Fibronectin Gene Up-regulation by Arnica montana in Human Macrophages: Validation by Real-Time Polymerase Chain Reaction Assay.

BACKGROUND AND AIM: Arnica montana L. (Arnica m.) is a popular traditional medicine, used for its therapeutic properties in healing traumas, but little is known about its biological action on tissue formation and repair. This new work tested the effects of Arnica m. homeopathic dilutions on human macrophages, key cells in tissue defence and repair. MATERIALS AND METHODS: Macrophages derived from the THP-1 cell line were differentiated with interleukin-4 to induce a 'wound-healing'-like phenotype, and treated with various dilutions of Arnica m. centesimal (100 times) dilutions (2c, 3c, 5c, 9c, and 15c) or control solvent for 24 hours. RNA samples from cultured cells were analysed by real-time quantitative polymerase chain reaction in five separate experiments. RESULTS: Arnica montana at the 2c dilution (final concentration of sesquiterpene lactones in cell culture = 10-8 mol/L) significantly stimulated the expression of three genes which code for regulatory proteins of the extracellular matrix, namely FN1 (fibronectin 1, % increase of 21.8 ± standard error of the mean 4.6), low-density lipoprotein-receptor-related protein 1 (% increase of 33.4 ± 6.1) and heparan sulphate proteoglycan 2 (% increase of 21.6 ± 9.1). Among these genes, the most quantitatively expressed was FN1. In addition, FN1, unlike other candidate genes, was upregulated in cells treated with higher dilutions/dynamisations (3c, 5c, and 15c) of Arnica m. CONCLUSION: The results support evidence that the extracellular matrix is a potential therapeutic target of Arnica m., with positive effects on cell adhesion and migration during tissue development and healing.

Isopathic Use of Auto-Sarcode of DNA as Anti-Miasmatic Homeopathic Medicine and Modulator of Gene Expression?

INTRODUCTION: In addition to the four pillars of homeopathy, vitalism and the miasmatic theory are often used to explain the health-disease process. According to Hahnemann's concepts, homeopathic miasms are the main obstacle to the cure of chronic diseases, with psora being the fundamental cause of all forms of diseases. According to modern genetics, the disease-promoting epigenetic alterations are the fundamental cause of the manifestation of chronic diseases. OBJECTIVE: This article develops a philosophical-scientific correlation between chronic miasms and disease-promoting epigenetic modifications, aiming to justify the isopathic use of auto-sarcode of an individual's DNA as homeopathic medicine. RESULTS: Based on the study of homeopathic doctrine and epigenetics, a conceptual and functional correlation is observed between homeopathic chronic miasms and disease-promoting epigenetic modifications. Additionally, several experimental studies suggest that homeopathy's mechanism of action may be by modulating gene expression. CONCLUSIONS: By the philosophical-scientific correlations described, it is inferred that disease-promoting epigenetic alterations are the biological representation of the chronic miasms, suggesting the isopathic use of auto-sarcode of DNA as homeopathic therapeutic modulator of gene expression for the management of chronic diseases.

Effects of ultra-high dilutions of sodium butyrate on viability and gene expression in HEK 293 cells.

BACKGROUND: Several recent studies reported the capability of high diluted homeopathic medicines to modulate gene expression in cell cultures. In line with these studies, we examined whether ultra-high dilutions (30C and 200C) of sodium butyrate (SB) can affect the expression levels of genes involved in acquisition of a senescence-associated secretory phenotype (SASP) in human embryonic kidney (HEK) 293 cells. METHODS: Cell viability was evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The expression levels of TNF-α, interleukin (IL)-2, IL-4, IL-6 and IL-10 genes were determined by real-time PCR assay. RESULTS: Exposure to both 30C and 200C during 48 h led to a significant decrease of the level of expression of TNF-α gene, while expression of IL-2 gene was increased when exposed to 30C, and expression of IL-10 gene was decreased when exposed to 200C. No changes in expression levels of all genes studied were observed in cells treated with both 30C and 200C remedies of SB during the 24 h. CONCLUSION: Observed changes in gene expression levels after exposure to 30C and 200C remedies of SB during 48 h suggest that extremely low concentrations of this agent can modulate the transcriptome of HEK 293 cells. These results are in line with findings from other studies confirming the ability of homeopathic remedies to modulate gene expression in cell cultures.

Arnica montana effects on gene expression in a human macrophage cell line. Evaluation by quantitative Real-Time PCR.

BACKGROUND: Arnica montana is a popular traditional remedy widely used in complementary medicine, also for its wound healing properties. Despite its acknowledged action in clinical settings at various doses, the molecular aspects relating to how A. montana promotes wound healing remain to be elucidated. To fill this gap, we evaluated the whole plant extract, in a wide range of dilutions, in THP-1 human cells, differentiated into mature macrophages and into an alternative IL-4-activated phenotype involved in tissue remodelling and healing. METHODS: Real-time quantitative Reverse Transcription Polymerase Chain Reaction (PCR) analysis was used to study the changes in the expression of a customized panel of key genes, mainly cytokines, receptors and transcription factors. RESULTS: On macrophages differentiated towards the wound healing phenotype, A. montana affected the expression of several genes. In particular CXC chemokine ligand 1 (CXCL1), coding for an chief chemokine, exhibited the most consistent increase of expression, while also CXC chemokine ligand 2 (CXCL2), Interleukin8 (IL8) and bone morphogenetic protein (BMP2) were slightly up-regulated, suggesting a positive influence of A. montana on neutrophil recruitment and on angiogenesis. MMP1, coding for a metalloproteinase capable of cleaving extracellular matrix substrates, was down-regulated. Most results showed non-linearity of the dose-effect relationship. CONCLUSIONS: This exploratory study provides new insights into the cellular and molecular mechanisms of action of A. montana as a promoter of healing, since some of the genes it modifies are key regulators of tissue remodelling, inflammation and chemotaxis.

Blueberry Improves the Therapeutic Effect of Etanercept on Patients with Juvenile Idiopathic Arthritis: Phase III Study.

Juvenile idiopathic arthritis (JIA) is the most common arthritis in the adolescents under the age of 16. Etanercept, an inhibitor of tumor necrosis factor, is often used to treat JIA despite its significant side effects. Homeopathic remedies, such as blueberries, have anti-inflammatory properties with fewer unwanted effects and should be considered as a primary treatment. We aimed to explore the efficacy and safety of combination therapy of blueberry and etanercept for JIA. Two hundred and one JIA patients were selected, and randomly and evenly assigned to three groups: ETA (50 mg of etanercept twice weekly), ETABJ (matched etanercept and 50 ml blueberry juice daily) and ETAPJ (matched etanercept and placebo juice). The severity of JIA was measured using American College of Rheumatology scales (ACR) 20, 50 and 70. The levels of pro-inflammatory cytokines, interleukin-1 (IL1) alpha and IL1 beta, and interleukin-1 receptor antagonist (IL1RA) were measured by qRT-PCR and ELISA. After a 6-month follow-up, the ACR20, ACR50 and ACR70 in an ETABJ group were higher than those in other two groups (P < 0.05), suggesting clinically meaningful improvement in JIA. Meanwhile, the symptoms and side effects were reduced significantly or absent in an ETABJ group, including mental diseases, retrobulbar optic neuritis, gaining weight, infection, cutaneous vasculitis, diarrhea, uveitis and pancytopenia. Blueberries reduced the levels of IL1 alpha and beta, and increased the level of IL1RA. Thus, a combination therapy of blueberry and etanercept can reduce the severity of JIA and should be developed as a new method for JIA therapy.

[Effect of retinociacdi combined extracts from testudinis carapacis et plastri on proliferating in MSCs and its mechanism].

OBJECTIVE: To explore the effect of retinociacdi (RA) combined extracts from Testudinis Carapacis et Plastri(PTE) on proliferating in MSCs and its mechanism. METHODS: Transfected PGL3-ID1 using the calcium phosphate co-precipitation method in rat MSCs. PTE combined with RA and retinociacdi receptor inhibitor(Ro41) acted on transfected MSCs with respective concentrations of 10(-6), 10(-7) and 10(-8) mol/L. Luciferase activity measurement was used to detect the activity of RAR and IDI 36 h later. PTE acted on MSCs 36 h,3 d and 7 d for respective concentrations of 1, 3, 30 and 100 microg/mL,then collected cells to detect RAR with RT-PCR. PTE combined with RA for 10(-7) mol/L and Ro41 for 10(-6) mol/L respectively on MSCs for 36 h,and then collected cells to detect RAR and ID1 with RT-PCR. RESULTS: PTE promoted expression of ID1 on MSCs. When combined with RA, the promotion effect became greater and it promoted expression of RAR at the same time; When inhibited RA using Ro41, the promotion of IDI was weaken by PTE. CONCLUSION: RA promotes expression of IDI on MSCs, PTE regulates proliferation and differentiation of MSCs by expression of nuclear receptor RAR.

[Anti-hepatic fibrosis effects research on serum containing extracts of Periplaneta americana in vitro].

OBJECTIVE: To study the anti-hepatic fibrosis effect of serum containing extracts of Periplaneta americana. METHODS: The serum contained extracts of Periplaneta americana was prepared with serologic pharmacological method. MTT method was used to observe the effect of serum containing extracts from periplaneta americana on hepatic stellate cells (HSC), and Elisa method was used to detect the contents of TGF-beta1 and collagen I in supernatant. RESULTS: Serum containing extracts I and II (15%) of Periplaneta americana had inhibitory effect on HCS (P < 0.05) after HSC were cultured with serum containing extracts of different concentration of Periolaneta americana for 24, 48 and 72 h. At 24 and 48 h, serum containing extracts I and II of Periplaneta americana decreased the content of collagen I in supernatant without significant difference (P < 0.05). Serum containing extracts I (15%, 9%, 5.4%) of Periplaneta americana could reduce generation of TGF-beta1 in supernatant for 24 h (P < 0.05). As for 48 h, only high concentration serum containing extracts I (15%) deceased the content of TGF-beta1 in supernatant. For 24 and 48 h,serum containing extracts II couldn't reduce the content of TGF-beta1 in supernatant (P < 0.05). CONCLUSION: It has definite effect on anti-hepatic fibrosis with serum containing extracts of Periplaneta americana in vitro. The mechanism may be related to inhibiting HSC propagation and reducing the production of TGF-beta1.

Endogenous morphine: up-to-date review 2011.

Positive evolutionary pressure has apparently preserved the ability to synthesize chemically authentic morphine, albeit in homeopathic concentrations, throughout animal phyla. Despite the establishment of a progressively rigorous and mechanistically focused historical literature extending from the mid 1970s to the mid 1980s that supported the expression of chemically authentic morphine by animal cellular and organ systems, prejudicial scepticism and early dismissal by scientists and clinicians most often obscured widespread acceptance of the biological importance and medical implications of endogenous morphine. The current critical paper presents and evaluates key recent coordinated studies in endogenous morphine research, highlighting those that have advanced our understanding of the functional roles of cognate alkaloid-selective µ(3) and µ(4) opiate receptors. We propose that the expression of endogenous morphine by animal and human cells is designed to mediate homeopathic regulation of metabolic activity via activation of cognate µ(3) and µ(4) receptors that serve as transductive conduits for shortcircuit Ca(++) fluxes. The implications of endogenous morphine coupling to nitric oxide regulation of mitochondrial function, with special reference to the cardiovascular system, are now formulated after many years of neglect.

Effect of Ganoderma lucidum extract on adipocyte differentiation and adiponectin gene expression in the murine pre-adipocyte cell line, 3T3-L1.

Ganoderma lucidum (G. lucidum), a traditional Chinese medicine, has been used for the treatment of various diseases including cancer and atherosclerosis. In this study, the positive effect of G. lucidum on metabolic syndrome was investigated in more detail by the use of 3T3-L1 pre-adipocyte cells. Treatment of 3T3-L1 cells with G. lucidum extract (GE) significantly promoted adipocyte differentiation and adiponectin production in a dose-dependent manner, as assessed by Oil-Red O staining, quantitative RT-PCR and ELISA. Treatment with GW9662, an inhibitor for peroxisome proliferator-activated receptor-gamma (PPARgamma), significantly attenuated GE-dependent adipocyte differentiation and adiponectin gene expression, suggesting the involvement of PPARgamma. Moreover, a reporter gene assay using GAL4-PPAR fusion proteins revealed that GE enhances GAL4-PPARgamma and GAL4-PPARalpha activities. These results indicate the presence of natural compounds possessing PPARgamma and PPARalpha activating properties in G. lucidum.

[Effects and mechanism of Plastrum testudinis extracts on PC12 apoptosis].

OBJECTIVE: To observe the inhibitive effects of Plastrum testudinis Extracts (PTE) on 6-Hydroxydopamine (6-OHDA) induced PC12 cells apoptosis and explore its mechanism. METHODS: PC12 apoptosis model was established by serum starvation and damaged for 24 hours. The cells were randomly divided into four groups:control group, 6-OHDA group, PTE 3, 30 microg/mL group. Cell optical density was determined by MTT; Ratio of cell apoptosis was examined by Annexin V/PI double stain flow cytometry (FCM), and Western blot was applied to detect the BCL-X/L expression. RESULTS: MTT and FCM analysis demonstrated that PTE can elevate PC12 cells viability and reduce their apoptotic ratio in a dose dependent manner. Western blot showed that PTE promoted the expression of BCL-X/L. CONCLUSION: PTE can inhibit the apoptosis of PC12 induced by 6-OHDA in a dose dependent manner, and its mechanism maybe associated partially with up-regulating BCL-X/L signaling pathway.

Symphytum officinale augments osteogenesis in human bone marrow-derived mesenchymal stem cells in vitro as they differentiate into osteoblasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Mesenchymal stem cells (MSCs) are multipotent stem cells possessing regenerative potential. Symphytum officinale (SO) is a medicinal plant and in homoeopathic literature, believed to accelerate bone healing. AIM OF THE STUDY: This study aimed to determine if homoeopathic doses of SO could augment osteogenesis in MSCs as they differentiate into osteoblasts in vitro. MATERIALS AND METHODS: Bone marrow samples were obtained from patients who underwent bone grafting procedures (n = 15). MSCs were isolated, expanded and characterized by flow cytometry (CD90, CD105). Cytotoxicity of SO was evaluated by MTT assay. Osteogenic differentiation was induced in MSCs with ß-glycerophosphate, ascorbic acid and dexamethasone over 2 weeks. Different homoeopathic doses of SO (MT, 3C, 6C, 12C and 30C) were added to the basic differentiation medium (BDM) and efficiency of MSCs differentiating into osteoblasts were measured by evaluating expression of Osteocalcin using flow cytometry, and alkaline phosphatase activity using ELISA. Gene expression analyses for osteoblast markers (Runx-2, Osteopontin and Osteocalcin) were evaluated in differentiated osteoblasts using qPCR. RESULTS: Flow cytometry (CD90, CD105) detected MSCs isolated from bone marrow (93-98%). MTT assay showed that the selected doses of SO did not induce any cytotoxicity in MSCs (24 hours). The efficiency of osteogenic differentiation (2 weeks) for different doses of Symphytum officinale was determined by flow cytometry (n = 10) for osteoblast marker, Osteocalcin, and most doses of Symphytum officinale enhanced osteogenesis. Interestingly, gene expression analysis for Runx-2 (n = 10), Osteopontin (n = 10), Osteocalcin (n = 10) and alkaline phosphatase activity (n = 8) also showed increased osteogenesis with the addition of Symphytum officinale to BDM, specially mother tincture. CONCLUSIONS: Our findings suggest that homoeopathic dose (specially mother tincture) of Symphytum officinale has the potential to enhance osteogenesis.

[Effect of Dahuangzhechong pill on the gene expression spectra of preventing arterial thrombosis].

OBJECTIVE: To investigate the effect of Dahuangzhechong pill on the gene expression spectra of preventing arterial thrombosis, and reveal its mechanism on molecule level. METHODS: Mononuclear cell and blood platelet of the arterial thrombosis patients were separated before and after treatment by Dahuangzhechong pill. Their RNA was extracted respectively and the genes expressions were detected using gene array containing 14,000 gene. RESULTS: 44 genes up-expressed and 299 genes down-expressed in blood platelet, 252 genes expression increased and 299 genes expression decreased in mononuclear cell genes after treated with Dahuangzhechong pill. The cluster analysis showed that the genes contained ion channel and transport protein, apoptosis related protein, DNA synthesis, repair and transcription factor, cell receptor, cell signal and transducin, and protein translation and synthesis, etc. CONCLUSION: Dahuangzhechong pill may prevent arterial thrombosis through genes containing ion channel and transport protein, apoptosis related protein, DNA synthesis, repair and transcription factor, cell receptor, cell signal and transducin, and protein translation and synthesis, etc.

[Inhibition effects of compound leech eye drops on apoptosis of lens epithelial cells and expressions of Bcl-2 and Bax genes in rats].

OBJECTIVE: To investigate the inhibition effects of compound leech eye drops (Co-SZ) on apoptosis of lens epithelial cells (LECs) induced by hydrogen peroxide (H2O2) and the expressions of apoptosis-related genes Bcl-2 and Bax in rats. METHODS: All fresh transparent LECs in SD rats were bathed in culture medium with H2O2 in vitro, meanwhile Co-SZ were added in the culture medium. All LECs were incubated for 24 hours. The apoptosis rate of LECs was determined by terminal deoxynucleotidyl transferase mediated biotin-dUTP nick end labeling method (TUNEL). The changes of LEC ultrastructure and the formation of apoptotic body were observed by transmission electron microscopy. The expressions of apoptosis-related genes Bcl-2 and Bax were detected by streptavdin-peroxidase-biotin method. RESULTS: The apoptosis rate of LECs in the Co-SZ-treated group was significantly lower than that in the H2O2-treated group. The changes of apoptotic LEC ultrastructure in the Co-SZ-treated group were less than those in the H2O2-treated group. The expression of Bcl-2 protein was up-regulated and the expression of Bax protein was down-regulated in the Co-SZ-treated group as compared with the H2O2-treated group. CONCLUSION: The LEC apoptosis induced by H2O2 can be inhibited by Co-SZ. The molecular mechanisms of Co-SZ in inhibiting LEC apoptosis may be related to regulating the expressions of apoptosis-related genes Bcl-2 and Bax.

The Protective Effect of Chrysanthemum indicum Extract against Ankylosing Spondylitis in Mouse Models.

In traditional Chinese and Korean homeopathic medicine, Chrysanthemum indicum Linné (Asteraceae) is a time-honored herb, prescribed for the resolution of symptoms associated with inflammatory and hypertensive conditions as well as those affecting the lungs and its associated structures. The goal of this work is to investigate the defensive role of Chrysanthemum indicum extract in fighting ankylosing spondylitis (AS) using mouse models, through which the manifestation and extent of the disease progression were measured with quantitative analysis of the intervertebral joints. Markers of inflammation as well as oxidative stress were also analysed. Western blot was used to quantify the levels of Nuclear Factor-κB (NF-κB) p65, Dickkopf-1 (DKK-1), and sclerostin (SOST). Consequently, the findings of this experiment demonstrated that AS in mice that were given Chrysanthemum indicum extract had lower level of TNF-α, IL-1ß, and IL-6 (P < 0.05) and increased level of catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) (P < 0.05). The results also revealed that Chrysanthemum indicum supplemented with diet contributed to a decrease in Nuclear Factor-κB (NF-κB) p65 protein expression (P < 0.05) and higher levels of DKK-1 and SOST proteins (P < 0.05). Therefore, we concluded that the beneficial role of Chrysanthemum indicum in AS is manifested through downregulating oxidative stress, inhibiting inflammatory mediators and NF-κB, and increasing DKK-1 and SOST levels.

Differential regulation of FSH and inhibin gene expression and synthesis by testosterone in immature and mature male rats.

Direct effects of testosterone on gonadotrophins at the pituitary level were studied in intact and castrated immature (age 10 days) and mature (70 days) male rats. Gonadotrophin-releasing hormone action was blocked by treatment with a potent GnRH antagonist, Ac-D-pClPhe-D-pClPhe-D-Trp-Ser-Tyr-D-Arg-Leu-Arg-Pro-D-Ala-+ ++NH2CH3COOH (Ant; Organon 30276; 1.0 mg/kg body weight per day) injected subcutaneously. Silicone elastomer capsules were used for the testosterone treatment. Both treatments commenced on the day of orchiectomy and lasted for 7 days. In adult male rats Ant treatment suppressed serum testosterone from 9.5 +/- 2.5 (S.E.M.) nmol/l to below the limit of detection (< 0.10 nmol/l; P < 0.01), and the testosterone implants reversed the decrease. Treatment with Ant decreased the pituitary content of FSH-beta subunit mRNA in intact and orchiectomized rats to 14% of their respective controls (P < 0.01). These levels were increased to 80-81% of controls (not significant) in both groups by combined treatment with testosterone and Ant. Orchiectomy alone increased FSH-beta subunit mRNA by 202% (P < 0.01). In intact immature rats Ant treatment decreased the level of pituitary FSH-beta subunit mRNA to 21% (P < 0.01), and a partial recovery (P < 0.01) to 42% of controls was observed with combined Ant+testosterone treatment. In contrast, in orchiectomized immature rats, where ANT decreased FSH-beta subunit levels to 48% of controls (P < 0.01), testosterone was able to reverse these mRNA levels completely (114% of controls). No evidence for the direct pituitary effects of testosterone were found in the mRNA of the common alpha or LH-beta subunits. In adult rats, the testicular inhibin alpha and beta A subunit mRNA levels were increased (P < 0.01) by Ant+testosterone compared with Ant-treated animals, but there were no differences in serum immunoreactive inhibin between any of the uncastrated adult groups. In intact immature rats, Ant+testosterone treatment increased (P < 0.01) inhibin beta A subunit mRNA levels compared with controls and Ant-treated animals. Ant decreased the level fo peripheral inhibin immunoreactivity from 8.3 +/- 2.0 U/ml to 2.1 +/- 0.4 U/ml (P < 0.01) and testosterone reversed it to 5.8 +/- 0.6 U/ml (not significant). In conclusion, our observations indicated that testosterone is able to stimulate FSH gene expression and secretion directly in immature and adult rats, but the testosterone response is enhanced at both ages by orchiectomy, even more so in the immature rat.(ABSTRACT TRUNCATED AT 400 WORDS)

Progesterone stimulates Krox-20 gene expression in Schwann cells.

The gene of the zinc finger transcription factor Krox-20 (Egr-2) is expressed in Schwann cells and plays an important role in myelination of peripheral nerves. We have shown that progesterone promotes myelination in the regenerating sciatic nerve and in cocultures of Schwann cells and sensory neurones. To determine whether progesterone regulates Krox-20 expression, we measured its effects on Krox-20 mRNA levels in the MSC80 mouse Schwann cell line by semi-quantitative RT-PCR. Although low levels of Krox-20 mRNA are detectable in MSC80 cells cultured in defined medium, treatment with 10(-6) M progesterone induces a rapid (15 min) and transient increase in the levels of Krox-20 mRNA. Lower doses of progesterone (10(-9), 10(-8) and 10(-7) M) are also effective in increasing Krox-20 mRNA. Other steroids including testosterone, dexamethasone, and estradiol are ineffective when added to the culture medium at 10(-6) M for 1 h. The induction of Krox-20 mRNA was also observed with the selective progesterone agonist Organon 2058 and was abolished by treating the MSC80 Schwann cells with the progesterone antagonist RU486, indicating that progesterone induces Krox-20 mRNA expression by binding to its intracellular receptor. The induction of Krox-20 by progesterone was also demonstrated in primary cultures of Schwann cells isolated from neonatal rat sciatic nerves, at the mRNA level by RT-PCR and at the protein level by immunohistochemistry. As Krox-20 is a necessary step for the initiation of myelin formation in peripheral nerves, its stimulation by progesterone suggests an important signalling function for this steroid in myelination.

[Investigation on NB4 cell responses to realgar by cDNA microarray].

OBJECTIVE: To elucidate the molecular mechanism of realgar-induced apoptosis and differentiation of acute promyelocytic leukemia(APL) cell line NB4. METHOD: The response of NB4 cells to realgar was explored with a cDNA microarray representing 1003 different human genes. RESULT: The analysis of gene expression profiles indicated that 9 genes were up-regulated and 37 genes were down-regulated. Among the 9 up-regulated genes, 2 genes were involved in proteasome degradation pathway. CONCLUSION: PSMC2, PSMD1 and ITGB1 genes may play a role in the apoptosis and differentiation of NB4 cells.

Embracing complexity: organicism for the 21st century.

Organicism (materialistic holism) has provided the philosophical underpinnings for embryology since the time of Kant. It had influenced the founders of developmental mechanics, and the importance of organicism to embryology was explicitly recognized by such figures as O. Hertwig, H. Spemann, R. Harrison, A. M. Dalq, J. Needham, and C. H. Waddington. Many of the principles of organicism remain in contemporary developmental biology, but they are rarely defined as such. A combination of genetic reductionism and the adoption of holism by unscientific communities has led to the devaluation of organicism as a fruitful heuristic for research. This essay attempts to define organicism, provide a brief history of its importance to experimental embryology, outline some sociologically based reasons for its decline, and document its value in contemporary developmental biology. Based on principles or organicism, developmental biology should become a science of emerging complexity. However, this does mean that some of us will have to learn calculus.