Decarbonization in Biobanking: A Potential New Scientific Area

Introduction

The continuing emission of greenhouse gases into the atmosphere results in raising the earth's temperature. As a consequence, the frequency and strength of extreme weather conditions all over the world are apparently increasing. This gradual climate change has both direct and indirect effects in many aspects of life, including food production, access to water, as well as the (re)emergence of diseases. ¹ Eugene Linden provided an excellent review of climate change in his recent book of “Fire and Flood: A People's History of Climate Change, from 1979 to the Present.” ² Briefly, in the 1850s, it was pointed out that the carbon dioxide (CO₂) gas heated up faster than air. In the 1890s, it was first conceived that additional atmospheric CO₂ could warm the planet. In the 1950s, the human-produced CO₂ emitted into the atmosphere was first estimated, while as of 1979, the effects of CO₂ on the climate were explored.

Importantly, climate change allows for a number of pathogens to acquire greater areas of geographical distribution, and as such providing an increased probability of spillover events for zoonotic infections.^3,4 The COVID-19 pandemic has strengthened those discussions even further.

Therefore, calls to reduce or entirely remove the carbon footprint of ongoing activities, collectively termed as decarbonization, have become increasingly more vocal. For example, such a call to action was recently published by Dzau et al for the U.S. Health Sector, ⁵ as well as by Atwoli et al in 2021, as a joint editorial, on behalf of more than 200 other health journals worldwide, calling for urgent action to limit greenhouse gas emissions to protect human health. ⁶ Some initial attempts at research in this area have also started to appear, as in the case of potential changes in gastrointestinal biopsies and their impact on CO₂ emissions. ⁷

These global movements encourage the biobanking field, as one of the foundational health care research infrastructures, to consider decarbonization as a potential novel research area both in terms of the molecules and the equipment used in research. In particular, the biobanking field includes a continuum of activities, from consent, sample and data collection and processing, storage, distribution and use of samples (and data, as appropriate), and the understanding of its carbon footprint and how this might be quantified, and subsequently mitigated, of importance. The current article provides a summary of the roundtable discussion during the 2022 ISBER Annual Meeting and Exhibits, as it focused on some of the abovementioned aspects, namely within laboratories engaging in sample cryopreservation and long-term storage, taking into account differences relating to low- and middle-income countries (LMICs).

Decarbonization in Biobanking: Challenges and Opportunities

Within the laboratories, and to reduce heating and/or cooling needs for equipment, several techniques have been implemented that allow the storage of substances at room temperature, including vacuuming, desiccating, and coating. However, the addition of protective agents to liquid analytes may be challenging for noncryogenic temperature preservation. Some biopharmaceuticals, which are composed of large-molecular-weight proteins, may include sugar or sugar alcohol to stabilize the medicinal properties of the proteins. ⁸ The mechanism of stabilization is believed to be the increase of the unfolding free energy by which the proteins thermodynamically favor keeping their native folded state.^9–13

In addition to this static equilibrium state of thermodynamics, the molecular dynamics of solvent molecules also dominate the deterioration speed of proteins.^14,15 For example, the addition of trehalose to the environmentally sensitive protein lactose dehydrogenase (LDH) increases the molecular rotational relaxation time of the water solvent, by which its enzymatic activity is improved twice as much compared with that without trehalose, after 40 days of preservation at 40°C. ¹⁶ More advanced methods for noncryogenic preservation than the addition of sugar or sugar alcohol may be the dry preservation method that is often used in pharmaceuticals. This method requires the vitrification (glass transition) of the sugar/sugar alcohol solution by dehydration that nearly inhibits the molecular motion while keeping its native folded state.

The most widely used dehydration method allowing stabilized proteins to be produced is freeze-drying. In this method, the samples are cooled down to a cryogenic temperature to form a partial glass state and massive ice followed by the sublimation of ice with slow warming under low pressure. ¹⁷ With regard to energy consumption and the throughput of samples, freeze-drying may be not suitable for liquid analytes. Instead, simple vacuum drying of thin liquid films at room temperature also forms vitrified additive solutions with stabilized protein.^18,19

At a technical level, the main challenge of decarbonization in biobanking is essentially equivalent to saving on energy consumption, as the majority of repositories contain ultracold freezers powered by electricity. Thus, especially in the case of biobanks, reducing the electric energy consumption of deep freezers, for example, those operating at around −80°C 24 hours per day, is the main issue. A simple estimation illustrates that a surprisingly large amount of electric energy is consumed by biobank facilities per year. A typical nonchlorofluorocarbon (CFC) deep freezer consumes 1 W (1 J/s) per unit vessel size of 1 L. ²⁰ Assuming that the average space occupied by a single stored analyte, including tissues, is 50 mL, such an analyte consumes an electric power of 50 mW. When a deep freezer works 24 hours per day, it consumes an electric energy of 1.2 Wh ( = 4.32 kJ) in a day, or 438 Wh per year for an analyte.

Although a single analyte does not consume a large amount of electric energy per se, biobanks contain considerable numbers of analytes in storage, thus consuming huge amounts of electricity. For example, the number of analytes in U.S. biobanks in 2000 was estimated at 300 million or more.^21,22 With this number, U.S. biobanks in 2000 consumed 131 GWh per year, which is about the electric energy consumed by 30,000 persons per year in the United States ²³ or equivalent to 30,523 tons of CO₂ emitted in the atmosphere (0.233 kg of CO₂e per kWh of electricity). ²⁴ However, these are estimates from 20 years ago, and before the introduction of high-throughput molecular technologies as part of downstream analyses of biobanked samples. In addition, it is very challenging to estimate the size of an average biobank due to the dearth of relevant information.

However, based on published information, an average size biobank would include at a minimum four or five −80°C freezers. ²⁵ As such, current consumption (even though data are lacking) is likely to be a multiple of the above, despite any performance improvements in the storage equipment in terms of energy consumption since that date.

Another energy-demanding aspect in biobanking relates to the use of liquid nitrogen (LN2). The rationale for using LN2 instead of electricity for long-term storage of biological substances relates to the ability of LN2 to reach lower temperatures, providing a very stable ultralow-temperature environment. The need for using LN2 is to guarantee that there is as little as possible degradation of the biological substances stored in biobanks. For example, it is known that there is some limited degradation of RNA in −80°C storage within a window of 5 years. Alternatives for improving the RNA preservation are to use a combination of liquid stabilizing solutions (e.g., RNAlater or equivalent) and −80°C, or LN2. ²⁶

Thus, LN2 is used widely both in the industrial manufacturing and health care fields, and consumption has grown steadily over the last two decades, according to a conservative estimate growing from USD 12.48B in 2015 to USD 16.14B in 2020, at an estimated compound annual growth rate of 5.28%. ²⁷ While the safety aspect of LN2 is very well-documented through occupational accidents involving staff^28,29 and stored samples, ³⁰ there is a dearth of information relating to the energy consumption in relation to regular LN2 usage.

There exists some anecdotal evidence regarding LN2 pricing (i.e., as a proxy of achieving an initial comparable measure of consumption). For example, currently, in the United States, LN2 costs can range from a low of around $0.30/L to a high of $6.50/L. The daily cost of LN2 varies depending on the volume of the tanks and is about $30,000/year for large biobanks. ³⁰ This is similar to the anecdotal experiences at the International Agency for Research on Cancer biobank, a major cancer biobank with more than 40 LN2 tanks, where annual consumption is ∼$30,000/year (Kozlakidis, pers. comm.).

According to the current estimates 0.4–0.5 kWh are required to produce 1 L of LN2. ³¹ As such, the above consumption rates of ∼$30,000/year would equate to ∼8825 L/year, and an estimated use of 3.97 MWh/year (using the average value from the ranges shown above), equivalent to the average annual energy consumption of two U.S. households ²³ or the equivalent of 0.925 tons of CO₂ emitted in the atmosphere per year. ²⁴ Taking the above together, there is an urgent need to understand the LN2 landscape in biobanking and move beyond sparse anecdotal evidence, if decarbonization is to be planned, implemented, and measured. Having said that, the impact on the decrease of the carbon footprint of electrically powered repositories is likely to be more significant than similar efforts regarding LN2-facilitated long-term storage.

In comparison with high-income countries (HICs), LMICs have a smaller number of biobanks per country with less well-resourced facilities. The priority of LMIC biobanks remains to cryopreserve the samples, so that their populations can be represented in international research as much as possible, and decarbonization has not entered the frame of discussions due to the additional financial investments it might entail. If decarbonization is to be achieved by investing in high-quality deep freezers alone, then this is a very difficult proposition for LMIC biobanks to afford, even if the decarbonization urgency is well understood. However, the current LMIC biobank preference remains cost-driven, including low-cost freezers that tend to consume more electricity (over 12 kWh/24 h) and heat emissions are more than 512 kcal/h. Unfortunately, low-cost freezers often are not CFC/hydrochlorofluorocarbon (CFC/HCFC) free and not using green reagents (Yadav, pers. comm.).

In addition, it might be even more challenging to estimate net energy consumption, in situations where electrical and LN2 supply is not always a regular occurrence. Despite these challenges, LMIC biobanks can contribute in decarbonization by using smart approaches, such as apps for pooling sample transfers across locations, which have the potential to introduce more environmental-friendly actions. For example, in India, there are such apps available (indicative example: “Porter app,”) through which samples from different locations can be pooled by a single person and/or vehicle.

Thus, there appears to be a context-dependent dichotomy in the opportunities that are to be pursued for decarbonization between HICs and LMICs. In HICs, new technologies that are more efficient in terms of energy and LN2 consumption, and which emerge through technical innovation can be afforded, tested, and scaled up as part of existing biobanking facilities and networks (e.g., new compressor technologies; Stirling engine; and others). By contrast, in LMICs, the intense resource competition is unlikely to justify investment in newer, more expensive technologies. However, LMIC biobanks have the opportunity to trailblaze decarbonization through behavioral and operational changes. In particular, as LMIC biobanks are relatively unable to decarbonize biobanking through additional investment in latest technology equipment, (and their maintenance thereof), then decarbonization might be achieved through an innovative use of existing equipment and facilities.

This would include operational changes (e.g., perhaps differently organized interactions with the operating theaters, so that there is a collection of tissues, but with a minimized need for sample processing and transportation; cross-functional organizational structures that can reduce overlap work on individual samples), as well as behavioral changes (e.g., perhaps moving LMIC biobanks closer to a just-in-time model, where the number of samples stored for projects long term is reduced, and more LMIC biobanks service prospective collections and short-term storage facilitated through an active, ongoing communication of needs with stakeholders). Eventually, it is anticipated that LMIC biobanks will be able to codevelop “tropicalized” laboratory equipment, that is, equipment that is designed to perform optimally within their context, ³² as summarized in Table 1.

Discussion

The themes identified in this ISBER roundtable discussion demonstrate that despite biobanks being considered significant consumers of energy and LN2, the discussion remains at a higher theoretical level at present due to lack of evidence. This happens due to a number of reasons, primarily the lack of information for comparative calculation of consumption between different settings per year and over time as biobanks grow and/or modernize their fleet of equipment. The call to action that has often been seen in the literature remains a high-level call to action (i.e., in terms of overall direction of travel and policy support), but this as yet has not translated to specific calls/activities within defined scientific fields. As such, the current article remains foundational and the first for the field of biobanking specifically.

However, the way decarbonization has been projected currently might be more relevant to HICs where the decarbonization aims are better developed over a number of years. The same cannot be said for LMICs, where decarbonization, as much as biobanking, is a relatively new idea, and solutions proposed to achieve reductions in the carbon footprint by equipment replacement remain unaffordable. As such, context-dependent solutions need to be designed for LMIC settings to allow for greener choices to be made, however, this also entails a greater awareness of the current challenges and opportunities on the part of biobank stakeholders. Having said that, energy consumption of equipment is not the only way in which a CO₂ reduction can be achieved in biobanks, as, for example, noncryogenic preservation techniques might be used more widely, allowing for molecular analytes to remain stable at room temperature for greater lengths of time, thus reducing the need for storage at low temperatures.

Finally, biobanking can become greener indirectly by increasing the overall utilization rate of the sample collected, and this relates directly to short- and term-goals that have been presented previously.^33,34

Conclusion

Decarbonization in biobanking should not be viewed as an academic exercise. It is likely to become increasingly visible as global energy costs rise, and should be viewed as a means to achieving a better way of biobanking. Thus, technological innovation, a greater awareness of the current situation, and behavioral change are important pieces of the puzzle in the route to improving the future of biobanking, even if the eventually implemented routes between HICs and LMICs might be distinctly different. This article sets the foundation for raising awareness of the subject and of the subsequent steps that need to be undertaken. Maintaining a focused discussion on the subject is likely to provide informed and implementable biobank-specific recommendations in the near future.