Understanding the stem cell controversy

Understanding stem cell controversy

What do you feel when you hear the phrase ‘stem cell research’?

Hope? Disgust? Anger? Confusion?

Maybe you aren’t sure what to feel because you know just enough about the topic to be dangerous.

The last one was me until recently. If it describes you too, then I’m here to help.

Over the last two decades, stem cell research has tangled up science, religion and politics into a messy world-wide controversy.  Many people have strong opinions either for or against it.

Some are hopeful that it will lead to cures for common diseases, such as Alzheimer’s and Parkinson’s. Others are horrified and feel it represents a dark side to science that must be stopped.

So let’s dive into the messy world of stem cell research and figure out what it is, how it works and why it is so controversial.

What is a stem cell?

To understand this whole debate, we first need to know what a stem cell is.

A stem cell is a generic cell, like a blank canvas, that can divide to form a cell with a particular purpose. Think of it like an untrained and unemployed worker. It has nothing to do at the moment, but you can employ it and train it to do whatever job is needed.

For a cell, this process is called differentiation. A stem cell is called an undifferentiated cell because it hasn’t yet been programmed to form a specific cell type.

There are two main types of stem cells commonly discussed: adult stem cells and embryonic stem cells. The latter are the source of most, but not all, of the controversy.

Adult stem cells

Adult stem cells are found in many of our major organs, such as brain, liver, skin, gut and heart. They can replicate to form a limited number of different cell types, depending where they are located. We say that they are ‘multipotent’ because they can form multiple cell types. A neural stem cell in the brain, for example, can form any of the major cell types in the brain.

The way that most cells reproduce themselves is by a process called symmetric division. They split into two identical smaller cells which then grow back to the original size. Each new cell, or ‘daughter cell’, serves the same function as the original.

But stem cells work a bit differently. They reproduce by a process called asymmetric division. When they split, one cell contains proteins with information about what its new function will be. The other contains no such proteins and remains a stem cell. This ensures that the stem cells in your body can’t be used up.

The whole point of adult stem cells is tissue regeneration and repair. When you are injured or some of your cells die, localized stem cells start dividing to form whatever cell types are needed to renew or repair the damaged tissue.

stem cells repair and regenerate tissue

The purpose of adult stem cells is to repair and regenerate tissue.

There are obvious benefits to studying these stem cells, as they can shed light onto how the repair and healing process works. They also have therapeutic and curative potential, as they might be used to replace diseased tissue with properly functioning, healthy tissue.

However, their potential is limited by their specificity and the difficulty of culturing them in a lab. Scientists cannot take stem cells from your liver, culture them in a lab, and then use them to fix your heart. It won’t work because liver stem cells don’t know how to become the various cell types of your heart. Plus they just don’t like to grow in labs.

Embryonic stem cells

Embryonic stem cells, on the other hand, are what we call ‘pluripotent‘. This means they can become any of the 220+ different cell types in your body. They are truly versatile.

The problem is, you don’t have any, and neither do I. They can only be found in embryos. Normally, scientists obtain them from a particular stage of embryonic development called a blastocyst.

Blastocyst embryo

Blastocyst embryo. Imags is from Togo picture gallery maintained by Database Center for Life Science (DBCLS).

A blastocyst is a ball of human cells formed 4-5 days after fertilization (the merging of the egg and sperm), which contains an inner layer of pluripotent stem cells. The outer layer of the ball becomes the placenta and the stem cells within become the whole person.

By the way, if you have trouble remembering the name blastocyst, just think of an exploding cyst (gross!).

Anyway, these stem cells divide and differentiate into the 37 trillion specialized cells that make up your body. By approximately 9 days after fertilization, the blastocyst has become something else called the gastrula (think of gastritis), which no longer contains pluripotent stem cells.

So there is a window of about 5 days during which these pluripotent stem cells of the blastocyst exist and can be harvested by scientists. And this—

“WAIT, WAIT, WAIT, WAIT!!”

-Yes, smartypants in the front row?

“You said these pluripotent stem cells can form any specialized cell in the body, and they exist only from 4-5 days after fertilization until 9 days after fertilization.”

That’s correct, yes.

“Well… what happens BEFORE the blastocyst, in the first 4-5 days? Don’t there need to be pluripotent cells already?”

Good catch. Ok, the truth is that pluripotent stem cells cannot form quite all human cell types. For example, they can’t form the cells of the placenta.

But totipotent stem cells can.

“What are you talking about? Totipotent?! What’s that?”

Sorry. Totipotent stem cells are the cells that divide from the zygote (the cell that results when the egg and sperm fuse during reproduction) during the first few days after fertilization. And they can form any cell needed to make a complete human person, even the placenta and all specialized embryonic cells.

But here’s where it gets tricky. The zygote, the single cell that exists before any division takes place, is also totipotent, and this has led to some misunderstandings. You see, the zygote is not only able to produce all the cells needed to make a complete human, but it is also able to organize them into a complete human person.

The post-zygotic totipotent cells lack this second ability.

Post-zygotic totipotent cells cannot become human beings. If you implant one into a uterus, it will become a tumor, not a person.

A zygote is totipotent, but it is not a stem cell because, unlike stem cells, it cannot copy itself.

minion photocopying himself

When a zygote splits into two cells, neither of those cells are zygotes. Only the merging of a sperm and egg can produce a zygote.

Anyway, clearly pluripotent and totipotent stem cells have greater research and therapeutic potential than multipotent stem cells, due to their much greater versatility.

The problem is, we have to get them from embryos. But how?

How do we get embryonic stem cells?

The majority of embryos used in stem cell research come from in vitro fertilization clinics. Eggs are harvested from a woman who either can’t or doesn’t want to reproduce the old-fashioned way. They are then fertilized outside her body with the intention of later being implanted into her uterus.

The normal practice is to fertilize more than one egg to increase the chances of success. The extra embryos are frozen and stored using a process called cryopreservation.

freezer for cryopreservation

Image by Lab of Ralf Reski. Source: International Moss Stock Center. Licensed under the GNU Free Documentation License.

But cold storage isn’t cheap and the prospective parents get the bill. They are then left to decide what to do about it.

There are a number of options, including:

  • Keep them for later, when they want to have more children. This only postpones the decision, as they may still have embryos left when they are finished having children.
  • Have them thawed and disposed of, either by the clinic, by burial, or by having them implanted in the uterus at a time of the cycle when it is not possible to get pregnant. In any case, the embryo does not survive.
  • Donate them to infertile couples who want to have children. You can imagine that this is a very difficult decision, as it can be like giving up a child for adoption. You will know that your child is out there somewhere, but you will likely not be able to have any contact with them or even know anything about them.
  • Donate them to science. They will be destroyed during research, but the research may help others to live longer, healthier lives.
  • Keep them in storage indefinitely. Again, it’s essentially just a way to postpone the decision, and it comes with a yearly cost that could be in the thousands of dollars.

Many choose to donate the extra embryos to science, as this gives them the best overall feeling.

But not everyone is happy about this, because an embryo represents a potential human life, and harvesting stem cells from the embryo destroys it. Depending on when you believe life begins, this method could involve the taking of an innocent life.

Even so, one can argue that it’s a trade-off because the purpose is to alleviate future human suffering. Some people grudgingly accept that.

But many do not.

On the other hand, many people hold the belief that it’s a travesty not to use excess embryos for research, as most of them will otherwise be discarded anyway, and it’s certainly more dignified to let an embryo contribute to curing diseases rather than let its existence be without purpose.

Cloning

Another (potential) way to get embryonic stem cells is to create an embryo through a cloning procedure, the same way Dolly the sheep was cloned.

sheep

The procedure works by replacing the nucleus of an egg with the nucleus of an adult somatic (non-reproductive) cell, avoiding fertilization. In this case you avoid using embryos from fertilization clinics, but the embryo is still destroyed by the harvesting procedure, and you have the added controversy surrounding human cloning.

The idea of human cloning scares the bejeezus out of most people because it raises all kinds of questions about individuality and specialness.

We all want to believe we are unique.

If we actually succeeded in cloning a human, would it have a soul? Can you clone a soul? Do we even have souls? How different would the clone be from its ‘parent’? Would a clone be truly human?

There are plenty of opinions, but no one really knows, and that’s why it’s scary. It feels like playing God, but without the benefit of all-knowingness.

For now, we are not likely to find out, because reproductive cloning is banned in most countries. Cloning for stem cell research (called therapeutic cloning) is mostly allowed, but does not involve implantation, so a fully formed human will never be produced from it.

Nonetheless, some people believe strongly that any type of human cloning is strictly immoral, or at least in a dangerous gray area that should be avoided.

A further complication is that the procedure requires eggs, which are obtained by paying women thousands of dollars to be donors. This raises a whole new set of ethical concerns about inducing women (usually poor or cash-strapped women) to sell their body parts for money.

So far, no one has succeeded at therapeutic cloning.

An end in sight to the controversy?

In 2006, scientists at the Shinya Yamanaka lab in Japan managed to reprogram adult skin cells into pluripotent stem cells. These are known as iPSCs, induced pluripotent stem cells. This generated a lot of excitement because it could mean a way to continue active stem cell research without the distracting controversies of cloning, paid egg donations, and embryo destruction. There is (so far) nothing controversial about taking skin cell samples.

Each adult would be able to have their own personal stem cell line just by giving a skin sample. Since organs produced from stem cells generated by your own skin would contain your exact genetics, there should be no issue of rejection that we currently face with transplanted organs.

Is the end of controversy in sight? Is this a free ticket to uninhibited stem cell research?

sad, happy, angry, worried

Well, not so much. Not yet, at least.

You see, the process of reversion to a pluripotent state is done by infecting the skin cells with a virus. And this virus just happens to be able to cause cancer. Replacing Alzheimer’s disease with cancer is a less-than-desirable outcome for most people, so the kinks will still need to be worked out of the procedure before it will be a viable replacement for embryonic stem cell research.

Nonetheless, in March 2017 scientists conducted a clinical trial, and successfully transplanted retinal cells derived through iPS into the eye of a patient suffering from AMD (age-related macular degeneration). I’m sure there will be a lot of interest in the long-term results.

Problems with definitions of potency.

The iPSC procedure has raised yet another controversy. It turns out that somatic cells can be reprogrammed to be not just pluripotent, but totipotent. In fact, scientists have successfully reprogrammed them to mimic the state of a two-celled embryo (the state directly after the division of the zygote). This has sparked concerns about reprogramming a cell into an actual zygote, which could then grow into a human (another form of cloning).

Some scientists claim that this is not something to worry about because it is impossible. A reprogrammed cell may be versatile in terms of which cell type it can become, but it still lacks the assembly instructions to organize cells into a human being. These come from the egg, which is why putting the nucleus of a somatic cell into an egg is a (potentially) viable cloning procedure.

A somatic cell on its own simply can’t become a person.

However, there may be a way around this. Mice have been cloned from iPSCs by a method called tetraploid complementation (try to say that 10 times fast!). This involves the fusion and culturing of two blastomere cells, which are early embryonic cells after the division of the zygote, to form a tetraploid blastocyst (!).

This scary-sounding word ‘tetraploid’ may bring to mind images of juice cartons or creepy 4-legged aliens, or perhaps creepy 4-legged juice-carton aliens with straws for heads (or was that just me?), but it simply means that the embryo has four copies of each chromosome rather than the usual two (called diploid).

Reprogrammed somatic cells (iPSCs) are then injected into the blastocyst. The blastocyst becomes the placenta, while the injected cells become the mouse.

So it turns out that it may not be entirely accurate to say that a somatic cell can’t become a person. It can’t become a zygote, but maybe it can become a person.

That’s kind of neat when you think about it. Each one of your cells might be able to become a whole you. One could say that you have the potential to become approximately 47 trillion versions of yourself. You could repopulate the Earth more than 6,000 times on your own!

Conclusion and future outlook

Although progress has been made and there are more potential options, the controversy around stem cell research is not yet over. Nor is it likely to end in the near future. But, as most things do in the world of science, stem cell research will continue to move forward, for better or worse. Whether you choose to embrace it or fight it is up to you and your own conscience and beliefs.

I, for one, am optimistic that some good will come from stem cell research (although I don’t expect any miracle cures). But I do think we should continue to proceed with caution, as history tells us that unregulated and reckless progress rarely ends well (see Chernobyl, see DDT, see the Great Pacific garbage patch, see sugar).

What do you think?


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