The National Institutes of Health has spent millions of dollars over the past decade funding the mass production of a creature that is part mouse and part human.

Every one of these most peculiar rodents requires live tissue extracted from the liver and thymus of a human child–and every child who donates tissue to create such mice is first killed by a medical doctor. They are victims of abortions that cannot take place until at least the eighth week of pregnancy, when the fetal liver is finally formed.

Although history may someday record the saga of this mouse as one of the greatest horror stories in the annals of medicine, it actually begins with what may be described as a small miracle.

The miracle happened in 1980 at a cancer research center in Philadelphia, when an

ordinary laboratory mouse gave birth to an extraordinary litter of pups.

Mel Bosma, a researcher at the center, discovered that four of these pups carried an abnormality that would prove deadly to them but of great value to man. They suffered from a genetic disorder called Severe Combined Immunodeficiency (SCID).

In essence, these mice had no natural means of fighting disease. Unlike a human being with Acquired Immune Deficiency Syndrome (AIDS)–whose immune system has been destroyed by the Human Immunodeficiency Virus (HIV)–these first-ever SCID mice were born without a functioning immune system.

Saving Chimpanzees

Bosma recognized the enormous potential these mice might have for medical research and preserved them for breeding.

Several years later, J. Michael McCune, an investigator at Stanford Medical School, was grappling with what was then one of the most basic obstacles confronting doctors searching for an AIDS cure. Ordinary laboratory mice could not be infected with HIV because HIV–which, after all, is a "human" virus–cannot penetrate the cells that make up the mouse immune system. That means that ordinary laboratory mice are useless for testing AIDS vaccines and therapies.

The chimpanzees that were being used in some AIDS research were an expensive and politically incorrect species, a stumbling block that severely limited the scope of the preliminary research that could be done on developing an AIDS cure.

As McCune later described it to a reporter for The Business Journal, he struck upon a way to solve this problem as he was driving in his car up Interstate 280 toward the city of San Francisco: Why not transplant the human immune system into a mouse?

This was not a science-fiction fantasy. The discovery of the SCID mouse had made the hypothesis plausible enough to test.

In a normal mammal, the immune system would reject tissue transplanted from another body–especially if that other body was of another species. But because the SCID mouse lacked a working immune system, researchers theorized it might not reject transplanted human tissue.

That, however, would solve only half the problem. The other half was that human tissue–adult human tissue, anyway–would itself reject the mouse. Medical researchers call this "graft-versus-host" disease.

This is where the babies came in.

Up to a certain point as it develops within its mother’s womb, an unborn child’s immune system has not learned to recognize its own body. The blood cells that are dedicated to fighting disease, which develop initially in the child’s liver, have not yet passed through the thymus where they are educated to recognize their own body so they can discriminate between their own healthy cells and the agents of a disease.

If the organs and tissues that constitute the basic elements of a baby’s immune system could be removed before its disease-fighting cells became educated, and if this removed immune system could be implanted in a SCID mouse, that mouse might develop into a brave new laboratory animal: part rodent, part human.

Many things had to fall into place in American law and culture to make such an experiment possible. Abortions had to be legalized. Women had to be willing to have them. Doctors had to be willing to perform them. Technicians had to be willing to fish out body parts from the fresh remains of aborted babies. Researchers had to be willing to implant those body parts in mice.

And, of course, somebody had to be willing to pay for it all.

By 1988–only 15 years after the Supreme Court’s Roe v. Wade decision had converted abortion from a crime in most of the United States to a "constitutional right"–all of the requisite legal, cultural and scientific elements had fallen into place. The bill, as it turned out, would be sent to U.S. taxpayers.

On Sept. 14, 1988, Stanford University sent out a press release announcing the success of its efforts to build a mouse with a human immune system. Later that month, McCune and his associates, including Dr. Irving Weissman, a Stanford pathologist, published their results in the journal Science.

They named their creation the SCID-hu mouse, "hu" being short for "human."

In Science, under the heading, "Construction of the SCID hu," McCune and his associates explained their creation in these terms: "Human fetal thymus, liver, lymph node, and spleen were obtained and prepared for introduction into SCID mice by surgical implantation or by intravenous injection. . . . With a bank of frozen tissues available, it becomes readily possible to construct SCID-hu mice with a variety of human lymphoid organs of defined (and, as desired, different) genetic origin."

The scientists noted that the age of the aborted fetus was of significance. The unborn child had to be old enough to have a functioning liver that produced blood cells, but not so old that those cells had already "migrated through the human fetal thymus," become differentiated, and learned to recognize their own body and fight off disease. The prime moment was between 8 and 24 weeks, with the optimum time being before 20 weeks.

Where did the "donor" babies come from? Stanford answered the question dryly in its 1988 press release: "The human immune system is seeded into the mice using small quantities of tissues from aborted fetuses obtained under strict human-use guidelines."

In an interview, Janet M. Young, of the Basic Science Program of the Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID)–which funds much of the nation’s SCID-hu research–could not answer specific questions about the conditions under which the tissue is retrieved from aborted babies and referred the question to Dr. McCune. Dr. McCune did not return calls placed to his office in San Francisco.

But C. Ward Kischer, emeritus professor of embryology at the Arizona University College of Medicine and an expert on fetal development, offered his own interpretation of what the procedure must be like.

The unborn child does not begin to develop a liver until about five weeks, said Kischer. A baby aborted in the first month, in other words, would be useless for creating a SCID-hu mouse. At eight weeks, he said, the liver starts to perform its "hematopoietic" function, producing the undifferentiated blood cells that will later pass through the thymus and begin creating the baby’s immune system.

But at this point, he said, the baby is only about one inch long and an abortion would likely be done by the Dilation and Curettage (D&C) method. At 15 weeks, he said, the baby would be about five inches long, and still likely to be aborted by D&C. At 20 weeks it would be about 7 inches long, and still, if aborted, a likely candidate for the D&C procedure.

The thymus, which is in the baby’s neck, he said, begins to significantly develop only after birth. "Even at 20 weeks," he said, "it is really, really small."

Kischer said he finds it hard to believe the researchers could retrieve livers and thymuses from babies aborted by D&C between the 8th and 20th week of gestation. "To find the liver in a dismembered early fetus is next to impossible," he said. "I don’t see how they can do it."

"If they insert a curette into the uterus and start scraping the wall," he said, "there is absolutely zero assurance that the curette will not dismember that embryo or fetus. They will start to cut it up. And if you start cutting it up, and you get the products of conception out and put them in a petri dish, how are you going to determine what is liver and what isn’t? It’s impossible."

Back in 1988, the Los Angeles Times reported the invention of the SCID-hu mouse on page one. A few other major papers gave it a one-day run. Some played it as a humanitarian boon to chimpanzees.

"My hope is our mice can remove all the pressure on chimps," Dr. Weissman told the Chicago Tribune. "There are only a few hundred chimpanzees in the world available for medical research. . . . If our mouse model works there’s no reason to use a primate model that doesn’t seem to be complete, that’s being done with animals that are in incredibly short supply and are in danger of extinction."

He was confident, apparently, in a continuing supply of aborted babies.

Once the SCID-hu mouse had been created, its inventors set about demonstrating its applicability to AIDS research. Working under a grant from the NIH, they injected the mice with HIV, to prove that the human blood cells floating through its rodent veins could indeed be infected with a human virus. The work was done in a specially secured laboratory to ensure that AIDS-carrying mice could not escape into city streets.

"SCID-hu mice were infected within the confines of a specially adapted animal bio-safety level (BSL) 3 facility," the researchers wrote in Science. "A flank incision exposed the growing human thymus or lymph node implant of anesthetized SCID-hu mice. Graded doses of HIV-1 . . .were introduced by direct intrathymic or intranodal inoculation. The mice were maintained in micro-isolator cages, inside a sealed glove box, within the BSL3 facility."

These facilities even have an airlock designed to prevent the movement of airborne particles from the inside to the outside.

In a follow-up experiment, the researchers treated HIV-infected mice with AZT to see if the drug would inhibit the proliferation of the virus. The test could not have been more successful. The researchers again chronicled their triumph in the pages of Science:

"The SCID-hu mouse will be useful for measuring the in vivo efficacy of the antiviral compounds and may provide a test system in which their administration could be experimentally altered to achieve optimal efficacy. The same techniques that are used to analyze antiviral compounds against HIV should be directly transferable to the analysis of interventions against other human pathogens."

They had discovered a scientific and commercial gold mine–and Stanford moved to secure the rights to it. "Since the work may lead to new avenues of therapeutics," the school said in a press release, "Stanford University is seeking a patent on the process that leads to a mouse with human-blood-forming and immune potential."

The government granted the patent. McCune and Weissman secured startup capital from venture capitalists, including Eli Jacobs, one of the owners of the Baltimore Orioles, and began a biotechnology company named Systemix. Stanford gave them a license to commercially use the mouse.

On Aug. 1, 1990, Systemix issued a press release reporting that the NIH had awarded it a "multimillion dollar, five-year contract" to test anti-AIDS drugs using the mouse.

"This contract represents an important step for the NIH, for us and for patients with HIV infection," McCune said in the press release. "Now, drugs that look promising in the lab can be selected on the basis of their activity in relevant animal models, prior to their use in man."

This was not precisely correct, of course. Systemix would be testing the drugs in man–but only in those whose lives had been terminated and their immune systems stripped out and implanted in mice.

In late 1991, the Swiss pharmaceutical firm, Sandoz, purchased 60% of Systemix. The San Francisco Chronicle reported: "The deal also is a windfall for the Stanford scientists whose discovery got Systemix started. Dr. J. Michael McCune, 37, a former Stanford postdoctoral student, and his mentor, renowned Stanford immunologist Dr. Irving L. Weissman, 51, each have options to buy stock at 28 cents per share. The stock closed yesterday at 55 in over-the-counter trading. McCune and Weissman can each acquire $24 million worth of Systemix stock by shelling out $105,000 apiece."

The February 1992 issue of The Business Journal added: "For a biotech company, Systemix has progressed at light speed. Ms. [Linda] Sonntag [Systemix’s CEO] attributes the company’s rapid development largely to Dr. McCune’s mouse. ‘The premise was that the SCID-hu mouse tool would expedite R&D dramatically, and it proved to be true,’ she said. ‘Without the SCID-hu mouse, we would not be where we are now.’"

The utility of the SCID-hu mouse spawned numerous federal grants that made use of the animal. By 1998, the NIH was handing out 43 separate grants for research that used it. Last year, 45 NIH grants specifically mentioned use of the SCID-hu.

On June 18, 1993, the National Institutes of Allergy and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH) put out a request for grant proposals that appeared to ratchet up the government’s involvement in manufacturing SCID-hu mice. The agencies were soliciting proposals to create what they called "core facilities" at regional government-funded Centers for AIDS Research (CFAR). The request for proposals said: "Examples of such Cores that may be supported by the NIAID include . . . SCID/hu Mice Facilities . . . Examples of such Cores that may be supported by NIMH include . . . SCID/hu Mice Facilities."

In an interview, NIAID’s Young said that the language about "SCID/hu mice Facilities" was only included in the solicitation for proposals as an example to the investigators of the general sort of thing the NIAID would fund. The NIH, she said, was not specifically recommending or promoting the creation of these facilities.

Nonetheless, at least five universities participated in creating federally funded "core facilities" for the manufacture of SCID-hu mice under the auspices of NIH grants. These were the University of California at Los Angeles, the University of Alabama at Birmingham, the Aaron Diamond AIDS Research Center jointly operated by Columbia and Rockefeller universities and the Albert Einstein College of Medicine.

Not all of these continue to operate under CFAR auspices. Currently, said Young, "There are three Centers for AIDS Research (CFAR) sites that support SCID/hu core facilities. These are CFARs at: University of California at Los Angeles (UCLA), University of Alabama at Birmingham (UAB), and Dana Farber Cancer Institute (DFCI). The latter has very few mice and a small number of investigators interested in this model. The CFAR at Aaron Diamond AIDS Research Center has not had a SCID/hu facility for approximately 4 years now . . . Albert Einstein College of Medicine no longer has a CFAR grant."

One of the grant abstracts for the SCID/hu facility at UCLA indicates that the university was looking into implanting human brain tissue in the mice. States the abstract: "The SCID-hu Mouse/Human Chimera Core Facility is designed to provide access to state-of-the-art-mouse/human chimera technology for UCLA-affiliated AIDS investigators. This facility will provide breeding of SCID mice at a reduced rate, housing for SCID mice, and a BSL3 laboratory for manipulation and housing of chimeric mice infected with human retroviruses.

"Consultation on construction of mouse/human chimeras (hu- PBL-SCID and SCID-hu) is also available. In addition, there is a developmental component to this core, which has helped to established the SCID-hu mouse as an in vivo model for virus-induced pathology. This component approaches to combat AIDS, and will participate in development of a model for growth of human brain tissue in vivo. This latter system will be used to investigate mechanisms of neuropathogenesis of AIDS."

The hu-PBL-SCID mouse mentioned in the text is a rival lab animal to the SCID-hu, which, unlike the SCID-hu, takes only blood from umbilical cords or adult donors, and does not require human fetal tissue.

In addition to the SCID-hu mice being created at CFAR "core facilities"–and also in some instances by individual NIH-funded researchers around the country who are not associated with a CFAR–the NIAID continues to contract directly itself with an outside provider to create SCID-hu mice for testing AIDS drugs.

On Aug. 19, 1999, the NIH put out a request for proposals for a new SCID-hu contract that revealed some crucial details about SCID-hu construction.

The proposal informed prospective contractors that "Up to 1200 SCID-hu thy/liv mice (50 per experiment) and 125 unengrafted SCID mice will be needed for evaluations of single and combination therapies per year. The Contractor shall be capable of providing up to 100 SCID-hu thy/liv mice per month, in groups of 50 animals engrafted with tissue from a single donor."

What is more, the NIAID instructed potential contractors to include a "description of the methods used . . . to quality assure/control viral stocks, tissue donors, and engrafted mice."

The agency further instructed would-be contractors that they would have to "quality assure" "donor tissue" even if "any of the components of the model are provided by a Subcontractor."

After an inquiry by Human Events, NIH said it would refuse to release the winning proposal for this contract even if it was requested to do so under the Freedom of Information Act. The agency cited language in the 1997 Defense Authorization bill that exempted federal agencies from releasing even successful proposals from government contractors under FOIA.

So, for now, the details of just exactly how the contractor demonstrated to the government it was going to assure the quality of the human fetal livers and thymuses it intended to transplant into "up to 1200" mice remains a government secret.

The contract, by the way, was awarded to the J. David Gladstone Foundation, a California organization associated with Dr. Mike McCune, the SCID-hu’s inventor.

Dr. McCune did not return calls.

© Human Events, 2001