Developmental Disabilities Leadership Forum: Leadership Perspectives in Developmental Disability: An on-line Journal for Consumers, Professionals, Family and Friends
DDLeadership Forum Home | Journal Archives | Search the Forum | Feedback
Volume 2 , Issue 1 Date: Winter, 2002 Topic: Genetics:
Scientific Advances...Human Choices

The Revolutionary Revolution - 21st Century Biotechnology

by Sam Rhine

In 1942, Aldous Huxley authored his time-honored science fiction classic ‘Brave New World’. Among the many predictions he made in the book was the coming of man-made-man…assembly line productions of human babies! The now famous term ‘test tube baby’ was a product of this prediction. Huxley made a subtle guess in 1932 that test-tube-babies would not actually become reality for 600 years. Interestingly, the first in vitro fertilization baby was reported 40 years after he made the 600-year suggestion! In 1958 Huxley penned a sequel, ‘Brave New World Revisited’. In the forward of that work Huxley is apologetic to his reading audience. The apology was because in his predictions in 1932 he did not foresee the most earth-shaking event that actually would occur between 1932 and 1958. It arrived on August 6, 1945…Hiroshima…the coming of atomic energy. He states, “the coming of atomic energy marks a great revolution in human history” but not the most significant revolution. Indeed another revolution, he called it a ‘revolutionary revolution’ would be coming in the future and “this revolutionary revolution will come not in the external world, but in the souls and flesh of human beings”.

Today in 2002, 70 years after Brave New World, we find ourselves immersed in this new revolution: a revolution in biology, medicine and biotechnology. Some simply call the revolutionary revolution - 21st Century Biotechnology. To that special part of the medical community focused on the causes and prevention of developmental disabilities, this new revolution has powerful significance. It could one day lead to new and faster means of diagnosis and modes of therapy and even perhaps - prevention and treatment of all developmental disabilities.

The Human Genome Project (HGP)

The power to propel the revolutionary revolution will come from the completion of the Human Genome Project and the utilization of that information for the benefit of patients with developmental disabilities (DD). The HGP is an ongoing but soon to be completed international project with over 15 countries working cooperatively for 15 years to determine the detailed sequence of the human genome - the sum total of all our genetic information - the details of all of our DNA.

Our DNA is made up of four basic small molecules called nucleotides: Adenine (A), Thymine (T), Guanine (G) and Cytosine (C), aligned in precise linear order along the length of our chromosomes. The entire human genome is made up of approximately 3,200,000,000 nucleotides strung along our 23 pairs of chromosomes. Only about 3% of the DNA sequence is actually part of one of the approximately 35,000 human genes. The ultimate goal of the HGP is to determine the exact sequence order of the nucleotides or in other words - get 3,200,000,000 A’s, T’s, G’s and C’s all worked out in correct order

The HGP began in 1990 and was projected to be completed by 2005 at a cost of $3,000,000,000 or about $1 per nucleotide. However with the rapid advances in biotechnology the ‘rough draft’ of the genome was announced in at the White House on June of 2000 and was published in February of 2001.

What will the completion of the HGP mean to the DD community? The project will ultimately provide us with the detailed sequence of all 35,000 human genes. We must remember the job of a gene is to direct the production of a particular protein molecule…genes make proteins. When there is a mistake (mutation) in a gene it leads to a mistake in that protein. The mistake in the protein can lead to a genetic disease such as sickle cell anemia, PKU, Fragile X, muscular dystrophy, etc. From the completed HGP we will one day know the exact DNA sequence of every human gene and from there determine the exact molecular details of every human protein. Or in other words we will have the molecular basis to understand every human disease. That should then yield information that can be used to more simply diagnose and develop therapy and prevention strategies for all human disease. What would a future world be like if we could prevent or treat every human medical condition?!

Already gene therapy methodologies that can replace a harmful, mutated gene with a normal copy of that gene and thereby fix the abnormal protein have been developed. A teenaged girl in Maryland has had gene therapy to correct an inherited immune deficiency. Last year sight was restored to a laboratory animal, a dog, by replacing one mistaken gene. In that case the inserted therapeutic gene started producing a normal version of the protein to override the abnormal protein and vision returned. Investigators have even been able to insert a gene into mice to increase their IQ. The HGP will one day lead to the identification of all human genes that affect intelligence. The entire sequence of chromosome #21 has been delineated. One small region on that chromosome must be in triplicate to cause Down syndrome. We hope the identification and understanding of all the genes in that region of #21 will lead to future therapy for Down syndrome.

Some experts feel that within 10 years we will all have access to a ‘DNA Chip’. That will permit any individual to have an evaluation of his or her own personal DNA sequence. Any mutated gene carried in a hidden condition could be identified. We all carry 5 or 6 harmful hidden genes. The chip would bring them from a hidden condition out into the open so we could deal their implications. The chip could also help anyone get a preview of their future predispositions: cancer, bipolar disorder, diabetes, etc. The chip might also be used for prenatal diagnosis in the future. One of the big issues with the chip of course is: Do you want to know?? Who should have access to your chip information?? How do we protect genetic privacy??

Human Stem Cells

Another major part of the revolutionary revolution will revolve around the use of human stem cells for medical therapy. The human fetus is put together in the first 49 days. By day 49 all the parts have formed and the fetus will lie on the face of a man’s watch and the weight is ½ an ounce. Day #1 the egg is fertilized and by day #49 we have a miniature human! The human body is made up of about 210 different types of cells.

The human embryo at day #6, six days after fertilization, is a tiny hollow sphere, called the blastocyst, the size of the tip of a straight pin. Within the sphere, eccentrically placed, is a small cluster of about 40 cells. The cluster of cells is called the inner cell mass (ICM). Each of the individual 40 cells that make up the ICM is an Embryonic Stem Cell (ESC). The fetus will form from the ICM. ICM is said to be totipotent, that cluster of cells has the ‘total potential’ to become a new individual. That microscopic cluster of 40 identical cells will become a fetus with 210 types of cells in the next 43 days!

The Embryonic Stem Cells of the ICM immediately form four other major groups of stem cells: Hematopoetic (HSC), Mesenchymal (MSC), Endodermal (ESC) and Neural (NSC). All of the various 210 human cells come from those four groups. HSC found in the bone marrow, will form all the blood cells; MSC also found in the bone marrow will form bone, muscle, cartilage, tendon and adipose; Endodermal SC found in the lining of the digestive track will form the digestive system and lungs and the NSC will form the brain and spinal cord. The Embryonic Stem Cells disappear in 10 days. The other four groups will be with you for the rest of your lives. Since those four groups are found in everyone today they are called the Adult Stem Cells (ASC).

Exciting things have already been happening with the ASCs. One group has taken MSC from the bone marrow and directed them in the laboratory to become heart cells. They can then be used to replace heart cells damaged during a heart attack. One group has redirected HSC from the bone marrow to become brain cells. One day they might be used to make replacement cells for someone with Parkinson’s, Alzheimer’s or Huntington’s disease. Each of the four Adult Stem Cell groups is multipotent. They can make many cells in their group but not all 210 cells.

There are also ongoing investigations to look at the potential for Embryonic Stem Cells to be coaxed in the laboratory to become any of those 210 human cell types. These cells are pluripotent - they can make any of 210 cells. They also have a special enzyme called telomerase, which gives them biologic immortality – they can grow forever in the laboratory. Adult Stem Cells lack that enzyme and therefore have a limited proliferation capacity. Embryonic Stem Cells have already been used to produce three types of human brain cells and human heart muscle cells. However, these cells can only be obtained by destroying a human blastocyst embryo. That raises serious ethical questions about their use! If the revolutionary revolution biotechnology could find a way to biopsy the ICM to get a few cells, and that was first done in the 1970s, perhaps we could get immortal cells without having to destroy an embryo. Or if we can find a way to turn on the immortality gene in the Adult Stem Cells we might make them grow forever and make their use more attractive.

The potential of stem cells for medical therapy for the developmentally disabled population is truly amazing, but very difficult ethical hurdles must be dealt with before that potential may be realized.

Picture of Sam RhineSam Rhine is the Director of the Genetic Education Center, Fortville, Indiana. He is an internationally renowned Educator in the areas of human genetics; reproductive biology; bioethics; causes & prevention of disabilities; and HIV & the prevention of AIDS. During the past 29 years he has presented the most current scientific advances in over 7500 programs internationally on genetics, birth defects, HIV and AIDS.

Sam Rhine founded and directs the nationwide Genetic Update Conferences (GUCs), which provide the most up-to-date information about Genetics and Reproductive Biology for high school students and their teachers. He is on the adjunct faculty and teaches classes at Indiana University in Bloomington, Indiana University – Purdue University at Indianapolis, the University of St. Thomas in Houston, University of Texas Pan American in Edinburgh, Texas and St. Petersburg State University in St. Petersburg, Russia.

One expert in genetics education described Sam Rhine as "the most effective human genetics educator in America today". He is widely recognized for his dynamic conference presentations as he takes his audience into the 21st Century world of biotechnology.

The Shriver Center

The Forum is a project of the UCE at the Shriver Center, a division of the University of Massachusetts Medical School. Technical Support is provided by New England INDEX. This is an Official Page/Publication of the University of Massachusetts Medical School

University of Massachusetts Medical School
The DD Leadership Forum is funded by the Maternal and Child Health Bureau, federal Department of Health and Human Services.
© 2000 University of Massachusetts. All rights reserved.