Approaching the golden age of epigenomics and epitranscriptomics

A new twist on epigenetics

If epigenomics is crucial to discard the genetic predestination paradigm, now we can add a new 'omics to the paradigm: epitranscriptomics. Last February, Nature published interesting news related to recent scientific developments:

The epigenome helps to explain how cells with identical DNA can develop into the multitude of specialized types that make up different tissues. The marks help cells in the heart, for example, maintain their identity and not turn into neurons or fat cells. Misplaced epigenetic marks are often found in cancerous cells.

 Chuan He and Tao Pan are two researchers that have been working on new ways of controlling gene expression

He and others have shown that a methyl group attached to adenine, one of the four bases in RNA, has crucial roles in cell differentiation, and may contribute to cancer, obesity and more. In 2015, He’s lab and two other teams uncovered the same chemical mark on adenine bases in DNA (methyl marks had previously been found only on cytosine), suggesting that the epigenome may be even richer than previously imagined.

The team had shown for the first time that RNA methylation was reversible, just like the marks found on DNA and histones.

Methylated adenine bases are the focus of research on gene expression.

Exercise as a socially contagious activity

Exercise contagion in a global social network

Disciplines as diverse as economics, sociology, medicine, computer science, political science and physics have recently become interested in the interdependence of behaviours across the human social network. In particular, scientists have begun to ask whether our health and other behaviours are contagious, in that our decisions and actions affect the decisions and actions of our peers. If behavioural contagions exist, understanding how, when and to what extent they manifest in different behaviours will enable us to transition from independent intervention strategies to more effective interdependent interventions that incorporate individuals’ social contexts into their treatments

A new  study offers some of the first hard evidence that health-related habits can spread — and so perhaps could be deliberately seeded and encouraged — by social influence and peer pressure. Previous research has sought such a contagious effect in factors such as obesity and smoking, but the results have been inconclusive.

Studies in social differences in health have a a new hurdle to tackle. How to boost social permeability? As Mackenback said in The Lancet on health inequalities: now it's personal.

PS. These are the results of the study in one figure:

The useless prediction of the end of liberalism

Francis Fukuyama predicted 25 years ago the end of history, the triumph of liberal democracy and the arrival of post-ideological world, Now Y. N. Harari predicts the end of liberalism and the arrival of a post-humanism (?). All these efforts are useless in my opinion and the reason is obvious, those that predict the future don't have more information than any other human being. They could devote their time to fruitful initiatives.
If I knew that the second half of Homo Deus was devoted to the end of liberalism and the birth of a post-humanism, I wouldn't have read it. I always try to avoid snake-oil sellers. Reading is an asymmetric information game, the writer knows more than the reader. I would suggest to start a global snake-oil writers lists to reduce asymmetric information.
The New Yorker publishes a sound review of the book,

Harari’s larger contention is that our homocentric creed, devoted to human liberty and happiness, will be destroyed by the approaching post-humanist horizon. Free will and individualism are, he says, illusions. We must reconceive ourselves as mere meat machines running algorithms, soon to be overtaken by metal machines running better ones. By then, we will no longer be able to sustain our comforting creed of “autonomy,” the belief, which he finds in Rousseau, that “I will find deep within myself a clear and single inner voice, which is my authentic self,” and that “my authentic self is completely free.” In reality, Harari maintains, we have merely a self-deluding, “narrating self,” one that recites obviously tendentious stories, shaped by our evolutionary history to help us cope with life. We are—this is his most emphatic point—already machines of a kind, robots unaware of our own programming. Humanism will be replaced by Dataism; and if the humanist revolution made us masters the Dataist revolution will make us pets.

Does this makes any sense? Is it possible to remain as the current best seller with such a message?

Norah Jones. It's a tragedy

When science and regulation don't talk to each other

An Evidence Framework for Genetic Testing

National Academy of Sciences and Food and Drug Administration don't talk to each other. At the same time that NASEM publishes a report on how to assess genetic testing, FDA clears genetic testing for 23andme without any precise assessment, for the following tests:

• Parkinson’s disease, a nervous system disorder impacting movement
• Late-onset Alzheimer’s disease, a progressive brain disorder that destroys memory and thinking skills
• Celiac disease, a disorder resulting in the inability to digest gluten
• Alpha-1 antitrypsin deficiency, a disorder that raises the risk of lung and liver disease
• Early-onset primary dystonia, a movement disorder involving involuntary muscle contractions and other uncontrolled movements
• Factor XI deficiency, a blood clotting disorder
• Gaucher disease type 1, an organ and tissue disorder
• Glucose-6-Phosphate Dehydrogenase deficiency, also known as G6PD, a red blood cell condition
• Hereditary hemochromatosis, an iron overload disorder
• Hereditary thrombophilia, a blood clot disorder

Meanwhile NASEM recommends a decision framework for the use of genetic tests in clinical care:

1. Define genetic test scenarios on the basis of the clinical setting, the purpose of the test, the population, the outcomes of interest, and comparablealternative methods.
2. For each genetic test scenario, conduct an initial structured assessment to determine whether the test should be covered, denied, or subject to additional evaluation.
3. Conduct or support evidence-based systematic reviews for genetic test scenarios that require additional evaluation.
4. Conduct or support a structured decision process to produce clinical guidance for a genetic test scenario.
5. Publicly share resulting decisions and justification about evaluated genetic test scenarios, and retain decisions in a repository.
6. Implement timely review and revision of decisions on the basis of new data.
7. Identify evidence gaps to be addressed by research.

If you want further details, check Mathew Herper blog. My first impression after reading it is that this move, paves the way for recreational genetic testing. An approach that should be completely banned by legislation. If FDA has done so, let's wait for what it may happen in Europe where the regulator is still planning a change of the regulation in 2022!!! Meanwhile, the door is open (to the worst for citizens).

New album by Txarango. Enjoy it!

Learning to say no

Cost effective but unaffordable: an emerging challenge for health systems

There are big questions unanswered in health policy, and the social willingness to pay for a costly and effective technology is one of them. In a recent article, a description and controversies of NHS budget impact policies are explained:

The budget impact test means that technologies costing the NHS more than an additional £20m a year will be “slow tracked,” regardless of their cost effectiveness or other social or ethical values. This risks undermining the existing opportunity costs framework.

Therefore if there is a costly and effective therapy that has an impact budget greater than 20m, than next steps are uncertain in UK. This is the setting.
Really this affects all health politicians, and the issue is related to prioritisation and price regulation. The "solution" to the first issue is to delay prioritisation to the next minister, and what it is possible is to renegotiate prices of drugs. As I have said many times, prices are a fiction, because what it is under negotiation is a contract with the government, therfore the whole amount (p·q).

Budget impact is essentially the price per patient multiplied by the number of patients treated. Yet the prevalence of someone’s condition should not determine their access to treatment. The principle of equity means that like cases should be treated as like; the NHS Constitution requires the NHS to respond to the clinical needs of patients as individuals.

Righ now in Catalonia cost-effectiveness is a also a fiction, since prices are confidential, and it is not possible to estimate the ratio. Budget impact is the option.

Prix Pictet. Photo Exhibition in Barcelona

You can't miss it

Paying the bill of gene therapy

GENE THERAPY: Understanding the Science, Assessing the Evidence, and Paying for Value

Approximately 12-14 investigational gene therapies for additional ultra-rare conditions and some for more common conditions, such as haemophilia and sickle cell disease, are progressing through the developmental pathway and are expected to reach regulatory approval within the next 2-3 years

These therapies rely mostly on viral vector techniques, therefore they don't take into account the coming genome editing, the most disruptive one and the most recent as well. If this new technologies reach the market, how should be paid and applied?. This is what a recent report explains and gives details for decision makers. It is really welcome, the issue deserves a deeper understanding.

Situation in Europe
Glybera and Strimvelis, have been granted marketing authorization in the European Union by the European Medicines Agency (EMA):
- Glybera was approved by the EMA in 2012, but has since become the world’s most expensive short-term treatment (Adams, 2016), and as such has not been widely successful - it has only been used by one patient, with the prescribing clinician overcoming steep bureaucratic hurdles to obtain insurer funding (Abou-El-Enein et al., 2016a).
- Strimvelis received marketing authorization in 2016. Patients can currently only be treated in Milan, due to the treatment’s extremely short shelf life which dictates that cells must be infused back into the patient in less than six hours.

More efforts should be devoted to understand this emerging market and assess its value.

Caro Emerald

Rethinking income inequality and health (once again)

Income Inequality and Health: Strong Theories,Weaker Evidence

The inequality frame is usually flawed, and this is specially clear when the metholodogy and data to support the statements are biased. Let me suggest today this article that summarises perfectly common misunderstandings on this relationship. It would be a great input for a review and remake of recent papers.
The summary:

What is already known about this topic? A large body of research has examined the association between income inequality and average health. A separate body of research has explored income disparities in health. These two traditions should be seen as complementary, because high and rising income inequality is unlikely to affect the health of all socioeconomic groups equally. 

What is added by this report? Although plausible theories suggest that rising income inequality can affect both average health and health disparities, empirical tests provide only modest support for some of these theories. We argue that understanding the effects of income inequality on health requires attention to mechanisms that affect the health of different income groups, thus changing average health, disparities in health, or both. 

What are the implications for public health practice, policy, and research? Progress is likely to require disentangling direct effects of rising income inequality, which operate through changes in an individual’s own income, from indirect effects, which operate through changes in other people’s income. Indirect effects of rising income inequality may change a society’s political and economic institutions, social cohesion, culture, and norms of behavior, all of which can then affect individuals’ health even if their income remains unchanged.

PS. If someone needs an estimate of morbidity, please avoid inconsistent approaches. If someone needs policy guidance don't trust on cross-sectional data on such a difficult issue.

PS. My posts on health inequalities.