Tuesday, November 12, 2019

Thoughts on Death in an Aging World

It has nearly been a year since I created The Philosophy Meetup Kingston , a group that currently has 130 local members! In that time I have organized 35 events to bring philosophy into the pubs of Kingston, and get locals engaging with philosophical topics ranging from the existence of god, to personal identity, ethics, human happiness, politics and science. It was been a very enriching experience for me. An opportunity to meet new people and make new friends, address topics I haven't thought about for a long time, and hear a more diverse range of insights and perspectives than what I am likely to be exposed to in a university classroom setting.

I haven't been blogging very much the past few years as I have been more actively involved in "experiential learning" of various sorts. Teaching for 5 summers in prison, running a social support group for divorced fathers, and trying to bring philosophy into elementary classes and pubs. These activities have all been very rewarding for me, and helped me develop as a human being and academic.

For tonight's Philosophy Meetup we are discussing the ethics of assisted dying (a dozen people have signed up to attend). The assigned resources for members to watch in advance are this and this.

This is a topic that, at least professionally, I haven't given serious attention to. So to gather my thoughts I thought I would grapple with trying to answer the following (rather macabre) question: "What would constitute my “ideal death”?”.

I came up with a list of 5 criteria that would definitely make the list of my ideal death. They are:

(1) my death would be forestalled for as long as possible (so I have the opportunity to enjoy the joys of a lengthy (but finite) life
(2) it be a sudden death vs prolonged one
(3) that it be painless vs painful
(4) that it be one that imposes minimal (e.g. caring) burdens on loved ones and family and
(5) it be an economical vs expensive death.

The problem is, (1) is in conflict with (2)-(5). So the real pressing question becomes- what is the most reasonable and feasible “non-ideal” death we should aspire for in an aging world?

Perhaps one useful way to think through the muddy waters of navigating the tough trade-offs that must be made (e.g. should we delay death when it causes more pain, expenses or caring burdens on others?) is to think about the role of autonomy in our death. Would we like (ideally or even non-ideally) to have some control over when our death occurs. Of course there is a concern with raising this point, as it begins to sound like it sanctions suicide. A person who, in a distraught mental state, might assess the benefits of going on living as not sufficient to warrant living thus opts for suicide and justifies this as an "autonomous decision". I want to guard against that type of conclusion.

The role autonomy should play here is very constrained and contextual. All-else-being equal, the ideal death would not be the result of a conscious decision we make when there was an alternative option that entailed more time living a functional and flourishing life. But in circumstances where there is a terminal illness/severe frailty involved, then granting a person autonomy over when they die seems to me to be very compelling.

Professionally my research hasn't focused on these questions as I have been much more interested in the question of how we can forestall the onset of disease, frailty and death by retarding the aging process itself. But having witnessed one parent die of chronic disease this past year, and another survive over a decade on chemotherapy, I feel this is a topic I will devote some serious time and reflection to. And hopefully write up my ideas as something to contribute to the academic debates on the ethics of assisted suicide.


Monday, October 21, 2019

Russian ‘CRISPR-baby’

Nature News has the scoop on the latest case of gene edited human eggs, this time an alteration to prevent deafness:
...he [Rebrikov] will soon publish the results of his egg experiments, which also involved testing CRISPR’s ability to repair the gene linked to deafness, called GJB2, in bodily cells taken from people with this mutation. People with two mutated copies of GJB2 cannot hear well without interventions, such as hearing aids or cochlear implants. Rebrikov says these results will lay the groundwork for the clinical work.

Rebrikov adds that he has permission from a local review board to do his research, but that this does not allow transfer of gene-edited eggs into the womb and subsequent pregnancy.

....Rebrikov told Bloomberg last month that he wants to follow regulations that have been internationally agreed on when moving gene editing to the clinic. But he also expressed frustration that none exist yet.


Sunday, October 20, 2019

Publishing Advance to Graduate Students

Tomorrow I am giving advice to graduate students on publishing their first article and I thought I would write up some general reflections on what I intend to say here. I will cover the basics of: the Why? When? What? and Where? of publishing.

Firstly let's start with the question "Why aspire to publish?" I would identify two general types of answers: (1) it is your calling, and (2) for instrumental (careerist) reasons.

Regarding (1), for those students who have undertaken the PhD program because they aspire to become scholars and teachers, publishing is an intrinsically rewarding process because they find great satisfaction in the creation and distribution of knowledge. After doing extensive reading and research, an aspiring scholar reaches a point where they want to actually contribute to (and not simply learn about and observe) a debate. This is the most foundational reason for wanting to publish, and a passion that (if nurtured and cared for) can sustain a scholar throughout their entire career. If you do not have a passion to create and disseminate knowledge, you should consider a career outside of academia.

For (2), there is the motto "publish or perish". It is a motto that starkly conveys the reality of the job market. Landing that first tenure-track job, and ultimately getting tenure, will require you to publish often and in quality venues. It is imperative that doctoral students know this reality of their career aspirations so they can come up with an effective plan early on for putting themselves in the best position possible for the competitive job market.

When to publish? I myself began to submit to journals while still in the MA program. My very first publication was based on my MA thesis and it appeared in a graduate student journal. I probably tried to get published too early. I had (prematurely) sent out a few other things to more established journals in the field but they were all rejected. One was based on a graduate level history course I took as an MA student on utopian socialism. Another one was part of my MA thesis. Those were, with only one other exception, the only things I sent out to journals that never found there way, in some form or other, into a published article or chapter. But I gained valuable insight into the publishing process via referee and editor feedback.

During my three year PhD program I was very proactive about sending chapters of the dissertation out for publication, so that by the time I defended my PhD in 1999 I had published here, here and here (twice). Having papers out in print as I hit the job market really helped me land academic appointments as they were a tangible benefit to the RAE process in the UK where a scholar's top publications are assessed as part of a department's research score.

What to publish?
Your best work. Chapters of your dissertation. A strong term paper. This was the first publication I had that was independent of my dissertation, and took 10 years from the time I first developed the ideas in a graduate level course as an MA student till when the final published paper appeared in print. As I was working on my dissertation I took the view that nearly every chapter I was writing should be a "stand alone" publishable journal article. Not every chapter ending up being that. But I think this helped motivate me to write the dissertation in less than 3 years, and to successfully publish substantive parts of it in decent journals.

Where to publish? Early on in one's career I would avoid publishing in invited edited collections, and focus instead only on getting peer-reviewed articles published in respectable journals. Those carry the most weight in terms of career advancement. Furthermore, proving yourself in the peer review process of journal publishing will, I believe, make you a better scholar. Your ideas will be vetted by a more diverse and rigorous "market place of ideas" than in conference proceedings or edited volumes with scholars you might have connections with/shared viewpoints.

As with most things, there are some complex tradeoffs to consider when deciding which journals to submit your work to. The rejection rates are very high in the top journals, so is it wise to submit your work to those journals (which might take months to hear the outcome) when you are trying to be competitive on the job market? This is not easy to answer. You are likely to get differing advice on the importance of quality vs quantity of journal publications. Personally I think you should send your very best work to the best journals, and have a plan to send to second-tier journals in the event they are rejected. But avoid submitting your work to low quality journals, conference proceedings etc. as they will carry much less weight and impact than respected journals. It was only after 17 years of publishing almost exclusively in peer-reviewed journals that I agreed to publish more in invited edited collections. But even then I am very selective about doing so. They have to be quality venues and on topics I am curious to write about and believe are genuinely significant. I never write things to just fill my CV.

That is my two cents worth of advice to junior scholars about getting the ball rolling with publications. All the best to everyone starting that part of their journey!


Saturday, September 28, 2019

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.


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).


Thursday, September 12, 2019

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.


Sunday, September 08, 2019

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


Friday, August 30, 2019

Study on the genetic basis of human sexuality

Nature News has the scoop here on the latest study (published in Science here) into the genetics of sexual orientation.

A sample from the news item:

The largest study to date on the genetic basis of sexuality has revealed five spots on the human genome that are linked to same-sex sexual behaviour — but none of the markers are reliable enough to predict someone’s sexuality.

....Although some researchers and LGBTQ advocates might question the wisdom of conducting this kind of research, Birney says that it’s important. There has been a lot of sociological research on same-sex sexual behaviours, he says, but this is an incredibly complicated topic. It’s time to bring a strong, biologically based perspective to the discussion, Birney says.

The abstract for the study:

Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in same-sex sexual behavior, only partially overlapped between males and females, and do not allow meaningful prediction of an individual’s sexual behavior. Comparing these GWAS results with those for the proportion of same-sex to total number of sexual partners among nonheterosexuals suggests that there is no single continuum from opposite-sex to same-sex sexual behavior. Overall, our findings provide insights into the genetics underlying same-sex sexual behavior and underscore the complexity of sexuality.