The Floating University

What's Up, Doc? 

 I. A New Era In Medicine

  1. Regenerative medicine will change our lives and the practice of medicine in the same monumental ways in which the discovery of bacterial infections and penicillin changed everything a century ago.
  1. The biology of regenerative medicine is based in the study of stem cells and genetics. It has to do with understanding with how our bodies are made, maintained, and replenished.  Ultimately, it will open the door to manipulating our bodies in a way that allows us to change who we are and what our lives are like.
II. Cells are the basic unit of biology, not DNA
  1. Much has been made of the recent advances in mapping the human genome.   However, human beings are much more than their DNA.  
  1. What has been lost in this obsession with DNA is the idea that the real unit of biology is not DNA, but the cell.  Cells are alive, cells make more cells, and cells are the units that allow us to harness the future of our bodies.
  1. In order to make sense of how genetics, DNA, and cell biology interact, one must delve into developmental biology.
  1. QUESTION:  How does an egg become a human being?  How does an egg make a human body? 
  2. Cell Division, Growth, and Differentiation.  
  1. The first step in creating a human being is fertilization of the egg by a single sperm.  Once fertilized, cell division occurs rapidly over the first few days of development.  An early stage of development called the blastocyst, which consists of about 100 cells, will give rise to the human body.  
  2. At 70 days an embryo is recognizably human.  How does this happen?  Certainly cell division plays a role, as does cell growth.  But perhaps the most important step in human development is the process that allows cells to become different from one another - and ultimately transforms the blastocyst into a human being.  This process is known as differentiation.
  3. Differentiation produces 350 different types of cells from a single egg and in the last century we’ve learned quite a bit about how this happens.
  4. The first thing we know is that there are approximately 25,000 human genes - bits of DNA that code for proteins - that contain the instructions for building all the proteins found in our cells.  The puzzle then for a developmental biologist is to figure out how do those 25,000 genes get mixed and matched to make all the different kinds of cells.  
  5. Much work is being done to understand exactly how these codes work.  This represents an exciting and important problem for the next generation of biologists.
  6. While we don’t know exactly how our cells are differentiated, an important point discovered just in the last few decades is that while cells become different, they retain the capacity to do everything else. This is quite an amazing potential and it was demonstrated or identified by an important experiment called cloning.
IV. Cloning: The hidden potential within our cells
  • To better understand the potential locked within our cells, it’s important to understand how cloning works.
    1. First, the nucleus of an egg cell, which contains all the genetic information, is removed.
    1. Next, the nucleus from another cell is removed and injected into the egg cell.  This sparks development.
    1. Cell division proceeds and gives rise to the blastocyst stage, which will give rise to the whole embryo.
    1. Many animals have been cloned: Sheep, cows, goats, pigs, rabbits, horses, ferrets, cats, and dogs. What’s missing from this list is humans.
    1. No one has ever cloned a human and developmental biologists have no interest in cloning humans because they’ve already learned the biological principles behind cloning.
    1. QUESTION:  But it does raise an interesting ethical question: should one clone humans?
    1. What we can conclude from cloning is the following: the nuclei of the cells of your body can be reprogrammed by egg cytoplasm so that they can become fully potent stem cells and make an entire new animal. That is, during development from a fertilized egg to an adult human, there are no irreversible changes to the genes, altogether called our genome, during development.
    2. The cells in your body have astounding potential.  They have locked in their nucleus the capacity to make any other part of your body.  Regenerative medicine is all about harnessing that potential to make new cells and to treat and cure diseases.
    1. The end goal of regenerative medicine sounds like science fiction.  If you’re in an accident and lose some tissue or an organ or as is more common, you’re suffering from a disease, a liver disease or a heart disease or a disease of the skin, Doctors will be able to use your body's own inherent capacity for development to replace or repair those lost tissues.
    V. Regeneration
    1. Our bodies have the capacity to do some replenishment on their own.  Your skin is constantly renewed. The same is true for the cells in your intestines.  The cells that make up the lining of your intestines are replaced almost every week.
    1. So, your body has the capacity to renew and replenish some of your tissues, but clearly, we don’t have an obvious capacity for major organ replacement.  If you were to lose part of your brain or to lose a limb, your body doesn’t have the capacity to replenish or replace that.   Yet, all your cells have the necessary information to do so.
    1. QUESTION:  Why don’t all body parts regenerate?
    1. Much can be learned about regeneration from the common salamander. These animals can regenerate their tail, their limbs, their lower jaw, and some of their internal organs.
    1. When a salamander loses a limb a special skin, called the “wound epidermis” grows over the stump and an amazing process takes place inside.
    1. Bone and muscle cells within the wound epidermis begin to change.  They are de-differentiated, they become unspecialized, and create a mound of cells that will then go on to grow and recapitulate or reproduce a normal process of development.  In this way, it can take as little as 70 days for a salamander to regenerate a lost limb.
    1. Salamanders have figured out how to use the information locked in their cells to regenerate major organs or tissues.  A great challenge for developmental biologists now is to figure out how to harness those processes to use them in human biology.
    1. QUESTION: If a salamander can do it, why can’t we?
    VI.  Cell Turnover
    1. QUESTION:  We’ve already discussed how humans can regenerate certain tissues; how does this happen?
    1. There are two ways this is done.  One way is for a fully specialized, differentiated cell to just divide and make two.  That happens for cells in our pancreas and in the kidney, for example.
    1. But for many tissues in our body, there’s a special cell called a “stem cell” that is responsible for differentiation.
    1. A stem cell has two essential properties: self-renewal and the capacity to make specialized cells.
    1. Among stem cells, one has truly special abilities and it’s called an embryonic stem cell.
    VII.  Miracle Grow: Embryonic stem cells
    1. An embryonic stem cell can not only self-renew like all other stem cells, but its special capacity is to make all different kinds of cells
    1. It can make blood, nerve, pancreatic, skin, blood, heart, kidney, muscle, bone, intestinal, lung, liver, and stomach cells.
    1. Students in Melton’s lab are growing colonies of human embryonic stem cells and turning them into beating heart cells.
    1. To do this, they take a rat heart and removing all of the cells, leaving just the matrix, a kind of scaffolding for a heart.
    2. Next they seed the scaffold with human or mouse embryonic stem cells that have been turned into heart progenitors.
    3. These cells will go on to form a clump of beating heart cells.
    4. This is the beginning of a field called bioengineering where scientists and doctors are thinking about how we would make organs and then eventually transplant them into people.
    1. QUESTION:  Where do these embryonic stem cells come from?  Where do we get human embryonic stem cells?
    1. The cells used are derived from materials from in vitro fertilization clinics.  When a couple donates sperm and eggs in the hopes of having a child, there are almost always leftover fertilized human eggs.
    1. It’s estimated that there are about 400,000 such eggs in freezers in the United States.  These eggs are the materials used to explore the potential trapped inside stem cells.
    1. While the potential to cure disease and reduce suffering justifies the use of embryonic stem cells, controversy continues to surround their use.  Recently, there has been pioneering work on another way of creating a human stem cell, called a pluripotent stem cell.
    VIII. Settling Controversy with Pluripotent Stem Cells
    1. Pluripotent stem cells have many, but not exactly all of the properties of the human embryonic stem cell.
    1. Pluripotent stem cells can be created using skin cells and then adding DNA or RNA genes that encode reprogramming factors to these skin cells.
    1. In the next few years, biologists will find ways of turning these pluripotent stem cells into a fully potent cell, just like a human embryonic stem cell, thereby removing the need for dealing with fertilized human eggs.  
    1. QUESTION:  What will these stem cells be used for?
    IX. Stem Cells & Degenerative Disease
    1. Degenerative diseases are diseases where a particular cell type in the body becomes dysfunctional or destroyed.  According to the CDC, 6 of the top 10 killers of Americans are degenerative diseases and approximately 65% of the Americans who died in 2009 died of degenerative diseases.
    1. Some common degenerative diseases are: Alzheimer’s, Parkinson’s, ALS, cardiovascular disease, and diabetes.
    1. What all of these degenerative diseases have in common is that they have a genetic makeup that inclines the patient to get the disease, but doesn’t guarantee that they will get it.
    1. In the next few years, regenerative medicine will lead to new treatments for these diseases in one of two ways: through the replacement of missing or damaged cells or through the creation of drugs that retard the progress of degenerative disease.
    X. Case Study: Diabetes
    1. It’s estimated that the cost of treating diabetes in America is approximately $178 billion dollars per year. So clearly this is a very important social and health problem that needs to be addressed.  
    1. In diabetics cells in the pancreas called beta cells are lost.  These beta cells are responsible for making insulin.  
    1. Without insulin, the amount of sugar in your blood goes unchecked.  This leads to high cholesterol, high blood pressure, clogged arteries, and heart attack.
    1. Juvenile or Type I diabetes is an autoimmune disease where the body’s own immune system wrongly identifies its own pancreatic beta cells and kills them off.  Regenerative medicine is being used to development new techniques for the treatment of Type I diabetes.
    1. Scientists are working on ways to manipulate stem cells to grow new beta cells that could then be transplanted into a diabetic to restore the lost pancreatic function.
    1. This represents one of the two goals for the use of stem cells, i.e. to make cells that are deficient in disease and use those for transplantation.  In the next few years, we will be able to see major advances in that for treatment of diabetes and some neurodegenerative diseases.
    XI. Case Study: New Drugs
    1. Stem cells will be very important in the discovery of new and more effective drug treatments.
    1. Instead of testing experimental drugs on volunteers suffering from degenerative disease, stem cells could be used to generate diseased cells that could then be manufactured in large numbers and tested with experimental drugs without risk.
    1. This may lead to faster and more effective treatments that lead to longer more healthy lives for people with degenerative disease.
    XII. Stem Cells and Aging:  The New Fountain of Youth?
    1. By looking at the biology of stem cells, it may be possible to change the rate of the aging process.
    1. Young people have robust organs, wounds that heal quickly, and high tissue turnover while older people have frail organs, wounds that heal slowly, and low tissue turnover rates.
    1. QUESTION:  Will regenerative medicine let us live forever?
    1. While it won’t be possible to reverse aging, it seems certain that regenerative medicine will lead to significantly slower aging and this science could even potentially lead to the possibility of animal immortality.
    XIII. Exploring the Frontiers of Biomedicine
    1. In our society today, science is looking for ways to make our limited resources renewable.  
    1. Health is a limited resource and through regenerative medicine, biologists are hoping on making it a renewable resource.
    1. The scientific discoveries that make the field of regenerative medicine so exciting are fundamentally different than other kinds of successes.  These discoveries are revealing truths about nature that were previously unknown to mankind.  They are also leading to better treatment or potentially to the cure of degenerative diseases that affect almost every human on earth.
    1. People who like these kinds of challenges would find being a biologist a fantastically rewarding and enjoyable career.