Our time in the womb is one of the most vulnerable periods of our existence. Pregnant women are warned to steer clear of certain foods and alcohol, and doctors refrain from medical interventions unless absolutely necessary, to avoid the faintest risk of causing birth defects.
Yet it is this very stage that is now being considered for some of the most daring and radical medical procedures yet devised: stem cell and gene therapies. “It’s really the ultimate preventative therapy,” says Alan Flake, a surgeon at the Children’s Hospital of Philadelphia in Pennsylvania. “The idea is to avoid any manifestations of disease.”
The idea may sound alarming, but there is a clear rationale behind it. Use these therapies on an adult, and the body part that you are trying to fix is fully formed. Use them before birth, on the other hand, and you may solve the problem before it even arises. “This will set a new paradigm for treatment of many genetic disorders in future,” says Flake.
Flake has been performing surgery on unborn babies for nearly 30 years, using techniques refined on pregnant animals to ensure they met the challenges of working on tiny bodies and avoided triggering miscarriage. The first operation on a human fetus took place in 1981 to fix a blocked urethra, the tube that carries urine out of the bladder. Since then the field has grown to encompass many types of surgery, such as correction of spinal cord defects to prevent spina bifida.
While fetal surgery may now be mainstream, performing stem cell therapy or gene therapy in the womb would arguably be an order of magnitude more challenging. Yet these techniques seem to represent the future of medicine, offering the chance to vanquish otherwise incurable illnesses by re-engineering the body at the cellular level. Several groups around the world are currently testing them out on animals in the womb.
Of the two, stem cell therapy has the longer history: we have been carrying it out on adults since the 1950s, in the form of bone marrow transplants. Bone marrow contains stem cells that give rise to all the different blood cells, from those that make up the immune system to the oxygen-carrying red blood cells. Bone marrow transplants are mainly carried out to treat cancers of immune cells, such as leukaemia, or the various genetic disorders of red blood cells that give rise to anaemia.
One of Flake’s interests is sickle-cell anaemia, in which red blood cells are distorted into a sickle shape by a mutation in the gene for haemoglobin. People with the condition are usually treated with blood transfusions and drugs to ease the symptoms, but even so they may well die in their 40s or 50s. Some are offered a bone marrow transplant, although perhaps only 1 in 3 can find a donor who is a good match genetically and whose cells are thus unlikely to be rejected by their body. “The biggest issue with treating disease with stem cells is the immune system,” says Flake.
And therein lies the main reason for trying a bone marrow transplant in an unborn baby: its immune system is not fully formed. At around the fourteenth week of pregnancy, the fetus’s immune system learns not to attack its own body by killing off any immune cells that react to the fetus’s own tissues. This raises the prospect of introducing donor stem cells during this learning window and so fooling the immune system into accepting those cells. “You can develop a state of complete tolerance to the donor,” says Flake. “If it works for sickle cell, then there are at least 30 related genetic disorders that could be treated.”