US Impeachment Inquiry: My Prediction

As a political theorist I never really stick my neck out to try to make predictions about how the real world of politics will unfold (which is like trying to predict the weather!). But here I will detail what I think is the most likely outcome of the current impeachment inquiry into President Trump- I think Trump will actually resign before the end of the year.

I know this outcome will sound very unlikely given how tenacious a political opponent Trump is (he doesn't back away from any fight), but in this case I actually think he has backed himself into a corner with no real exit option. If the Trump Administration delays/obstructs the impeachment inquiry it will look very bad for him politically (costing him re-election). And if he provides the documents and testimony Democrats are seeking things will look even worse for him (they already look unsalvageable in my opinion, either because he will be impeached or at least lose the election as more troubling details come to light). And what this does is put the Republicans in Congress and the Senate in a "no win" situation. So far many of these players have remained quite. But they can't stay like that for long.

Many political pundits have expressed puzzlement with the fact that the Trump Administration released the phone memo this week that paraphrased the conversation between President Trump and President Zelensky. It certainly was out of character given that his modus operandi is to be uncooperative. Some pundits have suggested the Trump Administration released the memo because they think there is nothing to hide. I actually suspect the opposite is the case. I think it is very likely that the Trump Administration already realized that this recorded phone conversation to the Ukraine President, in conjunction with the whistle blower's complaint, and the attempts to cover it all up are BIG issues and ones that Trump's Presidency is unlikely to survive. I think the memo was released as the first (gradual) part of the resignation process. And now the Trump Administration's focus will be on how to have Trump exit in a manner that (1) makes him look as good as possible- which in Trump's eyes is as the victim of the liberal media and a Democratic conspiracy and (2) leave the Republican Party intact. That is the best end-game for both Trump and for the Republican Party (not to mention also for the American people!).

That is just my two cents worth as an uniformed observer trying to make sense of political developments south of the border. It is a very sad state of affairs, but also one that could be very instructive to the future health of American politics.

Cheers,
Colin

UPdate: and (3) before Trump resigns, he will try to inflict maximal damage on the Democratic party and their potential Presidential candidates. Of course that has always been on his radar anyways (and what caused his impeachment problems), but it will get even worse (and has since to whistle blower story broke last week).

Cheers,
Colin

Off-Target Toxicity in Cancer Drugs

Science Translational Medicine has this interesting article. The abstract:

Ninety-seven percent of drug-indication pairs that are tested in clinical trials in oncology never advance to receive U.S. Food and Drug Administration approval. While lack of efficacy and dose-limiting toxicities are the most common causes of trial failure, the reason(s) why so many new drugs encounter these problems is not well understood. Using CRISPR-Cas9 mutagenesis, we investigated a set of cancer drugs and drug targets in various stages of clinical testing. We show that—contrary to previous reports obtained predominantly with RNA interference and small-molecule inhibitors—the proteins ostensibly targeted by these drugs are nonessential for cancer cell proliferation. Moreover, the efficacy of each drug that we tested was unaffected by the loss of its putative target, indicating that these compounds kill cells via off-target effects. By applying a genetic target-deconvolution strategy, we found that the mischaracterized anticancer agent OTS964 is actually a potent inhibitor of the cyclin-dependent kinase CDK11 and that multiple cancer types are addicted to CDK11 expression. We suggest that stringent genetic validation of the mechanism of action of cancer drugs in the preclinical setting may decrease the number of therapies tested in human patients that fail to provide any clinical benefit.

Cheers,
Colin

Small Experiment Appears to Reverse Aging in Humans!

Nature News has this interesting news item on a small experiment in humans to reverse the process of biological aging!

The details:

For one year, nine healthy volunteers took a cocktail of three common drugs — growth hormone and two diabetes medications — and on average shed 2.5 years of their biological ages, measured by analysing marks on a person’s genomes. The participants’ immune systems also showed signs of rejuvenation.

....Checking the effect of the drugs on the participants’ epigenetic clocks was an afterthought. The clinical study had finished when Fahy approached Horvath to conduct an analysis.

Horvath used four different epigenetic clocks to assess each patient’s biological age, and he found significant reversal for each trial participant in all of the tests. “This told me that the biological effect of the treatment was robust,” he says. What’s more, the effect persisted in the six participants who provided a final blood sample six months after stopping the trial, he says.

The abstract from the study:

Epigenetic “clocks” can now surpass chronological age in accuracy for estimating
biological age. Here, we use four such age estimators to show that epigenetic aging
can be reversed in humans. Using a protocol intended to regenerate the thymus, we
observed protective immunological changes, improved risk indices for many age‐re‐
lated diseases, and a mean epigenetic age approximately 1.5 years less than baseline
after 1 year of treatment (−2.5‐year change compared to no treatment at the end of
the study). The rate of epigenetic aging reversal relative to chronological age acceler‐
ated from −1.6 year/year from 0–9 month to −6.5 year/year from 9–12 month. The
GrimAge predictor of human morbidity and mortality showed a 2‐year decrease in
epigenetic vs. chronological age that persisted six months after discontinuing treat‐
ment. This is to our knowledge the first report of an increase, based on an epigenetic
age estimator, in predicted human lifespan by means of a currently accessible aging
intervention.

Cheers,
Colin