How to Get Away with Murder Ivy League Style

Woe to the inhabiters of the earth and of the sea! for the devil is come down unto you, having great wrath, because he knoweth that he hath but a short time (Revelation 12:12).

There was no preventing the death by gene therapy of 18-year-old Jesse Gelsinger.  I tried.  Free will was exercised.  I am not the judge, and neither is any other person.  The Lord is the one and only Judge.

Scientists wish to genetically engineer people and plants.  In people, this means replacing or compensating for a defective gene by introducing a functional version of the defective gene into the body to treat, if not cure, the disease.  Usually the correct DNA is introduced into the body via a genetically-engineered virus.

Gene therapy was first attempted in 1990 to treat a genetic disorder called adenosine deaminase severe combined immunodeficiency (ADA-SCID), or boy in the plastic bubble disease, which results in vulnerability to infectious diseases so extreme that the patient may be forced to live in a sterile environment.  The first gene therapy patient only experienced a temporary benefit.  Several patients in France developed leukemia after receiving gene therapy for an immune deficiency during the late 1990s and early 2000s.  Leukemia was easier to treat in young children than SCID, they said, if they survived.

In September of 1999, 18-year-old Jesse Gelsinger ended up sacrificing his life in effort to advance gene therapy from an experiment to a cure for those to come after him with the same genetic disorder resulting in a liver disease.

These setbacks could only hold back the field of human gene therapy for so long.  Today, more than 2300 clinical trials using gene therapies are in progress, according to Genetic Engineering & Biotechnology News, July 1, 2017.  On July 12, 2017, it was announced that FDA Panel recommends approval for gene-altering leukemia treatment.

I ended up in the field of human gene therapy during the pursuit of my PhD degree during 1993 to 1997.  Really, I just went to graduate school to find out how something we cannot even see can kill us, like the human immunodeficiency virus (HIV).  To earn a PhD degree in a hard science field, you must discover new knowledge, take courses, teach undergraduate students, publish or perish, and pass demanding comprehensive examinations (written and oral).

During the oral portion of my qualification examinations to determine whether or not I was even qualified to continue pursuing my PhD degree, I was unexpectedly interrogated as a Nazi by all but one of the then-members of my thesis committee.  They questioned whether it was appropriate for them to allow someone like me, genetically German, to be in the field of human gene therapy.  They asked me questions about which genes or characteristics I felt were superior.  It went on to the point where I began crying hysterically during the exam and could not stop crying for days afterwards.  I was crying in the bathtub.  I seriously considered quitting with a Master’s degree.  But my husband said, “I think you should finish it.”  When I asked him why, he replied, “because you started it.”  He was right, and I got out of the tub.  The one member of my PhD thesis committee who was absent during my qualifying exam turned out to be a real scientist and a real friend, and I somehow managed to change who was on my PhD thesis committee.

After I gave my thesis defense (oral presentation in the big auditorium, I was so nervous), the professors who had been the nastiest to me along the way approached the podium with tears in their eyes to tell me it was the best defense they had ever experienced.  As my PhD advisor taught me so well, success is the best revenge.

 

Once I earned my Doctor of Philosophy title, I thought I knew a thing or two.  And then I received a lesson in coercion.

Jim came to Indiana University School of Medicine in Indianapolis to give us a lecture.  He came from the Ivy League on the east coast.  I could get in to Harvard University when I graduated high school near the top of my class, but the cost of attending was out of my league.  Too bad, I thought, because only the people who have that pedigree can make it in this construct.  But now, finally, my redemption had maybe arrived, or so I thought.  Jim was one of the most famous gene therapy researchers in the world.

The Ivy League has connotations of academic excellence, selectivity in admissions, and social elitism.  It is a collegiate athletic conference comprising sports teams from eight private institutions of higher education in the Northeastern United States, but the conference name is commonly used to refer to those eight schools as a group beyond the sports context.  Seven of the nine Colonial Colleges chartered before the American Revolution are Ivy League institutions.  The origin of the name lies in the ivy-covered older college buildings long revered by the students.  Indeed, it was customary for students to plant ivy at university buildings each spring in the 1800s.  Wikipedia

Jim’s real motive was to scout out a new slave to bring adeno-associated virus technology to his lab.  I despised his weak character immediately, but he wanted me.  If I agreed to go to his lab, then I could graduate.  If not, then I would have to be a student for at least another year.  Jim wanted my PhD advisor’s vector, and I think my PhD advisor wanted something from Jim’s lab, too (maybe a vector, but I seem to remember shipping him something).  Also, I think my PhD advisor, from India with short, bald, brown man syndrome, wanted in the old boys’ club.  Apparently, I was needed to bridge the relationship between the labs and ensure material transfers, which seems pretty ridiculous if all were simply on the up-and-up.  But this is the pattern of how things are done – not in writing, not provable, no data.  And that’s why when you’re in that situation, you’re fucked.

I went to Jim’s lab with my PhD degree.  There were 20-30 people in his lab, mostly PhDs and MDs.

It was an “open space” lab concept (one giant open lab with row after row of work benches) to promote collaboration, but it was not a collaborative environment.  Well, what do you expect when 1,000 of you are going to compete for the same job?

What was the definition of success?  Dr. Ho, for example, published a very high-profile paper on HIV resistance.  Turns out it was a contaminant.  That’s the nature of science, they said.  And it won’t hurt Ho’s reputation at all.

Peer-review is too political.  It’s hard to be righteous in a system where the self-serving are in power.  Righteousness is feared and gets punished.  The system favors those who make decisions based on politics rather than right versus wrong.

Jim was smart, but only in the sense of memorizing and copying.  He was not at the level of creating new and unique contributions.  Jim played the intimidation game, but I wasn’t afraid of him and that made him nervous.  I think he wanted to fuck me, and that made me nervous.

He asked me where I was living.  When I told him where I had rented an apartment in a huge, old house, he freaked out and said that I could not stay there under any circumstances because it was too dangerous!  He was right about that.  The only twist is that my animal spirit is the puma who travels back and forth between the light and dark places, everywhere, anywhere, at will and by nature.  Fuck his unfunded mandate.  Philadelphia is outrageously expensive, complete with an extra 10% city tax.  My annual salary was about $28,000 before state, federal and city tax.  My husband lived in another state, and we had to pay a lot to visit each other.  At Christmas, Jim invited his laboratory workers to his mansion house for a party.  Others swooned with envy of his wealth and status while I fought back the nausea.

I carried my S&W Tactical .40 cal semi-auto pistol with me everywhere to keep those crack addicts at bay lest those eyes glowing a sickly yellow in the dark shadows decided to jump out at me from behind the bushes.  Maybe it was the confidence I had in my ability to defend myself (I got several guys off at the shooting range, which I took as a good sign), or the bulge of my gun at my side, or the hard look in my eyes, or all of the above that made it clear I would not be an easy victim.  It is surprising how lazy people are, especially criminals.  And so, the puma jumped from perch to perch to take in the views.

I didn’t believe the data I saw every Monday morning during our 8:00 am lab meetings.  Jim would tell the Chinese Research Associate what he wanted, and the Chinese guy would ALWAYS produce it, without fail.  Clearly this was not science.  The data were too clean, too fast, too perfect, and they always confirmed the predetermined hypothesis.

I spoke up during lab meetings and asked fundamental questions.  The data were not generated by conventional, accepted methodologies or presented in the standard formats, so direct comparison was not possible and the data were not convincing.  There was intense opposition to doing it the standard way.

One of the MDs had been a neuropathologist, pathology specialty.  The “health maintenance organization (HMO),” a medical insurance group, said we don’t need so many doctors and cut his job out.  What an oxymoron HMO is.  The MD had a wife and kids and needed a job, so he, too, worked for Jim.  The MD did gene therapy experiments on monkeys.  He was deeply disturbed about the monkeys’ hematocrits.  I know this because the MD’s lab bench was adjacent to my own and he was suffering right along with those monkeys he was using.  The monkeys were sick, and I got the feeling some were even dead or dying.

A conflict of interest is a situation in which a person or organization is involved in multiple interests, financial or otherwise, one of which could possibly corrupt the motivation or decision-making of that individual or organization (Wikipedia).  Jim started Genovo, a for-profit biotechnology company funding the clinical trial.  Both the university and Jim had financial interests in Genovo.  Jim also chaired the department of molecular and cellular engineering at the university.  In his university lab, research was being done for Genovo, which paid the university for their services.  Jim’s lab received $2.8 million a year from Genovo.  The ties between Jim’s lab, the university, and Genovo were so entangled that the university created a conflict-of-interest committee to oversee the Genovo relationship.  A fox in charge of the hen house, clearly.  If the gene therapy trial would have worked, it would have meant company money and university money, patents, and maybe even the Nobel prize.  Ambition and drive to make a breakthrough are also sources of conflicts of interest.

Science is set up to encourage over-specifying.  There is always a desperation to publish or you will surely perish.  And in this context, science works you to death, robs you of friends and family, and still it’s never enough.  You don’t have time to think.  You’re pointing the finger, and they are wielding clubs.  It is a real-life David and Goliath situation.

“Do you think my lab is bamboozling me?” Jim asked me during a meeting between the two of us in his office during which I confronted him.

“Yes!” I replied, emphatically.

But he wouldn’t slow down.  Egomaniac.  Sociopath?  God complex.

The rationalization to go too fast is that we learn the most the fastest by making mistakes.  And yes, some people will die, but it’s for a good cause and, indeed, that’s the necessary sacrifice to potentially benefit others.  A fundamental, philosophical issue is the risk-to-benefit ratio.  Assessment of the risk-to-benefit ratio is very subjective.  The benefits also include huge profits for certain stakeholders, and I have no doubt that assessments of risk versus benefit would be different if considerable financial incentives were taken out of the equation.  Unfortunately, you probably also must think about removing fame and glory to avoid recklessness behavior of unchecked, selfish, immoral and unethical egos.

Risks of human gene therapy include the risk of generating novel recombinant viruses that are virulent and that threaten us all!  It may sound far-fetched, but it has likely already happened.  A novel virus was certainly generated inadvertently during my experiments.

I discovered wild-type AAV-like virus particles, but my PhD advisor did not believe me.  Nobody ever believes anything I say!  I finally convinced him, though.  And then he took the discovery from me and gave it to a co-worker to sequence the viruses and bury my name in the least important position in the list on the front of the publication.

 

Some argue that the origins of HIV are from SIV in monkey cells used to make vaccines for Africans.  Some even argue it was purposeful versus accidental contamination.

The problem is that everyone is afraid to speak up.  Like during our orientation at the Mayo Clinic, it was made clear that if you make accusations, for sure it will go in your file and then an investigation will be conducted.  Plus, when people are bullshitting and being rewarded for it (e.g., Dr. Ho above), it encourages more of the same.

I was in Jim’s lab for 5 months, from Oct. 1997 to March 1998.  I left because I saw the inevitable train wreck coming and could not be a part of it since I am not a Nazi.  Sure enough, about a year and a half after I left, Jesse died (Sept. 1999).  Everyone told me it was career suicide when I quit Jim’s lab, especially once they heard my ridiculous and crazy reason for leaving.  My husband, the Archangel Michael, was the only one who understood and believed me.  Even the head of the department where I had earned my PhD degree made it clear that I was not welcome to come back there.  He was the same guy who begrudgingly nominated me for the Kinsley Award (only one nominee per department), and then I won!  He wanted to nominate a Korean guy who did research overlapping his own, but that guy’s thesis was too poorly written.

“No one could have predicted such a response as was seen in Jesse,” they said.  Yet, immune responses to viral vectors were being studied in Jim’s lab and results were being published.  Immune responses elicited by viral vectors were destroying infected cells, thereby diminishing expression of the “therapeutic” gene.

I think that Jim gave Jesse too much virus in a desperate measure to achieve therapeutically efficacious levels of recombinant protein OTC (ornithine transcarbamylase) and prove efficacy.  I think Jim figured that Jesse was young and strong and could handle it.  The 18th subject enrolled in the study in 1999, Jesse was dead four days after receiving the experimental treatment.  His immune system reacted fiercely in attacking the adenovirus vector.  Following an adenovirus-induced fever, he suffered jaundice and was comatose by the second evening after receiving treatment.  A cascade of organ failures ensued:  a blood clotting disorder, a catastrophic rise in ammonia levels, kidney failure, lung failure, and ultimately brain death.

Too much virus means more virus administered than could be justified based on pre-clinical safety studies in monkeys and rodents.  Later, it came out that monkeys died and those deaths were not reported to FDA and were not disclosed to human subjects in the process of gaining their consent.

Informed consent failed as evidenced by the fact that Jesse’s parents did not even accompany him to Philadelphia for the trial.  They thought the risk was lower than it actually was, and didn’t realize that the potential outcome of the experiment could be death.  Of course, the possibility of death was probably mentioned somewhere in the fine print of the consent form, like on forms you sign before horseback riding, rafting, or entering an amusement park.

FDA only knows what they are told!

Protocol violations included: (1) double blood ammonia level than original level and enrolled anyway, (2) four prior patients in the experiment had adverse events, (3) monkeys died and were not reported, and (4) risks were downplayed to the parents.

Robert Erickson, University of Arizona, Tucson, also raised concerns, also to no avail.

“Don’t be driven out of the field,” an ethics professor told me.  Ha!  Leaving Jim’s lab was deemed career suicide.  When I told my PhD advisor I feared that Jim would kill someone, he scorned and said, “if that were going to happen, then it would have happened already.”  He regarded me as crazy and told me he would lock me up in an insane asylum himself if only he could.  This was the same man who had repeatedly told me that he saw it written on the side of a bus in India that “it’s nice to be important, but it’s even more important to be nice.”  Consider small colleges, the ethics professor advised me.

I remain disappointed in Jesse’s father that he took the money in the end (undisclosed settlement amount).  Ironically, Gelsinger became guilty of the same flaw that killed his son.  I think Paul Gelsinger raised a lot of awareness because he is super smart and quite verbally eloquent.  Therefore, I believe he could have raised even more awareness if he had continued the fight versus settling.  But I am not the Judge!

Another very interesting aspect of this case is that there was no perceived benefit to Jesse himself for participating in this trial.  The patients this therapy was ultimately meant to cure were infants born with a more severe form of OTC deficiency, which can result in death within the first days of life, or coma, developmental delay, mental retardation, progressive liver damage, etc.  It was considered unethical to perform the gene therapy trials in infants, so people like Jesse with a less severe form of this rare metabolic disorder were enrolled in the trial.  This is in interesting contrast to proposed pesticide trials.  In the case of pesticides, it was considered unethical to conduct formal trials in humans to determine safe levels of ingestion over time, because there was no benefit to the subjects.  A conundrum, for some.  Instead, most people are unconsented subjects with no monitoring or follow-up.  So, how is it ethical to test gene therapy in subjects like Jesse, but not ethical to test pesticides in willing subjects? It’s not!

I am telling this story now in fulfillment of my duty as an artist to reflect the times because now is the time described in the Book of Revelation.  Now is when it is most important for you to know the truth.  And what is the truth?  God is the truth.

I have achieved the highest level of education and great success as a scientist against great odds.  At times, I have not had enough to eat.  At other times, I have eaten the fanciest meals in the fanciest castles with the fanciest royalty.  Still, I have found nothing other than the Lord to believe in.

How do we know that this is Armageddon?  The necessities of water, food, shelter, clothing, and footwear have been taken under the control of evil forces.  “Big business and science are run by selfish individuals who see nature as objects to be exploited,” said Mae-Wan Ho as a senior research fellow at Open University in England.

Genetic engineering of crops has been going on even though scientists have submitted strong cautions and evidence substantiating their concerns.  People opposed to genetic engineering are concerned about the risks of altered genes escaping into non-crop plants and the risks of pests, such as insects and viruses, developing a resistance to genetically modified plant pesticides.

We need to be moving away from unsustainable food production back to sustainable food production.

The corruption is so widespread that I believe this is the time described in the Book of Revelation.

FDA approved AquaBounty Technologies’ application to sell AquAdvantage salmon to U.S. consumers on November 19, 2015.   The decision marks the first time a genetically-modified animal has been approved to enter the U.S. food supply.  To create salmon that grow faster, AquaBounty Technologies added a growth hormone-regulating gene from a Pacific Chinook salmon with a promoter from an ocean pout to the Atlantic salmon’s 40,000 genes.  Wikipedia

This frankenfish does not even have to be labeled as such in the grocery store.  There are concerns that the wild salmon population could be driven to extinction by relatively few AquAdvantage salmon.  There are also concerns about the genetic stability and the long-term effects on consumers and the environment of this risky and unnecessary technology.  Cheating often comes with dreadful consequences.  Forgive them for they know not what they do.

What if it is Armageddon?  It is better to trust in the Lord than to put confidence in man (Psalms 118:8 KJV).

Therefore, I am a huge proponent of organic marijuana and hemp, even though I hold patents on synthetic cannabinoids.  I should know what I am talking about because I am a medical marijuana patient.  I have chronic pain from being hit by drunk drivers, from surgeries, from a nervous breakdown and from many other causes.

Pain has a purpose, which is to let you know to stop it, or you will die.  So, pain is a good thing.  It is like realizing that you were wrong and feeling bad about it.  Otherwise, you would just go right back to being wrong again. 

Repentance means acknowledging your sins, praying to God for help and refraining from sinning any more.  Salvation requires repentance and acknowledgement of one God.  Salvation is conjunction with God.  The ultimate self-help book is the book that helps you connect directly with God so that you learn the truth for yourself.  Constituting the ultimate self-help book, the Instructions for Helping to Improve the Human Condition are freely available on this website.  Reading the Instructions for Helping to Improve the Human Condition is guaranteed to make you sexier.  So, be heart-healthy, y’all!  I love you!