Ethics, Conscience and Cheating

Is there a difference between matters of conscience and things you shouldn't do? If there is something that would just get you in trouble but you don't believe it's wrong, how do you decide what to do?

The blog, Adventures in Science and Ethics, is one of the ScienceBlogs that I follow. (I love her "Friday Sprog Blogging" about her kids and the discussions about being a woman and having a family in Academia.)

There's a conversation on morality and cheating:

A reasonable ethical decision is one that you can defend -- to others, not just to yourself. You can give reasons why, of the choices available, this was the right way to go.

A course of action that you are taking pains to hide -- one which you would not want to have to defend to others -- is a red flag, ethically speaking.

Being able to justify a course of action to others is a more stringent requirement than being able to justify it to yourself. Folks who see themselves as living up to a high moral standard ought to keep that in mind and make sure their deeds can meet this requirement.

I was raised on the Bible, being taught to respect the authorities and to understand that a sin is a sin is a sin. However, I have a sense of "that's not fair" when I think of putting highway speed limits on the same plane as hurting someone else or even cheating on a test.

Old Dog, New Tricks

I've been working on my LifeEthics.org website and got most of the boxes lined up and the links all work! But the cool thing is that I've made a window for "Bioethics Headlines" as part of the main page.

Not bad for an old lady who learned to type at 40, if I do say so myself. BTW, Microsoft Publisher makes a decent web page composer.

Translation of Yamanaka, Yu "induced Pluripotent Stem Cells" (Revised)

Scientists who report their findings are expected to discuss the problems as well as the outcome of their research. This is usually found in the "Discussion," "Conclusions" or "Results" section of the paper. This is the best place to figure out what the researches intended, what they did and what the report means. (Then you go back and check to see if they proved what they "discussed." And then, you wait for other labs to confirm it.)

The actual (Takahashi et al., "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors," Cell (2007).) Cell article on reprogrammed adult fibroblast skin cells, the "induced Pluripotent Stem Cells) or "iPS," is available for free, here. The Science Magazine report about similar work by James Thomson from Wisconsin (the researcher who reported the production of human embryonic stem cells in the first place) is supposed to be published November 22, 2007. (Editorial note 11/30/07 – Science published the Thompson and Yu report the same day that Tamanaka's report was published, two days ahead of schedule. See my “translation,” here.)

To the best of my understanding, here's a translation into layman's terms about what the Takahashi/Yamaka report means:

While it took a lot of cells and more time than the researchers first expected because the human iPS grew much slower than the mouse iPS,

1. The cells that grew looked and functioned like human embryonic stem cells with a few minor differences,
2. They believe they proved that their technique is responsible for all the new pluripotent cells that were found in their cultures(there weren't any cells from another culture introduced accidentally or on purpose and which would make them look more successful than they were),
3. The cells could be directed to develop nerve cells and heart cells,
4. They were able to use several types of adult specialized cells to achieve iPS, and
5. The researchers suggest several possible ways to overcome the drawbacks of the process.

The authors believe that the inefficiency or the need to begin with lots of adult cells and wait a little longer for a substantial amount of human iPS should not be a "practical" problem because the adult cells are easy to obtain and labs all over the world should be able to reproduce their results. Since the technique should be well-funded (it qualifies for US Federal funding and is ethical, since no human beings have to die), the authors believe it will be possible for lots of researchers to work on them.

If I were to predict the future, I would anticipate banks of iPS - or even specialized or intermediate forms of cells that are produced from iPS - being stored for each of us, just in case. In the very long term, we will learn more about stimulating our on bodies' stem cells from research on these cells, so that we can repair or prevent damage without transplants or waiting for cultures to grow in the lab.

The major hurdle is that the cells were produced by the Recombinant DNA technique, using retroviruses in plasmids.

The retroviruses are a class of viruses that actually insert themselves into the DNA strands of animal or plant cells to become a part of that cell’s DNA and are copied when the cell reproduces. They are manufactured in the lab in the form of plasmids in order to carry genes into the experimental cells.

Plasmids are little bits of DNA, a mini-virus in a circle. Think of a chain with pairs of magnets or interlocking puzzle pieces that connect the ends and make a loop. When open, the plasmid becomes a strand of DNA which has ends that are "sticky.” When placed in a culture with mouse or human cells, the plasmids infect the cells and then move into the nuclei of the cells. The retroviral DNA is inserted or inserts itself into the DNA of the host cell because the sticky ends of the plasmid strand match or mate to certain areas of the host DNA.

Plasmids can be manufactured to carry copies of genes that researchers want to insert into the DNA of experimental cells. The technique is common in commercial and experimental labs for at least the last 30 years. In fact, "Recombinant DNA" is used to induce strains of bacteria and yeast cells in cultures to manufacture vaccines like the flu and Hepatitis B vaccine and the insulin used by diabetics these days. The particular retroviruses used by Tamanaka are said to be "strongly silenced in humans." In other words, they don't normally get reproduced as viruses when the cell divides. Once they are taken up in the cell DNA, the viruses used in research don't break out to become infectious viruses, again. However, some of them can induce the cells to form tumors or cancers if injected in an animal or human.


One of the possible problems that the article notes is that the new iPS cells each had several copies of the retrovirus included in their DNA. There is a concern that these bits may be responsible for the tumors that were seen in the mice used in the experiments. Before iPS can be used in humans, it will be necessary to learn to remove all the viral particles or to learn to make the cells without viruses that can cause tumors. Otherwise, there is a risk of causing cancer in patients.

The researchers note that another group of scientists have already reported that it is possible to insert one of the genes without using retroviruses and that the hope is to either find a way to insert the other three genes or to remove all traces of the virus.

There's also a suggestion that what they are actually inducing to grow is a sub-set of fibroblasts with the tendency to become embryonic-like stem cells.

CNN objects to conscience

This subject again.

CNN, that bastion of upstanding plants ethics, objects to doctors with morals - or at least the ones who act on them.

The CNN video (not a "news piece") shows interviews with a woman who was refused contraception by one doctor and a second interview with another doctor who is Catholic and who does not believe that contraception is moral and so he does not prescribe it.

The reporter is shocked that 60% of doctors feel that it's okay to tell patients our moral views.

The reporter asked the patient whether she felt "rejected." The woman said that she did and that she felt that the doctor was judging her and imposing his morals on her. She said that any doctor who would not do what his patients wanted should not be in practice.

The woman isn't judging or imposing her morals on every doctor, is it?

Doctors make "judgments" all the time. We are not simply dispensers of products that people want. We must "impose" our judgment on patients who smoke (a perfectly legal drug) and drink (ditto) or who have become overweight from eating legal food and choosing not to exercise enough to burn off calories faster than they take them in. We are responsible for determining whether a patient is becoming addicted to pain medications, asking for a note for missing work when they were never sick, or a handicapped parking sticker when they're not disabled.

Much more often, we make judgments about the cause of a patient's symptoms or disease and how best to treat it. Our job is not to make the patient feel good about themselves, although most doctors I've met prefer to do so. What we do is diagnose and treat in order to help the patient be as healthy as we are able.

While I don't object to non-abortifacient contraception, it is an elective service in most cases. It is very rarely necessary to maintain the health of the body of patients. It is truly a "choice."

As I've said before, it would be simpler for people who feel that contraception is important to arrange to pay doctors who will write and dispense those medications and devices to go around to the areas where they are needed.

The alternative is to find a way to trust a doctor who will act against his conscience - to do what he considers the wrong thing for your pet issue - to do the right thing every other time.


Hat Tip: Blog.bioethics.net

Emotional Debate on "Physician Assisted Suicide"

On Tuesday night, November 26th, I drove to Houston to hear Wesley J. Smith, debate Physician Assisted Suicide (PAS) with Kathryn Tucker, the Director of Legal Services for Compassion & Choices, which was once the old Hemlock Society and then Compassion in Dying. Mr. Smith is the author of The Culture of Death and Forced Exit: Euthanasia, Assisted Suicide, and the New Duty to Die. The only biographical data I can find on Ms.Tucker is this pdf.

The Holocaust Museum Houston has teamed up with the University of Texas Health Science Center at Houston to present the Dr. Michael E. DeBakey Medical Ethics Lecture Series, called ""Medical Ethics and the Holocaust: How Healing Becomes Killing--Eugenics, Euthanasia and Extermination."

From the first, opening night, presentation featuring the-soon-to-be-unpopular James Watson and two other Nobel Laureates, it seems that we are being exposed to an ethics lab, rather than a history and theoretical series. The speakers the first night, including a doctor, Eric Kandel, M.D., 2000 Nobel Laureate, Medicine or Physiology, who was a child in Vienna on Krystallnacht before his family escaped to the US, told us not to worry about research on human embryos as long as the parents give "informed consent." Ironically, after descriptions of the build up to the Holocaust, Dr. Kandel reassured us that that we would gradually get accustomed to embryonic stem cell research.

I could tell that Mr. Smith and Ms. Tucker were irritated with each other during the program. In her introduction, Ms. Tucker referred to an earlier debate that had taken place that day when, as Wesley later told us, "it got angry." I got the idea that the moderator, Dr.Sheldon Rubenfeld, was slightly testy, although he did a good job moderating the questions, as always.

Ms. Tucker' s history of redefining, renaming, and litigating did not reassure me.

She was the lawyer in the case of a family suing a doctor for failing to give their loved one enough medicine to control pain at the end of his life and has fought laws against PAS for 10 years. Ms. Tucker misrepresented "terminal sedation," as though it is always intended to lead to death, rather than "deliberately inducing and maintaining deep sleep but not deliberately causing death in very specific circumstances." It was a surprise to hear Ms. Tucker warn against "back alley deaths" although it turns out that it wasn't the first time I'd heard the term. She frequently used the word, "choice," comparing the patient's choice at the end of life with a woman's right to "Reproductive Choice."

The silliest part of the evening - we were discussing death, after all - was when Ms. Tucker chided Mr. Smith for using the wrong terminology, "Physician Assisted Suicide." She showed us the recently revised policy statements of the American Medical Women's Association and the American Public Health Association. Because these two second tier (that's a word I learned from John Gearhart while attending the ASBH conference this year) organizations revised their own terminology to avoid the "emotionally charged" nature of certain words within the last year, Ms. Tucker shamed Mr. Smith for using the American Medical Association's terminology and legal term instead of calling the act "Aid in Dying."

Mr. Smith pointed more clearly to the problem of emotions when he remarked that it is often acknowledged in these debates that "existential pain," or the emotional component of pain, may be worse than physical pain.

No matter what we call it, death is always going to be an emotionally charged subject and is rarely dignified or controlled. For one thing, the body loses control of the bowels and bladder at death, as well as everything else. The questions from the audience were examples of people who approach the subject of end of life care from a strictly emotional viewpoint, rather than thinking it through to its logical consequences. The emotion is getting stronger as technology introduces more and more variables.

However, when we are discussing Medicine and the death of the body as well as of the mind and spirit, we should confine our conversations to the physical consequences. To be trite: When you're dead, you're dead.

There is no legal question as to whether "Assisting" or "Aiding" death is different from withdrawing care. We don't pinch the patient's nose or remove the oxygen from the room when we withhold or withdraw a ventilator. Physician Assisted Death, in contrast, is an irrevocable interventional act against the living processes of the body using State regulated medical knowledge and medicines, and should be treated as the violation of medical ethics that it is. The history of Western medicine, at least between Hippocrates and Roe, has always condemned intentional use of medicine to positively end the life of the body.

Mr. Smith and I have had several discussions about the ethics at the end of life, especially the Texas Advance Directive Act, which he refers to as the "Futile Care Act." We agree that doctors should never intend to cause death but that they may withhold or withdraw intervention at the request of the patient. We disagree, though, about whether a doctor may refuse to intervene because our best medical judgment is that the intervention will cause increasing damage to the body and prolong death.

I found myself, a Family Physician who cares for people at all stages of life, theoretically squeezed between two legal pressures, one law to force me to act with the purpose of killing a patient and another that would force me to act even though my medical judgment is that the intervention caused harm. Several people from the audience also advocated for legal consequences for doctors who failed to follow patients' end of life wishes by prolonging their lives.

To be honest, if I had to "choose" between the two, I would choose against Ms. Tucker's extreme, which would leave me with Mr. Smith's. I could live with that.

However, I hope that society will teach doctors to never take life while expecting the profession to assist one another in determining when medical intervention causes more bodily harm than healing, when a patient's bodily processes are breaking down faster than we can heal or maintain them.

(Edited 11/20/07 for grammar and order - BBN)

Embryonic Stem Cells in humans?

There are stories about embryonic stem cells being used by a doctor in India, Dr. Geeta Shroff who works at in vitro fertilization clinic. Dr. Shroff has not published her work at Nu Tech Mediworld, will not allow other researchers to examine her cells, cultures or techniques, and the research was rejected by the Indian Council of Medical Research (ICMR). According to this article from the UK's Guardian, Dr. Shroff is a fertility specialist who became famous for a technique allowing the determination of a baby's sex without a scan or amniocentesis. (It's illegal to check on the baby's sex in India, now, because of the numbers of baby girls who were aborted in that country.)

Wise Young, M.D., Ph.D. is an expert from the W. M. Keck Center for Collaborative Neuroscience at Rutgersin treatment and research on Spinal Cord Injury (SCI) and he is my hero because he runs a bulletin board for people from all over the world who are looking for hope for their SCI. Dr. Wise and I disagree on embryonic stem cell research, but we do agree on this woman's methods:

1. There is no evidence that Dr. Schroff is injecting embryonic stem cells. The fact that she is so secretive about the cells after having done 150 patients suggests that she in fact is not injecting embryonic stem cells. Why not show the cells and describe them? She does not describe how she pre-differentiates the cells, if at all, before transplantation. The lack of such information is very suspicious.

2. I wonder how much Dr. Shroff knows about spinal cord injury and how rigorous she has been in examining the patients, whether the patients were incomplete or complete before the surgery. She probably assumes that no patients walk after spinal cord injury.

3. The fact that this "works" on every disease that she has tried it on is also very suspicious. There is no such thing as a universal treatment.

There's this long thread at "Care Cures" concerning young people who have had the doctor's "shots" over the last two years. Look at the last 5 pages, with stories from people who believe the treatment is a scam.

Dr. Shroff says that she experimented on embryos donated to her by patients at her IVF clinic and that one of those embryos yielded what she calls a very successful line that she has been using in patients. The patients say that they receive shots of the stem cells over months, while they undergo therapy at the clinic.

There's not much information on the Web, nothing at all at the National Library of Medicine listing of scientific and medical research, the National Biotechnology Information Center, Pub Med, and no listed articles by Dr. Schroff or clinic websites that can be found with a Google search, just a few stories from individuals and a few news articles.


Here's the website of a woman, Amanda, who received treatment in India in August, 2007. one from the Skye news service about a woman from Australia. This article from the Australian "60 minutes," has a discussion with another researcher, Hans Keirstead, Ph.D., who is described as a "wiz-kid" associated with the Christopher Reeve Foundation at the University of California-Irving, who has published quite a bit of basic research in animals with embryonic stem cells and who claims that Dr. Shroff is unethical for using humans as her "guinea pigs."

Medicare Pie Cut Thinner

Think of the money that Medicare pays doctors for seeing patients as though it's a pie called the "Sustainable Growth Rate." This pie is not going to get bigger unless Congress cooks some more pies by New Years. Otherwise, when more patients join Medicare and more pieces are needed next year, we will have to cut the pieces that doctors are paid each time we see a patient into smaller and smaller pieces.

I wimped out: I closed my office in 2003 because I saw the costs of the requirements for medical reporting and "privacy" coming and I figured that I could work part time for other people and make more money than I was making as a solo doc. (And I hate the business part of medicine.) I'm not sure how many others are making the same decision, but we often read about "boutique" practices and docs who won't take Medicare or new Medicare patients. Have you noticed how many doctors in your town are adding things like Botox shots, laser therapy and other cash-pay services?

Medicare will cut doctors' reimbursement by 10% in January if Congress doesn't act before the end of the year. This cut is separate from the Veterans Administration, Medicaid and SCHIP funding and is written into the current law. Since many doctors have contracts with insurance companies that pay based on Medicare, the cuts will go even deeper.

If you don't understand the impact that this cut will have, ask the next person you meet who is over 65 years old whether they had to change doctors when they became Medicare eligible. Ask them whether they have any choice other than to use Medicare and how hard it is to get in to see their doctor.

As I've said before, get ready for it to become even harder.

10 years ago, financial advisers told us that Family Physicians shouldn't have more than 20% of our patient population mix made up of Medicare patients if we wanted to stay in business. Since that time, most doctors have worked harder to be more efficient and have cut out any costs in the office that we don't need. My colleagues cannot afford a 10% cut in pay, while all of our costs continue to go up.

Primary care docs are paid about $160 per hour for office visits by Medicare. We are more likely to see the patients who have 5 or 6 diagnoses, 10 or 12 medicines to straighten out, and who bring in a family member to each visit. These patients take time. If the payment goes down to $155 per hour, most doctors will not be able to afford the cut.

In order to earn that money, we need the office and furniture, utilities, supplies for the patient room and office staff, at least a couple of staff members to check patients in and assist us, someone to answer the phones, those phones, refrigerators for medications, someone to handle the billing and banking, and all of the fees and insurance that normal businesses handle, like property taxes, slip and fall insurance, fire insurance, employee tax to the State, property tax on the building, furniture and supplies, and unemployment insurance, etc.


Then, we have malpractice insurance, professional dues to the County Medical Society and most likely our State and national AMA dues in order to remain "Board Certified," State licensing fees, DEA licenses from both the State and Federal systems, hazardous waste disposal fees, CLIA (office lab) fees, and the fees to keep our computer systems that are increasingly mandated by law if we want to be paid the full $160. The new electronic medical records can cost as much as $30-$40,000 per doctor up front and several hundreds to thousands per month.

In addition to these costs, Medicare requires the highest level of reporting, risk and red-tape. This year, there was a planned delay of payment from the Federal government for 2 weeks at the end of October built into the Federal budget to make it appear balanced. There were also unplanned delays when doctors began using the new National Provider Numbers phased in this year as part of the Medicare laws. (A lot of that expensive computer software in the office, at the insurance companies, and at the Center for Medicare and Medicaid Services couldn't handle the numbers.)

Now do you see why I hate business?

For more information and history, read this article or watch this video from the Texas Academy of Family Physicians.

Please consider calling your Representative to the House, your two State Senators, and the White House and ask them to protect Medicare payments to doctors.

Genealogy for fun and profit

The blogs are buzzing over new home tests to access your gene profile.
Biology in a Digital World and the Women's Bioethics Blog are talking about the $999 test.

However, the genealogy lists are doing testing for family lines (the tests are sold by the website) instead of the old way of talking and searching church records. See the groups of families who are following the heredity of the men by surname and markers on their Y chromosomes (passed only from men to their sons, since girls don't have a Y chromosome) and both men and women by their mitochondrial DNA (passed from mother to all her children in the oocyte cytoplasm) at Ancestry.com DNA, where you can buy your own test and join your free family group list serve or message board at RootsWeb.

I do wonder about the consequences of some of the tests, that are bound to reveal that some one fell off the family tree.

And I worry more about all the false positives for genetic abnormalities that will show up. The last I heard (in a conference, so no link), there were lots of "abnormalities" that we find on our tests - but we don't know the significance of most of them. In other words there are variations in genes that we have not tied to diseases.

But I did see one great post, a man who said that he would never test his children - they are his children, no matter what the DNA. I wish I could find it again, because the man's my hero.

Germans Praise Stem Cell Breakthrough

It turns out that it's not just American Christian right-wingers who are grateful that there's an alternative to embryonic stem cells from the destruction of human embryos.

Japanese scientist Shinya Yamanaka wins top German cancer prize

Heidelberg, Germany (dpa) - Shinya Yamanaka, the Japanese scientist who last week revealed a revolutionary new technique to manufacture stem cells, was chosen Monday as winner of a top German prize for cancer research.

He is to receive the annual 50,000 euro (74,000-dollar) Meyenburg Cancer Research Prize awarded at the German Cancer Research Centre in Heidelberg.

The new technique, in which only four genes in ordinary skin cells need to be manipulated, has brought relief in Germany and the United States where there is ethical resistance to using stem cells from killed human embryos.

Yamanaka's team's research was published this month in the scientific journal Cell, along with related findings by allied US scientists in Wisconsin.

The award committee said the study of induced pluripotent stem (iPS) cells was a key step to new forms of cancer therapy, since cancer cells themselves probably formed the same way.

Explaining the process would suggest ways to prevent it and thus save people from cancer.

The prize was created by a rich German couple, Wilhelm and Maria Meyenburg, and has been awarded annually since 1981.

Varied and deep rooted (cost of health care)

I'd just add a few observations to the New York Times editorial (free registration required) on the cost of health care in the US.

I'm a big proponent of making patients responsible for more of their health care costs. Health Savings Accounts, long term care insurance, and even deductibles are good ideas. I would also add that the vast majority of the people on Medicaid and public assistance could do some sort of public service work in payment for their health care. (Medicare, disability, and veteran's health care has been paid for already.)


I especially like the idea that primary care should be emphasized. How about *paying* doctors to do it instead of ensuring that we lose money for every Medicaid and Medicare patient we see?

And they don't mention some of the problems that I see:

1. Over the counter medicines that probably aren't needed in the first place and don't do what they are believed to do. Did anyone notice that the baby cold medicines are not useful and no longer standard of care? And please don't get me started on homeopathy - I'll irritate a couple of million of my readers if I go on about the useless idea that a substance diluted millions of times in water can't do anything.

2. Botox, cosmetic surgery, and beauty treatments - Do these services, when provided by a physician go into that giant number?

3. The hidden costs of school-based health care and the need for "notes" from doctors for school and work. I doubt that many people are aware of how much of Medicaid money is spent on "mainstreaming" and on learning disabilities in our school systems. I'm sure that few would understand the pressures that doctors face to provide the testing, medications, and follow up required to get mom back to work after the baby is too sick for daycare or school, for the note for the Tuesday patient who says they had food poisoning on Monday, or for the demand from a school or from the parents to get the 7 year old tested for a learning disability for all sorts of reasons.

4. Salaries and perks for insurance big wigs that could pay for the healthcare system of a couple of nations. United Healthcare, which threatens to swallow up every insurance company in the nation, has paid at least $120 Million dollars to its CEO for at least 10 years.

5. I don't want it to go away -- but -- Medicare pays for quite a bit of the research and medical education in the country. We need to see this research and the doctors, medicines and treatments that come from these funds as the valuable commodity they are and quit dinging "health care costs" for it.

Biographic article on Yamanaka

Here's a cute biography of Shinya Yamanaka, lead researcher from the Japanese team that reported reprogramming of adult cells into embryonic-like stem cells.

As an M.D. myself, I find it interesting that, unlike veterinarians James Thomson of Wisconsin and Time Magazine Person of the Year, Hu Suk Hwang, Dr. Yamanaka is a human doctor, trained in orthopedics:

Yamanaka has spent most of his life in western Japan. A native of Osaka, he earned his medical degree at Kobe University and a doctorate in pharmacology at Osaka City University.

After completing his residency in orthopedic surgery, Yamanaka headed to the University of California, San Francisco, to do postdoctoral studies that laid the groundwork for his current research.

He does express concern about the possible uses of his research by unethical researchers:

Yamanaka worries about the road some people might take.

"We need to come up with some sort of rules about what kind of cells can be used and to what ends. Otherwise, someone may put this technology to use in troubling ways,” Yamanaka said.

The research's ethical and social implications are never far from the table in Yamanaka's laboratory, said Kazutoshi Takahashi, a junior professor who participated in the project.

"The potential problems are cut down when you use this method given that we don't have to use embryonic stem cells, and that's a good thing,” Takahashi said.

Since the debate isn't yet over about ethical vs. unethical stem cells and since some people (like embryonic and fetal stem cell researcher and sometimes guest Science editor, John Gearhart, MD) have admitted to putting pressure on researchers to make sure that they follow the official line to pursue "all promising areas" (echoed here by the stem cell industry trade association organization, BIO) kinds of stem cell research, I hesitated to post this link and the quotes. But someone should record the true "debate."

UTexas: Modified virus fights stem cell cancer

Viral gene therapy (similar to techniques used in the stem cell breakthrough last week) has been used by University of Texas MD Anderson Cancer Center researchers in animal models and reported in the September 19, 2007 issue of the Journal of the National Cancer Institute. From MD Anderson:

Since 2004 scientists have found that brain tumors are driven by haywire stem cells that replicate themselves, differentiate into other types of cells, and bear protein markers like normal stem cells.

"Research has shown that these cancer stem cells are the origin of the tumor, that they resist the chemotherapy and radiation that we give to our patients, and that they drive the renewed growth of the tumor after surgery," Fueyo said. "So we decided to test Delta-24-RGD against glioma stem cells and tumors grown from them."

Researchers used a virus to infect the cells of aggressive tumors of the cells that support brain cells, glioblastoma multiforme. Gliomablastomas are 60% of brain cancers and patients have a survival rate as short as 2 to 3 months, with less than 10%-25% survival after 2 years even with current aggressive therapy. The virus is modified so that it is "selective" for cancer: it only infects the cancer tumors and cannot infect others.

The team first developed mice with transplanted human brain cells derived from stem cells found in four samples of glioblastoma multiforme. The researchers then developed a customized virus, Delta-24-RGD, to fight the cancer. According to a 2003 MD Anderson press release on the trials, the virus infection inserts copies of a certain gene, retinoblastoma protein (Rb), that acts as a "brake" on the cell duplication system of the cell. In order to make the therapy more efficient and safer, the virus also insert a gene to for a cell surface receptor, a sort of "docking" area on the outside of the cell.

The cell surface receptor for viruses is one of the ways that we are studying to fight both cancers (see this free article from this month's JNCI) and viral infections, themselves. The goal is vaccinations to affect genetic causes of cancer (as in these two reports) or to prevent viruses from binding to the cells and infecting them in the first place.

"Modest" Increase in Sexually Transmitted Diseases

After a decline in STD's in the late '80's and '90's that is believed to have been driven by "safer sex" strategies brought on by the spread of HIV, numbers of infections have increased for the second year in a row.

The increase may actually be the result of increased efforts at screening and more sensitive tests, according to the CDC.

The report notes that the greatest risk is found in men having sex with men and girls 15-19. These numbers may simply reflect the fact that these populations are more likely to be screened for diseases and that there's been a push to increase screening, particularly in the former demographic.

There's a physiological explanation about why younger girls are more likely to catch diseases like chlamydia and HPV, the virus that causes abnormal pap smears and can lead to cervical cancer. There's also a behavioral explanation: younger girls are more likely to engage in riskier behavior, have higher-risk partners and have more partners.

The cells of the cervix of the young girl are more susceptible to injury and to invection. As the girl matures, the columnar epithelium is replaced by squamous cell epithelium. (At the risk of grossing people out being indelicate - think of it as the difference between the tissues of the inside of your cheeks and the tissue on the outside of the lips.)

(Similar risk factors probably apply to the men having sex with men category, too, although I didn't see any specific discussion about these risks for girls or men in the mainstream press articles here, here, and here. This this article in a gay publication does review the girl's tissue changes and the difficulty of notifying the partner of an infected patient who is more likely to have anonymous sex partners. )


It is alarming, however, that the two vulnerable groups are also the people who are most likely to have life-long consequences of STD's. The girls risk early pregnancy and infertility and the men having sex with men risk truly deadly diseases like drug resistant strains of HIV/AIDS, syphilis, and gonorrhea.

I'm afraid that this report will fuel criticism of abstinence education. But let's face it, teaching condom use and oral contraceptives are not the answer for either of these populations.

We know a little about what works and a lot about what doesn't.

Edit, 11/27/07, grammar typos.

"Fertilized eggs" and cloned human embryos (The future, again)

"ScienceBlogs" is one of the examples I give when I'm trying to explain the anti-life, anti-religion atmosphere that is pushed (like a religion itself) in our universities and by the Powers That Be in science academia and publishing. I think I may have identified one or two of the bloggers as believers (proof that miracles happen?), but no one identifies as pro-life or even respectful of us.

Normally, the community in the 66 blogs over at "ScienceBlogs" talk to each other, but I read them to see what's going on. Since I have a tendency to tilt at windmills, occasionally I post. The gang over there is so unhappy with the breakthrough on embryonic like stem cells from adult stem cells that it's almost like reading up on the Clintons at one of the Pink or websites. (Watch out for the language.)

I posted a reply to the atheist blogger (look for the "Red A" banner suggested by Richard Dawkins), PZMyers, who wrote some silliness at his blog, "Pharyngula" today. (I ignored the nonsensical non sequitur that the President hadn't shown any interest in alternative fuel - I can remember months of jokes about the saw grass and there's a Kennedy blocking the wind farms on the East Coast, for Pete's sake.) But I did point out that there's been no impediment (other than in the funding of Ph.D. candidates who moan about staying up 'till 2 AM - standard for pre-meds and interns in the old days) because of the Bush administration policy on stem cell research.

One poster replied with 500 words to convince me that "fertilized eggs" do not have any moral standing, cloned human embryos would not be cloned humans and that reprogrammed, mesenchymal or any of the other ethical stem cells do not have the promise that embryonic stem cells do. Along with the problem of how long it takes to direct embryonic stem cells.

First, an egg ceases to be an egg when it's fertilized. At that point, it's an embryo.

Second, the poster is not keeping up. The mainstream press and science publishers no longer argue that somatic cell nuclear transfer doesn't result in an cloned embryonic primate or human.

Third, again, you've got to keep up: James Thomson has said that the reprogrammed cells, "are probably more clinically relevant than embryonic stem cells," he explains. "Immune rejection should not be a problem using these cells.""

In the near future, the treatments will come from stem cells and precursor cells - it probably won't be necessary to start at the embryonic stem cell or pluripotent stem cell stage. While each line of multipotent adult stem cells is more limited than the ideal embryonic stem cell line, there are many kinds of multipotent lines. I expect the lessons we learn from the Yamanaka and Thomson techniques to be used to begin at these more differentiated cells, which can be directed faster and easier than the pluripotent cells, with their innate pathonemnonic tendency to form tumors.

In the long run, we hope to prove John Gearhart right: he's been on record for 5 (Washington Fax, November, 2002) years that, "Stem cells won't be used as therapies, but will spawn them."

Just as we use stimulating factors to encourage the production of blood cells, rather than transfusing as often as we once did, the plan is to learn to turn the necessary genes on to produce the specific transcription factors that will stimulate stem cells. We'll learn about "tropic factors" like the brain-derived neurotropic factor that seems to regulate the development of nerve cells and nerve repair.


5 years ago, we hadn't found all the stem cells and precursors that we know about, now. We didn't realize that women continue to make oocytes after birth, that there are neuron stem cells and precursors, that we can make functional liver tissue masses from umbilical cord blood. We certainly didn't know as much as we do - and how little we know - about Oct4 and the other regulatory homeodomains. We didn't understand about niches and the vital role of the physical environment and conditions beyond those chemicals.

The poster does use one of my favorite phrases, however: "We stand on the shoulders of giants." He forgets that that will be true for our children of the future, also.

Governments threaten physicians for anti-abortion policy

In our Nation, with our First Amendment, why doesn't someone threaten all the bodies placing restrictions on conscience clauses and against religious-based practices?

In Portugal, the Health Minister has been threatening to take the Portugal Medical Association to Court for its policy that states that doctors should respect human life from fertilization to natural death.

More here, here, and here.

Then, there's the woman doc in England, who is being threatened with charges of "unprofessional conduct" and being removed from the National Health Services, for telling women to "think twice" before they have an abortion.

The American College of Obstetricians has a new statement on ethics, #385, entitled, "The Limits on Conscientious Refusal in Reproductive Medicine."

Worse, according to the American Association of Pro-Life Obstetricians and Gynecologists, ACOG ACOG sent a letter to Senators in Washington:

"Dr. Michael Mennuti, writing as the President of the American College of Obstetrics and Gynecology (ACOG), has requested the United States Congress to “require doctors with moral objections to refer for abortions.” Urging the Senators to alter the current Abortion Non-Discrimination Act, Mennuti states, “Doctors who morally object to abortion should be required to refer patients to other physicians [for an abortion].”"

Any ethics statement by ACOG carries the weight of "standard of care," and places all doctors, nurses and other medical professionals at risk of legal penalties if we do not follow the guidelines.

Even though I haven't delivered a baby in 10 years, I may still be the primary care doc for a woman who sees an obstetrician for her pregnancy and I still care for a women in the first 20 weeks of pregnancy, as far as diagnosing the pregnancy and caring for threatened miscarriage and tubal pregnancies. I am careful to meet the guidelines of ACOG, because I know that I could be sued - and it would be a slam dunk for the patient if I am ever accused of varying from them.

ACOG now says that I shouldn't care at all for women who might be or are pregnant unless I am willing to make arrangements for an abortion if the woman wants one. That organization also says that hospitals shouldn't offer emergency care for rape victims or maternity care if the organization has objections to elective abortion or sterilization.

The ACOG statement essentially mandates that all of us must offer abortion and/or referral for abortion - and that if we don't offer abortion ourselves, we probably should either practice "in close proximity" to some one who does and/or that we shouldn't practice in areas that don't have easy access to an abortion!

Family Practitioners and other pediatricians are more likely to be religious and those who practice in Rural areas are more likely to be from a rural area. If ACOG's policy is followed, there would be an acute shortage of primary care doctors for women of childbearing age.

The Position Statement mixes "emergency" and "reproductive" care, and severely goof in calling the conscience an inner voice that tells us that we couldn't live with ourselves if did so and so. As Dr. Robert Orr (a Family Physician and ethicist) says in his rebuttal written for the Christian Medical and Dental Association, the conscience is much more - the conscience cannot be separated from the world view of the person and people of faith often consider the knowledge of right and wrong and the conscience that leads us to follow it to be part of what we call the "Image of God."

Non-believers can be "pro-life" and they also have consciences which they should not be forced to violate.

Again, a person who will go against her or his conscience is a person who will do what he knows is wrong

I still think it would be simpler for all the proponents of abortion to pay to move the abortionists around than for them to try to force docs to act against our conscience.

Buy "Yamanaka StemCell Factors"

No, Really!!! Your "Plasmid Cart" is empty!

I'm studying up to be able to answer some very tough questions by Lydia from an earlier post.

While "Googling" "Oct 3/4," I found this ad, for "Yamanaka StemCell Factors." as sold by "www.addgene.com."

Addgene.com is selling the plasmids mentioned in Takahashi and Yamanaka's "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors."

More Questions on Embryonic Stem Cells

Lydia asked about my comments on embryonic-like cells derived from umbilical cord blood.

Umbilical cord blood itself appears to be at least multipotent. However, Texan and British researchers worked with NASA to produce "embryonic-like" stem cells by manipulating them with filters and a special centrifuge. Here's my post from August, 2005 on those cells.

And here's the press release from McGuckin's university in the UK.

And here's the abstract from the Journal, Cell Proliferation,

"Production of stem cells with embryonic characteristics from human umbilical cord blood"

C. P. McGuckin, N. Forraz, M.-O. Baradez, S. Navran, Synthecon Corporation, Houston, and J. Zhao, R. Urban, Tilton, L. Denner

When will embryonic stem cells reach the clinic? The answer is simple – not soon! To produce large quantities of homogeneous tissue for transplantation, without feeder layers, and with the appropriate recipient's immunological phenotype, is a significant scientific hindrance, although adult stem (ADS) cells provide an alternative, more ethically acceptable, source. The annual global 100 million human birth rate proposes umbilical cord blood (UCB) as the largest untouched stem cell source, with advantages of naive immune status and relatively unshortened telomere length. Here, we report the world's first reproducible production of cells expressing embryonic stem cell markers, – cord-blood-derived embryonic-like stem cells (CBEs). UCB, after elective birth by Caesarean section, has been separated by sequential immunomagnetic removal of nucleate granulocytes, erythrocytes and haemopoietic myeloid/lymphoid progenitors. After 7 days of high density culture in microflasks, (105 cells/ml, IMDM, FCS 10%, thrombopoietin 10 ng/ml, flt3-ligand 50 ng/ml, c-kit ligand 20 ng/ml). CBE colonies formed adherent to the substrata; these were maintained for 6 weeks, then were subcultured and continued for a minimum 13 weeks. CBEs were positive for TRA-1-60, TRA-1-81, SSEA-4, SSEA-3 and Oct-4, but not SSEA-1, indicative of restriction in the human stem cell compartment. The CBEs were also microgravity–bioreactor cultured with hepatocyte growth medium (IMDM, FCS 10%, HGF 20 ng/ml, bFGF 10 ng/ml, EGF 10 ng/ml, c-kit ligand 10 ng/ml). After 4 weeks the cells were found to express characteristic hepatic markers, cytokeratin-18, α-foetoprotein and albumin. Thus, such CBEs are a viable human alternative from embryonic stem cells for stem cell research, without ethical constraint and with potential for clinical applications.

These cells were later used to produce functional liver tissue and alveolar lung cells.

There have also been bone marrow cells that share the characteristic markers of embryonic stem cells. (Reported here.)

New Stem Cells Questions and Answers

A reader posts some questions that I'll try to answer. (Thanks, Janet!)

The most important thing to remember is that the new iPS cells appear to be like embryonic stem cells, but they can be made without killing anyone and they can be made to match the patient.


"Does this new procedure use any cells from the unborn to induce pluripotency in the adult skin cell thus creating a stem cell?"

Both labs in the news actually showed their final process using adult cells that did not require the death of any human individual at any age.

However, one of the groups (Thomson's, from Wisconsin) proved that the process is possible by using embryonic stem cells and fetal cells from abortions, while the other group (Yamanaka's, from Japan) used mouse cells for the basic science before using adult skin cells.

"If it does, then it cannot be considered an ADULT stem cell. So, it seems there would need be a third category of stem cells.

"If it does not use cells from the unborn, then could the iPS be considered an ADULT stem cell? It would be simpler to explain. Or because it is not a stem cell to begin with but is induced to become an ADULT stem cell, do we still need a third category for stem cells.

"I think that if the cells that are reprogrammed came from tissues after birth, they are adult stem cells, and the research using them is "adult stem cell research." (or non-destructive stem cell research resulting in induced pluripotent stem cells.)"

It can get complicated, and you do have to read "the fine print" in the reports to figure out the source.

I've always thought of the two groups as divided into

1. Destructive Research - that depends on the intentional destruction of individual human beings at any age is unethical vs.
2. Non-destructive Research - ethical research methods that do not intentionially cause injury to human beings.

For simplicity, most people call the first "embryonic" and the others "adult."

For instance, umbilical and amniotic fluid cells are ethical, non-destructive stem cells that are technically "fetal stem cells."

In contrast,
1. "embryonic" means the cells came from embryos - in humans that's up to 8 weeks gestation.

2. Most of the "fetal cells" used in research come from harvesting the bodies of children who are aborted, between the age of 8 weeks and term. These are sold as tissue cultures by commercial labs. Some of the cultures have been cultivated for 20 or 30 years and the genes and growth habits have been studied and they can be counted on to do what they are supposed to do.

3. Sometimes the "fetal" tissues are harvested after a natural miscarriage. These are considered ethical. (I don't think there are any commercially available standard tissue cultures from miscarriages.)

"I realize this is very basic and elementary to the posts that you get from doctors and other scientists but I believe that we must have clear definitions BASED ACCORDING TO WHERE THE STEM CELLS COME FROM to educate the voter and to keep the issues clear so that legislation isn't passed to support this new procedure with wording that would allow funding to inadvertently go to human embryonic stem cell research and human cloning."

Usually name is based on where the cells came from, but if the cells acted like the very early embryo - if they were truly "totipotent" like the zygote which is able to make both the body and the placenta - then research on them would be unethical.

The problem with "therapeutic" cloning, for instance, is that it would create a new human embryo that is capable of self-directed, organized development.

Even if he or she will be killed or die naturally in a few days, it's not right to create human beings with the intention of destroying them or using them for the benefit of others and to their own harm.

"Irregardless of the media and the bloggers who support human embryonic stem cell research and human cloning, most Americans do not believe in the Communist philosophy that the end justifies the means. No matter what our vocation or business, we draw the line when the means are immoral. We expect other Americans to do the same, including scientists and researchers. Destroying one human being to help another is clearly immoral and we should not have to fund it. We will vote accordingly."

I agree. We believe that "self-" should always be part of "sacrifice."

"George Bush and the Catholic Church hold us in thrall"

That's what Terry over at the Womens Bioethics Project Blog says. Terry has a big problem with the breakthrough in stem cell research that so many of us are thrilled with, and says,

It is amazing to see how the Catholic Church and George Bush can hold us all in thrall regarding human embryonic stem cell research. Because of the opposition to deriving stem cells from human embryos which destroys the embryo, eminent scientists are now reduced to attempting to find stem cell alternatives and have done so - by creating induced pluripotent stem cell lines derived from human somatic cells, an advance (?) which is being heralded today in the NY Times. In other words, we can regress human skin cells to an embryonic state by introducing retroviruses including c-Myc (cancer cells) to do so. The only problem with this is that it also creates tertomas which are nasty little creatures - effectively a germ cell tumor which may contain hair, teeth, bones, eyeballs, torsos and hands. Yuk, as Leon Kass would say. Here's an idea: instead of trying to create human embryonic stem cells from someone's nose or foreskin, let us do the research on embryos as nature intended.

Really Terry? "As nature intended?"" Nature intended for us to "use the original container," when it came to embryos.


Most of the basic research was done in mice - look at the history of Yamanaka & Takahashi's research, along with the reports published by Jaenisch this summer.

And Terry's way off on the teratomasas draw back: the *ability* to form teratomas in immune-deficient mice is one of the tests necessary if a researcher wants to prove that the cells are embryonic-like or pluripotent stem cells. (As opposed to multipotent - the fact that his cells did not make teratomas was one criticism of Atala's amniotic stem cell work. Gearhart was specific about the pressure he and others placed on Atala, so I expect to hear more about that in the future.)

Embryonic stem cells have always had all the problems that Terry mentions - including the retrovirus manipulation in many cases, look up "first transplantable lung cells" from the Houston, Texas Stem cell researchers here and here - in addition to the ethical problem of requiring the destruction of human embryos and the necessity to consider buying or bartering for oocytes.

Embryonic stem cells have the same concerns about the ability to reliably direct the cells toward the desired cell line, about the lack of regulation inherent in the primitive cells in culture, and ensuring that a more primitive cell - a future tumor - was not transplanted with the derived, less plastic cells.

One huge advantage that the new process offers that has never been achieved before, is the ability to make patient specific cells for everyone, not just the elite few who can afford to buy the oocytes.

The viruses used are strongly "silenced" or suppressed in the culture conditions used to direct development and are well known - the research to remove them from the DNA is not predicted to be all that hard. But that shouldn't really be a problem form long: between the two researchers and the information coming out of other labs, I wouldn't be surprised if we are able to skip the transfection in a year or two.

In the meantime, Wilmut has announced that the science is driving him to abandon embryonic research and cloning (especially using animal oocytes and human nuclear DNA to form a cimera), Yamanaka and Thomson are getting ready to patent and sell their cell lines for drug research and basic science, as well as anticipating future transplants.

Thousands of Researchers Now Jobless

I don't think that the Scientific Activist ("Reporting from the Crossroads of Science and Politics") is at all happy with the "framing" of the reports on the reprogrammed adult stem cells. (beware the language)

However, I did learn where some of the speculation about iPS cells being "like an embryo." may have come from.

"Activist" says that this article from Jaenisch, et al from last summer indicates that the cells are capable of forming embryos and gestating to become a live, born mouse.

Actually, the article discusses the production of chimeras and the production of a viable embryo after the reprogrammed mouse cells are injected into "tetraploid blastocysts."

A blastocyst is an embryo. So, the Activist and Art Caplan are pointing to different ways to make chimeras, not cells that are unique individuals with an innate self-driven organization - they are not organisms.

In other words, the reprogrammed cells act like embryonic stem cells, but not like embryos - not like the cell that is a zygote - they can't make the placenta and direct their own organized embryonic development. The iPS (and embryonic stem cells from the inner cell mass) require more manipulation and the innate organization of another organism, the embryo into which they are implanted.

Thomson framed: "iPS more relevant than embryonic"

Framing Science has a great quote from James Thomson, whose lab announced that they had proven a way to reprogram adult cells to become more primitive, embryonic-like stem cells, called "induced Pluripotent Cells."

I don't know how I missed this one yesterday:

". . . says Thomson, the scientist who in 1998 isolated stem cells from human embryos for the first time. "They are probably more clinically relevant than embryonic stem cells," he explains. "Immune rejection should not be a problem using these cells."

While you're over there, take a look at the articles from yesterday and today on what Dr. Nesbit believes is the significance of "The Discovery" and about the art of "framing science." If you're not familiar with the concept of framing, read some of the early and/or labeled posts to find out what it means to "frame" anything, science in particular.
(with a handy little list of words and meanings that you need to understand if you are at all interested in how science is reported and "framed" to influence the rest of us.)

Court upholds Texas Prenatal Protection Act

In 2003, the Texas Legislature passed a Prenatal Protection Act, which named the unborn children of Texas individuals from fertilization to natural death. Texas law also calls the "individual" a "person." With the world the way it is after Roe versus Wade, and because most of us have compassion for a woman who believes she doesn't have a real choice, we had to make exceptions for the decisions of the mother, including abortion and - even when the child is not in her womb - for those she empowers, such as doctors and techs at in vitro fertilization clinics.

However, the law in Texas protects a woman and her child against some one else taking the life of her child against her wishes. We will also punish the murderer when we can't protect them.

Today, the Sixth Texas Court of Appeals upheld the conviction of a man for killing his pregnant girlfriend under our Prenatal Protection Act.

The man was dating two women when one became pregnant. He told the other woman that he would "take care of it," and then shot the mother of his child 3 times with a shotgun, once in the face.The jury determined that he knew the woman was pregnant and that he intended to kill them both. He was convicted of capital murder and sentenced to life imprisonment.

The Court decision plainly states:
"By expressly defining capital murder such that one of the victims may be any unborn child from fertilization throughout all stages of gestation, the statute leaves no ambiguity as to what conduct is proscribed. In particular, the plain language of the statute prohibits the intentional or knowing killing of any unborn human, regardless of age. No ordinary person reading the statute would have any doubt as to whether it encompasses victims at all stages of gestation."

We know that violence often begins when a woman is pregnant and that 25% to 30% of deaths during pregnancy are due to homicide, usually at the hands of the father of the child.

I hope that this Court opinion and the original law will save lives. I wish for a day when no one is in danger of being intentionally killed by someone else, much less a loved one. And I hope that the publicity about this law will cause everyone - the person about to get behind the wheel after drinking as well as the abusive husband or boyfriend, to consider the risk of harming a mother too dangerous to even think about.

I believe we are much more likely to overturn Roe now than we have been at any time since 1973, while still ending up with restrictions in at least as many States as we had then. And I believe that the reason why this is so is because more than half of our citizens are unhappy with elective intentional abortion on demand as it is practiced in too many States today.

I also believe that a pro-life Congress could restrict the Courts from interfering with the States' legislative actions on abortion tomorrow, on the grounds that it's obvious that the unborn are persons.

For one thing, we have 4-D ultrasounds now and babies born as young as 20 weeks go home healthy.
In addition, many minds were changed - are still being changed - by the debate over partial birth abortion.


However, the reality is that there is zero chance of getting a Human Life Amendment through the Senate, much less getting 2/3 of the States to ratify it if the States themselves are not already doing it. (Please read up on how the 13th and 14th were ratified: the Legislators from the Southern States were not allowed to participate.)

Far too many men and women think of abortion as insurance against their bad decisions, rather than one more (awful) bad decision.

There are still too many people who think rape and incest are appropriate reasons in themselves for an abortion. They haven't heard how many women decide to carry their children to term after rape or considered the very real humanity of the unborn child, who shouldn't be punished for his father's crime.

But we do have a chance at returning the choice to the States where the majority would restrict abortion except to save the life of the mother. And each person that we teach to think of the unborn child as a person, the closer we get to ending elective intentional abortion.

Translating Thomson’s “Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells”

Yu, Thomson, and all, from Wisconsin published their paper on reprogrammed induced Pluripotent Stem (iPS) cells from adult cells online in Science Express online, yesterday, just after the Yamanaka/Takahashi team from Japan published theirs in the journal, Cell. (The Thomson paper was not scheduled to go live online until the 22nd.)

As discussed on this blog, yesterday, Yamanaka’s group built on their earlier research published in 2006 and 2007, using mouse fibroblasts to prove that four genes, Oct4, Sox2, c-myc, and Klf4, could reprogram those cells to a state that resembled embryonic stem cells in all tests that they tried. Then, they used fibroblasts from commercially available samples from 1) a skin biopsy taken from the face of a 36 year-old Caucasian woman, 2) synovial cells (joint lining) from a 69 year old Caucasian male, and 3) neonate foreskin skin fibroblasts.

(This last is a common source of skin fibroblasts, with easily and ethically accessed skin tissue, collected at the circumcision of newborn boys.)

The Thomson team did not begin the basic research using mouse cells and did not simply go forward using the genes from the earlier experiments on mouse cells. Instead, they started at the beginning, using human Embryonic Stem Cells (hESC) that had been directed to become a special type of white blood cell, CD45+. This type of cell can be manipulated to demonstrate whether they had the functioning gene, Oct4 (a definite marker that is used to prove whether or not a cell is a hESC), by growing them in the presence of gentamycin, an antibacterial.

By adding some genes and removing others, the team determined that they had, “identified a core set of 4 genes, OCT4, SOX2, NANOG, and LIN28, that were capable of reprogramming human ES cell-derived somatic cells.” They also discovered that the cells could be reprogrammed into embryonic-like cells without Nanog, but that Nanog made it possible to recover more reprogrammed cells.

(From the text accompanying Fig.1: "In three independent experiments using different preparations of
mesenchymal cells, individual removal of either OCT4 or SOX2 from reprogramming combinations eliminated the appearance of reprogrammed clones, whereas the individual removal of either NANOG or LIN28 reduced the number of reprogrammed clones, but did not eliminate such clones entirely.")

Next, they tested this combination of genes in a commercially available, genetically modified cell culture, IMR90 fetal fibroblasts. (These cells were cultured from a little girl aborted at 16 weeks gestation. ) These cells are fetal cells, not adult cells, and they were chosen because they have been studied and the genome is well known. They do not grow well in the fluids and conditions that encourage cultures of hESCs and the researchers could identify them by the way that they look.

Next, in order to prove that the genes could reprogram “adult cells,” the team used fibroblast cultures from foreskins to produce 4 different cultures of reprogrammed induced Pluripotent Stem Cells.

The authors conclude,

"The human iPS cells described here meet the defining criteria we originally proposed for human ES cells, with the significant exception that the iPS cells are not derived from embryos. Similar to human ES cells, human iPS cells should prove useful for studying the development and function of human tissues, for discovering and testing new drugs, and for transplantation medicine."

Edited typos 11/21/07 17:30 PM (That could be the next neuroscience break through: why don't we see our typos until later?)

On the power of Naming (iPS and Art Caplan's Off the Wall Question)

Art Caplan, Ph.D., is one of the pseudoeditors over at the Journal of American Bioethics blog, bioethics.net and a founding member of the "Progressive Bioethics Initiative," along with Robin Alta Charo, the subject of one of yesterday's posts. Dr. Caplan writes a regular "Breaking Bioethics" column for MSNBC.

Art took the liberty of renaming the induced pluripotent stem cells (iPS) that were such big news yesterday. He calls them "panacea cells."

I wondered why so many people were calling iPS cells "embryonic stem cells," when cells with similar markers derived from umbilical cord blood were called "embryonic-like stem cells."

Obviously, these are not technically "embryonic," they are reprogrammed adult stem cells. Technically, all research on iPS cells derived from fibroblasts (a cell found in the skin and many organs that regenerates the connective tissue) should be thought of as research on "adult stem cells."

However, Art asks the oddest questions in his opinion piece:

Lastly, some may wonder if a reprogrammed panacea cell acts like an embryo, should it then be classified as a human embryo?

True, a reprogrammed cell cannot implant in the womb but it can do everything else an embryo does. Is this form of genetic engineering a solution to the issue of avoiding human embryo destruction or merely a new route to a similar destination?

iPC's do not "act like an embryo. They cannot "do everything that an embryo does."

Embryonic stem cells harvested by disaggregating (destroying) an embryo at the blastocyst stage do not have the ability to "act like and embryo," once they are removed from the embryo itself. At least by the third or fourth division (and possibly from the first cell division), the cells are differentiated into cells that will become either trophoblast (the future placenta) or Inner Cell Mass (the body proper of the embryonic individual).


These cells do not demonstrate the abilities that the zygote or early, pre-blastocyst stage cells do. There is no mention in either article of the development of trophoblast cells - the cells that become the placenta - or of any organization that gives them the appearance of an embryo in the petri dish.

The only purpose that these questions serve is as segue to Art's final points in favor of continued research into cloned human embryos and embryonic stem cells derived from human embryos:

My view is that genetically altering body cells creates something that does not have the same moral standing as what is made from a sperm and an egg. That is why I favor continued work to create cloned human embryos as well.

I'm afraid that Dr. Caplan is confused or he is deliberately attempting to mislead his readers in support of a philosophical agenda, not science or ethics.

"I want" ethics reigns, even with good stem cell news

I found someone willing to admit that she's not happy with today's news on the production of embryo-like stem cells without the destruction of embryos or harm to women from donating eggs.

Robin Alta Charo is a lawyer who, as part of the Clinton administration's National Bioethics Advisory Commission, helped fabricate the policy to allow research on embryonic stem cells if the embryos were killed using someone else's money. She's part of the surprisingly small community that pushes for cloning, embryo destruction and Federal funding of the research, as well as attempting to regulate the very institutions, boards, and corporations they oversee. (See my article "Ethicists for hire?" for more on the relationships. Or, simply Google "R. Alta Charo" - for some reason she drops the "Robin.")

Charo is on record as hoping that cloning and regenerative medicine will finally prove that we humans aren't anything special, and maybe even that there's no God. If you think I'm exaggerating, listen to the lecture recording available, here.)


Anyway, the Science and Cell reports on research that produces cells that appear indistinguishable from embryonic stem cells that were published online today, are not the best of news to Ms. Charo.

From the ScienceDaily excerpt of the University of Wisconsin press release, with the cute title, "Reprogramming the Debate: Stem Cell Finding Alters Ethical Controversy,"

"It's going to fuel those who call for preferential federal funding only for non-embryonic stem cell research and it will certainly complicate any efforts to expand funding for embryonic stem cell research at the federal level," she says.
. . .
"Any piece of research like this that suggests that we can get cell lines that are equally usable without having to go through an embryo in intermediate steps is going to undermine any effort on the part of Congress to overturn the Bush policy," she says.

"No matter how well this new technique can be used for many of the disease-research and disease-treatment applications foreseen for embryonic stem cell and cloning research, however, calls for criminalization or wholesale de-funding of embryonic stem cell and cloning research are not warranted," Charo adds. "Criminalizing any area of science, as opposed to merely regulating it, would be contrary to the political and constitutional traditions of academic and scientific freedom, as well as the historical spirit of inquiry that characterizes this country."

From the Wisconsin article linked above,

Charo serves on several expert advisory boards of organizations with an interest in stem cell research, including CuresNow, the Juvenile Diabetes Research Foundation, the International Society for Stem Cell Research and WiCell, as well as on the advisory board to the Wisconsin Stem Cell Research Program.

In 2005, she was appointed to the ethics standards working group of the California Institute for Regenerative Medicine. Also in 2005, she helped to draft the National Academies' Guidelines for Embryonic Stem Cell Research, and in 2006 she was appointed to co-chair the National Academies' Human Embryonic Stem Cell Research Advisory Committee.

I'm sure that we shouldn't assume that those connections with Wi-Cell, the California Institute for Regenerative Medicine, or even her associations with the Alan Guttmacher Institute and Planned Parenthood have anything to do with her dislike for what many consider good news. And ignore the comments about the "Bush Administration." Charo's involvement with the Progressive Bioethics movement, couldn't have anything to do with politics.

Science Magazine on "Race" to Stem Cell Breakthrough

The Thomson article is online (abstract is free, article is behind a pay wall), but I haven't had a chance to read it.

In the meantime, Science Magazine has a news article on both the publication from Wisconsin's Thomson and the previously discussed Takahashi/Yamanaka article in Cell.

Be sure and read the last sentence!!!!

Now the race to repeat the feat in human cells has ended in a tie: Two groups report today that they have reprogrammed human skin cells into so-called induced pluripotent cells (iPCs). In a paper published online in Cell, Yamanaka and his colleagues show that their mouse technique works with human cells as well. And in a paper published online in Science, James Thomson of the University of Wisconsin, Madison, and his colleagues report success in reprogramming human cells, again by inserting just four genes, two of which are different from those Yamanaka uses.

Thomson's team started from scratch, identifying its own list of 14 candidate reprogramming genes. Like Yamanaka's group, the team used a systematic process of elimination to identify four factors: OCT3 and SOX2, as Yamanaka used, and two different genes, NANOG and LIN28. The group reprogrammed cells from fetal skin and from the foreskin of a newborn boy. The researchers were able to transform about one in 10,000 cells, less than Yamanaka's technique achieved, Thomson says, but still enough to create several cell lines from a single experiment.

Although promising, both techniques share a downside. The retroviruses used to insert the genes could cause tumors in tissues grown from the cells. The crucial next step, everyone agrees, is to find a way to reprogram cells by switching on the genes rather than inserting new copies. The field is moving quickly toward that goal, says stem cell researcher Douglas Melton of Harvard University. "It is not hard to imagine a time when you could add small molecules that would tickle the same networks as these genes" and produce reprogrammed cells without genetic alterations, he says.

Once the kinks are worked out, "the whole field is going to completely change," says stem cell researcher Jose Cibelli of Michigan State University in East Lansing. "People working on ethics will have to find something new to worry about."

(edited November 21, 2007 to adjust the title. I over reacted in calling this statement and "insult.")

Translation of "Induced Pluripotent (Human) Stem Cells"

Please see the revised version of this post, published November 30, 2007.

Reprogramming Stem Cells - Links to Articles

I got the authors backwards. Here's the corrected version:


Takahashi et al. (including Yamanaka), Cell Online, free pdf.

There's a "Preview" article in pdf here.
Still waiting for Science to post Thomson's report online.

Embryonic Stem Cells from Patient's Own Adult Stem Cells

Well, they did it!

From Reuter's, UK:

WASHINGTON (Reuters) - Two separate teams of researchers announced on Tuesday they had transformed ordinary skin cells into batches of cells that look and act like embryonic stem cells -- but without using cloning technology and without making embryos.

Their breakthroughs could make possible the long-sought goal of tailor-made medicine, but without the political, scientific and ethical roadblock of using human embryos.

Both teams call the new cells induced pluripotent stem cells and say they look and act like embryonic stem cells -- the master cells that give rise to every cell and tissue in the body.

. . .

James Thomson of the University of Wisconsin in Madison and colleagues reported their finding in the journal Science while Shinya Yamanaka of Kyoto University in Japan and colleagues reported theirs in the journal Cell.

I haven't read either article, so -- long pause ---

Limits on "I want" ethics

While we're all waiting for the announcement that Shinya Yamanaka's lab has or has not published on human embryonic-like stem cells dedifferentiated from adult stem cells . . . (The press releases hit while I was writing this post.)


Wesley Smith's blog, Secondhand Smoke has a good discussion titled, " Just Because Someone Wants Something, Does That Mean Doctors Should Do It?," that goes along with the conscience and limits on science debates that seems to be the theme of this blog over the last couple of weeks.


The limits should probably be based on the individuals' right to life and liberty as in, "Is it permissible for a person to infringe on his own rights?" and "Does the desired event risk life and liberty of others?" These themes are what I consider the basis for "First, do no harm."

There are questions that need to be asked.

1. Nothing should be allowed that is designed to intentionally kill a human being. (The Nuremberg Code says "except, perhaps, in those experiments where the experimental physicians also serve as subjects,” but I don't believe that even doctors are allowed to infringe our own right to life and liberty.)

2. Will society be asked act to make special accommodations for the the intentionally mutilated (or the obese, the smoker, the Jehovah's Witness or vaccine denier, etc.)? (How much of my life, liberty and property do you claim?)

3. Will the rights of certain individuals be infringed upon by a demand for an action from someone else that is repugnant to the one being forced to act? (Traditional ethics that society may restrain, but not compel, action except in limited situations such as parents' duty to their children, doctors' and lawyers' duties to their patients and clients. )