Dr. He, Theatrics or Therapy?
Recently Dr. He Jiankui, from the Southern University of Science and Technology in Shenzhen China, created an uproar in the medical community when he anounced he used CRISPR-Cas9 technology to perform, what he called, “gene surgery” on the DNA of embryos, naturally produced by a man and a women. Dr. He said his surgery eliminated the CCR5 gene, used by Human Immunodeficiency Virus (HIV) to enter and infect host cells and cause HIV to occur in children resulting from the maturing embryos. The father was afflicted with HIV and so the parents had avoided conception to avoid their children being afflicted with AIDS.
Condemnation of Dr. He’s work was swift and hyperbolic. It centered on Dr. He’s claim that he edited genes in two human embryos, created when germ cells ( sperm from the father and egg from the mother) united to create the embryo.
It appears that Dr. He was not using CRISPR-Cas9 “to repair” damaged DNA. Rather he used the CRISPR technology to cut-out the CCR5 gene, used by Human Immunodeficiency Virus (HIV) to enter and infect host cells and cause HIV to occur in children resulting from the maturing embryos.
In an LA Times interview with Michael Snyder, the director of the Center for Genomics and Personalized Medicine at Stanford University. Dr. Snyder notes that “germ-line editing, such as Dr. He performed, is “more consequential” than editing somatic cells in an individual. He notes, as do others, that editing the germ cells can result in unintended changes elsewhere in the DNA. These unintended changes can be harmful and may be passed from generation to generation. Further, the procedure has not been tested on primates to ensure its safety.
In Dr. He’s case the ethical issue appears to be compounded:
- He not only “operated” on germline cells which can be inherited by future generations without complete understanding of the implications for those generations
- Also he didn’t “repair a damaged gene”! Rather he cut-out a naturally-working gene ( CCR5 gene), all-be-it one that can lead to AIDS — acquired immune deficiency syndrome
Dr’ He’s work is particularly problematic when as Dr. Kevin Lee, Chief Scientific Officer Grace Science Foundation, writes
“Most diseases play out in the body’s somatic cells, not in “germline” cells from which genetic information is passed on to subsequent generations. Gene editing-based treatments in somatic cells for life-threatening illnesses is an area of tremendous medical need, and is not subject to the same ethical concerns as genetic manipulation of human embryos.” —
Taking all of the above into consideration it certainly appears as if Dr. He’s use of CRISPR-Cas9 was more theatrical than therapeutic. While he says he demonstrated that CRISPR-Cas9 can be used to eliminate a potentially lethal gene, he did so using germeline cells that will be inherited by any children born to the women whose genes he edited.
In 1998 oncologist Dr. Ian Tannock wrote “for the next few years, cancer management, outside the context of a clinical trial, will continue to be based almost entirely on surgery, radiation therapy, and systemic treatment with chemotherapy or hormones.” While the best techniques medicine has to offer at the time, all three of are used after cancerous genes have afflicted tissue and organs, quite brutal compared to what may be available by editing the parts of a patient’s DNA/genes that give rise to the cancerous tissue.
““Two things — huge attention to Angelina Jolie’ s preventive double mastectomy and a drop in the cost of genetic testing — changed the world very dramatically,” says Dr. Allison Kurian, an oncologist and an epidemiologist at the Stanford University Medical Center. The genetic testing that five years ago cost $4,000 and was not covered by insurance is now about $250 and broadly accessible.”
It’s now possible, Dr. Kurian says, to test for mutations on as many as 40 genes associated with breast cancer. “As a result, there has been a complete about-face in the field,” she says. “Our problem is no longer purely getting genetic information.
Almost every known multicellular organism gets cancer. Almost every known cell type in the body (breast, lung, testicle, etc) can become cancerous.
“What struck me from the outset is that something as pervasive and stubborn as cancer must be a deep part of the story of life itself. Sure enough, cancer is found in almost all multicellular organisms, suggesting its origins stretch back hundreds of millions of years.” — Dr. Paul Davies
For Dr. Davies and his colleague Dr. Lineweaver, another cosmologist and astro-biologist, the behavior of cancer cells is anything but berserk. The origins of cancer did not lie in some random mutation making all these cells go berserk. The origins of cancer must lie in the origins of life itself.
Dr. Davies says “cancer is a highly organized, systemic method of survival. It’s no accident that cancer survives everything the body throws at it. It’s not a random collection of genetic mutations. Developing those specific attributes is as likely as throwing a pile of bricks into the air and having them land exactly as a house. Considering the body’s massive deployment of weaponery to kill cancer cells, it is impossible that cancer survives only as a freak accident.”
“The effects of CRISPR were thought to be unpredictable and seemingly random, but by analysing hundreds of edits we were shocked to find that there are actually simple, predictable patterns behind it all. This will fundamentally change the way we use CRISPR, allowing us to study gene function with greater precision and significantly accelerating our science.” — Paola Scaffidi, Cancer Epigenetics Laboratory
It’s beyond time for the medical community to take back “gene surgery” from the theater and aggressively apply it therapeutically and as systematically as cancer itself thrives and survives. Hundreds of thousands afflicted by the “Emperor of All Maladies” despearately deserve the relief such an approach may offer. We, the families of those who are afflicted, need the medical community to supplement the cutting knife of the surgeon with the molecular knife of the geneticist.
Even before that we need the geneticists to identify the hundreds of genes that are the source of all types of cancers ( See — International Cancer Genome Consortium — ICGC, http://www.icgc.org/home ) so that genetic therapies can be developed and applied.) This is work now being carried-on by teams of researchers lead by Associate Professor Rolf Skotheim, affiliated with the Centre for Cancer Biomedicine and the Research Group for Biomedical Informatics at the University of Oslo.
According to Dr. Skotheim, “this is a matter of millions of nucleotides that must be mapped correctly in the system of coordinates of the genetic material. Once we have managed to find the RNA versions that are only found in cancer cells, we will have made significant progress. However, the work to get that far requires advanced statistical analyses and supercomputing," That is why Dr. Skotheim’s teams are using one of the world's fastest computers to detect which versions of genes are only found in cancer cells.
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Notes:
3 Dr. Vincent T. DeVita, Jr. M.D. The Death of Cancer, Sarah Crichton Books, New York 2016
4 Beyond the Somatic Mutation Theory of Cancer — Dr. Jason Fung — Medium ( https://medium.com/@drjasonfung/beyond-the-somatic-mutation-theory-of-cancer-f71854acd05d )
6 https://medicalxpress.com/news/2015-02-supercomputing-reveals-genetic-code-cancer.html
