Nitrogen-fixing GM crops to “transform the lives of small farmers”

Background

Nitrogen is essential for plant growth, but despite it being the most abundant element in the atmosphere, its availability for plants is limited. Plants are only able to use nitrogen in reduced forms – nitrate or ammonium. Some plants – like legumes – provide their own through a symbiotic relationship with bacteria that fix nitrogen from the air into the soil (as ammonia), which is then drawn up by the plants through their roots. In return, plants house these bacteria in their root nodules and provide them with sugars and oxygen.

Other types of crops – including major cereal crops such as maize, wheat, and rice – typically rely on added fertilisers for nitrogen, including manure, compost, and chemical fertilisers. These added fertilisers can be expensive for farmers and associated with a host of environmental problems, including fossil fuel use in production and water pollution from run-off.

In organic and agroecological farming, the nitrogen needs of cereal crops are sometimes met by rotating them with legume crops. The legumes enrich the soil with nitrogen, which feeds next year’s cereal crop. The rotation system also protects against the buildup of crop-specific pathogens and pests.

However, many conventional farmers prefer to grow one crop on a large scale for years at a time. Therefore, for nearly 50 years, researchers have tried to genetically engineer major cereal crops to have nitrogen-fixing ability.⁸ They were hoping this endeavour could benefit farmers and ecosystems by reducing or eliminating the need for additional fertiliser, especially in Africa,⁹ where many farmers cannot afford artificial fertiliser.

Claims

There has been little change in the language used to describe these GM ventures over the past decades. In 1980, a paper by scientists at UC Davis concluded that it is “a realistic long-term goal to genetically engineer new nitrogen-fixing plants.” ² And a briefing paper by the UK government’s Parliamentary and Scientific Committee from 1990 speaks of nitrogen fixation as a “current commercial target” of genetic engineering research.¹⁰

The rhetoric was dialled up in 2012, when the Bill & Melinda Gates Foundation gave £6.4m to the John Innes Centre in Norwich, UK for a five-year project to engineer cereals such as corn and barley to extract nitrogen from the atmosphere, rather than relying on ammonia-based fertilisers. According to Katherine Kahn of the Gates Foundation, the research had “the long-term potential … to transform the lives of small farmers” as it “could dramatically boost the crop yields in Africa”.¹¹

In 2014, the UK government’s Council for Science and Technology still described the target of nitrogen-fixing cereals as a “long-term and high-reward programme”.⁴

Results

Nitrogen fixation is a complex biological process. Engineering cereal crops to acquire this ability has proved difficult. Despite decades of research and a great deal of funding, no nitrogen-fixing plant has been engineered.

Recent papers continue to refer to the potential for success:

• A paper published in 2020 noted the biological “challenges” to achieving nitrogen-fixing cereal crops, but stated, “Recent advances are creating paths to transgenic nitrogen-fixing cereal crops” as a “feasible and sustainable alternative” to synthetic nitrogen fertilisers. The authors added that “Gene editing of associative nitrogen-fixing bacteria may be a near-term solution”.¹² Associative nitrogen fixation is performed by free-living bacteria, as opposed to bacteria growing inside the plant.

• In 2021 the Regulatory Horizons Council “Report on genetic technologies” invoked the potential of a new generation of GM techniques, stating that gene editing could “(potentially) improve plants’ ability to fix nitrogen”.⁵

• In 2022, University of Oxford researchers claimed a “major breakthrough in establishing the ability of cereals… to make their own nitrogen fertiliser”.¹³ However, a close reading of the study reveals failings on multiple levels (see below). 

• A 2023 paper from the UK’s Royal Society described the transfer of genes that confer the ability to form nitrogen-fixing associations with bacteria to cereal crops as a “longer term” goal.¹⁴

The endeavour continues across several areas of research. Two approaches stand out: engineering a symbiosis between plants and bacteria and transferring nitrogen-fixing genes from bacteria directly into the plant, as detailed below.

1. Engineering a symbiosis between plants and nitrogen-fixing bacteria

Inspired by the mechanisms of leguminous plants, researchers have been attempting to create a similar process in cereal crops. Nitrogen-fixing symbiosis involves hundreds of processes¹⁵ and many genes in both the bacteria and the host plant. Conferring this trait on a cereal crop would require the association and coordination of these two vastly different organisms.¹⁶

In natural systems, these processes can be broken down into four steps – the plant reading the signals produced by the bacteria in the soil, creating a nodule-like structure to house the bacteria, appropriate colonisation of the nodules by bacteria, and establishment of a suitable environment for the nitrogen-fixing process inside the nodule.¹⁷ Scientific knowledge is currently most advanced for the first step – signalling between the bacteria and the cereal crop¹⁸ – but is still not fully understood.¹⁹

Scientists have attempted to reproduce these natural processes by using GM. As an example, research into free-living nitrogen fixing bacteria (not in nodules) paired with specially adapted GM cereal plants was presented in 2022 as a proof-of-concept success. In the research, scientists at the Sainsbury Laboratory in the UK demonstrated some communication between a GM barley plant and GM nitrogen-fixing bacteria.²⁰ The Sainsbury Laboratory’s accompanying press release was titled, “An engineered barley plant that ‘orders’ soil bacteria to manufacture ammonia fertiliser”.¹⁵ The University of Oxford, which collaborated with the Sainsbury Laboratory, hailed the research as “a major breakthrough in establishing the ability of cereals… to make their own nitrogen fertiliser in the form of ammonia”.²¹

The scientists had engineered the GM barley to produce a signalling molecule called rhizopine that controls the genes in the rhizobia bacteria growing on the surface of the plants’ roots. The researchers showed that plants secreting rhizopine were able to influence nitrogen fixation by the bacterium on their roots. The GM bacteria were engineered to have an improved response to rhizopine, so that they produced the enzyme nitrogenase, which bacteria use to fix atmospheric nitrogen. The intention was for the bacteria to only fix nitrogen on the barley and not on other plants, such as weeds.²²  

The bacteria on the surface of the GM barley did produce extra nitrogenase (the first step towards nitrogen fixation), whereas bacteria on the non-GM plant did not.²⁰

Failures on multiple levels: Despite the claims made for this study, a close reading reveals failures on multiple levels. The GM bacteria were defective in colonising the roots;²³ the bacteria did not respond well to the signal;²⁴ the bacteria were only on the plant surfaces so they would only donate some of the nitrogen they produced to the barley;²⁵ and the level of nitrogen-fixing activity by the GM bacteria on the GM barley was poor (“suboptimal”) compared to the wild-type non-GM bacteria colonising the GM or non-GM barley.²⁶

Moreover, nitrogen fixation was established only by reducing the surrounding oxygen concentration to 1%, but that concentration is incompatible with plant growth.²⁰ So there is much work still to be done if such GM approaches are to replace or reduce synthetic fertilisers.

Other limitations of the study: The researchers did not mention whether the GM barley they engineered was a useful strain for further nitrogen-fixation experimentation or for farmers to grow in their fields. In addition, they engineered associative bacterial nitrogen fixation, not the more efficient nodule-type fixation. They state that “the costly energy demands” of this type of nitrogen fixation have driven “the evolution of multilayered genetic mechanisms” that repress nitrogen fixation and favour the assimilation of ammonia (which contains nitrogen), rather than releasing the nitrogen to plants. This evolutionary trend appears to impede the aims of this GM technology.

Also, because of the high energetic costs to the bacterium, any genetically engineered nitrogen-releasing bacterium will evolve away from the influence of the nitrogen-assimilating GM crop. This implies that new GM bacteria will continually have to be developed and reapplied by farmers to maintain nitrogen levels, with ongoing costs.

Moreover, the researchers used kanamycin (an antibiotic) resistance marker genes in engineering the bacteria. Due to the growing public health problem of antibiotic-resistant disease-causing bacteria, the use of antibiotic resistance genes in GMOs has been condemned by experts.²⁷ EU lawmakers decided that such genes should be phased out from GMOs by 2008²⁸ – but the GMO industry failed to comply.

General technical obstacles to GM nitrogen-fixing crops: There are other technical obstacles to overcome before the dream of GM cereal crops with a symbiotic relationship to nitrogen-fixing bacteria can become a reality. For example, the presence of oxygen inhibits a key enzyme (nitrogenase) that the bacteria use to fix atmospheric nitrogen.²⁹ Legumes have a highly evolved system to create a nodule environment with the exact amount of oxygen that the bacteria need to fuel their chemical reactions, and no more. It is challenging to replicate that environment in a non-legume plant.³⁰

The above-mentioned factors may explain why in natural systems, legumes capture nitrogen-fixing bacteria in nodules: there is a lower energetic cost and the nodules may provide a low oxygen environment, optimising the bacteria’s nitrogen-fixing activity.

The energy question: Nitrogen fixation is an energy-intensive process. It is not clear where this additional energy will come from in cereal crops. Hence there are concerns that achieving nitrogen fixation may decrease yields by diverting energy from other important functions or parts of the plant.³¹ A 2023 review on the status of work on nitrogen-fixing in plants described energy supply as “an important obstacle to be overcome”.³²

Non-GM nitrogen-fixing maize: In recent years an indigenous Mexican landrace variety of maize, known as Sierra Mixe, has been discovered to have some nitrogen-fixing capacity. The maize has aerial roots, which secrete a mucilage that provides the low oxygen environment needed for the functioning of the nitrogenase enzyme. Using its mucilage, Sierra Mixe maize meets 29%–82% of its nitrogen requirements through the activity of nitrogen-fixing bacteria.³³ Although the Sierra Mixe landrace cannot be used directly in most situations due to its long cropping season and size,³⁴ the discovery has provided a new avenue for research. However, indigenous communities are resisting attempts to privatise these genetic resources.³⁵

2. Transferring nitrogen-fixing genes from bacteria directly into the plant

The genes responsible for the nitrogen-fixing abilities of bacteria have been identified and work is under way to try to genetically engineer them directly into plants. This appears simpler than trying to replicate the entire process of a successful symbiotic relationship between a plant and the bacteria.

However, this approach has challenges of its own. The gene cluster responsible for nitrogen fixing in bacteria is large and, for it to have a chance of working in a cereal crop, the cellular components responsible for controlling the pathway under different conditions will also have to be transferred. Even if this transfer is successful, there is no guarantee the genes will work in a plant with different gene expression requirements from a microbe.³⁶

A series of articles published in 2020 reported that the Voigt Lab at the Massachusetts Institute of Technology (MIT) had some promising avenues for research to overcome these challenges.³⁷ Yet there have been no updates since, suggesting that any further successes have been limited.

Concerns about the glutamate dehydrogenase gene

A Union of Concerned Scientists report warned: “One particularly worrisome side effect of GE NUE [genetically engineered nitrogen use efficiency] genes is that they may indirectly increase the production of harmful substances in the edible parts of crops. Most crops have genes that produce harmful substances, but these genes are not expressed, or are expressed at low levels, in the edible parts of crops. Engineered genes, however (or genes manipulated through traditional breeding), may have the opposite effect due to complex interactions between the engineered gene and crop genes.”

The report cites as an example the glutamate dehydrogenase gene derived from E. coli bacteria, which has been studied as a possible NUE gene for engineering into plants: “When expressed in tobacco it altered the production of many plant compounds (some were increased and some were decreased), most notably the amounts of nine known carcinogens and 14 potential drugs… Although tobacco is not eaten by humans, this example illustrates the possibility of unpredictable and potentially harmful changes in food crops.”³⁸

Companies

Many companies and organisations have funded research into nitrogen-fixing GM crops. In 2009 the Union of Concerned Scientists surveyed the US Dept of Agriculture (USDA) database for field trials of “nitrogen metabolism altered” GM crops and found that the majority were conducted by either Monsanto (now Bayer) or Pioneer Hi Bred (now Corteva), with several being conducted by Arcadia.³⁸ Leading non-business funders of research in this area are the UK’s Biotechnology and Biological Sciences Research Council³⁹ and the Bill & Melinda Gates Foundation.⁴⁰

In recent years the large agribusiness companies have shifted their attention away from trying to develop GM nitrogen-fixing cereals to focus on “biologicals” (nitrogen-fixing microbes, which may or may not be GM) that are applied to seeds, crops, or soil.⁴¹

Patents

As there are multiple processes and research areas under investigation, there are thousands of patents on processes and genes related to nitrogen-fixing and nitrogen use efficiency in cereal crops and other plants (the term often used in patents for nitrogen use efficiency is “nitrogen metabolism”).⁴²

A patent search on “nitrogen metabolism altered transgenic crops” turns up over 27,000 records and shows that the field is dominated by a few large companies: Bayer/Monsanto, Pioneer Hi Bred (now Corteva), and Syngenta; and several academic institutions, including the Universities of Alberta, New York, and Guelph.⁴³ In 2014 Bayer filed a broadly focused patent on “plants having enhanced nitrogen use efficiency and methods of producing same”⁴⁴ (status pending).

The University of Florida filed a patent in 1996 on amino acid and nucleotide sequences related to the glutamate dehydrogenase (GDH) enzyme discovered in alga. According to the patent claims, plants genetically engineered with nucleotide sequences encoding subunits of the enzyme show improved properties: for example, increased growth and improved stress tolerance. Improved nitrogen metabolism is also covered by the patent. As the USDA helped fund the research, it has rights in the invention.⁴⁵

The numbers and claims of patents in this area stand in contrast to the limited success of the research projects that have been funded. Only time will reveal the extent of the gap between aspiration and reality.

Author: Ayms Mason. Reviewers/editors: Claire Robinson; Pat Thomas; Franziska Achterberg. Scientific reviewers: Dr Jonathan Latham; Dr Martha Mertens.

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23. The researchers write: “Finally, we found that AcΔnifA (pSIN02) are mildly defective in their ability to colonize barley roots”.[↩]
24. The researchers write: “We found that 3.60% of cells isolated from the RA and 4.56% of cells isolated from the RS fraction of T2 RhiP plants exhibited GFP fluorescence higher than the mean 99th percentile of that detected in bacteria recovered from wild-type plants (here defined as GFP+) (Fig. 2C), confirming these subpopulations were induced for PmocB::GFP.”[↩]
25. This is shown by the title of the paper: “associative nitrogen fixation” and wording in the abstract: “on the roots”. The signal is secreted by the plant into the soil and detected there by the A. caulinodans. See also “AcCherry (pSIR02) cells were subsequently recovered from the rhizoplane and endosphere (here termed root-associated, RA) and from the rhizosphere”. The rhizoplane and the endosphere refer to spaces outside the root, which is why the researchers call them root-associated.[↩]
26. The researchers write: “Partially effective nitrogenase activity was induced on both T1 and T2 RhiP barley, whereas it was not detected on wild-type plants (Fig. 4E). Compared to the wildtype Ac, which produced ∼70 nmol C2H4 h1 plant1 when colonizing wild-type or RhiP barley roots, nitrogenase in AcΔnifA carrying pSIN02 produced 10.24 nmols C2H4 h1 plant1 when colonizing T1 RhiP barley roots and 3.63 nmols C2H4 h1 plant1 when colonizing T2 RhiP barley roots, equating to ∼15% and 5% of wild-type levels, respectively”.[↩]
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42. For example, a search on the patent database lens.org for “nitrogen metabolism plants” gives over 147,000 results: https://www.lens.org/lens/search/patent/list?q=nitrogen%20metabolism%20plants[↩]
43. Lens.org. Patent search performed 7 Jul 2025. https://www.lens.org/lens/search/patent/list?q=nitrogen%20metabolism%20altered%20transgenic%20crops&p=4&n=10&s=_score&d=%2B&f=false&e=false&l=en&authorField=author&dateFilterField=publishedDate&orderBy=%2B_score&presentation=false&preview=true&stemmed=true&useAuthorId=false[↩]
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