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Sixty-two-year-old Lillian Cooper is losing her ability to walk. Dr. Jeffrey Isner of Tufts University proposes a gene therapy trial that could save her leg and allow her to resume her morning routine of mall walking. The radical new treatment involves making copies of human genes and inserting them into an artery, in hopes of growing new blood vessels and delivering a significantly greater volume of blood flow down to the lower leg. Time will tell if the experimental gene therapy works.

Curriculum Links
Background Information: Gene Therapy
Activity: Modeling Genetic Engineering
For Further Thought




nucleic acids
organic molecules


genetic engineering

heart disease


Gene therapy, while still in a very experimental stage, could one day provide cures to fatal diseases. The work is promising but controversial. Many people, scientists and nonscientists alike, believe that gene therapy raises questions, even as it promises answers. Genes (located on chromosomes) are sections of DNA that code for a certain protein. If genes do not do their job properly, necessary proteins are not manufactured in proper quantities for cells to do their jobs.

Gene therapy uses genes and techniques of genetic engineering to treat genetic disorders or chronic diseases. In theory, genetic defects can be corrected by either inserting a properly functioning version of the gene into the cells or by modifying the defective gene so it functions correctly. But what sounds simple is actually rather complex.

The first clinical trial of gene therapy began in 1990, when a little girl received gene therapy treatment for a fatal inherited disease of the immune system. Therapy involved using a genetically modified virus to carry a correctly functioning gene into her immune cells. The inserted gene then programmed the cells to produce a missing enzyme.

The gene therapy trial you see on FRONTIERS does not involve a virus. The patient receives copies of a human blood vessel growth factor gene, vegF (vascular endothelial growth factor). The genes are inserted into cells in the patient's arteries, with the hope of stimulating the growth of new blood vessels.


One method of introducing genetically-engineered material into human cells involves retroviruses that can be modified to carry human gene sequences into cells where the DNA coding for certain proteins is defective. Retroviruses insert themselves into the DNA of the infected cells and will replicate along with the infected cells during normal cell division.

This activity is an attempt to model aspects of a gene therapy trial that used a retrovirus to insert a normal gene into the cells lining the lungs of patients with cystic fibrosis. A retrovirus is an RNA virus that reproduces by transcribing itself to a form of DNA. Retroviruses are used in gene therapy because they are organisms capable of naturally changing the DNA of cells they infect. (RNA viruses insert themselves into the host cell's DNA and replicate along with the cell and its daughters.) Whether the virus is RNA or DNA does not matter, as long as a good gene is added to the cell.

In this model, the retroviruses act as vectors to carry the correct DNA into cells being treated. (A vector is an agent that carries something from one organism to another.)

The basic procedure in this technique of genetic engineering involves identifying the gene responsible for the defect, isolating it from cells where it's working properly, packaging it into the retrovirus for transport into the patient's cells with the improperly functioning gene, and ultimately incorporating it into the DNA of the host cells for proper expression of the gene.


  • 2 containers; either beakers or petri dishes or clear soda bottles

  • 1 smaller container; you can use a 1 L clear soda bottle with cap

  • 9 pieces of yarn, each 1 M in length (2 red, 2 blue, 2 yellow, 1
  • scissors

  • OPTIONAL: pipe cleaners, glue or tape

Make a model to demonstrate how a virus can be used as a vector for gene therapy.


Work in teams of two students each to construct a model to demonstrate how gene therapy works. Each model should include:

  • a human cell with its defective gene,

  • a human cell with a properly functioning gene,

  • a retrovirus (with its own DNA).
These directions are for one model but you can brainstorm ways to make models using other materials.

  1. Label the beakers or containers. These containers represent human body cells. Take the two red pieces of yarn and tie each into a loop and drop one loop into each beaker. Repeat the process for the two blue pieces of yarn, again putting a loop of each color into each beaker. These represent normal chromosomes in these two cells. Now take one yellow section and tie it at each end to the ends of the white section. Drop it into one of the beakers. This represents a chromosome with a defective gene. To the other yellow section, tie the green section at each end and drop it into the other container. The green section represents the healthy gene we want.

  2. Prepare the retrovirus. Optional: Remove the cap from the smaller bottle and attach pipe cleaners to the side of the cap with tape or hot glue. Once dry, bend the pipe cleaners into shapes like little spider legs, so that when the cap is placed on the container, you can stand the container upside down on its "legs." The pipe cleaners represent the attachment fibers on typical bacteriophage ("bacteria-eating") viruses.

  3. Put the piece of purple yarn into the smaller container. Replace the cap. This represents a retrovirus with its own DNA. Viral DNA is not always in a loop, so you do not have to tie the purple strand into a loop.
Recombining DNA

To demonstrate retrovirus use in gene therapy, use the model to represent the various steps involved:

  1. The beaker with the red/blue/yellow-and-white loops represents a human body cell with its chromosomes (the colored loops). On one of the chromosomes (the yellow one), there is a defective gene, shown as a white section. This is equivalent to "identifying the location of the defective gene."

  2. The beaker with the red/blue/yellow-and-green loops represents a human body cell with its chromosomes (the colored loops). On the yellow chromosome, there is a normally functioning gene, shown as a green section. This is equivalent to "identifying the location of the properly functioning gene."

  3. Remove the "normal" chromosome (the yellow-and-green loop) from its beaker. Cut the green section out of the loop, leaving a bit of yellow at each end. This is equivalent to using restriction enzymes to cut the DNA and transfer it to other cells.

  4. Open the "virus" and remove the strand of purple yarn. This is equivalent to removing its DNA. The purple strand represents the vital genetic information that will carry the human gene into the cells it infects.

  5. Cut the purple strand into two pieces (not necessarily of equal length) and tie one to each end of the strand from step Then put the recombined strand back into the virus. This represents using enzymes to open the viral DNA and insert the human DNA into it and then putting the "recombined" DNA back into the virus.

  6. Now have a student remove, at random, one of the colored loops from the defective cell beaker (the one with the red/blue/yellow-and-white loops). Cut this loop anywhere. Remove the viral DNA and tie it to the cut ends of the loop you removed. Then put the recombined loop back into the beaker with the other loops. This simulates the viral DNA inserting itself, along with the functioning human gene, at random, into the chromosomes of a cell with a defective gene.

  1. What are some of the reasons gene therapy doesn't always work, even when scientists have figured out a method?

  2. Can you design a better way of getting the correct version of the DNA into the cell as represented by this model?

  3. What might happen if you insert the new DNA into the middle of a gene already present in the cell that is doing its job properly?

  4. What are some other examples of retroviruses? Can you find any science news stories about retroviruses or gene therapy?


  • Human growth hormone is already being used by some athletes for size and strength gains. Do you think it is acceptable to use human growth hormones to make people taller? Why or why not?

  • Suppose a genetic defect responsible for mental retardation could be found and repaired. Would it be ethical to use this procedure to make normal people smarter?

  • Who should benefit from gene therapy? Is it ethical to treat an inheritable disease if all you do is cure the individual, yet not incorporate the change into the person's reproductive cells so their children will be free of the threat of the disease? Investigate Huntington's chorea or cystic fibrosis in connection with this issue.


Scientific American Frontiers
Fall 1990 to Spring 2000
Sponsored by GTE Corporation,
now a part of Verizon Communications Inc.