Public Health in the Precision-Medicine Era

Ronald Bayer, Ph.D., and Sandro Galea, M.D., Dr.P.H.

“The NIH’s most recent Estimates of Funding for Various Research, Condition, and Disease Categories report (www.report.nih.gov/categorical_spending.aspx) shows, for example, that total support in fiscal year 2014 for research areas including the words ‘gene,’ ‘genome,’ or ‘genetic’ was about 50% greater than funding for areas including the word ‘prevention.’…The proportion of NIH-funded projects with the words ‘public’ or ‘population’ in their title, for example, has dropped by 90% over the past 10 years, according to the NIH Reporter.”

“Without minimizing the possible gains to clinical care from greater realization of precision medicine’s promise, we worry that an unstinting focus on precision medicine by trusted spokespeople for health is a mistake — and a distraction from the goal of producing a healthier population.”

Read More


Source

NEJM: Public Health in the Precision-Medicine Era by Ronald Bayer, Ph.D., and Sandro Galea, M.D., Dr.P.H.

Does Pure Nicotine Cause Cancer?

Cigarettes contain many chemicals that increase the risk of cancer. Polycyclic hydrocarbons and tobacco-specific N-nitrosamines are some of the more well-known carcinogens in this class.

But now, e-cigarettes appear to be isolating nicotine, and leaving behind many of the old toxins from cigarettes. This sounds like e-cigarettes may be “better” for the modern smoker. Are smokers of e-cigarettes increasing their chances of cancer later in their lives? If so, what is the risk of cancer from smoking pure nicotine?

For the sake of discussion, let’s ignore the possibility for novel cancer-inducing chemicals introduced from the various oils and heating mechanisms in e-cigarettes. Let’s assume it is possible to have a method of smoking that only exposes the smoker to nicotine and nothing else. Would this method of smoking still cause cancer?

This review of the literature on Nicotine from 2015 suggests the answer is “yes”. Nicotine alone still increases the risk of cancer for the smoker of pure nicotine.

“Several lines of evidence indicate that nicotine may contribute to the development of cancer.

“Evidence from experimental in vitro studies on cell cultures, in vivo studies on rodents as well as studies on humans inclusive of epidemiological studies indicate that nicotine itself, independent of other tobacco constituents, may stimulate a number of effects of importance in cancer development (5, 6).”


Source

NCBI: Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment – A Review

Importance of Stupidity in Science

The Importance of Stupidity in Scientific Research

“Science makes me feel stupid too. It’s just that I’ve gotten used to it. So used to it, in fact, that I actively seek out new opportunities to feel stupid. I wouldn’t know what to do without that feeling. I even think it’s supposed to be this way.”

The more comfortable we become with being stupid, the deeper we will wade into the unknown and the more likely we are to make big discoveries.

“Productive stupidity means being ignorant by choice. Focusing on important questions puts us in the awkward position of being ignorant. One of the beautiful things about science is that it allows us to bumble along, getting it wrong time after time, and feel perfectly fine as long as we learn something each time. No doubt, this can be difficult for students who are accustomed to getting the answers right. No doubt, reasonable levels of confidence and emotional resilience help, but I think scientific education might do more to ease what is a very big transition: from learning what other people once discovered to making your own discoveries. The more comfortable we become with being stupid, the deeper we will wade into the unknown and the more likely we are to make big discoveries.”


Source

The Journal of Cell Science: The Importance of Stupidity in Scientific Research

The Evolutionary Advantages of Being Stupid

“By sacrificing intelligence, diving mammals become endowed with a greater capacity to withstand oxygen depletion, an attribute which presumably has important survival value. Thus, relative stupidity may be more important for species survival under some conditions than relative intelligence.1”

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“In one sense the turtle has traded off intelligence for an amazing ability to withstand profound O2 depletion. Whatever the ultimate wisdom of this choice from an evolutionary standpoint, it may be pointed out that the turtle has survived (on an instinctive and reflex basis) largely unchanged as a stupid animal for over 200,000,000 years [15]. These studies indicate that the possession of a very small brain which does not function vigorously may have important survival value.”

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“It is of some interest that this same analysis may be applied to mammalian species during fetal development. It is well known that the brains of immature mammals are better able to withstand anoxia and ischemia than those of more mature animals [17]…increased metabolic demand associated with increasing functional and structural brain complexity is found postnatally and is paralleled by a decreasing resistance to anoxia [18]. In any case the fetal brain, like turtle brain, is relatively stupid but capable of withstanding extreme O2 depletion.”

“The brain which designed spaceships has also designed the hydrogen bomb. The brain which created the Eroica created the crematories of Auschwitz….The development of a brain in which intelligence is not invariably coupled to constructive purposes could easily prove to be a lethal evolutionary trait.”

It might be more useful to be ‘stupid’ rather than ‘intelligent.’

“Modern molecular biology suggests that the structure and function of the brain depends on mechanisms which are common to all cells. Thus, sensory experience [21], memory [22], and learning [23] involve the biosynthesis of new protein, macromolecular metabolism, the RNA and DNA systems, energy metabolism, and ion transport.2 It is fascinating that brain RNA and brain protein increase during  learning in a manner quite similar to increases in these components in skeletal muscle during prolonged physical exercise [24].”

“In the context of this essay two conclusions might be drawn with respect to these findings.

  1. “The differences in intellectual capacity between various species are quantitative rather than qualitative. The qualitative difference is extensive but does not necessarily constitute an evolutionary discontinuity.
  2. “Intelligence is a trait which has arisen through the same processes which give rise to other biological properties. As such, it is subject to the same evolutionary pressures as other biological properties and may play the same evolutionary role as that played by other biological properties.”

“Whatever the merits of the present analysis, perhaps it will prove useful to question whether man is really the most superior species, whether intelligence is really a property with great importance for the survival of the species, whether evolution always proceeds in an upward direction, and whether man as a species is immortal.”

“It could be argued that the major virtue of intelligence is to provide the possibilities of additional degrees of freedom of choice which are not available to other species. How these degrees of freedom will be used is not clear. If through an atomic holocaust man as a species disappears and the turtle (of all the vertebrates) inherits the earth, then truly it will be an evolutionary victory of stupidity over intelligence!”


 

Source

NCBI: The Evolutionary Advantages of Being Stupid (1973)

Case Report: 382 Day Therapeutic Fast

Features of a successful therapeutic fast of 382 days’ duration

A 27-year-old man weighing 456 pounds fasted for 382 days under clinical supervision. He lost 276 pounds (final weight 180 pounds) for an average weight loss of 0.76 pounds per day. The man was followed-up 5 years later, and he had maintained his weight at 196 lbs. This case report was published in 1973.

The authors describe case studies of other obese patients who died from fasting therapy:

“There have been reports of five fatalities coinciding with the treatment of obesity by total starvation (Cubberley, Polster & Schulman, 1965; Spencer, 1968; Garnett et al., 1969; Runcie & Thomson, 1970). One was attributed to lactic acidosis during the refeeding period following a 3 week fast (Cubberley et al., 1965). Two were considered to be due to ventricular failure, occurring during the fast, at 3 and 8 weeks respectively in patients who had shown evidence of heart failure before beginning the fast (Spencer, 1968). One patient (Runcie & Thomson, 1970) died on the thirteenth day of his fast from small bowel obstruction. Only one of the five ‘fasting’ deaths has been associated with a fast of more than 200 days’ duration. It occurred during the refeeding period after a fast of 210 days in an apparently well young woman (Garnett et al., 1969). Following this particular report doubt has been cast on the safety of the treatment of obesity by total fasting (Garnett et al., 1969; Rooth & Carlstrom, 1970). However, the allopurinol which had been given may have had unfavourable effects on nucleotide metabolism (Stewart & Fleming, 1969).”

The authors conclude:

“Short-term fasts, although demonstrating to the obese patient his ability to lose weight, have a poor long-term outlook with respect to subsequent weight gain (MacCuish et al., 1968). We have found, like Munro and colleagues (1970), that prolonged supervised therapeutic starvation of the obese patient can be a safe therapy, which is also effective if the ideal weight is reached. There is, however, likely to be occasionally a risk in some individuals, attributable to failures in different aspects of the adaptative response to fasting. Until the characteristics of these variations in response are identified, and shown to be capable of detection in their prodromal stages, extended starvation therapy must be used cautiously…Starvation therapy can be completely successful, as in the present instance.”


 

Sources

NCBI: Features of a successful therapeutic fast of 382 days’ duration

PDF: Features of a successful therapeutic fast of 382 days’ duration

Writing the Introduction to an Epidemiology Paper

This is some brief guidance from my advisor on how to write the introduction section of an epidemiology scientific paper. When addressing previous papers in the introduction, do so only briefly. Generally, save the thorough literature review for the discussion.


Paragraph 1

What is the public health or clinical importance of the topic? What is the primary problem that will be addressed? How many people will be affected? What level of impact does this problem have? Statistics from the World Health Organization are often cited here.


Paragraph 2

What is currently known about the problem?

For example, what has been published on health related quality of life (HRQOL) in type 2 diabetes mellitus (T2DM) patients?

Briefly describe a variety of primary literature papers on the topic. State the lacking knowledge that will be addressed by the rest of the paper.

There is much known about HRQOL in T2DM in populations of White Americans, but there have been no studies to date describing HRQOL in Pacific Islanders diagnosed with T2DM.

Address challenges unique to this study.

Are there variations in HRQOL perceptions among different cultures?


Paragraph 3

Clearly and concisely state the primary aim of this study.

For example, in the current analysis we will study the impact of T2DM on HRQOL in a population of Pacific Islanders living in Oahu, Hawaii.

Say something specific about the population being studied.

The Pacific Islander Cohort of Hawaiians is a longitudinal, population-based cohort that has been ongoing since 1999, with followup every 4 years.

Explain why this study is novel. Tell what you are going to show.

 Hemoglobin A1c (HbA1c) is a validated clinical measure of T2DM severity (citation here), and the SF-36 is a validated health questionnaire measuring HRQOL (citation here). To the extent of our knowledge, this is the first study to study a potential quantitative association between HbA1c and the SF-36 in a population-based cohort of Pacific Islanders.


Mendeley Reference Management

Mendeley is a convenient, free research resource that allows you to manage primary literature references. Mendeley’s Citation Plugin allows easy citations in Microsoft Word while drafting scientific papers from your library.

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