What is your personal experience of the difference in the way basic science research is conducted in the USA and India?

As a biomedical researcher, I consider the research I did during my Ph.D. in India to be the most rigorous by far. It was the only project where statistics were appropriately and correctly applied right from the first step, the experiment design, continuing with blinding of the samples through to data analysis.

Goal of my Ph.D. project was to figure out if prior exposure to environmental mycobacteria (NTM, Nontuberculous mycobacteria) could explain why the largest TB vaccine trial had failed to protect against adult pulmonary TB. Conducted from 1967 to 1980 on ~360000 people across 209 villages and 1 town in South India, prior exposure to environmental mycobacteria emerged as a plausible reason. Only there was no data on NTM in this environment, if yes, what species and where, in the soil/water/dust. I was just one person. How could I cover such a vast population over such a vast area? That's where statistics entered the picture, exactly where it should, in the experimental design itself. A professional statistician crunched the numbers to determine how many villages I should cover, how many houses per village, which villages, i.e., make sure I comprehensively sampled the entire trial area in as unbiased a manner as possible. Starting with this design, he carefully shepherded every step of my Ph.D. project and even blinded the samples I brought back from the field, only decoding them after I'd generated all the data. Since I don't have any other experience on basic research in India, I don't know if my experience if generalizable so I'll leave it at that. 

Moving on from differences between India and US, I'll highlight two dubious practices that are rampant in basic biomedical research the world over, at least if we go by the published literature. Overarching problem consists of two features

1. Statistics are misused, usually applied only at the back end to analyze the data after it's been generated, instead of the optimal approach which is to apply them from the beginning in the experiment design itself.

2.Definition of scientific misconduct is too narrow, completely ignoring the most prevalent practice, which isn't outright fraud but rather data selection.

Compared to basic research, rigorous statistical science applied to human clinical trials is the norm. Only very slowly is this mindset permeating into basic research to replace this ridiculous state of affairs. Last year, we saw the publication of the first randomized clinical trial in mice (1). 

The US ORI (United States Office of Research Integrity) defines Scientific misconduct as consisting of data fabrication, data falsification or plagiarism. But far more than any of these, the most prevalent practice is something that's not even on the radar, data selection, i.e., cherry-picking data. Practice is rampant. Rarely do animal model studies show data combined from different experiments. Take a look at any recent paper, even ones published in Nature or Science. Invariably a figure legend would say something along the lines of, 'Data from one representative experiment out of 3, 4 or 5 different experiments is shown'. Why not show combined data from all experiments performed? How could such a shoddy practice be the norm? Simply means intra-group variation between experiments was greater than inter-group variation within one single experiment. Either experimenters are shoddy or techniques too unrefined. Either way, cannot trust such data. And this is still the norm in basic biomedical research.  

Bibliography:

1.  Llovera, Gemma, et al. "Results of a preclinical randomized controlled multicenter trial (pRCT): Anti-CD49d treatment for acute brain ischemia." Science Translational Medicine 7.299 (2015): 299ra121-299ra121. http://stm.sciencemag.org/conten...

https://www.quora.com/What-is-Tirumalai-Kamalas-personal-experience-of-the-difference-in-the-way-basic-science-research-is-conducted-in-the-USA-and-India/answer/Tirumalai-Kamala

Do you have advice on how to convince anti-vaxxers to get their shots?

No dearth of advice on the internet how to convince anti-vaxxers to get their shots or rather more accurately, encourage them to get their children vaccinated. From professors to young mothers, an array of well-meaning people seek to show them the error of their ways. Does this approach work? More pertinently, could it? Is it possible to change minds without understanding why they think the way they do? I too used to think that summoning an abundance of rigorous, irrefutable facts would suffice. Is it though? Would it work on me? Honestly, I'm not sure.

Facts, figures, data appeal more to the intellect, less to emotions. A bullet-point list of truisms likely to provoke approving nods from vaccine aficionados would fall off anti-vaxxers' backs like the proverbial water. Just the way it goes with entrenched beliefs, appeals to reason alone don't suffice. The amalgam of conspiracy theories about government, big pharma, science, the medical profession that typically fuel anti-vaxxers is based on a mix of unrealistic expectations, mistrust and fear, fear for the well-being of their children. Wouldn't appeal to reason boomerang, likely perceived as patronizing? As well, the internet so easily fosters a bubble mentality. Stay ensconced in echo chambers that parrot one's own viewpoint and one need never subject oneself to the discomfort of questioning one's belief. The problem won't go away through mocking/hectoring/lecturing, and is likely of our own making.

An argument more likely to pierce such a bubble would be personal accounts of former anti-vaxxers who changed their minds, and got themselves and their children vaccinated. Such people once inhabited similar mind-sets. Their accounts would resonate more because they'd appeal to emotion instead of to reason alone. They'd address the underlying fear that drives much of this thinking. Former anti-vaxxers had the same fear and yet they found a way to surmount them. Recently, some former anti-vaxxers have come forward with just such stories of changes in stance (1, 2). Sharing these essays with current anti-vaxxers would do both them and the rest of us more of a service compared to an exchange across entrenched beliefs that's only likely to become increasingly rancorous.

How is the problem one of our own making? Exploring this issue opens a bigger can of worms about current human culture and collective memory and in its wake leaves more uncomfortable questions. Each of us comes from somewhere, a specific family, culture, history. Each of us living today has to only go back one, two or three generations at most to find accounts of relatives who died or were maimed from polio, small pox, pertussis, rubella, rabies, tetanus, vaccine-preventable diseases all. What happened to their stories? Why aren't the accounts of their lives and tragic, vaccine-preventable disabilities or deaths part of their families' lore? Surely it can't be that anti-vaxxers have absolutely no one in their 20th century family tree who died from a vaccine-preventable disease? That would just defy statistics. This is the deeply unsettling bit.

School and formal education attend to one aspect of  identity formation and beliefs. The other part comes from family and community. The recent anti-vaxxer movement in places like the US and Australia suggests that something fundamental may be changing in the way generational information and knowledge is transmitted within families and communities. Or maybe I'm the fool for walking down this path. Maybe selective amnesia always attended collective human memory. In which case, we are and will always be fools condemned to repeat the past, to paraphrase George Santayana. Yet somehow I suspect I'm not wrong in thinking increasingly isolated online living and entrenched mistrust against one big group or the other goes hand in hand. If I'm right, our current mode of increasingly disembodied online living is only more likely to bring out the potential for irrationality in each and every one of us. Maybe anti-vaxxers and other fringe groups are merely harbingers of worse to come.

Foot-notes

1. Kashana Cauley, The Atlantic, Mar 6, 2015. I Used to Be an Anti-Vaxer
2. Sage Stargrove, The Guardian, Feb 28, 2015. I'm finally getting vaccinated. But not because of your shaming

https://www.quora.com/Do-you-have-advice-on-how-to-convince-anti-vaxxers-to-get-their-shots/answer/Tirumalai-Kamala

If Tirumalai Kamala could have one source of funding, would it be from a major government (US, Canada, Europe, etc.) or from private enterprise?

I'd choose private enterprise any day. For several reasons. By now, it's rather clear government funding of research is stuck in a rut. Highly risk-averse. Grant reviewers part of a well-ensconced old boys club with no signs of impending unseating. Younger generation being trained in the same mould. Result? Same old, same old. I'll illustrate with one telling example. HIV. Appeared on the radar in the early 1980s. 1984 is when Anthony S. Fauci became Director of NIAID (National Institute of Allergy and Infectious Diseases), the US government's premier research agency tasked with infectious disease research. 32 years and counting at the helm, no sign of an approved prophylactic or even a therapeutic HIV vaccine. This wasn’t because enough resources weren’t committed to the task. During the height of NIH's gravy train from 1998 to 2003 when its budget doubled, a sizeable chunk unsurprisingly made its way into NIAID which set about creating its own vaccine research wing, the Vaccine Research Center. Established with much fanfare in 1999, still no approved HIV vaccine on the horizon.  

Meantime, in 2014 a privately funded French group published a highly novel mode of vaccine protection against SIV, the monkey version of HIV (1). Using a highly unorthodox vaccination, either in the stomach or the vagina, all three vaccines they tried protected against SIV. The protection mechanism was completely unexpected and novel. Not antibodies. Not cytotoxic killer cells. Rather a new type of regulatory CD8 T cell that suppressed the activation of SIV-specific CD4 T cells. Why is that so important? SIV/HIV activate CD4 T cells, apparently for their own purpose. Activated CD4 T cells are the Trojan horses SIV/HIV use to establish stable infection in the body. Trojan horse because activated CD4 T cells also proliferate actively. Situation tailor-made for creating more cells for SIV/HIV to infect. By halting such CD4 T cell activation, these unconventional CD8 T cells are stopping SIV in its tracks. Maybe same could happen with HIV as well.

The same group published preliminary data from this series of studies in 2012 (2), data that sank like a stone in the tight-knit HIV research community. As Jose Esparza and Marc HV Van Regenmortel editorialize (3),

“The 2012 publication from this group had very little impact in the field, perhaps because it was received with a degree of skepticism. After all, 30 years of intense vaccine research had not resulted in a practical effective vaccine, although an HIV vaccine is sorely needed to bring the HIV epidemic under control. No stone should remain unturned in its search, and the approach reported in this journal should not be dismissed a priori. Instead, it should be carefully considered by other scientists and appropriately confirmed or refuted by additional research”. “Out-of-the- paradigm approaches, such as the one proposed by Andrieu et al., should be further explored”.

And Marc HV Van Regenmortel further elaborated about their earlier 2012 study (4)

“This remarkable and totally unexpected breakthrough was obtained by an investigator-driven research that was not funded by the usual governmental and large scale organizations that support most of the ongoing HIV vaccine research world-wide. It was sponsored by a private benefactor who funded the project to the tune of 13 million Euros. This illustrates once again that success in basic vaccine research is unpredictable and that “risky” projects based on unorthodox thinking may deserve as much funding as the “safe” projects that are often preferred because they abide by current fashionable paradigms”.

Bibliography

1. Andrieu, Jean-Marie, et al. "Mucosal SIV vaccines comprising inactivated virus particles and bacterial adjuvants induce CD8+ T-regulatory cells that suppress SIV-positive CD4+ T-cell activation and prevent SIV infection in the macaque model." Frontiers in immunology 5 (2014). http://www.ncbi.nlm.nih.gov/pmc/... 

2. Lu, Wei, et al. "Induction of CD8+ regulatory T cells protects macaques against SIV challenge." Cell reports 2.6 (2012): 1736-1746. http://www.sciencedirect.com/sci...

3. Esparza, José, and Marc HV Van Regenmortel. "More surprises in the development of an HIV vaccine." Frontiers in immunology 5 (2014): 329. http://www.ncbi.nlm.nih.gov/pmc/... 

4. Regenmortel, M. H. V. V. "An oral tolerogenic vaccine protects macaques from SIV infection without eliciting SIV-specific antibodies nor CTLs." J AIDS Clin Res 4 (2013): e112. http://www.omicsonline.org/2155-...

https://www.quora.com/If-Tirumalai-Kamala-could-have-one-source-of-funding-would-it-be-from-a-major-government-US-Canada-Europe-etc-or-from-private-enterprise/answer/Tirumalai-Kamala

How can we redesign the PhD experience in order to minimize suffering of graduate students?

It's a truism that we get the outcomes that are rewarded.

PhD supervisors are typically rewarded for their publications and for the grants they receive. Rewards entail tangible benefits to their career such as promotions, nominations to influential committees, editorial positions on journals, decision-making powers in their workplaces such as university departments, and the like.

While most academic workplaces vociferously tout the importance of mentoring, including training and teaching, it's also patently obvious they offer practically no tangible rewards for good mentoring. Are there even objectively defined assessments of good academic mentoring? What does it mean to be a good mentor? What distinguishes good training and teaching from bad? Is objectively defined mentoring even considered by promotion committees? Has anyone ever heard of a professor getting promoted because they were a good mentor who trained and taught their PhD students well? Clearly academic mentoring is not just a case of There's many a slip 'twixt the cup and the lip, but also of lip-service.

For far too long and far too often, PhD students, and in many scientific fields, post-docs as well, are mere fodder that helps a PhD supervisor advance their own career. Tasked with shepherding PhD students but not offered any tangible rewards for doing so, any wonder in the typical PhD supervisor's world, PhD students and post-docs all too often end up as extra pairs of hands, cheap labor to instead help bring about the outcomes that do reward their PhD supervisors, namely, publications and successful grant applications?

The average PhD experience would likely greatly improve if instead tangible training-based outcomes were part and parcel of assessing a PhD supervisor and had a bearing on their future career. Where are the metrics such as how many of their PhD students later found a job or even how many stayed in the same field? Who tracks such metrics? Likely no one. After all, such a system doesn't exist even for the US National Institutes of Health postdoctoral training program, probably the largest such training program in one place anywhere in the US, maybe even the world.

Put another way, currently, academia tangibly rewards academics for their individual selfishness, not responsible stewardship of their chosen study fields. Such a system is obviously unsustainable in the long run. Problem is it takes years for the insurmountable nature of such unsustainability to become undeniably evident, a situation analogous to Climate change for example.

So we come back to where we started, namely, that we get the outcomes that are rewarded, not the ones we ostensibly seek. Unless good mentoring, i.e., good training and teaching is a) defined more objectively, and b) PhD supervisors get tangibly rewarded or punished using such objectively defined criteria, PhD programs will continue in the same vein, i.e., causing far too many PhD students unnecessary stress and suffering.

https://www.quora.com/How-can-we-redesign-the-PhD-experience-in-order-to-minimize-suffering-of-graduate-students/answer/Tirumalai-Kamala