SCID patient Katlyn Demerchant could not leave a sterile room without falling
dangerously ill. She received a gene therapy treatment in 2007
that helped alleviate her immune deficiency. Image: NIH Clinical Center
After years of doubts and dangers, gene therapy is showing promise as one of our best hopes for fighting lethal and debilitating diseases (see the DISCOVER feature "The Second Coming of Gene Therapy"). In the lab, replacing malfunctioning genes with working ones has succeeded in curing or treating animals with hemophilia, (the animal analogs of) depression, and other afflictions. In clinical trials in people, it’s brought sight to the blind, allowed kids without immune systems to live normally, and contributed to one of the most talked-about cancer discoveries of the year, a promising experimental treatment for leukemia.
Of course, the technique was not brought to us from above by Prometheus—it all rests on a mountain of basic science research, most of it publicly funded.
1952: Hershey and Chase show that DNA is the genetic material, bearing heritable traits from generation to generation. Most scientists previously thought the leading contender for that role was proteins, though experiments in 1944 had suggested DNA was more likely. Hershey goes on to win the Nobel Prize.
Funded in part by the NIH.
1966: Marshall Nirnberg and colleagues crack the genetic code [pdf] , a discovery that’s key to our understanding of how exactly DNA relates to heritable traits. The team show that amino acids—the building blocks of proteins, which control our cells’ functions—are each coded for by specific sections of DNA three base pairs long. Nirnberg wins the Nobel Prize in 1968 for this work.
Funded by the NIH.
1966: Edward Tatum suggests in a speech that genetic disease might be treated with “genetic engineering.” He suggests that nonpathogenic viruses be used to transfer genes to patients’ cells, as researchers had previously observed that viruses could, at least temporarily, introduce DNA into bacterial and mammalian cells.
In the same year, Joshua Lederberg, who had mentioned the idea of gene therapy as early as 1963, wrote an article for The American Naturalist describing how it might be done, describing it as “virogenic therapy.” First, however, researchers needed a method for isolating the gene they’d like to insert.
1969: Jonathan Beckwith at Harvard and colleagues are the first to purify a gene [pdf], using viruses to selectively snap up the proper gene from a soup of DNA from pureed E. coli. Once researchers learn to isolate genes, though, they still have to figure out how to introduce them into viruses.
Funded in part by the NIH and the NSF.
1972: Paul Berg and collaborators do pioneering work towards using a virus to stably insert genes of the researcher’s choice into a cell’s genome. He is eventually able to make E. coli produce human insulin, a key step towards using cells as tiny drug factories. For this work, he wins the Nobel Prize in 1980.
Funded in part by the US Public Health Services, the parent agency of the NIH.
1982: In the early 80s, scientists realize that retroviruses have tremendous potential to deliver genes stably into large numbers of cells, and start producing lab-safe versions. In one such study by Ronald Evans and colleagues, the gene for rat growth hormone is stably inserted into mouse cells by a retrovirus. Putting this knowledge to use, scientists begin to use viruses to treat cells removed from patients with genetic diseases.
Funded by the NIH.
