Coast, taking a position at Memorial Sloan Kettering, the renowned cancer center in New York City. There, he attempted to create a better form of radiotherapy by using liposomes to irradiate cancerous tissues from within. He then switched his attention to gene therapy, another medical field that required innovative ways to deliver drugs to the human body. After the Gelsinger incident mentioned in the previous chapter, nonviral vectors were in high demand. Around the turn of the millennium, Kostarelos moved back to the United Kingdom, at a time when the definition of nanotechnology was beginning to change. The National Cancer Institute in the United States made significant investments in the field, and nanotech began to assume a clear identity, one very different from anything proposed by Drexler. Kostarelos took a position at University College London and was later named Personal Chair of Nanomedicine and Head of the Centre in 2007. When the university asked him what he wanted his chair to be named, his decision drew taunts from his colleagues in clinical medicine, who reminded him he was no practitioner of medicine.
I spoke to Kostarelos on a lengthy Zoom call, and he recalled the difficulties of the early years. “When a new field is morphed, there are so many influences and actors that it’s quite difficult to identify what is the critical parameter that decides things,” he told me. “There were a bunch of guys like Drexler who were coming from the semiconducting, hardcore engineering space. These guys were not practicing chemists.”
He said the work proposed by Feynman and Drexler used shrunken down machines that came from engineering, while his reality was work in soft biological matter on a similar scale. “At some point in the late ’90s and early 2000s, there was a scientific need, the community needed to define ‘what the hell do we mean by nano, anyway?’ And I think that’s where we see the more, kind of boring definitions of the one to one hundred convention. The convention now is that as long as you’re between one and one hundred nanometers in scale at least in one dimension of what you’re designing, you’re doing nano.”
Despite progress made at the start of the millennium, the common perception of nanotechnology always involved miniature machines of some kind. “I believe Hollywood has a big play in this, with those movies of miniaturized submarines. I really think that art is affecting conception here,” Kostarelos said. That view of nanotechnology was aided by the voices being amplified in the immortalist community.
Ray Kurzweil, the famed inventor, futurist, and expert in AI, is one such voice. He holds a special place in the hopes of immortalists, mostly because of his work predicting a singularity event which will effectively end biological death. In his book The Singularity Is Near: When Humans Transcend Biology, he stressed that biology could only take our species so far.
“Biology will never be able to match what we will be capable of engineering once we fully understand biology’s principles of operation,” he wrote.[17] Concerning nanotechnology, Kurzweil described microscopic machines traveling through human bodies, fixing damaged cells and organs, and wiping out disease. In an interview in 2009, Kurzweil insisted anyone alive by 2040 or 2050 would be close to immortal, mostly due to nanotechnology. He even predicted nanobots would eventually replace biological blood at some point in the future. “It’s radical life extension,” Kurzweil told ComputerWorld. “The full realization of nanobots will basically eliminate biological disease and aging. I think we’ll see widespread use in twenty years of [nanotech] devices that perform certain functions for us. In thirty or forty years, we will overcome disease and aging. The nanobots will scout out organs and cells that need repairs and simply fix them. It will lead to profound extensions of our health and longevity.”[18]
Kurzweil and Drexler’s visions for nanotechnology gave immortalists exactly the type of hope they crave. But those possibilities remain a long way off, judging by the field today. There are areas of great promise, but putting a timeline on any progress is difficult, partly because the area is so complex. Modern nanotechnology is an interdisciplinary science. Researchers seek to understand and master the tiniest particles and their chemical, physical, and mechanical properties, work that overlaps and blurs the boundaries between physics, chemistry, biology, medicine, electronics, and information technology. Nanomedicine has become a major branch of nanotechnology, and scientists like Kostarelos established that it had the potential to change medicine greatly. They hope nanotechnology can make significant and life-changing progress at every stage of treating disease. Drug delivery, where Kostarelos conducted the bulk of his work, offers the most hope of imminent breakthrough. In fact, the lipid nanoparticles worked on all those years ago recently brought a momentous change to the world, rescuing it from one of its bleakest hours.
• • •
In December 2020, after a year of death, suffering, isolation, and fear, the world finally received some good news: regulators approved two vaccines, one from Pfizer-BioNTech and the other from Moderna, in both the United States and the United Kingdom.[19][20] Finally, some degree of normality appeared to be attainable again. The vaccines were unlike anything used in humans before, and their delivery relied on nanotechnology.
The goal of the vaccines is to deliver mRNA—a genetic messenger instructing cells to develop spike proteins so they can fight the virus before it can do any damage. If the mRNA is the letter containing instructions, then the lipid nanoparticles are the fatty molecular envelopes. These envelopes, which work far more effectively than your average courier, ensure the mRNA evades the biological bouncers guarding what goes in and out of our systems and reaches the targeted cells without losing any of the potency of the message. In the past, lipid nanoparticles have been used to deliver both vaccines and drugs. The chemotherapy Doxil and cholesterol-lowering treatments Repatha and Praluent utilize them to ensure they hit the targeted cells while causing the least amount of damage and side effects. Nanoparticles are also being tested to be used with CRISPR-Cas9 to target organs.[21]
But for those involved in using nanoparticles for drug delivery, the new COVID-19 vaccines were something of a milestone. Dr. Robert Langer, the cofounder of Moderna who boasts an astonishing set of achievements across scientific disciplines, explained to me on a call his hopes, now the vaccine is widely distributed. “I think it’s a big moment. Of course, I’ve been working on this stuff for fifty years, but I think it’s a real validation of drug delivery. It’s hardly the only one, but it’s a very visible one. And it will save millions of lives, and end the pandemic.”
Bringing an end to a global pandemic is a good start for any medical technology, yet Langer was also excited for what comes next. He was particularly looking forward to technology that would deliver drugs across the blood-brain barrier, which could help treat Alzheimer’s, and targeting of blood vessels to ward off heart disease. Better targeting is a major goal for nanotechnology-enabled drug delivery. “If you have cancer, for example, can you target 100 percent of the drug to a tumor? Probably you can’t, but how do you maximize the amount that gets into the tumor? And I would say the same thing for targeting any part of the body for any disease. It’s like the idea of Urlich’s magic bullet—could you target something it finds where it needs to go, and every bit of it goes there? I think that’s the biggest challenge, but that’s hardly going to be solved overnight.”
Improving the targeting of drugs would make them safer. Cancer patients are often treated with chemotherapy, which makes them ill because the drug goes all over the body. But if you could give someone a drug that specifically targeted the tumor it was going to eradicate, not only would that drug be more effective, but the side effects would be minimal as well.
Drug delivery is not the only use for nanomedicine, of course. The field as a whole is expanding, in part due to a more multidisciplinary approach to education. Like Kostarelos, Langer hopped around disciplines of science. After he got his PhD, he opted to practice his postdoctoral work in a hospital surgery lab, where he was the only engineer.
“I loved it and felt it was very important scientifically, and I felt you could make a real impact, so I’ve done that all my life,” he told me. “I would say in the last ten or fifteen years, that kind of strategy has been adopted more and more. There’s a whole area that myself and Phil Sharpe and other people at MIT have called convergence, and I think we see more and more schools adopting that in different institutes.” Now he sees more students interested in taking the same route he did, and it’s easy to see why, given his long list of accomplishments. Langer’s peers gave him the nickname “the Edison of Medicine” after he was awarded an h-index score (which measures the number of papers a person has published and how often they are cited) of 230, the highest ever for an engineer. He has over 1,284 patents issued and pending worldwide, and his lab has produced forty companies, all but one of which are still operating.[22] Moderna is undoubtedly enjoying its high profile and is now worth tens of billions of dollars after its vaccine success. Langer believes the government needs to create the ideal environment for companies like Moderna to thrive in, but his penchant for launching commercial companies from his research doesn’t sit well with the entire scientific community, particularly those outside of the United States.
“The important thing about people like Bob, they believe that by spinning out companies and becoming prominent in the biotech field, they are pushing the envelope,” argued Kostarelos. “That’s a very American approach. It’s not how things are done in Europe or the rest of the world. Asia is kind of copying the American paradigm that Bob and others have established. This is where I completely disagree with my American colleagues. I do not think that blind capitalism is a solution to the problem.”
Parrish described one of the problems cutting edge medical science faces in the previous chapter—that it takes too long for a discovery to become a drug, and then for the drug to reach patients. The lightning speed at which the COVID vaccines were developed and approved gave some people hope, but Langer feels it won’t last long. He recalled to me the negative press attention Moderna got when it was first developing the vaccine, something he said went away when the efficacy data was released. “Now they just say it’s all about money and stuff like that, they want it for free, patents should go away. I think people have forgotten about what they thought a year ago, people have short memories. I expect that we’re already going back and people are saying medical research costs too much and things like that. I personally don’t expect a giant change. I wish I was wrong, and maybe I will be wrong, but I don’t think so.”
He believes favorable tax systems for biotechnology investors would help advance medical technology further, and he wants to see increased research funding from the National Institute of Health and a beefier budget for the FDA so it can approve more treatments.[23] Kostarelos agrees entirely with the latter two points but laughed when told of the tax breaks for investors. He sees the commercialization of medical technology as one of the great dangers of his field, and something that will only get worse as more progress is made.
Kostarelos is no longer working on drug delivery and has instead turned his attention to an even more complex problem—interfacing with the brain through nanotechnology. He hopes this technology will provide a cure to many neurological problems, including Alzheimer’s, Parkinson’s, and even blindness. But he’s also terrified of making a breakthrough.
“I have this very personal dilemma which I expressed with my very close scientific friends, which is why are we doing this? Why am I developing the next neural interface?” Kostarelos said. “Why do we want to put the research and emphasis in developing the next generation of neural interface technologies? The answer is very simple: because we are trying to make people that suffer now live a better quality of life. That is very straightforward.”
But over time, this explanation has made less and less sense to the scientist.
“It’s the type of approach I hear when a scientist is interviewed after receiving the Nobel Prize. ‘Why did you do this?’ ‘Well I want to change the world for a better place.’ What kind of superficial bullshit is this? Everyone wants to do that.”
Kostarelos is worried that someone else is working on the same neural technology but without any kind of transparency or collaboration with the rest of the scientific community. While he wants to use the technology to solve a medical issue and reduce suffering in the world, others may simply want to build a weapon. If nanotechnology were used to create neural interfaces for military purposes, we would enter a new era of warfare featuring super soldiers straight out of Hollywood. A military force might experiment on willing soldiers, but the rest of the world will not have given any kind of consent to develop this world-changing tech.
“What I’m worried about is there will be experimentation done secretly in the context of an elite force that has consented to play a part in this experiment. And then gradually after this failed or not attempt, we will never hear anything, even us scientists,” Kostarelos explained. “Suddenly we will see a gradual acceptance and rolling out commercially or capitalistically of those interventions, similar to the plastic surgery body enhancements but in a functional way. And that’s where the discussion may start, but that would be too late then. That would be a different type of conversation, by the way. That would be about do we condone or do we have objections on the commercialization of this, not whether we as a society want to go down that route.”
“Bob [Langer] and his colleagues have…shown that this paradigm of taking technologies and commercializing them and pushing them out into the market very quickly and very profitabl[y] works, at least for the short term. Also, because people are getting more and more accepting of new technologies faster. It’s this capitalistic notion of ‘let’s try it, if it doesn’t work we’ll drop it and we’ll take the new thing coming along.’ There’s not a lot of conscious thinking of what would be the impact.”
My time researching nanotechnology was something of a roller-coaster. I was fascinated by Drexler’s vision, then terrified about what it would become. When it appeared to be largely fanciful, the reality seemed much more soothing, especially when used in vaccines and disease-crushing drugs. But even if Drexler’s gray goo was nothing more than fantasy, the dangers of developing nanotechnology further are frightening. We cannot continue to have debates over the dangers of technology after the genie has been let out of the bottle. Yet it seemed to me that the immortalists had willingly overlooked the dangers of the path they were advocating. If successful, they could potentially save billions of lives, but at what cost?