Research into senescent cells could result in extended human lifespans and significant policy implications

Improved housing, sanitation, and healthcare have significantly increased humans’ life expectancy, and biomedical advances have the potential to further extend people’s lives. The life expectancy of a person born in 1860 was only about 39 years; a person born today can expect to live about 79 years. Now some researchers are studying whether altering humans’ senescent cells could increase lifespans to an even greater extent.

Cellular senescence – a process by which cells stop replicating after a set amount of time – is vital to prevent devastating cancers, but also contributes to age-related diseases. Every time a cell replicates, its DNA accumulates a low number of errors. If cells replicate unchecked, these errors can snowball, forming masses of non-functioning cells that damage healthy tissues. For example, the cells responsible for malignant cancers, which can be deadly, do not show any sign of senescence. On the other hand, senescent cells, which are alive but no longer dividing, can build up in a person’s tissues, release harmful chemicals, and contribute to age-related health issues.

Reducing the numbers of senescent cells in peoples’ bodies could extend human lives. Studies in mice have shown that removing senescent cells can help mice live longer and maintain their physical abilities. Treated mice lived, on average, 36 percent longer than mice that retained senescent cells. Furthermore, old mice given a drug that reduces the number of senescent cells were able to survive COVID-19 in significantly higher numbers than old mice not given the drug. While these results are promising, whether the results can be reproduced in humans is an open question. Some early trials in humans testing drugs that reduce populations of senescent cells are targeting specific diseases, such as age-related macular degeneration, glaucoma, and chronic obstructive pulmonary disease.

If it becomes possible to further diminish the effects of aging over the next few decades, there would be substantial policy implications. For example, greater longevity could mean older Americans experience longer periods of dependency on their families or the government, increasing retirement and medical costs. People might also stay healthier for longer, which may necessitate an increase of the retirement age. As this research into human longevity matures, it is important that policymakers consider the fiscal, legal, and medical implications of extending human lives.

This CSPI Science and Technology Policy Snapshot expands upon a scientific exchange between Congressman Bill Foster (D, IL-11) and his new FAS-organized Science Council.

To reduce the burden on traditional data centers, improving on DNA data storage could be the key

The pace at which data – such as photos, videos, and social media posts – are being generated is ramping up drastically, exceeding the scaling limits of traditional silicon-based data storage technologies, and DNA could be deployed to help meet this challenge. As an indication of the massive amount of data storage that may be required, one model predicts that by the year 2030, electricity use by data centers could approach about eight percent of total global electricity demand. New paradigms for data storage, such as the use of DNA for preserving information, are necessary.

DNA is genetic material that contains plans for the design of living things, but DNA can also be used to store data created by living things. DNA is an attractive material for data storage – it is stable, writable, readable, and information dense. In theory, the entire world’s data could be stored in a coffee mug-sized portion of DNA.

So how does storing, for example, a video, in DNA work? (See Figure 1.) First, an algorithm is used to encode the video into the As, Ts, Cs, and Gs that make up DNA molecules. The DNA molecules are then synthesized, and stored. To access the data, the DNA molecules would be sequenced, and the DNA sequences translated using the same algorithm, reproducing the video.

Figure 1.

Data storage and retrieval in DNA. First, data – like those stored on a computer hard drive – are processed by an algorithm that translates 1s and 0s into DNA sequences made up of As, Ts, Cs, and Gs. DNA strands with those sequences are then synthesized – or written – and stored either in living cells (in vivo) or in the test tube (in vitro). Data can be retrieved from storage in part by using PCR – the same technology deployed to test for the coronavirus that causes COVID-19 – to selectively target specific data packages. The PCR products can be read with DNA sequencing instruments, providing the original DNA sequences, and reproducing the data. Figure adapted from Ceze, Nivala, and Strauss 2019, Nature Reviews Genetics.

DNA is a polymer – a substance consisting of a high number of similar building blocks that are linked together – and other polymers can be used to store information, too. For example, plastic polymers are being explored for information-storage applications; one group synthesized a plastic polymer that, when read out, reproduced a quote by Jane Austen. By expanding experimental development efforts into (i) increasing the rates at which DNA can be synthesized and sequenced and (ii) detecting and correcting for errors in DNA synthesis, and by pursuing fundamental research into data storage across a variety of polymers, it is possible the U.S. science and technology enterprise could devise a polymer-based method for rapid data storage and retrieval, and meet the data storage challenge.

This CSPI Science and Technology Policy Snapshot expands upon a scientific exchange between Congressman Bill Foster (D, IL-11) and his new FAS-organized Science Council.

Benchtop DNA synthesizers could become more ubiquitous, and it’s up to policymakers to chart the way forward

The genetic blueprints for humans, plants, disease-causing bacteria, and all other living things are written in DNA, and machines capable of synthesizing DNA are becoming more accessible to potential users. Benchtop DNA synthesizers promise to increase the speed and efficiency of research in academic and industrial laboratories; however, it will be critical to incorporate safeguards into benchtop machines to prevent the printing of DNA sequences that would be used for harmful purposes. Researchers should be permitted to operate a benchtop DNA synthesizer to, for instance, make genetic material that is then used by a microbe to build a biofuel. But, aside from research conducted by pre-approved specialists, printing DNA that codes for deadly agents like the ricin or diphtheria protein toxins, for example, should be prohibited. As instruments capable of small-scale, rapid-turnaround DNA synthesis are already starting to enter the market, policymakers may be faced with a new era of democratized DNA synthesis, and should grapple with how to maximize the benefits of this technology while minimizing potential harm.

A National Academies of Sciences, Engineering, and Medicine report speculated that by 2027, individuals both with and without formal scientific training would be rapidly prototyping and developing biological designs and products. In both institutional and DIY contexts, there are protections that could be put in place to drastically reduce the likelihood of the misuse of benchtop DNA synthesizers. For instance, a January 2020 report from the World Economic Forum, crafted in collaboration with the Nuclear Threat Initiative, recommends that benchtop DNA synthesizers:

• Be sold to and accessed by only legitimate, validated users;
• Incorporate a mechanism that compares DNA sequences entered into the machine for synthesis to a database of pathogen and toxin DNA sequences before DNA strands are printed;
• Allow synthesis of potentially hazardous DNA only for users preauthorized for such sequences, and prohibit the synthesis of pathogen or toxin DNA requested by unauthorized actors; and
• Be used by individuals who have received training in biosafety and biosecurity.

Before efficient benchtop DNA synthesizers become even more ubiquitous, decision-makers have an opportunity to craft forward-thinking policies that both (i) protect the technology from misuse and (ii) promote its potential to advance human health, a cleaner environment, and many other public goods.

This CSPI Science and Technology Policy Snapshot expands upon a scientific exchange between Congressman Bill Foster (D, IL-11) and his new FAS-organized Science Council.

The field of synthetic biology has enormous potential for constructively impacting society, already contributing products such as drugs, food ingredients, and living fertilizers. As the field continues to develop, standardization of synthetic biology tools, techniques, and processes could help realize that potential. The rapid growth of the semiconductor industry in the 20th century, and its push for standardization, serves as a potential model for the synthetic biology industry. This idea was explored during a late April hearing held by the Senate Commerce, Science, and Transportation Committee, convened to discuss the nomination of Dr. Eric Lander to be director of the Office of Science and Technology Policy.

The potential of synthetic biology

It is critical for the U.S. to continue to lead in synthetic biology. Synthetic biology has the potential to revolutionize many sectors, such as healthcare and agriculture. For example, researchers are working to engineer immune cells to treat cancer, correct defective genes, and optimize antibody and vaccine production. In agriculture, synthetic biology could be used to optimize plants’ ability to use nitrogen and phosphorus, decreasing the amount of chemical fertilizer necessary, or to increase the nutritional value of foodstuffs. Policymakers recognize the potential of synthetic biology; for instance, the discipline is listed as a key research priority in the Endless Frontier Act, and is the primary focus of a separate bipartisan bill that aims to support U.S. synthetic biology.

During the hearing, Dr. Lander suggested (1:06:05) that to make synthetic biology technologies accessible to even more innovators, the federal government should play a role in creating and disseminating synthetic biology “toolkits,” as well as sharing best practices for their use. Dr. Lander related this to the early stages of working with semiconductor toolkits and assembling integrated circuits. Standardization contributed to the advancement of the semiconductor industry, and to take full advantage of synthetic biology’s potential, standards, and standardization, could play a role. Setting standards allows for exact measurements and more precise communication between researchers. For synthetic biology specifically, standardization would support the ability to scale production and take on even more complex tasks. Some of the challenges surrounding standards are the possibility that standardization could reduce researchers’ flexibility and creativity, as well as identifying which systems or processes should be standardized, and successfully deciding on what those standards should be.

Many standardization attempts in synthetic biology have been focused on bacteria because they are generally more easily engineered than other types of cells, and they can produce valuable compounds for both research and industrial uses. Cell-free systems, where components of interest are produced artificially or extracted or enriched from other cells and then refined in vitro, have been successfully standardized, but unfortunately, these systems lack the ability to scale or produce important substances without human intervention. Some areas that researchers are looking to standardize further include the design of strands of DNA, and the production of data and biosystem models.

One federal agency, the National Institute for Standards and Technology (NIST), is already working on establishing standards in synthetic biology. NIST is currently working with researchers and manufacturers to develop measurement tools to help compare and reproduce scientific results. One accomplishment was to produce human genome reference materials to help compare the genes of people with different lineages, increase confidence in DNA sequencing, and improve genetic tests. NIST has also helped develop reference materials for monoclonal antibodies and RNA, as well as developed the first method to use DNA to authenticate mouse cell lines used in genetic research.

Standardization would help improve communication between researchers, and quality assurance across the field. The act of standardizing research processes and manufacturing has aided many other industries before, and, as Dr. Lander referenced, one of those is the semiconductor industry.

Semiconductors and standardization

The advent of semiconductors, which are now critical to electronic devices, began in the early 1800s, and research and development continued into the 1900s. A semiconductor is a material whose ability to conduct electricity falls between that of a conductor, such as most metals, and an insulator, such as rubber or glass. Unlike most metals, whose ability to conduct electricity decreases as they get hotter, semiconductors improve their electrical conductivity as they increase in temperature. A large number of semiconductors are made of silicon, though there are other materials, like germanium and gallium arsenide, used as well. Their unique properties make semiconductors extremely important in all modern electrical devices.

When first developed, semiconductors were not standardized. By 1972, there were more than 2,000 different specifications for silicon semiconductor wafers. One of the major industry organizations, the Semiconductor Equipment and Materials International (SEMI), decided to develop standards for semiconductors and published its first book of these standards in 1978.

These SEMI standards are developed through a network of small volunteer task forces. When a new standard needs to be devised, a task force is created with volunteers from SEMI’s industry member organizations. Any proposed standards are reviewed and voted on by the entire membership. If there are any negative votes, open forum meetings are convened to discuss why those organizations opposed the standards, additional evidence is presented, and if the opposition is considered persuasive, the proposed standards are sent back to the task force for revision. Only after all negative votes have been considered and addressed are the standards approved. All standards developed by SEMI are re-evaluated every five years to ensure they remain up to date.

There have been many benefits to standardization in the semiconductor industry. For example, standardizing the sizes of semiconductors allowed manufacturers to focus on ways to decrease production costs and increase performance without having to devote a substantial amount of time to the fabrication process. Furthermore, measurement standards have allowed scientists to efficiently build upon past research, obtain follow-on funding, and work toward commercialization of new semiconductor technologies.

Moving forward

Synthetic biology will contribute to important advances in medicine, agriculture, and numerous other sectors in the coming years. However, there are still questions as to how to develop standards that allow researchers to more effectively compare data, reproduce results, and create products. The semiconductor industry can be a useful example of how standardization aided the rapid growth of an industry that has revolutionized people’s lives. As different legislative initiatives make their way through the congressional policymaking process, the discussion around synthetic biology standards will only become more necessary. We encourage the CSPI community to serve as a resource to Congress and the federal government in this area as we monitor for future policy developments.