Machine Learning and Gene Editing at the Helm of a Societal Evolution.

The integration of artificial intelligence (AI) and biotechnology, whilst in its infancy, presents significant opportunities and risks, and proactive policy is needed to manage these emerging technologies. Whilst AI continues to have significant and broad impact, its relevance and complexity magnify when integrated with other emerging technologies. The confluence of Machine Learning (ML), a subset of AI, with gene editing (GE) in particular can foster substantial benefits as well as daunting risks that range from ethics to national security. These complex technologies have implications for multiple sectors, ranging from agriculture and medicine to economic competition and national security. Consideration of technology advancements and policies in different geographic regions, and involvement of multiple organisations further confound this complexity. As the impact of ML and GE expands, forward looking policy is needed to mitigate risks and leverage opportunities. Thus, this study explores the technological and policy implications of the intersection of ML and GE, with a focus on the United States (US), the United Kingdom (UK), China, and the European Union (EU). Analysis of technical and policy developments over time and an assessment of their current state have informed policy recommendations that can help manage beneficial use of technology advancements and their convergence, which can be applied to other sectors. This study is intended for policymakers to prompt reflection on how to best approach the convergence of the two technologies. Technical practitioners may also find it valuable as a resource to consider the type of information and policy stakeholders engage with.

Low-density plasma formation in aqueous biological media using sub-nanosecond laser pulses.

We demonstrate the formation of low- and high-density plasmas in aqueous media using sub-nanosecond laser pulses delivered at low numerical aperture (NA = 0.25). We observe two distinct regimes of plasma formation in deionized water, phosphate buffered saline, Minimum Essential Medium (MEM), and MEM supplemented with phenol red. Optical breakdown is first initiated in a low-energy regime and characterized by bubble formation without plasma luminescence with threshold pulse energies in the range of Ep ≈ 4-5 µJ, depending on media formulation. The onset of this regime occurs over a very narrow interval of pulse energies and produces small bubbles (Rmax = 2-20 µm) due to a tiny conversion (η < 0.01%) of laser energy to bubble energy EB. The lack of visible plasma luminescence, sharp energy onset, and low bubble energy conversion are all hallmarks of low-density plasma (LDP) formation. At higher pulse energies (Ep = 11-20 µJ), the process transitions to a second regime characterized by plasma luminescence and large bubble formation. Bubbles formed in this regime are 1-2 orders of magnitude larger in size [Formula: see text] due to a roughly two-order-of-magnitude increase in bubble energy conversion (η ≳ 3%). These characteristics are consistent with high-density plasma formation produced by avalanche ionization and thermal runaway. Additionally, we show that supplementation of MEM with fetal bovine serum (FBS) limits optical breakdown to this high-energy regime. The ability to produce LDPs using sub-nanosecond pulses focused at low NA in a variety of cell culture media formulations without FBS can provide for cellular manipulation at high throughput with precision approaching that of femtosecond pulses delivered at high NA.

Spatially sculpted laser scissors for study of DNA damage and repair.

We present a simple and efficient method for controlled linear induction of DNA damage in live cells. By passing a pulsed laser beam through a cylindrical lens prior to expansion, an elongated elliptical beam profile is created with the ability to expose controlled linear patterns while keeping the beam and the sample stationary. The length and orientation of the beam at the sample plane were reliably controlled by an adjustable aperture and rotation of the cylindrical lens, respectively. Localized immunostaining by the DNA double strand break (DSB) markers phosphorylated H2AX (gamma H2AX) and Nbs1 in the nuclei of HeLa cells exposed to the "line scissors" was shown via confocal imaging. The line scissors method proved more efficient than the scanning mirror and scanning stage methods at induction of DNA DSB damage with the added benefit of having a greater potential for high throughput applications.

Digital holographic microscopy for quantitative cell dynamic evaluation during laser microsurgery.

Digital holographic microscopy allows determination of dynamic changes in the optical thickness profile of a transparent object with sub-wavelength accuracy. Here, we report a quantitative phase laser microsurgery system for evaluation of cellular/ sub-cellular dynamic changes during laser micro-dissection. The proposed method takes advantage of the precise optical manipulation by the laser microbeam and quantitative phase imaging by digital holographic microscopy with high spatial and temporal resolution. This system will permit quantitative evaluation of the damage and/or the repair of the cell or cell organelles in real time.

Quantitative phase evaluation of dynamic changes on cell membrane during laser microsurgery.

The ability to inject exogenous material as well as to alter subcellular structures in a minimally invasive manner using a laser microbeam has been useful for cell biologists to study the structure-function relationship in complex biological systems. We describe a quantitative phase laser microsurgery system, which takes advantage of the combination of laser microirradiation and short-coherence interference microscopy. Using this method, quantitative phase images and the dynamic changes of phase during the process of laser microsurgery of red blood cells (RBCs) can be evaluated in real time. This system would enable absolute quantitation of localized alteration/damage to transparent phase objects, such as the cell membrane or intracellular structures, being exposed to the laser microbeam. Such quantitation was not possible using conventional phase-contrast microscopy.