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Mitochondrial DNA is Evolving, and That’s Amazing!

October 13, 2013 3 comments

This week in the news there have been a number of articles about a new technology that has allowed the creation of an embryo from three parents, and boy it is creating controversy.

Three parents you say?

Yes.  Of a sort.

The case in point regards a woman who unfortunately had a child with a deadly mitochondrial disease.   Mitochondria are organelles (“small organs”) inside each of our cells where ATP, our primary energy source, is made.  Mitochondria are special in that unlike other organelles, they carry their own DNA.  In the case of this woman’s tragically afflicted baby, defective DNA that could not support much life.

Geneticists have developed technology to create an healthy embryo without the defective mitochondria by placing a nuclei from the woman’s mitochondrially defective egg into a donor egg, after removing that egg’s nuclei.   They then fertilized the new proto-egg with the husband’s sperm to create a new embryo.   In essence, the egg had three parents – two in the nuclei, and a third one in the mitochondria.

And the world shuddered.

From all corners were cries of “we’re playing GOD!!!”.  “We are altering the human race!!”  “We’re no better than Mengele!!”

Most of this comes from a bright line we have put around genetics research that says we will not genetically engineer human beings.  Legitimate bioethicists have felt that this is something we should not do, because of a ‘slippery slope’ towards eugenics.  Religious radicals are just uncomfortable with advancement in science in any kind.  They say it is because it is against God, but I think it is because a true understanding of how the universe works deprecates the validity of their religion, and thus sparks a crisis of faith.

But either way, most people think that manipulating human DNA is unethical.

I, for some reason, don’t see it this way.  In fact, I couldn’t be happier that we have made this leap, and hope we keep leaping.   We are coming to understand how we are put together, and in such we are coming to understand how to manipulate that process.  That is exciting, not concerning.

We are not “Playing God”.   For us to be “Playing God”, a “God” would have to have been the reason we came to be on this earth.  And unequivocally, it is not.   The evidence for evolution is so unbreakably strong that to claim that we are here because of “God” is purely ignorant.  Humans are on this earth because our genes were selected for over millions of years, not because somebody put us here.  If you believe in God, fine.  But please don’t hold humanity back from our future by claiming that we are breaking your religious rules.

Even worse is the claim that to genetically engineer a human is akin to Nazi experiments.   True, Hitler wanted to manipulate the future of humanity.   But he didn’t want to do it by changing the genetic information of the future.  He did it by murdering the people who were already here.  To claim these are the same thing is an affront to geneticists, and is too good for Hitler.

In truth, I am absolutely head over heels excited to hear that we were able to eliminate a deadly genetic disease from a family through genetic means.  What this means to me is that we are actually CURING disease, not just treating the symptoms that it produces.

Evolution is something that is terribly misunderstood.  Its detractors really don’t get how it works.  People who don’t understand it think it is about the selection of individuals over others, and thus don’t believe it could ever have ended up in us, but that is not really how it works.  It is the selection of GENES that drives evolution, not the selection of individuals.

The problem in this case is that mitochondrial genes do not reproduce sexually, but are rather copied directly from their parent mitochondira, and as such they do not evolve.  As such, problems in the mitochondria are passed on forever, never changing except by random mutation.

But now, for the first time, mitochondrial DNA is evolving.  Perhaps not by natural selection, but it is evolving nonetheless.  And that is exciting.

Don’t take this to believe that I am ignorant of the potential problems.  But they are technical, not ethical.  Obviously we can not open the doors to unlimited human experimentation, but this is a first step, and it is a good one.

Categories: Fun Stuff, General

What Not To Wear (Med School Interview Edition)

November 11, 2012 13 comments

Yesterday I was going through my closet and separating out a lot of clothes that I no longer wear to give to Goodwill.  Among the many things I selected to never see again, I noted a tie that I wore to my original medical school interviews.  An wow.. it was a problem.  Did I really wear this?  I then decided to actually put together the outfit that I wore to my interviews.  And now I realize… its a miracle I ever got in.

I grew up in Oregon, where no one ever wears a tie, and no one ever dresses up.  When it came to interview for medical school, I truly had no appropriate clothes.  I consulted my father, who suggested the outfit you see here:

Note the tie that is missing the material in the back to allow the tie to line up.  No problem there.. just use a paperclip.  Really.  While my father was trying to lead me in the right direction, little did I know this was the same father who fifteen years later would wear a tee shirt to my wedding.

So basically, I walk into medical school interviews looking like this:

Note the rather ill-fitting sport jacket, Mathlete regulation length tie, and unmatched pants that are too small.  Ignore the pleats, they were actually in fashion then.

But how was I to know? I was a computer science major and a total geek.  This was dressing up big time.  I was fully expecting that when I went to interview I would be looking sharp.

Not so much.  When I arrived to my first interview at Baylor College of Medicine I found myself terribly underdressed compared to all the Brooks Brothers suits sitting next to me.   While I looked maybe all right, they looked good.  And more importantly, they all looked the same, and I looked different.

And perhaps that was my mistake, in that this was what I was actually going for.   I knew that a suit was the right thing to wear, but I had a rebellious streak in me that said ‘screw that! I don’t need to buy and wear a suit!  What matters is my brain and what I have accomplished!”  I also had a bloodstream that ran with Oregon blood, where most people respond to a person in a suit with the comment “so who died?” And so I proudly wore clothes that looked right out the closet of my University of Oregon math professor Schlomo Libeskind, who inspired my love for higher mathematics and modeled wearing beltless polyester pants up to his nipples.

Fortunately, I survived the process and indeed was accepted to medical school, though not as many as I thought I should have given my academic record.  As I was looking back in this during residency interviews, I decided that this time was not going to make the same mistake twice!  I was going to wear a suit!

And I chose this:

My mother had found it at a thrift store and extolled its beauty.  It was in fact a suit, and it was in fact from a fine Italian brand.  Furthermore, it was a suit that when new was quite expensive.

But what it was not was a suit that fit me.  It was way too big then, just as it is today.  Furthermore, being found at a thrift store, it was in fashion twenty years earlier, not at the time it was being worn.  It was also brown, which still set me aside from all the other blue and black suits that interviewed for residency with me.

I did get some “nice suit” comments followed by furtive glances to the side or floor.  As a person who now plays a lot of poker, I now realize that those comments were purely ironic.   I also heard “bless your heart” in the South a number of times, which by the third year of my residency in Charleston,SC I knew was actually an expression of kind condescension.

Fortunately, despite this suit, I got into the residency I wanted.  Apparently being the rare highly qualified male applicant to an OB/GYN residency was worth more than the ill-fitting suit cost me.   And at the end of my residency, the chairman took me to a fine men’s store with the invitation “Son… they’re having a sale.. and you need a nice suit for your faculty interview.”  “But I have a suit!”  “Son… you’re going to a be a faculty physician… you need more than one suit.”

* * * * *

At the time, I didn’t think this dressing up business was important, but now as a  faculty member I realize that it was.  There is no doubt that on the days that I interviewed in those clothes, the faculty were laughing about me at the applicant review sessions.   I have no doubt that at my medical school interview they were saying “how about that Fogelson guy with that sportcoat and no belt?”  And at my residency interview I’m sure it was “how ’bout that huge brown suit guy!”.  Of course, does that really hurt a person?  As a person who interviews and ranks applicants, I can say that it almost certainly does.  An applicant has only a few minutes to convince someone that on a very subjective level that they deserve to be in the medical school or residency.   In the end, you hope that your interviewer is talking about how smart and accomplished you are, and not about how you were dressed.   It seems so superficial, but that doesn’t make it not true.

So the truth is this:  When you interview for a job in medicine, your clothes should be invisible.  They should be well fitting, relatively conservative, and ordinary.  They should be neither particularly bad nor the height of fashion, leaving your interviewers nothing to comment on other that what really matters – the person wearing the clothes.

When I interviewed for medical school, I interviewed at 8 schools and was accepted at one.  I had great MCAT scores and way more medical experience than could be expected of any applicant.  If I had been dressed like this I probably would have gotten into a lot more schools:

You Know Nothing Jon Snow

September 8, 2012 7 comments

As a physician, I occasionally encounter patients who feel like they know a great deal more about medicine than they actually do.  Sometimes its a family member of a patient.     Occasionally they are right, in that they have a particular cache of knowledge about a particular condition that surpasses me.  In those circumstances, such patients or family members are able to augment their care.   Far more often, however, their expertise is far less than they think.

For example, I once cared for someone who clearly needed a blood transfusion.  A family member was in strong opposition, mostly because that family member was Jehovah Witness, even though the patient was not.   That family member presented all kinds of information about alternatives to blood transfusion, and clearly right from a pamphlet they had read.  At a fundamental level, said family member believed that there was always an alternative to blood transfusion and it was never actually necessary.
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Some thoughts on Male Circumcision

November 21, 2011 196 comments

One of the interesting things about running a semi-popular blog is that from time to time the blog community decides to take up a topic and run with it, completely without any stimulation from me.  This happened recently on the Academic OB/GYN Facebook page, where a group of concerned individuals carried on a serious and passionate discussion about the merits of circumcision.   As such discussions tend to be, this one was dominated by the anti-circumcision activists, with occasional interjections by those that were less concerned about the issue, including myself.

Circumcision is an interesting issue because it crosses multiple boundaries.  It is a social tradition in many cultures, and in some cases considered a religious mandate.  It is also an ethical issue for many, with some feeling that it is an assault on an infant with long term negative impact on their psychosocial health.  For some it is just cosmetic.

As a young person, I always thought that my penis looked like penises were supposed to look. It looked like my father’s and my brother’s, and anyone else’s I had ever seen.  For the most part, I was blissfully unaware that a penis could look any other way, until one day in high school when my world completely changed.  I happened to see a friend’s penis we were showering after wrestling practice, and in that flash of a moment all kinds of things went through my mind.  Did he have some kind of growth on his penis?  Could he pee out of that thing?  A few other choice thoughts.  I can still remember the shock to this day.  All I had ever seen looked like mine, and in that moment what I saw was foreign, revolting even.  You see, from my frame of reference he looked like an alien.  It took me a few minutes and SNAP! it came to me like a ton of bricks – he has a foreskin.  He probably doesn’t have an alien death ray then.   I can relax about that one.

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Categories: General

Grand Rounds for January 4 2011

Academic OB/GYN was featured on the web’s Medical Grand Rounds for January 4 2011.  Lots of good stuff worth checking out.

Categories: General

Academic OB/GYN at ACOG!

Well folks – I’m in San Francisco at ACOG.   In addition to the dinner monday, we will be doing a fair amount of ACOG content.   Check back for daily summaries of what’s going on at ACOG, including podcasts with interviews with poster presenters and industry folks.

If anyone wants to come to the dinner monday night, please RSVP soon!  We’ve got about 16 coming so far.  Sage Healthcare is sponsoring, so come on out and enjoy some great food and drink and meet other fans of Academic OB/GYN!

Categories: ACOG ACM, Fun Stuff, General

HIPAA, Medical Case Reports, and Unbalanced Benefit in News Reporting

February 4, 2010 20 comments

On January 12, 2010, a magnitude 7.0 earthquake rocked the island country of Haiti, destroying much of the capital Port Au Prince and leading to the deaths of as many as 200,000 people.  Since this time, thousands of images of the resulting carnage have been published in both traditional media and on internet sites.

Recently there has been some discussion about the appropriateness of some of these images, particularly those that depict individual humans in despair or even in death.  Some have argued that such images should not be published without the express consent of the person depicted, or with the consent of the next-of-kin in cases of the dead.  Media, for the most part, has held that in cases of extreme human events the benefit of publicizing the truth outweighs whatever emotional harm might come to an individual through publication of their plight.  They argue that the many outweigh the few, in this case.

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How can Academic OB/GYN help you?

November 2, 2009 11 comments

Academic OB/GYN isn’t just about me blathering on about current literature and interviewing folks – its about YOU too!   If there is any way I can help you, I want to know.    Send research questions, and I’ll try to answer them.  Need a video of some kind of surgery, I’ll try to make it.   Want a place to publish your ideas about our field, the blog’s all yours.  Wanna get some ideas from your colleagues that read the blog?   We can do it.

This thing is growing folks, and you can help.

Every time an Academic OB/GYN viewer asks a question, a blog post gets its wings…..

email@academicobgyn.com

tweet @academicobgyn

Facebook Academic OB/GYN

or just leave a comment!

Still active, if not posting…..

The Academic OB/GYN podcast continues to go on strong despite the lack of new content.  We’re now over 3,000 downloads, which is great!   I want to assure listeners that I’m still working on new content but have been held back by my real job, and my upcoming move to Charleston, SC.   Once I’m settled in my new location I plan to move the blog to a private server and start creating more podcasts.  So stay tuned…

Misoprostol for post partum hemmorhage? meh.

November 5, 2007 6 comments

Ok – here’s a bit of rant inspired by something on call last night.

A multiparous patient labors for about 8 hours during a pitocin induction and develops a postpartum hemmorhage. Pit, methergine, and eventually hemabate are given with minimal response. The resident decides to place rectal misoprostol, and the uterus gains tone about a minute later. The resident remarks how well the miso worked and how we should us it more in the future.

This drives me crazy.

1) There are no venous channels that run from the rectum to the uterus. People act like they are doing something special by putting it in the rectum or even in the vagina, when in reality they are just using either as a mucous membrane to absorb the drug. The pharmacokinetics of miso are well studied, and it takes at least 1/2 hour to reach high levels of miso in the blood, and therefore in the uterus. There is no way that in one minute a lot of misoprostol got to the uterus. In fact, if one wanted the fastest effect, one should give it to the patient orally, as that causes the fastest rise in blood levels

2) Many studies have shown pitocin to be superior to misoprostol in treating and/or preventing postpartum hemmorhage. Why? Because of the above point – the IV pit gets to the uterus very fast. The miso takes 1/2 hour or more.

3) These thought open up a related irritation, which is the “novel” application of miso by placing it in the uterine cavity to cure uterine atony. The endometrium isn’t even a mucous membrane. Though the pharmacokinetics of this application have not been studied, I don’t think absorption will be so great, especially with all the blood rushing into the uterine cavity (the problem we’re trying to treat).  Blood comes out of the uterus.  It doesn’t go in.

So what happened in this case?

First the patient had atony. Then she got pit, which didn’t work well because pitocin receptors were very downregulated after the long induction. Then she got two effective uterotonics in fairly rapid succession – both of which were effective. Coincidentally, a bunch of misoprostol was placed rectally right around the time the IM methergine and hemabate reached the uterus, which despite its parental nature, still takes at least a few minutes. So residents, keep using that miso if you want, but I think its benefit is in preventing delayed atony 20 minutes later, not in the acute setting.

Of course, miso is great for third world nations where there are no IVs or refrigerators to keep parenteral uterotonics around. Or for causing first and second trimester abortions. Or for ripening the cervix in induction. Or for priming the cervix before a tough EMB. Or for dilating the cervix before a D and E procedure. Its just not that useful for postpartum hemmorhage, IMHO.

A related irritation – people who put patients on powerful antibiotics after they spike a 101.8 fever eight hours in at 400 mcg q6h second trimester miso induction, unruptured.  What makes you think they are infected?  They are unruptured, and happen to be on a powerful prostaglandin that reliably causes fever and chills at high doses.  Please, just reassure the patient and give them some tylenol.  Don’t use NSAIDs to break the fever, as the misoprostol is causing a fever downstream of the cyclooxygenase enzyme the the NSAID is blocking.  Not that the NSAIDs will antagonize the miso (which somebody tried to convince me of once), just that they don’t work that well a miso inspired fever.

What do you think?

Nicholas Fogelson, MD

Academic OB/GYN.com

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