How Safe Is DNA Research?
And How Could DNA Tests Go So Wrong?
What does it mean when a patient undergoes routine genetic testing and the results are “wrong”?
This happened to a Boston mom in her 50s, with three adult sons, who needed a kidney transplant. Specialists hoped one of her sons would be a match, the procedure would go forward and the mom and her children could look forward to many happy years together. The problem came when test results showed that two of her sons were not, in fact, her own children. The mom knew she had delivered and raised three healthy boys so this finding couldn’t be right.
Experts began checking the medical histories of the children, the grandparents and so forth. Could it be that two of the children were accidentally switched at birth by the hospital? The odds of such a mistake happening twice, years apart, were astonishingly small.
Thousands of miles away, in Washington state, a pregnant woman who applied for state aid to support her family was accused of fraud. She already had two children who otherwise qualified for financial assistance. However, when genetic tests were run to confirm familial ties, the lab running the tests determined these were not, in fact, her biological children.
In accordance with state law, when her third child was born, the state had a medical professional in attendance to run genetic tests to confirm the maternal relationship as soon as the baby arrived. Yet, once again the genetic tests came back showing the birth mother was not the baby’s genetic mother. The lawyer defending the mother in the state fraud case, was at wit’s end.
In California, a dad who was certain about the paternity of his children, wanted to confirm the familial relationship. The dad and the kids took paternity tests, but the lab found the kids were not his.
What could explain these terrifying and mystifying lab results?
Enter The Chimera
In Greek mythology there was a legendary creature known as the Chimera. It was described as having a fire-breathing lion head, a goat’s body and a serpent’s tail. According to legend, the Chimera roamed the countryside of Lycia in Asia Minor terrorizing towns until King Lobates asked Bellerophon to slay the Chimera. In fact, the King didn’t think Bellerophon would succeed (which is a sort of back story to the myth), but in any event Bellerophon rode Pegasus (the winged horse) into battle and slayed the Chimera.
Ever since Greek times, the notion of a being formed by different parts fused together into one, has held a fascination. In fact, modern science has established that the fusing of genetic material from two (or more) sources can come about either by accident or by intention.
As an example, if you visit a garden or a farm, you’ll likely encounter fruit trees or flowers where the top half of the plant (or an individual branch) has been grafted on to different root stock or trunk. The top half of the plant may have desirable features like scented flowers, for example, or the grafted branches may bear desirable fruit, but growers have grafted the plants together because they know the plant will better survive with heartier root stock. That grafted plant is a deliberately created chimera.
Can People be Chimeras?
The short answer is yes. Scientists actually don’t know how commonly this happens because the condition isn’t routinely tested. There are different kinds of chimerism, but according to scientific literature, about 100 cases in human beings have been documented.
The explanation in the three cases above, is that the mother or father in each of these cases was initially conceived as fraternal twins, but early in gestation, one of the twins dissolved and was absorbed into the surviving twin. The surviving twin had no reason to know he or she once had a fraternal twin. It wasn’t until the events described above that these people were diagnosed as having two distinct sets of DNA (DNA is, of course, the abbreviation for deoxyribonucleic acid).
The scientific term for people with complete duplicate sets of DNA at birth is called “tetragametic chimerism.” Such children are born with both their own full set of DNA and the DNA from the absorbed fraternal twin.
By the way, modern medicine can create human chimeras in other ways such as bone marrow transplants (where the bone marrow of the donor may produce blood with the DNA of the donor instead of the recipient). People who receive organ donations from other people or from animals are also considered chimeras. In those cases there is no mystery as to why a person tests positive for a duplicate set of DNA.
There are also cases where people are born with something less than two full sets of DNA, cases where fraternal twins trade chromosomes with each other prior to birth, and cases where mothers retain DNA from babies (sometimes referred to as “pregnancy souvenirs”), but the examples above involved tetragametic chimeras.
How Often Does This Happen?
The National Society of Genetic Counselors (“NSGC”) website explains “The majority of individuals with chimerism remain undiagnosed, so we are not sure how many people have this condition. However, we know that 20 to 30 percent of singleton pregnancies were originally a twin or a multiple pregnancy. Due to this statistic, it is quite possible that tetragametic chimerism is more common than current data implies.”
The NSGC explain “most often a person’s health is not negatively impacted by chimerism. A diagnosis may, however, change your life by gaining insight into unexplained events.”
What Does It Mean?
If you watch enough crime shows on TV, it seems almost axiomatic that once the cops find the criminal’s DNA, the verdict is in the bag, right? In fact, cases have been reported where the police incorrectly eliminated a suspect because of a chimeric-influenced DNA result.
On a more profound level, with the exception of those of us born with an actual twin, haven’t we been led to believe each of us has a single unique set of DNA? Our DNA has almost come to signify something like our own personal bar code assigned by nature or a higher power. But what if that’s not exactly true for all of us?
How do we know if we are a chimera? Scientific literature suggests people with different eye colors or significant patches of different pigmentation may be more likely to be chimeras. Where the original fraternal twins were different genders, this may affect reproductive capacity.
There have been at least two documented cases where children conceived through IVF were confirmed to be chimeras. According to some experts on this topic, the likelihood of a child being a chimera increases if the child is conceived through the IVF process.
Most human chimeras look like anyone else. The only way to be certain as to whether any of us might be a chimera is actual genetic testing and at this time there is no reason for widespread testing.
What Comes Next?
In the United States around twenty people die each day due to a shortage of donor organs. Given this fact, the goal of fighting other illnesses (like certain cancers) and the need to test new therapeutic drugs, scientists in several countries have been working on cross species DNA experiments.
Generally the closer the two species being tested, the more successful the crossing. For instance, rat DNA can be used to help mice develop missing organs. Sheep and goats are close enough that DNA infusions have been successful within those two groups.
Human DNA has also been injected in pig embryos in the hopes of creating organs that would be available for transplant into human patients in need of organs. The human cells injected into pig embryos survived for up to four weeks, but the number of surviving embryos was a small fraction of the initial number of trial embryos.
In China, a team of Chinese and U.S. scientists successfully merged human DNA in monkey embryos, but of the 132 chimeric embryos cultured, most died before day 17 of the experiment. That said, according to a report in The Guardian, by day 15 several of the combined embryos still contained around 4% — 7% of human cells.
The Island of Dr. Moreau
If you’ve watched late-night horror movies, you’ll have come across the Burt Lancaster movie “The Island of Dr. Moreau” based on the 1896 science fiction novel by H. G. Wells. There have actually been at least seven movies based on this H. G. Wells novel. The basic plot is that Lancaster, mad scientist and recluse, has fused animals and people to create a tribe of human-like animals who eventually rise up against him. Whether you re-read the Wells novel or watch one of the film versions, it’s worth having another think about human-animal chimeras given the direction in which science is headed.
Is some authority watching to make sure chimera experiments don’t go too far? According to a report in Nature, “ethical oversight falls mainly on local institutional review bodies. Their decisions on whether an experiment is permissible are typically informed by guidelines produced by the International Society for Stem Cell Research… The U.S. National Institute of Health, meanwhile, has been essentially silent on the topic since it stopped funding research involving embryonic human-animal stem-cell chimeras in 2016.”
For some, the idea of using animals to harvest organs or for medical testing is already over the ethical line. For others, the ethical danger of creating animals with the central nervous system, cognition or features of human beings is over the line. The list of other ethical concerns includes welfare and “ownership” of chimeras that include human biology and for some, the violation of human dignity.
Then there’s the risk of creating new zoonotic illnesses (meaning illnesses capable of passing between animals and people like HIV aids, plague, Lyme disease, rabies, West Nile Virus and Covid 19, among others). So there’s that.
At this point researchers believe they can limit the risk of creating human-animals through the timing of DNA fusion as well as editing those parts of DNA that would create neurons or contribute to reproductive function.
But sometimes scientific researchers make mistakes and maybe some researchers won’t be as scrupulous as we might hope. Even if such scientific limits are observed, such limits don’t address the other ethical and scientific concerns mentioned above.
Will guidelines and funding decisions keep pace with the capabilities of biological experiments? Can we even reach consensus on what experiments and procedures are ethical? Regardless of ethical limits that may be determined in the United States, other counties could certainly reach different conclusions about permissible scientific research.
In a paper published by the International Society For Stem Cell Research in October 2020, the authors candidly observed “Science will not sit idle.”
Sources used in preparing this article: Daily Beast, European Journal of Medical Genetics, Insider.com, International Society For Stem Cell Research, Journal of Law and Biosciences, National Society of Genetic Counselors, Nature, New England Journal of Medicine, New Scientist, Scientific American, Stanford Medicine — Department of Genetics, The Guardian and Wikipedia.
© 2022 L. E. Langner. All rights reserved.
