Source: Human Events; July 30, 2001

Did the Navy Start the Stem Cell Research Fire?

By Terence P. Jeffrey

The strategy that may lead to stem-cell-based cures for genetic diseases

such as sickle-cell anemia was first hatched by nuclear war planners in

the United States Navy.

The cures would use adult stem cells only and would not involve the

destruction of human lives, in the embryonic, or any other stage, of

development.

Here's the nightmare military scenario that gave rise to the medical

research that now may produce miraculous cures: A nuclear-armed

Russian-built Sunburn missile smashes into a U.S. aircraft carrier

steaming through the Western Pacific. The aircraft carrier sinks, and

all on board are instantly killed. But they aren't the only casualties:

Thousands of sailors on nearby vessels survive the blast but suffer

lethal doses of radiation.

Their bone marrow -- the part of the body that produces white blood

cells, the main component of the human immune system -- is functionally

destroyed. Each and every sailor has become like the boy in the bubble,

subject to deadly infection by disease-causing agents a normal immune

system would resist. The Navy, of course, could not put a cruiser or

destroyer, let alone an entire fleet, in a bubble. So such sailors would

be doomed -- unless a new therapy could be developed.

How could the Navy save these sailors? Or, for that matter, how could

the U.S. government save airmen, soldiers or civilians caught in the fallout

from a nuclear war?

This was the question the Department of Defense put to Dr. John P. Chute

and his colleagues. Chute is director of the adult stem cell research

lab at the Navy Medical Research Institute, an organization that two years

ago was fused into a partnership with the National Institute of Diabetes,

Digestive Diseases and Kidney Diseases (NIDDK).

First, Do No Harm

"We were charged by the Navy leadership with a very simple question,"

says Chute. "Could we come up with a method to take human adult stem cells

from various sources -- bone marrow, cord blood or peripheral blood -- and

develop a method to support the growth of stem cells outside the body,

so that you could rescue stem cells taken from an individual who had been

exposed to a lethal dose of radiation and then transplant those cells

back into his body to cure the individual?"

"When the Defense Department first entered into this," says Chute,

"there was no evidence in the scientific or medical literature that

adult-source stem cells could be expanded in vitro, period. People had studied this

question for decades, but without success."

Chute and his colleagues succeeded.

Working in collaboration with Dr. Ron Hoffman at the University of

Illinois at Chicago, they started with an experiment on baboons -- the

laboratory animal most similar to man. Three untreated control animals

died from bone marrow failure after exposure to a lethal dose of

radiation. Four other animals were also exposed to a lethal dose of

radiation, but only after some of their bone marrow had been extracted.

Blood stem cells -- known as "hematopoietic stem cells" (HSC) -- were

isolated from these bone marrow samples then cultured in a laboratory

flask using a proprietary method developed by Chute and his colleagues

and patented by the Navy. The HSC replicated in the flask. About ten days

later, the researchers transplanted the expanded numbers of HSC back

into the baboons. The cultured stem cells repopulated the bone marrow of the

animals, which began producing healthy white blood cells again. They

were cured.

"More than a year later," says Chute, "all the animals are healthy and

their immune systems are working normally."

Then Chute and his colleagues took the process a step further. Could

they culture stem cells removed from an animal's bone marrow after

administering lethal doses of radiation and still restore a functioning

immune system? They succeeded in doing this in laboratory mice, and are

about to begin an experiment to replicate the results in baboons.

This is the first demonstration that bone marrow stem cells can be

rescued following lethal doses of radiation. More importantly, this is a model

not only for the future treatment of casualties of nuclear or chemical

warfare, but also for someone who has undergone conventional radiation

or chemotherapy as a treatment for cancer.

So what could this mean for people stricken with sickle-cell anemia or

some other genetic disease?

In a person with sickle-cell anemia, the red blood cells carry a

defective gene that prevents the cells from effectively carrying oxygen to tissues

around the body. Fixing, or replacing, that defective gene would cure

the disease.

Using the stem cell methodology developed by the Navy, HSC potentially

could be removed from the bone marrow of a person with sickle-cell

anemia and cultured in a flask. The next step would be to "transfect" these

cells with a normal gene.

This means that a virus that attaches to white blood cells would be

joined with a normal version of the gene that is defective in a person with

sickle-cell anemia. This normal-gene-carrying virus would be placed into

the flask with the sick person's HSC. The virus would then insert the

normal gene into the HSC, fixing the person's stem cells as they

replicate in the lab.

Once enough of these "fixed" stem cells had been cultured, they would be

transplanted back into the person's bone marrow. The patient would then

start producing normal red blood cells in his own body.

How does this adult-stem-cell-based cure differ from the type of "cure"

that might be developed for sickle-cell anemia using human embryonic

stem cells? Well, a cure based on embryonic stem cells would have to overleap

several additional biological as well as moral barriers.

First, in a cure based on human embryonic stem cells, a living human

embryo would have to be killed to extract its stem cells. Then these

stem cells would have to be coaxed into becoming hematopoietic cells.

But then because these cells would be genetically different from the

sickle-cell anemia patient's, they could not simply be transplanted into

that patient as if they were his own adult stem cells. Just as if he

were receiving a heart or liver transplant, the patient would first have to

go on powerful immuno-suppressant drugs to prevent his body from rejecting

somebody else's (the embryo's) stem cells. Similar to a sailor surviving

a nuclear blast, the sickle-cell anemia patient would become subject to

opportunistic infections -- as a result of being "cured."

To get around this rejection problem, scientists researching human

embryonic stem cells are now pondering the use of human clones as a

source for stem cells. In this procedure, an ovum would be harvested from a

woman (or an animal), and its DNA sucked out. Then new DNA would be extracted

from a cell in the patient and inserted into the evacuated ovum, creating

the patient's embryonic clone. (Theoretically, if implanted in a womb,

this cloned embryo would grow to become an identical twin of the

patient.)

But in this prospective "cure" scenario, the clone would be killed for

its stem cells, which would be cultured in a flask, "transfected" with a

normal gene, and transplanted into the patient.

So, why go through all these elaborate and morally problematic steps,

when there is a technology already developed to replicate a patient's own

adult HSC in the laboratory?

That is precisely the question that should be put to President Bush and

Congress today. Why force taxpayers to fund highly speculative research

that involves destroying human lives, when there is at hand very

promising, less speculative research that could do the same job without

destroying human lives?

And it gets better.

Dr. Chute and his colleagues in the Navy stem cell program have been

working with a California-based company called Large Scale Biology Corp.

This company specializes in proteomics -- the science of identifying and

charting every protein in the human body. Isolating these proteins is

crucial to moving to the next phase of human stem cell research because

human stem cells, while still in the body, are triggered to replicate

themselves by particular proteins.

If Large Scale Biology can isolate the precise protein (or set of

proteins) that triggers HSC to self-renew, it is possible that this

protein could be mass-produced in tobacco plants through a process the

company has patented. Hypothetically, this mass-produced protein could

be put in pills, and the pills could be stored on warships. If a warship

were exposed to a nuclear blast, the pills could be distributed to the

sailors onboard.

The health-care vistas such a therapy could open are mind-boggling.

Perhaps some day a pill carrying the trigger-protein for cardiac muscle

cells could rebuild a man's damaged heart. Another protein pill could

repair the pancreas of a diabetic or the brain of a Parkinson's victim.

Best of all, such cures would not begin with the taking of an innocent

human life. Researchers could abide by the primary dictum of medical

ethics -- first, do no harm -- rather than pry open the portal to a new

Nietzschean world where one man is killed so another might live.