Monthly Archives: August 2014


heard on the street …. probably nothing but …..

So what’s interesting in this (possibly ridiculous) speculation….

Reviews of Providers: First, Zagat’s, then Zagats then Angie’s List, and now possibly Amazon? (for Amazon to offer customer reviews of health care providers). My assessment: 20% likely in next three years, 60% in ten. (Recommendations for services would be a very new step for Amazon)

Medical service packages: Amazon might offer services or packages of something that consumers actively shop for, and break the traditional pick-the-closest doctor/hospital mindset that most consumers have gotten used to.My assessment: 20% likely in next three years, 60% in ten.

LABS, VITALS, and IMAGING: These should be commodities. It is not too hard to picture vendors posting their prices and features. My assessment: 30% likely in next three years, 80% in ten.

MAJOR PROCEDURES: open heart surgery or transplants come to mind — those kinds of packages of services would also seem to lend themselves to an Amazonian open competition.My assessment: 10% likely in next three years, 50% in ten.

Amazon has amazing range, but it has its hands very full right now cracking food and beverage through Amazon Fresh (trucks were spotted this week in NYC and they took their LA expansion last year to all of California so they are moving!)

I could see this absorption taking three years, and then on to health care….thee rumblings are just Amazon learning and pre-planning.

Fab Labs

Another great idea from Clay Johnson: let’s create the first “Fab Lab” in Atlanta – at Serenbe.

“Fab” is short for “fabrication” – and a Fab Lab is part of a global network of Fab Labs, initiated by the MIT Center of Bits and Atoms to encourage fabrication by lay people.

The idea is that making things with tools, particular things that are a part of the emerging digital economy, is much easier and much more fun than people think. Participants can learn a lot, and create a lot.


Serenbe needs a Fab Lab!

A very rough guess was made to answer the question: what would it cost to make this happen? Clay’s best guess is $100K.

Where would the Fab Lab be housed? Not clear at this time, but surely we can find a great place.

The section below of the website makes it clear that there are four criteria, all of which we can meet:

1. Must be open to the public
2. Must subscribe to the FabLab charter
3. Must have a common set of tools and processes*
4. Must participate in the global network (there is a Fab Lab academy, and annual global summit, etc)

* a laser cutter for 2D/3D design and fabrication, a high precision milling machine for making circuits and molds for casting, a vinyl cutter for making flexible circuits and crafts, and a fairly sophisticated electronics workbench for prototyping circuits and programming micro controllers. Optional: large wood routing machine for furniture and housing applications and 3D printers.

From the Website
Who/What qualifies as a Fab Lab?
The four qualities and requirements listed below altogether create an enabling environment that we call a Fab Lab. If your lab effort meets all these criteria, “Welcome!” If you feel you are in synchrony with the Fab Lab form and spirit, please use our logo in your fundraising efforts, and keep us informed of your progress. Please register your lab effort or new fab lab on the world map here. Here are the criteria we currently use for defining a Fab Lab:

First and foremost, public access to the Fab Lab is essential. A Fab Lab is about democratizing access to the tools for personal expression and invention. So a Fab Lab must be open to the public for free or in-kind service/barter at least part of the time each week, that’s essential.

Fab Labs support and subscribe to the Fab Lab charter:

Fab Labs have to share a common set of tools and processes. A prototyping facility is not the equivalent of a Fab Lab. A 3D printer is not a Fab Lab. The idea is that all the labs can share knowledge, designs, and collaborate across international borders. If I make something here in Boston and send you the files and documentation, you should be able to reproduce it there, fairly painlessly. If I walk into a Fab Lab in Russia, I should be able to do the same things that I can do in Nairobi, Cape Town, Delhi, Amsterdam or Boston Fab Labs. The critical machines and materials are identified in this list: and there’s a list of open source software and freeware that we use online as well (embedded in Fab Academy modules here: ) But essentially it’s the processes and the codes and the capabilities that are important. So you want a laser cutter for 2D/3D design and fabrication, a high precision milling machine for making circuits and molds for casting, a vinyl cutter for making flexible circuits and crafts, a fairly sophisticated electronics workbench for prototyping circuits and programming microcontrollers, and if you can possibly find the funds, you’ll want the large wood routing machine for furniture and housing applications. We are also testing fairly inexpensive, but robust and with fair resolution 3D printers—the most current favorite is listed in the inventory.

Fab Labs must participate in the larger, global Fab Lab network, that is, you can’t isolate yourself. This is about being part of a global, knowledge-sharing community. The public videoconference is one way to do connect. Attending the annual Fab Lab meeting is another. FAB10 is in Barcelona this year, July 2-8. Collaborating and partnering with other labs in the network on workshops, challenges or projects is another way. Participating in Fab Academy is yet another way.


A few new insights about e-commerce:

Online US retail grew 9% in 2013. Forrester projects 9.5% CGR to 2018.

Food and Beverage

Today’s report plugs the e-commerce growth rate of food and beverage (itself the largest category in the US economy at $600 billion) at 21% through to 2018 – its small now, but will grow to about $18 billion by 2018.


Forbes article reporting that WalMart at shareholder meeting stated that they expect their $10 billion e-commerce business (3% of sales) to grow 30% to $13 billion.

“According to Forrester Research, U.S. online retail sales grew 9% in 2013 and are expected to grow at a compound annual growth rate of 9.5% through to 2018. Wal-Mart believes that it can deliver 30% e-commerce revenue growth this year driven by the industry growth, its 0mni-channel initiatives, enhanced product variety over the Internet, and better delivery efficiency. Moreover, the retailer can effectively leverage its vast presence to sustain a competitive advantage over the online giant Amazon. Wal-Mart witnessed 27% growth in its online revenues in the first quarter of fiscal 2015, which suggests that it is on course to deliver on its promise.”

More from article (with attribution)

How E-Commerce Is Finally Disrupting The $600 Billion-A-Year Grocery Industry


AUG. 20, 2014

At $600 billion a year in sales, food and beverage is by far the largest retail category in the U.S. by a wide margin. However, it’s also the category that has been the least disrupted by e-commerce; less than 1% of food and beverage sales currently occur online, according to BI Intelligence’s estimates.

But shopping habits are changing, and niche online grocery services that compete on convenience and selection are gaining traction. Meanwhile tech giants like Amazon are fronting the cost of expensive delivery infrastructure that has so far held back grocery e-commerce. 

In a new in-depth report, BI Intelligence looks at why the grocery business has proved so challenging to e-commerce companies — from consumer reluctance to complicated and expensive logistics — and what new strategies e-commerce startups and big-name tech companies are pursuing to push more grocery sales online. Between 2013 and 2018, online grocery sales will grow at a compound annual growth rate (CAGR) of 21.1%, reaching nearly $18 billion by the end of the forecast period. For comparison, offline grocery sales will rise by 3.1% annually during the same period. 
Here are some of the key findings explored in the report: 

There are a number of disadvantages to buying groceries online on both the consumer and business side, such as the cost and complexity of logistics, shipping fees, and the quality and freshness of orders. For online grocers to deliver the freshness consumers want, they have to be able to deliver orders fast while maintaining the quality of easily damaged foods like produce.

But there are still some advantages to online grocery shopping, in particular convenience and a large selection of products. Only 15% of U.S. adults have purchased general food items online, but 25% said they have bought specialty food and beverages online, which are hard to find elsewhere.

New startups that focus on concierge shopping and subscription prepared meals are innovating on the online grocery model and offering services that really are differentiated from traditional supermarket shopping. We believe these services could change the way people shop for food. In addition, established online grocers have an opportunity in enterprise grocery sales, which lowers costs through bulk purchases.

Some of the biggest names in tech — Amazon, eBay, and Google — are beginning to offer and promote same-day delivery services. As consumers get used to the convenience of ordering something online and receiving it the same day, grocery e-commerce may benefit too, with people more likely to buy food they know they will get quickly. While same-day delivery comes with a big price tag, 25% of millennials said they would pay a premium for same-day delivery.

Read more:


“Systems biology…is about putting together rather than taking apart, integration rather than reduction. It requires that we develop ways of thinking about integration that are as rigorous as our reductionist programmes, but different….It means changing our philosophy, in the full sense of the term” (Denis Noble).[5]

From Wikipedia, the free encyclopedia
For the journal Proteomics, see Proteomics (journal).

Proteomics is the large-scale study of proteins, particularly their structuresand functions.[1][2] Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells.

The term proteomics was first coined in 1997[3] to make an analogy with genomics, the study of the genome. The word proteome is a blend of protein and genome, and was coined by Marc Wilkins in 1994 while working on the concept as a PhD student.[4][5]

The proteome is the entire set of proteins,[4] produced or modified by an organism or system. This varies with time and distinct requirements, or stresses, that a cell or organism undergoes.

Proteomics is an interdisciplinary domain formed on the basis of the research and development of the Human Genome Project;[citation needed] it is also emerging scientific research and exploration of proteomes from the overall level of intracellular protein composition, structure, and its own unique activity patterns. It is an important component of functional genomics.

While proteomics generally refers to the large-scale experimental analysis of proteins, it is often specifically used for protein purification and mass spectrometry.

Contents [hide]
1 Complexity of the problem
1.1 Post-translational modifications
1.1.1 Phosphorylation
1.1.2 Ubiquitination
1.1.3 Additional modifications
1.2 Distinct proteins are made under distinct settings
2 Limitations of genomics and proteomics studies
3 Methods of studying proteins
3.1 Protein Detection with Immunoassays
3.2 Identifying proteins that are post-translationally modified
3.3 Determining the existence of proteins in complex mixtures
3.4 Computational methods in studying protein biomarkers
4 Establishing protein–protein interactions
5 Practical applications of proteomics
5.1 Biomarkers
5.2 Proteogenomics
5.3 Current research methodologies
6 Bioinformatics for Proteomics
7 Structural proteomics
8 Expression proteomics
9 Interaction proteomics
10 Proteomics and System Biology
11 Current Proteomic Technologies
11.1 Mass Spectrometry and Protein Profiling
11.2 Protein Chips
11.3 Reverse Phased Protein Microarrays
12 Emerging trends in Proteomics
12.1 Human Plasma Proteome
13 See also
13.1 Protein databases
13.2 Research centers
14 References
15 Bibliography
16 External links

Complexity of the problem

After genomics and transcriptomics, proteomics is the next step in the study of biological systems. It is more complicated than genomics because an organism’s genome is more or less constant, whereas the proteome differs from cell to cell and from time to time. Distinct genes are expressed in different cell types, which means that even the basic set of proteins that are produced in a cell needs to be identified.
In the past this phenomenon was done by mRNA analysis, but it was found not to correlate with protein content.[6][7] It is now known that mRNA is not always translated into protein,[8] and the amount of protein produced for a given amount of mRNA depends on the gene it is transcribed from and on the current physiological state of the cell. Proteomics confirms the presence of the protein and provides a direct measure of the quantity present.

Post-translational modifications
Not only does the translation from mRNA cause differences, but many proteins are also subjected to a wide variety of chemical modifications after translation. Many of these post-translational modifications are critical to the protein’s function.

One such modification is phosphorylation, which happens to many enzymes and structural proteins in the process of cell signaling. The addition of a phosphate to particular amino acids—most commonly serine and threonine[9] mediated by serine/threonine kinases, or more rarely tyrosine mediated by tyrosine kinases—causes a protein to become a target for binding or interacting with a distinct set of other proteins that recognize the phosphorylated domain.
Because protein phosphorylation is one of the most-studied protein modifications, many “proteomic” efforts are geared to determining the set of phosphorylated proteins in a particular cell or tissue-type under particular circumstances. This alerts the scientist to the signaling pathways that may be active in that instance.

Ubiquitin is a small protein that can be affixed to certain protein substrates by enzymes called E3 ubiquitin ligases. Determining which proteins are poly-ubiquitinated helps understand how protein pathways are regulated. This is, therefore, an additional legitimate “proteomic” study. Similarly, once a researcher determines which substrates are ubiquitinated by each ligase, determining the set of ligases expressed in a particular cell type is helpful.
Additional modifications[edit]
Listing all the protein modifications that might be studied in a “proteomics” project would require a discussion of most of biochemistry. Therefore, a short list illustrates the complexity of the problem. In addition to phosphorylation and ubiquitination, proteins can be subjected to (among others) methylation, acetylation, glycosylation, oxidation and nitrosylation. Some proteins undergo all these modifications, often in time-dependent combinations. This illustrates the potential complexity of studying protein structure and function.


Practical applications of proteomics

One major development to come from the study of human genes and proteins has been the identification of potential new drugs for the treatment of disease. This relies on genome and proteome information to identify proteins associated with a disease, which computer software can then use as targets for new drugs. For example, if a certain protein is implicated in a disease, its 3D structure provides the information to design drugs to interfere with the action of the protein. A molecule that fits the active site of an enzyme, but cannot be released by the enzyme, inactivates the enzyme. This is the basis of new drug-discovery tools, which aim to find new drugs to inactivate proteins involved in disease. As genetic differences among individuals are found, researchers expect to use these techniques to develop personalized drugs that are more effective for the individual.[19]
Proteomics is also used to reveal complex plant-insect interactions that help identify candidate genes involved in the defensive response of plants to herbivory.[20][21][


Proteomics and System Biology

Proteomics has recently come into the act as a promising force to transform biology and medicine. It is becoming increasingly apparent that changes in mRNA expression correlate poorly with protein expression changes. Proteins changes enormously in patterns of expressions across developmental and physiological responses. Proteins also face changes on the act of environmental perturbations. Proteins are the actual effectors driving cell behavior. The field of proteomics strives to characterize protein structure and function, protein-protein,protein-nucleic acid, protein-lipid, and enzyme-substrate interactions, protein processing and folding, protein activation, cellular and sub-cellular localization, protein turnover and synthesis rates, and even promoter usage. Integrating proteomic data with information such as gene, mRNA and metabolic profiles helps in better understanding of how the system works.[37]

See also[edit]

Activity based proteomics
Bottom-up proteomics
Functional genomics
Heat stabilization
List of biological databases
List of omics topics in biology
Proteomic chemistry
Shotgun proteomics
Top-down proteomics
Systems biology
Yeast two-hybrid system
Protein databases[edit]
Human Protein Atlas
Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)
Human Protein Reference Database
Model Organism Protein Expression Database (MOPED)
National Center for Biotechnology Information (NCBI)
Protein Data Bank (PDB)
Protein Information Resource (PIR)
Proteomics Identifications Database (PRIDE)
Proteopedia The collaborative, 3D encyclopedia of proteins and other molecules
Research centers[edit]
European Bioinformatics Institute
Netherlands Proteomics Centre (NPC)
Proteomics Research Resource for Integrative Biology (NIH)
Global map of proteomics labs

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Belhajjame, K. et al. Proteome Data Integration: Characteristics and Challenges. Proceedings of the UK e-Science All Hands Meeting, ISBN 1-904425-53-4, September 2005, Nottingham, UK.
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External links[edit]

Proteomics on the Open Directory Project
Look up proteomics in Wiktionary, the free dictionary.
Wikibooks has more on the topic of: Proteomics
At Wikiversity you can learn more and teach others aboutProteomics at:
The Department of Proteomics
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Personalized medicine
From Wikipedia, the free encyclopedia
Personalized medicine or PM is a medical model that proposes the customization of healthcare – with medical decisions, practices, and/or products being tailored to the individual patient. In this model, diagnostic testing is essential for selecting appropriate therapies; terms used to describe these tests include “”companion diagnostics”, “theranostics” (a portmanteau of therapeutics and diagnostics), and “therapygenetics”. The use of genetic information has played a major role in certain aspects of personalized medicine, and the term was even first coined in the context of genetics (though it has since broadened to encompass all sorts of personalization measures). To distinguish from the sense in which medicine has always been inherently “personal” to each patient, PM commonly denotes the use of some kind of technology or discovery enabling a level of personalization not previously feasible or practical.
Contents [hide]
1 Background
2 Technologies
3 Examples
3.1 Cancer management
4 Psychiatry and psychological therapy
5 See also
6 References
7 Further reading
8 External links

Traditional clinical diagnosis and management focuses on the individual patient’s clinical signs and symptoms, medical and family history, and data from laboratory and imaging evaluation to diagnose and treat illnesses. This is often a reactive approach to treatment, i.e., treatment/medication starts after the signs and symptoms appear.
Advances in medical genetics and human genetics have enabled a more detailed understanding of the impact of genetics in disease. Large collaborative research projects (for example, the Human genome project) have laid the groundwork for the understanding of the roles of genes in normal human development and physiology, revealed single nucleotide polymorphisms (SNPs) that account for some of the genetic variability between individuals, and made possible the use of genome-wide association studies (GWAS) to examine genetic variation and risk for many common diseases.
Historically, the pharmaceutical industry has developed medications based on empiric observations and more recently, known disease mechanisms.[citation needed] For example, antibiotics were based on the observation that microbes produce substances that inhibit other species. Agents that lower blood pressure have typically been designed to act on certain pathways involved in hypertension(such as renal salt and water absorption, vascular contractility, and cardiac output). Medications for high cholesterol target the absorption, metabolism, and generation of cholesterol. Treatments for diabetes are aimed at improving insulin release from the pancreas and sensitivity of the muscle and fat tissues to insulin action. Thus, medications are developed based on mechanisms of disease that have been extensively studied over the past century. It is hoped that recent advancements in the genetic etiologies of common diseases will improve pharmaceutical development.

Since the late 1990s, the advent of research using biobanks has brought advances in molecular biology, proteomics, metabolomicanalysis, genetic testing, and molecular medicine. Another significant development has been the notion of companion diagnostics, whereby molecular assays that measure levels of proteins, genes, or specific mutations are used to provide a specific therapy for an individual’s condition – by stratifying disease status, selecting the proper medication, and tailoring dosages to that patient’s specific needs. Additionally, such methods might be used to assess a patient’s risk factor for a number of conditions and tailor individualpreventative treatments.
Pharmacogenetics (also termed pharmacogenomics) is the field of study that examines the impact of genetic variation and responses to therapeutic interventions by biomarker (medicine).[1] This approach is aimed at tailoring drug therapy at a dosage that is most appropriate for an individual patient, with the potential benefits of increasing the efficacy and safety of medications.[2] Other benefits include reduced time, cost, and failure rates of clinical trials in the production of new drugs by using precise biomarkers.[3] Gene-centered research may also speed the development of novel therapeutics.[4]
The field of proteomics, or the comprehensive analysis and characterization of all of the proteins and protein isoforms encoded by thehuman genome, may eventually have a significant impact on medicine. This is because while the DNA genome[5] is the information archive, it is the proteins that do the work of the cell: the functional aspects of the cell are controlled by and through proteins, not genes.
It has also been demonstrated that pre-dose metabolic profiles from urine can be used to predict drug metabolism.[6][7]Pharmacometabolomics refers to the direct measurement of metabolites in an individual’s bodily fluids, in order to predict or evaluate the metabolism of pharmaceutical compounds.

Some examples of personalized medicine include:
Genotyping for SNPs in genes involved in the action and metabolism of warfarin (Coumadin). This medication is used clinically as an anticoagulant but requires periodic monitoring and is associated with adverse side affects. Recently, genetic variants in the gene encoding Cytochrome P450 enzyme CYP2C9, which metabolizes warfarin,[8] and the Vitamin K epoxide reductase gene (VKORC1), a target of coumarins,[9] have led to commercially-available testing that enables more accurate dosing based on algorithms that take into account the age, gender, weight, and genotype of an individual.
Genotyping variants in genes encoding Cytochrome P450 enzymes (CYP2D6, CYP2C19, and CYP2C9), which metabolize neuroleptic medications, to improve drug response and reduce side-effects.[10]
Cancer management[edit]
Oncology is a field of medicine with a long history of classifying tumor stages and subtypes based on anatomic and pathologic findings. This approach includes histological examination of tumor specimens from individual patients (such as HER2/NEU in breast cancer) to look for markers associated with prognosis and likely treatment responses. Thus, “personalized medicine” was in practice long before the term was coined. New molecular testing methods have enabled an extension of this approach to include testing for global gene, protein, and protein pathway activation expression profiles and/or somatic mutations in cancer cells from patients in order to better define the prognosis in these patients and to suggest treatment options that are most likely to succeed.[11][12]
Examples of personalized cancer management include:
Companion diagnostics for targeted therapies.
Trastuzumab (trade names Herclon, Herceptin) is a monoclonal antibody drug that interferes with the HER2/neu receptor. Its main use is to treat certain breast cancers. This drug is only used if a patient’s cancer is tested for overexpression the HER2/neu receptor. Two of the most common tests used are the (Dako) HercepTest and Genentech’s Herceptin.[13] Only Her2+ patients will be treated with Herceptin therapy (trastuzumab)[14]
Tyrosine kinase inhibitors such as imatinib (marketed as Gleevec) have been developed to treat chronic myeloid leukemia(CML), in which the BCR-ABL fusion gene (the product of a reciprocal translocation between chromosome 9 and chromosome 22) is present in >95% of cases and produces hyperactivated abl-driven protein signaling. These medications specifically inhibit the Ableson tyrosine kinase (ABL) protein and are thus a prime example of “rational drug design” based on knowledge of disease pathophysiology.[15]
Testing for disease-causing mutations in the BRCA1 and BRCA2 genes, which are implicated in hereditary breast–ovarian cancer syndromes. Discovery of a disease-causing mutation in a family can inform “at-risk” individuals as to whether they are at higher risk for cancer and may prompt individualized prophylactic therapy including mastectomy and removal of the ovaries. This testing involves complicated personal decisions and is undertaken in the context of detailed genetic counseling. More detailed molecular stratification of breast tumors may pave the way for future tailored treatments.[16] These tests are part of the emerging field ofcancer genetics, which is a specialized field of medical genetics concerned with hereditary cancer risk.
Psychiatry and psychological therapy[edit]

Efforts are underway to apply the tools of personalized medicine to psychiatry and psychological therapy; these technologies are still under development as of 2013.
In 2012 Professor Thalia Eley and her research team coined the term “therapygenetics” refers to a branch of psychiatric genetic research looking at the relationship between specific genetic variants and differences in the level of success of psychological therapy.[17][18] The field is parallel to pharmacogenetics, which explores the association between specific genetic variants and the efficacy of drug treatments. Therapygenetics work also relates to the differential susceptibility hypothesis [19] which proposes that individuals have a genetic predisposition to respond to a greater or lesser extent to their environment, be it positive or negative.
See also[edit]

Predictive medicine
Whole genome sequencing
Drug development
Translational Research
$1,000 genome

Jump up^ Shastry BS (2006). “Pharmacogenetics and the concept of individualized medicine”. Pharmacogenomics J. 6 (1): 16–21.doi:10.1038/sj.tpj.6500338. PMID 16302022.
Jump up^ Ozdemir, Vural; Williams-Jones, Bryn; Glatt, Stephen J; Tsuang, Ming T; Lohr, James B; Reist, Christopher (August 2006). “Shifting emphasis from pharmacogenomics to theranostics”. Nature Biotechnology 24 (8): 942–946. Retrieved 30 March 2013.
Jump up^ Galas, D. J., & Hood, L. (2009). “Systems Biology and Emerging Technologies Will Catalyze the Transition from Reactive Medicine to Predictive, Personalized, Preventive and Participatory (P4) Medicine”. Interdisciplinary Bio Central 1: 1–4.doi:10.4051/ibc.2009.2.0006.
Jump up^ Shastry BS (2006). “Pharmacogenetics and the concept of individualized medicine”. Pharmacogenomics J. 6 (1): 16–21.doi:10.1038/sj.tpj.6500338. PMID 16302022.
Jump up^ Harmon, Katherine (2010-06-28). “Genome Sequencing for the Rest of Us”. Scientific American. Retrieved 2010-08-13.
Jump up^ Clayton TA, Lindon JC, Cloarec O, et al. (April 2006). “Pharmaco-metabonomic phenotyping and personalized drug treatment”. Nature 440 (7087): 1073–7.doi:10.1038/nature04648. PMID 16625200.
Jump up^ Clayton TA, Baker D, Lindon JC, Everett JR, Nicholson JK (August 2009). “Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism”. Proc. Natl. Acad. Sci. U.S.A. 106(34): 14728–33. doi:10.1073/pnas.0904489106.PMC 2731842. PMID 19667173.
Jump up^ Schwarz UI (November 2003). “Clinical relevance of genetic polymorphisms in the human CYP2C9 gene”. Eur. J. Clin. Invest. 33. Suppl 2: 23–30. doi:10.1046/j.1365-2362.33.s2.6.x. PMID 14641553.
Jump up^ Oldenburg J, Watzka M, Rost S, Müller CR (July 2007). “VKORC1: molecular target of coumarins”. J. Thromb. Haemost. 5. Suppl 1: 1–6. doi:10.1111/j.1538-7836.2007.02549.x.PMID 17635701.
Jump up^ Cichon S, Nöthen MM, Rietschel M, Propping P (2000). “Pharmacogenetics of schizophrenia”. Am. J. Med. Genet. 97(1): 98–106. doi:10.1002/(SICI)1096-8628(200021)97:1<98::AID-AJMG12>3.0.CO;2-W.PMID 10813809.
Jump up^ Mansour JC, Schwarz RE (August 2008). “Molecular mechanisms for individualized cancer care”. J. Am. Coll. Surg.207 (2): 250–8. doi:10.1016/j.jamcollsurg.2008.03.003.PMID 18656055.
Jump up^ van’t Veer LJ, Bernards R (April 2008). “Enabling personalized cancer medicine through analysis of gene-expression patterns”.Nature 452 (7187): 564–70. doi:10.1038/nature06915.PMID 18385730.
Jump up^ Carney, Walter (2006). “HER2/neu Status is an Important Biomarker in Guiding Personalized HER2/neu Therapy”.Connection 9: 25–27.
Jump up^ Telli, M. L.; Hunt, S. A.; Carlson, R. W.; Guardino, A. E. (2007). “Trastuzumab-Related Cardiotoxicity: Calling Into Question the Concept of Reversibility”. Journal of Clinical Oncology 25 (23): 3525–3533.doi:10.1200/JCO.2007.11.0106. ISSN 0732-183X.PMID 17687157.
Jump up^ Saglio G, Morotti A, Mattioli G, et al. (December 2004). “Rational approaches to the design of therapeutics targeting molecular markers: the case of chronic myelogenous leukemia”.Ann. N. Y. Acad. Sci. 1028 (1): 423–31.doi:10.1196/annals.1322.050. PMID 15650267.
Jump up^ Gallagher, James (19 April 2012). “Breast cancer rules rewritten in ‘landmark’ study”. BBC News. Retrieved 19 April 2012.
Jump up^ Lester, KJ; Eley TC (2013). “Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders”. Biology of mood & anxiety disorders 3(1): 1–16. doi:10.1186/2045-5380-3-4. PMC 3575379.PMID 23388219.
Jump up^ Beevers, CG; McGeary JE (2012). “Therapygenetics: moving towards personalized psychotherapy treatment”. Trends in Cognitive Sciences 16 (1): 11–12.doi:10.1016/j.tics.2011.11.004. PMC 3253222.PMID 22104133.
Jump up^ Belsky J, Jonassaint C, Pluess M, Stanton M, Brummett B, Williams R (August 2009). “Vulnerability genes or plasticity genes?”. Mol. Psychiatry 14 (8): 746–54.doi:10.1038/mp.2009.44. PMC 2834322.PMID 19455150.
Further reading[edit]

Daskalaki A, Wierling C, Herwig R (2009), Computational tools and resources for systems biology approaches in cancer.In Computational Biology – Issues and Applications in Oncology, Series: Applied Bioinformatics and Biostatistics in Cancer Research, Pham, Tuan (Ed.), Springer, New York Dordrecht Heidelberg London. 2009:227-242.
Acharya et al. (2008), Gene Expression Signatures, clinicopathological features, and individualized therapy in breast cancer, JAMA 299: 1574.
Sadee W, Dai Z. (2005), Pharmacogenetics/genomics and personalized medicine, Hum Mol Genet. 2005 October 15;14 Spec No. 2:R207-14.
Steven H. Y. Wong (2006), Pharmacogenomics and Proteomics: Enabling the Practice of Personalized Medicine, American Association for Clinical Chemistry, ISBN 1-59425-046-4
Qing Yan (2008), Pharmacogenomics in Drug Discovery and Development, Humana Press, 2008, ISBN 1-58829-887-6.
Willard, H.W., and Ginsburg, G.S., (eds), (2009), Genomic and Personalized Medicine, Academic Press, 2009, ISBN 0-12-369420-5.
Haile, Lisa A. (2008), Making Personalized Medicine a Reality, Genetic Engineering & Biotechnology News Vol. 28, No. 1.
Hornberger J, Habraken H, Bloch DA. Minimum data needed on patient preferences for accurate, efficient medical decision making. Medical Care 1995; 33:297-310.
Lyman GH, Cosler LE, Kuderer NM, Hornberger J. Impact of a 21-gene RT-PCR assay on treatment decisions in early-stage breast cancer: an economic analysis based on prognostic and predictive validation studies. Cancer 2007; 109(6):1011-8.
Hornberger J, Cosler L and Lyman G. Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node–negative, estrogen-receptor–positive, early-stage breast cancer. Am J Managed Care 2005; 11:313-24.
A.Daskalaki & A.Lazakidou (2011). Quality Assurance in Healthcare Service Delivery, Nursing and Personalized Medicine: Technologies and Processes. IGI Global. ISBN 978-1-61350-120-7
Picard FJ, Bergeron MG., Rapid molecular theranostics in infectious diseases, Drug Discov Today. 2002 Nov 1;7(21):1092-101.
Hooper JW., The genetic map to theranostics, MLO Med Lab Obs. 2006 Jun;38(6):22-3, 25.
External links[edit]

CancerDriver : a free and open database to promote personalized medicine in oncology.
Personal genomics
Emerging technologies
Categories: Evidence-based medicineGeneticsGenomicsHealth informaticsMonoclonal antibodiesPharmacologyEmerging technologies


Science is advancing on microbiomes in the gut. The key to food is fiber, and the key to best fiber is long fibers, like cellulose, uncooked or slightly sauteed (cooking shortens fiber length). The best vegetable, in the view of Jeff Leach, is a leek.

Eating Well Article on Microbiome

= = = = = ARTICLE STARTS HERE = = = = =

How Good Gut Bacteria Could Transform Your Health
By Gretel H. Schueller, “The Wild World Within,” July/August 2014

Scientist Jeff Leach is studying gut microbes that have the potential to improve our weight, mood, allergies, heart and more.

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Fresh Leek Recipes

Barefoot and coated in fine desert dust, Jeff Leach hops around the fire, adjusting logs. Its roaring glow provides the only light as the sun sinks behind the Chisos Mountains and the desert air cools.
It’s dinnertime here in Terlingua, the tiny town in southwest Texas that Leach sometimes calls home. We’ve just finished piercing roughly chopped pieces of leek, onion, beef, green peppers and garlic onto metal skewers, and Leach works at balancing them over the fire. Juices sizzle and the roasting aroma makes my mouth water.
“Have you ever held a colon in your hands?” he asks. Whoa…
Talk of belly bacteria, stool samples, bowel movements or your colon isn’t supposed to be part of polite (or appetizing) dinner conversation. But eating with Leach requires new rules of etiquette. Actually, it requires rethinking a whole slew of “rules.”
Once you get talking to Leach and his research colleagues around the world, you quickly realize it’s not just about changing dinner-table etiquette—we may be changing how we talk about health entirely. It all centers on the trillions of bacteria living in our gut.
We are more microbe than human. We each carry an estimated four to ten times more bacterial cells than human cells. If you could mush all the bacteria together they’d be the size of a basketball and weigh about three pounds.
The invisible world of bacteria that live on and in us is called the microbiome; the gut microbiome is the term for the diverse collection living along our intestinal tract, where the bulk of our tiny partners make their home.

Research on the gut microbiome has exploded over the past few years. This bold new frontier may just provide the string theory of all human disease. “Name just about any ailment plaguing us and you’ll find some ­researchers discovering the microbial angle for a connection,” says Leach, whose latest book, Bloom: Reconnecting with Your Primal Gut in a Modern World, is due out this fall. Recent studies have implicated gut microbes in everything from autism and depression to cancer and diabetes to heart disease and obesity. “It’s a water­shed ­moment for human health,” says Leach.
He should know. Leach—with his frenetic energy, powerful charisma and uncanny ability to step back and connect diverse dots—is one of the most visible leaders of the gut-health movement. In 2012, Leach founded the Human Food Project, a global effort to study how diet affects the microbial world within us.

A major arm of that is the American Gut Project, thought to be the largest microbiome project in the world, co-led by Rob Knight, Ph.D., a professor at the University of Colorado’s BioFrontiers Institute and a Howard Hughes Medical Institute Early Career Scientist. The goal is to map the diversity of the ­human gut—and tease out patterns shaped by diet, age and lifestyle to understand the factors most important for a healthy gut microbiome.

So far, more than 7,000 people have signed up for the gut project. After completing a questionnaire and a 7-day food journal, and paying $99, participants send a fecal sample to be analyzed.

Some of the questions might seem odd: How many different plants do you eat in a week? Born by C-section? Own a pet? Used an anti­biotic in the past month?
But Leach explains that all of these things affect your microbiome. And what he and his colleagues are finding is that Americans generally have less-diverse gut microbiomes than other populations. No one knows what the perfect gut microbiome should look like—or if there even is one. But one thing is clear: diversity is key. And we’re losing it.

Building the Microbiome
Until the moment we are born, we are still 100 percent human. In other words, bacteria-free. Most of us get our first dose of microbes while traveling through the birth canal. The second big dose comes from breast milk. As babies grow, they pick up critters from dirt, pets, family members and friends. By age 3, the microbiome has pretty much set up camp.

But changing lifestyles are chipping away at that microbiome. Early studies indicate that children born by C-section—which reduces the microbes an infant is first exposed to—have a higher risk of celiac disease, obesity and type 1 diabetes. Add to that decreased breast-feeding and “our overzealous use of antibiotics,” says Leach, who compares what antibiotics do to the gut microbiome to clear-cutting a forest.

From birth to age 5, children receive more anti­biotics than during any other five-year period in their lives. One of Leach’s colleagues, New York University microbiologist Martin Blaser, M.D., believes antibiotics have “deranged” the micro­biome—even causing some species to go extinct—and that their overuse is why many health problems, including type 1 diabetes, obesity and allergies, are on the rise.

Numerous studies also show that scrubbing away our microbes may be weakening our bodies’ natural defenses—something Leach has experienced firsthand: 12 years ago, at age 2, his daughter was diagnosed with type 1 diabetes, an autoimmune disease.

“My daughter was born C-section—strike 1; breast-fed very short—strike 2; strike 3, she received antibiotics at a very young age; strike 4, she lived in an environment where we basically wet-wiped everything and bathed her twice a day.” Leach feels strongly that her disease is a by-product of our culture.

At the time, Leach, who has a Ph.D. in anthropology, was studying how ancient people acquired and cooked foods. “When my daughter was diagnosed, the only thing I could do was to try to under­stand why she was sick. I just started emailing microbiologists and asking questions.”

He learned that this autoimmune disease is an overreaction of the immune system. And the bulk of immune cells live in the gut. So into the gut he went—and stayed.

His new focus is actually not that much of a leap from anthropology. “If microbiome research is anything, it’s anthropology—about how people interact with their environment,” notes Leach.

Here in this remote desert town, Leach’s life is a sharp contrast to his sanitized suburban past.

e and his wife divorced and the children live with her most of the year.) When he’s not traveling for research, Leach spends time in an adobe ruin that he’s rehabbing.

The fire pit is his kitchen. He has an open-air shower and the toilet is in a doorless shed. Only one 7-by-12-foot room is closed to the elements; it includes a single cot, desk, laptop computers, leaning towers of research papers and…a few dozen poison-tipped arrows (we’ll get to those soon). Out here, Leach is reconnecting with his microbes because he knows how critical they are.

Most of our resident gut bacteria are real workhorses. Some aid in digestion and produce enzymes to break down foods. Others make vitamins, like B12 and K, and other vital compounds, such as the feel-good chemical serotonin. A few help keep the intestinal lining impenetrable. Some gut bacteria help regulate metabolism. And others boost immunity and fight pathogens.
Of course, not all bacteria are beneficial. Some amplify inflammation or cause life-threatening infections. But we carry them all naturally; they only create problems when the microbial balance becomes disturbed.

There are many ways our microbiome can get off-kilter and make us prone to infections or disease. For example, taking antibiotics shifts the balance of microbes in our gut. As a result, the infectious dose of Salmonella is a thousand times lower for someone who’s on antibiotics. Diet is another way we can tip the balance unfavorably.

Essential Fuel for Your Microbiome
“We should start thinking about diets from the perspective of what we should be feeding our gut microbes,” says Leach. “Nothing matters more.”
A seminal study published in Nature last year compared the gut microbiome of people eating an entirely animal-based diet (meats, cheeses and eggs) with one that was completely plant-based (grains, legumes, vegetables and fruits). Just one day on either diet was enough to dramatically shift the gut microbiome of participants. While researchers knew that diet could cause changes to the gut microbiome, this was the first study to show such a rapid effect in people.
Leach is doing similar, informal tests on himself. Since January 1 of this year, he’s been trying out different diets: fermented foods, vegan, raw food, Paleo and others. He’s following each one for 10 to 12 days, collecting daily stool samples. By “whacking his micro­biome around” (as he refers to it) he hopes to zero-in on the key foods that fuel the good and bad players of the gut.

His first trial was a high-fat (70 percent of calories), average-protein (25 percent) diet with little carbohydrate and near zero dietary fiber. This diet, he explains, starved his microbes of food. Proteobacteria, practically nonexistent before, increased.

“This group includes a lot of your bad guys—E. coli, Salmonella. They are associated with inflammation and may increase your risk of disease.” At the same time, numbers of actinobacteria, typically considered good guys and known to suppress proteobacteria, dropped.

He’s since done several variations of this diet—adjusting fat, carbs, protein and fiber. “It’s the fiber that’s the game changer,” Leach says. Adding 40 to 60 grams of fiber per day seems to shift his gut microbiome toward a diverse, more beneficial mix of microbes.

Here’s why: like all living things, bacteria need food to survive. They do that by fermenting—that’s the way these guys “eat”—dietary fiber. But gut bacteria are picky. Only certain types of fiber will do—and most of us don’t eat enough of the kind that bacteria need.

Fibers are like pearl necklaces of varying bead-length. Most fibers we eat are so short, they get chomped long before they make it to where bacteria are concentrated, the beginning of the large intestine, aka the colon.

Two fiber types long enough to survive the length of our GI tract are fructan and cellulose fibers—part of a group of foods known as prebiotics, foods that encourage the growth of good bacteria. Cellulose fibers are in the tough parts of veggies and fruit we tend to toss—like the stalks of broccoli and bottoms of asparagus—and the stringy bits of celery. Fructan fibers are found in many fruits and vegetables—from artichokes to onions.

But how you prepare these foods also matters. That’s because heat breaks down fibers. Consider the onion—a good source of fructan: the ­average chain length of fructan in an onion is 26. A little bit of cooking breaks the onion fibers down to 8 or 10 beads. The shorter the chain, the sweeter the food—which is why deliciously sweet caramelized onions retain little fructan fiber benefit.

Leach does a little show-and-tell at Terlingua’s only grocery, the Cottonwood General Store. “This is probably the healthiest thing in the store for your gut microbiome,” he says, holding a leek almost as long as his arm.

He points to the white part: “These store fructans. I’d say this probably does more good for you than a wheelbarrow full of yogurt.” Then, he points to the green top of the leek: “That’s the cellulose, which has a chain length of a couple thousand ‘beads.’”

A few onlookers stare at the leek in awe. Silence. “You could eat this whole leek and change your micro­biome in 48 hours,” Leach proclaims. In other words, if you eat this, the good guys will come.

In contrast, he pulls out a bag of baby carrots. “We think we’re doing well when we steam these for dinner,” Leach says. And for some purposes we are. But there’s not much here to feed your gut microbes.

When he’s not using himself to road-test various diets, Leach practices what he preaches, eating a (lightly sautéed) leek a day—“The whole thing,” he emphasizes, “from muddy roots to fibrous green tops.” In fact, he convinced this tiny grocery store in the middle of a desert to carry leeks.

Gut microbes feast away on those fibers in a fermentation frenzy. Some of fermentation’s most beneficial by-products are short-chain fatty acids that provide energy for intestinal cells, help repair the ­colon’s protective lining and increase the acidity of the colon. Most infection-causing bacteria—as well as other microscopic troublemakers like parasites—don’t do well in acidic environments.

A Gut Without Fiber
Starve your gut friends and the consequences can be toxic. Without fiber, the colon environment favors unsavory microbes. No fiber also means no more short-chain fatty acids, paving the way for less-desirable bacteria to flourish.
Over time, starving bacteria start eating us—specifically the lining of the ­colon. Normally, the intestinal lining is a selective barrier between our digestive tube and the rest of our body—harder to break into than a trendy club; good bacteria like bifidobacterium act as buff bouncers, making sure only the worthy get past. Over time, eating a low-fiber diet can weaken these defenses, allow­ing bits of dead bacteria to get into the bloodstream. “This is what causes low-grade inflammation,” Leach explains.

Chronic, low-grade inflammation can raise your risk for various chronic diseases—and it is a hallmark of metabolic syndrome, a collection of conditions that can include insulin resistance, elevated blood sugar and high blood pressure. Patrice Cani, Ph.D., a microbiologist at the Catholic University of Louvain in Belgium, is one of the leading researchers looking at the connection between inflammation and gut microbes.

His work has shown that a high-fat, low-fiber diet increases inflammation—that’s probably not a big surprise. The real shocker came when he and his colleagues fed gut-friendly plant fibers to mice on a high-fat diet: they were able to stop the whole inflammation cycle that fuels metabolic syndrome.

Our Original Microbiome
After our fireside dinner, Leach invites me into his adobe ruin to show me photos of the people he says will help us better understand the gut microbiome. They carry a gut microbe mix that’s close to the one our ancestors had, Leach believes. Photos of men hunting, straw huts and smiling children cover the walls. Leach is animated and starts pulling out souvenirs to show me: a drum, sandals made of old tires.

Then he brings out the arrows. Colorful feathers decorate the tail ends and the metal tips are sharp—and covered with dried blood. “Careful, don’t touch the tips. They’re poison.” The ­arrows belong to the Hadza of Tanzania, “the last true hunter-­gatherers in the world,” he says. “They live where humans evolved; it’s as close as we can get to the original microbiome.”

For the past year, Leach has been spending time with this dwindling tribe of roughly 300 people. The Hadza still hunt and gather the majority of their food, have limited access to antibiotics, are born naturally, breast-feed for two-plus years, drink untreated water and live outdoors 24-7—all things that encourage a diverse gut micro­biome.

While infant mortality—as in many developing countries—is high, Hadza adults are healthy and rarely suffer from “modern” diseases like heart disease, diabetes, allergies and cancer, according to Leach. Their diet shifts dramatically over the year: during the rainy season from February to April, as many as 80 percent of their calories come from honey; in contrast, late fall is characterized by meat bingeing. What remains constant is their average daily fiber intake: more than 100 grams. Most comes from the seeds and pulp of the fructan-rich baobab fruit and fibrous tubers.

It’s here with the Hadza that Leach sees the puzzle pieces fitting together—how the “dirty” world of the Hadza mirrors the robust world of their gut. “Once you’ve sat under a baobab tree for two weeks and watched how they drink water, build their houses, handle animals, travel—and the things they don’t do—there’s a lot of eureka moments.”

Fieldwork to help understand the bigger picture is what Leach does best. For the analysis and lab work, he has brought together a global “dream team,” as he calls them.
“Intellectually, [Leach’s] background and perspective are huge assets to the project,” says Justin Sonnenburg, Ph.D., a micro­biologist at Stanford University who collaborates with Leach and runs one of the labs involved in the Human Food Project. He receives some of the stool samples Leach collects from the tribe. Other samples arrive to other “dream team” members.

The first report on the Hadza micro­biome was recently published, showing the hunter-gatherers probably have the most diverse gut microbiome in the world, with hundreds more species than most other people. “It suggests that the microbiome is going through extinctions as food becomes more processed and less diverse,” notes Sonnenburg. “What does it mean if the world is heading down a path of reduced microbiome diversity?” He points to the fact that most Western diseases are spurred by inflammation.
This is why, taking a few lessons from the Hadza, we could do with a little re­wilding of our gut microbiome.

Right now, Leach is on a break from his diet experiment. So we sip tequila and eat some queso and chips at the local watering hole. (Not so gut-friendly, he acknowledges, but the occasional treat is OK.) I dunk a chip as Leach sketches a colon on my notepad.

Patrons at a nearby table nod with understanding—they’re familiar with Leach, who they sometimes affectionately call “Dr. Sh*t.” They appreciate his crusade as an environmentalist for the ecosystem within us.

There’s certainly more to be discovered in this diverse world tucked inside our ­bellies. But Leach believes we should already feel empowered. His basic message: increase and diversify your plant intake. The foods you pick “should be chewy, should get stuck in your teeth,” he says. “Eat the end of the asparagus, the stalk of the broccoli. Become a little more adventurous in the produce section. This is a part of your health you can control. You can shift your microbiome.”

Gretel H. Schueller has written for Scientific American, Discover and New Scientist. She is also a children’s book author.

Amazon Crush – Update

Amazon update

Thanks to Oliver Wyman, Fast Company and many others for this update on last post on Amazon… sense from reading all:

– Twitch is Amazing! Driving 40% of all internet bandwidth???? Is that even possible? With 55 million users spending an average of 100+ minutes per day??? That is enormous! Bezos obviously intrigued and willing to take a risk to get this three-year old start-up in its fold? But why exactly? Don’t know

– FRESH is moving out. Per plan, and announcement to stockholders and also per rumor, Amazon Fresh is in a soft launch mode. The big news was the launch in LA (after 7 years in Seattle tweaking), and then it was small news that they rounded out most of the the rest of California markets – that is a HUGE expansion in less than a year. Moreover, Amazon green trucks are riding through Manhattan, and a roll there is imminent. No word yet, but I really think Chicago might be next – rumors say I am right.

– Manufacturers think this isn’t their fight. Most of them are just glad they are not retailers. But the truth is that Amazon will cause a massive reduction in retailer margin, as well as many of the brand-building activities at retail that manufacturers are used to …. horrible merchandising will replace great merchandising, forget about cold beverage sales, forget about impulse sales, etc.

– the truth is that retail is not at risk – just the marginally profitable ones.

Here are the articles:

After years of anticipation, AmazonFresh has now expanded its U.S. home grocery delivery service beyond its home market of Seattle.

In June 2013, it launched in Los Angeles, with more markets expected to follow. From conversations with supermarket retailers all over the U.S. and globally, it is clear that online and multi-channel competitors have come into focus as a key competitive threat, and AmazonFresh is by far the most dangerous of the new breed. What is striking is the similarity between what we hear from food retailers today and what leaders of category killers were saying back in 2009 – and we know that the category killers’ fears of Amazon proved to be well-founded.

AmazonFresh, operating in pilot mode in Seattle since 2007, allows shopping online and on mobile apps. The assortment is surprisingly broad and deep, with between 10,000 and 30,000 items, depending on the market, including (for example) 400+ produce items, 500+ meat and seafood items, 1,300+ beverage items and 4,000+ health and beauty items. Unlike the traditional Amazon model, AmazonFresh prices on consumables are currently higher than those found in local supermarkets, as promotions are mostly absent – the current customer proposition focus is on convenience.

The differences between the Seattle and LA models (different membership and delivery pricing models and different assortment depth, to name a few) seem to indicate that Amazon is still trialling many elements of the business, but the rollout to additional markets suggests underlying confidence in the economics.

When Amazon decides to move from pilot to rollout, history indicates they will move very rapidly. The company has reportedly told vendors it could roll out to 40 U.S. markets by the end of 2014!

The direct impact that Amazon had on many category killers by winning market share is obvious, as is the impact on consumers’ price expectations, but one under-reported aspect of what is happening to category killers is the channel conflict competition Amazon provokes. Not only does Amazon take share, they also force category killers to shift transactions to their own websites. But those sites are not the basket-building machines that stores are. For one major category killer, the average online transaction has only a quarter of the number of items that the average in-store transaction has. So the incumbents face a conundrum – they must grow online sales, but doing so dramatically worsens their economics.
However, Amazon will never take as much share away from food retailers as it has taken from category killers. Food retailers’ natural defenses – low gross margins, focus on fresh product, “need it now” consumption patterns, the emotional aspect of personally selecting food to feed one’s family – mean the supermarket channel as a whole will not suffer the fate of Borders or even Best Buy.
The threat is not that stores will become obsolete; such notions are alarmist and naïve. But AmazonFresh can force dramatic change in the shape of the food retail industry with even modest market share. It doesn’t take complicated analysis to prove this. The industry overall runs with about a 2% bottom line and a 20% volume variable margin. This means
a 10% sales loss would wipe out the entire industry’s profit. Any experienced food retail executive knows that most chains have a “mushy middle” of stores that generate reasonable operating income with current sales volumes, but would quickly tip into negative store profit with a modest reduction in volume. We don’t know what Amazon’s ultimate ambitions in the food space are, but if they achieve even a 5% volume share it would force significant changes. Current players would have to either raise prices – kicking off the vicious cycle of volume loss, causing deleveraged fixed costs, leading to even more price rises – or close stores to bring costs into line. A 5% volume loss to AmazonFresh would result in 10-20% reduction in store count, because not all the volume from closed stores will be clawed back by surviving stores: as supermarkets become relatively less convenient, some of the volume would go to specialists (clubs, hard discounters, premium players) and online channels. It’s too early to know the full extent of the impact, but a good guess is that around one in eight supermarkets would have to close to maintain current profitability without raising prices.

Supermarkets should not count on their ability to weather this disruption the way they weathered the last major disruption: the Walmart supercenter tsunami, in the case of the U.S. Then, the best grocers got better, slashed cost out of their networks, improved their capabilities, and prospered at the expense of weaker competitors who couldn’t adapt fast enough. They had time to pull this off because Walmart couldn’t open a thousand supercenters overnight. But this time, the starting point is much, much more efficient – there will be a lot less “fat” to cut to preserve profitability in the face of falling volume – and the weaker players that were the victims last time are already gone. Most significantly, the rate of change in the competitive landscape will not be constrained by the process of opening new stores. Amazon only has to set up distribution centers and networks. It already has a strong consumer brand. This disruption could happen much faster than anything the industry has seen before.

Build a multi-channel offering. Of course, grocers must develop their own answer to online and mobile shopping. And it is better to cannibalize one’s own in-store sales than to surrender them to the competition. That said, it is very tricky to make the economics of these models work, so great care must be taken to manage the bottom line as online and mobile sales ramp up.

Get seriously good at fresh. The fresh categories represent a cushion around the rest of the customer offer. If customers believe they can’t get the same quality, freshness and selection online as they would in a store, it will be a formidable barrier to switching to on-line purchasing. So far AmazonFresh’s fresh product offering is highly variable (see Exhibit 1) but it stands to reason that they will get better with experience. And they have a built-in freshness advantage – as do all online grocers – because product take less time to go from the distribution center to the customer’s home. Most U.S. retailers are nowhere near where they could be, and the same is true in many other geographies. Getting good enough at fresh to fend off online competition means re-thinking the supply chain, store practices and merchandising standards. It means breaking the usual trade-off between availability and shrink, shifting the efficient frontier through better capabilities and greater accountability.
Prepare for a world with fewer stores. Possibly a lot fewer. Even an excellent multichannel platform and a rejuvenated fresh offer will not be nearly enough. We believe food retailers should be planning now for a world with far fewer stores. If, say, 15% of the square footage is going to have to close down, survival will depend on making sure the competition bears more than their fair share of the pain. So grocers’ competitive strategy should be focused on ensuring they get to keep more of their stores than the competition does, and being prepared to pounce when weakened competitors begin to wobble. This means understanding how to win store-by-store battles and drive maximum profit out of every square foot. To be clear, we are bullish on the supermarket industry. While the industry’s transformation will be painful for all and fatal for a few, the survivors will be better placed. Surviving stores will do much higher volume and, with higher fixed cost leverage, they could be massively more profitable. Stronger competition will force grocers to become even better operators and even more responsive to customer needs. Retailers who act fast can not only survive, but adapt their businesses to thrive in the new world.
Exhibit 1: PRELIMINARY CUSTOMER RESEARCH BY OLIVER WYMAN SHOWS a wide range of customer perceptions of the quality of AmazonFresh products

“The apples were the kind I would have hunted for and maybe not found. They looked great and the taste was fresh and sweet, the texture crisp which is exactly what I like. They were delicious.”
“The sell by date on the frozen beef says July 2013 [delivered in September 2013]. Granted it was frozen, this makes me believe it’s not fresh beef and I’m a little disappointed by that.”
“Some of the berries were very soft and leaking all over the box.”

Oliver Wyman is a global leader in management consulting that combines deep industry knowledge with specialized expertise in strategy, operations, risk management, and organization transformation.

Copyright © 2014 Oliver Wyman. All rights reserved.

FastCompany: AmazonFresh a “Trojan horse;” 20 more markets expected
Aug 11 2013, 18:15 ET

In a cover story on Jeff Bezos and Amazon (AMZN), FastCompany’s J.J. McCorvey observes the company’s new AmazonFresh grocery service (offered via its $299/year Prime Fresh free shipping plan) is a “Trojan horse” meant to give Amazon’s broader same-day delivery efforts needed scale.
Amazon is also hoping its same-day infrastructure (replete with Amazon trucks) will increase its appeal to 3rd-party sellers (now responsible for 40% of unit sales) by lowering delivery times. Merchants already cite access to Prime as a reason for outsourcing fulfillment to Amazon (and giving a ~20% cut).
EBAY could prove a formidable same-day rival. Instead of building its own soup-to-nuts infrastructure, eBay is relying on dozens of offline retailers (inc. major national chains) to help handle fulfillment. Google is also dipping its toes into same-day.
Currently available in L.A. and Seattle, AmazonFresh is expected to expand to 20 more markets, including some international ones. SunTrust recently predicted an NYC launch will happen in 2014.
Also mentioned by McCorvey: Amazon is now able to ship items less than 2.5 hours after an order is placed; and wants to further lower than number; Prime now covers 15M+ items (up from 1M in ’05); and Amazon is still “evaluating” how to use Kiva’s robots.
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The first thing you notice about Jeff Bezos is how he strides into a room.
A surprisingly diminutive figure, clad in blue jeans and a blue pinstripe button-down, Bezos flings open the door with an audible whoosh and instantly commands the space with his explosive voice, boisterous manner, and a look of total confidence. “How are you?” he booms, in a way that makes it sound like both a question and a high-decibel announcement.
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Each of the dozen buildings on Amazon’s Seattle campus is named for a milestone in the company’s history–Wainwright, for instance, honors its first customer. Bezos and I meet in a six-floor structure known as Day One North. The name means far more than the fact that Amazon, like every company in the universe, opened on a certain date (in this case, it’s July 16, 1995). No, Day One is a central motivating idea for Bezos, who has been reminding the public since his first letter to shareholders in 1997 that we are only at Day One in the development of both the Internet and his ambitious retail enterprise. In one recent update for shareholders he went so far as to assert, with typical I-know-something-you-don’t flair, that “the alarm clock hasn’t even gone off yet.” So I ask Bezos: “What exactly does the rest of day one look like?” He pauses to think, then exclaims, “We’re still asleep at that!”
He’s a liar.

Amazon is a company that is anything but asleep. Amazon, in fact, is an eyes-wide-open army fighting–and winning–a battle that no one can map as well as its general. Yes, it is still the ruthless king of books–especially after Apple’s recent loss in a book price-fixing suit. But nearly two decades after its real day one, the e-commerce giant has evolved light-years from being just a book peddler. More than 209 million active customers rely on Amazon for everything from flat-panel TVs to dog food. Over the past five years, the retailer has snatched up its most sophisticated competition–shoe seller Zappos and Quidsi, parent of such sites as,,, and It has purchased the robot maker Kiva Systems, because robots accelerate the speed at which Amazon can assemble customer orders, sometimes getting it down to 20 minutes from click to ship. Annual sales have quadrupled over the same period to a whopping $61 billion. Along the way, incidentally, Amazon also became the world’s most trusted company. Consumers voted it so in a recent Harris Poll, usurping the spot formerly held by Apple.

• Retail’s Game Of Thrones: Citizens of these kingdoms know the stakes–you innovate or you die.
Amazon has done a lot more than become a stellar retailer. It has reinvented, disrupted, redefined, and renovated the global marketplace. Last year, e-commerce sales around the world surpassed $1 trillion for the first time; Amazon accounted for more than 5% of that volume. This seemingly inevitable shift has claimed plenty of victims, with more to come. Big-box retailers like Circuit City and Best Buy bore the brunt of Amazon’s digital assault, while shopping-mall mainstays such as Sears and JCPenney have also seen sales tank. Malls in general, which once seemed to offer some shelter from the online pummeling, have been hollowed out. By Green Street Advisors’ estimate, 10% of the country’s large malls will close in the next decade. It has become painfully clear that the chance to sift through bins of sweaters simply isn’t enough of a draw for shoppers anymore. “It has been this way in retail forever,” says Kevin Sterneckert, a research VP at Gartner who focuses on shopping trends, and who lays out a strategy that should blow nobody’s mind: “If you don’t innovate and address who your customers are, you become irrelevant.” And now that means fending off threats from every phone, tablet, and laptop on the planet.
Amazon’s increasing dominance is now less about what it sells than how it sells. And that portends a second wave of change that will further devastate competitors and transform retail again. It’s not just “1-Click Ordering” on Amazon’s mobile app, which is tailor-made for impulse buying. It’s not just the company’s “Subscribe & Save” feature, which lets customers schedule regular replenishments of essentials like toilet paper and deodorant. It’s not just Amazon’s “Lockers” program, in which huge metal cabinets are installed at 7-Elevens and Staples in select cities, letting customers securely pick up packages at their convenience instead of risking missed (or stolen) deliveries.
No, it’s all this, plus something more primal: speed. Bezos has turned Amazon into an unprecedented speed demon that can give you anything you want. Right. Now. To best understand Amazon’s aggressive game plan–and its true ambitions–you need to begin with Amazon Prime, the company’s $79-per-year, second-day delivery program. “I think Amazon Prime is the best bargain in the history of shopping,” Bezos tells me, noting that the service now includes free shipping on more than 15 million items, up from the 1 million it launched with in 2005. Prime members also gain access to more than 40,000 streaming Instant Video programs and 300,000 free books in the Kindle Owners’ Lending Library. As annoying as this might be to Netflix, it is not intended primarily as an assault on that business. Rather, Bezos is willing to lose money on shipping and services in exchange for loyalty. Those 10 million Prime members (up from 5 million two years ago, according to Morningstar) are practically addicted to using Amazon. The average Prime member spends an astounding $1,224 a year on Amazon, which is $700 more than a regular user. Members’ purchases and membership fees make up more than a third of Amazon’s U.S. profit. And memberships are projected to rise 150%, to 25 million, by 2017.

Nadia Shouraboura of Hointer, a new store that represents how retail must adapt in the Age of Amazon
Robbie Schwietzer, VP of Prime, is more candid than his boss when explaining Prime’s true purpose: “Once you become a Prime member, your human nature takes over. You want to leverage your $79 as much as possible,” he says. “Not only do you buy more, but you buy in a broader set of categories. You discover all the selections we have that you otherwise wouldn’t have thought to look to Amazon for.” And what you buy at Amazon you won’t buy from your local retailer.
Prime is phase one in a three-tiered scheme that also involves expanding Amazon’s local fulfillment capabilities and a nascent program called AmazonFresh. Together, these pillars will remake consumers’ expectations about retail. Bezos seems to relish the coming changes. “In the old world, you could make a living by hoping that your customer didn’t know whether your price was actually competitive. That’s a very”–Bezos pauses for a second to rummage for the least insulting word–“tenuous strategy in the new world. [Now] you can’t convince people you have the low price; you actually have to have the low price. You can’t persuade people that your delivery speeds are fast; you actually have to have fast delivery speeds!” With that last challenge, he erupts in a thunderous laugh, throwing his cleanly depilated head so far back that you can see the dark fillings on his upper molars. He really does seem to know something the rest of us don’t. We’re still asleep, he says? The alarm clock at Amazon went off hours ago. Whether the rest of the retail world has woken up yet is another question.

Amazon’s 1-million-square-foot Phoenix fulfillment center produces a steady and syncopated rhythm. It is the turn of mechanical conveyor belts, the thud of boxes hitting metal, the beeping of forklifts moving to and fro, and the hum of more than 100 industrial-size air conditioners whirring away. This is the sound of speed–a sonic representation of what it takes to serve millions of customers scattered across the globe.
In centers like this one, of which there are 89 globally (with more to come), Amazon has built the complex machinery to make sure a product will ship out in less than 2.5 hours from the time a customer clicks place your order. From that click, a set of algorithms calculates the customer’s location, desired shipping speed, and product availability; it then dispatches the purchase request to “pickers” on duty at the nearest fulfillment center. The system directs the new order to the picker who is closest on the floor to that product, popping up with a bleep on the picker’s handheld scanner gun. These men and women roam the sea of product shelves with carts, guided by Amazon’s steady hand to the precise location of the product on the color-coded shelves. The picker gathers the item and puts it into a bin with other customer orders. And from there, the item zooms off on a conveyor belt to a boxing station, where a computer instructs a worker on what size box to grab and what items belong in that box. After the packer completes an order, the word success lights up in big green letters on a nearby computer screen. Then the package goes back on a conveyor, where the fastest delivery method is calculated by scanning the box, which is then kicked down a winding chute to the appropriate truck.
How one store merges digital and physical
If anyone can design a brick-and-mortar store for an e-commerce world, it should be Nadia Shouraboura. She used to be Amazon’s VP of global supply chain and fulfillment technology and has since created Hointer, a fully automated store run on software algorithms and machinery. She calls it a “microwarehouse” that marries digital’s instant gratification with in-store benefits. “In apparel, this will win,” she predicts. It works like this:
A customer enters the spare store, where there’s only one of every product in view. She pulls up the Hointer app, scans the QR code on a pair of jeans she likes, and enters her size.
Within 30 seconds of scanning the code, a pair of jeans in her size travels through a chute and lands in her dressing room. She can scan as many items as she likes.
Inside the dressing room, she tries on the jeans, but they’re too baggy. So she chucks them down another chute and selects a smaller size from the app.
The jeans fit! She pays on her phone or swipes her card at a kiosk, and leaves the store with her purchase. No sales clerk necessary.
The process is efficient, but still lower tech than it could be. Although Amazon shelled out $775 million last year for those orange Kiva robots, it says it’s still “evaluating” how to deploy the bots, and they’re nowhere to be seen here. “Fulfillment by Amazon” is still a very human endeavor–and the company’s creativity thrives within that limitation. A team at the Phoenix center is constantly thinking of ways to chip away at the 2.5-hour processing time. For instance, when products arrive from Amazon’s vendors and the 2 million third-party merchants who sell their goods on the site, workers now scan them into Amazon’s inventory system (again, with a handheld gun) instead of entering the details manually. Also, products have been stowed on shelves in what otherwise might appear to be a random way–for example, a single stuffed teddy bear might be next to a college biology book–because it reduces the potential distance a worker must trek between popular products that might be ordered together. Small tweaks like these have an impact: In the past two years, Amazon has reduced the time it took to move a product by a quarter. During the past holiday season, the company processed 306 items per second worldwide.
These centers aren’t just about warehouse speed, though: They’re also about proximity. Over the past several years, Bezos has poured billions into building them in areas closer and closer to customers. The Phoenix warehouse, one of four in the region, serves a metro area of nearly 4 million. Robbinsville, New Jersey, is roughly one hour from 8 million New Yorkers. Patterson, California, is an hour and a half from 7 million people living in the San Francisco Bay Area. Three locations in Texas–Coppell, Haslet, and Schertz–will serve not only the nearly 9 million citizens of the Dallas and San Antonio metro areas but also the other 17 million or so customers in the state (and possibly neighboring states too) who live only a few hundred miles away.
“What you see happening,” Bezos explains, “is that we can have inventory geographically near major urban populations. If we can be smart enough–and when I say ‘smart enough,’ I mean have the right technology, the right software systems, machine-learning tools–to position inventory in all the right places, over time, your items never get on an airplane. It’s lower cost, less fuel burned, and faster delivery.”
The holy grail of shipping–same-day delivery–is tantalizingly within reach. Amazon already offers that service in select cities, what it calls “local express” delivery, but the big trick is to do it nationally. And the crucial element of this ambitious plan is revealed by something wonkier than a bunch of buildings. It is something only an accountant could see coming: a cunning shift in tax strategy.


If you were a competitor who knew what to listen for, you’d practically hear the Jaws theme every time Bezos said the word taxes. For years, Amazon fervently avoided establishing what is called a “tax nexus”–that is, a large-enough physical presence–in states that could potentially force it to collect sales tax from its customers, something brick-and-mortar and mom-and-pop stores had long argued would finally remove Amazon’s unfair pricing advantage. In states that dared to challenge Amazon, the company would quickly yank operations. The scrutiny even extended to its sale of products by other merchants. “We had to be very careful, even with the third-party business, about not incurring tax-nexus stuff,” recalls John Rossman, a former Amazon executive and current managing director at Alvarez and Marsal, a Seattle-based consulting firm.
But Amazon has since changed its mind. It determined that the benefits of more fulfillment centers–and all the speed they’ll provide–will outweigh the tax cost they’ll incur. So it began negotiating with states for tax incentives. South Carolina agreed to let the company slide without collecting sales tax until 2016, in exchange for bringing 2,000 jobs to the state. In California, Amazon was given a year to start collecting taxes in exchange for building three new warehouses. And at the end of 2011, Amazon even threw its support behind a federal bill that would mandate all online retailers with sales of more than $1 million to collect tax in states in which they sold to customers. In 2012 alone, Amazon spent $2.5 million lobbying for issues that included what’s known as the Marketplace Fairness Act–the same law, essentially, it had once moved heaven and earth to eradicate. The bill recently cleared the U.S. Senate and awaits passage in the House.
“The general perception is companies thinking, Oh, great, finally a level playing field,” Rossman says. “But other retailers are going to regret the day. Sales tax was one of the few things impeding Amazon from expanding. Now it’s like wherever Amazon wants to be, whatever Amazon wants to do, they are going to do it.”

There’s yet another weapon in Amazon’s offensive, and it’s ready for rollout. It’s called AmazonFresh, a grocery delivery service that has long been available only in Seattle. The site has a selection of 100,000 items, and from my hotel room in that city on a recent Saturday at 11 a.m., I gave it a try. I clicked on chips, bananas, apples, yogurt, and a case of bottled water–along with a DVD of Silver Linings Playbook and a Moleskine reporter’s notebook. After checking out and paying the $10 delivery fee, I requested my goods to arrive during the 7 p.m. to 8 p.m window. At 7:15 that evening, De, my AmazonFresh delivery woman, showed up in the lobby. She helped carry my bags up the elevator and to my hotel room, and tried several times to refuse a $5 tip for the trouble I put her through in the name of research. It was simple, easy–and for Amazon competitors, very threatening.
De and the Kiva robots are central to what Amazon sees as the future of shopping: whatever you want, whenever you want it, wherever you want it, as fast as you demand it. AmazonFresh is expected to expand soon to 20 more urban markets–including some outside America. Los Angeles became the second AmazonFresh market, this past June, and customers there were offered something the folks in Seattle must wish they got: a free trial of Prime Fresh, the upgrade version of Amazon Prime, which provides free shipping of products and free delivery of groceries for orders over $35. Subscribers will pay an annual fee of $299. Considering that grocery delivery otherwise costs between $8 and $10 each time (depending on order size), the subscription covers itself after about 30 deliveries–which busy families will quickly exceed.
Bezos, in his cagey, friendly way, seems more excited about my Fresh experience than he is about describing Fresh’s future. He seems almost surprised that the service worked so well at a hotel, given that it was designed for home delivery. “Thank you!” he shouts. After peppering me with questions on how, precisely, the delivery went down, he finally gets around to addressing the service’s business purpose.
“We’d been doing a very efficient job with our current distribution model for a wide variety of things,” Bezos says. “Diapers? Fine, no problem. Even Cheerios. But there are a bunch of products that you can’t just wrap up in a cardboard box and ship ’em. It doesn’t work for milk. It doesn’t work for hamburger.” So he developed a service that would work–not because he suddenly wanted to become your full-service grocer but because of how often people buy food.
AmazonFresh is actually a Trojan horse, a service designed for a much greater purpose. “It was articulated [in the initial, internal pitch to Bezos] that this would work with the broader rollout of same-day delivery,” says Tom Furphy, a former Amazon executive who launched Fresh in 2007 and ran it until 2009. Creating a same-day delivery service poses tremendous logistical and economic hurdles. It’s the so-called last-mile problem–you can ship trucks’ worth of packages from a warehouse easily enough, but getting an individual package to wind its way through a single neighborhood and arrive at a single consumer’s door isn’t easy. The volume of freight and frequency of delivery must outweigh the costs of fuel and time, or else this last mile is wildly expensive. You can’t hire a battalion of Des unless they earn their keep. So by expanding grocery delivery, Amazon hopes to transform monthly customers to weekly–or even thrice-weekly–customers. And that, in turn, will produce the kind of order volume that makes same-day delivery worth investing in. “Think of the synergy between Prime, same-day delivery, and Fresh,” says Furphy. “When all of those things start working in concert, it can be a very beautiful thing.”

AmazonFresh is arguably the last link in Bezos’s big plan: to make Amazon the dominant servicer–not just seller–of the entire retail experience. The difference is crucial. Third-party sellers, retailers large and small, now account for 40% of Amazon’s product sales. Amazon generally gets up to a 20% slice of each transaction. Those sellers are also highly incentivized to use Fulfillment by Amazon (known as FBA). Rather than shipping their products themselves after a sale is made on the Amazon site, these retailers let Amazon do the heavy lifting, picking and packing at places like the Phoenix center. For the sellers, an FBA agreement grants them access to Prime shipping speeds, which can help them win new customers and can allow them to sell at slightly higher prices. For Amazon, FBA increases sales, profits, and the likelihood that any shopper can find any item on its website.
The burgeoning AmazonFresh transportation network will help expand these numbers. In Los Angeles and Seattle, a fleet of Fresh trucks delivers everything from full-course meals to chocolate from local merchants. The bright green branded trucks–with polite drivers in branded uniforms–let Amazon personify its brand, giving it the same kind of trustworthy familiarity that fueled the rise of UPS in the 1930s. “If you have all kinds of fly-by-night operations coming to your door, people don’t like that,” says Yossi Sheffi, professor and director of the MIT Center for Transportation and Logistics. “It’s different with someone in a U.S. Postal Service or FedEx uniform. Those brands inspire confidence.”
As Amazon evolves into a same-day delivery service, its active transportation fleet could become yet another competitive advantage. By supplementing its long-term relationships with UPS and FedEx with its own Fresh trucks, Amazon may well be able to deliver faster than retailers that depend entirely on outside services. “Pretty soon, if you’re a retailer with your online business, you’re going to be faced with a choice,” says Brian Walker, a former analyst at Forrester Research who is now with Hybris, a provider of e-commerce software. “You’re not going to be able to match Amazon, so you’re going to have to consider partnering with them and leveraging their network.”
This shift could even turn Amazon into a competitor to UPS and FedEx, the long-standing duopoly of next-day U.S. shipping. “If Amazon could do it at enough scale, they could offer shipping at a great value and still eke out some margin,” says Walker. “In classic Amazon fashion, they could leverage the infrastructure they’ve built for themselves, take a disruptive approach to the pricing, and run it as an efficiency play.”
Amazon has been down this road before. Its Web Services began as an efficient, reliable back end to handle its own web operations–then became so adept that it now provides digital services for an enormous range of customers, including Netflix and, reportedly, Apple. It’s not impossible to imagine Amazon doing the same with shipping. Last year, the company cut its shipping costs as a percentage of sales from 5.4% to 4.5%. As it builds more distribution centers, installs more lockers, and builds out its fleet, Amazon is likely to drive those efficiency costs down even further.
So is Amazon Freight Services Bezos’s next mission? When I ask, the laugh lines vanish from his face as if someone flipped a switch on his back. He contends that same-day delivery is too expensive outside of urban markets and that it only makes sense for Amazon to deliver its own products within the Fresh program. In China, he explains, Amazon does in fact deliver products via many couriers and bicycle messengers. “But in a country like the United States,” he says, “we have such a sophisticated last-mile delivery system that it makes more sense for Amazon to use that system to reach its customers in a rapid and accurate way.” When I ask whether he would consider, say, buying UPS, with its 90,000 trucks–or even more radically, purchasing the foundering USPS, with its 213,000 vehicles running daily through America’s cities and towns–Bezos scoffs. But he won’t precisely say no.

• Condoms, iPads, And Toilet Paper: A Day In The Life Of An Ebay Now Deliveryman
Rivals aren’t waiting for an answer. EBay has launched eBay Now, a $5 service that uses its own branded couriers in New York, San Francisco, and San Jose, to fetch products from local retail stores like Best Buy and Toys “R” Us and deliver them to customers within an hour. Google, fully aware that Amazon’s market share in product search is substantial (now 30% to Google’s 13%), has launched a pilot service called Google Shopping Express, which partners with courier companies. Walmart–which has booted all Kindles from its stores–started testing same-day delivery in select cities during the last holiday season, shipping items directly from its stores. (Joel Anderson, chief executive of, even suggested paying in-store shoppers to deliver online orders to other customers the same day. Come for a handsaw, leave with a job!)
These are the sort of ideas that retailers–both e-commerce and physical, large and small–will have to consider as Amazon expands. Guys like Jeff Jordan, partner at well-known venture firm Andreessen Horowitz, will make sure of it. His firm follows and invests in direct-to-consumer businesses. “We won’t invest in a company,” he says, “unless they can tell us why they won’t get steamrolled by Amazon.”

Given the astounding growth of Amazon, and the seemingly infinite ways it has defied the critics, Bezos may have proved himself the best CEO in the world at taking the long view. But he doesn’t like talking about it. “Did you bring the crystal ball? I left mine at home today,” he quips. He does, however, like discussing what the future might bring for his customers. In fact, he likes talking about his customer so much that the word can seem like a conversational tic; he used it 40 times, by my count, in just one interview. “It’s impossible to imagine that 10 years from now, I could interview an Amazon customer and they would tell me, ‘Yeah, I really love Amazon. I just wish your prices were a little higher,'” he says. “Or, ‘I just wish you’d deliver a little more slowly.'” In Bezos’s world, the goal of the coming decade is a lot like the goal of the past two: Be cheap. Be fast. That’s how you win.
There is, naturally, no guarantee that Bezos will simply win and win and win. The bigger Amazon gets, the greater the number and variety of stakeholders required to make the Amazon machine hum. Many seem to be getting increasingly frustrated. Consider Amazon’s third-party sellers–that group making up 40% of the company’s product sales. Earlier this year, Amazon issued a series of fee hikes for use of its fulfillment services, ranging from as low as 5 cents per smallish unit to as much as $100 for heavier or awkwardly shaped items (like a whiteboard, say, or roll-away bed). Many sellers took to Amazon’s forums to complain, and others threatened to go to eBay, which mostly leaves fulfillment to its sellers. “I think Amazon is a necessary evil,” says Louisa Eyler, distributor for Lock Laces, a shoelace product that sells as many as 3,000 units per week on Amazon. After the price hike, Eyler says her total fees for the $7.99 item went from $2.37 to $3.62. She says Amazon now makes more per unit than she does.
Or consider the frustrations of Amazon employees, who are striking at two of its eight German facilities in an effort to wrest higher wages and overtime pay. At the height of the conflict, on June 17, 1,300 workers walked off the job. (It is one of Amazon’s largest walk-offs in its biggest foreign market, and could result in shipping delays.) Meanwhile, Amazon workers in the U.S. have filed a lawsuit claiming that they’ve been subject to excessive security checks–to search for pilfered items–at warehouses. The suit alleges their wait could last as long as 25 minutes, an inconvenience Amazon would never subject its customers to. “It means there’s a broken process somewhere,” says Annette Gleneicki, an executive at Confirmit, a software company that helps businesses capture customer and employee feedback. “[Bezos] clearly inspires passion in his employees, but that’s only sustainable for so long.”
The company could be vulnerable on other fronts as well. Target and Walgreens have “geo-fenced” their stores so their mobile apps can guide customers directly to the products they desire. Walmart and Macy’s have begun making their stores do double-duty, both as a place to shop and a warehouse from which to ship products. (The strategy seems to be paying off for Macy’s, which recently reported a jump in first-quarter profit and is now fulfilling 10% of its online purchases from its stores.) They’re proving that retail won’t go away–it’ll learn and adapt. “Now you have smart brick-and-mortar stores saying, Why isn’t our experience more intuitive, as it is on the web?” says Doug Stephens, author of The Retail Revival: Re-Imagining Business for the New Age of Consumerism. “We should know a consumer when they walk in, and what they bought before, in the same way as Amazon’s recommendation engine.”
Bezos won’t admit to any deep concern. While Amazon’s paper-thin profits continue to perplex observers (the company netted only $82 million in the first quarter of 2013), the three primary weapons in its retail takeover–fulfillment centers, Amazon Prime, and now AmazonFresh–are coming to maturity. If the next year tells us anything about Amazon’s future, it should reveal whether Bezos’s decision to plow billions back into these operations will give the company an end-to-end service advantage that might be nearly impossible for its competitors to overcome.
The sun seems to be setting on Bezos’s big Day One. Before we part ways in Seattle, I ask him what we can expect to see on Day Two. “Day Two will be when the rate of change slows,” he replies. “But there’s still so much you can do with technology to improve the customer experience. And that’s the sense in which I believe it’s still Day One, and that it’s early in the day. If anything, the rate of change is accelerating.”
Of course, Bezos is the accelerator.

Amazon Buys Twitch For $970 Million In Cash

AUG. 25, 2014, 4:03 PM 13,994 21
Patrick T. Fallon/Getty Images
Twitch CEO Emmett Shear.

Amazon said on Monday it would pay $970 million in cash for Twitch, a live video-game-streaming site with more than 55 million users that’s like YouTube for video games.

As of July, Twitch had over 15 billion minutes of content, and users were spending more than 100 minutes a day on the site, on average. Twitch users can host live streams of their gaming sessions and broadcast them to the world. They can also chop up their sessions into segments for streaming later.
It’s also a resource for gamers who like to show off their unique skills. For example, there’s an entire community on Twitch dedicated to doing weird stuff like beating Zelda games in under 20 minutes or playing massively collaborative games of Pokemon.

A Twitch streaming session.

Twitch is a huge part of the internet, and it accounts for nearly 2% of all traffic in the U.S. during peak hours, according to a report by The Wall Street Journal. Only Netflix, Google, and Apple account for more traffic. In that respect, Twitch even streams more video than Hulu.

Twitch also accounts for 40% of all live-streamed internet content, according to Business Insider Intelligence:

BI Intelligence

What’s really impressive is that Twitch was able to become so big after just three years.

You can see Amazon’s purchase of Twitch as a play to take over the future of TV. More and more content is being streamed online, and more and more hours of video watching are being done on sites like YouTube, Netflix, and Hulu. Amazon has its own streaming video service called Amazon Instant that comes with Amazon Prime memberships. Amazon Instant includes thousands of streaming movies and TV shows, including original shows like “Alpha House.”

Alpha House is an original Amazon show.

Earlier Monday, multiple reports indicated Amazon was in late-stage talks to acquire Twitch. The news came as a big surprise because just last month it was reported that Google had agreed to acquire Twitch for about $1 billion. That deal, however, was never officially confirmed.

The Google-Twitch deal felt like a natural fit, since it would’ve been a good way for YouTube to expand its video offerings. Yahoo also tried to buy Twitch for $970 million, but Amazon swooped in and got it instead.
It’s unclear what had caused the Google-Twitch deal to fall through, but one possible reason is over antitrust issues. Since Google already owns YouTube, the world’s largest video streaming site, acquiring another massive video streaming site like Twitch could raise antitrust issues. According to Forbes, the two sides couldn’t agree on the potential break up fee.
Here’s the official announcement from Amazon:, Inc. (NASDAQ: AMZN) today announced that it has reached an agreement to acquire Twitch Interactive, Inc., the leading live video platform for gamers. In July, more than 55 million unique visitors viewed more than 15 billion minutes of content on Twitch produced by more than 1 million broadcasters, including individual gamers, pro players, publishers, developers, media outlets, conventions and stadium-filling esports organizations.
“Broadcasting and watching gameplay is a global phenomenon and Twitch has built a platform that brings together tens of millions of people who watch billions of minutes of games each month – from The International, to breaking the world record for Mario, to gaming conferences like E3. And, amazingly, Twitch is only three years old,” said Jeff Bezos, founder and CEO of “Like Twitch, we obsess over customers and like to think differently, and we look forward to learning from them and helping them move even faster to build new services for the gaming community.”
“Amazon and Twitch optimize for our customers first and are both believers in the future of gaming,” said Twitch CEO Emmett Shear. “Being part of Amazon will let us do even more for our community. We will be able to create tools and services faster than we could have independently. This change will mean great things for our community, and will let us bring Twitch to even more people around the world.”
Twitch launched in June 2011 to focus exclusively on live video for gamers. Under the terms of the agreement, which has been approved by Twitch’s shareholders, Amazon will acquire all of the outstanding shares of Twitch for approximately $970 million in cash, as adjusted for the assumption of options and other items. Subject to customary closing conditions, the acquisition is expected to close in the second half of 2014.
Here’s a letter from Twitch’s CEO:
Dear Twitch Community,
It’s almost unbelievable that slightly more than 3 years ago, Twitch didn’t exist. The moment we launched, we knew we had stumbled across something special. But what followed surprised us as much as anyone else, and the impact it’s had on both the community and us has been truly profound. Your talent, your passion, your dedication to gaming, your memes, your brilliance – these have made Twitch what it is today. Every day, we strive to live up to the standard set by you, the community. We want to create the very best place to share your gaming and life online, and that mission continues to guide us. Together with you, we’ve found new ways of connecting developers and publishers with their fans. We’ve created a whole new kind of career that lets people make a living sharing their love of games. We’ve brought billions of hours of entertainment, laughter, joy and the occasional ragequit. I think we can all call that a pretty good start. Today, I’m pleased to announce we’ve been acquired by Amazon. We chose Amazon because they believe in our community, they share our values and long-term vision, and they want to help us get there faster. We’re keeping most everything the same: our office, our employees, our brand, and most importantly our independence. But with Amazon’s support we’ll have the resources to bring you an even better Twitch. I personally want to thank you, each and every member of the Twitch community, for what you’ve created. Thank you for putting your faith in us. Thank you for sticking with us through growing pains and stumbles. Thank you for bringing your very best to us and sharing it with the world. Thank you, from a group of gamers who never dreamed they’d get to help shape the face of the industry that we love so much. It’s dangerous to go alone. On behalf of myself and everyone else at Twitch, thank you for coming with us. Emmett Shear, CEO
Disclosure: Jeff Bezos is an investor in Business Insider through his personal investment company Bezos Expeditions.
SEE ALSO:  Here’s Why Amazon Just Paid Nearly $1 Billion For A Site Where You Can Watch People Play Video Games

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Amazon Is Turning Into Google

AUG. 25, 2014, 7:15 PM 1,038 3

Amazon Inc.
Amazon CEO Jeff Bezos.

Tell me which company this sounds like:
A company that…
• Has its own mobile operating system for tablets and smartphones.
• Has its own app store.
• Sells digital music, books, movies, and TV shows.
• Will soon have an online ad network.
• Created a way to accept payments with a smartphone.
• Owns the servers that act as the backbone for several major apps and startups and even parts of the CIA.
• Is experimenting with drones.
It’s not Google. It’s Amazon.
But just like Google has expanded beyond search into everything from finding ways to cheat death to making cars that can drive themselves, Amazon has been increasingly expanding beyond its core e-commerce business.
And in recent months, that only seems to be speeding up.
Amazon’s $970 million purchase of Twitch, a site that lets you watch people play video games via a live stream, is its latest push into original video content and a move to transform itself into part media company. It’s a longer-term bet that the trend of watching stuff online versus cable will continue.
Add that on top of the stuff listed above, and Amazon suddenly sounds less like an online store for buying books and gifts and more like a company trying to insert itself into everything you do online. It sounds very Google-y.
Plus …
There’s experimentation with same-day delivery, grocery delivery, and point of sale systems for brick-and-mortar retailers. Those are all things Google is working on or has at least experimented with.
The only difference, of course, is that Google is wildly profitable while Amazon continues to post losses each quarter. (Next quarter could be a doozy. Amazon said to expect at least a $410 million operating loss.)
But it’s also a changing company, one that’s no longly simply “the everything store,” but an entity creeping its way into everything we do from shop to play games to run our small businesses.
Disclosure: Jeff Bezos is an investor in Business Insider through his personal investment company Bezos Expeditions.
SEE ALSO:  9 impressive stats about Twitch

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Bezos Confirms AmazonFresh Expansion Plans, Says Drones Are for Real
April 10, 2014, 9:15 AM PDT
By Jason Del Rey
Grocery delivery fans outside of Seattle and California, rejoice: Amazon plans to expand its AmazonFresh offering beyond its current three markets, CEO Jeff Bezos confirmed in his 2013 letter to shareholders published today.
“We’ll continue our methodical approach — measuring and refining AmazonFresh — with the goal of bringing this incredible service to more cities over time,” he said in the letter.
For five years, Fresh was only available in Seattle, before the company launched the program last year in Los Angeles and, six months later, San Francisco. Several reports over the past year have said Amazon plans to expand the delivery service into 10 to 20 more new markets this year, but this may be the first time Bezos has publicly acknowledged the expansion plans.
Through Fresh, shoppers can order deliveries of groceries and hundreds of thousands of other items, from TVs to toys, that arrive either that same day or the following morning. Industry observers believe that part of Amazon’s reason for delivering groceries is that it will create enough sales volume and delivery demand to justify delivering all other Amazon merchandise within one day.
Another highlight from the letter: Drones.
“The Prime Air team is already flight testing our 5th and 6th generation aerial vehicles,” Bezos wrote, “and we are in the design phase on generations 7 and 8.”
Is it possible that drone delivery is still a marketing stunt? Sure. If so, Bezos is sticking to the script.

More from this story

Headed your way: AmazonFresh widens range of grocery deliveries

Doorstep delivery: Our reporter gives AmazonFresh grocery service a whirl

Published: June 20, 2014 Updated: June 23, 2014 11:44 a.m.

Here are a few price comparisons based on items found online this week:
1 gallon of Alta Dena fat-free milk: $5.49 Vons vs. $4.99 AmazonFresh
59-ounce jug of Simply Lemonade: $2.50 Vons vs. $2 AmazonFresh
5 ounces organic baby romaine: $3.90 O private-label Vons brand vs. $3.39 Earthbound brand at AmazonFresh
24-pack of Aquafina 16.9-ounce bottled water: $5.49 Vons vs. $4.29 AmazonFresh
Tide Free and Gentle (100 ounces): $11.99 Vons vs. $11.97 AmazonFresh
20-pack Coke Zero: $8.29 Vons vs. $6.99 AmazonFresh

Winder Farms: A Utah-based delivery service in California, Utah and Nevada. Delivers roughly 300 farm fresh items. Delivery in Orange County and parts of Los Angeles County.
Good Eggs: Delivery of locally grown, sustainable goods from stores or farmers’ markets. Los Angeles County only.
Vons: Traditional market with home delivery in Orange County.
Instacart: Delivers from local stores like Whole Foods, Ralphs and Bristol Farms. Limited to a few ZIP codes in Los Angeles County.
Deliveer: Personal shoppers deliver groceries from Whole Foods Market, Trader Joe’s, Vons and Costco in Pasadena, San Marino, South Pasadena and Altadena. Expansion to other parts of Los Angeles County coming soon.
As Amazon’s fledgling grocery service in Southern California widens its reach, some boutique food suppliers say the experiment has proven to be a boon for business.
Huntington Meats saw sales go from single-digit growth to double digits after the first month of partnering with AmazonFresh, a doorstep food service that launched last summer in Los Angeles.
The 30-year-old butcher shop, known for its top-grade meats and wild game, partnered with AmazonFresh last summer. Co-owner Jim Cascone said his meat market sells the “whole store,” or 175 items, through the online site, from free-range chickens to ground elk.
Demand for his specialty goods continues to soar and was boosted in recent weeks when the company expanded its service to most of Orange County.
“We’re very pleased,” said Cascone. “We’re definitely getting a lot of business out of it.”
For other Amazon partners, the impact has been much less dramatic. Greg Daniels, executive chef-partner at Haven Collective, has been working with AmazonFresh the last six months. The company’s Provisions Market bottle and cheese shop in Old Towne Orange offers Amazon shoppers specialty cheeses, cured meats, chocolate and a wide selection of craft beer.
“Cheese is popular, and beer not too much yet,” said Daniels. “It’s definitely brand exposure more than money.”
Amazon’s doorstep service initially was limited to Los Angeles, four cities in Orange County and parts of Long Beach. Shoppers choose from a wide selection – some 500,000 items – of merchandise, groceries and specialty foods.
In recent weeks, AmazonFresh has expanded to Orange, Tustin, Garden Grove, Aliso Viejo, Santa Ana, Laguna Niguel and Mission Viejo in addition to Irvine, Anaheim, Huntington Beach and Newport Beach. All of Long Beach is also eligible for delivery, a company spokesperson said.
The expansion comes as Amazon sees positive results in the greater Los Angeles area.
“While I can’t share specific numbers, we are very pleased with the response from our customers so far,” AmazonFresh said in a statement.
AmazonFresh’s grocery delivery expansion comes as doorstep food services experience a resurgence after failing years ago.
In 2013, revenue from online grocery sales reached $6.5 billion, according to market research firm IBIS World. By 2018, sales are projected to reach $10.1 billion as time-strapped consumers seek convenient ways to shop through mobiles devices and home computers, IBIS said.
AmazonFresh entered Los Angeles last summer after testing its grocery service near its home turf in Seattle. The service is also available in San Francisco and Berkeley.
Other food delivery options in the region include Winder Farms, Good Eggs, Deliveer, Instacart and Vons.

AmazonFresh rolls into San Diego
By Katherine P. Harvey2:08 P.M.JULY 29, 2014Updated5:36 P.M.