Blood Test Can Detect Lymphoma Cells Before a Tumor Grows Back
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
When David M. Kurtz was doing his clinical fellowship at Stanford University Medical Center in 2009, specializing in lymphoma treatments, he found himself grappling with a question no one could answer. A typical regimen for these blood cancers prescribed six cycles of chemotherapy, but no one knew why. "The number seemed to be drawn out of a hat," Kurtz says. Some patients felt much better after just two doses, but had to endure the toxic effects of the entire course. For some elderly patients, the side effects of chemo are so harsh, they alone can kill. Others appeared to be cancer-free on the CT scans after the requisite six but then succumbed to it months later.
"Anecdotally, one patient decided to stop therapy after one dose because he felt it was so toxic that he opted for hospice instead," says Kurtz, now an oncologist at the center. "Five years down the road, he was alive and well. For him, just one dose was enough." Others would return for their one-year check up and find that their tumors grew back. Kurtz felt that while CT scans and MRIs were powerful tools, they weren't perfect ones. They couldn't tell him if there were any cancer cells left, stealthily waiting to germinate again. The scans only showed the tumor once it was back.
Blood cancers claim about 68,000 people a year, with a new diagnosis made about every three minutes, according to the Leukemia Research Foundation. For patients with B-cell lymphoma, which Kurtz focuses on, the survival chances are better than for some others. About 60 percent are cured, but the remaining 40 percent will relapse—possibly because they will have a negative CT scan, but still harbor malignant cells. "You can't see this on imaging," says Michael Green, who also treats blood cancers at University of Texas MD Anderson Medical Center.
The new blood test is sensitive enough to spot one cancerous perpetrator amongst one million other DNA molecules.
Kurtz wanted a better diagnostic tool, so he started working on a blood test that could capture the circulating tumor DNA or ctDNA. For that, he needed to identify the specific mutations typical for B-cell lymphomas. Working together with another fellow PhD student Jake Chabon, Kurtz finally zeroed-in on the tumor's genetic "appearance" in 2017—a pair of specific mutations sitting in close proximity to each other—a rare and telling sign. The human genome contains about 3 billion base pairs of nucleotides—molecules that compose genes—and in case of the B-cell lymphoma cells these two mutations were only a few base pairs apart. "That was the moment when the light bulb went on," Kurtz says.
The duo formed a company named Foresight Diagnostics, focusing on taking the blood test to the clinic. But knowing the tumor's mutational signature was only half the process. The other was fishing the tumor's DNA out of patients' bloodstream that contains millions of other DNA molecules, explains Chabon, now Foresight's CEO. It would be like looking for an escaped criminal in a large crowd. Kurtz and Chabon solved the problem by taking the tumor's "mug shot" first. Doctors would take the biopsy pre-treatment and sequence the tumor, as if taking the criminal's photo. After treatments, they would match the "mug shot" to all DNA molecules derived from the patient's blood sample to see if any molecular criminals managed to escape the chemo.
Foresight isn't the only company working on blood-based tumor detection tests, which are dubbed liquid biopsies—other companies such as Natera or ArcherDx developed their own. But in a recent study, the Foresight team showed that their method is significantly more sensitive in "fishing out" the cancer molecules than existing tests. Chabon says that this test can detect circulating tumor DNA in concentrations that are nearly 100 times lower than other methods. Put another way, it's sensitive enough to spot one cancerous perpetrator amongst one million other DNA molecules.
They also aim to extend their test to detect other malignancies such as lung, breast or colorectal cancers.
"It increases the sensitivity of detection and really catches most patients who are going to progress," says Green, the University of Texas oncologist who wasn't involved in the study, but is familiar with the method. It would also allow monitoring patients during treatment and making better-informed decisions about which therapy regimens would be most effective. "It's a minimally invasive test," Green says, and "it gives you a very high confidence about what's going on."
Having shown that the test works well, Kurtz and Chabon are planning a new trial in which oncologists would rely on their method to decide when to stop or continue chemo. They also aim to extend their test to detect other malignancies such as lung, breast or colorectal cancers. The latest genome sequencing technologies have sequenced and catalogued over 2,500 different tumor specimens and the Foresight team is analyzing this data, says Chabon, which gives the team the opportunity to create more molecular "mug shots."
The team hopes that that their blood cancer test will become available to patients within about five years, making doctors' job easier, and not only at the biological level. "When I tell patients, "good news, your cancer is in remission', they ask me, 'does it mean I'm cured?'" Kurtz says. "Right now I can't answer this question because I don't know—but I would like to." His company's test, he hopes, will enable him to reply with certainty. He'd very much like to have the power of that foresight.
This article is republished from our archives to coincide with Blood Cancer Awareness Month, which highlights progress in cancer diagnostics and treatment.
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
New elevators could lift up our access to space
Story by Big Think
When people first started exploring space in the 1960s, it cost upwards of $80,000 (adjusted for inflation) to put a single pound of payload into low-Earth orbit.
A major reason for this high cost was the need to build a new, expensive rocket for every launch. That really started to change when SpaceX began making cheap, reusable rockets, and today, the company is ferrying customer payloads to LEO at a price of just $1,300 per pound.
This is making space accessible to scientists, startups, and tourists who never could have afforded it previously, but the cheapest way to reach orbit might not be a rocket at all — it could be an elevator.
The space elevator
The seeds for a space elevator were first planted by Russian scientist Konstantin Tsiolkovsky in 1895, who, after visiting the 1,000-foot (305 m) Eiffel Tower, published a paper theorizing about the construction of a structure 22,000 miles (35,400 km) high.
This would provide access to geostationary orbit, an altitude where objects appear to remain fixed above Earth’s surface, but Tsiolkovsky conceded that no material could support the weight of such a tower.
We could then send electrically powered “climber” vehicles up and down the tether to deliver payloads to any Earth orbit.
In 1959, soon after Sputnik, Russian engineer Yuri N. Artsutanov proposed a way around this issue: instead of building a space elevator from the ground up, start at the top. More specifically, he suggested placing a satellite in geostationary orbit and dropping a tether from it down to Earth’s equator. As the tether descended, the satellite would ascend. Once attached to Earth’s surface, the tether would be kept taut, thanks to a combination of gravitational and centrifugal forces.
We could then send electrically powered “climber” vehicles up and down the tether to deliver payloads to any Earth orbit. According to physicist Bradley Edwards, who researched the concept for NASA about 20 years ago, it’d cost $10 billion and take 15 years to build a space elevator, but once operational, the cost of sending a payload to any Earth orbit could be as low as $100 per pound.
“Once you reduce the cost to almost a Fed-Ex kind of level, it opens the doors to lots of people, lots of countries, and lots of companies to get involved in space,” Edwards told Space.com in 2005.
In addition to the economic advantages, a space elevator would also be cleaner than using rockets — there’d be no burning of fuel, no harmful greenhouse emissions — and the new transport system wouldn’t contribute to the problem of space junk to the same degree that expendable rockets do.
So, why don’t we have one yet?
Tether troubles
Edwards wrote in his report for NASA that all of the technology needed to build a space elevator already existed except the material needed to build the tether, which needs to be light but also strong enough to withstand all the huge forces acting upon it.
The good news, according to the report, was that the perfect material — ultra-strong, ultra-tiny “nanotubes” of carbon — would be available in just two years.
“[S]teel is not strong enough, neither is Kevlar, carbon fiber, spider silk, or any other material other than carbon nanotubes,” wrote Edwards. “Fortunately for us, carbon nanotube research is extremely hot right now, and it is progressing quickly to commercial production.”Unfortunately, he misjudged how hard it would be to synthesize carbon nanotubes — to date, no one has been able to grow one longer than 21 inches (53 cm).
Further research into the material revealed that it tends to fray under extreme stress, too, meaning even if we could manufacture carbon nanotubes at the lengths needed, they’d be at risk of snapping, not only destroying the space elevator, but threatening lives on Earth.
Looking ahead
Carbon nanotubes might have been the early frontrunner as the tether material for space elevators, but there are other options, including graphene, an essentially two-dimensional form of carbon that is already easier to scale up than nanotubes (though still not easy).
Contrary to Edwards’ report, Johns Hopkins University researchers Sean Sun and Dan Popescu say Kevlar fibers could work — we would just need to constantly repair the tether, the same way the human body constantly repairs its tendons.
“Using sensors and artificially intelligent software, it would be possible to model the whole tether mathematically so as to predict when, where, and how the fibers would break,” the researchers wrote in Aeon in 2018.
“When they did, speedy robotic climbers patrolling up and down the tether would replace them, adjusting the rate of maintenance and repair as needed — mimicking the sensitivity of biological processes,” they continued.Astronomers from the University of Cambridge and Columbia University also think Kevlar could work for a space elevator — if we built it from the moon, rather than Earth.
They call their concept the Spaceline, and the idea is that a tether attached to the moon’s surface could extend toward Earth’s geostationary orbit, held taut by the pull of our planet’s gravity. We could then use rockets to deliver payloads — and potentially people — to solar-powered climber robots positioned at the end of this 200,000+ mile long tether. The bots could then travel up the line to the moon’s surface.
This wouldn’t eliminate the need for rockets to get into Earth’s orbit, but it would be a cheaper way to get to the moon. The forces acting on a lunar space elevator wouldn’t be as strong as one extending from Earth’s surface, either, according to the researchers, opening up more options for tether materials.
“[T]he necessary strength of the material is much lower than an Earth-based elevator — and thus it could be built from fibers that are already mass-produced … and relatively affordable,” they wrote in a paper shared on the preprint server arXiv.
After riding up the Earth-based space elevator, a capsule would fly to a space station attached to the tether of the moon-based one.
Electrically powered climber capsules could go up down the tether to deliver payloads to any Earth orbit.
Adobe Stock
Some Chinese researchers, meanwhile, aren’t giving up on the idea of using carbon nanotubes for a space elevator — in 2018, a team from Tsinghua University revealed that they’d developed nanotubes that they say are strong enough for a tether.
The researchers are still working on the issue of scaling up production, but in 2021, state-owned news outlet Xinhua released a video depicting an in-development concept, called “Sky Ladder,” that would consist of space elevators above Earth and the moon.
After riding up the Earth-based space elevator, a capsule would fly to a space station attached to the tether of the moon-based one. If the project could be pulled off — a huge if — China predicts Sky Ladder could cut the cost of sending people and goods to the moon by 96 percent.
The bottom line
In the 120 years since Tsiolkovsky looked at the Eiffel Tower and thought way bigger, tremendous progress has been made developing materials with the properties needed for a space elevator. At this point, it seems likely we could one day have a material that can be manufactured at the scale needed for a tether — but by the time that happens, the need for a space elevator may have evaporated.
Several aerospace companies are making progress with their own reusable rockets, and as those join the market with SpaceX, competition could cause launch prices to fall further.
California startup SpinLaunch, meanwhile, is developing a massive centrifuge to fling payloads into space, where much smaller rockets can propel them into orbit. If the company succeeds (another one of those big ifs), it says the system would slash the amount of fuel needed to reach orbit by 70 percent.
Even if SpinLaunch doesn’t get off the ground, several groups are developing environmentally friendly rocket fuels that produce far fewer (or no) harmful emissions. More work is needed to efficiently scale up their production, but overcoming that hurdle will likely be far easier than building a 22,000-mile (35,400-km) elevator to space.
New tech aims to make the ocean healthier for marine life
A defunct drydock basin arched by a rusting 19th century steel bridge seems an incongruous place to conduct state-of-the-art climate science. But this placid and protected sliver of water connecting Brooklyn’s Navy Yard to the East River was just right for Garrett Boudinot to float a small dock topped with water carbon-sensing gear. And while his system right now looks like a trio of plastic boxes wired up together, it aims to mediate the growing ocean acidification problem, caused by overabundance of dissolved carbon dioxide.
Boudinot, a biogeochemist and founder of a carbon-management startup called Vycarb, is honing his method for measuring CO2 levels in water, as well as (at least temporarily) correcting their negative effects. It’s a challenge that’s been occupying numerous climate scientists as the ocean heats up, and as states like New York recognize that reducing emissions won’t be enough to reach their climate goals; they’ll have to figure out how to remove carbon, too.
To date, though, methods for measuring CO2 in water at scale have been either intensely expensive, requiring fancy sensors that pump CO2 through membranes; or prohibitively complicated, involving a series of lab-based analyses. And that’s led to a bottleneck in efforts to remove carbon as well.
But recently, Boudinot cracked part of the code for measurement and mitigation, at least on a small scale. While the rest of the industry sorts out larger intricacies like getting ocean carbon markets up and running and driving carbon removal at billion-ton scale in centralized infrastructure, his decentralized method could have important, more immediate implications.
Specifically, for shellfish hatcheries, which grow seafood for human consumption and for coastal restoration projects. Some of these incubators for oysters and clams and scallops are already feeling the negative effects of excess carbon in water, and Vycarb’s tech could improve outcomes for the larval- and juvenile-stage mollusks they’re raising. “We’re learning from these folks about what their needs are, so that we’re developing our system as a solution that’s relevant,” Boudinot says.
Ocean acidification can wreak havoc on developing shellfish, inhibiting their shells from growing and leading to mass die-offs.
Ocean waters naturally absorb CO2 gas from the atmosphere. When CO2 accumulates faster than nature can dissipate it, it reacts with H2O molecules, forming carbonic acid, H2CO3, which makes the water column more acidic. On the West Coast, acidification occurs when deep, carbon dioxide-rich waters upwell onto the coast. This can wreak havoc on developing shellfish, inhibiting their shells from growing and leading to mass die-offs; this happened, disastrously, at Pacific Northwest oyster hatcheries in 2007.
This type of acidification will eventually come for the East Coast, too, says Ryan Wallace, assistant professor and graduate director of environmental studies and sciences at Long Island’s Adelphi University, who studies acidification. But at the moment, East Coast acidification has other sources: agricultural runoff, usually in the form of nitrogen, and human and animal waste entering coastal areas. These excess nutrient loads cause algae to grow, which isn’t a problem in and of itself, Wallace says; but when algae die, they’re consumed by bacteria, whose respiration in turn bumps up CO2 levels in water.
“Unfortunately, this is occurring at the bottom [of the water column], where shellfish organisms live and grow,” Wallace says. Acidification on the East Coast is minutely localized, occurring closest to where nutrients are being released, as well as seasonally; at least one local shellfish farm, on Fishers Island in the Long Island Sound, has contended with its effects.
The second Vycarb pilot, ready to be installed at the East Hampton shellfish hatchery.
Courtesy of Vycarb
Besides CO2, ocean water contains two other forms of dissolved carbon — carbonate (CO3-) and bicarbonate (HCO3) — at all times, at differing levels. At low pH (acidic), CO2 prevails; at medium pH, HCO3 is the dominant form; at higher pH, CO3 dominates. Boudinot’s invention is the first real-time measurement for all three, he says. From the dock at the Navy Yard, his pilot system uses carefully calibrated but low-cost sensors to gauge the water’s pH and its corresponding levels of CO2. When it detects elevated levels of the greenhouse gas, the system mitigates it on the spot. It does this by adding a bicarbonate powder that’s a byproduct of agricultural limestone mining in nearby Pennsylvania. Because the bicarbonate powder is alkaline, it increases the water pH and reduces the acidity. “We drive a chemical reaction to increase the pH to convert greenhouse gas- and acid-causing CO2 into bicarbonate, which is HCO3,” Boudinot says. “And HCO3 is what shellfish and fish and lots of marine life prefers over CO2.”
This de-acidifying “buffering” is something shellfish operations already do to water, usually by adding soda ash (NaHCO3), which is also alkaline. Some hatcheries add soda ash constantly, just in case; some wait till acidification causes significant problems. Generally, for an overly busy shellfish farmer to detect acidification takes time and effort. “We’re out there daily, taking a look at the pH and figuring out how much we need to dose it,” explains John “Barley” Dunne, director of the East Hampton Shellfish Hatchery on Long Island. “If this is an automatic system…that would be much less labor intensive — one less thing to monitor when we have so many other things we need to monitor.”
Across the Sound at the hatchery he runs, Dunne annually produces 30 million hard clams, 6 million oysters, and “if we’re lucky, some years we get a million bay scallops,” he says. These mollusks are destined for restoration projects around the town of East Hampton, where they’ll create habitat, filter water, and protect the coastline from sea level rise and storm surge. So far, Dunne’s hatchery has largely escaped the ill effects of acidification, although his bay scallops are having a finicky year and he’s checking to see if acidification might be part of the problem. But “I think it's important to have these solutions ready-at-hand for when the time comes,” he says. That’s why he’s hosting a second, 70-liter Vycarb pilot starting this summer on a dock adjacent to his East Hampton operation; it will amp up to a 50,000 liter-system in a few months.
If it can buffer water over a large area, absolutely this will benefit natural spawns. -- John “Barley” Dunne.
Boudinot hopes this new pilot will act as a proof of concept for hatcheries up and down the East Coast. The area from Maine to Nova Scotia is experiencing the worst of Atlantic acidification, due in part to increased Arctic meltwater combining with Gulf of St. Lawrence freshwater; that decreases saturation of calcium carbonate, making the water more acidic. Boudinot says his system should work to adjust low pH regardless of the cause or locale. The East Hampton system will eventually test and buffer-as-necessary the water that Dunne pumps from the Sound into 100-gallon land-based tanks where larvae grow for two weeks before being transferred to an in-Sound nursery to plump up.
Dunne says this could have positive effects — not only on his hatchery but on wild shellfish populations, too, reducing at least one stressor their larvae experience (others include increasing water temperatures and decreased oxygen levels). “If it can buffer water over a large area, absolutely this will [benefit] natural spawns,” he says.
No one believes the Vycarb model — even if it proves capable of functioning at much greater scale — is the sole solution to acidification in the ocean. Wallace says new water treatment plants in New York City, which reduce nitrogen released into coastal waters, are an important part of the equation. And “certainly, some green infrastructure would help,” says Boudinot, like restoring coastal and tidal wetlands to help filter nutrient runoff.
In the meantime, Boudinot continues to collect data in advance of amping up his own operations. Still unknown is the effect of releasing huge amounts of alkalinity into the ocean. Boudinot says a pH of 9 or higher can be too harsh for marine life, plus it can also trigger a release of CO2 from the water back into the atmosphere. For a third pilot, on Governor’s Island in New York Harbor, Vycarb will install yet another system from which Boudinot’s team will frequently sample to analyze some of those and other impacts. “Let's really make sure that we know what the results are,” he says. “Let's have data to show, because in this carbon world, things behave very differently out in the real world versus on paper.”