Innovita Research Foundation

I.R.F. / Aging news / General / 06011001

The Three Bridges to Longevity. Bridge Two (The Biotechnology Revolution)
Posted on: January 10, 2006

Bridge Two consists largely of the biotechnology revolution, which has already begun and which will find its full expression over the course on the next 15 years. Among the most important items of Bridge Two will include stem cell therapy, therapeutic cloning, recombinant gene technology or "pharming" (genetically modifying bacteria, plants and farm animals to produce desired proteins) and developing a deeper understanding of the human genome with the ultimate goal of creating designer proteins ("proteomics"). All of these therapies are very exciting and will change medicine as we know it, so that is completely unrecognizable from the medicine of today. By optimizing care of our present biological bodies and eliminating the expression of undesirable genes, the life expectancy for most people should easily exceed 100 years.

Stem cell therapies
Stem cells occur naturally in the human body and have the ability to differentiate themselves into many different cell types; for example, a stem cell found in a hair follicle can be coaxed to turn into a heart muscle cell or a nerve cell depending on the chemical environment in which it finds itself. Recently, there has been considerable political and ethical debate about the use of a specific type of stem cell that is found early in fetal development – the embryonic stem cell. Embryonic stem cells are characterized by an extreme degree of "plasticity", namely, the ability to change or differentiate into any type of tissue. Since the production of embryonic stem cells involves the destruction of human embryos, this has created a moral dilemma for many political and religious leaders, particularly in the United States. Fetal stem cells are found in two main varieties: totipotent and pluripotent stem cells. Totipotent stem cells are found in the embryo immediately after fertilization. Because some people feel that as soon as the embryo starts to divide it constitutes a human being, it is sacrosanct and must not be destroyed. A little further along the line of cell division come the pluripotent stem cells. These cells are not as plastic as the totipotent stem cells and cannot form every cell type, at least not with today's technologies, so they are not as valuable to scientists as the embryonic stem cells. However, even the totipotent stem cells can be encouraged to differentiate into many different cell types under the influence of specific growth factors. In the near future, it is not unrealistic to envision a scenario in which a patient suffers, say, a myocardial infarction and receives a transplant of cloned heart muscle cells generated from his own stem cells to replace the region of infracted myocardium. Patients with spinal cord injuries or a history of cerebrovascular accident may soon be able to receive stem cell implants to regenerate damaged tissues and restore function. A small number of stem cells persist into adult life. Most adult tissues have a few stem cells, but they are rare. Their function remains incompletely understood, but we may soon be able to transform these adult stem cells into any cell type in the body. As we perfect this technology the debate over embryonic stem cells will end, and we will be able to harness the full potential of this therapy. A group in South Korea recently was able to create a pure clone of embryonic stem cells, obviating the need for actual embryos. Woo Suk Hwang and Shin Yong Moon of Seoul National University have successfully cloned a line of human pluripotent stem cells. This research paves the way for production of human-replacement tissues and organs from a cloned stem cell line.

Another very powerful technique is known as "pharming". It involves recombinant technology. This refers to modifying or inserting desired genes into animals, plants and bacteria. Then these so-called "pharm" animals or plants create the desired proteins. An interesting variant of this therapy involves genetically modifying bananas or tomatoes to create a vaccine against hepatitis B. In order to get vaccinated, the patient would simply eat the banana or tomato. It is estimated that these plant derived vaccines could be produced for less than 2 cents per dose, a 99 per cent saving from conventional vaccines. So, in effect, there would be bananas and tomatoes growing in the field producing hepatitis vaccine. When we give patients human insulin, it is a bioengineered product that is made by recombinant bacteria; similarly, human growth hormone for injection is fabricated in the laboratory by recombinant bacteria. There now exist "pharms" comprised entirely of different "pharm" animals, in which the milk of the goats is used to create silk threads stronger than those created by spiders, and, in the fields are grown plants that are particularly high in protein such as tobacco and corn, which have had their genetic structure modified to create other desirable proteins.

Proteomics, in many ways, is an even more exciting field of development. Proteomics involves systematically creating desired proteins in the laboratory de novo. This may be the most important medical technological development to occur within the next two decades. In a typical scenario, doctors will determine what protein a patient needs to recover from a given illness and then the proteomics engineers in the laboratory will fabricate the needed protein molecules. The full expression of this therapy still lies 10-15 years away, but when this therapy is mature, it will offer incredibly powerful therapies. Proteomics will also be utilized for diagnostic tests, and medical diagnoses will be able to be made much more quickly. A major problem with proteomics relates to the three-dimensional configuration of proteins. While the chemical structure of a protein molecule can be written as a linear chain of amino acids, determining in advance the sequence of amino acids that will be needed to create a desired three-dimensional protein molecule with folding and cross-linking of the amino acids is an incredibly difficult task. Determining what chain of amino acids is required to create a desired three-dimensional structure remains a problem that exceeds the computational capacities of even the world's fastest computers. There are some new supercomputers designed to work on the protein folding problem. IBM has just introduced the Blue Gene/L, a supercomputer that operates at a speed out of 360 trillion operations per second and one of its main goals is solving the protein folding problem. It is anticipated within the next 10 years some early proteomics therapies will be available and significantly affect our abilities to diagnose and treat many diseases.

There are two types of cloning: reproductive cloning and therapeutic cloning. In reproductive cloning, you recreate an entirely genetically identical organism. Reproductive cloning has already been used in animals, but due to the thorny moral issues involved, has not been used in humans. "Dolly the sheep" was the first cloned animal, and there have been many additional animal species that had been cloned. Genetics Savings & Clone, Inc., for example, is a private company that is in business of cloning beloved pets for their owners. This is to be differentiated from therapeutic cloning in which you create individual tissues, not entire organisms. Therapeutic cloning uses germ cell lines before they are implanted and causes them to differentiate and develop into specific tissues or organs. Currently, researchers are growing simpler organs such as corneas and urinary bladders, and soon should be able to grow skin, blood vessels and other complex tissues and organs by cloning them from germ cells.

Gene therapies
Gene therapies are also very powerful aspects of the Bridge Two biochemical revolution. Some of the current therapies available include RNA interference (RNAi), and antisense RNA, which are available now, but are in a very primitive stage of development. RNA interference therapy involves taking short double stranded segments of RNA and inserting them into the cytoplasm of the cell. These match and lock onto portions of the native messenger RNA (mRNA) that is transcribed from mutated genes. This causes the native RNA segment to be cut apart and destroyed, silencing expression of the undesirable gene. Antisense RNA also blocks the mRNA created by the defective genes so they are unable to make undesired proteins. Antisense therapy uses mirror-image sequences of RNA (antisense RNA), which stick to the abnormal protein encoding RNA, preventing it from being expressed. It is hoped that these therapies which affect gene expression indirectly, by interfering with the mRNA coded for by the defective genes, will eventually lead to "somatic gene therapy", which is the holy grail of gene therapy. In somatic gene therapy the goal is to insert a desired gene directly into the patient's genome and delete or turn off undesired or defective genes. Somatic gene therapy is most important gene therapy of all, but is probably 25 years away. But when this therapy is mature, it will be possible take any type of adult or somatic cell in the body and turn it into any other cell type because all somatic cells contain all the genes needed to create every cell type. We will, for example, be able to turn hair follicle or fat cells into heart muscle cells simply by manipulating their genes. Gains are already being made in this arena by using adult stem cells. Adult liver stem cells have been transformed into pancreatic cells and adult muscle stem cells have been transformed into heart muscle cells, neural tissue, and blood vessels. Yet, as exciting as these Bridge Two therapies will be, they will pale in comparison to the Bridge Three therapies to which they will lead, the full flowering of which will occur 25 to 30 years from now.

Source: T. Grossman; Latest advances in antiaging medicine; Keio J Med. 2005 Jun;54(2):85-94.
< Previous |  Next >