“Lead us. Evolution, lead us
Up the future’s endless stair,
Chop us, change us, prod us, weed us,
For stagnation is despair:
Groping, guessing, yet progressing,
Lead us nobody knows where.”
— C.S. Lewis “Evolutionary Hymn”
The daunting pace of advances in bio-technology has far exceeded our ability to grasp the range of possibly positive and plausibly threatening consequences. This presents us with enormous ethical challenges in deciding how to proceed. Today it is hard to name outstanding figures who can speak with the authority of those scientists of a generation or two ago. As you will be able to read at the end of this blog, they most forcefully expressed their ethical concerns and their doubts, fears, and scientific aspirations.
When faced with serious genetic problems ranging from cancer to Alzheimer’s and from blindness to deafness, should scientists simply march ahead and work on ultimately altering the sequences of embryonic DNA produced by afflicted parents? Strong objections to such a course are being raised, arguing that this would interfere with the natural processes of life or even that we are brazenly trying to take over from God! The implications are, that once we start altering our hereditary potentials, there is no end. At first we may only be making corrections on single-cell disorders such as sickle-cell anemia, hemophilia, and Tay Sachs, but before long we would switch to making improvements — ultimately struggling to make humans more perfect or even more compatible with mechanical intelligence. As Herbert J. Muller wrote some 80 years ago: “We will reach down into the secret places of the great universe of its own nature, and by aid of its ever growing intelligence and co-operation, shape itself into an increasingly sublime creation.”1
The immediate challenge at hand is CRISPR. About three years ago, scientists developed a technology that is literally upending our perspective on the limits of biotechnology. It has become known as CRISPR-Cas9 which is similar to a biological word processing system allowing scientists to cut and paste the strands of DNA almost as easily as it is for me to change the lettering in this blog. (FYI: CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats.) CRISPR involves taking a strand of RNA, a chemical messenger, to target a section of our DNA and using an enzyme (a nuclease) that can cut unwanted genes and paste in the edited RNA. This sequence borrows from a process in nature that scientists have harnessed to snip and splice sections of DNA. To make this possible researchers found a specific slicer enzyme called Cas9.
This technological advance is key to the synthetic biology and gene editing revolution and represents an amazing improvement over existing techniques. However, alarm bells started to ring when scientists in China reported in April 2015 that they had used CRISPR for the first time to alter the DNA in a non-viable embryo. (That is, an embryo that could never have developed into a baby.) A group of 18 eminent scientists, legal experts and ethics specialists published a letter in Science calling for an immediate moratorium on experiments of this kind on embryos. Dr. Jennifer Doudna, one of the co-inventors of the CRISPR technique, wrote that “My colleagues and I felt it was critical to initiate a public discussion of the appropriate use of this technology, and to call for a voluntary ban on human germline editing for clinical applications at the present time.”
Henry Greely, a Stanford law professor and expert in ethics, who was another of the signers of the Science letter, said “You would be insane and criminally reckless to make a baby this way without 15 to 20 years of testing and proving that it was safe.” Many other scientists contended that far from being threatening or wrong, such research has the potential to provide permanent cures for genetic diseases. Further research also holds the potential to correct common disease defects such as metabolic disorders, diabetes and age related problems as well as creating cells that attack tumors or others that are resistant to HIV infections.
The National Academy of Sciences (NAS) and its Institute of Medicine consequently announced it is convening an international summit this December to “explore the scientific, ethical, and policy issues associated with human gene-editing research.” In addition, NAS will appoint a multidisciplinary, international committee to study the scientific basis and the ethical, legal, and social implications of human gene editing. Together this represents a concerted effort to confront the bio-technological challenges now facing mankind. In some ways this conference ultimately could prove as important for our future on this planet as the major Environmental Conference to be held by the United Nations at almost the same time in Paris.
Getting a clearer picture on the science behind CRISPR is important. So is developing an international guideline for gene editing. But the National Academy of Science’s meetings seem to have overlooked how much work and ethical expertise it will take to identify and assess the ethical issues surrounding CRISPR. There is concern that ethics has taken and will continue to take a back seat to science in discussions about CRISPR. The existing ethical frameworks are simply not adequate for managing the challenges posed by the new gene editing technology.
This is because CRISPR is unlike previous biotechnologies. The ethical frameworks that were developed for dealing with IVF, cloning, and stem cell research a generation ago are not adequate for dealing with the novel ethical concerns raised by CRISPR.
For example: CRISPR can introduce new variations in germlines, making permanent biological changes to future generations. This may be uncontroversial when it comes to preventing life-threatening diseases, but controlled human evolution has been suggested many times since Darwin, often with permanent, racist and disastrous consequences. Equally important, our genetic makeup is the result of changes, mutations, radiation, jumping genes and other additions. Like knowledge, our DNA structure is the result of millennia of additions. There is no natural mechanism which allows for the kind of subtractions involved in CRISPR. Could we now accept any justifiable, ethical philosophical or scientific objections to subtraction?
Deletions made on human genes could have unintentional and unpredictable consequences for future generations who might regret that this was done without their consent. We simply do not understand the operations of the human genome sufficiently to make long-lasting changes to our DNA. Altering just one gene could have unforeseen and widespread efforts on other parts of the genome which could then be passed down to future generations.
Laws in the UK ban genetic modification of embryos for clinical uses, but they are permitted in research labs under license from the Human Fertilization and Embryology Authority provided that the embryos are destroyed after 14 days. In the United States researchers are much freer, but there are deep concerns that genome editing is so simple and cheap that maverick scientists could use the procedure to modify human embryos which could be implanted into women.2 Dr. Francis Collins, Director of the National Institutes of Health, said back in April that the US government would not fund research for modifying the embryo DNA because there were “serious and unquantifiable safety issues” as well as significant ethical questions and no compelling medical reasons to carry out the research. While scientists and lawmakers might be able to control most of the global research taking place, there is little that can be done to stop experimentation taking place in a country like North Korea or corporations that might pursue their narrow commercial interests. The application of CRISPR techniques has resulted in a flurry of investment and commercial activity. Editas Medicine, which was granted a patent (being challenged by other applicants) to use in plants and animals, has raised $163 million from a group of investors over the past two years.3 And the pharmaceutical giant, AstraZeneca, plans to develop its use in cell cultures to explore the function of every gene in the human genome.
When it comes to bio-technology there are no deniers, but many opponents. Edward Lamphier, the founder of Sangamo Biosciences, wrote in Nature that genome editing in human embryos “could have unpredictable effects on future generations.” This makes it “dangerous and ethically unacceptable.”4 In an interview with Gina Kolata of the New York Times he added, “It literally boils down to: How do you feel about the human race and the human species?”5
The psychologist Steven Pinker, writing in an editorial for the Boston Globe, protested that CRISPR was a key to reducing human suffering and incurable diseases. Pinker maintained that bioethicists should not get in the way of progress. As it is, some research scientists already have become bogged down in red tape, bureaucratic restrictions, or sanctions based on unclear consent forms. To then impose moratoria or threats of prosecution based on such sweeping principles as “social justice,” rapidly could slow down progress and ultimately lead to scientists operating outside any agreement.
To the question: “Should we ever move forward with human germline genome editing,” 61% of the polled members of the Science Advisory Board, an international community of tens of thousands of scientific and medical experts, voted in favor and 39% voted against, but when asked: “Should we hold a moratorium on human germline genome editing?” 70% said “yes” and only 30% opposed. The ethical dilemmas facing the experts evidently could obstruct the tools which would give many future generations healthier and longer lives. Even in an impatient age when quick decisions almost have become obligatory and attention spans are on a steady decline, no effective decision on this dilemma is likely soon.
Personally, I would propose that the world put a hold on all laboratory experimentation in this area until and unless it is approved by an international body of experts operating under the aegis of some kind of new biological “security council” with enforcement powers. Nothing less will suffice.
1Herbert J. Muller, Out of the Night: A biologist’s view of the future, (1935)
2Ian Sample: “GM embryos: time to decide,” The Guardian, September 2, 2015, p. 1
3“Briefing Genome editing,” The Economist, August 22, 2015
4“Don’t Edit the Human Germline,” Nature, March 12, 2015
5Gina Kolata, “Gene Editing and Safety: Alarm Grows.” The New York Times, May 10, 2015
“Gene splicing and editing are going to change life on earth, both physically and economically. What is at stake in this biotechnical revolution is the ultimate ‘perfectibility’ of plants, animals and people.“ Yorick Blumenfeld Towards the Millennium: Optimistic Visions for Change, (1996) p.382
“[Humanity] will reach down into the secret places of the great universe of its own nature and by aid of its ever growing intelligence and co-operation, shape itself into an increasingly sublime creation.” Herbert J. Muller, Out of the Night: A biologists view of the future (1935)
“When does a ‘repaired’ or ‘manufactured’ man stop being a man… and become a robot, an object, an industrial production?“ Salvador Luria, “Modern Biology: A terrifying Power,” The Nation, October 20, 1969
“The human species is biologically an extraordinary success, precisely because its culture can change ever so much faster than its gene pool. This is the reason cultural evolution has become adaptively the most potent extension of biological evolution. For at least 10,000 years … man has been adapting his environments to his genes more often than his genes to his environment, It may be said that man has escaped from the clutches of his biological past and has become to some extent the master, rather than a slave, of his genes,” Theodosius Dobzhansky, Mankind Evolving (1962 ed.) p. 319
“If this thing is ever possible technologically, it will happen. It is no use expecting international agreements to stop it, or a self-denying ordinance among scientists, In fact, most of us, if the power were given us, would be morally confused, For the first application of genetic engineering almost certainly would be to eradicate the grosser genetic misinstructions — that is the prescriptions that produce dystonia or spina bifida or mongoloidism or other fearful forms of human suffering.” C.P. Snow (1973)
“…instead of shouting “no!” we should examine whether we could direct the course of evolution. We should then ask if- and how- we could control the pace at which we might proceed. And we should ask what we could do to adjust human beings to the personal and social consequences of seemingly unstoppable advances of biotechnology.” Jean Rostand, Can Man Be Modified? (1959)
“In the light of evolutionary biology man can now see himself as the sole agent of further evolutionary advances on this planet…Ever since he first began, man has been groping to discern the features of his destiny more clearly. In the light of the evidence now available, he could come to the realization that his destiny is to participate and lead in the creative process of evolution where new possibilities can be realized for life.” Julian Huxley, Evolution in Action (1953) p. 132
“Finally, consciousness itself may end or vanish in a humanity that has become completely etherealized, losing the close-knit organism, becoming masses of atoms in space communicating by radiation, and ultimately perhaps resolving itself entirely into light. That may be an end or a beginning, but from here it is out of sight.” J.D. Bernal, The World, the Flesh and the Devil, (1929), p. 113.
“What would this Man? Now upward will he soar,
And little less than Angel, would be more
Alexander Pope, An Essay on Man (1733)