The Next Chapter of Science

The beginning of a new year presents an opportunity to reflect on the past and look forward to the potential of the future.

In the following interviews, you’ll hear from renowned academic experts offering their take on the “fields to watch” as we progress into 2024. Join us as we explore how innovation, ethics and even aesthetics look set to influence the landscape of life science research, creating new possibilities for treating human diseases, feeding our growing population and nurturing the scientists of the future.

Chimeric antigen receptor (CAR) immune-cell therapy

Dr. Xingxing Zang

Dr. Xingxing Zang. Credit: Dr. Xingxing Zang.

Dr. Xingxing Zang is a professor and the Louis Goldstein Swan Chair at Albert Einstein College of Medicine. Zang’s laboratory focuses on the fundamental biology of new immune checkpoints and the development of translational immunotherapies in cancers, autoimmune diseases and metabolic diseases.

Zang highlights chimeric antigen receptor (CAR)-immune cell therapy, particularly CAR T therapy, as a major advancing field due to its “remarkable potential to revolutionize cancer treatment”.

“CAR T-cell therapy involves modifying a patient's own immune cells to target and destroy cancer cells, offering a personalized and potentially more effective treatment option for certain blood cancers like leukemia and lymphoma,” explains Zang.

“CAR T-therapy's success stories, where patients previously deemed untreatable have experienced remission, showcase its immense promise,” says Zang. “Its ability to provide durable responses in some cases has sparked significant interest among researchers, clinicians and patients alike.”

The success of CD19-targeted CAR T cells in treating B-cell malignancies, including acute lymphoblastic leukemia (ALL) and other types of lymphoma, has been extensively documented, says Zang: “Studies like the work of Dr. Carl June and colleagues published in the New England Journal of Medicine, demonstrated impressive results in relapsed/refractory ALL patients using CD19 CAR T therapy.”

“Another study demonstrated that CD19 CAR T therapy achieved an estimated 5-year overall survival rate in 42.6% of patients with refractory large B-cell lymphoma (LBCL),” Zang adds. LBCL refers to subtypes of non-Hodgkin lymphoma (NHL) that are particularly aggressive and have a high unmet need due to limited treatment options.

A number of technologies and research methods are helping to generate better CAR therapies, including gene editing techniques: “CRISPR/Cas9 and other gene-editing tools have revolutionized CAR T-cell therapy by enabling precise modifications in T cells. These tools facilitate targeted gene insertion, deletion or modification to enhance CAR T-cell efficacy, persistence and safety,” says Zang.

As CAR T cells are “living” medications, their production differs from the manufacturing of chemicals and proteins. “Streamlining and optimizing CAR T-cell manufacturing processes are critical,” Zang says, emphasizing that automation, closed systems and improved cell expansion technologies are contributing to scalable and standardized production of high-quality CAR T cells.

In the future, Zang believes that this type of therapy may hold promise for other diseases beyond cancer, including autoimmune diseases and neurodegeneration. “The principle behind using CAR T cells in autoimmunity involves redirecting these cells to target and suppress the immune cells responsible for the autoimmune response. CAR such as CAR-macrophages may be used to treat Alzheimer’s disease by removing amyloid plaques or tau tangles in the brain,” he says.

Plant molecular farming

Dr. Kathleen Hefferon

Dr. Kathleen Hefferon. Credit: Dr. Kathleen Hefferon.

Dr. Kathleen Hefferon is a lecturer in microbiology in the College of Agriculture and Life Sciences at Cornell University.

Plant molecular farming (PMF) is an emerging area of plant biotechnology. It combines disciplines such as plant agriculture and synthetic biology to enable the production of animal proteins in plants. “The science is based on growing the animal proteins themselves in plants, greenhouses or vertical farms,” explains Hefferon.

PMF typically involves introducing genes that encode specific proteins into a plant’s genome. The transgenic plant can then operate as a “factory” producing the target protein, which can then be extracted to obtain a final product.

“The alternative food protein space is geared toward finding ways to feed a growing population nutritious protein in a sustainable manner, and with animal welfare in mind,” Hefferon describes. “Using plants to produce these proteins seems a very fitting way to go. This is a solution based on synthetic biology that will decrease arable land usage and can be employed even within urban centers.”

Beyond food production, plant molecular farming has had success in the pharmaceutical industry, where plants can be used as biofactories to produce antibodies and antigens. “One noteworthy milestone has been the production of flu and COVID vaccines,” explains Hefferon. “These vaccines are efficacious, inexpensive and can be stored at room temperature for prolonged periods of time. Perfect for low- to middle-income countries.”

As for technologies and techniques that are progressing in this field, Hefferon says there is “a lot of work going on”, from increasing expression of proteins in plants, advancing protein purification methods and improving vertical farming infrastructure.

The core challenge faced by PMF is the ability to scale up – a common issue for new technologies. “There are regulatory hurdles involved in protein production,” says Hefferon. “The regulatory process is uneven across the globe, which can be cumbersome, but appears to be slowly opening up to new technologies such as genome editing.”

Psychedelic and psychedelic-inspired drugs

Dr. Amy Reichelt

Dr. Amy Reichelt. Credit: Dr. Amy Reichelt.

Dr. Amy Reichelt is a senior lecturer and adjunct professor at the University of Adelaide. She is a recognized leader in neuroscience and neuropharmacology, specializing in psychedelic clinical development, neurodegeneration and nutritional neurobiology.

Reichelt believes that the technological advancement of psychedelic and psychedelic-inspired drugs for the treatment of psychiatric and neurological conditions is a majorly advancing field. Particularly, she is impressed by the development of novel molecules that have the therapeutic benefits of classical psychedelics, but improved safety and therapeutic profiles.

Reichelt explains that pharmaceutical development of novel therapeutics for mental health conditions came to a “standstill” once selective serotonin receptor inhibitors, or SSRIs, hit the market over 20 years ago. “Neuroscience research into new therapeutic mechanisms has been underfunded. The resurgence of interest into psychedelic therapies has come at a time of dire need for new and effective treatments,” she adds.

Many countries regulate psychedelic drugs as controlled substances, enforcing restrictions on their use. Accessing psychedelic compounds and gaining approval to study them in a research setting has proven challenging for scientists, but not impossible.

“The work from lab groups led by individuals including Dr. David Olson, associate professor of chemistry, biochemistry and molecular medicine at the University of California, Davis, Dr. Charles Nichols, professor of pharmacology at LSU Health Sciences Centre in New Orleans and Dr. Alex Kwan, associate professor in the Meinig School of Biomedical Engineering at Cornell University, continue to break new ground in understanding the mechanistic basis of how psychedelic drugs work,” Reichelt says.

Reichelt is excited by research that demonstrates the neuroplasticity-enhancing capabilities of some psychedelic compounds, and their effects on inflammatory cascades in cellular models. This is important work, she says, considering the inflammatory component of some psychiatric and neurological conditions, which can impact neuroplasticity. “Moreover, the recent research published from Dr. Gul Dölen’s lab that showed how different psychedelics reopened windows of social learning in mice for varying durations is a seminal observation for understanding therapeutic effects,” Reichelt adds.

Which technologies are enhancing the field of psychedelics research? For Reichelt, advances in the use of two-photon imaging of neuronal structures in a live animal’s brain is an obvious first choice: “This has allowed a tangible understanding of how key cellular structures are modified by psychedelic drugs – and the potential durability of these effects.”

“Understanding more about the windows of plasticity that are opened or promoted by psychedelics enables targeted therapy protocols to be initiated in the period of time when the brain is most receptive to interventions,” says Reichelt.

Research into the therapeutic potential of psychedelic compounds has experienced somewhat of a “renaissance”, but many challenges remain before we are likely to see widespread use of such drugs in the clinic. Working with scheduled drugs requires “traversing a lot of roadblocks and bureaucracy,” Reichelt says. She hopes to see easier pathways to running both scientific and clinical trials with these drugs.

While public attitudes are shifting towards a more supportive outlook on psychedelic therapies, integrating such drugs into the healthcare system will not be an easy feat, Reichelt emphasizes: “Hopefully insurance payers and healthcare providers see the benefits to society. Because psychedelic treatments require clinicians to be present for safety for the duration of the acute drug effects (potentially eight hours or more), the scalability and cost is something that must be considered.”

“In addition, psychedelic drugs are not a panacea and greater understanding of their biological effects are still needed to effectively apply them clinically to treat mental and neurological health conditions.”

Ethical issues surrounding new approaches to gene editing

Tsutomu Sawai. Credit: Tsutomu Sawai.

Dr. Tsutomu Sawai is an associate professor in the graduate school of humanities and social sciences at Hiroshima University. His research interests surround practical ethics issues concerning new and emerging technologies, such as the application of genome and epigenome editing.

“Science and technology are surging forward, unlocking new possibilities for the present and future. Yet, the boundaries of research and technological innovation remain unclear, including who should define them,” Sawai says. He recently co-authored a forum piece in Stem Cell Reports discussing the ethical issues of epigenome editing.

Epigenetic compounds “mark” the genome, but they do not alter the underlying DNA sequence. Epigenome editing is therefore viewed as an attractive approach to modifying gene function, as it is considered reversible and carries a reduced risk of off-target effects. “Epigenome editing stands at the frontier of biotechnology, offering a tunable approach to gene regulation without altering the DNA sequence itself. Its reversible nature positions it as a promising candidate for treating a spectrum of genetic and chronic conditions,” Sawai explains.

He adds, “As medical applications of epigenome editing emerge, we are passionate about illuminating critical yet overlooked ethical considerations.” This includes the potential impact that transgenerational epigenetic inheritance – or TEI – could have on the future of epigenetic-based therapies, which are currently in development.

A paper published by Takashi et al in early 2023 found that even “advantageous” epigenome editing could have far-reaching consequences for subsequent generations. “This potential to influence our progeny necessitates a broader ethical reflection, extending beyond the immediate safety and efficacy of its medical use,” says Sawai. “With this in mind, our discourse cautions against undue optimism regarding the ethical and regulatory landscape of epigenome editing, especially concerning its transgenerational inheritance.”

What steps must be taken to decide how technologies such as epigenome editing are developed or authorized for human application? “Our first step is to rigorously establish when and how epigenome editing may affect future generations,” says Sawai. “We must then weigh the significance of this heritability in human applications. Should the hereditary impact of these interventions be deemed ethically and regulatorily negligible, it could shake the foundations of the current opposition to human germline genome editing, which is tightly controlled for this very reason.”

We currently find ourselves at a crossroads, Sawai concludes, tasked with aligning the ethics and regulations of epigenome editing with those established for human genome editing while “striving for consistency and foresight.”

The role of beauty in science

Dr. Brandon Vaidyanathan. Credit: The Catholic University of America.

Dr. Brandon Vaidyanathan is an associate professor and chair of the department of sociology and director of the Institutional Flourishing Lab at The Catholic University of America. Here, his current research examines the role of “beauty” in science.

Beauty is a term that isn’t often associated with scientific research. Consequently, you may be unfamiliar with this research area. As Vaidyanathan explains, it’s fairly novel: “There isn’t a term in place for this field yet, but I might call it ‘aesthetics in science’.”

“There is a very recent and growing body of work in philosophy and sociology that looks at how aesthetic factors (e.g., beauty, awe, wonder and other aesthetic emotions) shape scientists and the practice of science,” he says.

There is no “future” in science without scientists. Vaidyanathan leads Work and Well-Being in Science, the largest cross-national study investigating factors that affect the wellbeing of scientists. It is also the first international study to examine the role of aesthetics in science, surveying ~3500 scientists, and interviewing a further 215 in person. “I was drawn to research this area because, in qualitative research interviews with scientists for a previous project, our team was surprised to hear them regularly bring up ‘beauty’ as a key motivating factor,” he explains.

The Work and Well-Being in Science project published its results in the journal Frontiers in Psychology in 2022. A perspective piece, written by Vaidyanathan et al., is available in the Journal of Biosciences.

Vaidyanathan’s team found that most scientists view their work as an aesthetic quest – the “beauty of understanding”, a pleasure that derives from discovering the hidden or inner logic underlying what they are studying. “One key insight is that aesthetic factors are a major source of motivation for scientists to pursue their careers in the first place. We also find that aesthetic experience is very strongly associated with well-being among scientists,” Vaidyanathan says. “This is especially important in light of considerable research pointing to a mental health crisis in science. Our work underscores the need to preserve the intrinsic motivations and joys of doing science and address the obstacles to it (such as institutional pressures and toxic leadership) that scientists face.”

“I find beauty in [the] elegance and simplicity of experimental design. The fewer moving parts and parameters an experiment can involve while still attacking a particular problem or being able to shed light on a particular question in a very specific way, I find that extremely beautiful…Maybe it’s sort of an intellectual elegance, like a mathematical proof. So, I love that,” a respondent to the Work and Well-Being in Science survey said.

Vaidyanathan says more experimental and even neuropsychological work could also benefit this field, helping us to understand how aesthetic experiences affect scientists and their relevance to scientific practice. The methodology behind this type of data collection can prove challenging, though. “It is increasingly difficult to get a high response rate for surveys – even within financial incentives in place, most people don’t want to take a survey, and mail servers often filter out survey invitations as spam. It is also difficult to get scientists to participate in research,” Vaidyanathan expresses.

He notes that, beside the Work and Well-Being in Science project, other publications, including work by Cambridge philosopher Milena Ivanova highlights the importance of aesthetics in scientific experiments. “Prominent scientists such as Nobel Prize winner Frank Wilczek and Oxford biologist Richard Dawkins have also written books about aesthetics in science,” Vaidyanathan concludes.

That’s a wrap

As described by our expert interviewees, the future of science is one marked by the need for collaboration, ethical considerations and communication within the scientific community and with the public – particularly as technologies continue to evolve. The integration of fields such as biology, computer science and engineering will no doubt foster innovative solutions to the global challenges we face. But we must not overlook the role of scientists in science, a pertinent issue considering the pressures researchers face such as limited funding, resources and the pressure of “publish or perish”.

We’ve heard from the experts, and now we want to hear your take on the future of science. What field of research looks set to majorly impact science and society? What are the core challenges that scientists are facing, and how can we work to overcome them? What are your hopes for the future of academia?

Get in touch with the Technology Networks editorial team to share your thoughts.