Primer on Stem Cell Research

The stem cell debate is controversial and multifaceted. Stakes are high and opposing sides are impassioned by very strong yet very different beliefs. For those that are uninitiated in this issue, the story is usually best understood by beginning with in vitro fertilization (IVF).

In Vitro Fertilization

IVF is a medical technique which allows people--who are otherwise unable to have children without medical aid--to become parents. The process involves extracting multiple eggs from a female donor, fertilizing them with sperms and thus creating human embryos. Out of an entire batch of fertilized eggs, only a few are implanted into a woman each time--in hopes that one egg will implant in the uterine wall and eventually develop into a pregnancy--and the rest of the eggs are stored so that the process may be repeated if necessary. As time goes on, since more fertilized eggs are created than are actually implanted, there are naturally many leftovers; there are currently about 500,000 extra frozen embryos across thee U.S. Depending on the fertility clinic, these unused embryos will either be stored, or discarded.

The story begins here because these embryos are prime sources for extracting stem cells. However the process of such extraction destroys the embryos and different people have different ideas about its ethical implications.

What are Stem Cells?

Stem cells are special cells that have the ability to regenerate for long periods of time; scientist call this "self-renewal." Additionally, stem cells have the capability to turn into specialized cells with specialized functions, such as heart-muscle cells that beat, brain cells that transmit information, or pancreatic cells that produce insulin. Scientists refer to this characteristic as "multi-potency." (embryonic stem cells are considered pluri-potent, while adult stem cells are considered multi-potent)

Types of Stem Cells

There are two types of stem cells: embryonic stem cells and adult stem cells. Embryonic stem cells can be extracted from the excess frozen embryos that are kept in the fertility clinics. The stem cell tutorial website from the National Institute of Health makes the point that embryonic stem cells are never harvested from a woman's body; it is important to remind people that no embryos are ever created for the sole purpose of being used in stem-cell research here in the U.S.

In contrast, adult stem cells are rare, and found only in select sites of the human body. For example, hematopoietic ells are a type of stem cell found in the bone marrow; they form all of the blood cells in our body like red blood cells and white blood cells.

Advantages and Disadvantages of Each Type

Embryonic stem cells have the ability to become any cell type within the body, while adult stem cells are limited in their ability for differentiation. As an analogy, an embryonic stem cell is like a young character actor who is capable of playing virtually any role, while an adult stem cell is like a more seasoned actor with limited options, but has a good range nevertheless. Both are more "potent" compared to an action star with limited acting skills, who can only play one role.

According to the NIH, embryonic stem cells can be easily grown in culture, while adult stem cells are hard to come by and "methods for expanding their numbers in cell culture have not yet been worked out." On the other hand, if the methods for expanding adult stem cell do get worked out, the adult stem cells have the potential advantage of being reintroduced into the patient; this is extremely useful because adult stem cells harvested from a particular individual would not be rejected by that very individual.

What Scientists Want to Do with Stem Cells

Scientists want to learn more about stem cells and how they differentiate into different types of cells that make up our different organs. For example, research into the signaling process can elucidate crucial information about cancer and its relevant treatment. More importantly, scientists are interested in tissue regeneration--such as replacing cells that produce insulin in the pancreas (diabetes) , or cells that produce dopamine in the brain (Parkinson's disease).

Recent Law

On July 19, 2006, President Bush made the headlines by exercising his first ever veto and striking down the Stem Cell Research Enhancement Act of 2005, passed by Congress on the previous day. The bill would have allowed the excess embryos from fertility clinics to be utilized for stem cell research, given that the donors consent to it. Bush opposed the bill because he believes embryos are human and should not be used for research. Supporters of the bill, like Republican Senator Orrin hatch, find Bush's decision puzzling because the embryos were going to be discarded anyway.

Under the current administration policy, no new embryonic stem cells have been created with the support of federal funding since 2001.

The Mystery of Vaccine Shortage Revealed

I have come across several blog posts (here and here) about the flu vaccine shortage. Many people often question why the vaccine makers or why the government can't get this right--how hard is it to just make enough for everybody, and how many people have to die of the flu before we learn our lesson? I thought this is a good opportunity to explain why we seem to run out of flu vaccines all the time.

First of all, it takes a huge amount of effort and time to develop a vaccine. Production of the flu vaccine for the month of October has to be started in early spring; that is why when there's a shortage, supplies do not magically increase. But that doesn't explain why there are so few companies making flu vaccines and the ones that do, don't make enough to begin with. There are several reasons, most of which are related to market forces and government regulations. The bottom line is that the profit margin is simply too low in the vaccine business. The manufacturing cost has risen steadily due to government regulation and liability issues, but the price remains stubbornly low. The government, the major purchaser of the flu vaccine, uses its clout to force the price down. There is also the social perception that pharmaceutical companies shouldn't be "gouging" people during a time of need because it's immoral; any attempt to raise the price significantly will surely be met by public outcry.

Wall Street can be harsh; investors demand profits on their investments. Therefore when companies are faced with the decision of how to best invest their capital, other options like making blockbuster drugs become far more attractive than vaccines.

Why is it so costly to make vaccines?

1. Biological products like vaccines are extremely difficult to make. They are labor intensive and the risk of failure is high, compared to synthetic drugs. The vaccine production also happens in sequential steps; any disruption along the sequence means the whole lot has to be discarded and the production has to start over from step one.

2. Many companies found it hard to meet increasing government regulations on quality control and safety issues. In addition, vaccine plants are required to be updated regularly, which is also a huge cost. Most companies decided it was simply better not to upgrade their facilities and directed their resources elsewhere instead.

3. The demand for vaccines is quite irregular and unpredictable. To compound the problem, The shelf-lives of vaccines are limited; anything unsold has to be thrown away. It's difficult to anticipate how many vaccines will be needed every year and after companies had to throw out several hundred million dollars worth of vaccines just a few times, many got out of the business. Those companies that still remain find it more sensible to under-produce than to over-produce, in order to prevent waste.

Essentially, pharmaceutical companies don't have enough incentive to produce more vaccines.

So what can we do to change that?

There are several proposals to incentivize the pharmaceutical companies. Some have suggested that we can extend the patents on blockbuster drugs in exchange for vaccine supply. Some have suggested we give tax breaks for vaccine makers or simply allow them to charge more for their products. Some also propose that we make the government regulations slightly less stringent, just enough to encourage more companies to enter the fold. Many pharmaceutical companies also want the indemnification issue addressed by Congress; as of now, should a particular company step up during a time of emergency and make vaccines, that company can still be sued by people if complications arise. Potential litigation is unwelcome by anyone and Big Pharma is no exception.

As one can imagine, all of these suggestions are met with skepticism, even passionate opposition. Due to the general lack of understanding about the vaccine production process and its market, most layman scoff at the idea of "helping out the pharmaceutical companies."

Nevertheless, the lack of incentive for companies is completely real and will not go away unless something is done to change the current system. Just like everything else, this is a trade-off; what are you willing to give up for more vaccines?

(detailed and unbiased coverage on this issue appeared on PBS and the NY Times. NYT is free but signup required)


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