Much is known about the strong ecological impact that earthworms ( Qiū Yǐn; Pheretima) have on soil in terms of fertility, nutrient production, and tilling. Even more interesting though is the impact they have had on our understanding of innate immunity, and from this discovery, there has been a simultaneous recognition of their potential through their historical use as food and their use in treatment of certain chronic health problems that often afflict humans. This bifurcating growing knowledge base has stemmed from centuries of honing and practicing traditional and complementary forms of medicine such as Ayurveda (India) Traditional Chinese Medicine (China), Kampo (Japan), and Traditional Korean Medicine (Korea). Earthworms (Dilong) have also been credited as a model for research concerning the nervous and endocrine systems. One of the reasons behind the earthworm's tremendous impact on research into these biomedical endeavors is partly due to its lack of ethical restrictions, like those imposed on vertebrate models. Using invertebrate models as opposed to mice or other mammalian models bypasses ethical concerns. Moreover, financial constraints consistently hover over biological research that requires living subjects, preferably mammals. Earthworms are a rich source of several vital biological macromolecules and other nutrients. They have long been used as food in several cultures such as the Ye'Kuana in Venezuela, the Maori in New Zealand, and the nomadic populations in Papua New Guinea. Earthworms and their nutritious products have been shown to exert significant effects in treating humans for disorders of inflammation and blood coagulation. One area that continues to be examined is the earthworm's ability to regenerate lost appendages, and these effects have been extended to mammals. Evidence reveals that earthworm extracts may actually promote the regeneration of damaged nerves. This presentation will explore how earthworms may reveal significant advances and conclusions that decipher innate immunity. This is intimately associated with them as sources of their various nutritional and medicinal benefits.

Recent evidence supports that prokaryotes exhibit adaptive immunity in the form of CRISPR (Clustered Regularly Interspersed Short Palindromic Repeats) and Cas (CRISPR associated proteins). The CRISPR-Cas system confers resistance to exogenous genetic elements such as phages and plasmids by allowing for the recognition and silencing of these genetic elements. Moreover, CRISPR-Cas serves as a memory of past exposures. This suggests that the evolution of the immune system has counterparts among the prokaryotes, not exclusively among eukaryotes. Mathematical models have been proposed which simulate the evolutionary patterns of CRISPR, however large gaps in our understanding of CRISPR-Cas function and evolution still exist. The CRISPR-Cas system is analogous to small RNAs involved in resistance mechanisms throughout the tree of life, and a deeper understanding of the evolution of small RNA pathways is necessary before the relationship between these convergent systems is to be determined. Presented in this review are novel RNAi therapies based on CRISPR-Cas analogs and the potential for future therapies based on CRISPR-Cas system components.

The self-non-self theory has dominated immunology since the 1950s. In the 1990s, Matzinger and her colleagues suggested a new, competing theory, called the "danger theory." This theory has provoked mixed acclaim: enthusiasm and criticism. Here we assess the danger theory vis-à-vis recent experimental data on innate immunity, transplantation, cancers and tolerance to foreign entities, and try to elucidate more clearly whether danger is well defined.

Over the last few years, we have pursued the use and exploitation of invertebrate immune systems, most notably their humoral products, to determine what effects their complex molecules might exert on humans, specifically their potential for therapeutic applications. This endeavor, called "bioprospecting," is an emerging necessity for biomedical research. In order to treat the currently "untreatable," or to discover more efficient treatment modalities, all options and potential sources must be exhausted so that we can provide the best care to patients, that is, proceed from forest and ocean ecosystems through the laboratory to the bedside. Here, we review current research findings that have yielded therapeutic benefits, particularly as derived from soft and hard corals. Several applications have already been demonstrated, including anti-inflammatory properties, anticancer properties, bone repair, and neurological benefits.

Earthworms have provided ancient cultures with food and sources of medicinal cures. Ayurveda, traditional Chinese medicine (TCM), and practices in Japan, Vietnam, and Korea have focused first on earthworms as sources of food. Gradually fostering an approach to potential beneficial healing properties, there are renewed efforts through bioprospecting and evidence-based research to understand by means of rigorous investigations the mechanisms of action whether earthworms are used as food and/or as sources of potential medicinal products. Focusing on earthworms grew by serendipity from an extensive analysis of the earthworm's innate immune system. Their immune systems are replete with leukocytes and humoral products that exert credible health benefits. Their emerging functions with respect to evolution of innate immunity have long been superseded by their well-known ecological role in soil conservation. Earthworms as inexpensive, noncontroversial animal models (without ethical concerns) are not vectors of disease do not harbor parasites that threaten humans nor are they annoying pests. By recognizing their numerous ecological, environmental, and biomedical roles, substantiated by inexpensive and more comprehensive investigations, we will become more aware of their undiscovered beneficial properties.