TCS Daily

Is Dishonesty in Our Nature?

By Michael Cook - August 30, 2006 12:00 AM

What magic is there in embryonic stem cells to make some scientists so economical with the truth and some science journals so credulous? Only a few months after the disgraceful Korean stem cell scandal, another scientist has again announced a breakthrough, and has again been denounced as a liar.

Last week a Massachusetts company declared that it had mastered a technique for creating "ethical" embryonic stem cells which could break the logjam in America's stem cell politics. The world's leading science journal, Nature, rushed the news into its on-line express edition. Since stem cells could become the key medical platform for the 21st century, finding a way to harvest the most versatile variety without destroying human embryos would have been a major coup. And this is the way Advanced Cell Technology described its work in a press release.

"We have demonstrated, for the first time, that human embryonic stem cells can be generated without interfering with the embryo's potential for life," said lead author Robert Lanza.

CEO William Caldwell delivered the same message: "we do not destroy the embryo. That's the whole purpose of what we perceive to be a major scientific breakthrough." Ronald Green, a bioethicist at Dartmouth who heads ACT's Ethics Advisory Board, gave it his blessing. "This technique overcomes this [ethical] hurdle and has the potential to play a critical role in the advancement of regenerative medicine."

But their claim was false. None of the embryos described in the paper had survived. Talk of breaking the impasse was a con.

What Lanza's team had done was to biopsy an eight-cell human embryo and gently remove a single cell -- a standard technique nowadays in IVF. With this cell Lanza created a stem cell line while the embryo continued to develop normally. At least that was what he intended. In fact, although 16 embryos were dismembered into 91 separate cells, Lanza produced only two stem cell lines.

"It was a very disruptive, very wasteful, very inefficient procedure, and it left all the old embryos dead, just like the old method did," said Richard Doerflinger, the pro-life spokesman for US Catholic Bishops, who blew the whistle on ACT's claims. In a rare moment of consensus on the controversial issue of embryonic stem cells, even supporters of therapeutic cloning dismissed Lanza's work. "A pitiful attempt to look morally acceptable, rather than do valuable science," sneered Glenn McGee, editor of the American Journal of Bioethics. Even the Australian IVF industry dismissed ACT's claims as "absurd" and "over-sold".

The most astonishing feature of this shabby episode is that the publication as prestigious as Nature colluded in it. It rushed Lanza's article into print, accepted his line about an ethical breakthrough, and even posted an on-line image of a mature, healthy embryo which had survived a biopsy. Nature should have known about the dubious ethics of harvesting embryonic stem cells from biopsies. Only last year these were thoroughly canvassed in a major white paper by the President's Council for Bioethics.

Furthermore, Advanced Cell Technology has a track record as a publicity hound. A listed company which is perpetually in the red, it burst onto the front page back in 2001 claiming that it had cloned a human embryo and initiated a stem cell line. Nothing came of that extraordinary wave of publicity, but it no doubt put ACT scientists in the rolodexes of journalists across the world.

This episode should ring warning bells for everyone interested in the controversy over embryonic stem cells. ACT recently shifted its headquarters from Massachusetts to California in the hope of obtaining some of the US$3 billion in state money that will soon become available for work on embryonic stem cells and therapeutic cloning. Disbursement has been held up by legal action. But when the funds flow, the feeding frenzy will begin. "We have to have very discerning review boards so it doesn't become a boondoggle for companies that haven't succeeded," Dr. Irving Weissman, a prominent stem cell researcher at Stanford University, has commented.

After Nature's undiscerning treatment of Lanza's stem cell work, however, it seems more likely that destructive research on embryos will slip through with a wink and a nod.

This is tragic, since it may not be necessary to clone or destroy embryos to get those precious stem cells. In a highly significant development earlier this month, Japanese scientists reported in Cell, another major journal, that they had reprogrammed an adult mouse cell and converted it into something closely resembling an embryonic stem cell.

Researchers from a stem cell group at Harvard University grudgingly acknowledged that it was a "significant step" -- "unencumbered by neither the logistical constraints nor the societal concerns presented by somatic cell nuclear transfer [i.e., cloning]." If this success can be replicated with human cells, it might indeed transform America's stem cell politics.

Michael Cook is editor of BioEdge, a weekly bioethics newsletter. Email:



Follow the Money
Like global warming research, which Nature is very happy to push, stem cells are the next big money push into science.

"Trust me, I am a scientist."

Nature is for scientists
Nature is a science journal, not a political magazine. It serves the science community by publishing articles by other scientists describing their research. All scientists know that a research breakthrough reported in Nature may fall through, it is very common. A scientist would know that Nature printing an article by someone claiming stem cells can be cloned in a certain way does not make it so, at least not until others have been able to do it in their labs.

Scientific fraud is tempting because scientists are trusting. But nobody gets away with it, not the Korean who claimed to clone a person, not the physicist from Bell Labs, and not these guys. If a result doesn't hold up, it sinks.

Global warming, on the other hand, is holding up just fine, being confirmed and reconfirmed in many ways.

speaking of being trusting
It's amazing that this "trusting" nature of scientists only extends to certain, politically correct subjects.

And AGW is not holding up well at all, it's very foundations have been blasted to shreds.

The basis of all modern science is empiricism. Any scientist that isn't mindful of the potential of fraud, isn't trusting they are fools.

Caveat Emptor applies everywhere!

The Golden Stem Cell State
"After Nature's undiscerning treatment of Lanza's stem cell work, however, it seems more likely that destructive research on embryos will slip through with a wink and a nod."

In California, it will be perfectly legal to destroy embryos in publiclly-funded stem cell research. You might not agree with it, but at least California is not lying about the destruction of embryos.

Hey, lib, you obviously don't know any scientists. First of all, scientists are supposed to be skeptical, NOT trusting. Everything must be verified and confirmed by additional testing. No legitimate scientist "trusts" a new discovery without replication.

Furthermore, political or not, a science journal is NOT supposed to provide information that is inaccurate or even misleading. the journal has retracted much of its press release, as much of what was provided to the public was clearly misleading.

As for global warming, talk about mixing politics and science! The scientists have thrown out their objectivity and skepticism on this topic to keep the $$ flowing and participate in the PC crowd. Shame on them!


killing is ok, so long as you don't lie about it
that's a novel defense.

great article.
I am relieved to hear that this "breakthrough" was nonsense.
I have reason to conclude that one cannot remove any stem cells from embryos without damaging the embryo.

The assertion that stem cells are generic is simply unfounded. When the zygote, or fertilized egg, divides for the first time, one resulting egg has the father's DNA and the other has the mother's DNA. There are then paternal and maternal stem cells. One may safely assume the products of further cleavage remain distinctly maternal and paternal.

Embryonic stem cells then are not generic, they are to some degree specific right from the start.

While cloning less complex mammals may be possible because the differences between maternal and paternal embryonic stem cells are moot in the early stages of development, one has to conclude that the more complex the species under study the greater the difference between any given embryonic stem cells. And one must conclude that this greater difference is expressed earlier in gestation.

not true
When the sperm and the egg combine, so do the DNA. At that point there is no longer paternal DNA and maternal DNA, there is only babies DNA.

Law versus Morality
I didn't say that destroying an embryo was morally "ok" but legal.

For example, Mormons believe drinking any amount of alcohol is immoral but allow others of a different religious view point to buy, sell, and drink alcohol.

As for embyros, we do know this to be undisputably true: they do not have a brain and thus no personality and no memmories.

reviewing and confirming
Modern science works like this.

1. Scientist Bob (conventional names) does an experiment and takes measurements. He also has a theory that roughly fits his data. He writes an article and submits it to Nature for publication.

2. The editors at Nature try to figure out who in the world is expert enough to read and understand Bob's submission. This is guesswork because the editors themselves are not up on the latest in Bob's field. They identify maybe 5 "referees" who will be asked to read Bob's submission and report on its quality. With a bit of luck, maybe three of them will submit reports within a month or two -- scientists are busy and refereeing is time consuming and doesn't pay.

3. Referee Alice recieves a copy of Bob's submission from Nature along with a nice note asking her to review it. She reads it over to see whether the experimental technique is sound and the theory is plausable. She will trust that the data are reported honestly (though possibly incorrectly -- experimental error) unless she knows Bob is a liar or feels the data violate basic scientific principles. In a practical world, Alice may spend a lot or a little time with Bob's submission, and she will be more critical if Bob's results contradict her own. Even if she recommends publication, she takes no personal responsibilit for the results.

4. Editor Al takes the advice of the referees to the extent the referees agree and seeks additional refereeing in case the referees disagree. If 3 referees say "publish" Nature will publish.

5. Scientist Ted sees Bob's article in Nature and tries to duplicate the result, with an experiment similar to the one Bob describes. Alice did not do this, and was not expected to. If Ted can't get it to work he may (i) submit a paper to Nature trashing Bob's work, which may also be refereed by Alice, (ii) call Bob to figure out why their results are different.

Until several Teds appear, Bob's result is "interesting but unconfirmed". The journal does not take responsibility for the correctness or truthfulness of articles it publishes, though its reputation depends on careful refereeing.

Now for the trash talk: Hey, con, I'm a scientist (my department is ranked top in the US in its field by US News, I have an award for my scientific research signed by your idol, President Reagan) and you're not.

I don't get what your are saying.
I understand that the sperm and the egg only have single helixes.

both sperm and egg have double helixes
which combine when they combine.
Once they have combined, all cells have the exact same DNA.

This is how it works:
"While I was reading Alexander Kohn's splendid new book for review, three new pieces of the
scientific piracy, plagiarism, and forgery jigsaw emerged: the long-delayed report by Stewart and
Feder on the classic Darsee case; the investigation of Slutsky's work (who, if for nothing else, by
producing one scientific article every ten days must surely get into some book of records); and
the retraction after only six months of findings on oncogenes by some Americans who could not
reproduce the results obtained by their erstwhile Italian colleague. No part of the scientific
community emerges from these or Kohn's accounts with much credit. There are the editors who
insist on articles so short that tell-tale methodological details are omitted, or who decline to have a correspondence column where doubts can be raised; there are the referees who are too
incompetent, lazy, or biased to spot the defects in an article; there are the so-called co-authors
happy to accept "gift" authorship when they cannot take intellectual responsibility for any part
of the paper. And, above all, there is a scientific community too indifferent to develop a real gold
standard of scientific quality, preferring instead to accept numbers of published articles as the
measure of merit."

""Now I would like to challenge a simplistic value - that it is wrong to use unscrupulous means to advance one's career in biology.
Before you steadfastly answer yes, look closely at some role models of the profession ... why should less distinguished scientists be honest when unscrupulous behaviour is rewarded with celebrated scientific recognition? Science advances by finding answers to questions about nature. Whether or not a scientist is scrupulous has no bearing at all on scientific discoveries.""

Drinking only affects me.
Your position, to me, is akin to saying, if you don't like slavery, don't own one.

Recent studies have shown that the cells that form the frontal cortex start forming as early as 3 or 4 weeks after conception.

i'm getting quite confused
from wikipedia
Diploid cells have two copies (homologs) [homlog=One member of a chromosome pair] of each chromosome (both sex- and non-sex determining chromosomes), usually one from the mother and one from the father. Most somatic cells (body cells) of complex organisms are diploid.

As for embryos ...
we do know this to be undisputably true: they do not have a brain and thus no personality and no memmories.

So are you saying that there is some definitive existential event?

Regardless, you are in a dilemma. Can you define memory?

faith based post on a reality concept
Liberalgoodman you should know by now that none of these nuts have a clue. They read from the que cards handed out at their redneck rallies. Most of them seem to be ex army so are use to following orders and not doing to much thinking of their own.

I agree with both of these articles and neither contradicts what I wrote. Scientists are not all honest and published work is not always correct. Referees scrutinize submissions but have to accept reported data because they have not the money nor the time to repeat the experiments themselves. I've been around long enough that I'm used to miraculous sounding claims, particularly in the science sections of newspapers, turning out to be way overblown or flat out wrong. I would be particularly skeptical reading about a miracle cure discovered by a company hoping to profit from the news, as was the case here. I was skeptical when a for profit company started announding that it had sequenced the human genome, but there are more and more confirmations of that coming in, so it might be time to start believing it.

Nevertheless, I strongly believe on the basis of long personal experience that by far most scientists are honest. Deliberate scientific fraud is extremely rare. Of the thousands of articles published by Nature every year, maybe one or two involved deliberate fraud. Maybe 20% are completely wrong because of incompetence of the authors, 20% are wrong dispite competence of the authors, 20% report results already known (but not to the authors or the referees), and 40% are advances of science.

Our leaky scientific system might seem inefficient as a way to find truth. Think of courts, where the truth is supposed to emerge while lawyers (and even witnesses) are more interested in the outcome than the truth.

Follow Reagan's advice:
Trust, but verify.

4 Days vs 4 Weeks
"Recent studies have shown that the cells that form the frontal cortex start forming as early as 3 or 4 weeks after conception."

Well, you're in the ballbark -- that's a start.

The fact that the neural tube doesn't close until apx the 28th day is not a new discovery. I've posted about this before -- back when this site was called Tech Central Station (unfortunately Google's cache does not include those posts).

It's the neural tube that becomes the spine, and the closure at the top becomes the brain. In the following two weeks the hemispheres begin to differentiate and as do the three primary brain vesicles.

So scientifically speaking, you're correct to point out that the embryo is not considered a fetus until the 8th to 10th week of developement. However, the embyros used in IVF treatments and/or stem cell research are only several days old and have no physical form whereas the 4 week old embryo resembles a tadpole.

In otherwords, the embyros used in stem cell research do not have brain tissue.

I Think, Therefore I Am
"So are you saying that there is some definitive existential event?"

No, what I am saying is that there is a time when brain tissue does not exist in an embryo. At this point, it's safe to conclude that memories and thougths have not yet occurred, for the embryos has no physical capacity to generate thought.

The closing of the neural tube marks the beginning of brain development at which point it's not currently possible to what the embryo can or can not experience.

The definitive existential event -- the awakening of consciousness as we know -- happens some undetermined time afterward.

interesting word don't you think?


What would it mean to talk of the capacity for experience?

The pyramids have experienced a great deal of erosion.

The earth has experienced many billions of species.

Primates have experienced many changes on the journey to homo sapiens.

Leftwingers and Embryos
Leftwingers seem to lack the capacity to engage in higher cognitive thought and and invariably lack (anything approaching pleasant) personalities, so effective today, I won't PERSONALLY advocate their destruction, but won't interfere with anybody else who might wish to engage in destructive harvesting of their body parts.

Better Yet Memory vs. Fantasy
Since reality is merely a personal construct according to really hardcore leftist dogma, then any recollection is unable to be compared against some standard of reality, so we can't distinguish a leftist's memory against fantasy, in much the same way we can't distinguish their economic theories from fantasy.

Uh UH UH, How dare you use the word "baby"?
"It" only becomes a "baby" when "it", is wanted by the mother and the umbilical cord is cut, until then its a "fetus", lacking any being or rights.

If you continue to use words like "baby", we will have you bound and gagged for thoughtcrimes.

eh, no problem.
We're overcrowded as it is. Many unwanted babies. Screw it, put them to good use.

I want my babybackbabybackbabybackbabyback,

I want my babybackbabybackbabybackbabyback,

I want my babybackbabybackbabybackbabyback,

GET IN MY BELLY! Riiiiiiiiiiiiiiiiiibs!

we're hurting...
if your department is top in it's field.

Trash Talk
Now for the trash talk: Hey, con, I'm a scientist (my department is ranked top in the US in its field by US News, I have an award for my scientific research signed by your idol, President Reagan) and you're not.

Its true, the definition of an "expert" is someone who knows more and more about less and less, hence you abject ignorance of matters involving foreign affairs, economics, history or just about anything else you post upon. Stick to your area.

By the Way
The nature of the extent and limit of knowledge is properly the domain of that branch of philosophy known as epistomology, not science.

You have an honorarium from Reagan for that too?

So how many know what a stem cell is?
Having read this thread through, it appears that many have a hard time explain ing sexual reproduction at ths cellular level. If that is true how many Americans actually know what a stem cell actually is?

Why would a stem cell from another "person" not have rejection problems when transferred into the person with a disease or ailment?

As for scientists being objective, scientists are very human with all the likes, dislikes, biases etc of all other humans. Sadly,today some actually go through school and get their PhD and have no idea what Scientific Method is or what it means to test the null hypothesis. Many still apply statistics after they collect data not design their experiment understanding the limitations and assumptions of the statistical models they ultimately use.

As someone already said most great scientific discoveries are rejected by concensus of other leading scientists, though as much from jealousy or worse the lack of imagination than necessarily legitimate skepticism or good science.

Have Brain Cells, Will Think
I'm not sure I understand your point. Are you suggest than the pyramids have consciousness simply because they exist? If so, you're certainly entitled to your beliefs, but there's no science to support such a notion.

However Primates, like human beings, do have brains and thus have consciousness -- a fact that Science does support.

Mindless Fantasies
"Since reality is merely a personal construct according to really hardcore leftist dogma, then any recollection is unable to be compared against some standard of reality, so we can't distinguish a leftist's memory against fantasy, in much the same way we can't distinguish their economic theories from fantasy."

In any event, a brain is required to experience reality and fantasy. Once the brain dies -- or before it exists -- human flesh is incapable of entertaining absurd economic theories or the cold, hard facts.

Toti- Multi- Pluri- Potent
Stem cells come in several types, but they all have share some ability to develop into specific cell-types needed to sustain life -- like liver cells, blood cells, brain cells, etc. The potency of a given stem cell is measured by the number of types of cells in can develop into.

Stem Cell Research Foundation

Simply put, stem cells are primitive cells that give rise to other types of cells. Also called progenitor cells, there are several kinds of stem cells.

TOTIPOTENT cells are considered the "MASTER" CELLS of the body because they contain all the genetic information needed to create all the cells of the body plus the placenta, which nourishes the human embryo. Human cells have this capacity only during the first few divisions of a fertilized egg. After 3 - 4 divisions of totipotent cells, there follows a series of stages in which the cells become increasingly specialized.

The next stage of division results in PLURIPOTENT cells, which are highly versatile and can give rise to any cell type except the cells of the placenta or other supporting tissues for the uterus.

At the next stage, cells become MULTIPOTENT, meaning they can give rise to several other cell types, but those types are limited in number. An example of multipotent cells is hematopoietic cells—blood stem cells that can develop into several types of blood cells, but cannot develop into brain cells.

At the end of the long chain of cell divisions that make up the embryo are "TERMINALLY DIFFERENTIATED" CELLS -- cells that are considered to be permanently committed to a specific function.

Talks With Blastocysts
"I won't PERSONALLY advocate their destruction, but won't interfere with anybody else who might wish to engage in destructive harvesting of their body parts."

No problem, superheater.

You see, you can't harvest the body parts of another human unless they are legally declared dead. Sure their bodily organs might be kept functioning on life-support equipment, but brain function has ceased. Thus you're not destroying their life because it's already gone.

In the case of days-old embryos, conscious life hasn't even begun -- unless you claim to have the ability to communitcate with Blastocysts.

when sperm and egg combine, the double helix DNA in each is split. One strand from each cell combines to form a new double helix DNA strand. This is the DNA that is used in all cells that split from this single cell.

Mark's right, of course. Sexual reproduction gives the baby one chromosome (out of each chromosome pair) from the father and one from the mother. During egg and sperm generation (meiosis) the chromosomes split so that each egg and each sperm have only half of what normal cells need to function.

This meiosis results in eggs and sperm cells with various combinations of the alternative chromosomes. For this reason full brothers may be pretty similar or very different.

When these two gametes come together during fertilization the resulting cell now has the full complement of chromosomes, half from the mother and half from the father. And all the cells in the baby have the same genetics. If this growing ball of cells should break apart at an early stage producing identical twins then both babies have exactly the same genetics.

Such combinations of chromosomes from the mother and the father are the entire point of sexual reproduction. The idea that a baby would be a mosaic of maternal and paternal cells is quite mistaken.

I am surprised that you could be this confused about such a fundamental biological process. If many folks don't understand how this works, then the average citizen might also be in a weak position to understand stem cells.

In fact, without getting too moralistic about it, the sperm cell and the egg cell are both incapable of survival or perpetuation once they are outside of the body and sitting on a piece of glass. They do not constitute life. Combining them may create a cell with the full complement of genetics, but unless that cell is implanted into a uterus it cannot become a baby. However, if such a cell is converted into a tissue culture line, then that is its life form. From the first moment that it exists it is a cell culture and nothing else. This is not in any way different from harvesting a living cell from an adult and perpetuating it as a cell culture. We do that all the time and no one seems to have a problem with it. Is that cell culture a human being? No. Of course, not.

Another comment. If we are squeamish about the morality of cell culture in general and regarding stem cells in particular we should be assured that others will not hesitate to develop these technologies. For example, there are societies out there who believe that it is immoral for women to be educated. Those societies are getting left behind and they are angry about it. Let's be careful believing what our own priests tell us (that we do not otherwise understand), Christian soldiers.

I'm communicating w/ you, but..
I don't claim to need to communicate with somebody for them to be alive. I had a relative with alzheimers who wasn't there but was very much alive. Their "conscious life" was over, just like when you start adopting leftist politics, so I guess we should've started taking stuff they didn't need, you know corneas and stuff, after all, one of the bad thing about alz is the wandering about, so we could've put the corneas to good use and made care easier. Stupid us!

Let's be careful believing what our own secular priests (aka genetic experimenters) tell us (that we do not otherwise understand), Secular Soldiers.

For example, there are societies out there who believe that it is immoral for women to be mothers. Those societies are getting left behind and they don't have a clue about it.

You need a Brain to be Stupid
"I had a relative with alzheimers who wasn't there but was very much alive. Their 'conscious life' was over,"

Now that's a perfect example of poor scientific understanding.

A person with alzheimers has a diseased but still operational brain. Clearly the erosion of memories have a large impact on their awareness, but experiential imput -- that is, the ability to touch, taste, see, hear and smell -- is also a part of the conscious mind.

So no, their conscious life is not over, but it is increasingly limited. Life does not end until the brain ceases to function.

Ya, but..
They all have a strand of DNA from each parent.
So they are genetically unique.

My stem cells were/are different than yours.

Organ Donors
"My stem cells were/are different than yours."

Our blood cells also have different DNA, but if we share the same blood-type we could do a blood trasnfusion. And given we met tighter restrictions, we could even use the other's kidneys, liver, bone marrow, etc.

So what is your point?

Previous question
"Why would a stem cell from another "person" not have rejection problems when transferred into the person with a disease or ailment? "

Blood is apparently not rejected, however, organs are and drugs are required to prevent infection.

Very good post RH
I am anti-abortion (not in all cases, but suffice it to say I'm against open abortion as it now exists). On the other hand, I feel there is a lot of room for things like stem cell research. I also believe it can be done without violating an usable code of ethics, morality or law.

There should be no ethical reason not to allow research on embyros less than 20 days gestation. Those who protest this are just plain radicals.

"Blood is apparently not rejected, however, organs are and drugs are required to prevent infection."

There is some hope of reprogramming adult stem cells (the multi-potent kind) into fetal stem cells (the pluri-potent kind). However, forward thinking parents may opt to place the placental/embylical tissue of their children on ice.

The less fortunate will have to make due with stem cell therapy using donated stem cell and drugs to suppress their immune system's rejection of foreign tissue. Even so, it would be a large step forward from the organ-donor waiting lists of today.

So how many know what a stem cell is?
Makoshark makes an important point by drawing attention to the poor state of statistical understanding among research scientists. Based upon observations in my own field of hydroclimatology a high fraction of research builds in prior assumptions and/or data preselection whose effect is to lower the bar on failing the null hypothesis.

While replication is a way of sorting this problem out, a break on this is that colleagues collude, perhaps unconsciously, knowing that only positive results are publishable. This is especially the case in the climate change arena, preeminently with research into record breaking, trends and discontinuities.

thank you. Next question
how does a cell know what it is?

Presumably the DNA is the same material in every cell.

that was my point
cell division must occurr along two separate threads.
Paternal DNA replication and Maternal DNA replication.

My other point is - "they" "we" don't really know what a stem cell is.

To define a thing is very different than to describe a thing.

Control Genes and Proteins
how does a cell know what it is? Presumably the DNA is the same material in every cell.

Yep -- the same DNA that makes a skin cell on your knee is the same DNA that makes a nerve cell in your spinal column. When sexual reproduction creates the first cell of a new organism (the moment of fertilization) that cell is TOTIPOTENT -- meaning it's the ultimate generic cell.

Early cell division proceeds by creating more totipotent cells, so that 100 cell blatocysts used in IVF treatments and stem cell research is functionally uniform (unspecified). Specialization occurs when God waves his magic wand and says "Engage!" -- just kidding.

In reality, cell specialization occurs when control genes (genes are section of DNA) produce proteins that regulate cell growth. It's a bit technical, but the following describes the process in the simplified example of yeast

Genomic dissection of the cell-type-specification circuit in Saccharomyces cerevisiae
PNAS, December 28, 2004

...Typically, cell-type specification is based on a transcriptional circuit in which combinations of regulatory proteins determine the final pattern of gene expression that is appropriate to a given cell type.

Although unicellular, the yeast Saccharomyces cerevisiae has three distinct types of cells, and the cell-specification circuit is combinatorial (refs. 1–3 and Fig. 1). The a and {alpha} cell types are typically haploid in DNA content and mate with each other in an elaborate ritual that culminates in cellular and nuclear fusion.

These events produce the third type of cell, the a/{alpha} cell type, which is typically diploid. This cell type cannot mate but, when environmental conditions are appropriate, can undergo meiosis and sporulation, producing two a and two {alpha} cell types. The patterns of cell-type-specific gene expression are set up by a few sequence-specific DNA-binding proteins acting in various combinations.

Three critical proteins ({alpha}1, {alpha}2, and a1) are encoded by the mating-type (MAT) locus. A fourth key sequence-specific DNA-binding protein (Mcm1) is encoded elsewhere in the genome. In this article we use the term "cell-type-specification circuit" to refer to the regulatory scheme diagrammed in Fig. 1, because each component and branch of this scheme is necessary and sufficient to establish and maintain three cell types.

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