Appendix M: Gene Therapy Techniques

Ashanti DeSilva was born in Cleveland in 1985 with the genetic disorder that has come to be known as “Bubble Baby Disease”: her body lacked the gene required for making the protein adenosine deaminase, or ADA. (1)  Without ADA, her immune system was drastically impaired: just about any viruses or bacteria she encountered could easily attack her body and prove fatal.  She spent the first four years of her life in total isolation at home, kept alive by injections of synthetic ADA.  Her parents knew, moreover, that the effect of these injections was inevitably going to diminish over the coming years, and that their daughter would eventually die of her disease.  The only other alternative, a bone-marrow transplant, was impossible because no compatible donor could be found.

Out of desperation, Ashanti’s parents turned to what was at that time cutting-edge experimental medicine.  In 1990, when Ashanti was four years old, a team of doctors at the NIH Clinical Center in Maryland extracted blood cells from her veins, then used a hollowed-out virus vector to insert working copies of the ADA gene into those blood cells.  They were, in effect, repairing the deficient gene that had caused her disease.  When those genetically modified blood cells were injected back into Ashanti’s body, the results were dramatic.  Within six months, her immune system became sufficiently active to allow her to go safely out of the house; within two years, she was enrolled in school and began for the first time to experience a normal childhood.  Ashanti DeSilva is alive and healthy today, though she still has to receive weekly injections of synthetic ADA and also requires periodic renewal of the gene therapy to boost her immune response.  Her story constitutes the first successful case of somatic gene therapy on humans (though researchers remain uncertain about the extent to which her improved health was caused by the genetic component of her therapy as opposed to the traditional pharmaceutical aspect). (2)

The trajectory of gene therapy over the twenty-five years that followed was a bit of a roller coaster.  Initial cases like Ashanti’s raised hopes high, both among medical researchers and among those afflicted by genetic diseases, that a potent – some even used the word ‘miraculous’ – cure might soon be on the way.  (3) They were gravely disappointed: over the subsequent decade, the field suffered one major setback after another.  In 1999, an eighteen-year-old man named Jesse Gelsinger, who had volunteered for an experimental gene therapy trial at the University of Pennsylvania, died four days after his first treatment: it was later determined that his body had undergone a severe immune reaction to the virus vector that had been used to transport the repaired DNA into his cells.  (4) Then, in 2002, a French gene therapy trial on eleven children with severe immunodeficiency also went awry: though nine of the children responded well to the treatment, two developed leukemia.  Doctors discovered that the segment of new DNA inserted into the children’s cells had inadvertently activated a cancer-causing oncogene, called Lmo2, lying dormant in an adjacent section of the chromosome. (5) These developments caused the U.S. Food and Drug Administration (FDA) to order a temporary ban in 2003 on further gene therapy trials using these specific kinds of viral vectors, until they could be proven safer. (6)

Nevertheless, the researchers soldiered on, and in recent years they have begun registering significant new successes.  Recognizing the potentially problematic nature of viruses as vehicles for ferrying new DNA into cells, they have begun experimenting with entirely man-made vectors called liposomes, small lipid spheres that can carry DNA through a target cell’s membrane. (7) They also have turned to the nanoparticles known as dendrimers as a promising means of transmitting DNA segments to targeted tissues on tumors (see the discussion of dendrimers in Chapter 5).  If that method, which is currently being tested on mice, proves safe to use in humans, it could greatly advance the treatment of a variety of cancers. (8)

Methods relying on hollowed-out viral vectors, meanwhile, have proved increasingly safe and effective in recent years.  In 2005, researchers used such viruses to deliver new genes into the ear tissues of deaf guinea pigs, forcing the growth of fresh auditory cilia in the cochlea, and thereby restoring the animals’ hearing.  If the technique can be applied to humans – and scientists are confident that it eventually will be – this would yield a permanent cure for certain forms of hereditary deafness. (9) In 2006 a team at the National Cancer Institute used viruses to modify the genes of lymphocytes, or white blood cells, in seventeen human patients suffering from advanced melanoma: the re-engineered lymphocytes proved highly effective in targeting and destroying cancer cells, resulting in excellent clinical outcomes for many of the patients. (10) In 2008 four persons suffering from a genetic form of blindness had their eyesight partially restored by means of new genes delivered into their retinal tissues by a harmless form of adeno-associated virus. (11) In 2009, three different forms of gene therapy for HIV infection yielded promising results in clinical trials conducted in Germany and California: the German methods were particularly promising, as they resulted in the complete eradication of all HIV viruses from a patient’s body. (12) While it is still too soon to declare viral vectors safe for general use, the growing successes encountered by many such efforts bode well for gene therapy over coming decades.  To quote from the FDA web site:


“The FDA has not yet approved any human gene therapy product for sale. However, the amount of gene-related research and development occurring in the United States continues to grow at a fast rate and FDA is actively involved in overseeing this activity.  …  Such research could lead to gene-based treatments for cancer, cystic fibrosis, heart disease, hemophilia, wounds, infectious diseases such as AIDS, and graft-versus-host disease [or xenotransplantation reactions].” (13)


(1) Naam, More Than Human,  11-16; Ruth Sorelle, “The Gene Doctors,” Houston Chronicle (April 2, 1995), 11-12.

(2) W. French Anderson, “Gene Therapy: The Best of Times, the Worst of Times,” Science 288 (April 28, 2000), 627-29; Naam, More Than Human,  11-16; Ruth Sorelle, “The Gene Doctors,” Houston Chronicle(April 2, 1995), 11-12.  See the excellent web site on gene therapy maintained by the Human Genome Project at:  See also Ruth Chadwick, “Gene Therapy,” in Helga Kuhse and Peter Singer, eds., A Companion to Bioethics(Blackwell, 2001), 189-197; Gerald P. McKenny, “Religion and Gene Therapy,” in Justine Burley and John Harris, eds., A Companion to Genethics (Blackwell, 2002), 287-301.

(3) Larry Thompson, “Human Gene Therapy: Harsh Lessons, High Hopes,” FDA Consumer 34:5 (Sept. 2000), 19-24; Emma Young, “’Miracle’ gene therapy trial halted,” New Scientist (Oct. 3, 2002), available at:  For a discussion of the broader implications of genomic medicine see Ellen Wright Clayton, “Ethical, Legal, and Social Implications of Genomic Medicine,” New England Journal of Medicine 349:6 (Aug. 7, 2003), 562-69.

(4) Andrew Lustig, Baruch Brody, and Gerald McKenny, eds., Altering Nature: Volume Two: Religion, Biotechnology, and Public Policy (Springer, 2008), 170-72.

(5) “Gene therapy trial suffers new setback,” New Scientist (Feb. 12, 2005), available at:; Emma Young, “’Miracle’ gene therapy trial halted,” New Scientist (Oct. 3, 2002), available at:

(6) “What are some recent developments in gene therapy research?”  Web site on gene therapy maintained by the Human Genome Project at:

(7) Ibid.

(8) Edward Chisholm, et. al., “Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles,” Cancer Research 69, 2655 (March 15, 2009); “Nano-treatment to torpedo cancer,” BBC News Online (March 10, 2009).

(9) Andy Coghlan, “Gene therapy is first deafness ‘cure,’” New Scientist (Feb. 14, 2005), available at:

(10) “New Method of Gene Therapy Alters Immune Cells for Treatment of Advanced Melanoma; Technique May Also Apply to Other Common Cancers” (2006), article on web page of the National Cancer Institute, available at:

(11) Ewen Callaway, “Gene therapy success ‘reverses’ blindness,” New Scientist (April 28, 2008), available at:

(12) Andy Coghlan, “Gene therapy promises one-shot treatment for HIV,” New Scientist (February 18, 2009), available at:

(13) “Cellular and gene therapy products,” article on web site of the Food and Drug Administration, available at: