Hey, lady, you got something … right there

I find myself in San Antonio, Texas on Ash Wednesday, visiting a Catholic university.  Should I find some black crayon to blend in?  Coffee grounds?

Somebody went a little crazy with the mascara

Here’s a nice article on the religious use of ashes:


An excerpt:

The use of ashes in this case helps the communitas manifest publicly, but the ritual itself remains powerful without the visible signal. S received his ashes on Ash Wednesday night, and during the accompanying mass, the priest reminded the congregation that the wearing of ashes is only meaningful if you believe in the ritual itself. That is to say, whether you get ashes at 8:00 am and wipe them off immediately or at 8:00 pm and could only wear them for a few minutes, if you accepted the meaning behind the ritual then your place within the network is confirmed. The visibility made possible by this sign is a byproduct of the event, but it is not the object of the performance. However, if this is completely true then the homeless woman’s lack of ashes should not have impaired her ability to obtain more assistance. I don’t think it necessarily did, but her personality is known in these quarters quite well and I think her statements may have been viewed as manipulative given the context.

Understanding the Hayflick Limit, part 2

Telomerase makes new DNA from an RNA template

Last time, we started into telomeres, and I hinted at the function of telomerase.  Telomerase is an enzyme found in most organisms that adds bases to the ends of your chromosomes, extending the “aglet” (telomere) of the chromosome.  It does this in a rather startling way… it has its own RNA sequence that it uses as a template for making new DNA.  This is startling, at least to a virologist, in that it’s very much like what a retrovirus does.  Telomerase is considered a reverse transcriptase, meaning it takes an RNA template and makes complementary DNA from it.  This is opposite from the usual flow of information in the cell  (DNA –> RNA –> protein).  In the case of telomerase, what is copied is a simple motif of a a few bases repeated many thousands of times in a row.

Normal embryonic cells have active telomerase, as do some adult cells that have to divide often, like white blood cells.  Most cells, though, have their telomerase gene “shut off” so that no more can be made.  Remember that every time a cell divides, those telomeres get shorter by a few hundred bases, eventually getting too short to hold the ends, and the chromosome becomes unstable.  There are some diseases that result from premature shortening of the telomeres (Werner syndrome), and the patients have signs of premature aging (“progeria”).

The idea that the upper limit of our lifespan (“cellular senescence”) is somehow tied to a single biological phenomenon is intriguing.  If you, dear reader, immediately begin wondering whether this ticking clock can be silenced, or turned back, you are not alone.  I imagine every young scientist first learning about telomeres and telomerase imagines themselves as the saviors of mankind, or perhaps fulfilling the lines of the “Necronomicon”:

Cthulhu: telomerase positive

That is not dead which can eternal lie.
And with strange aeons even death may die.

So why can’t we just “turn on” the telomerase activity and stop the inevitable shortening of telomeres which causes cellular replication to fail in the elderly?  It has to be pointed out that some organisms do not succumb to senescence, and they are essentially immortal, although none of them are smart enough to clean up on long term, low risk investments.  Key examples are lobsters, jellyfish and coral.  Lobsters in particular are interesting because they have active telomerase throughout their lifespan, and they actually appear to be more fit the older they get.  That subject is a riddle that, so far as I know, remains unsolved.

Why do we poor mammals have to be content with a scant 100 or so years of life?  Why can’t we, like the lobsters, live forever?  The answer lies in one word:  cancer.  Cancer is built in to our biology.  Any system that requires exquisitely tight controls will eventually fail.  If that system governs the rate at which cells grow and divide, you will eventually have out of control growth.  The longer you walk this tight rope, exposed to mutagens in the air, the soil and the water, the greater the risk of failure.  Telomere shortening may have evolved as a way of keeping cancer in check, eliminating older cells that have been exposed to DNA damaging conditions.  Turn telomerase back on, and those geriatric cell lines will continue to accumulate damage, increasing with each division the chance of cancer developing.  It may not be a coincidence that the immortal animals live in dark oceans where UV damage is minimized.

Cruz Hernandez: 128 yrs old at death

That’s the cellular evolutionary view of senescence.  The organismal evolutionary view is more intuitive.  If old animals never die, and the number of animals that can be sustained in an ecosystem never changes, then the larger, older animals would outcompete the young, smaller animals for food and resources.  With no new generations, the gene pool becomes very static and the diversity remains low, making the population susceptible to pathogens.

“Futurists” like to talk about when the first immortal human will be born.  But I agree with Dr. Hayflick on this:

“When it becomes possible to slow, stop, or reverse the aging process in the simpler molecules that compose inanimate objects, such as machines, then that prospect may become tenable for the complex molecules that compose life forms. “

The concept of an immortal human with active telomerase ignores the central fact that older cells develop cancer.  Any proposal to immortalize humans must be prepared to deal with the escalating cancer and disease risk.  Aging and senescence are not just a matter of allowing cells to continue replicating.  It is dealing with the inborn errors of metabolism and biology.  As Dr. Hayflick suggests, if we can’t stop simple machines from breaking down, what hope do we have to prevent the same process in the very complex machine that is a human?

In a future post, I hope to explore those rare human cells that have achieved immortality as transformed cultures.

Understanding the “Hayflick Limit”

Leonard Hayflick, 1961 at the Wistar Institute

I met with an eminent scientist in the course of my work, and as part of the background research, I checked out his CV (curriculum vitae).  His background is substantial, Harvard education and NIH post-doc, but his mentor during his post-doc was Leonard Hayflick.  I knew about the Hayflick Limit from grad school, but I had never read the history of the phenomenon.  I thought it might make an interesting example of how science is conducted.  We’ll come to a definition shortly.

You may be aware that scientists routinely grow human cells in flasks.  It’s called cell culture or tissue culture.  We’re not talking about an arm or an ear, here.  The cells are only visible as a thin layer of translucent material, in the case of cells that adhere to a solid surface, or a slightly grainy slurry, in the case of cells in suspension.  We feed these cells, and they are bathed in, a solution containing salts, sugars, amino acids and other essential nutrients.  They also sometimes get antibiotics and growth stimulants.  Most also receive a healthy dose of serum, extracted from cow blood, in order to provide specialized proteins that stimulate growth.  We might say, for example, that our K-562 cells (immortalized cells from a patient with myelogenous leukemia) grow in RPMI1640 (a specific sugar/salt/amino acid solution) supplemented with 10% FBS (fetal bovine serum) plus pen/strep (penicillin/streptomycin) and L-glutamine (needed by some cells, and somewhat unstable in

Cell culture flasks with culture medium

storage).  It looks complicated, but is not much different from a recipe for chicken soup.  The flasks containing cells in their growth medium are placed in incubators, usually at 37 C and 5% CO2.  Periodically, the medium has to be changed, and if the cells are rapidly growing, they have to be passaged or “split”, removing a fraction of the growing cells, to avoid overgrowth.  We guard carefully against introducing infectious agents, since the cells have no immune system and any bacteria or fungus landing in the cell culture medium, loaded as it is with the materials of life, will rapidly overgrow, acidify the solution, and kill the cells.

So those are the very basics of growing mammalian cells in culture.  Now we come to the interesting part.  If I take a small scraping of your cheek and transfer them to a flask, they will grow for some time, then eventually they’ll stop growing and instead begin dissolving.  The number of divisions that occur before this happens is called the Hayflick limit.  Initially scientists assumed this was a technical problem with how they were culturing… not enough nutrients, or the introduction of bacteria or fungus pathogens… something was ending the life of the cells.

Some cells, however, could continue to grow almost indefinitely, almost always cancer cells or viral infected cells.

If they split the cells into two flasks, both cultures stopped replicating at about the same time, which made simultaneous infections unlikely.

Cells taken from embryonic tissues lasted much longer than mature cells taken from older patients.  Hayflick measured the number of times an embryonic cell could divide.  It converged on a value of about 50 divisions.  This would later be called the Hayflick limit.

Many cancer cells (~80%) do not obey the Hayflick limit, they are "immortalized".

So once the phenomenon was known and the puzzle was well-characterized, a number of hypotheses were advanced to explain the anomalous observation.  They focused on the exceptions to the Hayflick limit rules, cells that never stop growing, which we call immortalized cells.  These cells were almost universally taken from either cells infected with specific viruses, or from very active cancer cells.

So what do these two conditions have in common?  Both had damage to their DNA in certain specific regions that mediated cell division and self-destruct mechanisms.  Most cells recognize their genetic damage as a good reason to self-destruct, to undergo apoptosis.  These cells no longer had the ability to respond to that self-destruct signal.  That alone wouldn’t have been enough, though.  They had also acquired an enzyme that was able to add new sequences to the ends of their chromosomes.   These sequences are called telomeres.

Telomeres are to the chromosome as the aglet (the little plastic or metal collar) is to the shoelace.  The telomere prevents the DNA strand from “unraveling” by providing a long string of very tightly bound base pairs.  One of the consequences of copying your DNA is that a little chunk from the very end of each of your 46 chromosomes is lost every time they are copied.  When you are a fetus, you have nice long telomeres securing your chromosome ends.  As you age, as the result of replicating your DNA, they get shorter.  Eventually, they become too short to hold the ends together, and we think that’s why some cells must stop replicating.

Enter telomerase, a cellular enzyme that extends the length again.  In my next post, I’ll examine what it does in the cell; whether it can be harnessed to make us essentially immortal, and we’ll examine some of the claims of futurists and anti-aging researchers.  We’ll also look at why evolution favors our aging and eventual death, and those rare human genomes that have achieved near immortality.

I’ve just use something I learned on “Phineas and Ferb” in a science posting. Day complete.

Electronic cigarettes

The video that YouTube considers SPAM.

I think it’s going to be impossible to please all the people all the time on this topic.  Comments are open and welcome.  My “short-version” position for the TL;DNW (too long, did not watch) crowd is:

“Quitting cigarette smoking can only be a good thing, however not all nicotine replacements have met the same standards of evidence and testing.  Electronic cigarettes may yet be found to be effective and safe replacements for smoking, the evidence isn’t yet sufficient. but they should be regulated under the highest standards of safety and quality: the federal medical device codes.”

A new media, the same message

I started on the Internet the same way most people do.  I watched the “Charlie Bit My Finger” style videos, laughed at captioned pictures of cats, and then like most people I encountered someone with an opposing viewpoint.    In my case it was my first encounter with a Young Earth Creationist outside of my upbringing in rural Texas, where even my high school biology teacher openly professed her disdain for anything other than a literal interpretation of Genesis.

Young, Angry and Religious

A search for this creationist led me to Thunderf00t, and to potholer54 and ExtantDodo.  I had no idea that scientists ever visited the seedier parts of YouTube to engage with what I would come to call science denialists.  It hadn’t occurred to me that there were a large group of people out there on the Internet who cared about science, reason and rationality, but didn’t have the training and background to see the flaws in denialist arguments.

So I downloaded an evaluation copy of Camtasia Studio 6, dug out an old microphone/headset I picked up in college for $20, and made a video on the molecular evolution of the eye.  Two more on the same topic followed, all very detailed molecular biology of optical systems.  I think I had 100 views (combined) after a week, but I did get some very positive feedback.

My next video was on the Discovery Institute, and I issued a challenge to them to produce a gene which did not have the hallmarks of common descent: a non-phylogenic gene sequence.  Challenges were all the rage on YouTube at the time.  Fortunately for me, Thunderf00t watched it and liked it.  It sparked a friendship and collaboration, and our joint video went out to the entire atheist/rationalist community.  Overnight I went from less than 500 subscribers to several thousand.  I was hooked.

As time has gone by, my subscriber base has grown.  This only makes it more frustrating when I am sabotaged by the media site I use.  YouTube has made it difficult to trust that my content will be preserved, available to all those subscribers who have given the precious gift of their time and attention.

That’s why I’m starting this blog.  It will give me a place to put my video content so that regardless of forum, I can make it available to you, my subscriber.  It also opens up some new formats and possibilities.  I’m going to be exploring this new medium, so I hope you’ll consider checking back from time to time.

Thanks for following me here from YouTube, and if you’re just discovering my work, welcome!