Twenty-Five Years After My House Call To Dolly: What Have We Learned About Cloning And How Did We Learn It? – Forbes

Twenty-five years ago, the scientific breakthrough of mammalian cloning marked a monumental moment in medicine and science. Anticipating the collision it would have with ethical decision making in medicine, I, the only physician-scientist in the U.S. Senate at the time, journeyed to the University of Edinburgh in Scotland to personally visit Sir Ian Wilmut at his research lab at the Roslin Institute.

My house call to Dolly in 1997: I stand with Dolly, the first ever mammal to be cloned from an adult ... [+] somatic cell, during my journey to visit her creator and caretaker, Sir Ian Wilmut.

Professor Wilmut just months before in 1996 had cloned a sheep from an adult somatic cell, shocking the world. This was the first successful attempt of its kind. All over the world people were wondering: would we be cloning a human being next? We talked science, we talked ethics, and we talked about his creations potential impact on altering the course of human history. I also met and examined the cloned sheep, Dolly, in her stall.

Dolly, named after Tennessees own Dolly Parton, was a Finnish Dorset sheep cloned from a single, adult mammary gland cell. Her creation, birth, and short life were scientific feats that immediately sparked global concern and discourse on the increasingly complex moral and ethical dilemmas posed by a sudden discovery of life-manipulating science.

Wilmut and colleagues published their achievement in February 1997, having kept Dolly secret for seven months. We, as a society, were quickly forced to answer difficult, probing questions. A few months later on the Senate floor, I borrowed a question that the Washington Post editorial board had posed a few years before: Is there a line that should not be crossed even for scientific or other gain, and if so where is it?

Here are my remarks in the Senate chamber in 1998:

So it is vital that our public debate and reflection on scientific developments keep pace, and even anticipate and prepare for new scientific knowledge. The moral and ethical dilemmas inherent in the cloning of human beings may well be our greatest test to date. We do not simply seek knowledge, but the wisdom to apply that knowledge. As with each of the mind-boggling scientific advances of the last century, we know that there is the potential for both good and evil in this technology. Congressional Record February 2, 1998

Years removed, I now reflect back on the confusion, questions, and status quo that Dolly challenged.

Dolly was the first mammal to be successfully cloned from an adult somatic cell, which is any type of bodily cell that is not a reproductive germ cell. The process Wilmut developed is technically called somatic cell nuclear transfer, colloquially known as cloning. It is the process of transferring the nuclear DNA of a donor somatic cell into an enucleated oocyte, followed by embryo development and then transfer to a surrogate recipient, followed by live birth.

Dollys creation in a test tube and eventual birth marked a major milestone in scientific research, suggesting that an animal could be cloned to create an exact replica using genetic material derived from theoretically any type of body cell. It opened the world to staggering new possibilities in reproductive cloning and therapeutic cloning.

Soon after Dollys birth, another parallel and similarly monumental finding was made: in 1998 embryonic stem cells were discovered. These cells are a highly unique type of unprogrammed somatic cell with the exceptional ability to both reproduce unlimited exact copies of themselves and develop into more specialized cell types, such as heart, lung, kidney or skin cells. And though seemingly miraculous in potential, these cells could not be created or programmed from any other type of cell and could only be collected from embryos an ethical dilemma because collection for research required destruction of the embryo itself.

Dolly changed this. Her successful creation paved the way for future scientists to develop a technique to independently produce equally powerful pluripotent stem cells by reprogramming other adult somatic cells, revolutionizing genetic therapy, and completely nullifying the ethical dilemma of collecting embryonic stem cells from embryos. Similarly, Dolly also highlighted the potential for scientists to create new tissues and organs for diseased patients, and to preserve the genetic material of endangered species.

But, along with these positive contributions came widespread concern about the ethics of cloning, especially around potential attempts to clone another human being. Many, including myself, feared this type of technology, if left unregulated, would be misused and abused. Indeed, cloning evoked great scientific power that demanded even greater ethical responsibility, and there were no established ethical guardrails at the time to monitor this duty.

In retrospect, these fears have diminished in part due to proactive measures and to the inherent complexities of the human genome (cloning an entire human being is, after all, a large jump from cloning a sheep). Importantly, legislative and scientific communities have been resolute and unified in their opposition to cloning human beings.

Though a human embryo was indeed successfully cloned in 2013, no known progress has been made when it comes to attempts to clone a human being. Yet the technique to create Dolly has been repurposed widely and has led to numerous scientific innovations.

In 2003, six years after her birth, Dolly became sick and was euthanized. Her decline in health was due to the development of tumors in her chest; some examinations of her cells suggested that she was also aging prematurely.

Despite her relatively short life (the average sheep lifespan is ~10-12 years), Dollys influence on the scientific community has been profound. Not only did she force scientists and researchers to redefine the ethics of their field, but she also laid the foundation for other significant scientific advancements in the fast-evolving new field we know today as regenerative medicine.

One powerful example is gene therapy and editing, where specific genes are targeted, edited, and repaired to protect against disease, cancer, autoimmune disorders, and even rewiring immune system cells for treatment-resistant cancer patients. This revolutionary innovation is made possible by CRISPR technology (the same technology that enabled rapid vaccine development for COVID-19), which is currently celebrating its 10-year anniversary.

Genetic cloning was also made possible thanks to Dolly. This is a type of cloning where scientists create copies of genes within DNA segments to combine with plasmid DNA, or self-replicating genetic material, and then place this new plasmid into a host organism, such as a bacterium, yeast, or mammal cell. This process is used to develop vaccines and antigen tests and is also used to identify useful genetic traits in plants, which can be replicated on a larger scale through the genetic modification of seeds.

Further, cloning techniques have also helped to advance agricultural practices. Farmers can use cloning technology to quickly introduce favored characteristics of prize livestock (such as the ability to produce large amounts of high-quality milk) into a herd by cloning and breeding. These livestock will then further reproduce using traditional breeding or assisted reproductive technology.

Despite advances in genetic cloning and agricultural practices, cloning especially the additional attempts at cloning whole organisms remains variable and highly inefficient.

Successful attempts have been made by companies like Sooam Biotech Research and ViaGen Pets to clone dogs and kittens for wealthy pet owners. But, even today, the success rate of animal cloning is estimated to be less than 30%. In fact, many animal rights activists oppose the practice citing animal welfare. In 2015, the European Union banned the practice of livestock cloning.

Overall interest in cloning slowed as advances in adult stem cell research gained traction in the 2000s. This resulted primarily from scientists newfound ability to take adult human cells, for example skin cells, and reprogram them back into an earlier, more primitive but more powerful embryonic-like, pluripotent cells.

This technique was pioneered by Japanese scientist Shinya Yamanaka in 2006, for which he was awarded the 2012 Nobel Prize in Physiology or Medicine. Yamanakas discovery of reprogramming already specialized adult cells to create induced pluripotent stem cells (IPS) took the ethical issue of destroying embryos for research off the table. Some scientists continue to look to cloning as a way to develop genetically unique stem cells that can be used to reduce the risk of triggering an immune response.

Notes taken shortly after my visit with Dolly: "She has been seen by 2.5 billion people."

We have come a long way since my exploratory journey from the Senate floor in Washington, DC, to the stall and research laboratory that housed Dolly in Edinburgh in 1997.

For all the controversy that Dolly sparked during her short life, her contributions to society have been nothing short of remarkable. She forced thought leaders, researchers, and policymakers around the world to confront the ethics of cloning. And, she encouraged us, as a society, to weigh in and engage on the ethical considerations of increasingly frequent scientific discoveries.

On all of these fronts, we worked tirelessly to instill and adhere to a strong scientific code, focusing on the bettering of science, innovation, and technology for societal good. Cloning gave us that first glimpse into the future.

As I said on the floor of the Senate on February 3, 1998:

This cloning debate, I think, maybe for the first time in the history of this body [the US Senate], forces us to address what is inevitable as we look to the future, and that is a rapid-fire, one-after-another onslaught of new scientific technological innovation that has to be assimilated into our ethical-social fabric. Congressional Record February 3, 1998

What I said then still holds true today, Science and ethics must march hand in hand. Congressional Record February 11, 1998

Visit link:

Twenty-Five Years After My House Call To Dolly: What Have We Learned About Cloning And How Did We Learn It? - Forbes