Top Five Biotech Breakthroughs That Shaped 2023

Reflecting on Biotechnology this past year

Image generated with DALLE-3.

This headline is admittedly ‘clickbaity,’ but hear me out! 2023 has indeed been a big year for biotechnology, a domain increasingly intertwined with our everyday lives, influencing aspects like healthcare, longevity, and fitness. Throughout this year, many innovations have emerged, marking significant progress in both research and development and market stages. As we prepare for a new year, it’s valuable to look back on the past 12 months and perform some retrospective analysis. In this article, we’ll explore what I consider the top five biotech breakthroughs of 2023.

Rather than deep diving into each topic, this article will provide summaries of each breakthrough and an overall score for each. If any of these topics are of significant interest for a larger stand-alone piece, please leave a comment. I’m always open to expanding on these discussions in future articles. Now, let’s set the stage with criteria for selecting these top five breakthroughs and scoring them, ensuring our review is structured and comprehensive.

Criteria for Selection:

To identify these top five breakthroughs, we considered several key factors:

1. Novelty and Innovation:

• Focuses on the uniqueness and originality of the breakthrough, emphasizing developments that represent significant leaps in biotechnology.

• Criteria emphasize originality and transformative impact, highlighting breakthroughs that redefine or create new paradigms.

2. Technological Advancement:

• Concentrates on the technological aspect of the innovation.

• Encompasses either cutting-edge technology or innovative applications of existing technologies, with a distinct focus on technological sophistication rather than the broader concept of innovation.

3. Scientific Validation:

• Centers on evidence-based validation through scientific research and regulatory approvals.

• Innovations are backed by robust and credible empirical data in the form of peer-reviewed publications and or clinical data.

4. Impact and Efficacy:

• Assesses the practical benefits and potential impacts of the innovation on health outcomes and treatments.

• Criteria consider both potential and realized effects in healthcare, emphasizing the direct benefits to patient well-being and healthcare advancements.

5. Market and Healthcare Relevance:

• Evaluates the broader significance of the innovation within current healthcare challenges and the broader biotechnology market.

• Criteria consider the potential for widespread application and the impact on these market, emphasizing practical applicability and market implications.

The List

1. Weightloss with GLP-1 RA

Obesity is a rising global epidemic and has many associated health complications. However, 2023 was undeniably a year for weight-loss drugs! You’ve probably heard by now of popular drugs like Ozempic from Eli Lilly; in fact, we mentioned this in a previous article. This drug is part of a family known as GLP-1 receptor agonists (RAs). GLP-1 is a gastrointestinal secreted peptide hormone that potentiates insulin release and reduces glucagon’s concentration. Where did these come from, and how do they function? GLP-1 RA are hardly a new drug, with the first commercial product being available all the way back in 2005, specifically for Type II Diabetes. However, it wasn’t until later that the weight loss side-effect was discovered in this drug. While the mechanism is not fully understood, there are a few theories of how these act to reduce weight (Figure 1), which involve acting on several different organs and organ systems to reduce appetite and nutrient absorption (Brown et al, 2019). There have been several of these GLP-1 RA. They are undeniably successful in helping to reduce weight, but perhaps with some significant side effects (Sodhi et al, 2023). Regardless, their impact on biotechnology this past year firmly gives them a spot on this list.

Figure 1. “The possible mechanisms of weight loss caused by GLP-1. GI, Gastrointestinal; GLP-1, Glucagon-like peptide-1; GLP-1R, Glucagon-like peptide-1 receptor.” Wang et al, 2023.

2. CRISPR-based Gene Editing for Clinical Applications

The CRISPR-Cas9 system is a revolutionary gene-editing technology first developed approximately 11 years ago (Jinek et al, 2012). Since then, it has consistently been at the forefront of biotech breakthroughs. What makes this technology so special is its ability to make precise gene edits efficiently and its remarkable customizability. This effective tool has catalyzed significant advances in cell engineering, fundamentally changing our approach to genetic manipulation.

2023 marked a historic year for CRISPR, with a groundbreaking achievement with the drug Casgevy: the first clinical approval of CRISPR as a cell-based gene therapy for treating sickle cell disease in the UK and US. This blood disorder results in misshapen hemoglobin – the protein in red blood cells responsible for oxygen delivery – leading to severe health complications. This treatment involves the isolation of patient hematopoietic stem cells, modification with CRISPR-Cas9, and reimplantation into patients. While it appears this is a truly effective therapy, it comes with a steep expected price tag of approximately $2.2 million per patient.

The first clinical approval of a CRISPR-based treatment is indeed a critical milestone. The demonstration of safety and efficacy makes it likely that we are just standing at the precipice of many additional CRISPR therapies to combat various genetic diseases, particularly with this same strategy of isolating cells, engineering them, and reimplantation. As we move forward, it's exciting to contemplate how many more breakthroughs CRISPR will bring in the coming years, potentially opening floodgates to new, life-altering therapies.

3. AI-enabled Protein Engineering and Drug Discovery

AlphaFold, a groundbreaking development by DeepMind, has emerged as a pivotal force in computational biology. This advanced machine-learning algorithm is adept at accurately predicting the three-dimensional structures of proteins based solely on their amino acid sequences (Figure 2). The significance of this capability lies in the fact that a protein's shape is key to its function and interaction with other biological molecules.

In 2023, AlphaFold 2 achieved remarkable advancements that further cemented its role in transforming biomedical research. It now includes capabilities for predicting receptor sites on proteins and identifying potential drug molecules that could effectively bind to these sites. This has now exceeded 1 million users! It’s difficult to overstate how impactful this is for drug discovery, which is largely done by screening thousands of compounds. Drug screening has the potential to be massively streamlined for identifying promising therapeutics. Unsurprisingly, this work has been recognized with the prestigious Lasker Award (American Nobel Prize) and is a testament to its transformative impact in the realms of science and medicine.

Looking forward, the potential of AlphaFold to revolutionize our approach to disease and drug development is immense. What diseases might we better understand next, and what new treatments could emerge, thanks to the insights provided by AlphaFold? The possibilities are as vast as they are exciting, making AlphaFold a standout in 2023's biotech innovations.

Figure 2. Schematic depicting the function of AlphaFold (Skolnick et al, 2021).

4. ChatGPT and LLMs for broad impact movement towards AGI

2023 marked a significant milestone in the evolution of artificial intelligence with the widespread adoption and advancement of Large Language Models (LLMs). These AIs are designed to understand human text by consuming vast amounts of writing (e.g., books, articles, conversations, textbooks, etc) and being trained to predict what comes next in a sentence. The leader in the development of these LLMs is undoubtedly OpenAI with ChatGPT; however, many other tech companies have scrambled to catchup with similar models like Google's Bard, Meta’s LLaMA, X's Grok, and Anthropic's Claude-2, all of which have showcased remarkable capabilities of AI in understanding and generating human-like text.

The impact of LLMs in 2023 extended beyond mere text generation. These models demonstrated an ability to engage in complex conversations, understand context, solve word problems, and even generate creative content, effectively blurring the lines between human and machine-generated text. This has led to a broad impact across various sectors, from simplifying research processes to revolutionizing how we interact with technology. Other abilities with these LLMs include features like data analysis, which we reviewed from ChatGPTs code interpreter in a previous article.

You may be thinking to yourself, ‘I thought this was an article on biotechnology, why are we talking about LLMs?’ That would be a great question! Technology does not exist in a vacuum, LLMs are undeniably a disruptive technology that is already changing how we perform and communicate science. Already, LLMs are being used to help write and edit manuscripts and grants or even interpret data. In fact, I often use them as an aid for similar tasks!

This trend will likely continue, and the strides made by LLMs will continue to accelerate the race towards Artificial General Intelligence (AGI), a form of AI that can understand, learn, and apply its intelligence across a wide range of tasks much like a human. The advancements in LLMs signify a move closer to this goal, showcasing an AI's ability to handle diverse and complex tasks with a level of sophistication that was previously unattainable.

How will these advanced AI models transform our world in ways we have yet to imagine?

5. mRNA Therapies

In 2023, mRNA technologies have solidified their position as one of the top biotech innovations, extending well beyond the realm of COVID-19 vaccines. Generally, mRNA vaccines work by delivering mRNA encoding a piece of the virus into cells within the body, resulting in the production of a protein antigen, which then generates an acute immune response, training the body to recognize this antigen in the future. Their applications now span across developing vaccines for diverse diseases like malaria, leptospirosis, and norovirus, highlighting their adaptability in addressing global health challenges.

Beyond vaccines, mRNA therapies have the potential to also act as therapeutics. In such cases, rather than delivering mRNA used for training the immune system on a pathogen, these mRNA could encode a deficient protein of interest. This could have all types of interesting applications ranging from tissue rejuvenation and healing to disease treatment (Figure 3). Current strategies are exploring mRNA technologies in treating neurodevelopmental and neurodegenerative diseases, further underscoring their capacity for broad and transformative impact in medicine. These expanding applications embody the essence of biotechnological innovation, making mRNA technologies a standout in 2023's biotech advancements​.

Figure 3. Depiction of developmental pathways for mRNA vaccines and therapeutics (Rohner et al, 2022).

Honorable Mentions

There are many other biotechnology products that I am excited about and believe will make a splash in the years to come! I have listed a few below for those who are interested in checking these out.

• Synthetic embryos: Fascinating advances, but still early in development.

• Brain-machine interfaces and other wearables: Innovative but currently more in the experimental phase with limited direct healthcare applications in 2023.

• CAR-T cell therapy: A breakthrough cancer treatment, yet its high cost and complexity limited its broader impact compared to other candidates on the list.

• AAVs (Adeno-Associated Viruses): Crucial for gene therapy, but overshadowed by more revolutionary approaches in genetic editing and delivery systems this year.

• Cell-Based Therapies: Show great promise in regenerative medicine but are still evolving in terms of technology and market readiness.

• Organoids: Vital for research and drug testing, but their application in direct patient care is still under development.

• Lab-Grown Meat: A potential game-changer for sustainability and food production, but its impact on biotechnology in healthcare and medicine is still indirect and emerging.

• Generative AI for Cosmetic Procedures: A novel application of AI in aesthetics, but its clinical significance and broader healthcare impact remain limited for now.

• Assembly theory: This theory recently published in Nature describes a theory that bridges the starting of the universe with evolutionary biology. It’s extremely interesting but more theoretical and less directly applicable to current biotech advancements (Sharma et al, 2023).

Followup Article - 2023 letdowns in Biotechnology.

Do you agree with the list, or do you think major topics were left out? Would you like a deeper dive into any of these technologies? Comment below!

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References:

https://www.aafp.org/pubs/afp/afp-community-blog/entry/will-the-high-price-of-gene-therapy-for-sickle-cell-disease-put-this-cure-out-of-reach.html#:~:text=The%20approval%20of%20Casgevy%2C%20which,to%20afford%20it%20is%20unclear.

https://deepmind.google/technologies/alphafold/

https://laskerfoundation.org/winners/alphafold-a-technology-for-predicting-protein-structures/

https://www.nature.com/articles/d41587-023-00016-6

https://www.frontiersin.org/articles/10.3389/fendo.2023.1085799/full

Brown, E., Wilding, J.P., Barber, T.M., Alam, U. and Cuthbertson, D.J., 2019. Weight loss variability with SGLT2 inhibitors and GLP‐1 receptor agonists in type 2 diabetes mellitus and obesity: mechanistic possibilities. Obesity Reviews, 20(6), pp.816-828.

Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J.A. and Charpentier, E., 2012. A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. science, 337(6096), pp.816-821.

Rohner, E., Yang, R., Foo, K.S., Goedel, A. and Chien, K.R., 2022. Unlocking the promise of mRNA therapeutics. Nature biotechnology, 40(11), pp.1586-1600.

Sharma, A., Czégel, D., Lachmann, M., Kempes, C.P., Walker, S.I. and Cronin, L., 2023. Assembly theory explains and quantifies selection and evolution. Nature, pp.1-8

Skolnick, J., Gao, M., Zhou, H. and Singh, S., 2021. AlphaFold 2: why it works and its implications for understanding the relationships of protein sequence, structure, and function. Journal of chemical information and modeling, 61(10), pp.4827-4831.

Sodhi, M., Rezaeianzadeh, R., Kezouh, A. and Etminan, M., 2023. Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss. JAMA, 330(18), pp.1795-1797.

Tarazi, S., Aguilera-Castrejon, A., Joubran, C., Ghanem, N., Ashouokhi, S., Roncato, F., Wildschutz, E., Haddad, M., Oldak, B., Gomez-Cesar, E. and Livnat, N., 2022. Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs. Cell, 185(18), pp.3290-3306.

Wang, J.Y., Wang, Q.W., Yang, X.Y., Yang, W., Li, D.R., Jin, J.Y., Zhang, H.C. and Zhang, X.F., 2023. GLP− 1 receptor agonists for the treatment of obesity: Role as a promising approach. Frontiers in Endocrinology, 14, p.1085799.