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What would an ideal drug discovery/drug development process look like?
As a person who has made drugs and is planning on making a career out of it, I hope that a lot of things change by the time I reach the middle of my career. The ideal drug development process would and should look very different from the current system in place.The interesting thing is that most of the interactions that already exists should stay in place. A large problem with the current inefficiency of the drug discovery / development process is that the incentives and goals are misaligned for all of the individual players in the drug making process. It's certainly an acknowledged problem and everyone in the drug industry talks about it. To describe how deep of a hole we're in, I show you Eroom's law (Moore backwards) which suggests that the cost of developing a new drug doubles every nine years.EROOM's Law This is pretty unsustainable and Pharma knows it so there are a lot of experiments and proposals to change the drug development process so that failures occur earlier and successes are identified early and pushed through.Everything I will describe tackles the underlying goal of reducing the attrition rate and costs of the drug development pipeline. To briefly outline MY OWN opinions on what needs to happen to have a cost effective system I'm going to dive into:Adjusting the goals of academic research to focus on clinically relevant areas.Changing how medical research appropriately informs and guides that basic researchBridging the gaps between academic and industrial research by both academic efforts and increased drug companies' fundingDiversifying risk between the various stages of drug development by focusing on individual strengths.Revamping the clinical trial process, drug approval system, and influence of marketing to allow for smaller but faster trials.Integrating the drug distribution system into the healthcare networkCreating and rewiring the feedback loops between all of these systemsThe Role of Basic ScienceLet's start from the beginning. Academics are certainly the seed and start of medical discovery and innovation. They ask the questions we don't know the answers to and also find them and from their understanding of biology, chemistry, and medicine, the drug companies can take things to the next level.Unfortunately, the targets that are hot topics in academic will very often be undruggable targets or at least very hard to hit. Targets like protein-protein interactions, transcription factors, protein aggregates, ubiquitin modifiers, RNA, and epigenetic regulators. A great example of a protein target that receives a lot of attention but is completely undruggable is p53 as described in Can p53 be synthesized into a drug to target cancer? It's a target that is extremely dynamic, has a multitude of interactions, and has plenty of off-target effects. People may get the impression that maybe one day we'll figure a way how to make it a useful drug but in reality, we'll probably never hit it and it's merely an very interesting topic of study in molecular biology (with great scientific importance I would add).The result is ~2% of the human genes are actually druggable which largely separates what academics work on and say we can cure vs. what drug companies can actually cure.  I describe this more in my answer to Human Genome Project: Was all the promise publicized by the media during the mapping of the human genome simply hype? and Why has genomics been so unsuccessful in the discovery of new medicines?Every now and then, one of those "undruggable" targets become druggable with the invention of new technologies or chemistries. Things like recombinant technology, antibodies, stapled peptides, and PEGylation have made it possible to attack new targets. Indeed one of the widely assumed "undruggable" targets, K-RAS, was recently targeted by a team from Max Planck using a combination of structure-based drug design. Yet there is still is separation from what academics are working on and what companies can actually do.This was well stated by Stuart Schreiber (who, I note, gave me much of the structure of this portion of the argument): Academic research ... might have a greater impact if it were redirected to developing methods that change our view of what is doable.  While there is much talk about target-based drug discovery, the modern era hasn't produced much in terms of drugs and a large part is the failure for basic science researchers to choose good targets. The fixture to this issue would be toHave real MSTPs. A good number of MD/PhDs don't end up going into research or they lose too much momentum because of residency. Having true hybrid scientists will help bridge that gap between what patients need and what is actually possible.Clearer discussions on what is and isn't "druggable". As others have mentioned, scientists should be doing a better job looking at the final product rather than thinking about what applications their recent discovery can be applied to.Improvement on target identification. People need to recognize signal from noise and unfortunately there is a lot of noise.Commitments to developing new chemistries and technologies to target the "undruggable" space.Better academia/pharma interactions.The first two are cultural things that academics need to be less stubborn about. The third is an area ripe for progress. As mentioned by Taffy Williams and Mike Thompson, the advent of personalized medicine drastically improves the ability to relate a disease to it's molecular mechanism of action. Furthermore, HTS technologies are designed to be more amenable to diseased-based drug discovery rather than target or gene-based. To better connect academic research with disease, we need to go further into the chain to medical research.Connecting Physicians and ScientistsDrug discovery really starts with observations in the clinic. Doctors will observe patients and from recognizing patterns, they will have a better idea of what makes up a disease and maybe begin to have an idea of the underlying mechanism. I go into this more in my answer to How do pharmaceutical companies go about finding cures for diseases?The problem with this model is that doctors are notoriously bad at doing science and statistics and either see patterns out of nothing or will run trivial investigator initiated trials that are under-powered, biased, non-randomized, non-placebo controlled, and poorly designed. Again, a large reason why better Medical Scientists are required in medicine.The ideal situation is better data collection using Electronic Medical Records and releasing that data from the EMR companies so that information about patient habits, diagnoses of disease can be used. Unfortunately, this information is very difficult to get unless we have a complete overhaul of the healthcare system which I will go into later. I illustrate the value of having this data with the alternative route.For now, I suggest reading the 5 part series: How to build a good EMR by Jae Won JohThe existing model for data collection is the use of patient communities like Susan Komen and Cystic Fibrosis Foundation, which have been extremely helpful to both doctors and pharmaceutical companies. It helps to link symptoms to the underlying case of disease and pools together the patient populations to understand the epidemiology and guide companies to which drugs will have the broadest effect.As seen in questions below, there are very good reasons for pharmaceutical companies to create a strong patient community to better understand the disease and to help with clinical trial enrollment.How should Pharma work with online patient communities?Which pharma companies are currently working with online patient communities?Should pharmaceutical companies support existing online patient communities or create their own?This has been extremely effective in the Rare disease community in collecting and sharing data to better inform patients, doctors, and drug companies. However, a shared worldwide network that better captures all of the variance of the disease will vastly improve physicians' ability to systematically track trends along with maintain a consistent standard of care. Furthermore, in post-approval studies, this type of network allows us to better identify side effects and drug-tolerant patient populations.The Bridge to PharmaceuticaObviously this isn't merely academia's fault. Pharmaceutical companies need to carry their weight in the drug discovery side. Given the large amount of money that is already dumped into research it is important to prioritize research funding. However, the use of those funds are currently poorly utilized.I go more into the economics in the marketing section but for now, it is important to realize that there are large non-trivial cost barriers from translating an idea from academia to company. As every startup knows, there is something called the "valley of DEATH".Ignoring the y-axis "cumulative profit/loss" and replacing it with "expected value", the graph is essentially the same in the eyes of Venture Capital and investors. During the early stages of drug development, the probability of success is extremely low and expected value of the drug is equally low. Only after a lot of time and money does the "commercialization" or the proof of concept occurs and a drug becomes worth investing in.Unfortunately for the biotech industry, the valley of death usually coincides with a Phase II clinical trial which takes ~$20-100 million dollars to get to which can be demonstrated with the next figure .So either VCs need to start doing a series A earlier during the process and regularly fund companies pre-IND, pre-Phase III or another large player needs to step in. In addition, academic groups need to do a better job connecting their publications to the final product to reduce uncertainty and risk.This is probably the most exciting current area of drug development as it requires the least amount of momentum to achieve large meaningful results. Universities, Drug companies, and VCs are largely experimenting with how they are tacking this cap.Academics making their drug fundableI'll start with what Academics. I mentioned earlier that Academics tend to work on problems that don't usually yield to tangible results. However a deeper issue is not realizing the disconnect between a successful publication and the commercialization of that idea.The inability to draw in a licensing deal or VC funding can be summarized by:A poor understanding of the economics of the diseaseLack of meaningful clinically relevant dataAn inability in academia to weed out false positives.A poor understanding of the economics of the diseaseSince most PhDs aren't MBAs, they really have no clue how health insurance works and how much drugs actually cost. Typically the way how research is funded is:Find something coolFind what that cool thing doesSee if that thing it do is usefulJustify doing more research on that cool thing based on what it doesTotally reasonable way of doing research but it's also the reason why the NSF is getting in trouble with Lamar Smith. Essentially most of biological research is driven by finding random applications of the science rather than finding the appropriate application and making involved hypotheses to guide that science.For academics to seriously make an impact, they must first check in with the physicians to see what actually happens in the disease that they are interested in and then adjusting the drug in a manner than is suitable for that disease.For instance, several "cures" of HIV including bone marrow transplants and aggressive antibody treatments are impractical since a handful of "inexpensive" oral drugs will essentially do the same + be safer.Lack of meaningful Clinically relevant dataEveryone has seen the article "X cures cancer". What most people forget to do is to read the small text "this might be useful as a drug in 15-20 years". Typically these high-impact publications go along the lines of demonstrating efficacy in an early model system and then following up those observations with the next logical series of experiments.The common saying in the drug discovery world is that "you get what you screen for". As critics of the pharmaceutical industry will say, we're good at curing mice. While we still face the same drug development issues when we attempt to treat mice, the result remains the same, our drug discovery pipeline isn't optimized for finding drugs that treat human diseases. That is, things like chemical-based screening and target-based screening doesn't necessarily produce clinically relevant results. As mentioned, later, the major sources of failure come from lack of efficacy or toxicity. This basically suggests that you've chosen the wrong target to attack.The alternative is to design the screens to identify clinically relevant compounds from the start. Using disease-specific cell-based assays are one method. Using several filters for activity is another. There are also several efforts to build better mice models which actually have human immune systems and die from human cancers. The world of iPSCs also opens the door to the creation of immortalized cells that come directed from a diseased patient.The ideal scenario is to change drug discovery from a linear process to an integrated research pipeline which eliminates false positives from the start. I'll go more into the research integration later.Proposal for bridging the valley of death An inability in academia to weed out false positives.Certainly a sensitive topic in research is the question Is most medical research wrong? Why or why not?A classic paper Why Most Published Research Findings Are False by John Ioannidis suggests that there is an unfortunate tendency for publications to select for positive data. In my own answer, I claim that this falsehood comes from the misinterpretation of the data and answer by Manish Kothari and Michael W. Long also go along those lines. It surprisingly isn't because of fraud or data manipulation, it's more that people are pressured into seeing what they want to see and making the wrong analysis.This issue also reflects the very difficult task of reproducing research. As a personal example, we have one company that is trying to replicate our data using a similar experimental setup and they were failing to do so. In fact, they had to send "experts" to directly observe my labmate doing his experiment and even made him use their own reagents to confirm. Ultimately we narrowed it down to them using a poor source of a few reagents along with forgetting to mix certain chemicals in a certain order. Unfortunately the guy who figured this all out left so after we taught this information, we had to teach it all over again.A lesser known study done by Bayer and Amgen formed validation teams that essentially spend a year trying to reproduce other people's data. Their conclusion: ~20-25% of the data was reproducible; 2/3 of the data there were inconsistencies. Again, this isn't because of fraud or data manipulation. In many of these cases, the teams had to replace cell lines or change the assay formats to get the hypothesis to work. However, even then, there were inconsistencies. There is a lot of variation in biology and are several factors that may cause a false positive.The moral is: Just because your paper was accepted in Nature, it still doesn't mean that it's scientifically sound enough to spend $1 billion dollars on it. To successfully and scientifically validate your idea to the point where a company is willing to take a risk requires several confirmations of your idea. If the drug works in an assay, use a new assay; if it works in another assay, use a cell-based assay; if it works in a cell-based assay, use another cell-based assay; if it works in that cell-based assay, use a mouse; if it works in a mouse, use a rat; etc. See How do drug researchers address effects that only occur in rats?For intellectual pursuits, these studies may not be particularly rewarding but they are the scientifically correct thing to do and ultimately brings in investors. There is also the whole revamping of the publishing model which I will also go into later.I conclude this chapter with a brief telling of The Sirtuin Saga regarding Resveratrol.Triggered by a study by David Sinclair in 2003 that suggested that the molecule in red wine extended the lifespan of yeast cells and at one point showed the reduction of aging in mice. The resulted in the starting of the biotech company Sirtis which ultimately got acquired by GSK for $720 million. However, later studies suggested that the in vitro assays that suggested this activity had some artifacts due to the presence of the fluorescent molecule used in the experiment. Recent data suggests that the assay only worked in specific conditions but still worked. In the end, the scientists did isolated activity, they just started a ~$1 billion company off the wrong lead compound.  This debate itself has lead to multiple Quora questionsDo sirtuins really lengthen lifespan?Does resveratrol keep our cells from aging?Why is red wine good for you?If you ask Alex K. Chen for his opinion, the answer is maybe.Academic pipelinesIn order to get researchers to recognize these pitfalls, Universities have created internal pipelines to help academically minded people solidify business-friendly science that can be outsourced.Most of these groups help Professors and students get through the hurdles mentioned above and uses industrial expertise to indicate what risks remain with the proposed technology. Ultimately these ideas would become mature enough to be licensed or spun out into a company and allow Professors to get back to their professing.A few of these programs already exist and the best examples includeStanford SPARKMIT NEWDIGSNorthwetern CMIDDEmory Institute for Drug DevelopmentU Toronto MaRSUCSF CDDSDrug companies funding academicsAs the academics reduce their risk, companies and VCs need to do a better job taking risks. There are usually two schools of though on how to approach this problem.Drug companies should start pulling out the checkbooks and with an aggressive M&A or partnerships fund early stage researchDiversify the risk to Contract Research Organizations and let them handle early stage Clinical development.Those who believe in virtual and lean startups will tell you to go with option 2 and since they have a MBA, they are probably right. I will tell you to go with option 1 since only Pharmaceutical companies had the long term discipline and vision to prevent further fragmentation of an already shaky potential drug. The current reality is something in the middle since Pharma companies are too unweldy to move quickly through development and small biotechs are too desperate to do good science.The ideal model is a Pharma funded early stage pipeline program that operates independently of the mother program but has the financial and intellectual capital to success.Good examples of these early pipeline programs includeGenentech (gRED) / RocheChorus / LillyCORTEX / PfizerCentocor/ JnJBad examples of early pipeline programs that weren't independent includeGroton / PfizerSandwich / PfizerKalamazoo / PfizerWyeth / PfizerKent / PfizerSirtris / GSKResearch Triangle / GSKHarlow / GSKWhitehouse Station / MerckBasically don't be Pfizer. What essentially happened was that pharmaceutical management interfered with early R&D and started outsourcing certain functions to other countries with "expertise" for the sake of "efficiency". However, what that actually means is waiting for a chemist in China to ship their compound to the assay development team in North Carolina which uses a protein created in Switzerland. It's pretty much guaranteed to not work. What you really want is a small well funded mini biotech that cranks out a bunch of compounds.GSK had shifted to a Therapy Area Units (TAUs) system but they are in trouble since they keep on changing the model every 8 years whenever they get a new CEO. Novartis uses the NBIR model; JnJ never bothered to integrate their units; Roches has pRED and gRED; Merck stuck with MRL but the new R&D chief is proposing an aggressive reshuffling at the time of writing. Pfizer has changed their research model from independent research labs to "Centers of Therapeutic Innovation" which collaborate heavily with several Universities. They are essentially outsourcing all of their R&D to academic labs. Probably a wise move but probably not worth imploding their research units.In summary: Pharmaceutical Managers needs to stop moving units around every ten years especially involving products that take 15 years to work.Part of this is a disciplined approach to outsourcing which gets back to the MBA's approach to doing research. There is a lot of value in contracting out research.It allows companies to focus on what they are good at.Reduces training time of new hiresSpreads out capital costs (especially with contract manufacturing)Where this quickly goes wrong is when expertise gets lost and communications gets severed. I mentioned my own outsourcing story earlier and Derek Lowe has several deep and bitter discussions on the problems of outsourcing. When outsourcing causes you to spend more time troubleshooting your supply chain rather than doing science, you're sacrificing time and money. Making Marketing Departments SHUT UPAccording to Adithya Balasubramanian's answer to What is the detailed cost breakdown of an expensive clinical trial? ~90% of the cost to approve a single drug comes during the Phase III clinical trial. Phase III trials are expensive and unfortunately still fail 40% of the time.The major reasons behind failure: efficacy and toxicity. At some point we had information from Phase II trials that informed us that this drug had a pretty good shot at working. As indicated in the cost breakdown, In addition to the fact that they already cost a lot, Phase III trials are get more expensive because they are getting longer, more complicated, have a lower patient retention rate, lower patient enrollment rate. All in all, we are being too aggressive with the way how we design clinical trials and pushing compounds into phase III.A good example of getting impatient and going blindly into Phase 3 trial was the recent Pfizer, JnJ, and Elan efforts with Alzheimer's and blew over $1 billion on two trials with Bapineuzumab despite very indifferent Phase II data. See Where did most of the money in the failed Bapineuzmab Alzheimer’s antibody phase III trial go? The companies had their eye on the $5 billion / year Alzheimer's market but didn't allow the science to dictate their strategy and placed a bad gamble. My hypothesis is that we rush to Phase III too quickly and design the trials to be too broad. If the Phase II data indicates that the drug works in half of the patients, we should be testing the drug in the responsive half. The marketing team will say, that's too complicated, let's test all of the patients and get twice as much money obtaining a blockbuster.The unfortunate result is to appropriately design a suitable trial, you will need a larger subject population and a longer enrollment period to sufficiently power the trial. This ultimately will cost several times more and has a higher chance of failure than designing a smaller well powered trial. This comes back to efficacy and toxicity. If you have a good idea which patients will likely show the best efficacy and least toxicity, you should design your trial for those patients. As mentioned earlier, this is partially due to choosing an incorrect target. However, enrolling the patients that have the wrong target is also a sure way to get a dud.The clinical trial that goes against this tide was Herceptin which looked to attack a gene that was expressed in only 20% of Breast Cancers. From a disciplined scientific approach, Genentech resisted the pressure of increasing their market size 5x by narrowing into the smaller group of Her2-positive patients. Doing so allowed them to use a significantly smaller population (10-20 times smaller) and get approval more quickly.However, there is a reasonable question whether the marketing people were right. Recent reports do suggest that Herceptin works even for certain Her2 negative patients and a non-trivial proportion of Doctors don't pay attention to Her2 status prior to prescribing the drug. In the end, you want the broadest indication since it gets you the most money in the brief period of time the drug patent exists. Marketing got their Blockbuster anyways.You can't blame Pharma companies for thinking this way. I;m sure that some MBA has shown that taking these type of these aggressive gambles should actually get more money in the short term despite the higher failure rate. As a result, to incentivize a trend towards these smaller but better designed trials we need to have an overhaul of the drug approval process.A new interaction between the FDA, Insurance, and PharmacyWhile a lot of drugs fail simply because we didn't identify failiures early like in the case of Bapi, there are some drugs that failed since too many non-responders were enrolled. In my non-medical opinion, drugs like Vioxx and Avandia should probably be on the market since they do work despite what Steve Nissen says. Their problem is that they are being marketed to the wrong people.Despite the large controversy in data reporting for Rofecoxib (Vioxx), it was an extremely effective drug for some patients. It certainly had risks but both the US and Canada voted in favor of allowing the drug to be returned since they thought that the benefits outweighed the risks. However, the publicity hit already happened and Merck decided to permanently withdraw the drug.Another good drug that had devastating side effects was Thalidomide, the drug that triggered the strengthening of the FDA in the first place. The drug infamously caused numerous birth-defects and was quickly withdrawn from the market. As we can see in Can Thalidomide -- a drug with an exceptionally controversial history -- actually be used to treat multiple diseases as claimed in the article cited below? the once dangerous drug has reemerged as a potential Multiple Myeloma drug.This brings us into need to change the drug approval process. The potential of Pharmacogenomics can significantly change our ability to rationally identify patients who will respond well to drugs. This allows us to better design clinical trials that will enroll patients.The risk of these trials are still high and there are real concerns about generating enough of a profit to bridge the valley of death.The appropriate proposal is the use of adaptive licensing, which takes advantage of accelerated approvals to start charging patients to recuperate the costs of drug development but under extremely restrictive conditions. However, while it may cost more per patient initially, it does lower the barrier to entry and reduces the time spent in the valley of death.Depiction of Adaptive licensing A good example is the recent approval of Lomitapide which ran a tiny 29 patient phase III trial for the ultra-rare genetic disease homozygous familial hypercholesterolaemia and got FDA and EMA approval for only that indication. However, the compound has potential efficacy in hetereozygous patients and with the initial approval in the small patient population, they should have enough cashflow to initiate the larger phase III trials.This is heavily on the FDA to allow these trial designs to occur. Their role is to ensure that efficacy and safety are in place. With that in mind, they need to reassure companies that they won't consider these early stage Phase III trials as "proof of concept" trials and are willing to look at earlier NDA fillings.It should be acknowledged that reducing the patient population does complicate enrollment and as indicated by several answerers in What are some of the biggest challenges with setting up and conducting clinical trials? enrollment is one of the hardest steps with clinical trials. However, by tapping in to the patient communities and the use of smaller trial designs, I am hopeful that this dilemma can be resolved.Closing the Feedback LoopTypically when you see something about drug development you see funnel like this:I've always hated this diagram.It makes the entire drug development process seems extremely linear and essentially the secret to getting a drug is taking more shots. Also it assumes that failure is built into the process.The real drug development diagram looks more like the next two diagrams The key thing that makes these proposed systems work is the ability to use the current data to better design future experiments. Rather than working on several compounds and removing them by a process of elimination, you're working on a single product that gradually gets refined and polished by the time it reaches approval. Failures should lead to new hypotheses and guide the development rather than close the door. For this loop to be complete several things need to change.Doctors and InsuranceThese folks were blamed before but now they are getting blamed again. For adaptive approvals to work, Doctors will have to restrain one of their most powerful tools: off-label use. At the same time, insurance companies need to do a better job enabling off-label use when it is appropriate.As mentioned, Doctors need to do a better job observing and reporting patient outcomes. With the increased role of Phase IV monitoring this becomes even more important. Doctors will also need to adjust to the increased role of companion diagnostics and personalized genomics information. For instance, an abnormally large percentage of doctors prescribe herceptin without checking their patient's HER2 status. While the next wave of doctors are beginning to be trained with this mindset, a full overhaul of medical practice won't occur for at least another 30 years when veterans finally die out (however, we still want our Drs on Quora to live forever). However, even the current medical education that was given to people like Jae Won Joh and James Pan doesn't fully integrate a mindset of using personalized medicine.Insurance companies will also need to shift from a high-deductible mindset to a preventative mindset. Drugs in the US are still extremely expensive to the end-user and insurance companies aren't doing enough to negotiate those prices down and appropriately. They will also need to shift from a disease-based model to a target-based model. We can no longer treat breast cancer as breast cancer but instead, treat HER2-positives vs. EGFR-positive cancers. With these systems in place, drug repurposing would become more easy to recognize and push through.Completing this side of the feedback loop will be a key step. For this to happen, Electronic Medical Records will have to be commonplace and better and systematic data collection needs to be implemented.The interesting arena of clinical trials with personalized medicine are the MD Anderson BATTLE Trial and the British Columbia Cancer Agency's Utilization of Genomic Information to Augment Chemotherapy Decision-making for People With Incurable Malignancies in combination with PREDICT. These efforts use full genome sequencing from single-patients in attempts to do personalized cancer treatments. However, according to Marco Marra (I saw him at a conference), there are all sorts of logistical hurdles including biopsy collection and access to off-label drugs. There is also the whole inability to making meaningful connections between genomic datasets and the root cause of cancer.Revamping Data TransparencyAs it can be seen in questions likeMedical Research: Are a significant fraction of drug studies private and not released out to the public?Food & Drug Administration: What is the best way to track the progress of experimental treatments undergoing clinical trials?Where can I find meta-analysis reports on clinical trials?Is every clinical trial recorded on ClinicalTrials.gov?Is that true the clinical trials or biology research data in university labs are chaos and not recorded properly for a feasible usage of the co-worker and the succeeded researcher?Is most medical research wrong? Why or why not?There are all sorts of problems with collecting and releasing data. Again, it's not as if we're doing all sorts of fraud and making stuff up (at least most of us). I've already talked about this extensively in the section: An inability in academia to weed out false positives. In addition to the steps to validate those results, another major change would be to incentivize the publication of more negative data.To ask private companies to publish negative results, we must first ask this of our own government sponsored researchers. The bias towards positive data and the lack of acknowledging the negative data is a huge problem in academia and often leaves well intentioned hypotheses to linger longer than they should. The reasons are numerous as described in Why don't academics regularly publish their negative results?However, there are new better outlets for publishing these results and with the onset of new low-cost open-access journals like PeerJ and PLoS One, the barriers toward publication are being reduced. Ultimately it will take a massive culture change before that happens.GSK and others have also recognized that lack of data sharing in Clinical trials have also hindered their ability to predict potential failures. Unfortunately, the current situation is a prisoner's dilemma where companies that share the data get hurt by the companies that don't but all of the companies would greatly benefit if everyone shares. However, through outside political pressure from the NIH and FDA along with internal pressure, this should be a dilemma that gets resolved as the inertia changes.  You can find out more at All Trials Registered. There is also an extensive discussion by Ben Goldacre that is summarized in What do medics, researchers, drug company employees or drug regulators think about 'Bad Pharma'?There currently is a lot of valuable data out there. Genome sequencing has open the floodgates in genotype information and doctors see interesting observations all the time. However, there isn't an efficient system capturing all of this knowledge and despite all of the hate towards the Patient Protection and Affordable Care Act, if it accomplishes anything, it will be the mandated migration to EMRs.The SummaryCongrats. You are approaching the end of this giant tirade about the stiff and stubborn drug making complex. I hope that people understand that there are a lot of factors at play and the high cost of drugs isn't entirely the drug industry's fault. In addition, there are complicated politics that prevent the major players from interacting. Do to this, we need to do a better job passing a compound from one stage to the next.Academics need to do a better job convincing companies of their science.Doctors need to do a better job relying their problems to the academics.Pharma companies need to do a better job funding the researchers.Pharma needs to do a better job designing their trials.The FDA needs to do a better job allow people to design these trials in that manner.Everyone needs to publish their data.At the end of the day, it comes down to having a system where science is relevant to the medicine and guides the drug development process. The industry needs to shift to a system where hitting singles and getting compounds through is more cost effective and efficient than swinging for homeruns. This is a topic that I talk about quite a bit and I suggest following In the Pipeline: and the Quora blog Making Drugs. Diagnosing the decline in pharmaceutical... [Nat Rev Drug Discov. 2012] Outsmarting Cancer: Why It's So Tough Druggability Small molecule inhibition of the KRAS-PDEδ interactio... [Nature. 2013] The State of the Art of Chemical Biology A critique of the molecular target-based drug disc... [Metab Eng. 2008] Osawa and Miyazaki, 2006 Organic synthesis toward small-molecule probes and drugs http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020124 Believe it or not: how much can we rely ... [Nat Rev Drug Discov. 2011] The Sirtuin Saga Thinning the Fog around Sirtuins | Guest Blog, Scientific American Blog Network http://www.sciencemag.org/content/334/6060/1194.full Making Changes Inside Merck's R&D An Outsourcing Blast Translational research: 4 ways to fix the clinical trial How A Failed Alzheimer's Drug Illustrates The Drug Industry's Gambling Problem[18 ] Adaptive Licensing: Taking the Next Step in the Evolution of Drug Approval Discovery of small molecule cancer drugs: successe... [Mol Oncol. 2012] GSK commits to publishing all clinical trial results (Wired UK)
Can my lenses be thinned after receiving my new glasses?
In short- no, but not for the reason you may think.When making recommendations on lens choices, patients with stronger lens powers are often offered “lens thinning “ with up to three tiers often offered using phrases such as 20%, 33%, 45% thinner than standard (there are several formulas available to calculate this as the exact amount of thinning depends upon lens power, index, decentration, but as gross estimates these aren’t far off the final outcome compared to a ‘standard’ CR39 lens).To most patients it’s not unreasonable to assume that some “thinning” process occurs resulting in the thinner, lighter, more cosmetically appealing lens. However this is not the case. opticians have access to a range of lens materials with differing indexes of refraction (ie light is transmitted at differing rates resulting in the bending of light by different amounts), which when designed appropriately can achieve the same degree of focus using a thinner, flatter lens.Typically in addition to the standard CR39 lens (a plastic similar to acrylic with an index of refraction of 1.49) there are three differing plastics in use as lenses (1.6, 1.67 and 1.74 index - these three being the most widely used thinning options), some specialist plastics (trivex at 1.55 and polycarbonate at 1.59 - both used as eye protection) and up to six different glass indexes used (1.523, 1.6, 1.7, 1.8, 1.9, 1.55-toughened)- though not as frequently today as historically. It’s also worth noting that you may see advertised differing indexes sl higher than above as these are measured to the helium D frauenhofer line, differing jurisdictions use differing reference standard so for example a lens measured in the UK as having 1.74 would be found to have an index of 1.76 in Japan (there was an instance a few years ago where a lens company took advantage of this to market their lenses as thinner than their competitors by claiming that the same lens had a higher index of refraction an would be thinner than others- despite being the same material).Coming full circle to your question- to get “thinner” lenses you would need to have new lenses made up in a material of higher refractive index than your current ones.Hope this helpsPS to compound things, in addition to lens material choices, different aspects of lens design need to be considered to create an optimum optical appliance for a patient, such as:Lens type (standard vision, bifocals, trifocals, progressives, degressives, anti fatigue, etc), viewing distance (affects selection of best form curve), use of lens (particularly progressives°ressives - how they’re used by the patient affects the lens design, office work, computer, driving, sport all need to be considered to select a lens design from the thousands of options available), colour (fixed tint, colour changing(which colour? Inside car ?) polarised, visual stress), coatings (single coating [rare], multi-layer [general broad-spectrum, colour bias [eg *Blue protect]), and of course fitting position in frame. This doesn’t account for the frame selection process which needs to take account of any limiting process from prescription power - it’s a huge amount of information that needs to be considered and drawn together for the patients benefit- this gives a taster to why the training for an optician takes a BSc and practice experience (Dispensing optician in the UK - separate tier of contact lens trained optician also available- these are Dispensing opticians with additional specialist contact lens training (typically an additional 2 years to complete)), it should also be noted that the term ophthalmic optician has not been recognised in the UK since the late 1980s from which time all ophthalmic optician training courses changed to train optometrists to better reflect the changing needs of UK eye care.*Blue protect type coatings: important to note that these are anti reflection coatings designed to minimise the scatter and reflection of light from short wavelength light sources (ironically they let more blue light through the lens than other coatings) which has been thought to contribute to fatigue when working on computers or when experiencing bright lights typically found in newer cars when driving. What these don’t do is “protect” the eyes from “harmful” blue light (worth noting that there is no satisfactory evidence to demonstrate that blue light causes harm ) and reduce future eye disease. This view originated from deceptive marketing from some lens producers and has gained widespread appeal (helped along by ignorance by some clinicians).
What is the future of war?
The next twenty years are going to showcase some of the most monstrously terrifying while holistically awe-inspiring feats of engineering in the history of warfare.To set the scene, imagine a time in the not so distant future. A despotic regime in the Horn of Africa is growing wealthy as their people toil though life in comparatively medieval conditions. A once nameless local warlord has grown to become a regional threat, disturbing the balance of power and trade from Central Africa to the waters on the far end of the Indian Ocean. He is backed by powerful Eastern allies caring enough for his nation's mineral wealth to ignore his history of human rights violations to the neighboring peoples who have fallen under his shadow. Emboldened by the regime's newly acquired military hardware, the dictator invades his neighbor to the South.AirSatellite imaging has shown diplomatic initiatives to prevent the invasion have failed. The dictator has already started his attack. Ground forces have crossed the border simultaneously with a series of air strikes. Armed with next generation aircraft, they are an imposing threat to dated military of their targets. As the air raid sirens blow, they scramble to arm and launch their small force of outdated warplanes built more than 40 years ago. In previous wars these planes were considered to be invincible, but today many of the pilots wonder if they now are little more than their own glorified coffins.Elsewhere, on a base in the the Arabian Sea the order has been given to launch a squadron of hypersonic fighter drones.Son of the BlackbirdEnvisioned as an unmanned aircraft, the SR-72 would fly at speeds up to Mach 6, or six times the speed of sound. At this speed, the aircraft would be so fast, an adversary would have no time to react or hide.“Hypersonic aircraft, coupled with hypersonic missiles, could penetrate denied airspace and strike at nearly any location across a continent in less than an hour,” said Brad Leland, Lockheed Martin program manager, Hypersonics. “Speed is the next aviation advancement to counter emerging threats in the next several decades. The technology would be a game-changer in theater, similar to how stealth is changing the battlespace today.”A hypersonic plane does not have to be an expensive, distant possibility. In fact, an SR-72 could be operational by 2030. For the past several years, Lockheed Martin Skunk Works® has been working with Aerojet Rocketdyne to develop a method to integrate an off-the-shelf turbine with a supersonic combustion ramjet air breathing jet engine to power the aircraft from standstill to Mach 6. The result is the SR-72 that Aviation Week has dubbed “son of Blackbird,” and integrated engine and airframe that is optimized at the system level for high performance and affordability."Meet the SR-72" - Lockheed Martin Press ReleaseAs the drones take off a nervous international film crew in a hotel more than 3200 km away prepare for the impending attack. As the minutes tick by a lucky cameraman on the balcony spots the enemy's planes in the distance. The tiny specs of silver grows ever more dangerous in the sky as four squadrons of enemy fighters become visible. Twenty six minutes after the invasion began the warplanes are now visible to the capitol city. As their profile becomes clearer the camera captures something its operator can't even see. He sees the jets in the distance and then a flash of light and smoke - first the lead plane followed soon after by all of the other fifteen in his formation. He thinks that they have fired their missiles, but then sees in the distance through his camera's zoom the puffs of smoke were actually explosions in the sky. Sixteen white clouds were showering debris on the city outskirts. A few moments later the city is rocked by a violent tremor and the deafening roar of a thousand screaming lions as windows throughout the city shatter and fall to the ground. No enemy planes are anywhere to be seen as the clouds of fallen invaders dissipates into nothingness. A few minutes later a second boom can be heard, this time much more faint. As its echoes fade the sirens are quieted and silence is all that is heard throughout the city.CyberspaceThe dictator sat at the head of a granite top table in the situation room of the jewel of his domain, the Republican Guard Headquarters Building with his most accomplished and senior staff to either side. They looked above the massive table to monitors on the far wall. As their forward strike fighters continued on their doomed mission, little did these leaders know that an enemy agent had already infiltrated the deepest recesses of their most guarded strongholds, and in fact, that very room. As they gleefully watched their monitors in the situation room, expecting to see the results of a stunning victory, the room abruptly went dark. Sudden night fell on the leadership with the deafening silence of the sudden halting of every light, screen, computer, and air vent in the building. The after image of the screens in the pitch blackness of the room was the only thing the dictator and his Generals could see. As the dim green square in their vision faded, fear and confusion took over when they realize that they are cut off from their information of the battlefield and their command over it."United States Cyber Command (USCYBERCOM) plans, coordinates, integrates, synchronizes and conducts activities to: direct the operations and defense of specified Department of Defense information networks and; prepare to, and when directed, conduct full spectrum military cyberspace operations in order to enable actions in all domains, ensure US/Allied freedom of action in cyberspace and deny the same to our adversaries."Stuxnet is a computer worm that was discovered in June 2010. It was designed to attack industrial Programmable Logic Controllers or PLCs. PLCs allow the automation of electromechanical processes such as those used to control machinery on factory assembly lines, amusement rides, or (most infamously) centrifuges for separating nuclear material. Exploiting four zero-day flaws, Stuxnet functions by targeting machines using the Microsoft Windows operating system and networks, then seeking out Siemens Step7 software. Stuxnet reportedly compromised Iranian PLCs, collecting information on industrial systems and causing the fast-spinning centrifuges to tear themselves apart. Stuxnet reportedly ruined almost one-fifth of Iran's nuclear centrifuges. Stuxnet has three modules: a worm that executes all routines related to the main payload of the attack; a link file that automatically executes the propagated copies of the worm; and a rootkit component responsible for hiding all malicious files and processes, preventing detection of the presence of Stuxnet. Israel, through Unit 8200, has been speculated to be the country behind Stuxnet in many media reports and by experts such as Richard A. Falkenrath, former Senior Director for Policy and Plans within the U.S. Office of Homeland Security.The helpless dictator and his highest ranking officials clumsily scurry and stumble amid the confusion and chaos of the situation room. Groping in the darkness one finally reaches the door, opening to reveal a likewise dimmed out hallway, stirring with frightened secretaries and officials. So deep in the building was the central administration section of the Republican Guard Headquarters that natural light from the outside had no chance of reaching them. The first few minutes ticked away as they fingered their ways down the hall, led by the soft glow of lighters in their pockets and the few flashlights that had been found in the office. The dictator's security team stormed the room as they grabbed their leader to take him to his secure command center. The Generals, now left behind, guided themselves to a point of light at the end of the hall. An exit sign was visible at the end of a hall above a door, natural light peeking out from around its perimeter. They opened the door to the blinding light of the setting sun.As they regained themselves, they looked out over the balcony of the building. They could see their dictator being rushed into a car and it screaming into the street. Within the car the dictator desperately tried to regain control of his country. He and his closest secretaries pulled their phones from their pockets to realize all the devices were now dead. All communication lines had been lost. One of them screamed out to destroy their phones since they may be being tracked. Frustrated, he threw his phone to floorboard and stomped it with his foot, followed by all the rest. As his car made its way down the momentous parade route of the Ministry of Defenses's new complex of buildings he saw that none was lit as it should be at this hour. Each had gone dark. In the distance he could see only the dark silhouettes of the National Palace and the Headquarters of the National Police, contrasted greatly by the bright lights in full illumination of the city behind them. Behind him he saw his grand Republican Guard building, now just a shadow, backlit by the rising of the full moon.He could never have known that days before a secret agent had slipped deep into nation's defense system. It had arrived when he had made one of his grand propaganda broadcast in the days and weeks leading up to today's attack. After a digitally broadcast display of his army on parade he gave a speech, invigorating his populace. After the grandiose display a commercial was broadcast telling his citizens of a news application where they could learn more about their great leader's plan to empower the people of their nation. A link was displayed on the screen where his citizens were asked to download the free news and information source. Tens of thousands of his people did as they were instructed. Had he only known that the program they downloaded was not the one he had provided. Unbeknownst to anyone, they were redirected through a series of proxies to a new program, one similar in every way, from look to functionality to the one the dictator had mentioned... that is, except for major difference. Embedded in the program was a new process. This additional program tracked the information of everyone who downloaded it. From a base far away, an information network was being created with the ID's, contacts, messaging identifiers, locations, bank account activity, medical history and locations of thousands of different users. Subtle messages were being generated and sporadically sent out across all user's social media and email accounts. Faithful believe in the words of their friends, family and coworkers endorsement of the very real, well-known and verified national news source encouraged millions of people to download the application. This truly viral media campaign had, in fact, been among the nation's most successful advertising campaigns. His national secretaries believed the great success was due to the people's great faith in the dictator and his dream for their nation. In days building up to right now, a virtual map of all the most influential systems and people had been developed automatically by the intrusive worm. Information on millions of his people was now accessible, most importantly many of his top aides, officials and officers. Entrances had been created into the most important networks in his country, from his military networks, the national banking system, his secret police force and intelligence networks and even into the power and sewer grids. As darkness fell over his city, a shadow that had loomed in his presence began to rise.His car made its way to his secure bunker deep within the Ministry of Defense's Complex in the capital. Helplessly he looked out his window when his car came to a stop. He screamed at the driver for an explanation of the delay when he looked ahead to see the streets ahead in hopeless gridlock. As the lights when dark in the Ministry, so did the traffic lights throughout the entire city. Now there was nothing directing the millions of people heading home from work on what seemed like a normal day. It was the only civilian system affected, yet it left the entire city and all its people in a complete standstill. As he looked out he saw the line of cars clustered before him and the growing congestion building behind him. He was trapped and completely vulnerable. Most were just normal commuters but now many were desperate government officials fleeing the Ministry. Realizing the danger he was in, his security team opened his car door and rushed him out of the vehicle. They would have to make the rest of the three mile trip on foot.He wouldn't reach his destination though. Among his entourage was the driver of his vehicle and his personal confidant. Not realizing the danger it posed, he had never thought to destroy his phone. Though the device appeared to be broken and disabled, as he discovered when attempting to reach Central Command, a message was still being sent.........."9°00'49.2"N, 38°45'44.9"E"..."Heading North by Northwest"..."3.2 meters per second"...SpaceAn overland invasion force has yet to receive word of their forward air strike's failure and the collapse of the Ministry of Defense in the capital. They view the radio blackout as a temporary interruption and continue on their mission as ordered until command can come back online. Formations of tank and troop carriers storm in through the African savanna. They can be seen nearing a local village by villagers high in the mountains. The dust their convoy column has risen is visible for miles. As the village comes in sight from the top of the hill, their column reforms and goes offroad. Spread out across the valley they loom upon the frightened villagers.High in orbit above the continent a satellite shifts into position.Project Thor is an idea for a weapons system that launches kinetic projectiles from Earth orbit to damage targets on the ground. Jerry Pournelle originated the concept while working in operations research at Boeing in the 1950s before becoming a science-fiction writer. The most described system is "an orbiting tungsten telephone pole with small fins and a computer in the back for guidance". The weapon can be down-scaled, an orbiting "crowbar" rather than a pole. The system described in the 2003 United States Air Force (USAF) report was that of 20-foot-long (6.1 m), 1-foot-diameter (0.30 m) tungsten rods, that are satellite controlled, and have global strike capability, with impact speeds of Mach 10.The time between deorbiting and impact would only be a few minutes, and depending on the orbits and positions in the orbits, the system would have a world-wide range. There is no requirement to deploy missiles, aircraft or other vehicles. Although the SALT II (1979) prohibited the deployment of orbital weapons of mass destruction, it did not prohibit the deployment of conventional weapons. The system is prohibited by neither the Outer Space Treaty nor the Anti-Ballistic Missile Treaty.The idea is that the weapon would inflict damage because it moves at orbital velocities, at least 9 kilometers per second. Smaller weapons can deliver measured amounts of energy as small as a 225 kg conventional bomb. Some systems are quoted as having the yield of a small tactical nuclear bomb.In the case of the system mentioned in the 2003 USAF report above, a 6.1 m × 0.3 m tungsten cylinder impacting at Mach 10 has a kinetic energy equivalent to approximately 11.5 tons of TNT (or 7.2 tons of dynamite). The mass of such a cylinder is itself greater than 9 tons, so it is clear that the practical applications of such a system are limited to those situations where its other characteristics provide a decisive advantage. Some other sources suggest a speed of 36,000 ft/s (11,000 m/s), which for the aforementioned rod would amount to a kinetic energy equivalent to 120 tons of TNT or 0.12 kt. With 6-8 satellites on a given orbit, a target could be hit within < 12–15 minutes from any given time, less than half the time taken by an ICBM and without the warning.As the raid nears the city, frightened villagers look back to their assailants. As they do they see a series of streaks dart across the sky. The momentary points of light rain havoc upon the enemy vehicles. Tanks are flattened and thrown across the landscape as troop vehicles disintegrate in plumes of dust. As they watch with awe three more flashes of light steak across the sky. They collide the Earth with a massive eruption of violence and astonished bewilderment. With fear and amazement, massive dust clouds rise from the impact sights as each eject a wave of force emanating from their points of impact. The waves spreads across the plain, felling trees and kicking up the grasses. The waves continue on towards the village, first one, then another and then another. They are knocked from their feet and look back on the blast. The area is nothing more than a massive cloud of dust which is now settling everywhere around them. Their attackers are all gone. SeaCombating a rise in piracy within their maritime jurisdictions, various world governments have adapted to be responsive with faster, lighter navies armed with fleets of advanced new ships combining stealth capabilities with high fire power armaments and speeds outmatching their agile rivals.As the regime begins to breakdown in Africa weapons and soldiers flow out and join up with local pirate factions looting shipping lanes across the Indian ocean. Little did one ship know, that it was already being closely followed by the US Navy's next generation of naval weapons.The littoral combat ship (LCS) is a class of relatively small surface vessels intended for operations in the littoral zone (close to shore) by the United States Navy. It was "envisioned to be a networked, agile, stealthy surface combatant capable of defeating anti-access and asymmetric threats in the littorals."The Freedom class and the Independence class are the first two variants of LCS by the U.S. Navy. LCS designs are slightly smaller than the U.S. Navy's guided missile frigates, and have been likened to corvettes of other navies. However, the LCS designs add the capabilities of a small assault transport with a flight deck and hangar large enough to base two SH-60B/F or MH-60R/S Seahawk helicopters, the capability to recover and launch small boats from a stern ramp, and enough cargo volume and payload to deliver a small assault force with fighting vehicles to a roll-on/roll-off port facility. The standard armament for the LCS are Mk 110 57 mm guns and Rolling Airframe Missiles. It will also be able to launch autonomous air, surface, and underwater vehicles. Although the LCS designs offer less air defense and surface-to-surface capabilities than comparable destroyers, the LCS concept emphasizes speed, flexible mission module space and a shallow draft.The concept behind the littoral combat ship, as described by former Secretary of the Navy Gordon R. England, is to "create a small, fast, maneuverable and relatively inexpensive member of the DD(X) family of ships." The ship is easy to reconfigure for different roles, including anti-submarine warfare, mine countermeasures, anti-surface warfare, intelligence, surveillance and reconnaissance, homeland defense, maritime intercept, special operations, and logistics. Due to its modular design, the LCS will be able to replace slower, more specialized ships such as minesweepers and larger assault ships.The pirates are occupied hunting down civilian traffic in the area... to busy to notice the ship rapidly gaining on them. Traveling at more than 50 knots these next generation littoral ship is one of the fastest vessels in existence. In little time at all it has closed with the pirate's ship. Desperate to evade, the pirates attempt to flee. Wishing to avoid a confrontation the Captain issues an edict for the ship to shut off it's engines using its latest version of the Long Range Acoustic Device in twelve of the major languages of the region. Fearing capture and acting in desperation the pirates turned their boat towards the US Navy ships. It was clear that they were attempting to ram the vessel. Warning shots were fired from the 110 cannons across the enemy bow. The ship continued to close. The cannons were zeroed on the ship and with the Captain's command the ship was torn to shreds by successive bursts of the overwhelming cruiser.A life raft was spotted behind the wreckage. The XO informed the Captain that it appeared they had jumped ship hoping that the ramming would sink the LCS. If the pirates were able to get back home having captures a video sinking the US Navy ship they could become wealthy men for the bounties that circulated among the area's various black market cartels. Today, however, they wouldn't be so fortunate and tonight they would be spending the night in the ship's brig. This was the second such arrest this week by the fleet with another seven expected before the end of the month. MedicineCorporal "Cy" Fannon is augmented with an artificial eye and hand after losing his in Venezuela. The "Cy" stands either for cyborg or cyclops. No one really knows which and no one is brave enough to ask. He's quiet, but when he looks at you with that creepy as hell robot eye, you'll do whatever he asks just to get him to stop eyeballin' you.After Venezuela, Fannon was given the opportunity to be med-sepped with full medical benefits from the VA. He was also presented with the opportunity to prototype some new of the DARPA tech ready for the field. He took the road of fool hardy and stayed in to be a human guinea pig for some robomed company's hopes of creating the future of robot warriors to put the rest of us out of a job.Futurists and researchers in prosthetic technology say that nearly everything depicted in [science fiction] films is possible; indeed, current advances in robotics, neuroscience, and microelectronics are bringing the visions of science fiction closer to reality every year. Over the next two decades, scientists expect to introduce bionic appendages that respond to thoughts, and chips implanted in the brain with the potential to download data directly into human memory banks.Devices including "neuroprosthetic" limbs for paralyzed people and "neurorobots" controlled by brain signals from human operators could be the ultimate applications of brain-machine interface technologies developed under a $26 million contract to Duke University sponsored by the Defense Advanced Research Projects Agency (DARPA). The contract is part of DARPA's Brain-Machine Interfaces Program (http://www.darpa.mil/dso/thrust/sp/bmi.htm), which seeks to develop new technologies for augmenting human performance by accessing the brain in real time and integrating the information into external devices.His first major augmentation was his neural unit installed into his skull. You can see the scar under his high reg, but it's not like the brick they've been installing in amputees for the past decade. Even if they don't have to move their arms and legs like robots anymore, half of them would fall over from the stupid giant controller unit. I don't even know how they sleep. Cy's got it all on the inside. I really don't know that all works. What powers the damn thing? Half of us wonder if the thing is fryin' his brain or something, either with microwave transmissions or just because he has a stinking computer console in his grape, but as long as he doesn't short circuit, I guess he's fine.Next, he got his arm. They've really perfected the art form with arms like his. Honestly, I didn't even know he had the thing until we went out to the bar one day back in San Diego. He crushed a beer can into a marble. I thought I was going to piss myself. It wasn't until he pulled off a flesh panel to show the gears, wires, and techogizzitry that I realized he had the prosthetic limb. It was all Star Wars or something. It's honestly a bit of an advantage. I know you're not supposed to say that a dude who got his hand blown off has an advantage, but as long as he keeps his arm still he always quals expert at the range and has the grip of a bear. Ok, he has to oil himself like some sort of freaky Marine Corps version of the Tin Man, but still I kind of wonder if he is better off with the robot arm.Lastly, and most obviously, is his freaky robot eye. He didn't take the natural ones. No, he went full Terminator. It's an on board camera with multiple sensors that far outperform us "norms". He can see with that thing far beyond normal people. He can focus the thing to full zoom at better than 20/1 vision, more than 20 times farther than any of the rest of us. What'll really freak you out is that he can see in infrared and night vision. It isn't as good as the installed unit of helmets, but he can see heat, which is so freaky. I don't really know what one would do with all that, but I suppose it's nice that he always knows which beer is coldest. I guess that is a good trade off. What's probably the most important though is that he can record everything. At night he'll go through and plug this cable into the port of his eye, review and upload all the important stuff he saw that day. I kind of wonder what he does with it. Makes me really worried to change in front of the guy, but oh well. His depth perception is still off though. When he is letting the system idle with the range finder off, Sergeant has fun throwin' stuff at him, knowin' that he has no hope of reacting correctly. In a way it helps us remember that he has vulnerabilities and isn't some sort of ubermensch gearing up to lead the robots in their take over of Earth. Diagnosed with retinitis pigmentosa as a teenager, Pontz has been almost completely blind for years. Now, thanks to a high-tech procedure that involved the surgical implantation of a “bionic eye,” he’s regained enough of his eyesight to catch small glimpses of his wife, grandson and cat.The artificial implant in Pontz’s left eye is part of a system developed by Second Sight that includes a small video camera and transmitter housed in a pair of glasses. Images from the camera are converted into a series of electrical pulses that are transmitted wirelessly to an array of electrodes on the surface of the retina. The pulses stimulate the retina’s remaining healthy cells, causing them to relay the signal to the optic nerve. The visual information then moves to the brain, where it is translated into patterns of light that can be recognized and interpreted, allowing the patient to regain some visual function.In any case, Corporal Cy is one messed up freak, but he is a crazy good Marine. He's specialized in ways the rest of us couldn't compete with. He is special and a great asset to the squad. He's unique in the Corps and all his augments make him perfect for his role with the team... as the squad's field operator.LandIn a valley to the South of the recently created Camp Mēga a pack of autonomous robots maneuvers through the valley. They are delivering supplies to the recently activated forward operations base. The four robots run in line through the dry river beds and plains, navigating the rocky feet of mountain cliffs. These are the GammaDogs, the latest's version of transportation vehicles built by the robotics firm Boston Dynamics, a subsidiary of SoftBank. They make thousands of these runs delivering the gear and equipment across the thousands of miles of terrain in the scope of military operations. They deliver everything from gear and equipment to medical supplies and food for the local villages and even care packages from home. They also have specialized combat variants which support the front line patrols by carrying packs and heavy ordinance of the troops in the field. When on their own, each time they make the journey it is a new one, so that their patterns are never discovered by enemy insurgent forces.BigDog is funded by the Defense Advanced Research Projects Agency (DARPA) in the hopes that it will be able to serve as a robotic pack mule to accompany soldiers in terrain too rough for conventional vehicles. Instead of wheels or treads, BigDog uses four legs for movement, allowing it to move across surfaces that would defeat wheels. The legs contain a variety of sensors, including joint position and ground contact. BigDog also features a laser gyroscope and a stereo vision system.Built onto the actuators are sensors for joint position and force, and movement is ultimately controlled through an onboard computer which manages the sensors. Approximately 50 sensors are located on BigDog. These measure the attitude and acceleration of the body, motion and force of joint actuators as well as engine speed, temperature and hydraulic pressure inside the robot's internal engine. Low-level control, such as position and force of the joints, and high-level control such as velocity and altitude during locomotion, are both controlled through the onboard computer.On March 18, 2008, Boston Dynamics released video footage of a new generation of BigDog known as AlphaDog. The footage shows BigDog's ability to walk on icy terrain and recover its balance when kicked from the side. The refined equivalent has been designed by Boston Dynamics to exceed the BigDog in terms of capabilities and use to dismounted soldiers. In February 2012, with further DARPA support, the militarized Legged Squad Support System (LS3) variant of BigDog demonstrated its capabilities during a hike over tough terrain.Starting in the summer of 2012, DARPA planned to complete the overall development of the system and refine its key capabilities in 18 months, ensuring its worth to dismounted warfighters before it is rolled out to squads operating in theatre. BigDog must be able to demonstrate its ability to complete a 20 mi (32 km) trek within 24 hours without refuelling while carrying a load of 400 lb (180 kg), whereas a refinement of its vision sensors will also be conducted.From one of these cliffs a shepherd watches with amazement. These must have been the "mule cars" he had heard spoken of at the market the last time he visited the village. Now he could see them in his valley. He marveled how at times they reminded him of the bison stampeding as they maneuvered through the valley below. Only these bisons moved too perfectly. Every action was with intent and with purpose. In a perfect line they leaped, bound, climbed and ran faster than he could believe possible of a machine. The small train of robots continued without pause where there was no road nor trail, leaving only puffs of smoke where their feet impacted the dry earth. Wanting to show his friends and family the wonder he saw today, he pulled out the phone from his pocket to capture the moment. IntelligenceAbove surveillance drones escort the train of GammaDog transport vehicles. They're armed with a battery of cameras and other detection equipment, able to see in 3D and infrared detection. Sonar systems allow them to make three dimensional maps of the area for battlefield planners. This latest model can fly in two modes, as a glider for endurance surveying or flapping its wings as a bird or, more precisely, as a bat. These bats measure just two feet in length. They are capable of surveillance silently from several hundred feet above the target to perching indiscriminately on the ledge of any building. It's powered through a solar membrane on its wings providing hours of additional flight time after the battery would have run dry. The COM-BATs are equipped with networking capabilities to share view points across multiple angles and a wide area. They communicate everything in real time to operators or higher level intelligence programs. Traveling in flights groups of four or more, they provide numerous layers of immediate information to troops in the field, war planners, and battlefield observers.Scientists at the University of Michigan College of Engineering are developing a six-inch robotic spy plane, modeled after a bat. Colloquially known as the COM-BAT program its purpose is gathering data such as sights, sounds, and smells in urban combat zones and transmitting the information back to combatants in real time. A $10 million grant was given for this project, which is being developed in the Center for Objective Microelectronics and Biomimetic Advanced Technology. The robotic bat is planned to perform short-term surveillance missions supporting advancing troops in the battlefield. It could perch at a street corner and send data regarding its immediate surroundings, or could land on a building for longer surveillance assignments. Real-time reports of its activity will constantly be sent to the commanding unit.The University of Michigan researchers are focusing on the microelectronics. They will develop sensors, communication tools, and batteries for the new “Bat” micro-aerial vehicle. Engineers envision tiny cameras for stereo vision, an array of mini microphones that could home in on sounds from different directions, and small detectors for nuclear radiation and poisonous gases. The robotic bat will also have the ability to navigate at night, using low-power miniaturized radar and a very sensitive navigation system. Its lithium battery will recharge using solar energy, wind, and vibrations, and the bat will communicate with the troops using radio signals.The robot’s body is designed to be about six inches long and to weigh about a quarter of a pound. Its expected energy consumption will be 1W. They will work to develop quantum dot solar cells that double the efficiency of current solar cells. Furthermore, they expect their autonomous navigation system, which would allow the robot to direct its own movements, to be 1,000 times smaller and more energy efficient than systems in use today. If the planned improvements will indeed be successful, the researchers believe they will provide the bat with a communication system ten times smaller, lighter and more energy efficient than currently available systems.Today, one of the tiny planes has spotted something through its on board infrared camera. There is a man on the ledge above the pass. One of the BATS leaves the group of escorts to investigate. With his cameras the plane circles above the unsuspecting man. The plane relays images to a remote operations intelligence server. The server's image recognition software sees that the target is a military aged male. He has with him an AK-47, though this is common in such a dangerous country. However now the man has pulled from his pocket a device the program recognizes from its database to be one of the old phones of a few decades ago. The system analyzes the angular projection and determines that this man could have attempting to capture images from the mule team down below. The event is flagged "Orange".The Orange rating triggers the server to initiate a series of queries to determine more information on the target. The GPS location was cross-referenced with the country's land listings and it was found that the land was leased to a family by their patriarch Solomon Selassie. Another query to the nation's record office of public health pulled a birth certificate and health care history information. That information indicated Solomon to be too old to be the man seen in the recording, however, Solomon had a son, Yared. Yared's age and medical information matched the apparent height and age of the target. Further investigation of his record showed school records with photos. Facial recognition with aging calculated a high probability that the target in question was indeed Yared Selassie. A search for information on Yared connected the search program to his account with the local phone company service provider. A data package had indeed just been sent from Yared's device to another device in Yared's network.Fortunately for Yared, he had no known background with the now displaced regime. He also had no criminal record and was not connected with any known agents of the regime in the last 10 years. His ID had not been one of those gathered during the initial cyber infiltration a few weeks ago so no logs of him existed yet in the military's watch list, which indicated that he had little contact with the rest of the world and with the regime at all. By all known accounts, the program results seemed to indicate that he was indeed a peaceful shepherd farmer living deep in the African savanna. The event would be logged as Yellow for cautionary and suspicious activity. He would have an identity file created under the database where his information would be easily accessible and the event would be called any time in the future if Yared may come into investigation. Any future suspicious actions by him would likely result in his apprehension.His GPS location was also flagged Yellow. In the event of future activity there, Yared would likely be a source of information if not also suspect. The Selassie home was also flagged White - for informational - along with the rest of the family and known contacts of Yared. If Yared were to ever become considered dangerous, they would be considered sources of potential information or potential accomplices and the house would be watched. Today, however, Yared was not in danger of arrest. Logs were created in all the relevant databases and a report was generated on Yared, the location and infraction in question. The report would be delivered to the Provisional Constable's email. The entire process up to this point had been automated and no human would have any knowledge of the event until the Constable read his email. It would be one of a few dozen he would receive that week. He would probably forward this one on to one of his deputies and in a few weeks the deputy would dispatch an officer with security detachment to investigate the Selassie house. They would discover the reason for taking the photo and if everything was determined to be all clear the family would be advised not to take any more photos of military equipment again. The family would be scanned with the Biometric Automated Toolset. Their photos, fingerprints, DNA and numerous other identifiers would be logged to their identifying files. After that the Selassie family's life would go back to normal, though a new mountain of information on them would be readily available for intelligence agencies and perhaps more dangerously, the new regime to come once the Americans left.As the report was generated and sent to the Constable, the BAT was directed to call off its surveillance of Yared and return to escorting the transports. Yared watched the train move out of the valley completely unaware of what had transpired. He returned his phone to his pocket, gathered his things and moved his small flock down the mountain back towards his home.Light InfantryCommand is nervous following an up-tic in civilian protests throughout the region. Numerous activist groups are coming out as they attempt of built something resembling a government to replace the shattered regime. Most are harmless and benevolent. Many want to bring about real change for the region and are anxiously seeking to take advantage of their first real chance at leadership roles in more than a decade. Others, however, push for more dangerous agendas. Remnant forces still vie for power, sometimes through democratic means and other times in the form of a new brewing insurgency. Many of the old leadership in the defunct regime escaped overseas and are now channeling money, and propaganda into the country. Enough of the old regime's officers saw the coming storm and saw to it that stockpiles of weapons and ammunition mysteriously disappeared prior to our arrival. Now, many of those weapons, along with thousands more are being smuggled in through the unregulated black market, and are finding their way to the quickly organizing insurgency forces.That's where we come in. We are Marines expeditionary rifle squad of the 31st Marine Expeditionary Unit, 2nd Battalion 5th Marines. We were stationed in the area to ensure that stability is maintained while a constitution is drafted. The squad's marching orders were to conduct an unmounted patrol through the city. Tensions are high since there is currently a massive rally taking place all along the parade route of the old Ministry of Defense's complex. The streets of the complex are crowded with tens of thousands of people. Marine platoons are on patrol in the event that this peaceful rally turns into something far worse. You'd probably have guessed that by now all military activity would have been replaced by all the drones flyin' around, but history has shown us that some jobs, just like these, you just can't trust a rumba to replace boots on the ground. Not that they haven't tried, but after the mess in 2022, they realized the only real future was one that married the drones with infantry into a holistic combat unit. So that explains why there are still morons like me trudging around in places like this.Marine Expeditionary Rifle SquadPurpose: Significantly increase future Marine Air Ground Task Force (MAGTF) ability to conduct squad level combat operations in an uncertain environment across the ROMO for the Joint Force. Improved ability to operate in both traditional and irregular warfare environments while retaining the ability to conduct forcible entry operations from the sea.Attributesgreater lethalityaccurate identification and classification of targetsunencumbered mobilitysecure, reliable, MAGTF- integrated command and controlballistic and fragmentation protectionclimate and terrain protectionability to administer low level medical aidimproved training and leadershipProvide greater improvement to the current rifle squad’s ability as a total package to engage the enemy across a wider range of operations with an increase in survivability and better access to support forces.- LtCol Chris Woodburn, USMCThe squad was composed of the ten of us, nine Marines and a doc in two fire teams and the Staff Sergeant.Our fire team leaders are Sergeant Nguyen and Corporal Piers. They each carry an M-35 Infantry Automatic Rifle attached with M-207 grenade launchers. For the 207, they carry an assortment of goodies they can launch depending on the mission requirements. For today, they are armed with tear gas, flares, and one grenade that can be fired above, through a window or into a dark alley, bursts open and out pops a tiny little drone cam to check out what overhead drones might miss. They also have regular explosive varieties and incendiaries, but today is just supposed to be a routine patrol. More important than their armaments, they're also equipped with networked Tee-Cud helmets. Tee-Cuds are the common name for the Tactical Command Heads Up Display integrated combat helmet systems. They are complete helmet systems with a ballistic visor that covers their entire face. Inside is a broad spectrum networking node that communicates information to and from the higher ups. This feeds into a heads up display that projects an augmented reality layer over everything they see. Team members, allies, non-combatants and enemies are highlighted with a colored filter to seek to avoid identity confusion in the heat of battle. They also have combat relevant data on each of the members of their team from ammunition count to a 3D geographic mapping projection complete with possible fields of fire. The Tee-Cuds run off of the Layar based MZ Scout Systems. Scout is an augmented reality browser and AI that coordinates all the networked visual data. The entire system is voice activated, sensitive enough to a whisper, so different commands will initiate different actions from Scout. Each Marine goes through a certification week where they have to speak a ton of random lines and sentences to create a unique voice ID and only the ID's on the team can operate the system. The team leaders can say "Squad" which will temporarily open a channel with their squad. "View..." can open any viewpoint from different squad members to overhead observation or strike drones, as well as other personnel within the area of operations. Saying, "Command" or the command's designation can open a direct channel with command headquarters for requests of information, backup or to send out a nine line request. The Tee-Cuds give the team leaders an unmatched view of the battlespace and their own team's condition warfighters of only a few decades prior would have died to get their hands on.Next, there are the SAW gunners. SAW stands for Squad Automatic Weapon, which used to be the name of an old weapon system the position used to use, but being that they even today they can somewhat reliably cut whatever they want to in half, the name stuck. That said, they are armed with M3, the largest non-crew served weapon in the Corps' history. The M3 is the automatic machine gun currently used for squad suppression fire. Depending on the situation, the M3 can fire a belt of high velocity rounds, or high mass yield rounds for heavy impact. In the semi-automatic setting it can fire a kinetic impact round that can punch through walls from six hundred yards. The gunners themselves would never be able to lift the damn thing, though, if it weren't for the exoskeleton assist. With the rigging the SAW gunners can carry a load of over 400 lbs for six hours and never break a sweat. SAW gunners, as well as the other members not equipped with Tee-Cuds, wear Scouters. Scouters are units that attach into the helmets over one ear and have a small ballistic visor that completely covers one eye. The Scouters operate on the same Layar based Scout system. It can project limited amounts of information in the same way as the Tee-Cuds on the ballistic lens, but with less detail and scope. It is also voice activated and the commands are all the same. The only difference between the leadership level Tee-Cuds and the scouters is that the scouters don't come with the full heads up display and can be worn separately without the helmet. After the SAW gunners are the assistant light machine gunners. The A-gunners assist the the SAWs. They provide direct fire back-up and can provide emergency assistance to the SAW gunners' equipment in the field. They are armed with the M1300 CSASS, a compact semi-automatic sniper system rifle engineered for squad level sniper support. The weapon can deliver a variety of rounds to the enemy from sixteen hundred yards or deliver deadly fast accuracy with mid-range engagements.The newest members of the squads are designated riflemen. They are equipped with standard M-35 Infantry Automatic Rifles and extra ammo. They also carry the M-483 Light Infantry Missile System. It's a small pod you drop on the ground and arm. Once armed, the squad leader, or the operator, will designate a target and issue the command to fire. From there, the system will fire a self-guided missile about the size of two soda cans directly into the air before it directs itself to the target from above. Besides that, they are boots and if you're lucky they will only almost get you killed once a day. They're really good for getting ammo from the Heavy Dog and digging holes when you don't want to tire out the robots.Last are the field operators. In the mid to late 2020's infantry integration with drone warfare became paramount. As I mentioned before, militaries around the world realized that there are just too many things you can't do with a drone that require on the ground support to accomplish. Swarms of robot jets overhead and mini tank guns look cool in movies, but 90% of the time wars are fought by you actually walking up and asking a bystander if something jacked-up is going on that the good guys should know about. When the bean counters in Washington finally realized that a drone can't exactly prevent looting or arrest someone without having their onboard camera's kicked in by a six year old, they realized that next generation infantry integration was the way to go. With that came the field operators.Field-ops have constant command of drone escorts during patrols and missions. They are equipped with the same Tee-Cuds as the team leaders, but their systems are set up to direct the feeds of information from surveillance and attack drones overhead, paint targets as either hostile or non, coordinate battlefield intelligence with the squad and to also directly command drones in combat. They are equipped with sidearms for immediate emergency protection, but their main offensive weapons are their gloves. Hundreds of sensors in the gloves catch every subtle movement as a command to manipulate drone movement and observational capabilities. At any given moment, the Field-ops are overseeing dozens of nodes all around the battlefield. They are aware of hundreds of moving objects from people, vehicles and drones. They have as close to a complete holistic view of the battlefield as has ever been available to a frontline infantry unit. Working Field-ops is supposedly like nothing else. Even though they are right there with us, many describe their job as an out of body experience. The role used to go squad and fire team leaders, but the tsunami of data bombarding them left them unable to manage both the drones and their teams, so the tasks were delegated to the newly created unit. Their omnipotence is flushed down the toilet, though, when their focus is so deep on planes buzzing overhead that they completely lose track of where they are, trip, and fall flat on their face. Obstacle avoidance is their most requested new feature since they'll find themselves on the ground all the damn time. It's honestly a little embarrassing that they are the future of warfare. A field-ops' idea of a good day is hunkered on a rooftop or in the back of a vehicle controlling the battlefield without fear of tripping over a rock or something. They come off as clumsy and distracted, but when they get in their zone, they are the deadliest thing in the battlezone. They command the swarm and the respect of any enemy they might seek.Along with our doc, the last member of the squad is its leader, Staff Sergeant Ramirez. He's been to every major conflict in the last eleven years; Odessa, Yangong, Valencia. They say that back in the day a squad like ours would have been led by just a Sergeant or even a Corporal, but I guess with the modernization of the new Corps, this is what it takes. The Squad leader is armed identically to the Fire Team leaders. He carries the same M-35 with the 207 attachment and is equipped with the same Tee-Cuds as the others. Besides his experience, he doesn't differ greatly from the two team leaders. This was by design in case he should be incapacitated than one of them could be able to step into his role.This is the modern Marine Corps infantry unit. Two fire teams complete with leaders, SAW gunners, A-gunners and dedicated riflemen supplemented with corpsmen, Squad Leader and with the advent of the Field Operators, the eleven man Marine Expeditionary Rifle Squad was complete.We made our way down the street. Far off in the distance you could hear the sounds of the rally. Here though, all you could hear was Cpl. Fannon picking himself up off the ground again and the sound of the SAW gunner's hydraulic joints. Chatter over the inter squad channels reported the same quiet.We turned another corner into an alley. It was completely devoid of movement and deathly silent. As half the squad made their way into the alley, SSgt Ramirez turns the corner and calls for an all stop. The squad darts for cover along the alley. Fannon started a detailed scan of the area. From one view he noticed a small group of men on the next street. He could see inside a few windows and could see people shutting their windows. From one of his aerial units he noticed a window at the end of the alley with a suspicious pipe moving out of it. He flew the unit around the building to get a clearer view of the window. As his view became clearer he saw a man aiming his rifle on the squad."CONTACT FRONT! SECOND FLOOR!"Support"Contact". The term has been part of infantry training and battlefield tactics for a century. Now the word has evolved to much more. This single word initiates a mobilization of a vast movement of men and machines in a worldwide effort towards the acts of locating, closing with and eliminating the enemy through fire and maneuver.When Corporal "Cy" Fannon gave the call for Contact Front he initiated a command within MZ Scout System that forwarded the alert to seventeen other commands. These commands included Forward Operations North East Africa, the Coordinated Unmanned Asset Command, Marine Air Ground Task Force Central Command, and a myriad of other units. Alarm bells rang out and operators manning stations across the globe came online, now with all of their attention directed to a small alleyway in a small city and one particular squad of Marines. Monitors across the globe lit up with the view scopes of the Marine's Tee-Cuds. A voice came in through the NCO channel. It was a woman's voice.Corporal Piers was surprised. He was a newly promoted Corporal and unfamiliar with assaults from the NCO's point of view. He'd handled engagements before, but now the flood of information on his visor and responsibility to the Marines within his charge left him momentarily frozen. Her voice brought him back."This is the Operator. Standing by for SITREP."With her sudden call to awakening, his training kicked in. He knew of the operators and had experienced them in dozens of exercises when he was given his fire time, but he was still surprised by what he heard over his headset. Usually, everything in training is nothing like the real thing. Adrenaline and confusion are elements that are difficult to replicate in the training environments without Marines actually getting killed. Everything amps up, but this voice didn't. He knew it was their job to watch over the combat patrols and coordinate relief, reinforcements, or additional assets when need. She was calm and relaxed, like listening to the weather girl or the melodic tones of the host for some late night easy listen radio stream. She made it sound as if dropping in on Marines embraced in the heat of combat was something she did everyday. Perhaps she did. As Cpl Piers gathered himself in the midst of the chaos that was enveloping the Marines, she was calm, the collected voice of serenity reminding the Marines that they were not alone.Cpl Piers composed himself not a moment soon enough. What started as a single shooter foolish enough to get caught before the ambush, had in fact been a well orchestrated attack by more than a dozen insurgents. They had prepared the alleyway for what must have been some time in hopes of catching the Marines off guard. Such a defeat would be a massive symbolic victory for the insurgency, ushering in new recruits by the droves. As Piers and the others took up defendable locations in the alley, the scope of the danger became apparent to the Marines. Windows all along the narrow street were suddenly filled with men and metal. Bullets rained down like tears from heaven.Staff Sergeant Ramirez was already on the bounce. He knew something didn't feel right about this alley in the first place. The call for contact only confirmed what his instincts had prepared him for."Operator, this is Echo Six Romeo. Incoming SITREP..."... individual troops can look forward to the JTRS Handheld, Manpack and Small Form Fit AN/PRC-154 Rifleman radio. Developed by General Dynamics C4 Systems. Rifleman is designed to deliver networking connectivity to frontline troops in a lightweight, ruggedized, body worn device. The radio transmits voice and data simultaneously via SRW. Perhaps most importantly, Rifleman radios are capable of interfacing with smart phones.Cutting-edge wireless networking technologies, potentially capable of supporting both JTRS and smart phone devices, are now arriving in the form of mesh networks, including mobile ad hoc networks (MANETs) that can provide virtually instant high-bandwidth networking capabilities for handheld radios, ground and airborne vehicle communications and security and tactical wireless sensors. The military is increasingly turning to wireless mesh networks technology for sensor-driven environmental control, yard management, and security and tactical applications. A mesh network provides continuous asset visibility from any location in the system’s range, noted Mark Lieberman, automatic identification technology program manager for the Defense Logistics Agency, headquartered at Fort Belvoir, Va..John Edwards - Telecommunications Industry Analyst - Defense Systems[dot]comSSgt Ramirez listed relevant information in the hasty situation report. The operator, not flinching and with no obvious distress in her voice, replied back to the NCO channel,"Very well Echo Six Romeo. I've secured a roaming aerial interceptor squadron for your field operator. Echo Four Foxtrot, you should see the new units displayed on the Active Unit Window of your Tee-Cud. Do you see them?""Yes, Operator. I see them," Cpl. Fannon replied."Very well. They should be arriving in the next three minutes. Echo Six, I've opened a channel to higher command, designated "Snakepit". I've also opened a channel with the other patrol unit leaders in the city. CASEVAC has been alerted and are standing by. I'll be standing by for further assistance as needed.""Understood. Echo Six out."The squad was entrenched in the alleyway. Windows all along street slammed open to become places of cover for concealed insurgency forces, ducking away as quickly as they had appeared. They popped in and out to spray momentary bursts of fire on the Marines below, only to replaced by another in another window, and then another and another. The alley was unsecurable. The minimal cover and overhead deployment of enemy forces meant that the Marines would be chow in minutes if something wasn't done.Fannon was a bit occupied at the moment. He was the only one with a clear bird's eye view of the scene with aerial strike capabilities. His view, however, was obscured by the buildings. As he was trying to gain a clear sight on the window, a burst of rifle fire ricocheted next to his head. He ducked away in search of new cover. By the time he felt secure enough to focus on the drones, it had already moved on beyond view of the window. He would have to wait on the next one to make a pass. More rifle fire cracked as it struck the building next to him. The squad may lose its field operator if he didn't secure his most valuable asset: his life."Operator, I'm in heavy fire! I need to find cover and am requesting QRF assist!""Understood field op." She knew who had said it even though he hadn't said much by the indicator denoting which helmet made transition. "Patching in UAV Pilot Quick Reaction Force with special instructions to secure your immediate location."With a few adept keystrokes of the operator's hand, a red light lit in an installation in Colorado. A team of four pilots were already in their seats. They had been watching the feed and listening to the instructions. The operator opened a channel between them and the field op. As he scurried and dodged his way through the alley, he was relieved to see the individual units in his active asset window switch over from autonomous operation to full remote. One by one their icons switched from green to orange and faded to a translucent fuzz on the side of his display. He could now focus himself on finding a securable location for the time being. Fortunately for him, SSgt Ramirez was also aware of his desperation and had sent one of the squad's riflemen, LCpl Dodd, to secure him.As the two sought some mild semblance of safety, the drones above and all around came alive in a way not like before. Under normal operations, they circle around in simple methodically programmed patterns or hovering at points spherically encompassing the squad, waiting for the field op to call for them. Now, all of them were under the direct control of a team of remote pilots thousands of miles away.Interoperability Functional DescriptionThe ability of systems, units, or forces to provide services to and accept services from other systems, units, or forces and to make use of the services, units, or forces; and to use the services so exchanged to enable them to operate effectively together. An example for the use of this policy would be the condition achieved among communications-electronics systems or items of communications electronics equipment when information or services can be exchanged directly and satisfactorily between them and/or their users.Interoperability is integral to the continued success of missions using unmanned systems and represents a long-term objective of the Services and their stakeholders. The urgent needs in theater and corresponding rapid acquisition approach during recent years have resulted in thecurrent fleet of unmanned systems that generally do not interoperate with each other or with external systems. The combat development community is calling for interoperability as a critical element to the future unmanned systems fleet. The ability for manned and unmanned systems to share information will increase combat capability, enhance situational awareness, and improve flexibility of resources. Interoperability will improve the ability for unmanned systems to operate in synergy in the execution of assigned tasks. Properly stabilized, implemented, andmaintained, interoperability can serve as a force multiplier, improve warfighter capabilities, decrease integration timelines, simplify logistics, and reduce total ownership costs.Department of Defense - Unmanned Systems Integrated Roadmap FY2013-2038The individual birds started their maneuvers. They were each taking actions for the different specialties of each vehicle. Four target acquisition units were actively darting in and out of the building's windows seeking runaway insurgents, following them through hallways and as far as the trail would take them. When their scanners found something, other specialist operators were busy tagging each person as either friend or foe and adding an identifier so that the tracking system could keep watch as need be. Hunter strike craft pursued the insurgents relentlessly, able to dart in and out and descend from anywhere upon their targets. In the few seconds since the squad had taken fire, the alleyway had descended into a hornet's nest of firefighting from both man and machine.With the time bought by the swarm, Fannon and the other Marine were able to secure a location in the kitchen of one of the buildings along the alley. Fannon hunkered down in a back corner of the room. Dodd provided security for the two. He now posted himself along the window, regularly checking to make sure the two were safe while Cpl Fannon focused on the battle overhead.As he gained his bearing, Fannon began receiving instructions and information from the rest of the squad, along with communications from the other pilots. Now keyed back into the engagement at hand, he took control of the ships around him and began to coordinate his assets with the rest of the squad's counter offensive. He took back manual control of the remotely piloted unmanned assets as objective necessity dictated.One might wonder why Fannon would take back control at all. While the team back in CONUS was fully capable of carrying out the mission of taking down all enemies they saw with guns, explosive ordinance, and maneuver warfare, there was too much they could not know. They lacked the unit briefings on specific engagements for this particular region, since their area of operations was the entire planet as need be. They lacked a thorough understanding of the area, population centers, business centers and key hotspots and places to avoid fire. Mostly, they lacked clear communication with the entire squad. Fannon, more correctly, the Field Operator, did. What might be perceived as a design flaw was actually a well engineered aspect of the overall future of infantry warfare.They used to just have an open channel to everyone involved in the battles. The idea of a flat system of communication seemed a Utopian ideal. Any boots on the ground could speak directly with the people they needed to to get whatever assistance they would need. Anyone who might be able to help could just chime in if they thought they could be of service. On paper it is miraculous. So long as you were a part of the picture in the slightest your voice was overhead on the channel. Every command, every request, every observation, every opinion, every scream; everyone was talking and not enough were listening. It got to be a real nightmare scenario. Everyone from the General on down would be barking out conflicting orders to the troops on the ground. Debates out rules of engagement would clutter up the messages needing to be sent as terrified Marines lay frozen in forced inaction. Pilots for bombing runs and pilots for casualty evacuation were all speaking and yelling at the same time. Even engineering unit commanders would be giving his two cents on what to be be careful of so as not to blow up their precious fiber optic line more than two miles away. There might be as many as a hundred people squawking at once. And do you know who wasn't listened to at all? Why, it was that Lance Corporal Schmuckatelli on the ground, getting cut to pieces by machine gun fire in the jungle, the very Marine who started the conversation. It was a cluster.So they turned to the NCO's. The Non Commissioned Officers of the infantry squad were elevated to new levels of responsibility. Besides leading the fight, these warriors were now also the information hubs, directed to guide battlefield data and unit instructions from higher to the field troops assigned to them. At any given movement these troops may be relaying information from several different scopes and fields of view. They are now the levies holding back a paralyzing flood of information. The training necessary for their vocation puts them on par with any master level technician or specialty artisan in the world, not the least of which being the field operators. They are all career military and with their training, each holding the civilian equivalent to degrees in various fields from electrical engineering, telecommunications or logistics, they might be living easily overseeing some automated package delivery service, driverless taxi or even building the next gen automated warfare. At home they would have the life, but they chose something different. By being the channel through which all sources of information are funneled, their focused implementation of command and information allow them to direct the application of force on battlefield as if it were the strings of a marionette.Want more future of war? This answer has grown a full length novel mixing the same focus on technology and tactics while providing a character driven narrative I'm sure you will all enjoy. If you would like to check out my book inspired by this answer, The Next Warrior follow the blog The Next Warrior and follow this link to the start of the book.The Next Warrior by Jon DavisAirMeet the SR-72This Stealthy, Hypersonic Drone Could Become The Most Exotic Plane EverCyberspaceUnited States Cyber CommandStuxnetSpaceKinetic bombardmentRods From God - New York TimesU.S. Air Force Transformation Flight Plan, United States Air Force, November 2003 - http://www.au.af.mil/au/awc/awcgate/af/af_trans_flightplan_nov03.pdfSeaLittoral combat shipIndependence-class littoral combat shipMedicineNew Prosthetics Keep Amputee Soldiers on Active Duty - US NewsProsthetics in the VA: Past, Present, and FutureThe future of artificial limbsMichigan Man Among 1st In US To Get ‘Bionic Eye’ - CBS DetroitLandBigDogBigDog - The Most Advanced Rough-Terrain Robot on EarthIntelligenceBat-Inspired Spy Plane - The Future Of Things | Science and Technology of TomorrowLight InfantryHeadquarters Marine Corps - Combat Development and Integration: Marine Expeditionary Rifle SquadSupportA look at the future of mobile military communications on the battlefield -- Defense SystemsUnmanned Systems Integrated Roadmap FY2013-2038 - Page on defense.gov - Kinetic Bombardment is currently still relegated to science fiction rather than actually being planned out for the future of warfare, though it was referrenced as a possible avenue in the U.S. Air Force Transformation Flight Plan , November 2003 linked above. The idea comes with massive logistical and engineering problems that are beyond our current reach. Most importantly is that the delivery of massive tungsten rods into space would be an impossibly costly endeavor and likely be more costly than any possible advantages gained from the practice. Given the recent advancements in the private space industry, however, the idea of space born military instruments like this becomes more a possibility every day.Also, I am still unclear if such a reaction would throw out nuclear fallout. Since there is no nuclear reaction taking place I don't see it happening. Of course I have also read that fallout comes from the churning of already radioactive material below the earth's surface which I really don't get. Either way, I'm not a physicist so if you physicists who have just been yearning to teach me a lesson, please clear that up in the comments. The fate of a fictitious village rests on your shoulders. - The littoral combat ships are not actually the future of warfare. They are happening right now. The US Navy already has a fleet of these ships in deployment. My story involved an slightly exaggerated ship that is an update of the current version. The reason I didn't change the story to focus on some future super sub or next generation aircraft carrier is because of how speculative their future roles will be. What is certain is the role LCS's will play in the next several decades as an important element in ensuring peace along the world's coastal regions. That's why I wanted to focus on them, because no matter what happens, these are going to be a part of the Navy's future. - OK. The eyeball thing is pretty weird. Truth be told, I borrowed the idea from Orson Scott Card's sequel to Ender's Game, Speaker for the Dead. All this to say the character who had one was freaky too. As far as Corporal Fannon's eye, I really don't even know if it will be close to possible to fit all those technologies into such a small platform whether in the next twenty years or ever. Every day tech is improving and bionic eyes are a reality even today, but heat vision, night vision and twenty times zoom, let alone the ability to record. Well I probably stretched my creative license on that one. Maybe making a Marine into a modern day Predator was asking too much, but don't even pretend that you don't want Cpl. Cy's cyborg eye. - A lot of people may be curious why I chose to write a story surrounding a glorified pack mule, but in reality, I think this machine has a much more important role than any future weapon that we might be talking about today. More important than a new self guided rounds or a gun that shoots around corners is the logistical mastery of the field. Armies march on their stomach as it is said and the ability to deliver gear and supplies cheaply and safely will be a massive advantage from modern delivery systems. Add to this that the VA paid out about $57 billion on disability benefits last year and the most common injuries from veterans today are related to stress injuries of heavy, burdensome equipment. Given this information, it makes a lot of sense for the military to utilize a robot as a form of loss prevention on the bodies of future vets its going to provide medical care for otherwise. Finally, the ability of an autonomous system to maneuver through random routes, never taking the same one twice, illuminates the most deadly foe of the War on Terror, roadside bombs known as IED's. By avoiding the major arteries that roads are, logistical support can be delivered without the expense of air drop or helicopters. It provides an unimaginable scaling opportunity for the US military on many different fronts, providing the technology works as we all hope it does. - Yeah, the Scouters are from Dragon Ball Z. That's over 9000! Thank you Google Glass for fulfilling my childhood fantasies that didn't include Bulma. - Those of you who are sharp will have noticed another Easter Egg in this story. More than half the technologies mentioned are built of products and companies currently owned by Google.Liked this? You might also like my YouTube Channel. You can also connect with The War Elephant on Facebook. If you want to help me make more content like this, please visit my Patreon Page to find out more.