Mitochondrial Donors in IVF

I want to revisit the article I posted about "three-parent babies." It's vaguely related to my research, but also I just find it plain fascinating (I do, after all, have something of a bias for mitochondrial research.)

The article describes a new technology that would allow people with mitochondrial diseases to avoid passing it on to their children. This technology involves the use of a mitochondrial donor for in-vitro fertilization. Let me start by explaining how this works.

Mitochondria have their own DNA, separate from the nuclear genome. When you think about your genes, you traditionally picture your 46 chromosomes, housed in the nucleus. You get half of it from your mother, half from your father. The mitochondrial genome is different in many respects, but for my purposes right now, I'll say just this: it's entirely maternally inherited. You don't have any mtDNA from your father, at all.

This means that if your mother carries genes for a mitochondrial disorder, you have a 100% chance of inheriting it. If your father has it, you have a 0% chance.

This is where IVF comes in. In mitochondrial research there is a technique called cybridization. This is a process where you take the nucleus from one cell and the mitochondria from another cell and combine them for a "cybrid" (cytoplasmic hybrid) cell containing two different sets of DNA. This is something that my lab does routinely, and it's great for screening for the effects of mitochondrial mutations without any "background" nuclear mutations confounding your results.

Image from nydailynews.com

In this context, rather than eliminating confounding variables, cybridization would eliminate the disease genes by using a mitochondrial donor. So, in essence, the IVF would go like this: take sperm and egg from the couple seeking IVF, and another egg from a mitochondrial donor. Fertilize the mother-to-be's egg with the sperm, then remove the nucleus from the now fertilized embryo, and move it over to the mitochondrial donor's egg (removing the donor egg's nucleus first). In this manner, you have now created an embryo with nuclear DNA from the two parents-to-be, and mitochondrial DNA from a third donor.

What this means for women with a family history of mitochondrial disease is that there is some hope that they will not have to pass on that disease to their children. While these diseases are rare, they are often severe, and it can be devastating to people trying to start a family. But this therapy has broader implications scientifically, socially and ethically.

On one level, the idea of the "three-parent baby" is completely accurate, but at the same time it is extremely misleading. All of your physical traits are encoded in the nuclear genome. Everything that makes you your parents' child is there. The nuclear genome encodes for something on the order of 30,000 proteins, while the mitochondrial genome encodes for 14. Why, then, can a mutation there have such a profound impact on a person's health? Well, those 14 proteins are very important. They make all the energy your cells need to run. Without them, your body shuts down. But again: they don't have anything to do with your physical characteristics.

Image from Nature.com

One thing that would absolutely change, and this is something I find fascinating, is your haplogroup. Haplogroups are genetic categories that define where your ancestors came from. They trace migration patterns of early humans all the way back to the original Homo Sapiens that lived in Africa. The DNA that is used to determine your haplogroup is mitochondrial DNA, entirely. All of human migration patterns are traced through maternal lineage, and the fastest way to do that is by looking at the mitochondria. At the moment, this is a useful technique: mitochondria are maternally inherited, so it's safe to assume that your mitochondrial DNA reflects your maternal lineage. But once this technology becomes available, there will suddenly be a small portion of the population for which this assumption is not true. Their mtDNA would reflect the haplogroup of the mitochondrial donor, not their mother.

I think another issue that the idea of the "three-parent baby" brings up, which is something of a red herring, is that suddenly we will have groups of three people caring for and being responsible for children. I don't think this will happen. Just as sperm donors are not held to any kind of parental responsibility, a mitochondrial donor would be free of any obligation. Does this raise ethical problems for custody, parental status, etc.etc.? No, I don't think so. Instead of trying to shoe-horn a completely new technology into existing definitions, I think it would be simpler and more accurate to adjust our ideas about what assumptions we make about someone's DNA, and what it means for their personal identity. A child who had a mitochondrial donor is just that; their parents are still their two (nuclear) parents. But, and I'm sure this is predictable coming from me, it's still really, really cool.

On the Male Birth Control Pill

Here's an article from WebMD to start you off. The bottom line is this: some researchers recently developed a pill that reversibly stops sperm development without hormonal therapy, and it's showing promising results in mice. This and other articles outlining this study list the side effects of hormonal therapies, and applaud this new technology for its ability to avoid them.

I heard about this study from a number of friends, one after the other, and they all had exactly the same reaction: "Hey, aren't those the very same side-effects that women have to suffer through with traditional hormonal birth control? Why is it okay for women to deal with that, but not men?" And to this I say simply: Hold up a minute.

In order to explain, I want to take some time to outline one of the most basic principles in biomedical ethics. When a drug or therapy is being tested for mass-market distribution, one of the first things considered is: do the benefits outweigh the side-effects? If the answer is no, it's a dud.

What is birth control for? It prevents pregnancy. From a purely social angle, this is a tool that benefits everyone (a concept I've outlined at great length on this blog), but these are biomedical ethics we're dealing with, not social ethics. Medically, pregnancy puts a massive burden on women. Its impact is felt for years, or in actuality, the rest of the woman's life. Pregnancy significantly alters a woman's health, but for men? The implications are entirely social and emotional. I'm not trying to imply that they are somehow less significant, only that they do not enter the equation when considering male birth control.

Because pregnancy is such a huge event for women, just about any form of birth control is considered acceptable. Once hormonal birth control was developed, it hit the market almost immediately. Why? Because nearly any side effects are acceptable when weighed against the alternative (an unplanned pregnancy).

But for men, this is a tricky question. We're talking about an entirely medical solution to an entirely social problem. The social impact of pregnancy for men is an invisible factor in the biomedical ethics equation. It simply can't be taken into account. There is no physical damage incurred upon men by pregnancy, and as such, almost any side effect whatsoever is considered unacceptable in this situation. I'm going to go out on a limb here and say that this makes the scenario entirely unique. Can you name any other medical advancements that have been developed solely to solve a social problem? Any medical treatment for which the tolerance level for side effects is zero? I can't think of even one. In that respect, this technology has no precedent.

So, before you go blowing the whistle, take a step back. I know this feels like chauvinism, but upon closer inspection, I think you'll find it's an entirely appropriate solution to a subtly complex problem.

So, what about the feminist issues I mentioned in my last post? This is exactly it: while family planning measures benefit everyone, a lack of access to said resources only hurts women. If you don't provide comprehensive sex education, birth control in its various forms and access to safe abortions, who suffers? The answer, without caveat, is women. Women have to bear the burden of unplanned pregnancy entirely. There are repercussions on every level of a woman's life when she has a baby she didn't plan on having. Her health, her social status, her financial stability, her emotional wellbeing are all shaken to the core. Men deal with a fraction of this laundry list of problems - if that - when these situations arise.

So, I try to be polite and academic when I remind you that family planning is for families, not just women, but the bottom line is, while it helps provide the resources we need to build a healthier, more stable society, it's also a massive safety net for women. Why are women staying in school longer? Why are women getting a wider variety of jobs? Why are women earning more money? Why are women having fewer health problems later in life? Why are women having fewer children and having their pregnancies appropriately spaced? Because birth control is widely available. Women can grow and flourish in every area of their lives with the comfort of knowing that they won't be derailed and devastated by an unplanned pregnancy. This issue, while important for everyone, cuts deepest for women. It's just an unavoidable truth; we can't change our biology, we can't change how we reproduce, but we can change the way we interact with that reality - by exerting control over our reproductive functions with modern medical technologies.

I'm sorry, sometimes I just need to geek out about that. The fact that we can even do that is amazing. It blows my mind sometimes that anyone would ever fight it. It's a beautiful time we live in. Relish it. You can live your life as you see fit. Across human history, that is a rarity in the truest sense.

But I digress. This advancement (aside from being really cool) is an interesting new piece in the game of sex politics. What will it mean? Will things be more balanced? Will responsibility for family planning finally be shared in equal parts? Will birth control for men be empowering for women? Will it even be popular? Or will it flutter around in relative obscurity, like the female condom? Will it be the first nail in the coffin of the "war on women?" Before we can answer any of these questions, it has to get past testing in mice. But it is a fascinating technology with a wide variety of possible social outcomes.

No matter which way it goes, I'm of the opinion that yet another resource in the family planning arsenal is never a bad thing.

Birth Control, Revisited

A few months ago I wrote a post about birth control, where I tried to outline what it represents on a social and societal level. There is a central piece to that argument that I want to try and make clearer, if I can. In that entry, I said: "...while the hormone pills used for birth control are chemically acting on the woman's body alone and for the purpose of preventing ovulation, that's just not the point. The point is about broader social consequences of not providing people with the tools they need to plan their families carefully, safely and responsibly." 

I was recently reading this article about Sandra Fluke and representative Joe Walsh, and there was a quote from Mr. Walsh at the bottom that got me thinking about this argument all over again: "We’ve got parents in this country who are struggling to buy sneakers that their kids can wear to school that just started," Walsh said. "We’ve got parents up and down my district who are barely keeping their house. And, and, and, we have to be confronted by a woman, the Democratic Party this is what they stand for. They're going to put a woman in front of us who is complaining that the country — you, me and you — won’t pay the 9 dollars per month to pay for her contraceptives."

I want to revisit my original argument by breaking down Mr. Walsh's comments for you. In doing so, I hope to shed some light on why there is suddenly such heated debate about birth control among politicians lately. 

There are many groups (Planned Parenthood, in particular) that have worked to bring the cost of birth control down for some time. But President Obama has made the issue a lot more public with his new legislation regarding health care and health insurance. Obama - along with what seems like the majority of the democratic party - believes that birth control should be widely available and as near to free as possible, at the very least, extremely affordable. I think this sudden popularization of the subject has brought up some deep rifts that weren't previously obvious - but why? It seems an innocuous subject, after all 99% of women of child-bearing age in the United States use birth control. It's not exactly a politically safe topic to oppose. But I think the issue of access - of tax dollars paying for it - brings to the surface some differences in the way people view birth control. In particular, there are two main paradigms that attempt to define just what birth control is, and what it means for women, for men and for families. I'd like to compare and contrast these two views.

The first is the view held by Mr. Walsh and others who - on average- tend to be on the far right end of the political spectrum. That is that birth control is medication for women. It enables a certain lifestyle for women (that is to say, the ability to be sexually active, possibly outside of the bounds of committed relationships, without the fear or concern of pregnancy). It is, in their minds, a women's issue. Birth control is women's business, and furthermore, there is some implication that it's frivolous to boot. It's a luxury - after all, you don't have to be sexually active. Abstinence is still an option. Because you have made a choice to be sexually active, then it only makes sense that you should pay for the luxuries that make this lifestyle possible out-of-pocket.

There is a certain aspect to this argument that brings the speaker's own opinions into play. I would personally describe a sexually active lifestyle as "modern," but many people view a modern lifestyle as luxurious. So I think this is a personal distinction that doesn't have any place in politics. It's not the place of politicians to push their beliefs on the populace (despite the fact that they do it regularly). But I digress, because I also find the heart of this paradigm - idea that birth control is only for the benefit of the woman - to be incorrect. To understand why, let's examine the other side.

What Mr. Obama, Ms. Fluke and others who share their ideology would rather discuss, as opposed to hormonal birth control for women, is the idea of family planning. This is more of a blanket concept that refers to the freedom to reproduce when, where, how, and with whom you choose. I like this part of the argument because it remembers to acknowledge that we are discussing nothing less than the ability to create life. Heavy stuff.

But the next step in this argument is notably more political. Because true, modern family planning necessitates a certain level of control over one's own biology, and this brings into the picture a host of resources developed by modern medicine that cost money. The assumption that people should simultaneously be able to live a modern (read: sexually active) lifestyle and still plan their families with a staggering level of control implies that a massive health infrastructure needs to be in place in order to bring those resources to the public. In this way, Obama's recent actions on this topic make sense. It's a logical consequence of his personal view on family planning.

This part of the second paradigm brings me back around to my original point. Hormonal birth control for women is simply one of a suite of tools in the family planning tool belt. It's the most powerful mechanism currently available for preventing pregnancy without necessitating abstinence. It happens to be used by the woman, but that's just the biological reality of the drug, and it doesn't change its broader social purpose. Men have the right to control over their reproductive activities, too. Which is why condoms are so cheap and commonly available; at present, it's the greatest tool a man has to protect himself against accidental pregnancy. But birth control is far more effective when used properly, and I think men have the same right to the peace of mind it provides as women do.

In closing, the two lenses through which people view hormonal birth control are as follows: it is either medication for women, or it is a social tool that, by necessity (because we cannot change biology) must be employed by women in order to work. These two views are obviously in direct conflict with one another, and tend to drive very different political actions with regard to birth control. It's probably obvious that I tend to align with Mr. Obama on this subject. But I don't blame people like Mr. Walsh for making this type of error. Birth control is a singular drug in that it has such strong social implications, and it can be difficult to see beyond the basic chemical mechanism to the larger role in people's lives and in society.

Now, if you're concerned that my attempt to paint hormonal birth control as a tool for the benefit of all people overlooks some very large feminist issues, you'd be right. And that's something I'd like to address in my next entry, which will be on the male birth control pill. I'll try to get it posted soon.