From Tylenol to Opium

Korea version | 한국말 버젼
살면서 가끔 이런 생각을 한다.
만약 이 세상에 타이레놀이 없다면, 나는 아이를 어떻게 키웠을까, 끼울까?
열이 나고, 밤새 힘들었던 순간들. 부모라면 누구나 타이레놀의 경이에 의지해 본 경험이 있을 것이다.

우리는 익숙하게 타이레놀을 사용하지만, 타이레놀의 역사는 언제 시작된 것일까?

타이레놀의 긴 역사
많은 사람들이 타이레놀을 현대 의약품이라고 생각하지만, 그 역사는 생각보다 길다.
1955년 미국 McNeil Laboratories는 Tylenol이라는 이름으로 어린이용 해열제를 출시했다. 이후 1959년 Johnson & Johnson이 회사를 인수하면서 타이레놀은 미국 전역으로 보급되었고, 오늘날 가장 널리 사용되는 진통·해열제 중 하나가 되었다. 하지만 아세트아미노펜 자체는 훨씬 오래전인 1878년 미국 화학자 Harmon Northrop Morse에 의해 처음 합성되었다.
1890년대부터 진통과 해열 목적으로 사용되기 시작했지만, 당시에는 이미 의학계를 지배하고 있던 더 강력한 약물이 있었다. 바로 아편(Opium)이다.

인류와 함께한 진통제, 아편
아편은 인류가 수천 년 동안 사용해 온 천연 진통제이자 만병통치약이었다.
양귀비에서 얻어지는 이 물질은 통증을 줄이는 놀라운 효과를 가지고 있다.하지만 문제는 진통 효과만큼이나 강력한 의존성 중독성이다.

19세기 초 독일의 젊은 화학 견습생 Friedrich Sertürner는 아편 속에서 가장 강력한 활성 성분을 분리하는 데 성공한다. 그는 이 물질에 꿈의 신 Morpheus의 이름을 따서 Morphine이라는 이름을 붙였다. 당시 그는 자신에게 직접 약물을 투여하며 실험했고, 훗날 이 물질이 위험할 수 있다는 강력한 경고를 남긴다. 그러나 의학계는 모르핀의 강력한 진통 효과에 매료되었다.
1827년 Merck가 대량생산을 시작하면서 모르핀은 전 세계 의료 현장으로 빠르게 퍼졌다.

더 강한 약을 향한 욕망
1853년 스코틀랜드 의사 Alexander Wood는 주사기를 이용해 모르핀을 직접 체내에 주입하면 더 적은 양으로 효과를 낼 수 있다고 생각했다. 그 결과 모르핀 주사는 빠르게 확산되었다. 그 첫번째 약물과다 복용의 희생량은 Wood의 부인이었다.

당시 의사들은 더 강력하면서도 중독성이 적은 진통제를 찾았다. 그리고 그 과정에서 탄생한 것이 Heroin (acetylated morphine)이었다. 1898년 Bayer는 모르핀을 화학적으로 변형한 약물을 Heroin이라는 이름으로 판매하기 시작했다. 그 당신 관련 연구자들은 이 약물이 모르핀보다 안전하고 중독성이 적을 것이라는 성급한 결론을 내렸다. 하지만 그것은 치명적인 오판이었다. 헤로인은 더 빠르게 뇌에 도달했고, 더 강한 쾌감과 의존성을 만들었다. 20세기 초가 되자 의사들과 연구자들은 헤로인의 위험성을 인식하기 시작했고, 미국은 1924년 Heroin Act를 통해 헤로인의 제조와 판매를 금지한다.

Natural은 Safe를 의미하지 않는다
흥미로운 점은 모르핀, 헤로인, 그리고 현대의 오피오이드 진통제들이 모두 자연에서 시작되었다는 사실이다.
양귀비는 아름다운 꽃이다. 어떤 사람은 꽃이 아름답다고 말하고, 어떤 사람은 향기가 좋다고 말한다. 하지만 그 아름다운 꽃은 동시에 인류 역사상 가장 강력한 진통제와 가장 심각한 약물 의존 문제를 만들어낸 출발점이다.

우리는 종종 "천연 성분"이라는 말을 들으면 안전하다고 생각하고 상업적으로 이용된다. 그러나 역사는 그렇지 않다고 말한다. 독버섯도 천연이고, 아편도 천연이다. Natural과 Safe는 결코 같은 의미가 아니다.

타이레놀에서 다시 시작된 질문
아마 그래서 합성의약품인 타이레놀이 더 흥미로운지도 모른다.
오늘날 수많은 부모들이 아이의 열을 내리기 위해 사용하는 비교적 안전한 약. 이 약은 안전하지만, 시럽을 물처럼 마시면 물론 안 된다. 간에 치명적인 해로움을 끼칠 수 있다.
100년 넘게 사용되어 왔지만 아직도 작용기전이 완전히 밝혀지지 않은 약 (아무래도 열을 낮춘다는 것 자체가 면역작용을 통제하고, 그 결과가 우회적으로 아픔을 통제할 것같다).
그리고 무엇보다 아편이나 모르핀과는 전혀 다른 길을 걸어온 진통제.

진통제의 역사를 돌아보면, 그것은 단순한 의학의 발전사가 아니다.

인간의 고통을 줄이려는 노력과 과학적 호기심, 때로는 성급한 결론, 그리고 상업적 이해관계가 끊임없이 교차하고 있는 역사이다.

타이레놀에서 시작된 오늘의 글은… 야산의 양귀비 꽃 (지금 이시대에는 야산에 양귀비 꽃은 없겠지만..)으로 이어졌다. 난 실재로 양귀비 꽃에 대해 초등학교 수업 때 들은 적은 있어도 본 적은 없다.

Sometimes I find myself wondering: if Tylenol had never existed, how would I have raised my children?

The fevers, the countless nights spent comforting a restless child who couldn’t sleep. Almost every parent has probably relied on Tylenol at some point.

We use Tylenol so routinely today that we rarely stop to think about it. But when did the history of pain relief actually begin?

The Long History of Tylenol

Many people think of Tylenol as a modern medicine, but its history is much longer than most realize.

In 1955, McNeil Laboratories introduced a children’s fever reducer under the brand name Tylenol. After Johnson & Johnson acquired the company in 1959, Tylenol became widely available across the United States and eventually grew into one of the most commonly used pain relievers and fever reducers in the world.

Acetaminophen itself, however, dates back much further. It was first synthesized in 1878 by the American🇺🇸 chemist Harmon Northrop Morse. By the 1890s, it was already being used to relieve pain and reduce fever. Yet at the time, medicine was dominated by a much more powerful substance. That substance was opium.

Opium: The Painkiller That Accompanied Human History

Opium is a natural pain reliever that humans have used for thousands of years.

Derived from the opium poppy, it possesses remarkable pain-relieving properties. The problem, however, is that its power to relieve pain is matched by its ability to create dependence.

In the early nineteenth century, a young German🇩🇪 chemical apprentice named Friedrich Sertürner succeeded in isolating the most potent active ingredient found in opium. He named the substance Morphine after Morpheus, the Greek god of dreams.

Like many early scientists, Sertürner experimented on himself. He administered the substance to his own body and later warned that it could be dangerous. Nevertheless, the medical community was captivated by morphine’s extraordinary ability to relieve pain.

When Merck began mass-producing morphine in 1827, it rapidly spread throughout medical practice around the world.

The Desire for a Stronger Drug

In 1853, the Scottish🏴󠁧󠁢󠁳󠁣󠁴󠁿 physician Alexander Wood believed that injecting morphine directly into the body would allow doctors to achieve the same effects with smaller doses. As a result, injectable morphine quickly gained popularity and The first victim of the injected morphine was Wood’s wife.

At the same time, physicians continued searching for a painkiller that was even more effective while being less addictive.

Out of that research came heroin, acetylated morphine.

In 1898, Bayer began marketing a chemically modified form of morphine under the name Heroin.

Early researchers hoped that this new drug would be safer and less addictive than morphine. It was a devastating miscalculation.

Heroin reached the brain more rapidly, produced stronger feelings of euphoria, and ultimately proved even more addictive. By the early twentieth century, doctors and researchers had begun recognizing its dangers. In 1924, the United States passed the Heroin Act, effectively banning the manufacture and sale of heroin.

Natural Does Not Mean Safe

One of the most interesting aspects of this story is that morphine, heroin, and modern opioid painkillers all originated from nature.

The poppy is a beautiful flower. Some people admire its appearance. Others appreciate its fragrance. Yet this beautiful flower also became the starting point for some of the most powerful pain-relieving drugs and some of the most devastating addiction problems in human history.

We often assume that something described as “natural” must also be safe. History tells a different story.

Poisonous mushrooms are natural. Opium is natural. Natural and safe are not the same thing.

A Question That Returns to Tylenol

Perhaps that is one reason why Tylenol, a synthetic drug, remains so fascinating.

It is the medicine countless parents use to bring down a child’s fever. Of course, while this medication is safe, you certainly must not drink the syrup as if it were water. Doing so could cause fatal harm to your liver.

It has been used for well over a century, yet its precise mechanism of action is still not completely understood. (It seems that lowering a fever essentially regulates the immune response, and that this, in turn, indirectly helps control the pain.)

Most importantly, it followed a path very different from that of opium or morphine🪜.

When we look back at the history of painkillers, we are looking at more than the history of medicine.

It is also the story of humanity’s effort to reduce suffering, a story shaped by scientific curiosity, occasional premature conclusions, and powerful commercial interests 🤑.

Today’s reflections began with Tylenol, but somehow led me all the way to the poppy flower 🌺.

Growing up, I heard about poppies in elementary school, but I have never actually seen one in person. Perhaps wild opium poppies once existed in fields and hillsides somewhere in Korea, but certainly not today.

AAV Serotypes for Intravenous Gene Therapy (1)

Today, I wrote a bit about AAV serotypes and doses, and target organs, inspired after reading Reporter’s notebook 

CAP-002 case

clinical fatalities and the limits of IV-delivery

A child died in Capsida’s CAP-002 trial in September 2025,  the first patient treated with an engineered, IV-administered, BBB-crossing AAV for STXBP1 encephalopathy. 

Capsida Biotherapeutics voluntarily halted the SYNRGY trial (NCT06983158) after the first treated paediatric patient with developmental and epileptic encephalopathy (DEE) caused by STXBP1 mutations, died. The cause of death remains under investigation. CAP-002 is notable because its capsid was specifically engineered to cross the blood-brain barrier (BBB) via IV infusion, without intracranial injection. Regulators did not enforce the hold. However, Capsida self-imposed it while searching for the root cause.👍


Now, we should check some adverse events linked to IV AAVs. 

Reported patient deaths linked to IV AAV by serotype
SerotypeDrug / companyIndicationCause of deathStatus
AAV9Zolgensma (Novartis)Spinal muscular atrophy (SMA)Acute liver failure (ALF)2 deaths, 2022 (Zhang et al.)
AAV9Multiple high-dose trialsVarious CNS / neuromuscularThrombotic microangiopathy (TMA)Multiple cases (Zhang et al.)
AAV9 (NGN-40)NeurogeneRett syndromeRare hyperinflammatory syndrome1 deathPhase I/II (Joshua Silverwood)
AAV9-based (RP-A501)Rocket PharmaceuticalsDanon diseaseFatal acute systemic infection1 death, Phase II (Annabel Kartal Allen)
AAV8ASPIRO trial (AT132)X-linked myotubular myopathy (XLMM)Cholestatic liver failure4 deathsPhase I/II (Shieh et al.)
AAVrh74Elevidys (Sarepta)Duchenne muscular dystrophyAcute liver failure3 deaths (Annabel Kartal Allen)
Engineered AAV (CAP-002)Capsida BiotherapeuticsSTXBP1 encephalopathyUnknown — under investigation1 death, Sept 2025 (Annabel Kartal Allen)

What the AAV5 story teaches us

Now, we have to think about AAV5’s successful story. A decade of relative safety, why?

In August 2022, Europe approved the world’s first AAV5-based gene therapy for severe hemophilia A – Roctavian (valoctocogene roxaparvovec), developed by BioMarin. The FDA followed in June 2023. Since Phase 1/2 trials began in the mid-2010s, hundreds of patients have received a single IV infusion of AAV5, and to date, no patient deaths have been directly attributed to the therapy. In a field where other AAV programs have seen multiple fatalities, this is a notable record.

Hemophilia A is caused by a missing clotting protein (Factor VIII) that is normally made in the liver. So the therapeutic goal of Roctavian is simply to deliver a working gene to liver cells  and the liver happens to be exactly where AAV naturally travels after an IV injection. The vector does not need to fight its way past any biological barriers. It goes where it was always going to go.

So what makes AAV5 different? The answer is not the stereotype itself [I think, and some others would agree with me although it is some part of stories].  


The dose matters. 

Because the liver is the natural destination for IV-delivered AAV5-based gene therapies, a relatively modest dose is enough to achieve a therapeutic effect in hemophilia. Roctavian is given at 4–6 × 10¹³ vg/kg, roughly half to a third of the doses used in CNS or muscle-targeting programs. That difference in dose is, in large part, the difference between a therapy with an acceptable safety profile and one that has killed patients.

Why does the target organ change everything?

Think of it this way. When you give AAV through an IV, the vector enters the bloodstream and travels throughout the body. The liver acts like a sponge as always. It absorbs a large fraction of whatever AAV is circulating, regardless of where the doctor wants it to go. This is simply how our body works.

For hemophilia, this is actually favorable: you want the gene delivered to liver cells, and the liver is already soaking it up. A dose of 4–6 × 10¹³ vg/kg is enough to transduce enough liver cells to restore Factor VIII production. The liver handles this dose without triggering a dangerous immune response in most patients.

But for diseases of the brain or muscle, the liver is an obstacle, not a destination. To get enough AAV past the blood-brain barrier or into muscle tissue, you have to flood the entire system with a much larger dose, often 2 to 10 times higher. The liver still absorbs most of it, now overwhelmed by vectors it was never meant to receive in such quantities. The result, in the worst cases, is acute liver failure, immune storms, or vascular damage.

The safety record of AAV5 in hemophilia is genuinely encouraging, but it would be a mistake to conclude that AAV5 is simply a “safe” serotype. The real lesson is more specific and more important: IV gene therapy works best and most safely when the target organ is the liver. AAV5 has never been tested at the doses that CNS or muscle delivery would require, so we simply do not know how it would perform in that context.

What the full clinical picture tells us is that the moment gene therapy asks AAV to travel beyond the liver via IV, the dose requirements climb into a range where serious toxicity and death become real risks regardless of which serotype is used. AAV8, AAV9, and AAVrh74 have all produced fatal outcomes in this higher dose regime. Engineered capsids designed to cross the blood-brain barrier represent the field’s attempt to break this trade-off, but as the September 2025 death in Capsida’s trial shows, even the most advanced designed next-generation vectors carry unknowns that only human trials can reveal [The dose not disclosed yet]

A lower dose of IV gene therapy targeting other organs might be successful, which underscores the need for more efficient AAV engineering or local injection to resolve these matters.


Reference

Annabel Kartal Allen. “Child Dies in Phase I Capsida Gene Therapy Trial.” Child Dies in Phase I Capsida Gene Therapy Trial, Clinicaltrialsarena, 12 Sept. 2025″

Joshua Silverwood. “Patient Dies in Neurogene’s Phase I/II Rett Syndrome Trial.” Patient Dies in Neurogene’s Phase I/II Rett Syndrome Trial, Clinicaltrialsarena, 22 Nov. 2024″

Shieh, Perry B., et al. “Safety and Efficacy of Gene Replacement Therapy for X-Linked Myotubular Myopathy (ASPIRO): A Multinational, Open-Label, Dose-Escalation Trial.” The Lancet Neurology, vol. 22, no. 12, Dec. 2023, pp. 1125–39. DOI.org (Crossref)

Zhang, Wenwen, et al. “Comprehensive Analysis of Adverse Events Associated with Onasemnogene Abeparvovec (Zolgensma) in Spinal Muscular Atrophy Patients: Insights from FAERS Database.” Frontiers in Pharmacology, vol. 15, Jan. 2025, p. 1475884.

Antibodies: From Lab Bench to Therapeutic Drugs

I’ve always been fascinated by antibodies. My journey began in 2000, when I first took an undergraduate immunology class. During graduate school in Medical Biotechnology, I dove deeper—advanced immunology in 2001, psychoneuroimmunology in 2002—researching NKT cells and CD1d in autoimmune diseases. Back then, my curiosity was pure: I just wanted to understand how things worked. Papers, grants, and impact factors? I didn’t think about those. Honestly, even now, grant writing still feels like a mountain to climb!

Until 2018, during my third postdoc, I never actively pursued grants. I was fortunate to be in well-funded labs, free to follow my interests, attend meetings, and write papers when inspiration struck. That freedom was exhilarating. I often chose research topics my supervisors weren’t interested in—at least initially—giving me the joy of discovery.

But freedom has a cost. By the time I tried to apply for my own grant, it felt late. I wrote one in 2018, only to have my name removed by my PIs and replaced with a colleague’s. They told me it would increase our chances of funding. I also learned a hard lesson: in both academia and industry, even great data isn’t always shareable due to patents. At the end of the day, the only guaranteed rewards were a paycheck and the sheer pleasure of exploring science.

Sometimes I wonder if I should have pursued a Ph.D. in immunology instead of neurobiology. I missed a lot of immunology along the way. Still, I wouldn’t trade my journey—it shaped the scientist I am today.


Generating Antibodies: My Hands-On Experience

If you’ve worked in biology or medicine, you know antibodies are everywhere. They’re essential for research and diagnostics, from simple antibody staining to generating completely new reagents.

During my Ph.D., I generated antibodies both in-house and through companies. I provided expression constructs, sometimes purified proteins, and worked with animals like mice or ferrets. It took time, patience, and more than a few failed attempts—especially for antibodies against certain domains. For instance, when generating pan-antibodies against protocadherin 7, we eventually produced polyclonal antibodies, but monoclonal antibodies just didn’t cooperate.

Fast forward to 2020–2021: antibody engineering has advanced tremendously. I created numerous AAV constructs, including Fab and scFv, analyzing backbones, VH, VL, CDRs in detail. Companies sometimes tweaked CDRs sequences, either randomly or with AI. Even Fc regions required careful attention, as they could influence adverse effects in the case of Fc-fused proteins and full antibody drugs. To generate AAV constructs, all other parts, such as promoter regions, signal peptides, linkers, polyA, WPRE, etc., should be considered. The next steps are to check whether the antibody-based fragments are secreted and work properly by Western blots and ELISA. Of course, in the case of AAV constructs, we should check AAV property and yields and have AAV first.


Fc and Fab: The Power of Two

Antibodies have two main regions: Fab and Fc.

  • Fab or variable regions bind to antigens
  • Fc, often called the “effector arm or tail,” performs critical functions:
    1. Cell-mediated and humoral immune activation: Fc binds Fc receptors on macrophages, neutrophils, NK cells, and dendritic cells and leads to ADCC (antibody-dependent cellular cytotoxicity) and ADCP (antibody-dependent cellular phagocytosis).
    2. Complement system activation: Fc triggers pathogen lysis, opsonization, and inflammation.
    3. Half-life regulation: Fc binds neonatal Fc receptor (FcRn) in endothelial cells, protecting antibodies from degradation.
    4. Maternal-fetal transfer: IgG Fc interacts with FcRn in the placenta, passing immunity to the fetus.

When designing therapeutic antibodies, deciding whether to keep, engineer, or remove Fc is crucial. Fab fragments penetrate tissues better but have shorter half-lives. Fc is often necessary for cancer therapies, whereas autoimmune or blocking therapeutics benefit from Fc engineering to avoid harming self-tissues.


A Look at Therapeutic Antibodies

Here’s an overview of some major monoclonal antibody drugs and their Fc strategies:

DrugTargetIndicationFc StrategyEngineering / Mutations
RituximabCD20B-cell lymphoma, RAActive Fc → ADCC + CDCNone
TrastuzumabHER2HER2+ breast & gastric cancerActive Fc → ADCCNone
AdalimumabTNF-αRA, Crohn’s, psoriasisNeutralizingNone
CetuximabEGFRColorectal & head/neck cancerActive Fc → ADCCNone
NivolumabPD-1Melanoma, NSCLCFc-silent → avoids killing T cellsIgG4 backbone + S228P
PembrolizumabPD-1SimilarFc-silentIgG4 backbone + S228P
OmalizumabIgESevere asthma, urticariaFc engineered to avoid mast cell activationIgG1 backbone; avoids C1q binding
BevacizumabVEGF-AColorectal cancer, AMDNeutralizing; Fc not criticalWild-type IgG1

Key patterns:

  • Cancer drugs keep Fc active to kill tumor cells.
  • Checkpoint inhibitors silence Fc to avoid killing PD-1+ T cells.
  • Anti-cytokine drugs have no effector function, but increase half-life by FcRn recycling.
  • Anti-IgE drugs engineer Fc to prevent dangerous immune activation.

Fc-Free Antibodies: A Growing Field

Fc-free antibody fragments are also gaining attention. As of August 27, 2025:

StatusCount%
FDA-approved1527%
Terminated / Withdrawn1018%
Under Clinical Development2647%
Regulatory review47%
database for Therapeutic Antibodies (db.antibodysociety.org)

Even though Fc can trigger strong immune responses, careful control – through dosing or engineering – can make it highly beneficial. Fc-free fragments face challenges like short half-life or lack of effector function, explaining why some have been terminated.


Antibody research is a perfect blend of biology, engineering, and clinical innovation. It’s a field full of stories – both successes and failures – that teach us how to translate basic science into therapies. 

I’ve recently started reading again a book on therapeutic antibody engineering (2012), and I plan to share insights and reflections here from time to time.

Cabbage looper | Owlet Moths | Trichoplusia ni

May 22, 2025 by Sooyoung

Today, I searched for Trichoplusia ni (cabbage looper) and the reason why it is used for protein expression.

The cabbage looper is a medium-sized moth commonly called owlet moth, and it is known for its distinctive looping movement as a caterpillar. So, the caterpillar is commonly called a cabbage looper, and the adult cabbage loopers are called owlet moths.

A picture of owlet moth from webpage, russellipm.com

You may visit YouTube to see Looper. 🐛

Why it is used for protein expression and how the technology has been developed:

Trichoplusia ni (cabbage looper) is used for protein expression due to its ability to produce recombinant proteins at high levels and with good quality, particularly for SECRETED proteins. Its insect cell lines, such as Tni-FNL, have demonstrated superior protein production compared to other winged insect (lepidopteran) cell lines of Spodoptera frugiperda (fall armyworm moth). Furthermore, some Trichoplusia ni cell lines (Tni-FNL) have shown improved growth rates and the ability to grow at lower temperatures. 

Who developed:

The High Five (BTI-Tn-5B1-4) cell line, derived from the cabbage looper (Trichoplusia ni) eggs, was first developed by the Boyce Thompson Institute for Plant Research in 1970. Another Trichoplusia ni cell line, Tni-FNL, was developed by researchers at the National Cancer Institute in 2018.

What we think about protein expression:

Protein yield, Scale-up, Toxicity, Post-translational modification, growth characteristics, how could be advanced further…..

Further reading materials and original references:

Pymol

There are molecules that we can not see with our naked eyes. Protein is one of them.

You may see some proteins using PyMOL on your computer.

You could install free PyMOL in your terminal using brew:

Brew install pymol

Now, to see any protein there, use fetch command:

fetch 9DYH

You could get PDBIDs and more information from here: RCSB.

This is another useful command to arrange all PDBs in order: alignto 

alignto PDBID (eg 9DW7), object=all_to_PDBID (eg 9DW7)

You could start learning about protein structure by digging more websites. 🤞

Special Issue Guest Editer, Life, MDPI

I have served as a guest editor at Life (ISSN 2075-1729) since my workplace shut down and I lost my job. My workplace, USA Research and Development Center of Neurophth Therapeutics Inc., had decided to close our team when they started aggressively the clinical trial and just before obtaining the Series-C investment. I believe that our early development team actively studied and supported the company’s Business portfolio until our center closed. We, our team built up one center, and we observed as well their closing. Building something up took more time than shutting it down. The closing was quite quicker than I expected.

I met MDPI when I published a review paper, Twenty Years of Anti-Vascular Endothelial Growh Factor Therapeutics in Neovascular Age-Related Macular Degeneration Treatment at the journal of International Journal of Molecular Sciences. I started studying age-related macular degeneration in 2011, when I examined the retina of an aryl hydrocarbon receptor (AhR) knockout. Maybe any molecules in our body will have two sides of the balance– good and bad. Even vitamins and minerals are toxic when they are deficient and plenty. Especially, AhR was very interesting because it is one of important molecules for the balance of the immune system. I studied immunology for my master’s, because I thought that all diseases including brain and retina, had no exception from the immune system, after working as a BS research associate at the section of Neurodegenerative diseases, Korea National Institutes of Health, During mater degree program, I especially studied about NKT and non-classical major histocompatibility complex (MHC) molecule in the autoimmune diseases using molecular genetic engineering, animal and cell experiments. After that, I studied several adhesion molecules during brain development during my Ph.D program. My first publication of the first author was spatiotemporal expression patterns of non-clusteted protocadherin family members in the developing rat brain. I studied brain anatomy as well as brain primary neuronal culture with this project. When I came into the USA, I started basic research and translational studies using cells, engineered chemicals, nano-packed small molecules, peptides, antibodies, exosomes, and adeno-associated viruses in retina degenerating animal moldels. Sometimes, I developed new animal models and new analysis methods to test the candidate drugs. Some of them have been published. Many of them have not be published because some did not exhibit good enough efficiency, and some did show too good efficiency to be published ^.^. Actually, good efficiency is a really small piece and small step for the development in the view of company. Sometimes candidate drugs had enough good efficiency but the manufacturing was a hurdle, and some expected fancy drugs had toxicity, killing disease model animals. Synthetic nucleotide engineering was facinating to me, because somehow synthetic nucleotide engineering easily generates antibodies, antibody fragments, AAVs, fusion proteins, and any proteins, and nucleotide sequences could be all changed, and optimized to increase the yields of the proteins and still reduce the immune activation, which nobody knows the detailed profiles before testing them. Research and Development is a really initial step for drug development, but the tiny, tiny things of the early stage development could cause dramatic misfortune and a tragedy in patients’ safety.

To me, taking a role as a guest editor is an honor, and a chance to continue reading and following the field and learn a little other countries — China, Europe, and Eastern Asia, as well as Korea, where I was born, and the USA, where I’m. All the research situations were not the same, really based on the grant money, medical insurance, and the community acceptance based on different countries. While serving Life special edition as a guest editor, what I have learned so far is that we science communities should encourage us to share what we are studying in different countries, giving chances to collaborate and know and understand each other’s scientific environment and situation, and further science should give benefit, fun, hope, and new knowledge to the public.

One thing I have worried in the current science communities is…..

We, even our kids, like Youtube channels, and they check the number of their followers. This kind of behavior could be harmful to the basic scientific world. We scientists pursue grant trends, and check journal impact factors for their survival, but we scientists should remember their own questions, purpose, and fun. We adults, the senior old generation, should allow and help our young generation to pursue their own scientific questions and have trials and errors in our educational system, not only increasing publication records. I worry about our severely competitive academic world where the young generation has no chance for them to pursue their own questions, and not allow enough failure and early lost academic fun in pursuing their own questions.

In the end, I believe, that journals could or should help our science communities to make meaningful research, and promote sharing.

I accepted my role of a guest editor, Life, when I read the Aim and Scope of Life. At least I felt that Life is trying to serve a broad science and public communities, and communities’ questions, and scientific funs. However, I wondered why they decided on a similar journal name to elife: T.T.

If you want to visit Life, click here

If you want to vist the special issue of Retinal Diseases: From Molecular Mechanisms to Therapeutics, click here.

Thank you for reading!!

Plasmid extraction

Molecular work 01: Plasmid extraction:

For plasmids, gDNAs, RNAs etc extraction, nowadays, we use commercial kits. I do not know when we started using commercial kits, but in early 2000s, many laboratories still used non-commercial methods- lab made Sol I (lysozyme lysis buffer), II (Acid buffer) and III (Alkaline buffer), following Phenol, Chloroform, and Isopropanol clearance after extraction. The most successful companies for plasmid kits may be Quiagen and Macherey-Nagel. They have plasmid kids for Mini, Midi, Maxi, Giga, Endo toxin free! In my mind, MN yields were better than Quiagen, but Giga prep I have used only Qiagen kit, so I am not sure whether MN has Giga prep kits as well. Quiagen, Promega and MN are still the most successful companies I think. Quiagen’s market occupancy started before 2000 even in South Korea. Also someone who is old like me might know and used CsCl plasmid purification. What I learned first during my Master degree training, was plasmid purification using CsCl ultracentrifuge method. It was simple but took time. My Master degree mentor Dr. Seho Park preferred CsCl at that time. I do not know which method he likes currently.

A few years ago, I saw a biotech company where they work to make a plasmid isolation machine. I’m not quite sure whether they were successful. However, you may hear Thermo KingFisher Plasmid Pro that I never used on my hands. Also you may hear automated lab components provided from Molecular device. I am not sure how they are successful. Long time ago, we/some old generation like me still remember that even we manually moved PCR tubes from different temperature water baths to another for PCR reaction.

About the water

Last step is adding solution either TE (Tris EDTA) or water. I recommend that you have to keep in mind what you are doing, for the next steps, before adding either TE or water. Generally I recommend adding water for the next steps: Restriction enzyme treatment, in vitro (cell), and in vivo (animal) treatment etc. TE definitely is a good solution for storage, but if you keep your plasmid DNAs at -20 °C, they are really safe, not degrading. You also could aliquot them. Usually, if you use water, you could save/reduce amounts of restriction enzyme using small reaction volume. Endo toxin free molecular grade water is easy to purchase from Fisher.

GMP plasmids

Maybe some heard about GMP (Good manufacturing practice) plasmids. I just googled how many GMP plasmids supplying companies are globally. There are quite numbers of companies including Aldevron and Catalent.

Design a site like this with WordPress.com
Get started