Why nothing can grow on Mars*

The problem with terraforming the Red Planet

This piece was originally published on Asimov Press! This is the version with all of the footnotes. Thanks to Niko & everybody else who helped me talk through the ideas!

Why Nothing Can Grow on Mars*

Two years ago, a friend took me out to coffee and said, “I think we can engineer an organism that could terraform Mars.” 

Terraforming - transforming a planet so it can support life - has long been the dream of science-fiction authors and futurists who want humans to become a multi-planetary society. Mars is the obvious target for this,¹ and they imagine building giant space mirrors,² importing greenhouse gasses and dropping asteroids to make a planet habitable.³ But with modern synthetic biology, maybe it’s as simple as engineering the right organism and seeding it in the right place.

So what would it take to design an organism that could terraform Mars? Well, to start, that organism would need to survive and grow on the Martian surface. Here on Earth, life already thrives among radiation, toxins, and cold in extreme environments similar to what you’d find on the Red Planet.⁴ Even so, because these conditions don’t converge on Earth, few of these microbes are capable of thriving in multiple extreme conditions at once. However, biotechnology could bring all of those disparate adaptations together and make a microbe that could thrive on the barren, dry, toxic and irradiated surface of Mars. The attempt will help us understand the true limits of life, unconstrained by the extreme conditions of Earth. 

With that in mind, we’ve launched a new research nonprofit called Pioneer Labs dedicated to this question. Our mission for the next few years is to try to make an organism that could grow outside on Mars. ⁵

I don’t expect to succeed. For one, the surface of Mars is drier than almost any environment on Earth because of the low pressure, freezing temperatures and high salt. Anything growing on Mars needs adaptations never before seen on Earth. But even if we fail, we’ll have probed how extreme biology can get and we’ll know how much terraforming will need to be done manually before life can take over.

If we do succeed, then our microbes could start changing Mars just as terrestrial microbes changed ancient Earth. They can create greenhouse gasses to warm the planet, crack open nitrates in the soil to thicken the atmosphere, even release oxygen for living things to breathe. Progress will be slow, but turning the red planet green is the only way humans will ever walk freely on the Martian surface.

Everything that’s not a problem

Broadly speaking, there are five major obstacles that life would need to overcome to survive on Mars. Luckily, there are lifeforms on Earth that can thrive despite each of these challenges, though there’s nothing that can survive all five combined. By taking inspiration from each of these extreme organisms, we can get a sense of how to make life that can prevail on Mars.

Radiation

Radiation is usually the first consideration of space hazards,⁶ and it’s certainly a doozy for humans. 5 sieverts of radiation will kill half of the people exposed to it,⁷ and a trip to Mars and back delivers about one sievert of ionizing radiation in the form of big and fast particles that can penetrate even thick shielding.⁸  But microbes can survive about a thousand times more ionizing radiation than people can,⁹ and grow quickly enough to outpace any damage done. As a general rule, the ionizing radiation that NASA agonizes over when it comes to space missions can be ignored when thinking about microbes. 

What’s not negligible is ultraviolet light. You can protect astronauts from it with some glass or a thin sheet of metal, but if you put your microbes outside on Mars the UV will kill almost everything in mere minutes as the radiation shreds DNA and destabilizes proteins.¹⁰ That’s a problem for any prospective Mars microbe, but we can take inspiration from UV-resistant Earth microbes to see if there are ways around this. 

Deinococcus radiodurans was isolated in the 50’s by a scientist who was trying to sterilize canned meat with gamma radiation, and it’s the best studied radiation-resistant microbe.¹¹ While it can only survive a few minutes of Mars-levels of UV radiation, there are organisms that are even more resistant to UV, like metal-loving Hymenobacter species from the deserts of Chile¹² and S. solfataricus from an acidic volcano in Spain which seems able to survive Mars-levels of UV comfortably.¹³

This is surprising. There are no environments on Earth that even approach the amount of UV that regularly hits the surface of Mars, so there’s little reason for that level of radiation resistance to have evolved here. Still, these radiation-resistant microbes have dozens of non-overlapping ways to resist ultraviolet radiation, ranging from simple solutions like pigments that absorb radiation and antioxidants that protect against damage to having many genome copies so that they can be used as repair templates for each other.¹⁴

The best Earth UV-resistant organisms couldn’t thrive in Martian UV, but they’re part way there. I do think it’s likely that combining these adaptations with each other properly would result in a lifeform that could survive Mars’s levels of ultraviolet radiation without a problem - but that’s a hypothesis I look forward to testing.   

Toxins

Whenever you talk about going to Mars, people mention perchlorates, toxic chemicals that are used in herbicides, rocket fuel and bleach. On Earth, perchlorates are considered industrial waste, and are toxic to humans above 2 parts per billion.¹⁵ Martian soil is composed of around 1% perchlorate,¹⁶ and that’s enough to prevent plant growth.¹⁷ Additionally, any liquid water on Mars is expected to be saturated salty brine with perchlorate concentrations ranging from 15-50%.¹⁸ 

But microbes figured out workarounds for perchlorates a long time ago, and Debaryomyces hansenii, an unassuming species of yeast commonly found in cheese, can not just survive, but grow in 30% perchlorate.¹⁹ It uses a variety of adaptations to get there, providing a potential roadmap to tolerate extreme levels of perchlorate.²⁰ Other organisms are able to use perchlorate in their metabolism, turning perchlorate to water and chloride ions and getting energy out of the deal.²¹ NASA is collaborating with researchers at Berkeley to take advantage of this to detoxify Martian regolith so crops can grow in it.²²

Temperature

Mars is cold, and anything growing there would need to be comfortable being chilly. The average temperature is about -50°C, or -60°F. But that’s about as accurate as saying the average temperature of Earth is 15°C, or 60°F. At the equator Mars can get up to 25°C, but the poles get as cold as -150°C.²³ That’s cold enough for carbon dioxide to condense into dry ice right out of the air.

If we want a lifeform that can spread across Mars, it needs to be able to grow below the freezing temperature of water. The record-holder for low-temperature growth on Earth belongs to Planococcus halocryophilus, an arctic permafrost bacteria that can grow in the lab at -15°C.²⁴ The runner-up is Psychromonas ingrahamii, a cyanobacterial algae that exists in glacial brine pockets and can grow at -12°C.²⁵ That temperature tolerance means a significantly larger chunk of Mars is in reach, including about the equatorial third of the planet.²⁶ 

Atmosphere

The Martian atmosphere is about 1% as dense as Earth’s. It completely lacks oxygen, and instead is 95% carbon dioxide and 3% nitrogen.²⁷ This gas mix would kill most animals, but isn’t a big deal for microbes. In fact, many microbes are anaerobic, and either don’t need oxygen or are actively poisoned by it.²⁸ Furthermore, Cyanobacteria grow well in a simulated Martian atmosphere²⁹ and the high levels of carbon dioxide improve the rate of photosynthesis.³⁰

The low pressure is a separate issue, but itself is not a problem. Bacteria can grow just fine at low pressures, so long as they have the gases they need - oxygen for aerobic species, carbon dioxide for photosynthetic ones and nitrogen for nitrogen-fixers.³¹ Furthermore, a diverse set of bacteria from permafrost soil can grow well under Martian atmospheric pressures.³² 

Water

Water is essential for life as we know it.³³ There’s an organism from the siberian permafrost that’s active with the tiny amounts of water that gathers on salt crystals, and many dozens of other ways for lifeforms to conserve water,³⁴ but that water needs to come from somewhere in the first place and it must be a liquid. No organism can create water from nothing. Here’s a map of the surface water on Mars, with white meaning no water.³⁵

Most of the planet is totally dry, with the water frozen at the poles at -100°C³⁶ or stuck in hydrated minerals.³⁷ And while it was a big deal a few years ago when we had good evidence of liquid water on Mars,³⁸ it's important to consider the state of that water - brines that are kept liquid by extremely high concentrations of salt.

This brings us to the prevailing problem with life on Mars. 

The Water on Mars is not Available

If you dumped a lake of water onto Mars, some of it would evaporate in the low pressure and condense again at the frigid poles. The salty soil would absorb the rest, binding the water tightly enough that it wouldn’t evaporate in the low pressure atmosphere. 

It’s hard to overstate how thirsty the Mars soil is. It’s salty and dry enough to suck water right out of any organism currently living on Earth. The entire planet is basically a desiccant, like those little white packets in food packages that keep them dry and prevent spoilage.³⁹ In fact, adding salt to food is an ancient method of preservation that works by sucking up the water so it can’t be used by microbes. 

The desiccation of an environment is quantified by scientists as water activity, and it’s expressed as a number between zero and one. A water activity of 1 means pure water, while a water activity of 0 means that there is no accessible water, and any added water will be absorbed immediately. Foods with a water activity of 0.6 or lower are considered effectively immune to contamination because the lack of water prevents microbial growth.⁴⁰ Dried fruits are one example, with a water activity around 0.55. This means that they will never go bad if kept properly dry. 

The known lower limit of water activity for life is 0.585, found in Aspergillus penicillioides, a fungus that lives in dust and dry paper.⁴¹ There aren’t very many organisms that can grow below a water activity of 0.7, with only 12 species known as of 2014.⁴² Most of these organisms grow in organic environments, like paper or honey.⁴³ But the dry environment on Mars is caused by salts, which are harsher than carbohydrates. It follows that the salt mix and temperatures on Mars may mean you need a water activity around 0.75 or higher in order to seed life.⁴⁴ 

Any liquid water on Mars has a water activity below 0.5.⁴⁵ There’s no way anything we know of now could grow in it. The salt would suck the liquid out of cells faster than noon in the Sahara.

NASA has looked into this. After “a deliberate and systematic search spanning several years,” they concluded in a 58-page report that “Mars is either too cold or too dry to support the propagation of terrestrial life.”⁴⁶ In reaching this conclusion, NASA assumed that the limits of life are -20°C and a water activity of 0.5, both of which are very permissive given the demonstrated biophysical limits of life on Earth. 

Unlike radiation and perchlorate, where there are no analogous conditions on Earth, there are environments on our planet with water activities below 0.5, and nothing grows there. Various dried foods are one example, but another is bittern salt ponds with very high concentrations of salt.⁴⁷ If nothing has figured out how to grow in those environments over billions of years of evolution, then it’s probably a pretty hard limit for normal Earth-based life that requires water to function. 

However, not all hope is lost. A theoretical Mars organism might not be able to grow in the perchlorate brines that currently exist on Mars, but it could try to create a better environment for itself in a few different ways. 

One possibility is a secreted layer that can trap heat and water, acting like a greenhouse to protect a biological community from the raw Martian conditions, and potentially thawing cleaner ice for water.⁴⁸ The theoretical engineered organisms could create their own habitats, protected from the harsh conditions of Mars by their own biologically produced insulation. Biofilms already do this on Earth with sugar-based materials,⁴⁹ but that almost certainly wouldn’t be good enough for Mars because the sugars aren’t good enough at holding in heat and water. You’d need to use novel materials with better properties.⁵⁰ 

Another organism from which we can draw inspiration is lichens, which are symbiotes of fungi and algae. They can survive extreme conditions and are able to absorb water from the air. A lichen from Antarctica once spent 18 months on the outside of the ISS, exposed to vacuum and unshielded solar UV, and came back mostly alive.⁵¹ Researchers studied that species to see if it could live on Mars, and it kept photosynthesizing under Martian pressures and temperatures, but didn’t grow.⁵² However, lichens survive dry conditions by drying out and waiting for water to come back,⁵³ and on Mars, the water would never come back. I’m not sure what adaptation could fix this - maybe some kind of active water uptake or storage mechanism - but these lichens are achingly close to being able to extract enough water from the surprisingly humid Martian night and use that to propagate.⁵⁴ 

Ultimately, the lack of bioavailable water is the largest scientific barrier to anything growing on Mars without human intervention. Unlike the radiation, toxins, temperature and low pressure, I don’t know of any pre-existing adaptations on Earth that could get around this problem, and it’s much harder to invent new 

Legal Barriers to Terraforming

Even if we were to overcome the technical challenges of making an organism that can survive on Mars, being permitted to release that life is another issue. Currently, terraforming is prohibited by NASA policy,⁵⁵ and questionable under international agreement.⁵⁶ 

Furthermore, terraforming Mars to an Earth-like state would probably drive any life native to Mars extinct, as earth-derived organisms would invade and transform its habitat. We’ve spent several billion dollars searching unsuccessfully for life on the Red Planet,⁵⁷ but it’s very hard to prove it doesn’t exist. Taking such an irreversible step is a decision that needs to be made by nations, not by individuals.

There are loopholes that could allow terraforming to proceed regardless, but I would much rather that terraforming be unambiguously allowed by some body with the proper jurisdiction to grant such permission. Getting that agreement is just as big of a barrier to terraforming as everything technical described above, but proceeding unilaterally would be unethical and dangerous.⁵⁸ Luckily, there’s a lot of cool science to be done in the meantime to answer the practical questions of how terraforming would even happen. 

The Near Future of Engineered Microbes in Space

Life already survives many of the individual extreme conditions present on Mars. But no known organism can grow in the polyextreme environment made when they’re all combined together. By mixing extremophilic traits from across Earth, we can learn more about how extreme biology can get, and what it takes to survive the irradiates, toxic, cold, low pressure, and dry wasteland that is modern Mars.⁵⁹ 

Our goal at Pioneer Labs is to find the true limits of life, unshackled from the environments that exist on Earth. If we make the most Mars-like microbe possible then we know how much abiotic terraforming would need to happen before it could be unleashed to finish the job. And once we know how many space mirrors or tons of greenhouse gasses are necessary, we can start making a detailed plan for really terraforming Mars. 

Even if it is impossible for anything to grow on Mars as it is now, engineered biology will be vital for supporting civilization in the stars. Polyextreme life will reduce the investment required to manufacture therapeutics, food, structural materials and chemical feedstocks vital to sustaining humans.⁶⁰ This benefit will also extend to Earth, where much of the cost of biomanufacturing is wrapped up in catering to fragile organisms that require stable pH, temperature, and aeration conditions and can only grow on sterile and pure feedstocks.

In other words, Pioneer Labs is making a moonshot in humanity’s long quest to terraform Mars. Even if we fail, our home will be better because of it.

1. The Moon has no atmosphere, severely limited supplies of water, carbon and nitrogen, making it an unattractive target as anything more than a pit stop on the way to somewhere else. https://www.acityonmars.com/ goes over this, but wikipedia also does a pretty good job https://en.wikipedia.org/wiki/Lunar_resources

Venus is also a potential target for terraforming, but it would be impossible for microbes. The water activity in the Venusian clouds is about 0.004, because you have small amounts of water dissolved in a lot of sulfuric acid. https://www.nature.com/articles/s41550-021-01391-3  Any carbon on the ground (even diamond!) is quickly roasted into carbon dioxide by the sulfuric acid & broiling temperatures. https://arxiv.org/abs/2108.02286   

The moons of Saturn are somewhat more hospitable, as Enceladus probably has abundant amounts of liquid water below the surface, while Titan is home to flowing rivers of hydrocarbons. I will note that Enceladus has no atmosphere and potentially limited supplies of nitrogen https://en.wikipedia.org/wiki/Enceladus and Titan’s average temperature is -180°C https://en.wikipedia.org/wiki/Titan_(moon) Neither get any appreciable amount of sunlight.  However, Saturn is incredibly far away, and while it takes spacecraft about seven months to reach Mars, it takes about seven years to get all the way to Saturn. https://www.thrillist.com/tech/transit-times-to-planets-how-long-would-it-take-to-get-to-mars  

2.  They’d be on the scale of hundreds of kilometers wide. http://www.users.globalnet.co.uk/~mfogg/zubrin.htm

3. The wikipedia page on terraforming is pretty good if you want to read more.

4. https://link.springer.com/article/10.1007/s41745-023-00382-9

5. Note that I don’t say we’re going to send it to Mars. This is a nonprofit with the goal of expanding knowledge of the limits of life, not the goal of unilaterally terraforming Mars or a for-profit trying to sell Mars-growing organisms to any possible buyer. 

6. It’s literally listed first: https://www.nature.com/articles/s41526-020-00124-6

7. https://www.nrc.gov/reading-rm/basic-ref/glossary/lethal-dose-ld.html

8. Table 1, 870-1200 milliSieverts. This is received over a longer time than is probably needed for an acute dose, but it’s still in the same order of magnitude.  https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000669

9. Figure 3 is what I’m referencing. https://www.mdpi.com/2304-8158/9/7/878

10. These are spores, which are broadly considered some of the most durable things in biology. The UVC dose is about 3.61 watts per square meter.  https://www.sciencedirect.com/science/article/abs/pii/S0019103505004021

11. D. radiodurans is one of the best-understood extremophiles, and has a pretty cool history: https://en.wikipedia.org/wiki/Deinococcus_radiodurans

12. This paper also establishes the lethal UV radiation dose for D. radiodurans at about 627 joules per meter squared. https://www.sciencedirect.com/science/article/pii/S1011134415302037

13. They try three strains. The winner comes from a super hot, acidic and sulfurous volcano. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669584/

14.  This is a whole field, and there really are a ton of ways to protect against DNA damage. Some of my other favorite examples are fast protein turnover, high intracellular metal concentrations to stabilize proteins against damage and several really incredible mechanisms of DNA damage repair. Here are three reviews that are an appropriate introduction to the topic. https://ami-journals.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2672.2011.04971.x https://amb-express.springeropen.com/articles/10.1186/s13568-019-0862-x https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.01882/full 

15. That’s the Massachusets guideline. The EPA one is 24.5 ppb. https://www.mass.gov/guides/perchlorate-frequently-asked-questions

16. Table 1 https://agupubs.onlinelibrary.wiley.com/doi/full/10.1002/2016GL072199

17. I think the “Martian regolith” condition here is the most relevant. https://www.mdpi.com/2571-8789/5/3/37

18. 50% perchlorate is basically wet slush. Both figure 1 and figure 2 get the idea across https://pubs.acs.org/doi/10.1021/acsomega.0c00444

19. Table 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281446/

20. The primary adaptations are to synthesize sugars to keep osmotic pressure stabile, stabilize proteins through glycosylation proteins and the cell wall through modulating crosslinking. https://enviromicro-journals.onlinelibrary.wiley.com/doi/10.1111/1462-2920.16152 

21. https://www.hindawi.com/journals/ijmicro/2019/6981865/

22.  I’ve heard this work was successful, but as far as I’m aware it hasn’t been published yet. https://www.nasa.gov/general/a-synthetic-biology-architecture-to-detoxify-and-enrich-mars-soil-for-agriculture/

23. Basic facts, basic links. https://science.nasa.gov/mars/facts/

24. https://www.nature.com/articles/ismej20138#Sec2 It does require rich media though.

25. 10 day doubling time, but give a gram of cells a year at that rate and you have 30 kilotons. https://pubmed.ncbi.nlm.nih.gov/14994177/ There’s a separate claim of a yeast that can grow at -20°C, but that was in a warehouse kept ‘around’ -20, which I don’t trust.

26. https://planetologia.elte.hu/mcdd/climatemaps.html

27. https://en.wikipedia.org/wiki/Atmosphere_of_Mars

28. Anaerobic organisms tend to have really interesting metabolisms, and use alternate oxidation sources for their metabolism. The perchlorate reducers described above are mostly anaerobic   https://en.wikipedia.org/wiki/Anaerobic_organism

29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633435/

30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679102/

31. The real problem is dessication. https://www.frontiersin.org/articles/10.3389/fspas.2020.00030/full

32. This paper has a retraction notice because they didn’t properly follow IRB guidelines for human microbiome sampling. But all of the data is correct. https://pubmed.ncbi.nlm.nih.gov/27870556/

33. https://www.nature.com/articles/s41598-019-56267-4

34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159902/

35. Figure 3. https://pubs.usgs.gov/publication/70028887 This is an incredible source, though it was updated later by  https://pubmed.ncbi.nlm.nih.gov/25401393/. The second one is basically an 80-page version of this article.

36. http://hyperphysics.phy-astr.gsu.edu/hbase/Solar/mars3.html

37. https://www.mdpi.com/2075-4434/8/2/40

38.  https://www.nature.com/articles/ngeo2412

39. Most desiccants use silica gel, but the purpose is still to dry things out.  https://www.webmd.com/digestive-disorders/what-to-know-silica-gel

40. The table of water activities is interesting. Peanut butter is 0.7, and that’s a lot of why it takes a long time to go bad. https://www.gov.mb.ca/agriculture/food-safety/at-the-food-processor/water-content-water-activity.html

41. Aspergillus penicillioides doesn’t like the cold, and can grow in 57% glycerol, which is where that 0.585 number comes from. https://pubmed.ncbi.nlm.nih.gov/27871132/

42. https://ami-journals.onlinelibrary.wiley.com/doi/10.1111/1462-2920.12598

43. https://www.sciencedirect.com/science/article/abs/pii/S0168160510006550

44. Perchlorates are what is known as a ‘chaotropic’ salt, which disrupts hydrogen bonding networks. This paper uses magnesium chloride, which is also a chaotropic salt. Check Figure 1a & table 1.  https://pubmed.ncbi.nlm.nih.gov/17298378/#

45. Figure 1b https://www.nature.com/articles/ngeo2412

46. Here’s a PDF link. The executive summary conveys most of the important information, but there are some greet maps and citations in the main body. https://mepag.jpl.nasa.gov/reports/ast_2006_6_677.pdf There’s an update in 2014 that basically reaffirms the same conclusion. https://pubmed.ncbi.nlm.nih.gov/25401393/

47. Page 55 https://link.springer.com/book/10.1007/978-3-642-74370-2, also the last paragraph before the conclusion of https://www.science.org/doi/10.1126/science.176.4032.242

48. This paper describes the idea of creating local greenhouses out of aerogels to make biologically-compatible microclimates. https://www.nature.com/articles/s41550-019-0813-0 

49. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC99016/

50. https://pubs.acs.org/doi/abs/10.1021/acs.accounts.5b00380 Though a hybrid material would probably be more suitable. https://pubmed.ncbi.nlm.nih.gov/20166232/

51. https://www.cambridge.org/core/journals/international-journal-of-astrobiology/article/viability-of-the-lichen-xanthoria-elegans-and-its-symbionts-after-18-months-of-space-exposure-and-simulated-mars-conditions-on-the-iss/6063CBD82A3DE50340680EC6450ACAC6

52. I am kind of shocked at the amount of water that was performed in this experiment - but it seems right.  https://www.nature.com/articles/s41598-023-32008-6#

53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073698/

54. The Martian atmosphere hits 100% humidity during the night. Given the pressure that’s about the same water density as a summer day in Death Valley https://agupubs.onlinelibrary.wiley.com/doi/full/10.1029/2019JE006080

55. It’s mostly geared towards preventing Earth microbes from eating any Mars-native life before we have a chance to study it. https://sma.nasa.gov/sma-disciplines/planetary-protection

56. I’m referring here to the Outer Space Treaty harmful contamination clause, to which all space-faring nations are signatories https://www.spacefoundation.org/space_brief/international-space-law/ This clause is primarily meant to prevent spreading radioactive waste in space, but it could be argued that encouraging genetically engineered bugs to spread across a planet would also be harmful contamination. 

57. Around $17 billion on landers and rovers, though searching for life isn’t the only purpose of those craft.  https://www.weforum.org/agenda/2021/02/mars-nasa-space-exploration-cost-perseverance-viking-curiosity/

58. I’m inspired here by Zach and Kelly Weinersmith’s book A City on Mars, which focuses on the legal challenges of human space colonization, most of which are directly extensible to terraforming.

59. We’re also concerned about biocontainment here. In short, we have plans for a tiered sterilization strategy and avoiding use of anything pathogenic. We also don’t expect engineered extremophiles to have a competitive advantage outside their niche in the wild any more than natural extremophiles do.

60. This field is known as ‘in-situ resource utilization’, and here’s my favorite intro on it. https://escholarship.org/uc/item/4j68f6gb In short, NASA hopes to use local resources, to convert atmospheric carbon dioxide to plastics and fuel https://www.frontiersin.org/articles/10.3389/fspas.2021.711550/full, potentially using minimally-shielded and easily constructed ‘greenhouses’ https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.733244/full