Category: Uncategorized

Schrödinger’s Web
Jonathan P. Dowling
CRC Press, $40.95

When news broke last year that Google’s quantum computer Sycamore had performed a calculation faster than the fastest supercomputers could (SN: 12/16/19), it was the first time many people had ever heard of a quantum computer.

Quantum computers, which harness the strange probabilities of quantum mechanics, may prove revolutionary. They have the potential to achieve an exponential speedup over their classical counterparts, at least when it comes to solving some problems. But for now, these computers are still in their infancy, useful for only a few applications, just as the first digital computers were in the 1940s. So isn’t a book about the communications network that will link quantum computers — the quantum internet — more than a little ahead of itself?

Surprisingly, no. As theoretical physicist Jonathan Dowling makes clear in Schrödinger’s Web, early versions of the quantum internet are here already — for example, quantum communication has been taking place between Beijing and Shanghai via fiber-optic cables since 2016 — and more are coming fast. So now is the perfect time to read up.

Dowling, who helped found the U.S. government’s quantum computing program in the 1990s, is the perfect guide. Armed with a seemingly endless supply of outrageous anecdotes, memorable analogies, puns and quips, he makes the thorny theoretical details of the quantum internet both entertaining and accessible.

Readers wanting to dive right in to details of the quantum internet will have to be patient. “Photons are the particles that will power the quantum internet, so we had better be sure we know what the heck they are,” Dowling writes. Accordingly, the first third of the book is a historical overview of light, from Newton’s 17th century idea of light as “corpuscles” to experiments probing the quantum reality of photons, or particles of light, in the late 20th century. There are some small historical inaccuracies — the section on the Danish physicist Hans Christian Ørsted repeats an apocryphal tale about his “serendipitous” discovery of the link between electricity and magnetism — and the footnotes rely too much on Wikipedia. But Dowling accomplishes what he sets out to do: Help readers develop an understanding of the quantum nature of light.

Like Dowling’s 2013 book on quantum computers, Schrödinger’s Killer App, Schrödinger’s Web hammers home the nonintuitive truths at the heart of quantum mechanics. For example, key to the quantum internet is entanglement — that “spooky action at a distance” in which particles are linked across time and space, and measuring the properties of one particle instantly reveals the other’s properties. Two photons, for instance, can be entangled so they always have the opposite polarization, or angle of oscillation.

In the future, a user in New York could entangle two photons and then send one along a fiber-optic cable to San Francisco, where it would be received by a quantum computer. Because these photons are entangled, measuring the New York photon’s polarization would instantly reveal the San Francisco photon’s polarization. This strange reality of entanglement is what the quantum internet exploits for neat features, such as unhackable security; any eavesdropper would mess up the delicate entanglement and be revealed.
While his previous book contains more detailed explanations of quantum mechanics, Dowling still finds amusing new analogies, such as “Fuzz Lightyear,” a canine that runs along a superposition, or quantum combination, of two paths into neighbors’ yards. Fuzz helps explain physicist John Wheeler’s delayed-choice experiment, which illustrates the uncertainty, unreality and nonlocality of the quantum world. Fuzz’s path is random, the dog doesn’t exist on one path until we measure him, and measuring one path seems to instantly affect which yard Fuzz enters even if he’s light-years away.

The complexities of the quantum web are saved for last, and even with Dowling’s help, the details are not for the faint of heart. Readers will learn how to prepare Bell tests to check that a system of particles is entangled (SN: 8/28/15), navigate bureaucracy in the Department of Defense and send unhackable quantum communications with the dryly named BB84 and E91 protocols. Dowling also goes over some recent milestones in the development of a quantum internet, such as the 2017 quantum-secured videocall between scientists in China and Austria via satellite (SN: 9/29/17).

“Just like the classical internet, we really won’t figure out what the quantum internet is useful for until it is up and running,” Dowling writes, so people can start “playing around with it.” Some of his prognostications seem improbable. Will people really have quantum computers on their phones and exchange entangled photons across the quantum internet?

Dowling died unexpectedly in June at age 65, before he could see this future come to fruition. Once when I interviewed him, he invoked Arthur C. Clarke’s first law to justify why he thought another esteemed scientist was wrong. “The first law is that if a distinguished, elderly scientist tells you something is possible, he’s very likely right,” he said. “If he tells you something is impossible, he’s very likely wrong.”

Dowling died too soon to be considered elderly, but he was distinguished, and Schrödinger’s Web lays out a powerful case for the possibility of a quantum internet.

---

Buy Schrödinger’s Web from Amazon.com. Science News is a participant in the Amazon Services LLC Associates Program. Please see our FAQ for more details.

At Bumpass Hell in California’s Lassen Volcanic National Park, the ground is literally boiling, and the aroma of rotten eggs fills the air. Gas bubbles rise through puddles of mud, producing goopy popping sounds. Jets of scorching-hot steam blast from vents in the earth. The fearsome site was named for the cowboy Kendall Bumpass, who in 1865 got too close and stepped through the thin crust. Boiling, acidic water burned his leg so badly that it had to be amputated.

Some scientists contend that life on our planet arose in such seemingly inhospitable conditions. Long before creatures roamed the Earth, hot springs like Bumpass Hell may have promoted chemical reactions that linked together simple molecules in a first step toward complexity. Other scientists, however, place the starting point for Earth’s life underwater, at the deep hydrothermal vents where heated, mineral-rich water billows from cracks in the ocean floor.

As researchers study and debate where and how life on Earth first ignited, their findings offer an important bonus. Understanding the origins of life on this planet could offer hints about where to search for life elsewhere, says Natalie Batalha, an astrophysicist at the University of California, Santa Cruz. “It has very significant implications for the future of space exploration.” Chemist Wenonah Vercoutere agrees. “The rules of physics are the same throughout the whole universe,” says Vercoutere, of NASA’s Ames Research Center in Moffett Field, Calif. “So what is there to say that the rules of biology do not also carry through and are in place and active in the whole universe?”

Lure of the land

At its biochemical core, the recipe for life relies on only a few ingredients: chemical elements, water or other media where chemical reactions can occur and an energy source to power those reactions. On Earth, all of those ingredients exist at terrestrial hot springs, home to some hardy creatures. Great Boiling Spring in Nevada, for example, is a scalding 77° Celsius, yet microbes manage to eke out an existence in water near the spring’s clay banks, researchers reported in 2016 in Nature Communications. Such conditions may reflect what it was like on early Earth, so these life-forms are most likely “related to some of the organisms that were originally on this planet,” says Jennifer Pett-Ridge, a microbial ecologist at Lawrence Livermore National Laboratory in California.

Microorganisms at hot springs can form communities called microbial mats. Made up of layers of microbes, mats have been found in geothermal areas all over the world, including in Yellowstone National Park, the Garga hot spring in southern Russia and Lassen — home to Bumpass Hell.

Over time, microbial mats can form into stromatolites, structures of microbes and minerals that have accumulated on top of one another; the layered appearance of a stromatolite reflects the passage of time, like a tree’s growth rings. Researchers found evidence of stromatolites in the Dresser Formation, a 3.5-billion–year-old rock feature in the Western Australia outback, along with evidence of hot spring mineral deposits, describing the findings in 2017 in Nature Communications. These findings, plus other signs of past microbes, led the team to suggest that some of the earliest life on Earth flourished in a hot spring environment.

David Deamer, a biophysicist at UC Santa Cruz, has spent four and a half decades exploring how life on our planet may have begun. He started out studying lipids, oily molecules that make up the membranes surrounding cells. Deamer, a big proponent of hot springs as the source of life’s start, has shown that conditions at terrestrial hot springs can produce bubblelike vesicles, with an outer layer made up of lipids. Such structures may have been the ancestral precursors of modern-day cells (SN: 7/3/10, p. 22).

Bruce Damer, an astrobiologist at UC Santa Cruz who brings a computer science approach to questions about the origins of life, worked with Deamer to test whether conditions at hot springs could drive condensation reactions, which join two molecules into one larger composite.

When water splashes out of a hot spring and evaporates, molecules that were in the liquid could undergo condensation reactions and link up. A subsequent splash would add more molecules that could undergo additional condensation reactions as liquid dries again. Repeated rounds of wetting and drying could produce chains of molecules.

In 2018, Damer set up shop at an active geothermal area in New Zealand, named along the usual theme — Hells Gate — to test that hypothesis. He prepared vials with ingredients needed to assemble strands of RNA, a nucleic acid that acts as a messenger during protein synthesis and may have catalyzed chemical reactions involved in the origins of life on early Earth (SN: 4/10/04, p. 232). The concoction included two of the four RNA building blocks — the nucleotides that link together to form RNA chains.

Damer stood the open vials in a metal block, roughly the size of two CD cases stacked together, and set the contraption into a near-boiling hydrothermal pool. To simulate the sometimes-wet, sometimes-dry burbling of the primordial Earth, Damer squirted acidic hot spring water into the vials, let them dry out and then repeated the wet-dry cycle several more times. When he brought the vials back to the lab, he found that they contained RNA-like strands that were 100 to 200 nucleotides long.

These results, reported in December 2019 in Astrobiology, indicate that complex molecules can form at hot springs, supporting the hypothesis that life on Earth may have developed in such an environment. In 2020, Damer returned to Hells Gate with Deamer and colleagues to confirm Damer’s results and do more wet-dry cycling studies.

Nicholas Hud, a chemist at Georgia Tech in Atlanta, studies the origins of life from a slightly different perspective: He explores how DNA and RNA nucleotides originated. He agrees that molecules are more likely to link together by condensation reactions on land, where wet-dry cycles can occur, than in the ocean. These reactions produce water; the formation of such a chemical bond isn’t energetically favorable when there’s already a lot of water around. “The best place to form that is in a hot, dry place,” Hud says. “The worst place to form it is in a wet, hot place.”

Underwater visions

Yet, wet, hot environs are just the place for life to originate, other evidence suggests. At hydrothermal vents on the deep, dark ocean floor, heated water spews into seawater that’s just a few degrees Celsius above freezing (SN: 7/23/16, p. 8).

In 2017, researchers found fossils in 3.77-billion-year-old rocks from Quebec that originated from the ancient ocean floor and had signs of hydrothermal activity (SN: 4/1/17, p. 6). The researchers claim that the distinct structures resemble those of microbes, suggesting that deep-sea environments may have supported some of the earliest life on Earth.

These environments can be extreme: Some vents belch dark plumes of water as hot as 400° C. However, if vents played a role in nurturing early forms of life, it likely happened at milder vents. For example, Lost City is a hydrothermal area in the middle of the Atlantic Ocean where the fluid streaming from vents ranges in temperature from 40° to 90° C. The region is named for dramatic limestone chimneys that rise as much as 60 meters above the seafloor.

These spires are home to microbes that feed off the products of a chemical reaction known as serpentinization. “Hydrothermal vents are interesting because they are at the interface of water and rock,” says astrophysicist Laurie Barge of NASA’s Jet Propulsion Laboratory in Pasadena, Calif.

A chemical reaction between water and rock at sites like Lost City makes the water coming out of vents more alkaline than the water in the ocean, which has a higher concentration of positively charged hydrogen ions. The resulting gradient from alkaline to more acidic water is like the difference between the positive and negative ends of a battery and can serve as an energy source for chemical activity.

To study the conditions at underwater vents, Barge creates simulated environments in the lab that, she says, “can mimic what you see in the natural world.” To represent an ocean on early Earth, she fills an inverted glass bottle with an acidic mixture containing iron but no oxygen. One end of a plastic tube pokes through the narrow end of the bottle, connected to a steady supply of a basic, or alkaline, solution just like a vent.

When Barge and colleagues injected an alkaline vent solution containing RNA nucleotides into an ocean-simulating bottle, individual RNA nucleotides linked up into short chains. These strands were only three or four nucleotides long, but the results suggest that the conditions at deep-sea vents could have supported reactions that led to the emergence of life on Earth, the researchers proposed in 2015 in Astrobiology.

Problems with both

To Deamer, there are big barriers to putting life’s pieces together near underwater vents: The vastness of the ocean would dilute molecules so they wouldn’t be concentrated enough to drive chemical reactions. Also, there are “no wet-dry cycles underwater.” In his view, repeated evaporation is needed to pull together enough molecules to bump into each other and react to form longer chains. Plus, unlike a hot spring’s freshwater, salty ocean water inhibits the formation of membranes and reactions that link together molecules, he says.

However, Deamer’s hot springs theory has its critics as well. DNA and RNA strands are composed of alternating phosphate and sugar molecules, but sugars “are profoundly unstable in hot spring environments,” says David Des Marais, an astrobiologist at NASA’s Ames Research Center.

And it may be too soon to rule out wet-dry cycles underwater. “You can have a little bit of water get stuck in a pore,” says Bill Brazelton, a marine microbiologist at the University of Utah in Salt Lake City. And then, because the serpentinization reaction at a vent uses up water in making other molecules, “you can have these cycles of dehydration inside a rock underneath the ocean.”

It may be impossible to nail down how life truly began on Earth: Most geologic records of what actually happened during Earth’s earliest days have long disappeared. There are numerous alternative hypotheses for where life began, beyond terrestrial hot springs and deep-sea vents. Recent research, for example, suggests that asteroid impacts could have sent superheated seawater into the crust to produce hydrothermal systems resembling hot springs (SN: 7/4/20, p. 10).

“I think we have to admit that there might be more than one little torturous path that might have been traversed in order for life to begin,” Des Marais says.

Life beyond Earth

Researchers are using what they’ve learned about how and where life may have originated on Earth to guide the search for biological signatures beyond our planet. There are several promising locales in our solar system.

“One of the things that NASA is really interested in knowing is whether or not there could be life in the subsurface oceans of the icy moons, like Europa and Enceladus,” says Batalha, of UC Santa Cruz. Scientists have evidence that the two moons, one orbiting Jupiter and the other, Saturn, have oceans of salty, liquid water beneath their icy shells (SN Online: 6/14/19).

These moons are intriguing because, along with liquid water, both have plumes of water erupting from their surfaces (SN: 6/9/18, p. 11), suggesting ongoing hydrothermal activity. NASA’s Cassini space probe even identified compounds containing carbon, nitrogen and oxygen within Enceladus’ plumes, some of the ingredients of amino acids, the building blocks of proteins. Europa and Enceladus fascinate astronomers because activity on their ocean floors may resemble the hydrothermal vents found on our own planet and may provide the chemical conditions to support life (SN: 4/18/15, p. 10).

Icy moons may also promote condensation reactions. “Even if you were on an icy moon, you might have … freezing and thawing of ice,” Barge says. “So, I think it’s important to say, if wet-dry cycling is important, then we should look for any environment in the solar system that might be able to promote oscillating conditions of dehydration.”

But to find signs of past life, Damer and Deamer believe Mars is a more promising place to look. Mineral deposits indicate the presence of hot springs and hydrothermal activity in the planet’s past, which would have sustained the wetting and drying cycles that the two researchers see as crucial for condensation reactions to get life going.

Missions to the Red Planet are already under way. NASA’s Perseverance rover will be searching for signs of ancient life, such as telltale minerals in rock samples, at Mars’ Jezero crater when the mission lands in February 2021 (SN: 7/4/20 & 7/18/20, p. 30). Though at least 54.6 million kilometers separate them, Mars and Bumpass Hell may not be so different.

Birds of a fossil feather

Four-winged Microraptor, perhaps one of the earliest flying dinosaurs, may have molted just a bit at a time — similar to modern songbirds, Carolyn Gramling reported in “This dinosaur may have shed its feathers like modern songbirds” (SN: 8/15/20, p. 12).

Reader Jan Voelker asked if the dinosaur may somehow be related to the pileated woodpecker.

It’s hard to say just how closely related Microraptor might have been to woodpecker ancestors, Gramling says. Woodpeckers, along with toucans and honeyguides, belong to a biological order called Piciformes. “The evolutionary origins of the Piciformes are still quite murky,” she says. “There just isn’t a whole lot in the fossil record about their ancestors, although there are fossils of modern-looking Piciformes dating as far back as the Oligocene Epoch, which spanned 33.9 million to 23 m­illion years ago.” But Piciformes are members of Aves, the biological class that includes all modern birds and that evolved from small feathered dinosaurs living during the Mesozoic Era, 252 million to 66 million years ago. Microraptor, which lived some 120 m­illion years ago alongside ancient birds, is distantly related to Aves.

Eyes on the sky

A new X-ray map of the entire sky looks deeper into space than any other X-ray map, Maria Temming reported in “This is the most comprehensive X-ray map of the sky ever made” (SN: 8/15/20, p. 30).

Reader Bob Garfield wondered how the image was made. “Is this a composite of a complete, 360-degree image of the sky or is the device looking in one general direction?” Garfield asked.

It’s a composite image of the entire sky, Temming says. “The telescope rotates continually to look at each point in the sky for 150 to 200 seconds on average and then moves on. Scientists stretch out the spherical view of the whole sky into this distended, ellipse-type shape so you can see it all at once on a 2-D surface,” she says.

Old dog, new math

A new formula for converting a dog’s age into human years is based on a comparative study of biological aging in Labrador retrievers and people, Bethany Brookshire reported in “Calculating a dog’s age in human years is harder than you think” (SN: 8/15/20, p. 5).

Reader Sue Jordan wondered how old her 13-year-old dog, a male black Lab and border collie mix, would be in human years according to the new equation.

“He’s around 72 years old in human years,” Brookshire says. “Keep in mind that the study doesn’t apply fully to all dogs, as it was done only in Labrador retrievers.” Collies and Labs might age at different rates. “As scientists do more of these comparisons, they will probably come up with different equations for different breeds,” she says.

“That 72 is a rough estimate; no one can say exactly how old your pup is in human years. But no matter what, I bet he’s great,” Brookshire says.

On the clock

A theoretical universal cosmic clock that may beget time must tick faster than a billion trillion trillion times per second, Emily Conover reported in “The universe might have a fundamental clock that ticks very, very fast” (SN: 8/15/20, p. 9).

Reader Lou Puls wondered if the limitation on the rate at which the f­undamental clock might tick could explain the arrow of time, or the idea that the total entropy (or disorder)

in the universe can only increase over time.

That’s a good question, Conover says. “When I interviewed physicist Martin Bojowald of Penn State for this study, I asked him the same thing. Sadly, he said that, at the moment, there’s no connection. It seems there’s no way to explain the arrow of time with this fundamental clock. At least, not yet,” she says.

Correction

The x-axis of the graph in “Agriculture and fossil fuels are driving record-high methane emissions” (SN: 8/15/20, p. 8) was incorrectly labeled. Instead of “metric tons per year,” it should say “million metric tons per year.”

When Nigerian physician Garba Iliyasu was 10, a venomous snake bit a family member. The man survived, but “it was quite severe,” Iliyasu recalls. “[He] was bleeding profusely.… From the nose. From the mouth. From the ear.”

Since then, Iliyasu, a specialist in infectious and tropical diseases, has tended to hundreds of snakebite victims at Kaltungo General Hospital, a health care hub for the surrounding Gombe State. During the two annual peaks in snakebite cases — the spring planting and autumn harvest seasons — “we see like six, seven to 10 patients in a day, on average,” he says. The hospital has only a few dozen beds. “Most times, you see patients on the floor.”

In the Western world, snakebites are a minor issue. In the United States and Europe, cases are rare and hardly ever fatal. Even in Australia — notorious for its deadly, venomous snakes — bites account for just a handful of annual deaths.

But in sub-Saharan Africa, about 270,000 people are bitten every year, resulting in more than 55,000 cases of post-traumatic stress disorder, over 14,700 amputations and about 12,300 deaths, Iliyasu and colleagues estimated in Toxicon in March 2019. Add in India and other snakebite hot spots and the annual numbers rise to more than 2 million bites that need clinical treatment, according to the World Health Organization. Between 80,000 and 138,000 victims die, and about three times that number have a life–changing disability.

Snakebites are “a neglected disease that affects the neglected section of the society,” Iliyasu says. The worst effects occur in mostly poor, rural communities that depend on farming and herding. Visit these places, he says, and “you will see how devastating the effect of snakebite is.” Victims are often the primary breadwinners of their households, so every death and disability contributes to the cycle of poverty.

But snakebites are finally getting the attention they’ve long needed. In 2017, the WHO officially recognized snakebites as a neglected tropical disease. That designation has led to an influx of funding for innovative research; the largest, more than $100 million, came in 2019 from the Wellcome Trust.

Effective snakebite treatments do exist, and those antivenoms are considered the “gold standard” of care. If a victim receives the right antivenom soon after a bite — within an hour or two — then the chances of survival are “very, very high,” says Nicholas Casewell, a biomedical scientist at the Liverpool School of Tropical Medicine in England.

But that “if” looms large, with big challenges remaining, including the difficulties of speedy access to care and the fact that most anti-venoms work against just a few of the hundreds of dangerous species of venomous snakes. Antivenoms are also “a technology that has seen limited innovation for 120 years,” says Andreas Laustsen, a biotech researcher and entrepreneur at the Technical University of Denmark in Kongens Lyngby.

Now, researchers from disparate fields of science are coming together to reimagine the way snakebites are managed. Casewell, Laustsen and others are tweaking current treatments, repurposing pharmaceuticals and even engineering toxin-stopping nanoparticles. The work offers hope that people everywhere, even in remote areas, will eventually be able to safely coexist with snakes.

A tarnished gold standard

There’s a saying in snakebite care that “time is tissue.” The longer it takes to stop a snake’s venom from moving through the victim’s body, the more damage occurs. Destruction begins from the moment of a bite, and the cocktail of proteins and other molecules in the venom will continue to ravage until the immune system produces enough antibodies to remove or destroy those toxins. The problem is, by the time antibodies have ramped up, it’s often too late.

The tissue maxim is especially true for bites from vipers and other snakes with venoms that target the blood and soft tissues and thus tend to cause more physical damage. But speed is also important for bites from snakes with paralytic venoms, such as the Indian cobra (Naja naja) and southern Africa’s black mamba (Dendroaspis polylepi). Their nerve cell–targeting toxins will progressively slow muscles until the lungs and heart stop working.

That’s where antivenoms come in. They speed up the immune system’s clearance of toxins, because antivenoms are, themselves, antibodies pulled from the blood of large animals, usually horses, that have been injected with venom. When given soon after a snakebite, antivenoms work well.

But for myriad reasons, fast delivery often doesn’t happen.

In rural communities, there may be relatively few health care providers who can stock and administer the intravenously delivered drugs, which often require refrigeration. In India, for instance, the staff in rural public health clinics rarely have the resources or training to safely administer the drugs and monitor for treatment side effects.

Patients are often sent several hours away to larger regional hospitals with more expertise. “A lot of [bite victims] die on the way,” says Kartik Sunagar, an evolutionary biologist at the Indian Institute of Science in Bangalore. Sunagar wrote about the challenges of developing antivenoms with Casewell, Laustsen and venom scientist Timothy Jackson of Liverpool in the August Trends in Pharmacological Sciences.

Once a patient arrives at a hospital, delays can still occur, Laustsen says, because medical staff wait until they’re completely sure someone needs antivenom before administering it. A large portion of snakebites are “dry,” which means no venom is injected, so antivenom isn’t always required.

Deciding which antivenom to use can be difficult. To glom on to and remove toxic substances, antibodies need to match their target almost exactly. And since each snake species makes its own unique blend of toxins, most venoms need a specific antivenom. Because bite victims can rarely reliably identify the species that bit them, doctors must wait for clear signs of damage to emerge to determine the right antivenom.

A “better safe than sorry” approach may seem warranted, but injecting antivenom when it’s not needed or if it’s the wrong kind can put the patient at even greater risk. As helpful as horse-derived antibodies can be, “the human immune system will recognize them as foreign,” Laustsen notes, and may launch an attack. This reaction to the antivenom itself can be life-threatening if not treated promptly.

Friendlier options

For the last decade or so, researchers have been working to take horses out of the equation to make antivenoms safer — and maybe more affordable. Laustsen is exploring a couple of approaches to avoiding the body’s reactions to horse-made antibodies.

One option is to produce “humanized” antibodies in the lab by replacing the ends of a human antibody gene with the venom-neutralizing parts from an effective equine antibody gene, so the patient’s body wouldn’t see the antibody proteins as foreign. But, even better, he hopes to discover effective fully human antibodies. With both approaches, he says, “you would remove at least 90 percent of all the side effects.”

Taking horses out of the mix may also open the door for designing antibodies that work against venoms from more than a few species. Laustsen and colleagues described one promising approach July 1 in Scientific Reports. The key is to take human antibody genes and insert them into bacteria-infecting viruses, which build the antibodies into their shells.

Since large databases of human antibody genes already exist, a whole variety of different human antibodies can be inserted into viruses for high-throughput testing to find antibodies that can bind to — and perhaps neutralize — venom toxins.

As a proof of concept, Laustsen’s team tested 40 billion antibodies from people, and identified one particularly exciting candidate: It protected human cells in lab dishes from more than a dozen lethal toxins from three cobra species.

Once the most broadly effective antibodies are found, Laustsen hopes to copy a page from the insulin-production handbook. For diabetes treatment, insulin used to be extracted from the pancreases of animals; now, it’s made by engineered bacteria in large fermentation tanks. A similar process could work to produce broad-spectrum antivenom, he says.

Moving antibody production out of animals could also have another important benefit: lower production costs. Right now, “antivenom is one of the most expensive drugs that you can find in the rural areas,” explains Muhammad Hamza, a medical doctor who, like Iliyasu, splits his time between research at Nigeria’s Aminu Kano Teaching Hospital and treating patients at the regional treatment center in Gombe State. Many of Hamza’s patients could be saved by antivenom, he says, but they can’t afford to pay for it. If the government hasn’t kept the clinic stocked with free medicine, patients die.

In Nigeria, a vial of antivenom costs around $60 to $70, Iliyasu says. He’s seen patients sell their animals, homes and farms to pay for treatment.

Antivenoms engineered without animals would save patients money because the ideal mix of antibodies would be more potent. At least 70 percent of the antibodies in current antivenoms don’t neutralize venom toxins at all, Iliyasu notes. As a result, it often takes several vials of antivenom — sometimes as many as 10 — to treat a bite patient. Boosting the percentage of neutralizing antibodies in each vial would go a long way toward making antivenoms affordable, Iliyasu says — and that’s why he’s excited to see the move away from animal-based production.

A pill for snakebite

Other researchers are turning to existing drugs to expand options for snakebite treatments.

Venom toxins generally cause harm by performing specific molecular actions, such as cutting up certain proteins or fats within cells. Targeted molecules that interfere with that nefarious work could potentially stop the toxins.

The idea of using drugs other than antibodies to inhibit venom toxins isn’t new. But it wasn’t until the molecular and genetic technology revolutions of the late 20th century that scientists could really deconstruct venoms to figure out which components are responsible for a venom’s worst effects. “We now have a very good handle on what the toxins are,” Casewell says.

It’s unlikely that one drug, or even a combination, would be able to neutralize the diversity of harmful toxins present in snake venoms and work as effectively as traditional antivenoms. But Casewell’s aim isn’t to replace antivenoms; he wants to safely slow down the most pernicious venom toxins to buy patients time to get to a clinic.

He and colleagues have so far focused on metalloproteinases — toxins that chop up proteins and are major players in the lethal and destructive nature of tissue-destroying venoms, such as those in saw-scaled vipers (Echis spp.). Casewell’s group picked a few drugs already on the market that bind up the metal ions that these proteinases need to function, and right off the bat, the drugs were surprisingly successful.

The group demonstrated that an existing small molecule drug used to treat heavy metal poisoning could reduce the deadly damage of viper bites in lab animals (SN: 6/6/20, p. 12). And when paired with another drug that inhibits a family of toxins that chew up certain fats, the drug was even more powerful. In animal tests, the combination neutralized the venoms of a more diverse collection of five snake species from all over the world.

The work is “quite exciting,” Casewell says, because it means small molecule drugs might be able to overcome the problem of geographic fragmentation — each venom needs its own antidote — that keeps antivenom markets too small and nonlucrative for pharmaceutical companies to invest in.

As a bonus, such small molecules are available in pill form and don’t need refrigeration or expert administration, making them easier to distribute in rural communities. In that way, such drugs could become an important “bridge to care,” Iliyasu says.

Next generation of treatments

While pills alone may never be a stand-alone treatment for snakebites, there are other alternatives to conventional antivenoms, says Shih-Hui Lee of the University of California, Irvine. “We can use a polymer.”

Lee and colleague Kenneth Shea are new to the field of snakebite treatment. “We’re not snake venom people,” Shea admits. They’re not even biologists. The two are materials scientists. But their approach to overhauling antivenom is so out of the box that it’s getting noticed.

Both spent much of their careers designing carbon polymers — essentially, plastic nanoparticles — with specific, desirable properties. After a while, the duo started to wonder if their designer plastics, which could bind to certain parts of proteins, could mimic the actions of antibodies.

Shea started with melittin, a bee venom toxin. To his surprise, the polymer nanoparticles worked. When injected into mice shortly after the injection of a life-threatening dose of melittin, the particles bound up enough of the toxin to save the animals’ lives, Shea and colleagues reported in the Journal of the American Chemical Society in 2010.

Those results helped him recruit Lee to the antivenom project and convince well-respected snakebite expert José María Gutiérrez of the University of Costa Rica in San José to collaborate. With his help, Shea and Lee set their sights on phospholipase A2s, a large family of toxins found in many deadly snake venoms.

Once again, Lee says, the polymer nanoparticles neutralized the toxins. In 2018, the particles proved effective against another family of snake toxins called three-finger toxins. The “plastic” antibodies saved mice from cobra venom, and healthy mice that received them had no adverse reactions, the team reported in PLOS Neglected Tropical Diseases.

There are still some design challenges to overcome before testing the polymers in people. The team wants to put these synthetic antibodies into injectable devices — much like an EpiPen — but right now, the nanoparticles are probably too big. So the next hurdle is to make them smaller and more able to travel from the injection site in a muscle to the surrounding tissues.

But the biggest challenge is convincing funding agencies that synthetic antibodies should be on the table. The hesitancy is understandable, Shea says, as there’s nothing like these nanoparticles on the market. “This is untested, so there has to be an element of faith in this,” he says.

Still, Shea and Lee believe in their creation. Producing a broad-spectrum antivenom with the nanoparticles “is technically much less challenging” than with biological antibodies, Shea says, so if the team can secure investors, he thinks the nanoparticles have the potential to be “a quite cheap antidote.”

Others are stepping out of the box, as well. Thanks to the influx of funding in the last few years, researchers around the world are trying all sorts of unconventional approaches to snakebite remedies. There are labs hoping to design DNA molecules known as aptamers that act like antibodies. Others are turning to animals, such as opossums, that are naturally immune to venoms in the hopes of translating that immunity into new drugs. All of this work is leading to some truly exciting technological developments, Casewell says.

But none of it will matter if there aren’t also investments in infrastructure and education, Hamza warns. “It is one thing to have the drug.… It’s another thing to get it available to the remotest parts of the world.”

He’s more excited about smartphone apps that could tell people in remote areas where the closest available antivenom is, for instance. And something as simple as providing farmers solid boots with instructions on when and why to wear them could prevent countless snakebites from happening in the first place.

With millions of snakebites occurring every year, there’s certainly many opportunities to improve the situation — and all of them need attention, Casewell says. That attention is finally coming. “This is kind of a once-in-a-lifetime moment for snakebites,” he says.