The “Good” guys: the human-superorganism

Image Credit: Jon Berkeley / SPL @TheEconomist
Image Credit: Jon Berkeley / SPL @TheEconomist

“When one tugs at a single thing in nature, one finds it attached to the rest of the world.” – John Muir

Post Highlights:

  • We have over 10 times more microbial cells (estimated 100 trillion) than human cells in our bodies
  • Microorganisms make up about 1 to 3 percent of the body’s mass (in a 200-pound adult, that’s two to six pounds of bacteria) and are viewed by some scientists as an additional organ
  • Metagenomic sequencing is currently used by the Human Microbiome Project (HMP) to identify 10,000 microbial species that occupy the human ecosystem – between 81 and 99 percent of all microorganismal genera in healthy adults
  • 99% of all bacteria in the human body are either mutualists (we provide food and shelter and they help us function more efficiently) or harmless; less than 1% are disease causing in a healthy adult
  • This bacterial genomic contribution is critical for human survival – our microbiomes have been increasingly linked to disease of nutrition, heart disease, diabetes, multiple sclerosis and many other disorders
  • Our microbiomes are specialized but not monotonous: originally passed to us from our mothers, habituate to mirror those sharing the same living space, and may have plasticity of cultivation so to meet our health needs
  • Bacterial transfusions are being strategically employed to save lives of patients suffering from the vicious gut infection of antibiotic-resistent Clostridium difficile, which kills 14,000 people annually in the U.S. 

Cohabitation and the Rest of the Story

Bacteria: a word that often generates feelings of fear when mentioned in conversation.  Considering that many times our attention is drawn to the existence of bacteria in wake of sensationalized news reports of “outbreaks”.  This adverse reaction is justified rightly so.  The information that we get from the media is necessary, and many times we are alerted to events that are of accute importance to acknowledge.  However, the fear-based reaction that these news stories create are most likely due to a general misunderstanding of the symbiotic relationship that we share with our microscopic friends.

The rest of the story: Many scientists are now referring to the human body as a “super-organism” or an organism made up many organisms.  Our bodies are a thriving ecosystem for trillions of bacteria living in and on the organ systems.  It turns out that we are only 10 percent human: for every human cell that is intrinsic to our body, there are about 10 resident microbes — including commensals (generally harmless freeloaders) and mutualists (favor traders) and, in only a tiny number of cases, pathogens (disease causing). (See: New York Times article)

Colonization and Co-dependence

Some folks believe that we are the sole inhabiters of our bodies, and that the only genetic materials passed from parent to child are of human origin.  However, significant evidence paints an alternative picture of shared dependence and co-evolution between bacteria and us. http://elifesciences.org/content/2/e00458.short

Babies enter into the world from a sterile germ-free environment but the moment that a newborn passes through the birth canal, the mother’s endogenous bacteria begins to colonize.  Studies have found that a baby’s system is  immediately colonized by bacteria from the birth canal or mother’s skin when delivered by C-section.  Our bodies are continually colonized each day for the rest of our lives.  By studying fecal samples scientists have determined that we share similar microbiomes with cohabitating family members and pets (Song, SJ, 2013).

How might colonization suggest co-evolution?  For many years doctors were baffled by some of the complex carbs that make up human breast milk.  Evolutionary theory argues that every component of mother’s milk should have some value to the developing baby or natural selection would have long ago discarded it as a waste of the mother’s precious resources.  However, the human genome does not contain the enzyme coding gene to break down the complex carb oligosaccharides.

It turns out the oligosaccharides are there to nourish not the baby but one particular gut bacterium called Bifidobacterium infantis, which is uniquely well-suited to break down and make use of the specific oligosaccharides present in mother’s milk. When all goes well, the bifidobacteria proliferate and dominate, helping to keep the infant healthy by crowding out less savory microbial characters before they can become established and, perhaps most important, by nurturing the integrity of the epithelium — the lining of the intestines, which plays a critical role in protecting us from infection and inflammation. (See: New York Times article)  

…..Our gut microbes might actually be driving our appetites as well.  So when we begin to crave certain foods, it could very well be the intelligence of our bodies signaling to us that we need to increase a certain nutritional supplement to maintain healthy homeostasis.  However, we must keep in mind that many times that we have hunger pain it is actually a sign of dehydration.  Drink more water.

In previous years, it was believed that our genentic code was the key to unlock understanding of our health and potentials for disease state.  However, as we become more aware of the living ecosystems inside our bodies we are now realizing that our over-all health is also greatly attributed to the healthy baseline of the bacteria, which our longevity is dependent on.

Understanding the human genome and metagenome

The human genome is the complete set of genetic information for humans, our DNA is made up of coding and non-coding sequences.  The coding sequences are called genes and they are used to “write” the codes for a protein, which then is transformed through biochemical processes (something a little like magic, into what becomes eye color, hair, immune system, enzymes, blood types, etc.  The human genome contains about 98% genetic information that is either not transcribed into a protein or the function is unknown.  Whereas, the bacterial genome contains only 2% noncoding sequences.  The amount of non-coding DNA correlates with organism complexity and genome size; however, there are even exceptions to this rule.

Advances in DNA sequencing technologies have created a new field of research, called metagenomics, allowing comprehensive examination of microbial communities without the need for cultivation.  This technology allows a process that previously took 7-10 days to take one day.  The technology cost and speed has increased at a rate that leaves even Moore’s Law in the dust.  This is good news for us since it means that we will be able to have our entire human genome sequenced as easily as going in for a flu shot.

New biotechnology innovation from Illumina (HiSeq 2000 sequencing machine) has assisted in the metagenomic sequencing and characterization of 3.3 million microbial genes in the human gut alone.  Researchers estimate that the human microbiome contributes some 8 million unique protein-coding genes or 360 times more bacterial genes than human genes. (See: NIH NewsScientists estimate that the entire human genome, for example, has about 20,000 to 25,000 protein-coding genes (See: Scientific Journal in Nature).  

The 11T bacteria living inside us.  Check out the phylogenetic analysis below to see the family tree of our bacterial friends.

The NIH Human Microbiome Project is one of several international efforts designed to take advantage of large scale, high through multi ‘omics analyses to study the microbiome in human health. (See the infographic below for Metagenomic Phylogenetic Analysis)

http://www.nytimes.com/2012/06/19/science/studies-of-human-microbiome-yield-new-insights.html?pagewanted=1&_r=2&src=dayp&
Application of the Human Microbiome Project results obtained applying MetaPhlAn on the 690 shotgun sequencing samples.
Infographic credit: The Huttenhower Lab, Dept. of Biostatistics, Harvard School of Public Health

http://huttenhower.sph.harvard.edu/metaphlan

http://www.nytimes.com/2012/06/19/science/studies-of-human-microbiome-yield-new-insights.html?pagewanted=1&_r=1&src=dayp

There isn’t enough antibacterial soap or antibiotics in the world to completely rid our bodies of bacteria.  Even if there were, extricating bacteria from our systems would result in mass disfunction.

“We have defined the boundaries of normal microbial variation in humans,” said James M. Anderson, M.D., Ph.D., director of the NIH Division of Program Coordination, Planning and Strategic Initiatives, which includes the NIH Common Fund. “We now have a very good idea of what is normal for a healthy Western population and are beginning to learn how changes in the microbiome correlate with physiology and disease.”

 http://www.nature.com/articles/nature11550.epdf?referrer_access_token=l8hnHi25ZP2arbQ0nk79v9RgN0jAjWel9jnR3ZoTv0OVY5A-Al4l1ELdcH1RKF_2XB98h_40szxSCdizKPAM0ZZMIEKqqXMBelY9HXo5zIklGdeNC4OMY1SgBXpuUjEo

American Gut Project: http://humanfoodproject.com/americangut/

(http://www.nytimes.com/2010/07/13/science/13micro.html?_r=0)

References:
Pray, L. (2008) Eukaryotic genome complexity. Nature Education 1(1):96
Robinson, C. J. et al. (2010) From Structure to Function: the Ecology of Host Associated Microbial Communities
Sleator, Roy D. (2010) The human superorganism – Of microbes and men.  Medical Hypotheses, Vol 74 , Issue 2 , 214 – 215

Contagious or Not: A dissection of infectious disease

Bridging Biotech

Figure 1 - Infectious Disease  Photo Credit: Dr. Shannon Hedtke (Evolutionary Biology, The University of Texas) Figure 1 – Infectious Disease: Photo Credit – Dr. Shannon Hedtke (Evolutionary Biology 2011, The University of Texas)

I love Austin, TX, it’s an amazing place to call home.  Unfortunately, this past month it seems like microbes apparently share the same sentiment.  A new form of “keeping Austin weird”? — micro-organismic diversity. Infections seem to be running rampant, and practically everyone I know has been infected with some variation of virus, bacterium, or wandering DNA particle (manifesting in what we Austinites know intimately as allergies).  I’ve been astounded at the sheer diversity of these infections.  Just this past week five people tested positive for a highly pathogenic strain of Swine Flu at the place of my employment and many more of my friends have undiagnosed upper respiratory infections.  (see previous post on different forms of influenza:  http://meganjrutherford.com/2013/04/01/2-men-in-china-die-of-lesser-known-strain-of-bird-flu/ )

After two weeks of battling the fierce Austin allergens (mold and…

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The Biotech Frontier in Texas; Birdbrains & Adult Stem Cell Therapy

Bridging Biotech

Over a decade ago the polarizing topic of stem cell therapy came to the forefront of the media and stirred the sociopolitical undercurrents of the country.  The policies in question involved the use of embryonic stem cells for the purpose of research and eventually medical treatment of some of the most arduous diseases.

Fast-forward to 2013, currently the debate regarding the usage of  stem cells has been somewhat diffused by increased usage of autologous (cells or tissues obtained from the same individual) adult stem cells.  The usage of adult stem cells is less controversial because it does not require the destruction of an embryo.  The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found.  Adult stem cell treatments have been successfully used for more than 50 years to treat leukemia and related bone/blood cancers through bone marrow transplants

View original post 1,333 more words

Contagious or Not: A dissection of infectious disease

Figure 1 - Infectious Disease  Photo Credit: Dr. Shannon Hedtke (Evolutionary Biology, The University of Texas)
Figure 1 – Infectious Disease: Photo Credit – Dr. Shannon Hedtke (Evolutionary Biology 2011, The University of Texas)

I love Austin, TX, it’s an amazing place to call home.  Unfortunately, this past month it seems like microbes apparently share the same sentiment.  A new form of “keeping Austin weird”? — micro-organismic diversity. Infections seem to be running rampant, and practically everyone I know has been infected with some variation of virus, bacterium, or wandering DNA particle (manifesting in what we Austinites know intimately as allergies).  I’ve been astounded at the sheer diversity of these infections.  Just this past week five people tested positive for a highly pathogenic strain of Swine Flu at the place of my employment and many more of my friends have undiagnosed upper respiratory infections.  (see previous post on different forms of influenza:  http://meganjrutherford.com/2013/04/01/2-men-in-china-die-of-lesser-known-strain-of-bird-flu/ )

After two weeks of battling the fierce Austin allergens (mold and cedar), I was finally taken down by an unidentified microscopic visitor and soon banned from work thereafter because of fear that the unwelcomed microbe might spread.

I wasn’t too happy about being quarantined and the time I had spent studying microbiology led me to believe that I was not carrying a contagious pathogen [pathogen (Greek: πάθος pathos “suffering, passion” and γενής genēs “producer of”) — typically the term is used to mean an infectious agent — a microorganism, in the widest sense such as a virus, bacterium, prion, or fungus, that causes disease in its host (www.wikipedia.org)].

So I went to the doctor, surely a doctor could provide finite answers….  Wrong!  The physician performed a physical examination and then diagnosed me with “text-book” acute bronchitis based on the following symptoms:

  • Tenderness-to-the-touch in the throat and collar-bone region, due to infection of the trachea
  • Dry cough
  • Dark, thick mucus
  • Compromised breathing caused from inflamed and blocked airway passages (see image below)

    Figure 2 - Bronchitis Lung
    Figure 2 – Bronchitis Lung

He then wrote a prescription for the trusty Z-pak (street slang for Zythromax), a fast acting therapeutic antibiotic. Okay, awesome, so it’s confirmed that I have a bacterial infection since I need antibiotics to get better but what does that mean?  Can I go back to work or do I need to be quarantined?

Naturally, I tried to question the doctor further on the characteristics of a contagious bacterial infection but he quickly informed me that he was no doctor and that “he’s not smart enough to get paid the big bucks…”  *eye brow raised — sad face*  He was a physicians assistant (PA), not a doctor.  Ah, sweet ambiguity…

Upon arrival at the pharmacy, I questioned the pharmacist about chances that I might be contagious.  Again, I received the glazed over answer of “I believe so, but it depends… Didn’t you ask your doctor about that?”  I felt so bamboozled, why couldn’t any of these professionals tell me if I was a threat or not?

This post is dedicated to briefly classifying viruses, bacteria, and infections caused by microbes.   

Be a friend and keep your germs to yourself.
Be a friend and keep your germs to yourself.

Before getting into the gory details of infectious microorganisms, it’s important to understand that we have trillions of bacteria currently inhabiting our bodies.  The surfaces of the human body inside and out, for example the skin, mouth and the intestines, are covered in individual micro-organisms that don’t do us any harm. In fact they help to protect us from becoming infected with harmful microbes. They are known as the normal body flora.  Only about 1% of bacteria can invade our body and make us ill.  (Microbiology Online, 2014).

First things first: Influenza and how to differentiate it from the cold and allergies

Symptom Cold Flu Seasonal allergies
Cough Often (moderate) Often (severe) Sometimes
Diarrhea* Rarely Sometimes Never
Fatigue Sometimes Often Sometimes
Fever/chills Rarely Often Never
Headache Sometimes/Rarely Often Rarely/Never
Itchy eyes Rarely Rarely Often
Muscle/body aches Sometimes (minor) Often (severe) Rarely/Never
Runny/stuffy nose Often Often Sometimes
Sneezing Often Sometimes Often
Sore throat Often Sometimes Sometimes
Swelling of sinuses Often Rarely Never
Vomiting* Rarely Sometimes Never

http://www.healthline.com/health/cold-flu/contagious#1

The flu is a very scary threat to everyone.  It causes symptoms that come on hard and fast, and leave you feeling like you were hit by a truck.  Many complications can develop from the flu like pneumonia, bronchitis, sinus and ear infections.  Flu activity most commonly peaks in the US in January or February. However, seasonal flu activity can begin as early as October and continue to occur as late as May (CDC, 2013).  There are other viral and bacterial infections that share similar onset symptoms with the flu, which can make diagnosis complicated.  However, diagnostic instruments have now been developed that are able to rapidly test for the presence of the influenza virus and other infectious pathogens.  Recognizing the warning signs of different types of infections could prove to be very helpful.  Please see the tables below for side-by-side comparisons of 15 common infectious diseases.

Side-by-side comparison of 15 common infectious diseases

Table 3 - Contagious diseases:  Information gathered from: American Academy of Pediatrics; American Public Health Association; Centers for Disease Control and Prevention; Montana Department of Public Health and Human Services Communicable Disease Epidemiology Program; Wikipedia) Table Credit: Rutherford, MJ
Table 1 – Contagious disease: Information gathered from: American Academy of Pediatrics; American Public Health Association; Centers for Disease Control and Prevention; Montana Department of Public Health and Human Services Communicable Disease Epidemiology Program; Wikipedia) Table Credit: Rutherford, MJ

15 Common Infectious Diseases – Table PDF: 15 Contagious Diseases | Side-by-side

Table 2 - Contagious disease:  Information gathered from: American Academy of Pediatrics; American Public Health Association; Centers for Disease Control and Prevention; Montana Department of Public Health and Human Services Communicable Disease Epidemiology Program; Wikipedia) Table Credit: Rutherford, MJ
Table 2 – Contagious disease: Information gathered from: American Academy of Pediatrics; American Public Health Association; Centers for Disease Control and Prevention; Montana Department of Public Health and Human Services Communicable Disease Epidemiology Program; Wikipedia) Table Credit: Rutherford, MJ

15 Common Infectious Diseases – Table PDF: 15 Contagious Diseases | Side-by-side

Table 3 - Contagious disease:  Information gathered from: American Academy of Pediatrics; American Public Health Association; Centers for Disease Control and Prevention; Montana Department of Public Health and Human Services Communicable Disease Epidemiology Program; Wikipedia) Table Credit: Rutherford, MJ
Table 3 – Contagious disease: Information gathered from: American Academy of Pediatrics; American Public Health Association; Centers for Disease Control and Prevention; Montana Department of Public Health and Human Services Communicable Disease Epidemiology Program; Wikipedia) Table Credit: Rutherford, MJ

15 Common Infectious Diseases – Table PDF: 15 Contagious Diseases | Side-by-side

The Verdict: sweet ambiguity

There are multiple factors that come into play when trying to classify risks related to contagious disease, which may also contribute to the glazed over answers received from medical professionals.  As for my prognosis: acute bronchitis via bacterial infection, I guess that I’m “keeping Austin weird” since only about 5% of acute bronchitis cases are bacterial (treated with antibiotics).  Viruses cause about 90%-95% of cases of acute bronchitis in healthy adults. The most common viruses are rhinovirus, adenovirus, influenza A and B, and parainfluenza virus; bacteria are usually commensals (PubMed, 2008).

So based on this information, my immune system might have been weakened from trying to fight off the vast spectrum of viruses and allergens circulating throughout the city; and that’s when an opportunistic bacterium “carpe diemed” my bronchial tubes.  There are no reliable diagnostics or laboratory tests for the cause of acute bronchitis; the diagnosis is a clinical one.  Most likely I was not contagious, unless the strain of bacteria that I was carrying did not mesh well with someone else’s normal body flora.

The microbial world is alive and well in our bodies and our surroundings.  The events are cascading that lead to infection, but we depend on endogenous microorganisms for optimal health.  Trillions of bacteria are on our side (in our bodies), in the past 5 years many new findings have been made that will blow your mind on the importance of native flora to promote and protect the quality of our lives.  This will be the focus of the next post – more about the “Good Guys”.

Disclaimer:  I am not a medical doctor.  I have previously worked at a biotechnology company that develops molecular diagnostics to test for infectious disease.  The material in this post was compiled in an effort to inform and empower, but please consult a medical professional in the event of infection.

References:

http://www.aap.org/en-us/aap-store/clinical-publications/Pages/clinical-publications.aspx

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001969/

http://www.cdc.gov/outbreaks/index.html

http://www.cdc.gov/parvovirusb19/fifth-disease.html

http://www.dphhs.mt.gov/publichealth/cdepi/documents/CommunicableDiseaseResourceGuideForSchools.pdf

http://healthservices.unomaha.edu/selfcare.php?item=26

http://www.microbiologyonline.org.uk/about-microbiology/introducing-microbes/bacteria

http://www.aap.org/healthtopics/infectiousdiseases.cfm

http://www.apha.org/publications/bookstore/ccdmmobile.htm

http://www.webmd.com/a-to-z-guides/understanding-scarlet-fever-basics

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2278319/

New Hope for Multiple Sclerosis (MS) with Epidermal (Skin) Stem Cells

http://www.em.mpg.de/index.php?id=230&no_cache=1

Multiple Sclerosis treatment with stem cells derived from the epidermis (skin)

To follow-up on medical breakthroughs via stem cell treatment from the previous post, Stanford University researchers have created cells from ordinary skin cells that could “rewrap” and protect nerve cells damaged in multiple sclerosis (MS), spinal cord injuries and other conditions.  The popular article was posted today, April 15th in the San Francisco Business Times.  The scientific research article can be found in the journal Nature Biotechnology.

This is monumental for those that are sufferers or have loved ones that suffer from MS.  I am an “empath” since my father suffered from a primary progressive form of MS.  Up until recently, the only available cutting edge techniques involved a combination of chemotherapy (see the many effects of chemo here:  effects of chemo) in junction with MS pharmaceuticals.  This was not an agreeable option for my father since MS left him with subpartial functionality of his limbs.   The magnitude of muscular functionality loss is dependent on the progression of the disease state in each individual.

The published research is ground-breaking for several reasons.  It will allow patients to use their own skin stem cells  to treat the demyelinated oligodendrocytes (see explanation below).  The treatment by one’s own skin stem cells will by-pass the need for immunosuppression and this research could produce cell therapy in as little as three weeks.  Dr. Marius Wernig, offers encouraging words when asked about the abundant amount of research focused on myelin:  “I think that these myelinating cells — or oligodendrocyte precursor cells, or OPCs — have a high chance of working after transplantation.”

Figure: Confocal visualization of central protein in myelin (PLP) in cultivated oligodendrocytes with an EGFP-tag (in yello-green) and an intracellular marker (in red).
Figure: Confocal visualization of central protein in myelin in cultivated oligodendrocytes with an EGFP-tag (in yello-green) and an intracellular marker (in red).

Oligodendrocytes are the myelinating cells of the central nervous system (CNS). They are the end product of a cell lineage which has to undergo a complex and precisely timed program of proliferation (rapid increase in numbers), migration, differentiation, and myelination to finally produce the insulating sheath of axons.  This insulating sheath (myelin) is important for the rapid conduction of electrical nerve impulses, which allows the neural signals to be efficiently sent and received.

Demyelinating disease is any condition that results in damage to the protective covering (myelin sheath) that surrounds nerve fibers in your brain and spinal cord. When the myelin sheath is damaged, nerve impulses slow or even stop, causing neurological problems.  As you can guess, the effects of this are devastating.

References: 

Bradl, M. & Lassmann, H. 2009. Oligodendrocytes: biology and pathology. Acta Neuropathol. 2010 January; 119(1): 37-53  Published online 2009 October 22. doi:  10.1007/s00401-009-0601-5

The Biotech Frontier in Texas; Birdbrains & Adult Stem Cell Therapy

Over a decade ago the polarizing topic of stem cell therapy came to the forefront of the media and stirred the sociopolitical undercurrents of the country.  The policies in question involved the use of embryonic stem cells for the purpose of research and eventually medical treatment of some of the most arduous diseases.

Fast-forward to 2013, currently the debate regarding the usage of  stem cells has been somewhat diffused by increased usage of autologous (cells or tissues obtained from the same individual) adult stem cells.  The usage of adult stem cells is less controversial because it does not require the destruction of an embryo.  The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found.  Adult stem cell treatments have been successfully used for more than 50 years to treat leukemia and related bone/blood cancers through bone marrow transplants.  (See timeline below for the history of stem cells)

New Legislation in Texas

Figure 1 - photo illustration by: Todd Wiseman
Figure 1 – photo illustration by: Todd Wiseman

In April 2012, the Texas Medical Board passed new rules regarding the use of adult stem cell therapy. The new rules allow doctors to bypass FDA approval after they meet specific requirements set forth by the Texas Medical Board, which is also responsible for the licensing and disciplining of doctors.

How will the new rules affect you and me?  The new rules allow doctors to perform stem cell procedures as long as they are done for research and receive approval from an institutional review board selected by the governor of Texas.  The rules also require that patients sign informed consent forms.

Texas Gov. Rick Perry has been a long-time advocate for passing new legislation.  Perry has reported relief from very painful back problems after receiving injections of his own stem cells isolated from adipose (fat) tissue. Before treatment he found it difficult to walk up and down the stairs, but after two separate treatments (one was an injection of his own adult stem cells during surgery to fuse vertebrae in the governor’s spine, and the other was intravenously) he was able to run up and down the stairs.

This post will not try to address the multifaceted layers of government policy on treatment with stem cells, although they are very important and play an emotional part in the lives of many faced with pain and degeneration, but I hope to lay a foundation to understand the nature of adult stem cells and how they can be used for medical breakthroughs.

Need to Know Basics of Adult Stem Cells

Stem cells are the foundation for every organ, tissue and cell in the human body.  Stem cells may be able to repair or replace damaged tissue, thereby reversing diseases and injuries such as cancer, diabetes, cardiovascular disease and blood diseases, just to name a few.  Adult Stem Cells are non-embryonic cells that by definition, are unspecialized or undifferentiated cells that not only retain their ability to divide mitotically while still maintaining their undifferentiated state but also, given the right conditions, have the ability to differentiate into different types of cells including cells of different germ-origin – an ability referred to as transdifferentiation or plasticity (the quality of being easily shaped or molded).

Figure 2 - Known sources for Adult Stem Cells Image via docstoc.com
Figure 2 – Known sources for Adult Stem Cells
Image via docstoc.com

Birdsong and Hope for the Future 

We don’t commonly think about how amazing the logistics are in the development of birdsong, but one Argentinean man with a life-long passion for the study of birdsong revolutionized the understanding of stem cells and neurogenesis (the ability to produce new viable nervous tissue).

Canary

Fernando Nottebohm has long been fascinated with the similarities between human vocalizations and birdsong and in the 1960’s he began conducting research that revealed that male canaries experienced new neuronal growth in the song nuclei region of the brain prior to mating periods.  Surprisingly enough these findings were staunchly rejected, since the implication of similar neurogenesis in humans usurped long held beliefs about the brain’s inability to regenerate cells.

Nottebohm used a radio-actively labeled marker (thymidine) to show new neuronal cell growth.  Thymidine is an enzyme that has a key function in new DNA synthesis and cell division.   After injection, any new cells produced in the birdbrains would express radioactivity. Nottebohm and his team discovered large numbers of radioactive cells, many of which were nerve cells – new nerve cells were being made at an astonishing rate. The team wondered, could this regeneration be directed to heal damaged brain tissue?

Finally in 1998, inspired by Nottebohm’s work, Fred Gage and his team (using a technique very similar to Nottebohm’s radio-active marker) at the Salk Institute found that adult human brains were also able to make new nerve cells.

The Field of Stem Cell Research was Opened Wide

Suddenly, scientists could see the potential for using newly dividing brain cells to treat neurodegenerative disorders, such as Parkinson’s, Alzheimer’s, Stroke, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, etc. If these stem cells could be delivered to the damaged part of the brain, maybe they would divide and specialize, replenishing the damaged tissue and restoring people to good health.

Figure 1 - A cluster of neural cells derived from stem cells in the lab of UW-Madison stem cell researcher and neuro-developmental biologist Su-Chun Zhang. The motor neurons are shown in red; neural fibers appear green and the blue specks indicate DNA in cell nuclei.
Figure 3 – A cluster of neural cells derived from stem cells in the lab of UW-Madison stem cell researcher and neuro-developmental biologist Su-Chun Zhang. The motor neurons are shown in red; neural fibers appear green and the blue specks indicate DNA in cell nuclei.

The History of Stem Cell Research 

1956 First successful bone marrow transplant between a related donor and recipient is performed by Dr E. Donnall Thomas in New York. The patient, who has leukemia, is given radiotherapy and then treated with healthy bone marrow from an identical twin.
1960 Researchers discover bone marrow contains at least two kinds of stem cells — blood or hematopoietic stem cells that form all the types of blood cells in the body and stromal stem cells that form bone, cartilage, fat, and connective tissue.
1960 First research report to indicate that the brain may generate new nerve cells is published, but not widely accepted.
Studies done by Fernando Nottebohm on birdbrain and song nuclei led to discovery of neural stem cells.
1968 British scientist Robert Edwards and his student, Barry Bavister, became the first to fertilize a human egg in the test tube. This is the beginning of in vitro fertilisation (IVF) technologies.
1968 First bone marrow transplant for non-cancer treatment. Dr Robert Good uses a bone marrow transplant to treat an eight year old boy with severe combined immunodeficiency syndrome (SCID). The donor is an HLA-matched sister.
1973 First bone marrow transplant between unrelated patients. A five-year old patient in New York with SCID is treated with multiple infusions of bone marrow from a donor in Denmark.
1978 The first IVF baby is born in England.
1978 Blood stem cells are discovered in human umbilical cord blood.
1981 Mouse embryonic stem cells are derived for the first time from the inner cell mass of a mouse blastocyst and grown in vitro.
1984-1998 Pluripotent stem cells are isolated. When exposed to retinoic acid, these cells differentiate into neuron-like cells and other cell types.
1989 Preimplantation genetic diagnosis (PGD) is developed — a method where a single stem cell can be removed from an IVF embryo and tested for inherited diseases.
1990 Bone marrow donor program initiated.
1990 Dr Thomas receives the Nobel Prize in Physiology or Medicine for his pioneering work on bone marrow transplants.
1995 Scientists at the University of Wisconsin derive the first embryonic stem cells from non-human primates.
1998
Timeline for stem cell research

Stem cells from IVF

Scientists at the University of Wisconsin, led by James Thompson, isolate and grow the first stem cells from human embryos. The embryos used in these studies were created by IVF.

1999 Researchers discover that stem cells can be made to differentiate into different cell types.
2001 President George W. Bush permits federal funding of embryonic stem cell research, but only on the 64 existing stem cell lines.
2004 Researchers in South Korea claim to be the first to clone a human embryo and then harvest the stem cells for research. The research is later found to have been fabricated.
2004 California becomes the first state in the USA to provide its own fund for embryonic stem cell research.
2005 George W. Bush’s restrictions on embryonic stem cell research are loosened.

References:

Filip S, Mokrý J, Hruška I (2003) Adult stem cells and their importance in cell therapy. Folia Biol.(Prague) 49: 9-14.

http://www.biotechlearn.org.nz/themes/biotech_therapies/timeline_for_stem_cell_research

http://www.inquisitr.com/219258/stem-cells-treatment-law-in-texas-will-allow-doctors-to-offer-experimental-treatments/

http://www.ipscell.com/2012/04/the-real-but-oft-ignored-dangers-of-adult-stem-cell-treatments/

http://www.nature.com/news/stem-cells-in-texas-cowboy-culture-1.12404

http://news.bbc.co.uk/2/hi/science/nature/4544777.stm

http://www.nytimes.com/2012/04/14/us/new-rules-on-adult-stem-cells-approved-in-texas.html?_r=0

http://www.tellmeaboutstemcells.org/stem-cell-basics/the-difference.php

http://www.texastribune.org/2012/04/13/medical-board-adopts-controversial-stem-cell-rules/

Birdbrain Breathrough. In Smithonian: Science and Nature [World Wide Web].  Kiester, Edwin Jr., and Kiester, William Smithsonian magazine, June 2002 [cited Sunday, April 14, 2013] Available at http://www.smithsonianmag.com/science-nature/birdbrain.html?c=y&page=2

What are adult stem cells?. In Stem Cell Information [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2012 [cited Wednesday, April 10, 2013] Available at <http://stemcells.nih.gov/info/basics/pages/basics4.aspx>

2 Men in China Die of Lesser-Known Strain of Bird Flu

https://www.osc.edu/press/researchers-take-virus-tracking-software-worldwide

2 Men in China Die of Lesser-Known Strain of Bird Flu

The H7N9 Strain of Avian Influenza Virus (AIV) is Rare but Deadly

The three reported cases of H7N9 AIV are not linked and no other close contacts, such as family members have shown any symptoms as of March 31, 2013 but doctors are carefully monitoring the family.  Currently there does not appear to be any threat to the community.

Clinical Presentation of H7N9 and Treatment

All three cases of documented H7N9 began with fever, cough, respiratory tract infection, and pneumonia during the early stages of the illness. Five to ten days after the illness beganvere pneumonia with difficulty breathing, and some progressed into respiratory distress and two of the three died.

Treatment for H7N9 is limited to anti-influenza virus drugs; however, further research is needed to determine if this is the most effective treatment option.

The Avian Influenza Virus Becomes a Powerful Pathogen When Crossing the Species Barrier

Influenza A virus originates in ducks and expresses relatively mild symptoms in its ecological niche.  However, when the virus mutates and crosses species barriers it becomes a powerful pathogen.  Other bird species and mammals are more severely affected with symptoms ranging from very mild to very severe and ultimately death.  Figure 1 below shows how the virus can cross species barriers and mutate into different pathogenic strains.

Figure 1 - Influenza A Virus - Dabbling Duck - Illustration of the host range of influenza A virus with the natural reservoir of influenza A virus, accidental hosts, and the subtypes that have been identified in the different groups. Illustration by Rebecca Rönnmark and Eric Gisaeus.
Figure 1 – Influenza A Virus – Dabbling Duck – Illustration of the host range of influenza A virus with the natural reservoir of influenza A virus, accidental hosts, and the subtypes that have been identified in the different groups. Illustration by Rebecca Rönnmark and Eric Gisaeus.

Bioinformatics Provides Us With Tools to Trace The Avian Influenza Family Tree (Phylogenetics)

Phylogenetic analysis can be used to trace viral infection through a human population, and the Comparative Method uses phylogenies to trace the evolution of a specific genetic sequence or trait across different species.  Phylogentics is defined as the study of evolutionary relatedness among various groups of organisms through molecular sequencing data and morphological data matrices. Sequencing of DNA, RNA, and proteins provides us with genomic information that can be stored and used in computer analysis programs.  These programs employ algorithms to predict mutations and construct cladistics or phylogenetic (evolutionary) trees.

http://www.pnas.org/content/102/51/18590/F3.expansion.html
Figure 2 – Example of Phylogenetic Analysis of the viral polymerase that mediates adaptation of an avian influenza virus to a mammalian host

Copyright © 2005, The National Academy of Sciences

Cladistics and the Spread of the Avian Influenza

Cladistics refers to the scientific classification of living organisms, based on common ancestry, into evolutionary trees. Evolutionary trees are used by many researchers studying infectious diseases to understand the geographic and host origins of pathogens and how the pathogens change over time. Supramap puts phylogenies in a geographic context as well.

https://www.osc.edu/press/researchers-take-virus-tracking-software-worldwide
Figure 3 – Cladistics – AIV (H7) in 2012 – Screenshot of the spread of H7 influenza as produced by SUPRAMAP and visualized by Google Earth™. This view illustrates the historical spread of high pathogenic lineages (high-altitude red lines) and the recent local evolution of high pathogenicity (low-altitude red lines). [credit: Janies/OSU]
Resources:

Chinese Center for Disease Control and PreventionQuestions and answers about human infection with H7N9 avian influenza. (2013). Accessed April 1, 2013.

Decoded Science. Bird Flu H7N9: First Human Deaths in China. (2013). Accessed April 1, 2013

Infection Ecology and Epidemiology 2011. © 2011 John Wahlgren. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Ohio Super Computer Center. Researchers take virus tracking software worldwide. (2012). Accessed April 1, 2013

New York Times. 2 Men in China die of lesser-known strain of bird flu. (2013). Accessed April 1, 2013.

Gabriel G, Dauber B, Wolf T; et al. (2005) The viral polymerase that mediates adaptation of an avian influenza virus to a mammalian host. Proceedings of the National Academy of Sciences of the United States of America 102 (51 18590-18595) doi:10.1073/pnas.0507415102

World Health OrganizationAvian Influenza Fact Sheet. (2011). Accessed April 1, 2013.