How Natural Twins Are Formed
There are two types of twins: monozygotic (one egg) which produces identical twins and dizygotic (two egg) which produces fraternal twins. With fraternal twins, there are two separate fertilization processes, each with its own sperm and egg. With identical twins, there is only one fertilization process, but at some point, the inner cell mass (ICM) splits apart to form two completely separate embryos.

Identical twins happen in about 1 in 400 births. About 33% happen before day 5 after fertilization, 66% happen between days 5-9, and splits after day 9 are rare and increase the risk of conjoined twins.

Prior to day 5 - If the ICM splits prior to day 5, each embryo will develop its own trophoblast cells, and 2 separate chorion will form.

Between days 5-9 - At this stage, the trophoblast cells have already differentiated themselves from the ICM, so if the ICM splits at this point, there will only be 1 chorion that will encase the two embryos.

At day 9, another layer forms around the embryo called the amnion. This will eventually become the amniotic sac which surrounds the embryo with amniotic fluid. If the twinning division has occurred before day 9 - and in most cases it has - each embryo will form its own amnion. If, however, the ICM splits after day 9, there will only be 1 amnion. With only one chorion and one amnion, the chance of the embryos conjoining and possibly sharing organs or body parts increased dramatically.

Stem Cells As the Precursor To All Cells
Looking at twin development, we can see that even if the cell mass divides between days 5-9, each division will go on to form a fully developed human being. The ICM remains undifferentiated during this time and can form any part of the embryo.

It’s also safe to say that at this stage, the mass of stem cells bears no resemblance to what we think of when we think of a human being. It’s just a bunch of cells, not unlike a cluster of skin cells or organ cells. If you saw it at this stage, you wouldn’t be able to tell that it would go on to become a human, nor does it possess any type of consciousness or any of the other characteristics we use to describe what makes someone a “human being” or “person.”

In my third installment, I’ll talk more about when cells start to differentiate during the 2-3 weeks of development and the neural tube starts to form.

Reference:
Bioethics and the New Embryology, ISBN: 0716773457. Picture, slightly modified, taken from pg 17.

The simple answer is he thinks murder’s wrong. The president is not going to get on the slippery slope of taking something living and making it dead for the purposes of scientific research.

Since then, Snow has retracted his remarks about stem cell research being murder, but that has just fueled the controversy surrounding the debate.

In my next few articles, I’m going to talk about the stages of embryonic development during those first 5 days when the fertilized egg divides to form a blastocyst, which is what scientists use in embryonic stem cell research.

The Growth Of Embryonic Stem Cells
Obviously, to produce an embryo, a sperm must fertilize an egg, and each donate 23 chromosomes. The fertilized egg is then called a zygote. Over the course of the next few days, the zygote divides into 2 cells. Those two cells each divide to create 4 cells, and so forth, at a rate of one division every 12-18 hours.

By the time they reach 16 cells, they form a cluster called a morula, which consists of a small group of internal cells surrounded by a group of external cells. The outer cells become trophoblast cells, which will eventually go on to form the chorion, a portion of the placenta once the mass attaches to the uterus. The inner cell mass (ICM) becomes embryonic stem cells and will eventually form the embryo and its various surrounding sacs (yolk, waste and water).

Here’s a picture of 2 developing embryos (identical twins) with the different parts labeled.

When people talk about embryonic stem cell research, they talk about the 4-5 day old blastocyst made up of a few hundred cells. At this point during normal embryonic development, the cell mass has not yet attached to the uterus.

Cell Differentiation
At the point where the cell mass consists of 2, 4, or 8 cells, you can take any one of those cells, put it into a Petri dish full of nutrients, and it will go on to form a blastocyst complete with its own trophoblast cells and inner stem cells. For instance, if you take 1 of the cells from the 8 cell mass, you won’t get 1/8 of an embryo. It will grow into a full embryo that can be implanted into a woman and over 9 months, will grow into a baby.

By days 4-5, the cells have already somewhat specialized into the trophoblast and ICM. If you take an ICM cell at this point, it won’t form a trophoblast cell but it can form any of the types of cells that make up an embryo. In other words, at this stage, the ICM isn’t yet specifically determined to become a particular kind of cell - it can develop into any type of cell. The type of cell it eventually becomes depends on its interactions with other cells.

Unfortunately, up until recently, scientists working with stem cells ended up killing the embryo to get to the cells in the ICM. This week, however, a group of scientists have published a way to harvest stem cells without killing the embryo.

In the next article, I’ll discuss the phenomena of identical twins.

Reference:
Bioethics and the New Embryology, ISBN: 0716773457. Picture taken from pg 17.

The leading company providing cryopreservation has only 200 clients and has yet to use any frozen eggs. Worldwide, there have been somewhere between 150-200 live births from egg freezing, not enough to reliably determine a success rate. The American Society for Reproductive Medicine still calls the technique “investigational.”

On the other hand, the rate of live births from proven assistive reproduction technologies like in vitro fertilization is 30.2% for 35- to 37- year-olds and 20.2% for women 38 to 40. You’ll likely have better odds simply using your remaining fresh eggs. It’s not until you’re over 40 that IVF success rates drop to 11%.

It’s interesting to see just how far we’ve come since the first test tube baby, Louise Brown, was born on July 25, 1978, weighing at 5lb 12 oz. By 1999, 300,000 women around the world had conceived through IVF.

Geneticists have been looking for less intrusive ways to extract fetal cells, and now, a solution may be on the horizon. In 1998, Dennis Lo and his colleagues found that fetal DNA floats freely in the mother's bloodstream. The main problem is separating the mother's DNA from the fetus'. If the fetus is a boy, they look for a Y chromosome, but if the fetus is a girl, they need other criteria.

Recent research has found two ways to do this:

1. Lo and his colleagues found that fetal DNA can be detected with unmethylated Maspin, a tumor-supressing gene that's active in fetal cells of a placenta but not in the mother.
2. Sinuhe Hahn and coleagues found that the fetus' genetic materials which circulate in the mother's bloodstream are actually much shorter than the mother's. In a study of 32 pregnant women, when the group checked their results against chorinic villus sampling, they identified mutations with almost 100% accuracy.

Both tests simply require a sampling of the mother's blood.

Other geneticists are trying to find ways to extract whole fetal cells, rather than just the fetal DNA. Researcher Ester Guetta and colleagues have identified several types of fetal cells that circulate with placenta cells in the mother's blood stream. While extracting a lot of those cells is difficult to do, she's been able to take blood samples that hold 1-2 fetal cells per 20 ml of blood and multiply that number five fold in the lab over the course of 5-7 days. She's used the methodology to predict the fetus' gender with approx 93% accuracy.

Source: Science News (7/22/06) (subscription)

When Paabo first announced the project, he drew a lot of skepticism since there were very few bits of mitochondrial DNA to work with. Things have taken a turn for the better since Paabo announced he found nuclear DNA in a 45,000 year old Croatian Neanderthal museum specimen and has been able to sequence a million base pairs of it.

The researchers� hope is to recover the entire sequence of the Neanderthal genome, but that will depend on which they can recover enough DNA. From sampling so far, no particular gaps in the sequence are apparent. �We are hitting all the chromosomes and getting good coverage,� Dr. Egholm said. If no single specimen yields a full sequence, the genome might be recovered by combining DNA from several individuals.

One of the most important results that researchers are hoping for is to discover, from a three-way comparison between chimp, human and Neanderthal DNA, which genes have made humans human. The chimp and human genomes differ at just 1 percent of the sites on their DNA. At 1 percent, Neanderthals resemble humans at 96 percent of the sites, to judge from the preliminary work, and chimps at 4 percent. Analysis of the DNA at the sites at which humans differ from the two other species will help understand the evolution of specifically human traits "and perhaps even aspects of cognitive function," Dr. Paabo said.

Both the New York Times and Discover Magazine mention the possibility of cloning a Neanderthal and possibly bringing the species back from extinction, but at this point, that sounds a bit far fetched. Yes, we've been able to clone a sheep and other animals, but it's been almost a matter of luck that these animals have survived through birth. Most don't. And given the ethical debate surrounding human cloning, I'd image that cloning a Neanderthal would receive the same backlash.

Source: Discover Magazine (Sept 2006), New York Times

Author:

Human stem cell research is a major hot button topic that divides the conservative and scientific communities. Religious conservatives see it as tampering with nature and even playing God. Scientists, on the other hand, see the potential to treat many of the life threatening diseases of our times - from heart disease and diabetes to Parkinson's and Alzheimer's.

There's no question that there's been a lot of hype surrounding both sides, so it's refreshing that in The Stem Cell Divide provides a non-biased look at the science and politics surrounding this controversial topic.

The book is divided into 3 parts: Discovery of the Stem Cell's Unique Abilities, The Race to Harness the Power of Life, and Stem Cell Cures and Curses. There are two appendices: one describing how human cells are cultured and the other describing California's legislation concerning the funding of stem cell research. The book also has a fairly extensive glossary.

The first part of the book is concerned with stem cell basics. This section is designed to get novices up to speed with the history and process of stem cell research. Bellomo clearly explains why embryonic stem cells have advantages over adult stem cells, the scientific research up to this point, and our main sources for embryonic stem cells - namely stem cell cultures maintained by Dr. James Thomson of the University of Wisconsin and potentially, the thousands of unused embryos that are discarded at in vitro fertilization (IVF) clinics.

The second part of the book discusses the opposition President Bush has faced from his own party by his decision to veto any bill that allowed federal funding of embryonic stem cell research. Bellomo makes it extremely clear that the issue at hand is not whether embryonic stem cell research should be legal - it already is allowed, remains unrestricted, and is perfectly legal - but whether it should be federally funded.

On August 9, 2001, Bush announced that federal funding would only be allowed for researchers who experimented on the 60 or so existing embryonic stem cell lines. Determined to keep biotechs within the state, California responded with Proposition 71, legislature that essentially made conducting stem cell research a state constitutional right and allowed $3 billion in funds to be given over 10 years to stem cell research facilities, and specifically, embryonic stem cell research. That sparked a number of other states to also propose legislation to fund embryonic stem cell research.

At the federal level, President Bush has faced opposition in Congress. In May 2005, the Republican-controlled House passed a bill allowing federal funds to be used for embryonic stem cell research. Even staunch supporter, Dr. Bill Frist, broke from the Bush camp to support the legislation, saying

We should federally fund research only on embryonic stem cells derived from blastocysts left over from fertility therapy, which will not be implanted or adopted but instead are otherwise destined by the parents with absolute certainty to be discarded and destroyed.

Bellomo also addresses the rise and fall of Dr. Hwang Woo Suk, the South Korean researcher who claimed incredible advances in stem cell research and became somewhat of a celebrity in his home country. His promising career came to a crashing halt when it was made public that he had fabricated much of his results and had breached ethical guidelines when he paid women to donate their eggs for embryonic research. Scientists are still trying to decipher what, if any, part of his research is valid and what was fabricated.

Finally, in the third part of the book, Bellomo discusses the promises of therapeutic cloning - when embryonic stem cells are removed from the blastocyst, harvested in a culture dish and then injected with the nucleus from a donor cell so that the cell makes copies of the donor genetic material. Therapeutic cloning offers great potential to generate replacement tissues and organs for illnesses and injuries that currently have no cure and will greatly reduce the rejection rate for patients that need organ transplants. It is thought that if organs and tissues are grown from a patient's own cells, their body will be much less likely to reject the transplant than if that organ was donated by someone else.

Bellomo doesn't shy away from alternatives to embryonic stem cell research, covering briefly the pros and cons of using adult stem cells and germ cells, before tackling some of the key arguments for both sides.

Ethically, conservatives argue that embryonic stem cells are still the foundations of human life and therefore they have a right to life. As James Sherley of MIT says,

A human life begins when a diploid complement of human DNA is initiated to begin human development. Therefore, a life can be initiated by the fusion of sperm and egg or by the introduction of a diploid nucleus into an enucleated egg (ie cloning)

James Thomson argues from a different perspective.

The bottom line is that there are 400,000 frozen embryos in the United States, and a large percentage of those are going to be thrown out. Regardless of what you think the moral status of those embryos is, it makes sense to me that it's a better moral decision to use them to help people than to just throw them out. It's a very complex issue, but to me it boils down to that one thing.

Advancements in cellular research may eventually make therapeutic cloning more acceptable as scientists learn to remove the inner cell mass of a blastocyst without destroying the embryo or as research into how diseases develop helps find cures that don't require such practices. The final chapter offers predictions of where Bellomo sees the progress several years into the future.

While the byline of the book "The facts, the fiction, and the fear driving the greatest scientific, political, and religious debate of our time" suggests that it will tackle the ethical, religious, and political debate on stem cell research, the book only briefly tackles the ethical arguments for each side while focusing on the scientific process, experiments, and funding legislation.

The writing style is accessible and explains the science in clear terms with diagrams. This is a great, matter-of-fact overview of stem cell research that allows its readers to draw their own conclusions based on the facts presented. It will be useful to those looking for a comprehensive introduction to the subject as well as those looking to catch up with the latest research.

Author:

On July 5, 1996, Dolly, the first animal ever to have been cloned from an adult cell, was born under the watchful eyes of Ian Wilmut and his team of researchers at the Roslin Institute. Dolly's birth sparked all sorts of political and ethical concerns while providing hope that cloning might one day cure major illnesses like Parkinson's and diabetes. In After Dolly, Wilmut has teamed with award winning science journalist Roger Highfield to defend cloning and argue for continued scientific research.

Dolly's birth was a big deal because it was the first time any researcher was able to reverse cellular time. Before Dolly, researchers believed that development could only run in one direction - that all cells were derived from that one cell that came into being when the egg was fertilized. To create Dolly, Wilmut took a nucleus from a 6 year old sheep cell, transplanted it into an egg cell from a second sheep, and inserted it into the uterus of a third sheep where Dolly started developing and growing. All of this happened without the act of sex, a feat deemed "impossible" at the time.

Dolly went on to prove that a clone was not sterile. Throughout her life, she gave birth to six lambs, all conceived naturally and born healthy. She became a media superstar, featured in books, plays, and tv shows. And she sparked the desire among scientists to be the first to clone a human being.

Five years into her life, Dolly developed a limp and was diagnosed with arthritis in her knee. She was successfully treated, but her condition sparked new worries about the safety of cloning and side effects such as premature aging. Dolly lived a normal life for a sheep but died in February 2003, not as the result of premature aging like much of the media reported, but as the result from pulmonary adenomatosis, a common lung disease that affects adult sheep and took out four of Dolly's fellow barn-mates before they could stop it from spreading.

Genetics has always been a sticky subject when it comes to artificially aiding in human reproduction. Media coverage was mixed when Italian gynecologist, Severino Antinori, used donor eggs and in vitro fertilization to impregnate a 62-year-old woman in 1994. And many people have misconceptions about how the process works. For instance, if human cloning was possible, the clone would not be a carbon copy of the original. It would have its own personality in the same way that identical twins - which are examples of natural clones - have different personalities yet come from the same egg. There's also no way to duplicate exactly the environment in which the original was raised. The clone would have its own friends and teachers and interact with a different set of political, social, and cultural norms.

Wilmut has a strong underlying ethics and the book carefully explains that he believes cloning humans is unethical and inhumane. On the other hand, he is a strong proponent of human stem cell research and deriving cells from cloned human embryos to study and treat disease.

One day doctors will be able to use cloning to grow a patient's own cells and tissues to carry out repairs. Cells from these embryos will also speed the search for the next generation of blockbuster medicines and help reduce our dependence on animal research. As a bonus, this work will give profound insights into human development and how it can go wrong and into how to correct many terrible genetic diseases in the embryo.

The potential of cloning to alleviate suffering - even end it for some diseases - is so great in the medium term that I believe it would be immoral not to clone human embryos for treatments. In the long term, a vast range of alternative and embryo-free ways to grow cells and tissues, perhaps even organs, may also rest on the foundations of this research.

The book is a mixture between science and personal experience. Wilmut constructs his case for why stem cell research is necessary while providing insight into why he feels so strongly about this cause. Much of the book is a first hand case study of the Dolly phenomenon, the clones that came after her, and his work with stem cells. Wilmut takes care in explaining the biology behind the experiment in terms that laymen without a genetics background can understand. He even addresses the hype surrounding the Woo-Suk Hwang scandal in South Korea and its effects on stem cell research.

Finally, Wilmut doesn�t shy away from the question of when does life begin. Throughout his career, he has come up against staunch opposition who believe that life begins when the egg is fertilized and any attempts to experiment on a few day old embryo is equivalent to taking the life of a full human being. Wilmut approaches the subject with respect for the underlying religious and moral philosophy while clearly explaining his position on the subject - that he does not believe that a blastocyst is a person because it does not possess consciousness.

When the first in vitro fertilization baby was born in 1978, society threw the same types of arguments at scientists - they were taking "the first step down a 'slippery slope' leading to eugenics, deformed babies and doctors playing God." Similarly, there was such debate when individuals were declared dead due to brain death and their organs were used as transplants. And there were even objections when anesthesia was introduced during childbirth - the men in power had argued that women were intended to suffer as God's punishment. Wilmut sees stem cell research as the next scientific advancement that people fear, and therefore oppose, because it's new. Yes, there may be unintended negative consequences, but the benefits to society are far greater.

Overall, this is a great book for those interested in the Dolly phenomenon and the stem cell research debate. The book is laid out in nine chapters. It includes an overview of cloning, the creation of Dolly, discussions about embryology and when life begins, and the morality of designer babies and human cloning. It also includes an extensive source notes section and a glossary.