Adult stem cells in MS for reversal

In Multiple Sclerosis (MS), the immune system of a patient turns on his or her nervous system, destroying the myelin sheaths that serve as insulation around nerves, disrupting the transmission of nerve signals. The myelin damage often occurs in a patchy manner, at first. See the Medline Plus page from the National Institutes for Health for more information, including a patient tutorial in English and in Spanish. The Journal of the American Medical Association has a similar patient education page in pdf.

There have been trials using adult stem cell treatments in the form of bone marrow transplants and injection of adult stem cells in different manners for several years. (See ClinicalTrial.gov for some of these - if my search lapses, search "stem cell multiple sclerosis.)

The March issue of Lancet Neurobiology reports (Free access to the abstract) success from research at Northwestern University using the patients' own bone marrow stem cells, after harvesting those cells, preserving them, and then using chemotherapy to destroy the immune system before replacing the patient's stem cells. A review of the study is at the Science Daily and at this blog, Science Codex.

Here's the information on this trial from Clinical Trials.gov.

Any sort of bone marrow transplant is dangerous due to the lost red blood cells, platelets (to make blood clots), and the white blood cells that function as the immune system. This trial was set up to preserve all but the immune system. While it's still not a procedure to take lightly, it appears that the researchers at Northwestern have made it safer.

"Tea-bag" Adult Stem Cell Treatment for Stroke

British researchers report an amazing recovery for a 49 year old man who suffered a hemorrhagic stroke on October 15, 2008. The researchers at the company, "Biocompatibles," used adult stem cells from a healthy donor. The cells had been engineered to cause them to produce a protein that helps prevent "programmed" cell death (even after the bleeding stops and the pressure is removed) and embedded in tiny beads that had been sewn up in a cloth "tea-bag."

From the press release, published on the Medical News Today Neurology and Neuroscience website:

Stroke is one of the leading causes of death in the elderly population in the developed world. The incidence rate has been reported as 145 per 100,000. Hemorrhagic stroke is responsible for ~15 to 20% of all stroke and it is the least treatable form of stroke. It is associated with the highest morbidity and mortality rate of all stroke with only 44% of affected patients surviving the first 30 days. Only 20% of these survivors regain functional independence. The cascade of events starts with the sudden rupture of a blood vessel in the brain, causing haemorrhage and pressure inside the skull. Surgery may be used to relieve the pressure; but the haemorrhage causes a longer-term process of programmed cell death, or apoptosis, and it is this that causes the lasting neurological damage.

The CellBeads™ are delivered directly to the injury site during the surgery. They are programmed to deliver CM1, a proprietary version of a naturally occurring protein, GLP-1, which has been shown to have powerful anti-apoptotic effects. The delivery mechanism is a cluster of human adult mesenchymal stem cells obtained from a healthy donor and encapsulated in alginate beads. The cells are genetically engineered to produce the protein, which is delivered continuously, directly to the injury site. The alginate beads protect the stem cells from the body's immune system, which would otherwise destroy the foreign cells. CellBeads™ are transplanted within a retrievable mesh device and are removed completely after a treatment period of 14 days. Retrieval of the implant prevents possible long-term side effects from the transplanted cells.

The research is a "Phase I/II" trial, which means that the doctors and scientists are actually testing the safety of the treatment, and not the actual effectiveness of the treatment, itself. In other words, "does the treatment do more harm than good."

The CEO of Biocompatibles, Crispin Simon (that name is as British as tea bags), spoke to a Reuters reporter for a story published at Forbes online, stressing that the patient is young and other wise healthy, and had the standard of care for hemorrhagic strokes, surgery to relieve the pressure from the blood on the cells around the stroke. 10% to 20% of patients have similar recovery, without the Biocompatible beads.

Still, the report is a welcome source of hope for anyone who has watched and waited helplessly after a patient or a loved one had a hemorrhagic stroke.

Beyond Belief 3: Candles in the Dark, From early in October, 2008, video is on line. The program invites scientists to discuss ways in which science can enlighten society.

The first sessions I've watched so far are part of the Panel on "This Is Your Brain on Morality."

Jonathan Haidt, describes morality as,

"Moral systems are interlocking sets of values, practices, institutions, and evolved psychological mechanisms that work together to suppress or regulate selfishness and make social life possible."

He notes that human societies serve to to control the free riders who do not contribute, the selfish, or those who do not display altruism and/or who harm others. They do this by encouraging moral values such as:

1. Harm/care (Discussion in other segments identifies this as equaling empathy.)
2. fairness/reciprocity (This is later called fairness.)
3. In-Group loyalty (altruism or the cooperation in large unrelated groups)
4. Authority/respect (humans, unlike animals, don't depend on just fear, but involve feelings of love)
5. Purity (Proper use of the human body,not necessarily sex, but in terms of drug use, too. He notes that Liberals are likely to consider purity in food very important.)(I thought about the way that smoking has become unacceptable.)

Haidt says that "Any nation is a miracle in evolutionary terms," since large scale cooperation among unrelated groups is not seen among animals, as it is in humans. He believes that traditional societies tend to use all 5 foundations to control "free riders" or the selfish, while liberals tend to use the first two and discount the other three.

An example and a way to understand this concept described by Haidt is to note that "E pluribus unum" is the national motto of the United States. He believes that Liberals are easily painted by "the right" as obstacles in the unity or coherence of society by emphasizing their love for rebellion, autonomy, individuality. (Or "Change" vs. "Country First"? Well, so much for that.)

Haidt has some really clear ideas about good and bad and insight into politics that I'd never thought of, before. Watch the faces of the audience, especially during the last few minutes: I think they're having the same experience.

And then, Sam Harris ("Can We Ever Be Right on Right and Wrong?") proceeds to confront Jonathan Haidt while sucking all the joy out the audience when he starts talking about the failure of science to "demolish" the idea that science can't guide society on morality.

(Harris may have been angered by the teasing he took about how long he's been working on his Ph.D.)

Harris flatly states that there are moral truths, and believes that the study of "human brain science" can inform society on what "goodness is in the public domain." He focuses on religion and seems to imply that religion is a poison.

Harris embraces what he calls "bounded utilitarianism," without regard to Haidt's values as they could shed light on the morality of his examples, including empathy, fairness, and then, altruism. Just as most people are ignorant about "biology, history, chemistry, and everything else worth understanding," most of them are "ignorant about the basis for human well being." He claims that some day, it will be scientifically correct to say that some societies are better than others, because they produce "lives worth living" vs. "lives barely worth living." I believe that he fails in his argument - and chooses poor phrasing as above) and very weak examples that are easily proven immoral by such values as Haidt's.

Harris contrasts morality as "well being among conscious human beings" vs. "superstitious beliefs." He refutes the claim that people can know whether they are happy other than how they fit within their society and absolutely equates conservative religious Americans with the Taliban in Afghanistan -- with no recognition that he is calling on "empathy," "fairness," as his own values and discounting them in others. (And he displays his ignorance about fundamental evangelical Christianity by describing "The Rapture" incorrectly. That makes me wonder about those of his examples that I'm not familiar with.)

The videos can also be viewed (and turned into MP4's) on Google videos.

Surfing is brain exercise (buy your parents a computer)

Surfing the Internet stimulates middle-aged and elderly brains more than reading a book. In fact, the more you surf, the more stimulation of blood flow to the brain.

At left, a functional Magnetic Resonance Image (fMRI) of the brain while reading a book and at right, the brain while surfing the web. The red areas indicate increased blood flow.


From the press release at UCLA :

For the study, the UCLA team worked with 24 neurologically normal research volunteers between the ages of 55 and 76. Half of the study participants had experience searching the Internet, while the other half had no experience. Age, educational level and gender were similar between the two groups.

Study participants performed Web searches and book-reading tasks while undergoing functional magnetic resonance imaging (fMRI) scans, which recorded the subtle brain-circuitry changes experienced during these activities. This type of scan tracks the intensity of cell responses in the brain by measuring the level of cerebral blood flow during cognitive tasks.

All study participants showed significant brain activity during the book-reading task, demonstrating use of the regions controlling language, reading, memory and visual abilities, which are located in the temporal, parietal, occipital and other areas of the brain.

Internet searches revealed a major difference between the two groups. While all participants demonstrated the same brain activity that was seen during the book-reading task, the Web-savvy group also registered activity in the frontal, temporal and cingulate areas of the brain, which control decision-making and complex reasoning.

"Our most striking finding was that Internet searching appears to engage a greater extent of neural circuitry that is not activated during reading — but only in those with prior Internet experience," said Small, who is also the director of UCLA's Memory and Aging Research Center.

In fact, researchers found that during Web searching, volunteers with prior experience registered a twofold increase in brain activation when compared with those with little Internet experience.

The research is to be published in the American Journal of Geriatric Psychiatry. Additional coverage at the BBC and the UK's Daily Mail. Thanks to blog.bioethics.net for first alerting me to this study.

(Edited at 6 AM for citations and to add image.)

I forgot (a note on memory and humanity)

I know that you may not be able to tell, but I'm trying to make my blog posts shorter. So, I left some quotes out of this morning's post on memory. However, this quote from the Time Magazine article, "The Ethics of Erasing a Bad Memory" by Dr. Scott Haig, on human-ness needs to be repeated:

Much of what we read about brain science in the media today would have us believe that we're nothing more, really, than very fancy machines. And surely what we're learning about the physical brain is exciting and powerful — but thinking honestly, it remains so limited. We can trace the brain pathway of a drug "high," we can call it pleasure, but that tells us nothing about what so many people choose instead — deeper things that somehow beat out mere pleasure as the reasons for doing what we do. Those comforts — of ultimate meaning, virtue, peace and joy — have little to do with molecules.

Drugs, Sleep, Memory and Ethics

New information on the science of memory may one day finally tell me why I have a hard time remembering names and even faces, but I'll store a patient's potassium level without even trying. As with all science research, we'll have to decide whether and why the information we discover matters and how to use it.

Last night's post was on the bioethics questions in a television show dealing with a patient who asked for help forgetting a trauma - actually, the emotional memories, not the facts. A wide range of articles on memory research is the subject of yesterday's post at Bioethics.net. There are posts to articles and blog entries on old and new information on drugs that affect memory, and disorders of memory.

That post contains a link to this New York Times article (free registration required) on the significance of sleep and memories. (I love the title, "An Active, Purposeful Machine That Comes Out at Night to Play.") The same session at the American Society of Bioethics and Humanities conference that dealt with blunting the emotional memory of trauma also touched on the ethics of new medications that enable people to sleep less. The question asked was whether avoiding the need for sleep would allow time for more worthy pursuits - the question and answer period focused on what to consider a "worthy" activity. According to the NYT article, the question should be what is lost.

As is too often the case, science gives us some of the answers to our questions (those "power naps" are probably good for dealing with facts and later sleep appears to be useful for detecting patterns) and technology or means (propranolol, propofol, Provigil, etc.) to manipulate ourselves and our behavior, before we come to a consensus on the ethics - or even the ethical principles that apply - of using our knowledge.

The old saying "let's sleep on it" may have some measurable truth - and a lot of wisdom, after all.

Television Ethics: "Private Practice"

The TV show, "Private Practice," hasn't impressed me with its medical, social or psychiatric integrity. But, I found myself watching it tonight, October 24th, and was more impressed than usual. Tonight's show touches on a cutting-edge bioethics topic that was also mentioned at last week's American Society of Bioethics and Humanities.

Major Multiple Spoiler Alert!!! Don't read more if you've recorded the show to watch later.


(Let's forget the thread on the women who come in for their pelvic exam by the kid midwife - where the only exam the women are evidently getting is the actual *pelvic* exam. No eyes, ears, throat, lungs, breast or abdominal exam. My Family Physician, head-to-toe, cradle-to-grave soul can't bear it.)

(And we won't even ask the Mama in me how I feel about 13 year olds having sex. You might be surprised that I don't freak or judge, though, and pretty much treat the girls the same way that the lead doc does. The difference is that I go out of my way to explain to families when they first come to the office that I consider their child my patient in his or her own right and ask permission to treat without notifying - and, of course, without billing - them if the teen requests that I keep silent. I've always been able to convince the young person to turn to their parents for help, but manage to keep privileged information privileged as long as possible. As far as I know, I've only had one family leave my practice after I explained my policy.)

Okay, back to the cutting edge bioethics topic.

One of the guest characters asked the internal medicine doc for a medicine that helps patients forget.

Actually, the medicine, propanolol, will not help her forget. However, it can help some patients stop feeling the panic and other horrifying emotions that come after a near-death or traumatic event like a rape that causes "Post Traumatic Stress Disorder."

MSNBC had a review, here, about the treatment last year.


The technique can be used to blunt the emotional memory -- not the actual memory or physical damage -- of the traumatic event. Adrenaline or epinephrine is the "fight or flight" hormone or drug that is released when there is stress. It's what causes what I call "the near-car-wreck" feeling that we feel, well, when we nearly have a car wreck.

Epinephrine gives you a boost of energy, pumping sugar, cortisone and other hormones into the body, to allow that fight or flight response. Do you need to take off and escape or stand and battle with whatever it is that is threatening you? Epinephrine is also involved in stimulating the bone marrow to make blood and other organs to heal faster, too.

Unfortunately, sometimes the body makes epinephrine inappropriately, when there's no real danger or when the danger is not severe enough. When that happens, we call it a panic attack or an anxiety attack as people experience the physical and emotional symptoms that are associated with real danger. Their bodies are telling them that they are in danger, but there's no actual threat to confront. When it gets in the way of your life, it's a disorder. Long term panic and anxiety that can be related to a past trauma, and that sometimes causing a person to feel as though he's reliving the trauma, is called Post Traumatic Stress Disorder.

Propanolol is a "beta blocker" that blocks epinephrine and which we often use to treat hypertension and even panic attacks. If used during the time after a traumatic event in which the long-term memories are set in the brain and/or in conjunction with behavioral therapy, it appears that the memory is disconnected, "disassociated," from the emotions that the patient experienced during the trauma and during the flashbacks when the memory makes the patient feel as though he's reliving the event, later. The treatment of PTSD that seems to work best is behavioral therapy, teaching the patient to control his own body's reaction.

Some ethicists are concerned that we may blunt a necessary healing function of epinephrine and the other body and mind effects of the stress reaction. However, I think of the treatment of stress disorders in the same way that I think of treatment of pain. Pain may help us prevent injury and warn us of a threat to our health. But we treat pain that is out of proportion or that is not useful to protect us.

Liberal/conservative neuro-experiments?

Nature Neuroscience has reported on an experiment that is being touted as proving that "liberals" are smarter than "conservatives." Or, as the LATimes' Denise Gallene states, "that liberals tolerate ambiguity and conflict better than conservatives because of how their brains work."

I wonder whether these findings mean that all those visual field tests we've been doing could be affected? Which group would be more likely to have a skewed "blind spot"? For that matter, did the researchers have one of their own?

From a review in the LA Times:

Participants were college students whose politics ranged from "very liberal" to "very conservative." They were instructed to tap a keyboard when an M appeared on a computer monitor and to refrain from tapping when they saw a W.

M appeared four times more frequently than W, conditioning participants to press a key in knee-jerk fashion whenever they saw a letter.

Each participant was wired to an electroencephalograph that recorded activity in the anterior cingulate cortex, the part of the brain that detects conflicts between a habitual tendency (pressing a key) and a more appropriate response (not pressing the key). Liberals had more brain activity and made fewer mistakes than conservatives when they saw a W, researchers said. Liberals and conservatives were equally accurate in recognizing M.

Researchers got the same results when they repeated the experiment in reverse, asking another set of participants to tap when a W appeared.

Frank J. Sulloway, a researcher at UC Berkeley's Institute of Personality and Social Research who was not connected to the study, said the results "provided an elegant demonstration that individual differences on a conservative-liberal dimension are strongly related to brain activity."

Analyzing the data, Sulloway said liberals were 4.9 times as likely as conservatives to show activity in the brain circuits that deal with conflicts, and 2.2 times as likely to score in the top half of the distribution for accuracy.

Sulloway said the results could explain why President Bush demonstrated a single-minded commitment to the Iraq war and why some people perceived Sen. John F. Kerry, the liberal Massachusetts Democrat who opposed Bush in the 2004 presidential race, as a "flip-flopper" for changing his mind about the conflict.

Based on the results, he said, liberals could be expected to more readily accept new social, scientific or religious ideas.

The article is "currently unavailable online," but the website instructs us to contact subscriptions at subscriptions@nature.com. Hopefully this is some sort of elaborate practical joke. The potential weaknesses at the least include drawing conclusions from hand to eye coordination to poorly defined political affiliations among the self-described college students. I wonder about the "n" of the college students who call themselves "conservative." How many could there be? Would libertarians call themselves liberal or conservative?


In the meantime, here's the abstract:

Neurocognitive correlates of liberalism and conservatism

David M Amodio (1), John T Jost (1), Sarah L Master (2) & Cindy M Yee (2)
1.Department of Psychology, New York University, 6 Washington Place, New York, New York 10003, USA. 2. Department of Psychology, 1285 Franz Hall, University of California, Los Angeles, Los Angeles, California 90095, USA.

Political scientists and psychologists have noted that, on average, conservatives show more structured and persistent cognitive styles, whereas liberals are more responsive to informational complexity, ambiguity and novelty. We tested the hypothesis that these profiles relate to differences in general neurocognitive functioning using event-related potentials, and found that greater liberalism was associated with stronger conflict-related anterior cingulate activity, suggesting greater neurocognitive sensitivity to cues for altering a habitual response pattern.

Hat Tip to BioEdge, an email newsletter.

Nanofiber Scaffolds for Neural Stem Cells (and some truth)

Johns Hopkins researchers report that they have developed "nanofibers" impregnated with special proteins which allow them to grow neural stem cells from embryonic stem cells without "requiring high concentrations of growth factors."

One of the researchers, Neuroscientist Hongjun Song, comments on the immediate results of the research, which will not include actual patient therapy:

“Eventually, stem cells will be very important for treating disease using cell replacement therapy, but more immediately stem cells offer the opportunity to model human disease and find ways to screen for therapeutic drugs to treat the disease.”

Song is a member of the body which oversees stem cell research at Johns Hopkins, the "Stem Cell Policy and Ethics Program." This means that even though he has a vested interest in maintaining his own lab and promoting his research, he is among those at Johns Hopkins who determine how to follow the institution's mission:

• Facilitate the ability of the public to benefit from advances in cell engineering in morally responsible ways;
  
  
• Anticipate moral and policy challenges in stem cell science and cell engineering; and


• Provide opportunity for careful and interdisciplinary analysis of these challenges that will be of assistance to both policymakers and the public.

The inclusion of Song in justifying and lobbying for his own work under the guise of "ethics" is a serious conflict of interest and can not be called "morally responsible."

The good news is that some people see an end to the use of embryo destruction. From the article posted earlier today on trading eggs for in vitro fertilization fees:

In any case, the need for eggs may only be temporary.

They are, in fact, only a tool to reprogram the inserted DNA so that it will drive the development of an early embryo. Scientists hope to learn enough about that reprogramming process to let them take an ordinary cell from a person and use it to produce other kinds of cells, perhaps without going through an embryo stage. That might happen in 10 years, Murdoch estimated.

And then they wouldn't need eggs any more.

Brain wave biometric key

New Scientist Tech reports on news of a possible personal identification device in the works:

This novel biometric system should be difficult to forge, making it suitable for high-security applications, claim the researchers behind it. The system was developed by Dimitrios Tzovaras and colleagues at the Centre for Research and Technology Hellas, in Greece. It uses an established method for measuring activity in the brain, called electroencephalography (EEG).

EEG measurements identify the location and intensity of millisecond-long fluctuations in electrical activity in the brain via electrodes positioned around a person's scalp.

First tests are planned in Germany this year. Polish scientists working on the technology in another lab have found the identification to be 88% accurate.

However, John Daugman, a biometrics researcher at the University of Cambridge, UK, questions the practicality of the approach. He says an EEG cap could prove too cumbersome and invasive. "Wearing a wired helmet with sensors on one's scalp might change the ambiance of the workplace somewhat," he says.

Similarly, neuroimaging expert Olaf Hauk, also at the University of Cambridge, believes using the system in a wide variety of situations, particularly stressful ones, could complicate the results significantly. "EEG varies greatly depending on a person's alertness, or mental operations," Hauk told New Scientist. "You might not want to be taken for someone else at the airport just because you had a bad night before."

The authors of spy thrillers and milliners should be especially interested. Here's one hat designer who must be prescient with the motto, "The hat on your head is remarkably representative of what's going on inside your head.™"

HT to Kristina Kirby at Emerging Technology