What consequences can bring a recent 2 billion dollars raise of NIH budget?

Pumping more money into the NIH without structural reform of the US biomedical research enterprise is throwing good money after bad, i.e., sheer wastefulness. Why?

• First, decades back, US biomedical research coalesced around a sweatshop structure for staffing labs.
• Second, abolition of mandatory retirement on Jan 1, 1994, means that established PIs (Principal Investigators) who joined in the 1960s and 70s aren't leaving and continue milking the system for what it's worth, at the expense of younger generations.
• Finally, 'the doubling' cemented this already unsustainable structure. 'The doubling' refers to the NIH annual budget increase of 15% for 5 consecutive years from 1998 to 2003, abruptly doubling it from $13 billion to >$27 billion over a short 5 year period. Countrywide, university labs expanded and even increased in number, and more PhDs began entering an already saturated job market. With the Great Recession kicking off in 2007, the economy just couldn't absorb the glut. Some managed to cling on as post-docs, or did multiple post-docs while others left the field altogether.

Sweatshop structure of US biomedical research labs

Biomedical research labs across the US are increasingly staffed by temporary workers, namely, poorly paid graduate students and post-doctoral fellows. In return for hands-on training in the tools of their future trade, such workers perform the nuts and bolts of US biomedical research. Training done, they move on into an already saturated job market hoping the coin toss works in their favor for a faculty position in an ever-shrinking pool, shrinking largely because increasing number of older faculty aren't retiring while US universities can't realistically expand faculty positions to absorb all the newly minted PhDs. Costs aren't in favor of doing that. Upshot is US biomedical research labs operate under conditions of constant labor turnover.

Meantime, sampling a teeming supply of ready labor that applies for biomedical PhDs from all over the world (see figure below in the middle from 1), not just the US, US universities have evolved an assembly-line approach to plug this temporary worker shortage by filling research labs with increasing numbers of PhD students and post-docs. Thus, the US has been graduating a glut of biomedical research PhDs, more than the US job market could possibly absorb.

Faculty positions are mainstays for biomedical PhDs but existing US life sciences faculty positions can't absorb them all so more and more freshly minted PhDs spend many more years in post-doctoral positions. A rarity in the 1950s and 60s, today a post-doc after a PhD is thus the norm in biomedical research (see figure below in the right from 1).

The glut of money that poured into the NIH during 'the doubling' only exacerbated this pre-existing problem, making its way into the university system who graduated ever more life science PhDs (see figure below on the left from 1) even as their ever-aging faculties hung on to their positions. Faculty expansions from this period only contributed to this problem since they were immediately followed by precipitous NIH funding declines from 2004 till date. As research funds evaporated, predictable hyper-competitiveness set in and PIs, especially less secure junior faculty, spend more of their time chasing fewer research dollars, writing and revising more grant proposals. Inevitable gap in training and mentoring slides off onto the hapless shoulders of post-docs while graduate students cover more of the undergraduate tutoring responsibilities. Underpaid, overworked labor thus undergirds the present day US biomedical research enterprise.

Government policy encourages aging of US biomedical research faculty

In 1986, the US congress passed the 1986 Age Discrimination Act. A special exemption in this Act allowed colleges and universities to enforce mandatory faculty retirement at age 70 until 1994. The US Congress allowed this exemption to expire and mandatory retirement for university faculty was abolished on January 1, 1994, just as a big chunk of faculty hired in the early 1960s approached traditional retirement. Thus, tenured US faculty have lifetime employment. Already back in 2001, Orley Ashenfelter and David Card's analysis (2) of 16000 older faculty at 104 colleges and universities across the US found

• Average retirement rates for 70 and 71 year old faculty fell from ~75 and 60%, respectively, to ~30%.
• At age 72, 70 year old faculty who continued working increased from <10% to ~50% once mandatory retirement was abolished.

More proof of aging leadership in US biomedical research enterprise? Most lucrative and consequential for biomedical research faculty, the NIH R01 grants are unmistakably aging (see figure below from 3 with numbers from 4).

• Where in 1983, 18% were awarded to < or =36 years of age, they accounted for only ~3% in 2010.
• OTOH, > or =66 years of age accounted for almost nothing in 1980 but accounted for ~7% in 2010.

Since these trends stayed unchanged during 'the doubling', giving NIH more money isn't going to change this status quo.

The US economy cannot absorb the glut in biomedical research PhDs its universities generate

If not university faculty, then at least jobs in industry should be able to absorb newly minted biomedical PhDs and post-docs, right? No, US pharma employment has stayed flat for at least 20 years (see figure below from 5).

The $2 billion increase is thus meaningless for two reasons,

• If it remains a one-off. Since 2016 is presidential election season, all bets are off on what the future portends.
• Inflationary losses since 2003, when NIH budgets flattened or reduced, means that this increase merely takes funding back to 2003 levels. This is because a dollar's worth of research in 2003 would have cost $1.44 in 2015 (see figure below from 6), according to Federation of American Societies for Experimental Biology (FASEB).

In sheer money terms, 2016 NIH budget needs to be ~$48 billion in 2015 dollars to recoup 2003 research strength (see figure below from 7).

Absent structural reforms, i.e., finding solutions to the politically incendiary issues of the aging of US faculty and the sweatshop construct of US basic biomedical research labs, increase in NIH funding is thus social harm, not social good.

Bibliography

1. 2014 National Science Foundation Science and Engineering Indicators. http://www.nsf.gov/statistics/se...

2. Ashenfelter, Orley, and David Card. Did the elimination of mandatory retirement affect faculty retirement flows?. No. w8378. National bureau of economic research, 2001. http://www.econstor.eu/bitstream...

3. Sally Rockey. Feb 13, 2012. Age Distribution of NIH Principal Investigators and Medical School Faculty. http://nexus.od.nih.gov/all/2012...

4. Alberts, Bruce, et al. "Opinion: Addressing systemic problems in the biomedical research enterprise." Proceedings of the National Academy of Sciences 112.7 (2015): 1912-1913. http://www.pnas.org/content/112/...

5. Leadership In Decline. Assessing US International Competitiveness In Biomedical Research. The Information Technology And Innovation Foundation And United For Medical Research. Robert D. Atkinson, Stephen J. Ezell, L. Val Giddings, Luke A.SStewart, Scott M. Andes. May 2012.  http://www.unitedformedicalresea... 

6. From http://www.faseb.org/Portals/2/P...

7. On the Cusp of the 2016 Election: Why Is Politics Avoiding Science? April 2, 2015. On the Cusp of the 2016 Election: Why Is Politics Avoiding Science?

Further Reading

1. Teitelbaum, Michael S. "Structural disequilibria in biomedical research." Science 321.5889 (2008): 644-645.

2. Stephan, Paula E. "The biomedical workforce in the US: An example of positive feedbacks." International Centre for Economic Research Working Paper 11 (2010). http://sites.gsu.edu/pstephan/fi...

3. How We're Unintentionally Defunding the National Institutes of Health. Pacific Standard Magazine, Michael White, Nov 27, 2013. http://www.psmag.com/health-and-...

4. Chakma, Justin, et al. "Asia's ascent—global trends in biomedical R&D expenditures." New England Journal of Medicine 370.1 (2014): 3-6.

5. Updated: Fountain of youth: A congressman's plan to make NIH grantees younger. Science, Jocelyn Kaiser, Oct 6, 2014. Updated: Fountain of youth: A congressman's plan to make NIH grantees younger

6. Alberts, Bruce, et al. "Rescuing US biomedical research from its systemic flaws." Proceedings of the National Academy of Sciences 111.16 (2014): 5773-5777. http://www.pnas.org/content/111/... 

7. Daniels, Ronald J. "A generation at risk: Young investigators and the future of the biomedical workforce." Proceedings of the National Academy of Sciences 112.2 (2015): 313-318. http://www.pnas.org/content/112/...

8. Pickett, Christopher L., et al. "Toward a sustainable biomedical research enterprise: Finding consensus and implementing recommendations." Proceedings of the National Academy of Sciences 112.35 (2015): 10832-10836. http://www.pnas.org/content/112/...

https://www.quora.com/What-consequences-can-bring-a-recent-2-billion-dollars-raise-of-NIH-budget/answer/Tirumalai-Kamala

What is the difference between doing a PhD in a research lab outside a University campus and doing PhD in a lab inside a University campus?

The practicalities of doing a Ph.D. in a research lab outside a University versus doing one in it are quite similar. In either case, the student has to register with a University since they are the ones who grant the Ph.D. degree. For example, though I did my Ph.D. in a research lab run by the Indian Council of Medical Research, I was registered for the degree with the local medical university. However, the university played no role in the day-to-day management of my degree. They only figured towards the end by managing the process of my thesis examination, sending my thesis to outside examiners and helping conduct my viva-voce ('by live voice') exam.

The Ph.D. experience in a research lab is certainly quite different from one in an university. In the former, the Ph.D. student is in the midst of research lab employees and is typically among the junior-most members in the lab. In the latter, surrounded by other students many of whom are pursuing Bachelor's and Master's, the Ph.D. student isn't typically the junior-most. A research lab Ph.D. also typically works on their research project from day one all the way through. No course work.

So more of a work-like experience for a research lab Ph.D. student compared to a university student-like experience for a university Ph.D. student.

https://www.quora.com/What-is-the-difference-between-doing-a-PhD-in-a-research-lab-outside-a-University-campus-and-doing-PhD-in-a-lab-inside-a-University-campus/answer/Tirumalai-Kamala

What is your check list to follow before starting research?

There isn't one common checklist. Though many elements may overlap, each project requires its own checklist. Research process is also enormously different between academia and industry, an individual plodding from A to Z being quite common in the former, especially during Ph.D. and often during post-doc as well, while overlapping team-work is the norm in the latter. Starting with a broad-brush breakdown of basic immunology research into either mouse model or in vitro human cell studies,

Mouse model studies

Carefully research pertinent literature and draft an Animal Study Proposal (ASP). Submit ASP to the Institutional Animal Care and Use Committee (IACUC) and wait for their approval. Experiments involving animal models require prior approval by IACUCs. Typically, IACUCs meet once a month so already we see how planning is integral to basic biomedical research, especially if it involves animal models. The IACUC process ensures ethical animal use and is mandated by law.

ASPs need to detail how many animals are needed for a year, how many experiments, how many animals per year, age- and gender-matched or not, plus clear scientific rationale for each choice. ASPs also need to account for situations involving unrelieved pain and distress. Would any animal be exposed to such? If yes, then need to explain why this is scientifically necessary and also need to scientifically justify the numbers of such animals. ASPs typically undergo annual renewal, at which point changes in experiment designs, numbers, especially for increases in those likely to be subjected to unrelieved pain and distress need to be rigorously scientifically justified.

Special Knockout mouse, Genetically modified mouse require more extensive time outlays in creation and breeding. If procured commercially, need to factor cost and availability as well.

Human cell studies

Carefully research pertinent literature and draft a human research study protocol and submit to the Institutional review board (IRB). Typically, if the human cells are just blood cells, i.e., requiring collection of blood samples, then the process is considered minimal risk and merits expedited review (http://www.hhs.gov/ohrp/policy/e...). The IRB review process ensures that research involving human subjects is conducted ethically. Again, process requires advance planning since research can only proceed after IRB approval.

Questions can then be broken down into:

Sufficient supply of animals/human cell needed to do the entire study or not? If not, what's the plan? Proceed or wait?

How many experiments? Per week? Per month? Etc.

How many animals/human cell vials needed/experiment? Gender- and age-matched.

Need specialized media bottles or supplements or not? If yes, are they readily available or tend to be on back-order? If the latter, how long is the back-order? Also, if the latter, need to stockpile such materials prior to starting such an experiment series. In that case, how long such reagents are good for also becomes a critical issue. Some reagents may be good for a year or more, others only for a few months. If the latter, then need to decide if entire experimental series could be done with one stockpile or not. If not, then multiple lots of a specific reagent would be needed and the need to control for this variable needs to be incorporated into the experiment design.

Need Fetal Calf Serum (FCS*) as growth supplement or not? If yes, then need to order enough bottles of one lot of FCS from one particular vendor for an entire experimental series. Typically labs do or should screen for various FCS lots using their most common lab assays as the readouts and choose to purchase one FCS lot necessary to sustain their lab activities for several years. There is enormous lot-to-lot variation in FCS so biomedical experiments using it have to control for this.

Antibodies, assay kits, enzymes, recombinant proteins, other reagents, lab consumables: Need to prepare a checklist of the foreseeable reagents needed for the planned experiments and check their availability from vendors. Experiments should commence only once all the necessary reagents and equipment are available to hand. For e.g., a particular experimental series might require unusual, specialized lab consumables such as moulded 96- or 48-well transwells that may need to be ordered ahead of time and stockpiled for an entire experimental series or may need a standing order delivery of specific number of units periodically.

Protocols and Standard operating procedure (SOPs): Each slated experimental procedure should be clearly and succinctly written down, and shared with all team members who would be performing the experiments. In industry, SOPs may often need to go through a formal review process as well. Pilot experiments involving all team members are very useful to work out the kinks in new protocols and help minimize 'loss in translation' ahead of primetime. Once an experiment series is underway, it's also helpful to have a shared calendar charting all the steps. Different experiments can be color-coded. Shared calendars help work out schedules ahead of time, which in turn helps outline if staff need to come in on week-ends or holidays or not. Shared calendars also help distribute tasks among team members, and generally help keep the experimental pipeline running smoothly. Again, to minimize loss in translation, experiments should use standardized experiment templates, designed ahead of time as much as possible. In research teams therefore, daily conversations and discussions are the norm and necessity.

Data collection, storage and analysis, ontologies, etc.: If some repetitive procedures require complicated calculations or estimations, excel macros and the like, these should be written ahead of time and saved in a common folder accessible to all team members.  

Electronic notebooks are more optimal compared to paper for data capture. Data can be uploaded to a central server as recorded with no scope for post-experiment modifications, only additions. Minimizes scope for fraud, data selection and other unscrupulous or dubious research practices. Team members should use common data analysis macros or cheat-sheets to ensure uniform and comparable data analysis.

Basic theme? Research teams creating and adhering to a common experimental language, i.e., protocols, calendars, templates, calculations, data analysis approaches and ontologies, helps minimize experimental errors, misunderstandings and miscommunications. Each experiment series reveals scope for improvement such as greater granularity of detail required for successful reproducible experimentation. Electronic notebooks help here as well since date- and time-stamped notes can be recorded in real-time and saved at a central location, enabling ease of retrieval at future dates for post-study critique to tweak and improve the research process.

Some aspects explained in greater detail here: Tirumalai Kamala's answer to What are your hearty suggestions to the students new to research?

* FCS is used inter-changeably with FBS (Fetal Bovine Serum).

https://www.quora.com/What-is-your-check-list-to-follow-before-starting-research/answer/Tirumalai-Kamala

If you have contributed to a paper that is already published, can you use the same title, abstract, and images for a poster presentation?

'If you have contributed to a paper that is already published, can you use the same title, abstract, and images for a poster presentation?'
Yes, provided you have permission from the other authors of that paper and provided the meeting abstract submission policies allow submission of a published paper. For example, having clarified these two issues, I have presented posters of papers that were under review or already accepted for publication.

'Does it depend on whether I wrote it in the first place?'
No, but the poster that you plan to present should retain the list of authors from the published paper as is, of course, with those authors' permission. On the poster, you could put an asterisk after your name with the explanation of the asterisk noting you as the poster presenter. Under no circumstances should the poster list only your name as the author.

'Do people rewrite this info or just use the info from the paper? … I'm guessing it's frowned upon to literally copy/paste the abstract, but I really doubt I could write a better version that says the exact same thing'.
Tending to stricter word limits, usually poster abstracts are shorter compared to those of journal papers so you may not be able to use the exact same abstract anyway. Remember though that if you end up re-writing some phrases or sentences to conform to a strict word limit, you should get approval of the re-worded abstract from all the other authors. Your poster should also indicate that it's based on a published paper by clearly referencing it, i.e., title, list of authors, journal (year, volume, issue, page numbers), on the poster itself.

https://www.quora.com/If-you-have-contributed-to-a-paper-that-is-already-published-can-you-use-the-same-title-abstract-and-images-for-a-poster-presentation/answer/Tirumalai-Kamala

In 2010-2011, David Koch was asked to leave the National Cancer Institute at NIH for obfuscating the role of formaldehyde in causing cancer. Which scientists did he rely on most for generating doubt?

The question is slightly inaccurate. David Koch sat on the advisory board of the National Cancer Institute (NCI), the largest (by size and budget) permanent institute at the NIH. The NCI has the mandate for identifying and researching human carcinogens.

In the August 30, 2010 issue of the New Yorker, the award-winning journalist Jane Mayer published an investigative piece on the Koch family where, among other things, she reported, 'Koch Industries has been lobbying to prevent the E.P.A. from classifying formaldehyde, which the company produces in great quantities, as a ‘known carcinogen’ in humans' (Covert Operations - The New Yorker).

As Jane Meyer reports further in her piece, 'Scientists have long known that formaldehyde causes cancer in rats, and several major scientific studies have concluded that formaldehyde causes cancer in human beings—including one published last year by the National Cancer Institute, on whose advisory board Koch sits. The study tracked twenty-five thousand patients for an average of forty years; subjects exposed to higher amounts of formaldehyde had significantly higher rates of leukemia. These results helped lead an expert panel within the National Institutes of Health to conclude that formaldehyde should be categorized as a known carcinogen, and be strictly controlled by the government. Corporations have resisted regulations on formaldehyde for decades, however, and Koch Industries has been a large funder of members of Congress who have stymied the E.P.A., requiring it to defer new regulations until more studies are completed'.

Also, 'James Huff, an associate director at the National Institute for Environmental Health Sciences, a division of the N.I.H., told me that it was “disgusting” for Koch to be serving on the National Cancer Advisory Board: “It’s just not good for public health. Vested interests should not be on the board.” He went on, “Those boards are very important. They’re very influential as to whether N.C.I. goes into formaldehyde or not. Billions of dollars are involved in formaldehyde'.

And, 'Harold Varmus, the director of the National Cancer Institute, knows David Koch from Memorial Sloan-Kettering, which he used to run. He said that, at Sloan-Kettering, “a lot of people who gave to us had large business interests. The one thing we wouldn’t tolerate in our board members is tobacco.” When told of Koch Industries’ stance on formaldehyde, Varmus said that he was “surprised'.

Predictably, this piece created a media and activist firestorm around the clear conflict of interest in Koch, whose Koch Industries is the owner of one of the largest manufacturers of formaldehyde, sitting on an advisory board  of such import on public health policy. It was after this piece appeared in print that David Koch left his advisory board position at the NCI, as the New York Times reported on October 27, 2010  (Koch Leaves Federal Cancer Panel as Groups Urge Ethics Probe).

And it was after this piece appeared in print that the US government announced on June 9, 2011, that it was adding formaldehyde to a list of known human carcinogens (U.S. (finally) Labels Formaldehyde "Known Human Carcinogen").

Read Jane Meyer's New Yorker piece to understand how lobbying relevant government agencies such as the EPA (Environmental Protection Agency) was the approach to prevent or delay classifying formaldehyde as a known carcinogen in humans, not relying on specific scientists to create doubt.

https://www.quora.com/In-2010-2011-David-Koch-was-asked-to-leave-the-National-Cancer-Institute-at-NIH-for-obfuscating-the-role-of-formaldehyde-in-causing-cancer-Which-scientists-did-he-rely-on-most-for-generating-doubt/answer/Tirumalai-Kamala

Is it true that Bill Gates faced trial in India for illegally testing tribal children with vaccines? Source http://articles.economictimes.indiatimes.com/2014-08-31/news/53413161_1_hpv-vaccine-cervarix-human-papilloma-virus

No, that isn't completely accurate.

Who: Bill & Melinda Gates Foundation (BMGF), https://en.wikipedia.org/wiki/PATH_%28global_health_organization%29 (PATH) and Indian Council of Medical Research (ICMR)
The BMGF funds PATH, a Seattle-based NGO and main recipient of BMGF grant money for global public health initiatives. Since 1998, BMGF has funded PATH to the tune of ~$2 billion. The ICMR is the Indian Government's primary agency tasked with conducting biomedical research.

What: A Phase V human papilloma virus (HPV) Phase V vaccine trial in Andhra Pradesh & Gujarat, India
PATH carried out a large  HPV Phase V vaccine trial in India. Phase V means using approved, not test, vaccines. Certain forms of HPV are associated with cervical cancer. The vaccines in question, Gardasil from Merck and Cervarix from GlaxoSmithKline, were granted marketing approval in India in 2008 while the PATH-sponsored trial began in 2009 as a joint project with the ICMR, using donated vaccines.

• The purpose of the trial was to generate data to support the inclusion of the HPV vaccine in India's Universal Immunization Programme (UIP).
• Specifically recruiting from low-income rural, largely tribal, households, the trial was conducted on girls aged 10 to 14 using Gardasil in Khammam district of Andhra Pradesh (AP) state (n=13000), and using Cervarix in Vadodara in Gujarat state (n=10000).

The Problems
Public recognition of problems with this trial started with the reported death of 7 girls. This led to immediate suspension of the trial in 2010 even though it was supposed to run until 2011. Investigations showed these deaths weren't directly connected to the vaccines (see table from the initial official investigation report, 1).

However, investigations triggered by these deaths instead uncovered serious violations of the process of informed consent (see official investigation reports below from 1, see also 2). Aged 10 to 15, girls in this trial were obviously below the age of  consent meaning their participation in the trial required the consent of  parents/guardians. In the course of Government of India (GOI)  investigations, the trial investigators 'were asked to submit 100 consent forms, chosen randomly, for both AP and Gujarat for independent verification' (1). These consent forms turned out to have several problems (see reports below from 1).

Investigations (1) revealed that

• In Andhra Pradesh, 'Signatures of one parent were obtained on 9543 forms, thumb impression of one parent on 1948 forms and signatures of Hostel Warden/Head Master as Guardian in 2763 forms' 
• The investigators noted, 'The legality of the signing by the Hostel Warden/Head Master in Andhra Pradesh needs to be examined by an appropriate authority'. 
• In Gujarat, 'In Gujarat one parent has signed on 6217 forms, has provided thumb impression on 3944 forms and Legal guardian has signed or put thumb impression on 545 forms'.
• As a newspaper report summarized, signature of ~2800 consent forms had instead been signed by school teachers, principals or hostel wardens, even in cases where the girls had parents (2).

The Indian Parliament's Standing Committee on Health began its investigation in April 2010 and concluded that 'safety and rights of children were highly compromised and violated' (3).

The Committee's report (3) found

• The girls' consent was not fully informed.
• Post-vaccination adverse events weren't adequately monitored or reported.
• PATH and ICMR hadn't sought mandatory permission from the Drug Controller General of India (DCGI) or the Indian National Technical Advisory Group on Immunization (NTAGI).
• PATH wasn't even a registered legal entity when it began working with the ICMR.
• DGAI culpable for dereliction of duty.

The Committee's report stated, 'PATH resorted to an element of subterfuge by calling the clinical trial as 'observational studies' or 'demonstration project' and recommended legal action against PATH (3). However, the Union Government of India  decided legal action couldn't proceed based on the its assessment of the country's prevailing laws. Instead in 2014, it issued a warning letter to PATH (4).

PATH's dubious and unconvincing defense was that this wasn't a clinical trial, only an observational study of an already approved vaccine. As such, it argued that neither provision, i.e., informed consent and monitoring/reporting of post-vaccination adverse events, was necessary (5). This is patently incorrect.

Bibliography

1. http://icmr.nic.in/final/HPV%20P...
2. The Hindu, May 25, 2011. Editorial. A shockingly unethical trial
3. Page on preventdisease.com
4. The Hindu, August 25, 2012. Aarti Dhar. Government warns PATH
5. LaMontagne, D. Scott, and Jacqueline D. Sherris. "Addressing questions about the HPV vaccine project in India." Lancet Oncology 12.14 (2013): e492; Statement from PATH: cervical cancer demonstration project in India

Further Reading

1. Kumar, S., and D. Butler. "Calls in India for legal action against US charity. Nature News [Internet]. 2013 Sep 9 [cited 2013 Oct 22]." Calls in India for legal action against US charity
2. sSharma, Dinesh C. "Rights violation found in HPV vaccine studies in India." The Lancet Oncology 14.11 (2013): e443.

https://www.quora.com/Is-it-true-that-Bill-Gates-faced-trial-in-India-for-illegally-testing-tribal-children-with-vaccines/answer/Tirumalai-Kamala

What are the best ways to write a literature review?

I don't think best way is an appropriate or helpful way of putting it. Rather, literature reviews should be comprehensive, covering the topic’s history, key concepts, influential figures and notable developments. As well, they shouldn't shy away from contentious material. Rather they should attempt to persuasively present data and arguments for or against certain interpretations. This broad umbrella accommodates a variety of writing styles and analytical approaches.

Some examples may help explain the process. For e.g., a while back I wrote an answer about possible human- Mycobacterium tuberculosis co-evolution, Tirumalai Kamala's answer to What if Mycobacterium tuberculosis evolved as a cohabitating organism within the human body?. Like many of my Quora answers, this too took the form of a review so it may be a relevant example.

How to start? Start with what I call a hook. As simple as searching for Human Mycobacterium tuberculosis co-evolution in Home - PubMed - NCBI. In this particular example, I got 24 search results (see screenshot below). Several good leads (outlined in blue), i.e. hooks to get into the subject.

Got those papers, read them, looked up their references, looked up the papers that cited them. Read the abstracts to decide whether to download or not. Doing this builds up a database on the topic rather fast. Once done screening and collating this database, I can sort them into different bins according to subject matter (see screenshots below). In this particular example, I ended up with a database consisting of 9 papers I catalogued as General, 2 as Bottleneck, 15 as Canetti, 4 as Co-evolution, 2 as Deletions, 3 as M. africanum, 7 as M. bovis, 4 as Methods, 15 as Paleopathology, and 3 as Virulence Definitions, for a total of 64 papers. Not a thorough up and down, front and back dredging of source material by any stretch of the imagination. Answer intended only for a general, not specialist, audience after all but this is an example of the basic skeleton required for assembling the database needed for a literature review. As I go through this bunch, the answer starts to shape itself into existence and I start whittling the pile. What's useful? In this particular example, my shorthand for papers I cited have a green dot while ones I found useful for references have a blue dot (see screenshots below).

A similar process attends just about any kind of research I undertake. Cataloging and sorting plus a common file-naming system helps tremendously in gaining control over the reading material, and brings order to what starts out as utter chaos.

Another invaluable helper? Keyword search through a database using Command+F. Helps both with the binning process as well in mining the database for the portion of the answer dealing with a particular keyword.

Process is simple and straightforward in theory. In practice, it requires genuine unflagging interest, and tremendous focus and discipline. Certainly not for the faint-hearted. Especially the citation search. Often papers are cited 100s, even 1000s of times. Trawling though such citations requires a hardy stomach and a spine of steel. Of course, checking each and every citation isn't mandatory nor required for each review. Time and practice helps develop judgment regarding when to pause to pick up another reference or to move on. As well, I tend to read very fast so I can consume relatively vast amounts of information fairly quickly. Plus years of experience doing this. However, reading fast has its perils as well so experience has taught me to go over papers more than once. A gap in time helps plug gaps as fresh eyes bring more value to the task.

I find this general approach very versatile so much so that I use it both for work and elsewhere. For e.g., my hometown of Chennai recently suffered unprecedented floods that marooned the city and relegated it to the medieval age in one stroke. Since I have family there, I spent many waking hours tracking the situation on the ground the best I could on the internet. The material I found doing this formed the basis of my blog post cataloging what happened, why and what it says about the body politic, The 2015 South Indian Floods: The Front Page News Story that Global News Media Wantonly Neglected by Tirumalai Kamala on TK Talk.

Using a similar approach to catalog, collate and bin my starting material (see screenshot below), the post started to shape itself into existence. Again, Command+F is an irreplaceable help. Using it to find keywords such as 'drain', 'police', 'military', 'NDRF', etc., helped me quickly shape a narrative that made sense to my understanding of the situation. Quickly scan, copy-paste the relevant passages, move on. Soon, my post was done. 

So there you have it, a broad brush overview of my approach to review writing. How the review/answer starts to shape itself is the most mysterious aspect of this process. This is where the individual's unique Masala (or alchemy) makes all the difference. A feeling for narrative, bolstering arguments with tangible, verifiable, sometimes testable data, one part of the narrative flowing to the next, these are some of the essential elements. Often arguments in one section will stoke into existence logical questions. These can then serve as bridges connecting one section to the next, or even one para to the next. In this manner, hopefully a cogent narrative emerges, akin to a building, the original database the foundation and the review sections the above-ground structure the foundation makes possible. More comprehensive the database (foundation) that went into researching the review topic, better the review (building) and greater its value.

https://www.quora.com/What-are-the-best-ways-to-write-a-literature-review/answer/Tirumalai-Kamala