What If CRISPR Was Never Discovered?

The Actual History

The discovery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) represents one of the most significant scientific breakthroughs of the 21st century. The journey toward understanding this revolutionary gene-editing system began in 1987 when Japanese researcher Yoshizumi Ishino accidentally discovered unusual repeating DNA sequences while studying the E. coli genome. These strange repeating sequences, initially considered genetic curiosities, were later found in many bacteria and archaea.

Spanish microbiologist Francisco Mojica recognized the broader significance of these sequences in the 1990s and proposed the name CRISPR in 2002. Mojica hypothesized that these sequences functioned as part of a bacterial immune system against viral infections. This theory was experimentally confirmed in 2007 by a team at Danisco (now part of DuPont), showing that bacteria could integrate viral DNA fragments into their CRISPR arrays to recognize and destroy returning viruses.

The transformative moment came in 2012 when biochemist Jennifer Doudna of the University of California, Berkeley, and microbiologist Emmanuelle Charpentier, then at Umeå University in Sweden, published their groundbreaking paper in Science. They demonstrated that the CRISPR-Cas9 system could be programmed to cut specific DNA sequences, essentially creating a programmable gene-editing tool. This discovery simplified genetic engineering dramatically, making precise DNA editing accessible, affordable, and relatively straightforward compared to previous techniques.

Their work sparked an explosion of research and applications. By 2013, researchers had adapted CRISPR for editing mammalian cells, and by 2015, the first studies on human embryo editing appeared. The technology rapidly expanded beyond fundamental research into potential therapeutic applications for genetic diseases, agricultural improvements, and many other domains.

In 2020, Doudna and Charpentier were awarded the Nobel Prize in Chemistry for their revolutionary discovery. By 2025, CRISPR technologies have entered clinical trials for conditions including sickle cell disease, beta-thalassemia, various cancers, and several inherited disorders. The first CRISPR-based therapy, exa-cel (developed by CRISPR Therapeutics and Vertex Pharmaceuticals) received FDA approval in late 2023 for treating sickle cell disease, marking the first approved therapeutic application.

Beyond medicine, CRISPR has transformed agriculture, enabling faster development of crops with enhanced nutritional profiles, disease resistance, and climate adaptability. The technology has also found applications in biofuel production, environmental remediation, and basic research across countless biological questions.

Alongside these scientific advancements, robust debates about the ethical implications of gene editing have emerged, particularly regarding human germline editing following the controversial 2018 announcement by Chinese scientist He Jiankui that he had created the first CRISPR-edited babies. This led to international summits, regulatory frameworks, and ongoing discussions about the appropriate boundaries and governance of this powerful technology.

By 2025, CRISPR has become a foundational technology in biotechnology, fundamentally changing how scientists approach genetic manipulation and opening previously unimaginable possibilities for addressing genetic diseases, agricultural challenges, and environmental problems.

The Point of Divergence

What if CRISPR's gene-editing potential was never discovered? In this alternate timeline, we explore a scenario where the critical insights connecting CRISPR sequences to a programmable gene-editing tool never materialized, leaving biotechnology to advance along significantly different trajectories.

The divergence could have occurred through several plausible mechanisms:

First, the collaborative relationship between Jennifer Doudna and Emmanuelle Charpentier might never have formed. Their partnership began at a conference in Puerto Rico in 2011, where they decided to combine their respective expertise on CRISPR and the Cas9 protein. Without this chance meeting and subsequent collaboration, their groundbreaking 2012 paper demonstrating CRISPR-Cas9's programmable cutting abilities might never have been published.

Alternatively, their research could have taken a different direction entirely. Doudna initially studied CRISPR as a fascinating RNA system, not immediately recognizing its gene-editing potential. If she had focused on other aspects of RNA biochemistry instead, or if Charpentier had pursued different aspects of bacterial immunity, their research might not have converged on the crucial insight about programmable DNA targeting.

A third possibility involves the competitive scientific environment of 2011-2012. Several research groups, including those led by Virginijus Šikšnys, Feng Zhang, and George Church, were working on similar aspects of CRISPR biology. In our timeline, Doudna and Charpentier published first, followed closely by these other teams. In an alternate timeline, all these groups might have missed the critical insight about CRISPR's programmability, perhaps focusing instead on its natural role in bacterial immunity without recognizing its engineering potential.

Finally, the divergence could have occurred earlier in the CRISPR research timeline. If Francisco Mojica's early observations about CRISPR sequences hadn't gained traction, or if the 2007 experimental confirmation of CRISPR's role in bacterial immunity had failed or been interpreted differently, the foundation for later breakthroughs might never have been laid.

In this alternate timeline, CRISPR would remain merely an interesting bacterial immune system rather than becoming the revolutionary gene-editing platform that transformed biotechnology. The scientific community would continue pursuing genetic engineering through older, more cumbersome technologies like zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), which require designing new proteins for each DNA target and involve significantly more complex, expensive, and time-consuming processes.

Immediate Aftermath

Stalled Progress in Gene Editing Accessibility

The most immediate consequence of CRISPR's non-discovery would be the continued reliance on pre-CRISPR gene editing technologies. These approaches—primarily zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs)—would remain the cutting edge of genetic engineering through the 2010s and into the 2020s:

Restricted Research Community: Without CRISPR's accessibility and ease of use, genetic engineering would remain largely confined to specialized labs with substantial funding and expertise. The "democratization" of gene editing that occurred in our timeline—where even small academic labs, startups, and educational institutions could implement CRISPR—would not materialize.
Higher Economic Barriers: The costs associated with ZFN and TALEN approaches would continue to limit application scope. While our timeline saw CRISPR kits becoming available for a few hundred dollars, custom-designed ZFNs typically cost $5,000-$10,000 per target, putting routine gene editing experiments beyond the reach of many researchers.
Slower Experimental Timelines: Projects that take weeks with CRISPR would continue requiring months with alternative technologies. This slower pace would particularly impact high-throughput applications like genetic screens, which became feasible with CRISPR's efficiency.

Altered Scientific Career Trajectories

The absence of CRISPR's discovery would significantly reshape scientific careers and institutional development:

Different Nobel Laureates: Jennifer Doudna and Emmanuelle Charpentier would likely remain respected scientists in their fields but would not achieve the scientific celebrity status and Nobel recognition they received in our timeline. Their research programs would have continued in different directions, focused on other aspects of RNA biochemistry and bacterial defense mechanisms.
Institutional Changes: The Innovative Genomics Institute, established at UC Berkeley and UCSF to advance CRISPR research and applications, would not exist. Similarly, the numerous CRISPR-focused startups and research centers that emerged worldwide would never have been founded.
Divergent Funding Patterns: The massive influx of funding into gene editing technologies—both public grants and private investments—would follow different patterns. Research dollars might instead flow toward incremental improvements in existing technologies or alternative approaches to genetic manipulation.

Pharmaceutical and Biotechnology Industry Trajectory

The biotechnology sector would develop along a markedly different path:

Delayed Therapeutic Development: Without CRISPR's precision and efficiency, the development of gene therapies would progress much more slowly. Clinical trials targeting conditions like sickle cell disease, beta-thalassemia, and various genetic forms of blindness that began in the mid-2010s in our timeline would be delayed by years or even decades.
Different Corporate Landscape: The CRISPR-focused biotechnology companies that attracted billions in investment—firms like CRISPR Therapeutics, Editas Medicine, Intellia Therapeutics, and Caribou Biosciences—would not exist. The biotechnology investment landscape would feature different players, likely focused on conventional drug development approaches rather than genetic modification.
Continued Focus on Traditional Approaches: Pharmaceutical companies would maintain their emphasis on small-molecule drugs and biologics rather than pivoting significant resources toward genetic medicine. The excitement and hype surrounding precision genetic therapies would be substantially diminished.

Agricultural Applications and Food Security

The agricultural sector would experience significant differences in innovation trajectory:

Slower Crop Improvement: The rapid development of gene-edited crops with improved nutritional profiles, disease resistance, and climate adaptability would be severely handicapped. Projects like drought-resistant wheat or higher-yielding rice varieties would progress through conventional breeding or more cumbersome genetic engineering approaches, taking decades rather than years.
Regulatory Differences: The global conversation about regulating gene-edited crops would take a different form. In our timeline, many countries distinguished between CRISPR-edited crops (which often contain no foreign DNA) and traditional GMOs, creating new regulatory frameworks. Without CRISPR, these nuanced regulatory discussions would not occur.
Delayed Climate Adaptation: Agricultural adaptations to climate change would rely more heavily on conventional breeding methods, potentially limiting the speed and scope of developing crops suited to changing environmental conditions.

Academic and Educational Impacts

The scientific and educational landscape would reflect CRISPR's absence:

Different Research Priorities: Without the CRISPR revolution redirecting resources and attention, other biotechnology approaches might have received greater focus, potentially accelerating development in areas like synthetic biology, protein engineering, or systems biology that were somewhat overshadowed by CRISPR's dominance.
Educational Curriculum Changes: The undergraduate and graduate education in biological sciences would lack the prominent focus on CRISPR technologies that emerged in our timeline. Laboratory courses teaching CRISPR techniques as standard methodology would instead continue emphasizing older genetic engineering approaches.
Publication Landscape: The explosion of CRISPR-related publications—thousands per year by the mid-2010s—would not occur, significantly altering the scientific literature in fields ranging from molecular biology to medicine, agriculture, and bioethics.

Long-term Impact

Alternative Gene Editing Technologies

Without CRISPR dominating the gene editing landscape, scientific efforts would have pursued different technological pathways throughout the 2020s:

Enhanced Traditional Methods

Advanced ZFNs and TALENs: Substantial research funding would have flowed toward making these pre-CRISPR technologies more accessible, affordable, and efficient. By 2025, these systems would likely have improved significantly compared to their 2010 versions, with more modular design platforms and higher success rates.
Automated Design Systems: Computational approaches and machine learning would have been applied to optimize protein design for DNA targeting, potentially overcoming some of the technical barriers that made these systems cumbersome. Companies specializing in custom ZFN and TALEN design would have expanded, creating more standardized protocols.
Reduced Costs Through Scale: With continued investment, economies of scale might have gradually reduced the cost of these technologies, though likely not to CRISPR's level of accessibility. Custom nucleases might cost $1,000-$3,000 by 2025 rather than $5,000-$10,000, making them more accessible but still limiting widespread adoption.

Emergence of Alternative Technologies

RNA-Guided Systems Beyond CRISPR: Other RNA-guided systems might have been discovered or developed. Nature contains numerous nucleic acid manipulation systems that could potentially be repurposed for gene editing, such as group II introns or other bacterial defense mechanisms.
Synthetic Biology Approaches: Without CRISPR's dominance, synthetic biology might have pursued alternative gene modification strategies, such as recombinase-based systems or artificially evolved DNA-modifying enzymes designed for programmability.
Epigenetic Editing Focus: Greater emphasis might have been placed on technologies that modify gene expression without changing DNA sequences, leading to more advanced tools for targeted epigenetic modifications.

Medical and Therapeutic Consequences

The trajectory of genetic medicine would differ dramatically without CRISPR:

Slower Therapeutic Development Timeline

Delayed Gene Therapy Approvals: The first approved gene editing therapies would likely not appear until the 2030s rather than the early 2020s. Treatments for conditions like sickle cell disease that received approval in 2023 in our timeline would remain in early-stage development.
Focus on Traditional Gene Addition: Rather than precise gene correction, therapies would rely more heavily on gene addition approaches, where functional genes are added without removing defective copies. This approach is less ideal for many conditions but was the predominant pre-CRISPR strategy.
Higher Treatment Costs: Without CRISPR's relative simplicity and precision, gene therapies would require more complex manufacturing processes, likely resulting in even higher treatment costs than the multi-million-dollar price tags seen in our timeline.

Different Disease Focus

Prioritization of Simple Genetic Targets: Medical research would concentrate on diseases caused by single genes with straightforward correction pathways, avoiding complex genetic conditions that benefit from CRISPR's precision and multiplexing capabilities.
Cancer Immunotherapy Differences: The CAR-T cell therapies that have benefited from CRISPR optimization in our timeline would develop more slowly and with less sophistication, potentially limiting their efficacy against solid tumors and increasing their side effects.
Rare Disease Neglect: Many ultra-rare genetic disorders that became viable research targets due to CRISPR's flexibility would remain largely unaddressed, as the cost and difficulty of developing customized therapies would be prohibitive.

Agricultural and Environmental Impact

The global food system and environmental applications would develop along a different path:

Agricultural Innovation Gaps

Slower Climate Adaptation: Crop varieties adapted to changing climate conditions would emerge more gradually, primarily through conventional breeding supplemented by limited precision genetic engineering, potentially creating food security challenges as climate change accelerates.
Persistent Disease Vulnerabilities: Crop diseases that have been rapidly addressed with CRISPR in our timeline, such as banana Fusarium wilt or wheat rust resistance, would continue threatening global food security with fewer technological solutions available.
Continuing GMO Controversies: Without CRISPR enabling genetic modifications that contain no foreign DNA, the regulatory and public perception divide between GMO and non-GMO would remain stark, limiting adoption of engineered crops in regions with strong anti-GMO sentiment.

Environmental Applications

Delayed Genetic Biocontrol Methods: Approaches like gene drives for controlling disease vectors (e.g., malaria-carrying mosquitoes) would remain theoretical rather than entering field trials. Alternative pest management strategies would continue relying primarily on chemicals or traditional biological controls.
Bioremediation Limitations: Engineered microorganisms designed to degrade environmental pollutants or extract valuable materials from waste would develop more slowly, limiting biological solutions to environmental contamination.
Conservation Genetics Setbacks: Efforts to use genetic intervention to help endangered species overcome threats like disease susceptibility would face significant technical barriers, potentially leading to additional extinction events that might have been preventable with CRISPR technologies.

Global Scientific Leadership and Bioeconomy

The international scientific landscape would feature different power dynamics:

Altered Competitive Landscape

Different National Leaders: The countries that established early dominance in CRISPR research and applications—particularly the United States and China—might not have the same clear advantages in biotechnology. Nations with strong traditional biotech infrastructure might maintain more even footing in the global bioeconomy.
Reduced Biotech Investment Surge: The massive investment boom in gene editing technologies (over $5 billion invested in CRISPR companies by 2022 in our timeline) would not occur, resulting in a smaller overall biotechnology sector with fewer startups and less innovation.
Academic-Industry Relationship Changes: The explosion of university spinoff companies commercializing CRISPR applications would not materialize, potentially preserving more traditional boundaries between academic and commercial research.

Ethical and Regulatory Framework

Different Bioethical Focus: Without the specific capabilities of CRISPR, particularly its potential for human germline editing, bioethical debates would center on different issues. The international summits on human gene editing that formed in response to CRISPR would not exist or would take substantially different forms.
Alternative Regulatory Development: The regulatory frameworks specifically designed for CRISPR-edited organisms (like the USDA's approach to CRISPR-edited plants) would not develop, leaving conventional GMO regulations as the primary governance mechanism for biotechnology.
Delayed Human Enhancement Debates: Discussions about human genetic enhancement that accelerated due to CRISPR's potential would remain more theoretical and less urgent, potentially postponing important societal conversations about the future of human evolution.

Present Day Status (2025)

By 2025 in this alternate timeline:

Gene Therapy Landscape: Instead of having the first approved CRISPR therapies on the market, gene therapies would still primarily rely on viral vector delivery of functioning genes without precise editing capabilities.
Research Capabilities: Genetic research would progress more incrementally, with genome-wide studies and high-throughput genetic screens being significantly more expensive and time-consuming.
Economic Impact: The global bioeconomy would be substantially smaller, perhaps by hundreds of billions of dollars, with significantly fewer biotechnology startups and reduced investment in genetic engineering applications.
Educational Differences: A generation of young scientists would have trained without exposure to CRISPR techniques, resulting in a differently skilled scientific workforce and alternative research priorities.
Agricultural Readiness: Global agriculture would have fewer tools available to address climate change impacts, potentially creating greater food security challenges as weather patterns become more extreme.

This alternate 2025 would feature a biotechnology sector that, while still advancing, would lack the revolutionary leap forward that CRISPR provided, resulting in slower progress across numerous fields dependent on precise genetic manipulation.

Expert Opinions

Dr. Maria Gonzalez, Professor of Molecular Biology and Biotechnology at Stanford University, offers this perspective: "The non-discovery of CRISPR would represent one of the greatest 'what-ifs' in modern scientific history. Without CRISPR's accessibility and precision, we would likely still be muddling through with ZFNs and TALENs—technologies that work but are cumbersome and expensive. The democratization of gene editing that CRISPR enabled simply wouldn't have happened. Rather than thousands of labs worldwide working on genetic solutions to everything from medical challenges to climate change, we'd have a much smaller community with access to these tools. Progress would still occur, but at a fraction of the pace. I suspect we'd be at least 15-20 years behind our current capabilities, with many applications we now take for granted still in theoretical stages."

Dr. Jonathan Kim, Bioethicist and Director of the Center for Technology and Society, provides a contrasting view: "While the absence of CRISPR would certainly slow therapeutic development for genetic diseases, it might have provided a valuable pause—a longer period for ethical frameworks to develop before technological capabilities outpaced them. In our timeline, the rapid advance of CRISPR from basic research to human applications created a situation where ethical guardrails were often constructed reactively rather than proactively. The shocking announcement of CRISPR-edited babies in 2018 exemplified this problem. A world without CRISPR might have allowed more thoughtful consideration of how we should approach human genetic modification before the technology made it relatively simple to implement. The question isn't just whether we'd have fewer therapies by 2025, but whether we'd have a more robust societal consensus about how genetic technologies should be governed."

Dr. Elena Whitaker, Agricultural Geneticist and Climate Adaptation Specialist, explains: "Without CRISPR, our approach to food security and climate resilience would look radically different today. CRISPR accelerated crop improvement timelines from decades to years. Without it, we'd be far more dependent on conventional breeding supplemented by older genetic engineering approaches, significantly limiting our ability to rapidly adapt agriculture to changing conditions. By 2025, we'd likely see greater food price volatility and regional scarcities as crops faced increased stress from shifting climate patterns without the benefit of rapid genetic adaptation. The agricultural biotechnology sector would have remained concentrated among a few large corporations with the resources for conventional genetic engineering, rather than the more diverse ecosystem of innovators that CRISPR enabled. The consequences for global food security in a warming world could be profound."