UK Opens Public Consultation on Draft Regulations to Permit “Three-Person Embryos”
Posted by Jessica Cussins on March 6th, 2014
The UK Department of Health has released draft regulations and begun a three-month public consultation for what it terms “mitochondrial donation.” After the consultation concludes, final regulations will be written and then put before Parliament for a vote. According to media reports, it is possible that licensed fertility clinics in the UK could offer the techniques before the end of this year.
These controversial oocyte and embryo manipulation techniques, which would result in trans-generational changes to the human genome, have also been widely covered in the US media recently. Last week’s FDA public meeting to discuss them coincidentally took place two days prior to the UK’s announcement, which had been expected for months.
Certainly, each country is watching the other. Perhaps neither is quite sure it wants to be the first to violate the widespread international agreement against modifying the human germline, and incur the controversies that will inevitably ensue. But there also are those in both countries who are eager to stay at the forefront of a new biomedical field.
If the FDA pays any attention to what came out of its advisory committee meeting, it will require much more substantial research to be carried out prior to human clinical trials. For now, the UK is further along in its policy process. Unless members of Parliament are made aware of the many social and safety concerns raised by these techniques, a “rubber stamp” vote could be in the works. Based on the 47-page document the Department of Health has released, there are many reasons for concern.
MISREPRESENTATIONS IN THE SUMMARY
What should we call it? One of the document’s misrepresentations is its title. “Mitochondrial Donation” is the most euphemistic terminology for these techniques I’ve seen. As the document acknowledges, it’s not mitochondria that are being moved around; the techniques actually involve “the transfer of nuclear material between eggs and embryos.” And, of course the term “donation” is a well known euphemism for what really occurs in the market for women’s eggs.
How many people are affected? The “Executive summary” gets off to a bad start. The second and third sentences say,
“It is estimated that 1 in 200 children are born every year in the United Kingdom with some kind of mitochondrial DNA disorder. Serious mitochondrial disease can have a devastating effect on families including the premature death of children, painful debilitating and disabling suffering, long-term ill-health and low quality of life.” This framing will certainly encourage readers’ sympathy for anything that can lessen this level of devastation. But it is extremely misleading. While it is true that about 1 in 200 people have some kind of mitochondrial mutation, the vast majority are completely healthy. Most accounts clearly acknowledge this. But you have to make it to page 41 of the Department of Health’s document to come across the explanation that
“Mitochondrial disease currently affects around 12,000 people in the UK, with one in every 6,500 babies born with a form of the disease. The technique being legalized here will apply to the most severe cases in the first instance. An estimate provided by the Wellcome Trust Centre for Mitochondrial Research at the University of Newcastle suggests mitochondria donation treatment could apply to up to 10 cases per year initially.” That paints quite a different picture.
GM humans? The document’s sole mention of the highly problematic fact that, if approved, these techniques will result in genetically modified babies, is in one paragraph that states that they would “only substitute, rather than alter” DNA. Though this is an important distinction to make in writing regulations, the child’s DNA will be altered. In fact, the paragraph concludes that “it would though be a form of germ line modification.”
Is there really public support? In its discussion of last year’s public consultation conducted by the Human Fertilization and Embryology Authority (HFEA), the document does note that the majority of people who responded to the open questionnaire (which – with over 1,800 responses – had by far the largest numbers) were opposed to the technique. But it downplays the importance of this fact, saying that these views were from “a self-selected sample,” as if that should discredit them. On the contrary, the fact that this was the only section of the public consultation in which participants were not hand-selected by those in charge of the process says a lot.
What will it cost? A truly fascinating part of the document is the section that projects what these procedures would actually cost for the women who are interested in them. The estimated cost of a successful “mitochondria donation treatment” is 80,000 pounds (about $133,000). This cost accounts for two rounds of standard IVF to extract eggs from two women, one round of PGD to test for the presence of mitochondrial disease in the extracted embryos, and an assumption that it will take four cycles to generate a successful conception.
This price tag puts the proposed treatment out of reach for most people. Further, the document notes that “it is possible that this is an under-estimate of the actual cost.” That does seem likely, since there are important differences from traditional IVF that would likely drive up the costs. Finding egg donors would be more time consuming and expensive because each would have to undergo additional examination to make sure they have no mitochondrial mutations of their own; only a handful of embryologists have the skills to carry out this procedure; and it seems highly unlikely that success rates using these techniques would mirror those of traditional IVF.
CONCERNS WITH THE REGULATIONS
As the Department of Health document explains, when the UK in 2009 decided that the country’s law prohibiting human germline modification could be amended to allow mitochondrial manipulation techniques down the road,
“the Government of the day gave an assurance that such regulations would not be made until any proposed techniques were considered to be effective and safe for use in treatment.”
As Dr. David King, director of Human Genetics Alert, recently pointed out,
“The techniques have not passed the necessary safety tests so it is unnecessary and premature to rush ahead with legalization.”I agree. Nonetheless, here are some comments on the draft regulations as they currently stand.
Less risky alternatives. The Department of Health’s draft regulations set two preconditions for eggs and embryos that can be used in this procedure: they must have a particular risk of mitochondrial abnormality, and there must be significant risk that a person with this abnormality will develop a serious disability or illness. I think a further condition ought to be set: that there are no safer alternatives available. Given the UK clinics that already offer embryo screening (pre-implantation genetic diagnosis, or PGD) for the prevention of the transmission of mitochondrial disease, and the growing evidence of its efficacy in most cases, candidates for oocyte or embryo modification should consider it first.
Mandating no disclosure to children. The draft regulations state that at the age of 16, a person who thinks they were born following this technique could ask the HFEA for confirmation and view information on their donor’s medical history, but would not be given access to the donor’s identity. The regulations also say that women who provide their egg cytoplasm and mitochondria are determined to be “not related to any children who were, or might have been, born following treatment services using their donation,” so
“therefore no provision is made to allow access to information in connection with entering into a marriage, civil partnership or intimate physical relationship, nor to access information about other children who share the same donor.” This seems short-sighted. Even though the HFEA thinks that mitochondrial donors should be treated more like organ donors than gamete donors, we don’t know whether any kids that are born will feel the same way.
Though the chances might be low, I do think it’s possible that the UK will decide not to move forward with these experimental techniques. The document notes that
“The Government has decided to proceed with regulations. However, before taking the decision to submit regulations for the scrutiny and approval of Parliament, we will ask the HFEA to reconvene the Expert Panel a further time to provide an updated assessment of the safety and efficacy of these techniques.”
It adds that “When the amendment was made no commitment was given on a timescale for making regulations,” and in response to opposition at that time, it was determined that they would only be used “once the techniques involved were considered to be effective and safe for use in treatment.”
Could this be a hint that some of those involved want a potential out? The safety and efficacy of mitochondrial manipulations were just considered in detail at the FDA meeting, and a long litany of problems emerged. Hopefully, the UK Department of Health and the members of Parliament will take note. For that reason, taking part in this public consultation may turn out to be very important.
Previously on Biopolitical Times:
Litany of Unknowns Surface at FDA Meeting on Germline Mitochondrial Techniques
Posted by Jessica Cussins on March 6th, 2014
An FDA committee held a historic public meeting last week to discuss the scientific, technologic, and clinical issues related to experimental procedures that would alter the human germline. The February 25-26 meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee was webcast live, and will be available in archived form in a couple of weeks.
What was most striking about the meeting was that the committee members, many of whom are scientists themselves, are so wary of the techniques at this time. Questions about efficacy and safety – in fact a litany of concerns about every aspect of these techniques – largely dominated the discussions. And although the FDA’s pre-meeting briefing document explicitly put social and ethical issues outside the scope of the discussion, a myriad of these problems also edged their way in.
I highly recommend watching the webcast of the first day – particularly the afternoon session, which included public comments, discussion by committee members, and a summary of the deliberations by chair Evan Snyder. But if you don’t have time for that, please read on for an overview of what transpired.
The beginning of the first day was devoted to scientific presentations, most by researchers who are developing mitochondrial manipulation techniques: Gerald Shadel of Yale University, Salvatore DiMauro of Columbia University, Marc-André Sirard of Université Laval, Keith Latham of Michigan State University, Shoukhrat Mitalipov of Oregon Health and Science University (OHSU), Dieter Egli of Columbia University and the New York Stem Cell Foundation Research Institute, and Mary Herbert of Newcastle University.
The work described by Mitalipov at OHSU and by Herbert at Newcastle University has enjoyed the lion’s share of media attention. Their labs have been conducting animal and in vitro research on spindle transfer and pronuclear transfer, two of the mitochondrial manipulation techniques proposed as ways to enable women affected by mitochondrial disease to have unaffected and genetically related children. Both research teams are eager to move to human clinical trials in their respective countries.
After the research presentations, time was scheduled for public comments from people who had contacted the FDA in advance. Seven people were each given four minutes to speak; among them were Marcy Darnovsky, Executive Director of the Center for Genetics and Society; Jaydee Hanson, Director of the International Center for Technology Assessment; Stuart Newman, Professor of Cell Biology and Anatomy at New York Medical College; Enola Aird, Founder and Director of Mothers for a Human Future; and Sheldon Krimsky, Professor of Urban & Environmental Policy & Planning and Public Health and Family Medicine at the Tufts School of Medicine. (Links on their names go to samples of their writings on this issue.)
Not one member of the public spoke in favor of the techniques. The points raised by the speakers included these:
- If the FDA were to approve these techniques, it could be the first time any jurisdiction in the world had authorized intentional genetic modification of children and their descendants, and the agency would be making this decision with little or no input from the public or elected officials.
- The FDA is the wrong agency to have jurisdiction over such techniques.
- These techniques could be a gateway technology for human cloning and germline engineering.
- Any child resulting from this procedure would develop from a fertilized egg in which the non-mitochondrial maternal genes derive from a second woman, the intended mother, a situation with potentially harmful biological incompatibilities and deleterious trans-generational impacts.
- Approval of clinical trials would represent an unprecedented level of human experimentation for which there can never be truly informed consent.
- These techniques would pose risks to young women recruited to donate their eggs.
- Preferable alternatives for having healthy children are available to the small number of women who would be candidates for these techniques.
- These techniques may not be specific enough to prevent further attempts at inheritable genetic engineering.
- There has already been “mission creep” in proposals for applications of these techniques: the discussion has moved from considering them solely for the prevention of serious disease to also considering them for some cases of infertility.
The committee’s discussion followed. While different members seemed to lean in different directions about whether the techniques should move to clinical trials – some seemed in favor, some against, some undecided – the discussion was notable and informative because of the range and seriousness of the safety concerns raised by a large majority of them. (A roster of committee members gives their titles and affiliations.) Linda Dahlgren pointed out that data for clinical trials are not sufficient, and that the studies carried out so far have limited relevance as a proof of concept. Douglas Diekema said that, as head of an IRB, he would need to see larger sample sizes and long-term follow-up in the animal studies before he would be able to give approval. Sharon Reeder spoke as a woman who has mitochondrial disease about the huge physical toll giving birth took on her body, landing her in a wheelchair. She noted that it’s extremely challenging for children to live with chronically ill parents, and that she hopes more research will be done on treatments for people who already have mitochondrial diseases.
Larry Couture pointed out that we can’t predict the impact of these kinds of modifications down the line and that grading blastocysts is a not a good enough measure of health. He also refuted the argument that babies born to mixed-race couples could tell us anything about the health of babies resulting from these experiments, since they have inherited genes from two, and not three, people. Steven Goldman noted that in vitro trials will need to be very specific about which mutations in which tissues they are supposed to be treating, adding that the variability of mitochondrial diseases may make rigorous interpretation of clinical trials impossible. Tabassum Ahsan pointed out that better metrics would be needed for quality control of donor oocytes, and that it will be very difficult to define success in any trial. Timothy Cripe asserted that the bar for any pre-clinical trials will have to be high, given that this isn’t a treatment for sick people.
David Keefe’s remarks were particularly compelling. Apologizing for quoting Donald Rumsfeld’s notorious comments about “weapons of mass destruction” in Iraq, Keefe said, “There are things we know. There are things we don’t know. And there are things we don’t know we don’t know.” As a reminder, he cited the outcomes of DES and thalidomide, and argued that we must tread lightly. He asserted that using the techniques in question to treat infertility “should be taken off the table” and added that even using them to prevent the births of children with mitochondrial disease is a “very very slippery slope.” He pointed out that the US doesn’t regulate the fertility industry like the UK does, and that sick patients will put their trust in their doctors, who have a responsibility not to give them false hope.
Katharine Wenstrom reiterated that these patients are particularly vulnerable and that pregnancy for women with mitochondrial diseases can be extremely dangerous. She added that the inability to know whether the techniques had caused new problems for a child would be a huge burden for parents. John Gearhart expressed frustration over the term “mitochondrial manipulation or replacement” since technically it is nuclear replacement, or egg/embryo manipulation. Renee Reijo Pera commented that without first trying to develop techniques to see whether affected women might produce healthy eggs, we’re “over-engineering.” She noted the de facto “pact” against genetic manipulation of human embryos, and later told USA Today, "I just don't think that this is an avenue that we should pursue in humans."
In his summary remarks, committee chair Evan Snyder concluded that the discussion’s common theme had been the shared concern for the well-being of children born as a result of mitochondrial manipulation techniques. The sense of the committee, he said, was that there is not enough data either in animals or in vitro to move on to humans, and that these concerns involved both the preclinical data and the basic science. He asked: Are there better alternatives? What’s the unmet clinical need? And is this worth the risk? Acknowledging that some committee members found the data “very intriguing,” he went on to note that many felt that no one research model would be perfect. He added that long-term follow up in animal studies, of larger sample sizes, will be crucial; and that some studies may need to be mutation specific.
What will the FDA do next? The agency has not actually revealed whether it has received any formal proposals to approve clinical trials. And though it is not required to follow the guidance of its advisory committees, it often does. After the meeting, FDA press officer Jennifer Rodriguez told Reuters, “We have heard the concerns expressed at the advisory committee meeting, and will take the information back to consider whether we need to facilitate a public discussion and, if so, how best to do this.”
Chair Evan Snyder told reporters that he does not think the committee or the FDA will address the topic again within the year, though it will likely come up again after more animal research has been completed.
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Human Longevity, Inc.
Posted by Pete Shanks on March 6th, 2014
Craig Venter, the genomics and synthetic biology pioneer, launched a new company on March 4, Human Longevity, Inc. (HLI). The press release describes it as:
a genomics and cell therapy–based diagnostic and therapeutic company focused on extending the healthy, high performance human life span
HLI has raised $70 million, enough for 18 months of operations, partly from Illumina, which makes genome sequencing machines, two of which HLI has bought so far. The rest is from a few venture capitalists and/or individuals (details are sketchy), several of whom have invested in Venter's Synthetic Genomics company, which he will also continue to run.
The company seems to be put together by a tightly-knit group with multiple interconnections in the biotech and broader techie and indeed transhumanist world. The official co-founders are Venter, Bob Hariri, of Celgene Cellular Therapeutics, and Peter Diamandis, best known for the X Prize and Singularity University.
Diamandis seems to be the main fundraiser, which may explain the investment of the noted transhumanist Martine Rothblatt, who inter alia was executive producer of the documentary The Singularity Is Near. Hariri is a trustee of the J. Craig Venter Institute and on the advisory board for the Archon Genomics X Prize, which is chaired by Venter and connects them both with Diamandis.
The new company already has partnerships with the Venter Institute, Metabolon Inc., whose Scientific Advisory Board is graced by Venter and his colleague Hamilton Smith, and the University of California, San Diego, which has four representatives on the HLI Scientific Advisory Board.
It's a small world, right?
Asked on this conference call if HLI would be in touch with the new Sanford Stem Cell Clinical Center, Venter blandly noted that Larry Goldstein, who heads the Center, is on the HLI advisory board. Diamandis added:
"Stay tuned for more announcements on the stem cell side."
HLI seems to be squarely focused on the growing contingent of aging, and sometimes affluent, baby boomers. According to The New York Times:
Dr. Diamandis said the goal was not to make people live forever, but rather to make "100 years old the next 60."
It's not entirely clear how they are going to do that, but genome sequencing certainly comes into it. Venter has spoken casually about sequencing everyone in the country, with one focus being to find protective alleles: he himself has a "slightly increased risk" for Alzheimer's but shows absolutely no sign of amyloid plaque buildup (about 5:00 in this video), so "obviously, I have genes that are protecting me from getting Alzheimer's disease."
Stem cells are somehow relevant, and HLI will be sequencing cancer tumors as well as whole genomes. However, when pressed by Science writer Elizabeth Pannisi (on the conference call) as to how they could legally and ethically make commercial use of patients' data gathered for research the best Venter could come up with was:
"We're still working out a lot of these issues."
They face some stiff competition, including:
- BGI, the Chinese sequencing behemoth, which leaked plans for a partial $400 million IPO later this year, also wants to sequence the world (don't miss the movie); Venter claims that his Illumina machines are newer and better than BGI's Illumina machines but "we can't have enough players.
- The Google-backed Calico, which now features Ray Kurzweil (still hoping to be "functionally immortal"), remains tiny so far but hopes to produce "the ultimate disruptive technology."
- Editas, the genome editing company founded by, among others, George Church, may overlap with Venter's market. Church seems skeptical about HLI, whose plan he thinks is "all over the place."
- Knome, a whole-genome-analysis company (founded by, among others, George Church) closed a $13 million financing round in January.
- P5, a Sony-Illumina-M3 collaboration, was supposed to launch in February; it may be delayed but it seems to be part of a well-thought-out effort on the part of Sony to move heavily into the emerging high-tech medical market.
Venter, of course, is undaunted. He still firmly believes in the medical and commercial benefits of genomics. Asked if his vision for HLI was the same as his vision for Celera back in the 1990s, "where information from genomes would be sold to subscribers to lead to new therapeutics and diagnostic tests," he replied:
"This is Celera on steroids and cocaine."
Really? That's an ill-advised metaphor. How much better the company will do than its predecessor remains to be seen. Are Venter, Diamandis and Hariri talking themselves, as well as their investors, into a technophile fantasy of genetic omnipotence?
Previously on Biopolitical Times:
Amanda Knox and DNA Contamination
Posted by Osagie K. Obasagie on February 27th, 2014
The trial of former American exchange student Amanda Knox captivated much of America a few years ago – at least those who are fans of Nancy Grace. Her conviction for murdering housemate Meredith Kercher in Italy and subsequent acquittal were daily fodder for many newsfeeds. Thus, it should be no surprise that her retrial and recent conviction for the very same murder has rekindled the obsession that many have with this case.
Central to the inquiry is what, if any evidence, links Knox to the Kercher murder. Knox’s retrial led to new DNA tests on a knife that prosecutors said could be the murder weapon. But Greg Hampikian – founder and director of the Idaho Innocence Project – voiced serious concerns about this evidence. From the BBC:
some independent forensic scientists told the BBC this knife (which had been considered a possible murder weapon) should never have been given the importance it was because there was no evidence of blood found on it. . . . "I could see the problem with the case right away," says Dr Hampikian. . . .
A knife recovered from Sollecito's house was found to have Ms Knox's DNA on the handle and a small amount of DNA on the blade "consistent with the victim". . . . [Hampikian said] "That is significant because Miss Kercher had never gone to that house, so what is she doing on the blade of the knife? "While that may seem on its face to be evidence of a crime, in order to substantiate such a small amount of DNA you look for blood, and I can't emphasise enough how small this was - it was just a few cells." But there was no evidence of blood or any other body fluids found, the Boise State researcher points out. "You can't really wash the blood off and leave the DNA in any practical sense. That means that the few cells or molecules might have been from the laboratory after they amplified Miss Kercher's DNA," he explains. . . .
This concern was not his alone. There have been claims that the initial evidence was handled using dirty gloves and that investigators entered the crime scene without protective clothing. . . . To highlight how easily contamination in DNA evidence can occur, Dr Hampikian's team carried out a demonstration. They picked up used drink cans wearing clean gloves and then placed a new knife into an evidence bag without changing gloves. The knife was subsequently found to have tiny fragments of traceable DNA which had been transferred from the can.
The contamination of crime scene evidence has been known to falsely implicate suspects. While countless hours have been spent on this case, perhaps this is one area where the Italian courts should spend a little more time.
Previously on Biopolitical Times: