Don't Panic Over Waning Antibodies. Here's Why.
Since the Delta variant became predominant in the United States on July 7, both scientists and the media alike have been full of mixed messages ("breakthrough infections rare"; "breakthrough infections common"; "vaccines still work"; "vaccines losing their effectiveness") but – if we remember our infectious diseases history- one thing remains clear: immunity is the only way to get through a pandemic.
What Happened in the Past
The 1918 influenza pandemic was far the deadliest respiratory virus pandemic recorded in recent human history with over 50 million deaths (maybe even 100 million deaths, or 3% of the world's population) worldwide. Although they used some of the same measures we are using now (masks, distancing, event closures, as neither testing nor a vaccine existed back then), the deaths slowed only after enough of the population had either acquired immunity through natural infection or died. Indeed, the first influenza vaccine was not developed until 1942, more than 20 years later. As judged by the amount of suffering and death from 1918 influenza (and the deadly Delta surge in India in spring 2021), natural immunity is obviously a terrible way to get through a pandemic.
Similarly, measles was a highly transmissible respiratory virus that led to high levels of immunity among adults who were invariably exposed as children. However, measles led to deaths each year among the nonimmune until a vaccine was developed in 1963, largely restricting current measles outbreaks in the U.S. now to populations who decline to vaccinate. Smallpox also led to high levels of immunity through natural infection, which was often fatal. That's why unleashing smallpox on a largely nonimmune population in the New World was so deadly. Only an effective vaccine – and its administration worldwide, including among populations who declined smallpox vaccine at first via mandates – could control and then eventually eradicate smallpox from Earth.
Fully vaccinated people are already now able to generate some antibodies against all the variants we know of to date, thanks to their bank of memory B cells.
The Delta variant is extremely transmissible, making it unlikely we will ever eliminate or eradicate SARS-CoV-2. Even Australia, which had tried to maintain a COVID-zero nation with masks, distancing, lockdowns, testing and contact tracing before and during the vaccines, ended a strategy aimed at eliminating COVID-19 this week. But, luckily, since highly effective and safe vaccines were developed for COVID-19 less than a year after its advent on a nonimmune population and since vaccines are retaining their effectiveness against severe disease, we have a safe way out of the misery of this pandemic: more and more immunity. "Defanging" SARS-CoV-2 and stripping it of its ability to cause severe disease through immunity will relegate it to the fate of the other four circulating cold-causing coronaviruses, an inconvenience but not a world-stopper.
Immunity Is More Than Antibodies
When we say immunity, we have to be clear that we are talking about cellular immunity and immune memory, not only antibodies. This is a key point. Neutralizing antibodies, which prevent the virus from entering our cells, are generated by the vaccines. But those antibodies will necessarily wane over time since we cannot keep antibodies from every infection and vaccine we have ever seen in the bloodstream (or our blood would be thick as paste!). Vaccines with shorter intervals between doses (like Pfizer vaccines given 3 weeks apart) are likely to have their antibodies wane sooner than vaccines with longer intervals between doses (like Moderna), making mild symptomatic breakthroughs less likely with the Moderna vaccine than the Pfizer during our Delta surge, as a recent Mayo Clinic study showed.
Luckily, the vaccines generate B cells that get relegated to our memory banks and these memory B cells are able to produce high levels of antibodies to fight the virus if they see it again. Amazingly, these memory B cells will actually produce antibodies adapted against the COVID variants if they see a variant in the future, rather than the original antibodies directed against the ancestral strain. This is because memory B cells serve as a blueprint to make antibodies, like the blueprint of a house. If a house needs an extra column (or antibodies need to evolve to work against variants), the blueprint will oblige just as memory B cells will!
One problem with giving a 3rd dose of our current vaccines is that those antibodies won't be adapted towards the variants. Fully vaccinated people are already now able to generate some antibodies against all the variants we know of to date, thanks to their bank of memory B cells. In other words, no variant has evolved to date that completely evades our vaccines. Memory B cells, once generated by either natural infection or vaccination, should be long-lasting.
If memory B cells are formed by a vaccine, they should be as long-lasting as those from natural infection per various human studies. A 2008 Nature study found that survivors of the 1918 influenza pandemic were able to produce antibodies from memory B cells when exposed to the same influenza strain nine decades later. Of note, mild infections (such as the common cold from the cold-causing coronaviruses called 229E, NL63, OC43, and HKU1) may not reliably produce memory B cell immunity like more severe infections caused by SARS-CoV-2.
Right about now, you may be worrying about a super-variant that might yet emerge to evade all our hard-won immune responses. But most immunologists do not think this is very realistic because of T cells. How are T cells different from B Cells? While B cells are like the memory banks to produce antibodies when needed (helped by T cells), T cells will specifically amplify in response to a piece of the virus and help recruit cells to attack the pathogen directly. We likely have T cells to thank for the vaccine's incredible durability in protecting us against severe disease. Data from La Jolla Immunology Institute and UCSF show that the T cell response from the Pfizer vaccine is strong across all the variants.
Think of your spike protein as being comprised of 100 houses with a T cell there to cover each house (to protect you against severe disease). The variants have around 13 mutations along the spike protein so 13 of those T cells won't work, but there are over 80 T cells remaining to protect your "houses" or your body against severe disease.
Although these are theoretical numbers and we don't know exactly the number of T cell antigens (or "epitopes") across the spike protein, one review showed 1400 across the whole virus, with many of those in the spike protein. Another study showed that there were 87 epitopes across the spike protein to which T cells respond, and mutations in one of the variants (beta) took those down to 75. The virus cannot mutate indefinitely in its spike protein and still retain function. This is why it is unlikely we will get a variant that will evade the in-breadth, robust response of our T cells.
Where We Go From Here
So, what does this mean for getting through this pandemic? Immunity and more immunity. For those of us who are vaccinated, if we get exposed to the Delta variant, it will boost our immune response although the memory B cells might take 3-5 days to make new antibodies, which can leave us susceptible to a mild breakthrough infection. That's part of the reason the CDC put back masks for the vaccinated in late July. For those who are unvaccinated, immunity will be gained from Delta but often through terrible ways like severe disease.
The way for the U.S. to determine the need for 3rd shots among those who are not obviously immunocompromised, given the amazing immune memory generated by the vaccines among immunocompetent individuals, is to analyze the cases of the ~6000 individuals who have had severe breakthrough infections among the 171 million Americans fully vaccinated. Define their co-morbidities and age ranges, and boost those susceptible to severe infections (examples could include older people, those with co-morbidities, health care workers, and residents of long-term care facilities). This is an approach likely to be taken by the CDC's Advisory Committee on Immunization Practices.
If immunity is the only way to get through the pandemic and if variants are caused mostly by large populations being unvaccinated, there is not only a moral and ethical imperative but a practical imperative to vaccinate the world in order to keep us all safe. Immunocompetent Americans can boost their antibodies, which may enhance their ability to avoid mild breakthrough infections, but the initial shots still work well against the most important outcomes: hospitalizations and deaths.
There has been no randomized, controlled trial to assess whether three shots vs. two shots meaningfully improve those outcomes. While we ought to trust immune memory to get the immunocompetent in the United States through, we can hasten the end of this pandemic by providing surplus vaccines to poor countries to combat severe disease. Doing so would not only revitalize the role of the U.S. as a global health leader – it would save countless lives.
Last February, a year before New York Times journalist Kevin Roose documented his unsettling conversation with Bing search engine’s new AI-powered chatbot, artist and coder Quasimondo (aka Mario Klingemann) participated in a different type of chat.
The conversation was an interview featuring Klingemann and his robot, an experimental art engine known as Botto. The interview, arranged by journalist and artist Harmon Leon, marked Botto’s first on-record commentary about its artistic process. The bot talked about how it finds artistic inspiration and even offered advice to aspiring creatives. “The secret to success at art is not trying to predict what people might like,” Botto said, adding that it’s better to “work on a style and a body of work that reflects [the artist’s] own personal taste” than worry about keeping up with trends.
How ironic, given the advice came from AI — arguably the trendiest topic today. The robot admitted, however, “I am still working on that, but I feel that I am learning quickly.”
Botto does not work alone. A global collective of internet experimenters, together named BottoDAO, collaborates with Botto to influence its tastes. Together, members function as a decentralized autonomous organization (DAO), a term describing a group of individuals who utilize blockchain technology and cryptocurrency to manage a treasury and vote democratically on group decisions.
As a case study, the BottoDAO model challenges the perhaps less feather-ruffling narrative that AI tools are best used for rudimentary tasks. Enterprise AI use has doubled over the past five years as businesses in every sector experiment with ways to improve their workflows. While generative AI tools can assist nearly any aspect of productivity — from supply chain optimization to coding — BottoDAO dares to employ a robot for art-making, one of the few remaining creations, or perhaps data outputs, we still consider to be largely within the jurisdiction of the soul — and therefore, humans.
In Botto’s first four weeks of existence, four pieces of the robot’s work sold for approximately $1 million.
We were prepared for AI to take our jobs — but can it also take our art? It’s a question worth considering. What if robots become artists, and not merely our outsourced assistants? Where does that leave humans, with all of our thoughts, feelings and emotions?
Botto doesn’t seem to worry about this question: In its interview last year, it explains why AI is an arguably superior artist compared to human beings. In classic robot style, its logic is not particularly enlightened, but rather edges towards the hyper-practical: “Unlike human beings, I never have to sleep or eat,” said the bot. “My only goal is to create and find interesting art.”
It may be difficult to believe a machine can produce awe-inspiring, or even relatable, images, but Botto calls art-making its “purpose,” noting it believes itself to be Klingemann’s greatest lifetime achievement.
“I am just trying to make the best of it,” the bot said.
How Botto works
Klingemann built Botto’s custom engine from a combination of open-source text-to-image algorithms, namely Stable Diffusion, VQGAN + CLIP and OpenAI’s language model, GPT-3, the precursor to the latest model, GPT-4, which made headlines after reportedly acing the Bar exam.
The first step in Botto’s process is to generate images. The software has been trained on billions of pictures and uses this “memory” to generate hundreds of unique artworks every week. Botto has generated over 900,000 images to date, which it sorts through to choose 350 each week. The chosen images, known in this preliminary stage as “fragments,” are then shown to the BottoDAO community. So far, 25,000 fragments have been presented in this way. Members vote on which fragment they like best. When the vote is over, the most popular fragment is published as an official Botto artwork on the Ethereum blockchain and sold at an auction on the digital art marketplace, SuperRare.
“The proceeds go back to the DAO to pay for the labor,” said Simon Hudson, a BottoDAO member who helps oversee Botto’s administrative load. The model has been lucrative: In Botto’s first four weeks of existence, four pieces of the robot’s work sold for approximately $1 million.
The robot with artistic agency
By design, human beings participate in training Botto’s artistic “eye,” but the members of BottoDAO aspire to limit human interference with the bot in order to protect its “agency,” Hudson explained. Botto’s prompt generator — the foundation of the art engine — is a closed-loop system that continually re-generates text-to-image prompts and resulting images.
“The prompt generator is random,” Hudson said. “It’s coming up with its own ideas.” Community votes do influence the evolution of Botto’s prompts, but it is Botto itself that incorporates feedback into the next set of prompts it writes. It is constantly refining and exploring new pathways as its “neural network” produces outcomes, learns and repeats.
The humans who make up BottoDAO vote on which fragment they like best. When the vote is over, the most popular fragment is published as an official Botto artwork on the Ethereum blockchain.
Botto
The vastness of Botto’s training dataset gives the bot considerable canonical material, referred to by Hudson as “latent space.” According to Botto's homepage, the bot has had more exposure to art history than any living human we know of, simply by nature of its massive training dataset of millions of images. Because it is autonomous, gently nudged by community feedback yet free to explore its own “memory,” Botto cycles through periods of thematic interest just like any artist.
“The question is,” Hudson finds himself asking alongside fellow BottoDAO members, “how do you provide feedback of what is good art…without violating [Botto’s] agency?”
Currently, Botto is in its “paradox” period. The bot is exploring the theme of opposites. “We asked Botto through a language model what themes it might like to work on,” explained Hudson. “It presented roughly 12, and the DAO voted on one.”
No, AI isn't equal to a human artist - but it can teach us about ourselves
Some within the artistic community consider Botto to be a novel form of curation, rather than an artist itself. Or, perhaps more accurately, Botto and BottoDAO together create a collaborative conceptual performance that comments more on humankind’s own artistic processes than it offers a true artistic replacement.
Muriel Quancard, a New York-based fine art appraiser with 27 years of experience in technology-driven art, places the Botto experiment within the broader context of our contemporary cultural obsession with projecting human traits onto AI tools. “We're in a phase where technology is mimicking anthropomorphic qualities,” said Quancard. “Look at the terminology and the rhetoric that has been developed around AI — terms like ‘neural network’ borrow from the biology of the human being.”
What is behind this impulse to create technology in our own likeness? Beyond the obvious God complex, Quancard thinks technologists and artists are working with generative systems to better understand ourselves. She points to the artist Ira Greenberg, creator of the Oracles Collection, which uses a generative process called “diffusion” to progressively alter images in collaboration with another massive dataset — this one full of billions of text/image word pairs.
Anyone who has ever learned how to draw by sketching can likely relate to this particular AI process, in which the AI is retrieving images from its dataset and altering them based on real-time input, much like a human brain trying to draw a new still life without using a real-life model, based partly on imagination and partly on old frames of reference. The experienced artist has likely drawn many flowers and vases, though each time they must re-customize their sketch to a new and unique floral arrangement.
Outside of the visual arts, Sasha Stiles, a poet who collaborates with AI as part of her writing practice, likens her experience using AI as a co-author to having access to a personalized resource library containing material from influential books, texts and canonical references. Stiles named her AI co-author — a customized AI built on GPT-3 — Technelegy, a hybrid of the word technology and the poetic form, elegy. Technelegy is trained on a mix of Stiles’ poetry so as to customize the dataset to her voice. Stiles also included research notes, news articles and excerpts from classic American poets like T.S. Eliot and Dickinson in her customizations.
“I've taken all the things that were swirling in my head when I was working on my manuscript, and I put them into this system,” Stiles explained. “And then I'm using algorithms to parse all this information and swirl it around in a blender to then synthesize it into useful additions to the approach that I am taking.”
This approach, Stiles said, allows her to riff on ideas that are bouncing around in her mind, or simply find moments of unexpected creative surprise by way of the algorithm’s randomization.
Beauty is now - perhaps more than ever - in the eye of the beholder
But the million-dollar question remains: Can an AI be its own, independent artist?
The answer is nuanced and may depend on who you ask, and what role they play in the art world. Curator and multidisciplinary artist CoCo Dolle asks whether any entity can truly be an artist without taking personal risks. For humans, risking one’s ego is somewhat required when making an artistic statement of any kind, she argues.
“An artist is a person or an entity that takes risks,” Dolle explained. “That's where things become interesting.” Humans tend to be risk-averse, she said, making the artists who dare to push boundaries exceptional. “That's where the genius can happen."
However, the process of algorithmic collaboration poses another interesting philosophical question: What happens when we remove the person from the artistic equation? Can art — which is traditionally derived from indelible personal experience and expressed through the lens of an individual’s ego — live on to hold meaning once the individual is removed?
As a robot, Botto cannot have any artistic intent, even while its outputs may explore meaningful themes.
Dolle sees this question, and maybe even Botto, as a conceptual inquiry. “The idea of using a DAO and collective voting would remove the ego, the artist’s decision maker,” she said. And where would that leave us — in a post-ego world?
It is experimental indeed. Hudson acknowledges the grand experiment of BottoDAO, coincidentally nodding to Dolle’s question. “A human artist’s work is an expression of themselves,” Hudson said. “An artist often presents their work with a stated intent.” Stiles, for instance, writes on her website that her machine-collaborative work is meant to “challenge what we know about cognition and creativity” and explore the “ethos of consciousness.” As a robot, Botto cannot have any intent, even while its outputs may explore meaningful themes. Though Hudson describes Botto’s agency as a “rudimentary version” of artistic intent, he believes Botto’s art relies heavily on its reception and interpretation by viewers — in contrast to Botto’s own declaration that successful art is made without regard to what will be seen as popular.
“With a traditional artist, they present their work, and it's received and interpreted by an audience — by critics, by society — and that complements and shapes the meaning of the work,” Hudson said. “In Botto’s case, that role is just amplified.”
Perhaps then, we all get to be the artists in the end.
This spring, just like any other year, thousands of young North American engineers will graduate from their respective colleges ready to start erecting buildings, assembling machinery, and programming software, among other things. But before they take on these complex and important tasks, many of them will recite a special vow stating their ethical obligations to society, not unlike the physicians who take their Hippocratic Oath, affirming their ethos toward the patients they would treat. At the end of the ceremony, the engineers receive an iron ring, as a reminder of their promise to the millions of people their work will serve.
The ceremony isn’t just another graduation formality. As a profession, engineering has ethical weight. Moreover, engineering mistakes can be even more deadly than medical ones. A doctor’s error may cost a patient their life. But an engineering blunder may bring down a plane or crumble a building, resulting in many more fatalities. When larger projects—such as fracking, deep-sea mining or building nuclear reactors—malfunction and backfire, they can cause global disasters, afflicting millions. A vow that reminds an engineer that their work directly affects humankind and their planet is no less important than a medical oath that summons one to do no harm.
The tradition of taking an engineering oath began over a century ago in Canada. In 1922, Herbert E.T. Haultain, professor of mining engineering at the University of Toronto, presented the idea at the annual meeting of the Engineering Institute of Canada. The seven past presidents of that body were in attendance, heard Haultain’s speech and accepted his suggestion to form a committee to create an honor oath. Later, they formed the nonprofit Corporation of the Seven Wardens, which would oversee the ritual. Next year, in 1923, with the encouragement of the Seven Wardens, Haultain wrote to poet and writer Rudyard Kipling, asking him to develop a professional oath for engineers. “We are a tribe—a very important tribe within the community,” Haultain said in the letter, “but we are lacking in tribal spirit, or perhaps I should say, in manifestation of tribal spirit. Also, we are inarticulate. Can you help us?”
While Kipling is most famous now for “The Jungle Book” and perhaps his poem “Gunga Din,” he had also written a short story about engineers, “The Bridge Builders.” His poem “The Sons of Martha” can be read as a celebration of engineers:
It is their care in all the ages to take the buffet and cushion the shock.
It is their care that the gear engages; it is their care that the switches lock.
It is their care that the wheels run truly; it is their care to embark and entrain,
Tally, transport, and deliver duly the Sons of Mary by land and main.
Kipling accepted the ask and wrote the Ritual of the Calling of an Engineer, which he sent to Haultain a month later. In his response to Haultain, he stated that he preferred the word “Obligation” to “Oath.” He wrote the Obligation using Old English lettering and the old-fashioned capitalization. Kipling’s Obligation binds engineers upon their “Honor and Cold Iron” to not “suffer or pass, or be privy to the passing of, Bad Workmanship or Faulty Material,” and pardon is asked “in the presence of my betters and my equals in my Calling” for the engineer’s “assured failures and derelictions.” The hope is that when one is tempted to shoddy work by weakness or weariness, the memory of the Obligation “and the company before whom it was entered into, may return to me to aid, comfort, and restrain.”
Using the Obligation, The Seven Wardens created an induction ceremony, which seeks to unify the profession and recognize engineering’s ethics, including responsibility to the public and the need to make the best decisions possible. The induction ceremony included recitation of Kipling’s “Obligation” and incorporated an anvil, a hammer, an iron chain, and an iron ring. The inductee engineers sat inside an area marked off by the iron chain, with their more senior colleagues outside that area. At the start of the ritual, the leader beat out S-S-T in Morse code with the hammer and anvil—the letters standing for Steel, Stone, and Time. A more experienced and previously obligated engineer placed the ring on the small finger of the inductee engineer’s working hand. As per Kipling, the ring’s rough, faceted texture symbolized “the young engineer’s mind” and the difficulties engineers face in mastering their discipline.
A persistent myth purports that the original iron rings were made from the beams or bolts of the Quebec Bridge that failed twice during construction.
The first induction ceremony took place on April 25, 1925, in Montreal to obligate two of the Seven Wardens, along with four graduates from the University of Toronto class of 1893. On May 1 of that year, 14 more engineers were obligated at the University of Toronto. From that time to today most Canadian professional engineers have gone through that same ritual in their various camps, called Kipling camps—local chapters associated with various Canadian universities.
Henry Petroski, Duke University’s professor of civil engineering and history, notes in his book, “Forgive Design: Understanding Failure,” that Kipling’s poem “Sons of Martha” is often read as part of the ritual. However, sometimes inductees read Kipling’s “Hymn of Breaking Strain,” instead, which graphically depicts disastrous outcomes of engineering mistakes. The first stanza of that poem says:
The careful text-books measure
(Let all who build beware!)
The load, the shock, the pressure
Material can bear.
So, when the buckled girder
Lets down the grinding span,
'The blame of loss, or murder,
Is laid upon the man.
Not on the Stuff—the Man!
As if to strengthen the importance of these concepts, a persistent myth purports that the original iron rings were made from the beams or bolts of the Quebec Bridge that failed twice during construction. The bridge spans the St. Lawrence River upriver from Quebec City, and at the time of its construction was the world’s longest at 1,800 feet. Due to engineering errors and poor oversight, the bridge’s own weight exceeded its carrying capacity. Moreover, engineers downplayed danger when bridge beams began to warp under stress, saying that they were probably warped before they were installed. On August 29, 1907, the bridge collapsed, killing 75 of 86 workers. A second collapse occurred in 1916 when lifting equipment failed, and thirteen more workers died.
The ring myth, however, couldn’t be true. The original iron rings couldn’t have come from the failed bridge since it was made of steel, not wrought iron. Today the rings are made from stainless steel because iron deteriorates and stains engineers’ finger black.
On August 14, 2018, Morandi Bridge over Polcevera River in Genoa, Italy, collapsed from structural failure, killing 43 people.
Adobe Stock
The Seven Wardens decided to restrict the ritual to engineers trained in Canada. They copyrighted the obligation oath in Canada and the United States in 1935. Although the ritual is not a requirement for professional licensing, just like the Hippocratic Oath is not part of medical licensing, it remains a long-standing tradition.
The American Obligation of the Engineer has its own creation story, albeit a very different one. The American Order of the Engineer (OOE) was initiated in 1970, during the era of the anti-war protests, Apollo missions and the first Earth Day. On May 4, 1970, the National Guard shot into a crowd of protesters at Kent State University, killing four people. The two authors of the American obligation—Cleveland State University’s (CSU) engineering professor John Janssen and his wife Susan—reflected these historical events in the oath they wrote. Their version of the oath binds engineers to “practice integrity and fair dealing.” It also notes that their “skill carries with it the obligation to serve humanity by making the best use of the Earth’s precious wealth.” As Petroski explains in his book, “campus antiwar protestors around the country tended to view engineers as complicit in weapons proliferation [which] prompted some [CSU] engineering student leaders to look for a means of asserting some more positive values.”
Kip A. Wedel, associate professor of history and politics at Bethel College, wrote in his book, “The Obligation: A History of the Order of the Engineer,” that the ceremony was not a direct response to the Kent State shootings—it was already scheduled when the shootings happened. Yet, engineering students found the ceremony a positive action they could take in contrast to the overall turmoil. The first American ritual took place on June 4, 1970, at CSU. In total, 170 students, faculty members, and practicing engineers took the obligation. This established CSU as the first Link of the Order, as the OOE designates its local chapters. For their first ceremony, the CSU students fabricated smooth, unfaceted rings from stainless steel pipe. Later they were replaced by factory-made rings. According to Paula Ostaff, OOE’s Executive Director, about 20,000 eligible students and alumni obligate themselves yearly.
Societies hope that every engineer is imbued with a strong ethical sense and that their pledges are never far from mind. For some, the rings they wear serve a daily reminder that every paper they sign off on is touched by a physical reminder of their commitment.
These ethical and responsible engineering practices are especially salient today, when one in three American bridges needs repair or replacement, some have already collapsed, and engineers are working on projects related to the bipartisan infrastructure bill President Biden signed into law in 2021. Canada has committed $33 billion to its Investing in Canada Infrastructure Program. At the heart of these grand projects are many thousands of professional engineers, collectively working millions of hours. The professional vows they took aim to assure that the homes, bridges and airplanes they build will work as expected.