Lyman BioPharma Consulting LLC

Advice and Resources for the Biotech Industry

Advice and Resources for the Biotech Industry

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Biomedical Ethics: Moral Dilemmas with Lives in the Balance

A couple of years ago I had coffee with a young woman with a strong interest in bioethics. She was looking at potential future career paths, with a possible focus on biotechnology. I shared with her my observation that I had never heard of a biotech company actually employing a dedicated bioethicist. The lack of these positions in the industry, however, doesn’t negate the fact that a wide variety of ideological dilemmas are currently front-and-center in the halls of biomedicine. These complex issues call out for the wisdom of King Solomon to help point us in the right direction. Here are just some of the challenges we currently face:

CRISPR Babies: Is This Powerful Technology Ready for Prime Time?
CRISPR is a revolutionary, game changing technique that’s been widely used in laboratories worldwide to gain new biological insights via a variety of model systems. Trailing behind the initial lab work was a widespread hope that at some point the technology would move to the clinic and be used to save patients’ lives. It’s for this reason that venture capitalists helped start a number of companies to commercialize this new approach to modifying the DNA within cells. Many thought the first applications of this approach would be to correct errors in the DNA in individuals afflicted with diseases caused by single gene defects, such as Duchenne muscular dystrophy or hemophilia. Instead, the recent announcement that Chinese scientist He Jiankui had used CRISPR to modify the fetal DNA of two little girls so that they might be protected from HIV infection after birth ignited a firestorm of controversy for a number of reasons. This genetic brouhaha wasn’t confined to the West. Even in his home country the Chinese Academy of Medical Sciences objected to the “experiment”, saying Dr. He had violated “the laws, regulations, and ethical norms” of his native land. Even more troubling: a government review has led to accusations that He forged ethical review documents. Many worry that He’s efforts will set back research programs on CRISPR, thereby echoing the poorly planned gene therapy study that resulted in the tragic death of Jesse Gelsinger decades ago and set back the field of gene therapy for years.

New Pain Medications: Helpful Drugs, or Drivers of the Opioid Epidemic?
Most of us take over-the-counter pain medications, but occasionally we need something stronger, and our doctors give us a prescription for a codeine-containing drug. For some people, however, even these medications won’t relieve their suffering from continuous, unremitting pain. Several drug companies responded to this perceived need by bringing some uber-potent new painkillers to market. Zogenix introduced Zohyrdo ER, an extremely strong narcotic (it’s a long-lasting version of hydrocodone). While the drug may indeed be extremely beneficial for those with unremitting pain, critics have pointed out that it’s also likely to be abused and it might lead to fatal accidental overdoses. This concern led Governor Charlie Baker of Massachusetts to ban the sale of this pill in his state. Zogenix countered by suing in Federal Court to get a restraining order against the Governor’s actions.

Zohydro ER isn’t the only new narcotic out there. The U.S. military requested a strong, fast-acting pain medicine for use on their battlefields. AcelRx Pharmaceuticals responded by developing sufentanil (brand name Dsuvia), which the FDA approved in Nov. 2018. These tiny tablets contain a painkiller that is 10 times more potent than fentanyl (recently shown to be the largest contributor to drug overdose deaths in the U.S). Not surprisingly, drug abuse experts once again expressed concerns that this synthetic opioid will be diverted from the Armed Forces to become yet another lethal high in the back alleys of America.

Fetal Tissue Research: Government Restrictions Threaten to Impede Progress
New potential regulations from the U.S. Department of Health and Human Services threaten to curtail the use of fetal tissues in biomedical research. The use of these tissues will once again be the subject of a review that promises to look at the “serious regulatory, moral, and ethical considerations” involved. This subject has been a minefield for years, going back to the presidency of George W. Bush. In 2001 he introduced a ban on federal funding of research involving newly created embryonic stem cell lines derived from human embryos. The fact that some researchers need to use tissues derived from embryos or aborted fetuses to move their science forward lies at the heart of the problem. This issue really boils down not to a scientific discussion, but to a personal, deeply-felt (and in many cases religiously-based) feeling that this is something that should simply not be allowed in society. For a more in-depth review of this subject, see A guide to fetal tissue research: the controversy, the stakes, and the hunt for alternatives.

Right-to-Try Legislation: A Hidden Minefield for Desperate Patients
In May 2018 President Trump signed into law new federal legislation that governed the ability of seriously ill patients to obtain access to experimental drugs. While this new “Right-to-Try” law was passed to help the sickest patients, it may actually generate more problems for them. Some politicos have widely implied that biopharma companies and/or the FDA were the primary impediments to patients being able to gain access to potentially life saving medications. That was never the case. Most biopharma companies were happy to supply their drugs to needy patients, and the FDA rapidly approved >99% of these requests. Those companies that didn’t wish to supply their drugs were never required to do so, and they can still withhold the requested medicines, even under the new legislation. So what are the problems with this new law? Critical protections afforded to patients under FDA guidelines for clinical trials can be circumvented, and drugs that have barely entered the FDA-mandated testing process could be given to patients, with drug makers completely shielded from liability. Any deaths or injury caused by drugs under this legislation cannot be considered by the FDA in deciding whether or not to eventually approve or deny an application to sell the drug. And if a drug provided under this legislation sickens a patient, insurance companies don’t have to pay for treatment of that complication. Patients may also lose insurance coverage for hospice care. It’s for all of these reasons that some terminally ill patients stepped forward to voice their opposition to this new legislation.

Life-Saving Vaccines: Denial Campaigns Threaten Progress
Vaccines are widely recognized as one of mankind’s greatest achievement for promoting health and well being, along with nitrogen-based fertilizers, antibiotics, delivery of clean water, and sanitation systems. However, disinformation campaigns against vaccines in general, and a few vaccines in particular, have put our nation at risk. These stories are too numerous to count. An optional Arizona school program to educate children about the scientific benefits of vaccines was pulled this year when a small number of parents objected. Disgraced doctor Andrew Wakefield and his fraudulent autism/MMR vaccine hoax have put millions at risk. A misinformation campaign about the HPV vaccine has contributed to significant declines in vaccination rates in many countries. In Japan, the vaccination rate for girls fell from 70 percent to about 1 percent, even though the bad science at the heart of this scare was debunked, and government doctors were unable to find any evidence the vaccine was harmful. Whatever their reasons for promoting these bogus claims, these denial campaigns only serve to Make Infectious Diseases Great Again.

Genetically Modified Crops: Saving Lives, or Dangerous Foods?
The labeling of GMO (Genetically Modified Organism) foods is yet another contentious issue with biology at its core. The vast majority (around 85%) of foods available at your neighborhood supermarket contain GMO ingredients, even though they are not labeled as such. The U.S. House of Representatives recently voted to ban states from passing or enforcing laws that require the labeling of GMO foods. This is actually a political issue, because science turns out to be the one element that’s frequently missing from any discussions of whether or not such labeling should be allowed for GMO foods.

Let’s focus on a specific example of where fear and misinformation are trumping science. Golden rice is a variety of this staple crop that’s been genetically engineered to produce beta-carotene, a precursor of Vitamin A. It was developed as a humanitarian food source to help children who suffer from a deficiency of this essential nutrient. It’s estimated that Vitamin A deficiency leads to 1-2 million deaths worldwide each year along with a half a million cases of irreversible blindness. This rice could have a significant impact in fighting this international health care problem, but it’s not been successfully commercialized for a number of different reasons. These include a general opposition to genetically engineered foods in many countries, a desire to enact alternative approaches to attacking food deficiencies that go beyond Vitamin A-engineered rice, financial concerns, and a well-established distrust of corporate control of agricultural products.

Breakthrough Drugs: Ultimate Medicines, or Engines of Bankruptcy?
Whether or not the Affordable Care Act survives its recent court challenge, it’s clear that healthcare costs continue to rise, especially on drugs. Some pharma companies held their prices down last year due to withering criticism from President Trump, although across the industry drug prices actually went up. However, these companies have now indicated they’ll be getting back to their normal pattern of twice-yearly price hikes on many medications. Most Americans have no idea just how expensive many specialty drugs have become. A list of the 20 most expensive drugs (based on their list prices for a monthly dose) showed these ranged from $25K to more than $52K. These drugs actually look inexpensive when one looks at the prices of specialty medications for rare diseases. The most expensive drug currently is Glybera, priced at more than $1.3M per year (and not currently available in the U.S), but there are plenty of others that cost hundreds of thousands of dollars. A curative gene therapy treatment for spinal muscular atrophy, which may only have to be given once, may be priced in the four million dollar range. Diabetics in particular have taken to protesting after seeing their health put at risk by the constant escalation of insulin prices. Many of them have attempted to solve this problem by posting Go Fund Me campaigns to pay for the medicine that keeps them alive. Trying to delineate the fine line between affordability and company profitability remains a challenge, exacerbated by biopharma’s unique government monopoly business model and the strong need of consumers to manage their health.

Other bioethical issues that affect society include the use of gene drives to potentially eliminate disease-carrying organisms, sequencing the DNA of newborns to identify disease susceptibility, privacy concerns arising from the ability to identify anonymous people using their “de-identified” DNA sequence profiles, and the funding of patient advocacy groups by pharma companies who stand to profit from their efforts. Politics is once again looking like a primary driver of healthcare policy. There was a time at the turn of the last century when the “science” of eugenics developed a passionate following in the United States. Much of the enthusiasm for eugenics was driven by the passions and prejudices of the upper crust of American society. As a result, this field was only slowly abandoned when the “science” behind it was shown to simply have no evidentiary support. Eugenics advocates supported laws that restricted immigration, not just for economic reasons, but also because of fears that allowing outsiders into our country would spread disease and criminality. Here we are a century later, and these same misguided arguments are being pushed by some of our supposed “leaders” even though they still have no factual basis.

Then as now, people turned to the Supreme Court to help clarify and settle the issues. In one of the most egregious decisions ever made by our highest judicial panel, the court ruled 8-1 in Buck v. Bell that “a state statute permitting compulsory sterilization of the unfit, including the intellectually disabled, for the protection and health of the state" did not violate the Due Process clause of the Fourteenth Amendment to the United States Constitution.” The courts have never overturned this decision. It’s clear that Supreme Court decisions often reflect ideological and political differences, whether between the justices on the court, or driven by the tides of opinion that sweep across our country. We might hope that scientific decisions are guided by a set of facts using a highly rational process on which nearly all agree. Clearly, they are not. Climate change is one area where there’s a crystal clear disconnect between what the science says and how the Trump administration has responded. We need to employ more than a gut feeling to make decisions that may put the health and well-being of millions of people worldwide at risk. Moral dilemmas must be clearly debated and conclusions reached by the application of the best scientific evidence we can muster.